JPH04288165A - Organ implant and manufacture thereof - Google Patents

Abstract

PURPOSE:To obtain an organ implant excellent in handlability during an implantation and compatibility with blood and tissues. CONSTITUTION:A part a human or animal blood tissue undergoes a crosslinking processing by a joint use of a treatment using a solution having at least one multi-functional group selected from the group consisting of glutaric aldehyde, paraformaldehyde, formaldehyde and ethylalcohol and a microwave irradiation. This enables the producing of an organ implant which is excellent in compatibility with blood and tissues and handlability during an implantation, applicable for a tubular organ with a fine diameter and has calcification inhibited.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel organ transplant and a method for producing the same. To explain in detail,
The present invention relates to an organ transplant that is easy to handle during transplantation and has excellent compatibility with blood and tissue, and a method for producing the organ transplant.

0002

[Background Art] In recent years, with the arrival of an aging society, diseases caused by vascular lesions such as occlusive arterial disease and aneurysm formation have been increasing.With remarkable advances in medical care, bypass surgery (bypass) is being performed to treat the above diseases. , vascular transplantation (gr.
aft), PTBA (percutaneous b)
Alloon angioplasty (percutaneous balloon vasodilation) has become common practice, and PTLA (percutaneous laz
Percutaneous laser angioplasty (percutaneous laser angioplasty) has also entered the clinical stage and is currently being developed.

[0003] However, with PTBA, reocclusion of the blood vessel due to thickening of the intima after the treatment has become a new problem. Further, PTLA has problems such as the possibility of perforation of blood vessels and damage to adjacent tissues by the laser, the difficulty of cauterizing hard lesions accompanied by calcification of blood vessels, and the high cost of the machine.

[0004] Furthermore, replacement of blood vessels in diseased areas (vascular grafting) using autologous veins or artificial blood vessels, and bypass surgery have become widely practiced, and many patients are benefiting from them. However, the blood vessels to be replaced are limited to fairly large vessels with a diameter of 8 mm or more, and there are problems such as the inability to achieve long-term patency when used in vessels with a smaller diameter, and there are many limitations to these applications. , and much will depend on future research.

[0005] Therefore, if a small-diameter artificial blood vessel with antithrombotic properties and excellent tissue repair ability were developed, the range of applications would be greatly expanded, and this would bring great news to the field of vascular surgery.

[0006] Furthermore, if an artificial blood vessel with the above-mentioned excellent properties is developed, such artificial blood vessels will be necessary in the future when artificial livers, artificial pancreases, etc. are developed and implanted in living bodies. It can also be used as a conduit.

[0007] The current state of artificial blood vessels will be described in more detail below.

[0008] Conventionally, large-diameter artificial blood vessels of 8 mm or more have been made of porous polyester or microporous polytetrafluoroethylene. Artificial blood vessels made of polyester are made by forming neointimal cells on a base material and utilizing the natural antithrombotic properties of these neointimal cells. Therefore, porous polyester artificial blood vessels have excellent tissue penetration, and the newly formed neointima grows firmly on the inner surface of the artificial blood vessel, with little peeling, resulting in long-term patency. This is something to look forward to. On the other hand, artificial blood vessels using microporous polytetrafluoroethylene utilize the antithrombotic properties of the material, and have shown excellent initial antithrombotic effects.

However, if the inner diameter of the above-mentioned artificial blood vessel using porous polyester is large, blood clots will adhere to the inner surface immediately after implantation, but after that, intimal cells will cover the surface and the natural blood vessel will form. Although it is possible to obtain natural antithrombotic properties because it forms a surface structure similar to that of neointima, it is currently known that there is a limit to the extent and speed of neointimal formation. Furthermore, since polyester does not have excellent antithrombotic properties, if an artificial blood vessel with a small caliber, especially one with a diameter of 5 mm or less, is used, the artificial blood vessel is likely to be occluded by blood clots that adhere to it immediately after implantation. The problem with these artificial blood vessels is that they cannot be used for small-diameter blood vessels.

[0010] In addition, artificial blood vessels using microporous polytetrafluoroethylene are superior to polyester in terms of thrombus formation because the material used is inert to living organisms. At the same time, it is known that tissue repair tends to be extremely delayed because the bioreactivity is very slight. Furthermore, due to its microporous nature, it is difficult for living tissue to enter the wall of the artificial blood vessel, and therefore, it is difficult for neointima to form in the center of the artificial blood vessel.
Organization is delayed, and the bond between the living tissue formed on the outer surface of the artificial blood vessel and the living tissue formed on the inner surface becomes insufficient. For example, when using a brat access for dialysis, hematoma formation cause, or
The neointima that has grown from the anastomosis at both ends of the transplanted artificial blood vessel is likely to peel off. Furthermore, if this neointima is detached, this detached material may cause thrombus formation, which is undesirable. In addition, after artificial blood vessel transplantation, the neointima partially bulges near the anastomosis on the distal side of the blood vessel (
At present, there are still many problems that need to be resolved, such as thickening (thickening) and occlusion in the long term.

[0011] On the other hand, due to the limitations of artificial blood vessels made only of these synthetic polymer materials, products that utilize natural tissue such as human tissue or animal tissue and apply the excellent structure, physical properties, etc. that only natural tissue has are known. ing. For example, garlic (
No. 4,378,22 by Nimni et al.
No. 4 (1983), also Dardi
U.S. Patent No. 3,988,782 (1) by k) et al.
(976) describes a method for treating tissue using glutaraldehyde as a hardening agent. moreover,
After treating pig blood vessels with proteolytic enzymes,
A method of fixation using a mixed solution of formaldehyde and glutaraldehyde has been proposed by Miyata et al. (U.S. Pat. No. 4,098,57).
No. 1 (1978)). However, these methods have problems such as hardening of the transplanted tissue and long-term calcification caused by autolytic material, and much remains to be done in future research. There are also products using pig heart valves and human umbilical cords, which are manufactured by the immersion method using glutaraldehyde.
Each has problems such as calcification or low blood compatibility.

As described above, the current situation is that organ transplants that fully meet the needs of the medical field, particularly the field of vascular surgery, have not been obtained.

[0013]

SUMMARY OF THE INVENTION Therefore, the present invention is useful in the medical field, particularly in the field of vascular surgery, and has excellent healing properties, compatibility with blood and tissue, and ease of handling during transplantation, and is suitable for use in small-diameter hollow organs. It is also an object of the present invention to provide an organ transplant in which calcium deposition is suppressed and a method for producing the same.

[0014]

[Means for Solving the Problems] The above objectives are to provide at least one polyfunctional group selected from the group consisting of glutaraldehyde, paraformaldehyde, formaldehyde and ethyl alcohol to a part of human or animal tissue. This is achieved by an organ transplant characterized in that it has been crosslinked by a combination of treatment with a solution containing the same and microwave irradiation.

[0015] The above objects are also achieved by applying a solution containing at least one polyfunctional group selected from the group consisting of glutaraldehyde, paraformaldehyde, formaldehyde and ethyl alcohol to a part of human or animal tissue. This is achieved by a method for producing an organ transplant characterized by performing a crosslinking treatment by using a combination of treatment and microwave irradiation.

[0016]

[Action] The organ transplant of the present invention provides a solution containing at least one polyfunctional group selected from the group consisting of glutaraldehyde, paraformaldehyde, formaldehyde and ethyl alcohol to a part of human or animal tissue. The crosslinking treatment was carried out by using a combination of treatment with and microwave irradiation. Therefore, in the organ transplant of the present invention, by crosslinking the transplanted tissue in a multifunctional group solution by microwave irradiation, the multifunctional group solution can instantly and uniformly penetrate into the tissue. , compared to the conventional immersion fixation method, it can prevent self-lysis and also prevent tissue hardening.
As a result, good handling properties and excellent compatibility with tissues and blood can be obtained.

[0017] Furthermore, in the organ transplant of the present invention, the transplanted tissue is cross-linked by using a combination of treatment with a polyfunctional group solution and microwave irradiation, so that when treated with the polyfunctional group solution alone, In comparison, it is possible to crosslink structures with poor thermal conductivity in a short time, and
Penetration into tissues is also facilitated.

[0018] The transplanted tissue used in the present invention can be a part of human or animal tissue, and is not particularly limited as long as the inner diameter size and length are compatible with the organ to be transplanted. Examples include luminal organs such as blood vessels, ureters, and esophagus of mammals such as humans, pigs, cows, rabbits, goats, and dogs. Among these, blood vessels and ureters can be preferably used. In addition, when the transplanted tissue is a hollow organ, the inner diameter is 1 to 50 mm, more preferably 1 to 20 mm.
The length is preferably 1 to 150 m.
m, more preferably 1 to 70 mm. At this time, the thickness of the hollow organ is preferably approximately 1 mm.

The multifunctional solution used in the present invention is a fixative for denaturing proteins, and specifically includes glutaraldehyde, paraformaldehyde,
The solution has at least one type of polyfunctional group selected from the group consisting of formaldehyde and ethyl alcohol. Among these, glutaraldehyde can be preferably used. In addition, the concentration of the polyfunctional group solution at this time is 0.0 when the polyfunctional group solution is a glutaraldehyde solution.
The amount is 1 to 2%, preferably 1%, and as a solvent for the solution, phosphate buffer, cacodylate buffer, etc. can be used, and among these, phosphate buffer can be preferably used.

Microwave used in the present invention
"B" refers to electromagnetic waves with a frequency in the range of approximately 1 Mc to 1000 kmc, but preferably electromagnetic waves in the range of 5 Mc to 200 Mc can be used.

[0021] In the present invention, a microwave oven or the like can be used as an apparatus for performing microwave irradiation. Further, the microwave irradiation time is 1 to 90 seconds, preferably 20 to 50 seconds.

[0022] The method for producing the organ transplant of the present invention includes:
Although there is no particular limitation as long as treatment with a polyfunctional group solution and microwave irradiation are used together for the transplanted tissue, specific examples include the following methods. A transplanted tissue is collected from a human or an animal, thoroughly washed with physiological saline, etc., then immersed in a Triton X-100 solution, and then subjected to ultrasonic cleaning. The transplanted tissue subjected to the above treatment was placed in a glutaraldehyde solution, and microwave irradiation was performed using a household microwave oven to bring the temperature of the solution to 20 to 6.
Set to 0℃. After washing the transplanted tissue cross-linked in this way, it is stored in physiological saline or the like to obtain the intended organ transplant.

[0023] As shown in the above embodiments, in order to make the collagenase treatment more effective, it is preferable to perform the treatment with a surfactant such as trytone X-100. The concentration of the surfactant at this time is 0.01 to 10%, preferably 0.01%.
~0.1%, and the immersion time is 10~1%.
The time is 20 minutes, preferably 30 to 60 minutes.

[0024] In the embodiment described above, in order to absorb excess energy when performing microwave irradiation, 10 to 1000 ml, more preferably 200 ml
It is advisable to place a container containing ~500 ml of water at the end of the microwave oven.

Furthermore, in the above embodiment, the temperature of the glutaraldehyde solution is set at 20 to 60°C, because if the temperature is lower than 20°C, no crosslinking effect can be expected, which is not preferable. , the above liquid temperature is 60℃
Exceeding this is also undesirable as damage (degeneration) to the tissue (cells within the tissue) may occur.

[0026]

[Examples] The present invention will be explained in more detail below with reference to Examples and Comparative Examples.

Example 1 After ligating the branches of the abdominal aorta of a domestic rabbit, about 2 cm was harvested. The collected abdominal aorta was thoroughly washed with physiological saline and then immersed in a 1% Triton X-100 (Rohm and Haas) solution. After that, ultrasonic cleaning was performed, and 1%
It was placed in a glutaraldehyde solution and irradiated for 30 seconds in a household 500W microwave oven, and the liquid temperature was set at 40°C. In addition, at this time, in order to absorb excess energy, 2
A container containing 00 ml of water was placed at the end of the microwave. After irradiation, the abdominal aorta was further washed, and then stored in physiological saline to be used as Specimen 1.

As a result, sample 1 showed no change in color tone;
The texture was also soft.

Comparative Example 1 Blood vessels were collected in the same manner as in Example 1, except that they were immersed in a 1% glutaraldehyde solution for 24 hours without microwave irradiation. A control example (specimen 2) was prepared in the same manner as in Example 1.

As a result, Specimen 2 had a slightly yellow color and had a hard tissue.

Example 2, Comparative Example 2 A sample similar to that obtained in Example 1 and Comparative Example 1 (
Specimens 3 and 4, respectively) were transplanted into the blood vessels of rabbits by end-to-end anastomosis, and after 3 months, the transplanted rabbits were autopsied and macroscopically and histopathologically examined.

[0032] As a result, according to the naked eye observation, in Sample 3, the lumen surface exhibited a glossy white color, whereas in Sample 4, red blood clots remained diffusely.

Further, according to pathological observation, good neointima was formed in specimen 3, and no thrombus was observed at all. On the other hand, in sample 4, adhesion of thrombus was observed, and furthermore, some calcium deposition was also observed.

[0034]

Effects of the Invention As described above, the organ transplant of the present invention provides at least one substance selected from the group consisting of glutaraldehyde, paraformaldehyde, formaldehyde, and ethyl alcohol to a part of human or animal tissue. It is characterized in that crosslinking treatment is performed by using a combination of treatment with a solution having a polyfunctional group and microwave irradiation. For this reason,
The organ transplant of the present invention prevents tissue degeneration and hardening, suppresses calcium deposition, and has excellent handling properties and biocompatibility during transplantation.

[0035] Therefore, the organ transplant of the present invention can be applied to, for example, artificial blood vessels with reduced diameters, and brings great benefits in the medical field, particularly in the field of vascular surgery.

Claims (2)

[Claims] Claim 1: Treatment and microwave irradiation of a part of human or animal tissue with a solution containing at least one polyfunctional group selected from the group consisting of glutaraldehyde, paraformaldehyde, formaldehyde and ethyl alcohol. An organ transplant characterized by being cross-linked by the combined use of. 2. Treatment and microwave irradiation of a part of human or animal tissue with a solution containing at least one polyfunctional group selected from the group consisting of glutaraldehyde, paraformaldehyde, formaldehyde and ethyl alcohol. 1. A method for producing an organ transplant, characterized by performing crosslinking treatment by using in combination.