JPH03280948A - Compound artificial blood vessel - Google Patents

Abstract

PURPOSE:To quickly form a vascular endothelial cell so as to promote also infiltration of a capillary vessel by adjusting a bubble point to a specific range, in the case of a compound artificial blood vessel whose pipe wall is formed of compound material of porous poly ethylene tetrafluoride, collagen or thermo degenerated collagen and heparin. CONSTITUTION:A compound artificial blood vessel is formed of a wall of porous polyethylene tetrafluoride 1 and provided with many holes 2. A collagen layer 3 mixed with heparin is formed in the wall of the hole 2. The collagen layer 3 is formed so as to prevent the hole 2 from being closed, and an adhering amount of the collagen layer is adjusted so that a bubble point obtains 0.1 to 0.01kg/cm<2>.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to an artificial blood vessel that is applied to the aorta, peripheral arteries, coronary arteries, and the like.

BACKGROUND OF THE INVENTION Artificial blood vessels using porous polytetrafluoroethylene are currently widely used as blood vessel substitutes.

The pore diameter of the artificial blood vessel is often described in terms of fiber length (porous polytetrafluoroethylene china, which is currently in practical use).
The fiber length of the fiber is 17-20μ (Ashizawa et al., Artificial organs,
9(1), 98 (1980)). Research examples of artificial blood vessels combined with bio-derived materials include those with a diameter of 50μ to 100μ (Tamura et al., Artificial Organs, 1dan (3), 1500).
1987) and Alien et al., Journal
of Surgical Research (J, Surg, Res.
) 36(1), 80 (1984)).

On the other hand, as a composite artificial blood vessel that combines collagen and heparin with a porous polymer tube such as porous polytetrafluoroethylene, ■ a heparin-mixed collagen layer and a collagen layer are sequentially formed on the inner wall of a porous polytetrafluoroethylene tube. Artificial blood vessel consisting of three layers: ■ Artificial blood vessel in which the pores of a porous polymer tube are impregnated with heparin and a collagen layer is formed on the inner wall of the porous tube, ■ Heparin is ionized into collagen using a quaternary ammonium compound as a binder. Artificial blood vessels are known that are bonded and laminated on the inner wall surface of a porous polymer chinive.

Problems to be Solved by the Invention Artificial blood vessels using porous polytetrafluoroethylene tinib have been put into practical use alone, and research is also progressing into composite artificial blood vessels that are combined with biomaterials as described above. ing. The former has the disadvantage of poor tissue healing properties (cell penetration) due to the low affinity between porous H-tetrafluoroethylene and living tissues.The latter also overcomes the drawbacks of the former. However, the drawbacks have not necessarily been improved.As a result of intensive research into the cause of this problem, we found that if the pore diameter of the composite artificial blood vessel is too small, It became clear that the thin skin and capillaries of the living body could not penetrate, and tissue healing properties were not improved.

Means for Solving the Problems The present invention provides a composite artificial blood vessel whose vessel wall is a composite of porous polytetrafluoroethylene and collagen or heat-denatured collagen and heparin, which has a bubble point of 0.01 to 0. ．．
The present invention provides a composite artificial blood vessel characterized by a ratio of 1 to 9/cx'.

Here, the bubble point is the pressure at which air bubbles first appear when a porous tube is impregnated with isopropyl alcohol, the pores in the tube wall are filled with inpropyl alcohol, and then air pressure is applied from inside the tube. say.

At this time, it is known that the following equation holds.

P, bubble point δ: surface tension of isobrobyl alcohol θ, contact angle between the tube and isopropyl alcohol d: pore diameter Since pressure P is inversely proportional to pore diameter d, the first bubble comes out from the pore with the largest diameter. This determines the hole diameter.

FIG. 1 is a circumferential sectional view of the artificial blood vessel, and FIG. 2 is a longitudinal sectional view thereof. The artificial blood vessel consists of a wall of porous polytetrafluoroethylene 1 and has a large number of pores 2. Figure 2 is an enlarged view of the hole, and a collagen layer 3 mixed with heparin is formed on the wall of the hole. In the present invention, the collagen layer is formed so as not to block the pores, and the amount of collagen layer attached is such that the bubble point is 0.1 to 0.01k.
It is adjusted so that y/c11!1.

FIG. 3 shows a longitudinal sectional view of a conventional composite artificial blood vessel. In this composite artificial blood vessel, the pores are filled with a large amount of collagen mixed with heparin, and the pores are occluded.

In the present invention, the bubble point is 0.1 to 0,0
Collagen mixed and dispersed with heparin was added to the pores of porous polytetrafluoroethylene at a concentration of 1 kg/cz'.
Coat the holes so that they are not blocked as shown in Figure 2. If the hole is completely blocked as shown in FIG. 3, the effects of the present invention will not be exhibited as described below.

Collagen molecules have a three-helix structure and are bulky, and their aqueous solutions are heterogeneous and highly viscous. For this reason, it is difficult to thinly and uniformly coat the porous polytetrafluoroethylene pores with collagen molecules without clogging the pores. For such coating, it is desirable to use heat-denatured collagen.

That is, when the pores are completely occluded as shown in Fig. 3, the bubble point becomes more than Lkf/ct, which slows the formation of endothelial cells on the inner wall of the porous tetrafluoroethylene tube, and also prevents capillary invasion. Become slow.

On the other hand, after compositing the biomaterial, the bubble point is 0,0
Composite artificial blood vessels weighing less than 1 kg7 cm* are difficult to use as artificial blood vessels because of severe blood leakage during transplantation. As a countermeasure to this problem, it is possible to perform a pre-clotting operation using blood, but this operation would close the pores of the porous polytetrafluoroethylene tube.

According to the present invention, when the bubble point is adjusted to the above range and collagen mixed and dispersed with heparin is coated on the porous polytetrafluoroethylene pores, the formation of endothelial cells is accelerated, and the invasion of capillaries is also accelerated. .

The formation of a collagen layer mixed and dispersed with heparin is carried out as described in the following example.

EXAMPLES Hereinafter, the present invention will be specifically explained by showing examples and comparative examples.

Examples 1 to 4 and Comparative Examples 1 to 4 Three types of porous polytetrafluoroethylene tubes (inner diameter 2x
x, outer diameter 3xx, porosity approximately 75%, bubble point 0.
On 0.08.06 or 0.02, a 9/c strain was immersed in a 0.003% aqueous solution of thermally denatured beef-based collagen, and then dried. This operation was repeated six times. Also, the bubble point is 0.01 for a tube of 0.02 kg/cxt.
% of the above solution, the immersion drying operation was performed six times. These four types of collagen composite tinibs were cross-linked with gel taraldehyde, then impregnated with a 10% aqueous solution of water and dried (Examples 1 to 4).

Four types of composite tubes (Examples 1 to 4) and three types of untreated tubes (Comparative Examples 1 to 3) 3B were each implanted into the carotid artery of a rabbit.

On the other hand, a tube with a bubble point of 0.06 kg7 C1+' was immersed in a 0.3% collagen aqueous solution.
After drying, it was crosslinked with geltaraldehyde and immersed in an aqueous heparin solution. It was similarly transplanted into the rabbit condylar artery (Comparative Example 4)
.

Two weeks after transplantation, the endothelial cell coverage and the number of capillary invasions were counted and evaluated. The results are shown in Table-1.

[Brief explanation of the drawing]

FIG. 1 is a circumferential cross-sectional view of a composite artificial blood vessel, FIG. 2 is a longitudinal cross-sectional view of the composite artificial blood vessel of FIG. 1, and FIG. 3 is a circumferential cross-sectional view of a conventional composite artificial blood vessel. The pores are filled with bio-derived material. 1...Porous fluorinated ethylene tube, 2...pores, 3...heparin mixed collagen layer

Claims (1)

[Claims] 1. In a composite artificial blood vessel whose vessel wall is a composite of porous polytetrafluoroethylene and collagen or heat-denatured collagen and heparin, the bubble point is 0.01 to 0.1 kg.
/cm^2.