WO1993023090A1 - Artificial blood vessel - Google Patents

Artificial blood vessel Download PDF

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Publication number
WO1993023090A1
WO1993023090A1 PCT/US1993/004803 US9304803W WO9323090A1 WO 1993023090 A1 WO1993023090 A1 WO 1993023090A1 US 9304803 W US9304803 W US 9304803W WO 9323090 A1 WO9323090 A1 WO 9323090A1
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Prior art keywords
artificial blood
hydroxyapatite
blood vessel
artificial
blood vessels
Prior art date
Application number
PCT/US1993/004803
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French (fr)
Inventor
Masaki Ogawa
Original Assignee
Sherwood Medical Company
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Filing date
Publication date
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Publication of WO1993023090A1 publication Critical patent/WO1993023090A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A61L27/32—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00389—The prosthesis being coated or covered with a particular material
    • A61F2310/00592—Coating or prosthesis-covering structure made of ceramics or of ceramic-like compounds
    • A61F2310/00796—Coating or prosthesis-covering structure made of a phosphorus-containing compound, e.g. hydroxy(l)apatite

Definitions

  • the present invention pertains to artificial blood vessels, more specifically to artificial blood vessels which have significantly improved anti-clot characteristic and function well as small-diameter artificial blood vessels.
  • the artificial blood vessel made of the drawn polytetrafluoroethylene no initial blood leakage occurs, but it has a disadvantage that the pseudo intima does not develop on the inner surface as readily. Therefore, in the long run, it is inferior to the Dacron fabric artificial blood vessel with respect to the biological compatibility including anti-clot characteristic. Nevertheless, it is often used for the artificial blood vessel with smaller diameters because the inner opening is more easily
  • hydroxyapatite is a brittle ceramic with extremely large elastic moduli and therefore its compliance is substantially different from that of actual blood vessel. Therefore it is valuable in laboratory study, but will not readily provide practical artificial blood vessels.
  • Hydroxyapatite adsorbs a large amount of albumin among proteins in the blood plasma. It is a common knowledge among researchers that the layer of albumin adsorption exhibits excellent anti-clot characteristic.
  • Miomaterials Society (reprint, 1987, p. 6); the electrophoresis process in The Japan Ceramics Society. 1988, pp. 417-418; and the processes to precipitate hydroxyapatite from an artificial body fluid composed of ions of the same type and concentration as those in human blood plasma in Tokko Sho 61 (1986) - 10939, Tokko Hei 1 (1989) - 54290 and Tokkai Hei 2 (1990) -255515.
  • hydroxyapatite coating have been published. Nevertheless, there remain many problems to be resolved, which include: (a) The plasma jet process requires sophisticated and expensive equipment, and yet it does not readily produce fine coating and forms coating of apatite which is different from the apatite in the body because the source material, hydroxyapatite, is once melted at high temperatures.
  • hydroxyapatite the source material, is once melted at high temperatures.
  • the sintering and glass frit processes require heat treatments at temperatures 850°C or above and therefore can be applied only to base materials with high heat resistance and may form coating of apatite which is different from the apatite in the body because
  • hydroxyapatite the source material, is once treated at high temperatures.
  • the electrophoresis process can be applied only to metallic base materials with good electric conductivity because it uses the base material itself as an electrode and also forms coating of apatite which is different from the apatite in vivo because it uses sintered apatite as the source material.
  • the present invention is intended to resolve the difficulties in the existing technology described above and to provide artificial blood vessels which have improved anti-clot characteristic and function well as small diameter artificial blood vessels.
  • the artificial blood vessel developed in the present invention has the following features.
  • the said polymeric fabric is polyester
  • polyacrylonitrile or polyurethane preferably polyester.
  • a part of the phosphate or hydroxyl group in the said hydroxyapatite has been substituted by carbonic group.
  • the reasons for limiting the base material for the artificial blood vessel in this invention to polymeric fabrics are that their mechanical properties (such as the compliance) required for the artificial blood vessel have already been optimized, that they have been well proven to be safely used in the body, and that it is considered sensible to coat the base material or polymeric fabric with hydroxyapatite in order to provide practicable artificial blood vessels.
  • hydroxyapatite are that the said coating adsorbs albumin in the blood on contact and exhibits an excellent anti-clot characteristic, and that its excellent biological
  • hydroxyapatite may erode and disappear over a period of time after transplantation, and that, if the thickness exceeds 10 ⁇ m, its flexibility decreases significantly.
  • the range of the Ca/P ratio is limited to either 1.1 - 1.5, preferably 1.3 -1.4, or 1.75 - 2.5, preferably 1.8 - 2.2. This is base on the following. If this ratio is below 1.1, the peak for hydroxyapatite crystal in the thin film X-ray diffraction almost disappears. If it ranges from 1.5 to 1.75,
  • microcracks initiate in the coating formed, which readily lead to separation under cyclic strains encountered in practice. Also, if it exceeds 2.5, the peak for
  • the Ca/P ratio in hydroxyapatite is theoretically 1.67, whereas this ratio in actual living body is said to be about 1.5.
  • the Ca/P ratio in the coating formed in the present invention deviated from the theoretical value promotes formation of calcium phosphate in the microcrystalline or amorphous form in addition to hydroxyapatite, thus preventing crack
  • microcracks greatly affects the bonding strength between polymeric fabric constituting the base material and hydroxyapatite, namely, significantly decreases the bonding strength and the flexibility.
  • polymeric fabric base material and hydroxyapatite coating formed surprisingly, increases substantially. This fact had not been known at all previously.
  • the preferred polymeric fabrics used for the base material is polyester,
  • Polyester is
  • polyester base artificial blood vessel has been successfully used and is more
  • the preferable hydroxyapatite in the present invention is that with a part of its phosphate or hydroxyl group substituted by carbonic group, because in such form it is closer to hydroxyapatite in a living body and has better biological compatibility.
  • the artificial blood vessel in the present invention is prepared as follows.
  • the artificial blood vessel with inner diameter 6 mm made of polyester fabric USCI DeBakey P-005106 manufactured by Bird Co. is used for the base material and the glass powder, which has grain diameters 100 - 600 ⁇ m and the composition presented in Tokkai Hei 2 (1990) -25515, is filled in the said artificial blood vessel.
  • composition of CaO and SiO 2 combined is at least 70 mol%. More than 80% of the glass powder has grain diameters 100 - 600 ⁇ m.
  • composition of the said glass is as follows.
  • the artificial blood vessel filled with the glass powder was immersed in an artificial body fluid A
  • compositions of the artificial body fluids A and B are as follows.
  • a carbonate NaHCO 3 is included in these artificial body fluids. It has been verified that the hydroxyapatite layer formed from such artificial body fluids has a part of its phosphate group or hydroxyl group substituted by carbonic group. Hydroxyapatite in a living body is also known to have carbonic group replacing a part of its phosphate group or hydroxyl group.
  • the Ca/P ratio in hydroxyapatite was controlled by adjusting the ratio of dipotassium hydrogenphosphate/calcium chloride and the hydrogen ion concentration in the
  • the observation of the thickness of hydroxyapatite coating and the cracking were made by a scanning electron microscope.
  • the Ca/P ratio was measured by a polymer microanalyzer.
  • the tube fatigue tests were performed as follows.
  • the artificial blood vessel coated with hydroxyapatite was fixed inside an elastomer tube with the inner diameter 7.6 mm and the length 150 mm and this tube was placed around a pulley so that it was subjected to repeated 90° bending.

Abstract

Artificial blood vessels having significantly improved anticlot characteristic and function, particularly for small-diameter artificial blood vessels. The artificial blood vessels, made of polyester, polyacrylonitrile or polyurethane, have their inner surfaces coated with 1 - 15 νm thick, preferably 3 - 10 νm thick, hydroxyapatite. The hydroxyapatite in the coating has a calcium atoms/phophorus atoms ratio either in the range of 1 - 1.5, preferably 1.3 - 1.4, or in the range of 1.75 - 2.5, preferably 1.8 - 2.2.

Description

Artificial Blood Vessel
Technical Field
The present invention pertains to artificial blood vessels, more specifically to artificial blood vessels which have significantly improved anti-clot characteristic and function well as small-diameter artificial blood vessels.
Background Art
Many patents on the artificial blood vessel have been applied and lively presentations and discussions have been continued at the conferences, etc. However, it is the artificial blood vessel of polyester fibers (Dacron) by DuPont woven in the tubular form and the artificial blood vessel of drawn out polytetrafluoroethylene that have been practically used in medical field.
These two share the market and use of other artificial blood vessels has been limited to exceptional circumstances or laboratory studies. Generally, for the large artificial vessels with diameters 8 - 36 mm, the use of the artificial blood vessel made of Dacron fabric is predominant, which has become a synonym for artificial blood vessel.
There are several methods of weaving fabrics used for artificial blood vessels, which are roughly divided into two types, namely, the plane weave and knit (meias). Blood leaks at the time of the transplantation and the seam must be closed with the blood itself or a fibrin glue. On the other hand, since pseudo intima is formed on the inner surface and it has a long-term advantage that it stabilizes with time. However, the formation of pseudo intima tends to decrease the inner radius and therefore it has not been widely used for small artificial blood vessels.
For the artificial blood vessel made of the drawn polytetrafluoroethylene, no initial blood leakage occurs, but it has a disadvantage that the pseudo intima does not develop on the inner surface as readily. Therefore, in the long run, it is inferior to the Dacron fabric artificial blood vessel with respect to the biological compatibility including anti-clot characteristic. Nevertheless, it is often used for the artificial blood vessel with smaller diameters because the inner opening is more easily
maintained because of the less pseudo intima.
Another unique example of artificial blood vessels was introduced in Science and Medical Applications of
Hvdroxyapatite. JAAS. 1991, pp. 185-189, TAKAYAMA Press System Center Co., Inc. However, this sintered
hydroxyapatite is a brittle ceramic with extremely large elastic moduli and therefore its compliance is substantially different from that of actual blood vessel. Therefore it is valuable in laboratory study, but will not readily provide practical artificial blood vessels.
Disclosure of Invention
At present, for large artificial blood vessels with inner diameters greater than 8 mm, the artificial blood vessels available on the market pose no apparent
difficulties. However, for small artificial blood vessels with 3 - 6 mm inner diameters, while many researches have been published, none of them have produced artificial blood vessels with satisfactory performance.
The primary reason for this is that there are the following two fundamental problems.
(a) Artificial blood vessels which have initially superior anti-clot characteristic at transplantation develop the pseudo intima slowly or does not develop it at all, thus the proportion of artificial blood vessels which remain open for a long period of time is small. On the other hand,
artificial blood vessels which have poor initial anti-clot characteristic stabilize over a long period of time if the blockage does not occur at the beginning. However, the blockage often occurs due to the initial blood clotting and consequently, the proportion of artificial blood vessels which remain open is also small. (b) The blockage often occurs due to the thickening of the intima at anastosis, which develops several months after transplantation.
The inventor of the present invention, after
concentrated efforts to resolve these difficulties,
discovered that (1) Hydroxyapatite adsorbs a large amount of albumin among proteins in the blood plasma. It is a common knowledge among researchers that the layer of albumin adsorption exhibits excellent anti-clot characteristic.
(2) The less biologically compatible the artificial base material is, the more thickening of intima at anastomosis develops several months after transplantation.
On the basis of these discoveries, it is expected that hydroxyapatite which has proven excellent biological
compatibility can be used for artificial blood vessels, and the use of hydroxyapatite for artificial blood vessels was introduced in the said literature. However, as previously described in the section of Existing Technology, when the artificial blood vessel is made of hydroxyapatite itself, such artificial blood vessel is not satisfactorily used in practice. The inventor therefore continued the research and developed the process of coating polymeric fabrics with hydroxyapatite, which lead to the present invention.
The methods for hydroxyapatite coating have been disclosed in many publications. Among them are: the
sintering process in tokko Hei (1990) 13580; the plasma spray process for metallic implant materials in Tokko Sho 58 (1983) -50737; the plasma jet process for ceramic core materials in Tokko Sho 59 (1984) - 46911, Tokkai Sho 62 (1987) - 34539, Tokkai Sho 62 (1987) 57548, Tokkai Sho 63
(1988) - 46165 and others; the sputtering process in Tokkai Sho 58 (1983) - 109049; the flame jet process in the
Proceedings of the Japan Ceramics Society 1988 1st Fall Symposium, reprint, pp. 401-402; the glass frit baking process in The Proceedings of the 9th Conference of
Miomaterials Society (reprint, 1987, p. 6); the electrophoresis process in The Japan Ceramics Society. 1988, pp. 417-418; and the processes to precipitate hydroxyapatite from an artificial body fluid composed of ions of the same type and concentration as those in human blood plasma in Tokko Sho 61 (1986) - 10939, Tokko Hei 1 (1989) - 54290 and Tokkai Hei 2 (1990) -255515.
As described above, various techniques for the
hydroxyapatite coating have been published. Nevertheless, there remain many problems to be resolved, which include: (a) The plasma jet process requires sophisticated and expensive equipment, and yet it does not readily produce fine coating and forms coating of apatite which is different from the apatite in the body because the source material, hydroxyapatite, is once melted at high temperatures.
(b) The sputtering process requires sophisticated and expensive equipment and forms coating of apatite which is different from the apatite in the body because
hydroxyapatite, the source material, is once melted at high temperatures. (c) The sintering and glass frit processes require heat treatments at temperatures 850°C or above and therefore can be applied only to base materials with high heat resistance and may form coating of apatite which is different from the apatite in the body because
hydroxyapatite, the source material, is once treated at high temperatures.
(d) The electrophoresis process can be applied only to metallic base materials with good electric conductivity because it uses the base material itself as an electrode and also forms coating of apatite which is different from the apatite in vivo because it uses sintered apatite as the source material.
(e) The process of precipitating hydroxyapatite from an artificial body fluid has a handicap that no base materials, other than CaO/SiO2 base glass, which provide a good bonding with hydroxyapatite generated have been found. As an example of the methods of (e) above, a process of coating polyester fabrics with hydroxyapatite has been published in Kinzoku (Metals), No. 12, 29-35 (1991).
However, for hydroxyapatite having the calcium to phosphorus atomic ratio (Ca/P) close to its theoretical value 1.67, the bonding strength between such polyester fabric base material and the hydroxyapatite not sufficient and it is known that the bonding is easily separated under an external force and the corresponding strain. Therefore, it is obvious that it cannot be used for an artificial blood vessel in a living body where it is certainly subjected to repeated strains.
The present invention is intended to resolve the difficulties in the existing technology described above and to provide artificial blood vessels which have improved anti-clot characteristic and function well as small diameter artificial blood vessels.
In order to achieve the objective described above, the inventor improved the method of (e) and successfully
developed the artificial blood vessel pertaining to the present invention.
That is, the artificial blood vessel developed in the present invention has the following features.
(1) It is composed of the base material of polymeric fabric coated with 1 15μm thick, preferably 3 - lOμm thick,
hydroxyapatite.
(2) The range of Ca/P ratio of 'he said hydroxyapatite is 1.1 - 1.5, preferably 1.3 - 1.4.
(3) Or the range of Ca/P ratio of the said hydroxyapatite is 1.75 - 2.5, preferably 1.8 - 2.2.
(4) The said polymeric fabric is polyester,
polyacrylonitrile or polyurethane, preferably polyester. (5) A part of the phosphate or hydroxyl group in the said hydroxyapatite has been substituted by carbonic group.
The reasons for limiting the base material for the artificial blood vessel in this invention to polymeric fabrics are that their mechanical properties (such as the compliance) required for the artificial blood vessel have already been optimized, that they have been well proven to be safely used in the body, and that it is considered sensible to coat the base material or polymeric fabric with hydroxyapatite in order to provide practicable artificial blood vessels.
The reasons for coating the base material with
hydroxyapatite are that the said coating adsorbs albumin in the blood on contact and exhibits an excellent anti-clot characteristic, and that its excellent biological
compatibility effectively reduces the thickening of intima at the anastomosis.
The reasons for limiting the range of thickness of hydroxyapatite coating in the artificial blood vessels pertaining to the present invention to 1 - 15 μm, preferably 3 - 10 μm, are that, if the thickness is below 1 μm, uniform coating is not reliably produced in practice and the
hydroxyapatite may erode and disappear over a period of time after transplantation, and that, if the thickness exceeds 10 μm, its flexibility decreases significantly.
In addition, in the present invention, the range of the Ca/P ratio is limited to either 1.1 - 1.5, preferably 1.3 -1.4, or 1.75 - 2.5, preferably 1.8 - 2.2. This is base on the following. If this ratio is below 1.1, the peak for hydroxyapatite crystal in the thin film X-ray diffraction almost disappears. If it ranges from 1.5 to 1.75,
microcracks initiate in the coating formed, which readily lead to separation under cyclic strains encountered in practice. Also, if it exceeds 2.5, the peak for
hydroxyapatite crystal in the thin film X-ray diffraction virtually disappears as well.
These behaviors may be reasoned as follows. The Ca/P ratio in hydroxyapatite is theoretically 1.67, whereas this ratio in actual living body is said to be about 1.5. The Ca/P ratio in the coating formed in the present invention deviated from the theoretical value promotes formation of calcium phosphate in the microcrystalline or amorphous form in addition to hydroxyapatite, thus preventing crack
initiation.
The presence of such microcracks greatly affects the bonding strength between polymeric fabric constituting the base material and hydroxyapatite, namely, significantly decreases the bonding strength and the flexibility.
In addition, it was discovered that, when this ratio is shifted to a value greater than 1.67, that is that in the range of 1.7 - 2.5, the bonding strength between the
polymeric fabric base material and hydroxyapatite coating formed, surprisingly, increases substantially. This fact had not been known at all previously.
In the present invention, the preferred polymeric fabrics used for the base material is polyester,
polyacrylonitrile or polyurethane. Polyester is
particularly preferred because the polyester base artificial blood vessel has been successfully used and is more
reliable.
The preferable hydroxyapatite in the present invention is that with a part of its phosphate or hydroxyl group substituted by carbonic group, because in such form it is closer to hydroxyapatite in a living body and has better biological compatibility. Best Modes for Carrying Out the Invention
The artificial blood vessel in the present invention is prepared as follows. The artificial blood vessel with inner diameter 6 mm made of polyester fabric USCI DeBakey P-005106 manufactured by Bird Co. is used for the base material and the glass powder, which has grain diameters 100 - 600μm and the composition presented in Tokkai Hei 2 (1990) -25515, is filled in the said artificial blood vessel.
The ranges of CAO and SiO2 compositions in the said glass are
CaO 20 - 60 mol% SiO2 ....40 - 80 mol%
and the composition of CaO and SiO2 combined is at least 70 mol%. More than 80% of the glass powder has grain diameters 100 - 600μm.
The composition of the said glass is as follows.
CaO .....49.87 mol%
SiO2..... 35.46
P2O5..... 7.153
MgO ..... 7.111
CaF2..... 0.399
The artificial blood vessel filled with the glass powder was immersed in an artificial body fluid A
practically supersaturated with hydroxyapatite for 48 hours The compositions of the artificial body fluids A and B are as follows.
Artificial Body Fluid Artificial Body Fluid A B
NaCl 7 . 996 g 11.994 g
NaHCO3 0 . 350 0.525
KCl 0 .224 0.336
K2HPO4. 3H2O 0.228 0.342
MgCl 0. 305 0.458
CaCl2 0.278 0.417
Na2SO4 0. 071 0.107
1NHCl approx. 45 ml approx. 68 ml
Tris(hydroxymethyl)
aminomethane 6.057 8.086
A carbonate NaHCO3 is included in these artificial body fluids. It has been verified that the hydroxyapatite layer formed from such artificial body fluids has a part of its phosphate group or hydroxyl group substituted by carbonic group. Hydroxyapatite in a living body is also known to have carbonic group replacing a part of its phosphate group or hydroxyl group. After the artificial blood vessel was immersed in the artificial body fluid for 48 hours, the glass powder was removed from the artificial blood vessel and the inside was cleaned. Then the artificial blood vessel was immersed in the artificial body fluid B for 1 week. This artificial blood vessel was removed from the artificial body fluid, rinsed with water and dried. Then it was sterilized by ethylene oxide gas in a sterilizing bag.
The thickness of hydroxyapatite coating was controlled by changing the duration of immersion in the artificial body fluid. Tables I and II summarize the results of the
experiments described above for artificial blood vessels pertaining to the present invention, with various
thicknesses of hydroxyapatite coating.
Figure imgf000012_0001
Figure imgf000013_0001
The Ca/P ratio in hydroxyapatite was controlled by adjusting the ratio of dipotassium hydrogenphosphate/calcium chloride and the hydrogen ion concentration in the
artificial body fluid.
The observation of the thickness of hydroxyapatite coating and the cracking were made by a scanning electron microscope. The Ca/P ratio was measured by a polymer microanalyzer.
The tube fatigue tests were performed as follows. The artificial blood vessel coated with hydroxyapatite was fixed inside an elastomer tube with the inner diameter 7.6 mm and the length 150 mm and this tube was placed around a pulley so that it was subjected to repeated 90° bending. After fatigue loading by rotating the pulley at 200 r.p.m. for 30 minutes, the presence of separation and cracking of the coating was examined by a scanning electron microscope to evaluate the flexibility.
In addition, about 20 mm of pulmonary arteries of grown dogs were replaced by artificial blood vessels, which were removed and observed after 1 month, 2 months and 6 months to evaluate the anti-clot characteristic and thickening at anasomosis.
The features of the artificial blood vessel pertaining to the present invention described above made it possible to provide the artificial blood vessels which have much
superior anti-clot characteristic and function well as a small-diameter artificial blood vessels.

Claims

Claims
1. An artificial blood vessel characterized in that said blood vessel includes a base material made of a
polymeric fabric and a 1 - 15μm thick coating of
hydroxyapatite.
2. The artificial blood vessel described in Claim 1 further characterized in that said coating of hydroxyapatite is 3 - 10μm thick.
3. The artificial blood vessel described in Claims 1 or 2 characterized in that the Ca/P ratio of said
hydroxyapatite is in the range of 1.1 - 1.5
4. The artificial blood vessel described in Claims 1 or 2 characterized in that the Ca/P ratio of said
hydroxyapatite is in the range of 1.3 - 1.4.
5. The artificial blood vessel described in Claims 1 or 2 characterized in that the Ca/P ratio of said
hydroxyapatite is in the range of 1.75 - 2.5.
6. The artificial blood vessel described in Claims 1 or 2 characterized in that the Ca/P ratio of said
hydroxyapatite is in the range of 1.8 - 2.2.
7. The artificial blood vessel described in Claims 1, 2, 3, 4, 5 or 6 characterized in that said polymeric fabric material is polyester, polyacrylonitrile or polyurethane.
8. The artificial blood vessel described in Claims 1, 2, 3, 4, 5, 6 or 7 characterized in that a part of a
phosphate group or a hydroxyl group in said hydroxyapatite has been substituted by a carbonic group.
PCT/US1993/004803 1992-05-20 1993-05-20 Artificial blood vessel WO1993023090A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP4127157A JPH05317408A (en) 1992-05-20 1992-05-20 Artificial blood vessel
JP4/127157 1992-05-20

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EP1887968A2 (en) * 2005-06-08 2008-02-20 C.R.Bard, Inc. Grafts and stents having inorganic bio-compatible calcium salt
US8636794B2 (en) 2005-11-09 2014-01-28 C. R. Bard, Inc. Grafts and stent grafts having a radiopaque marker
US8652284B2 (en) 2005-06-17 2014-02-18 C. R. Bard, Inc. Vascular graft with kink resistance after clamping
US9198749B2 (en) 2006-10-12 2015-12-01 C. R. Bard, Inc. Vascular grafts with multiple channels and methods for making
US9572654B2 (en) 2004-08-31 2017-02-21 C.R. Bard, Inc. Self-sealing PTFE graft with kink resistance
CN107661538A (en) * 2017-11-09 2018-02-06 四川大学 Biomaterial for medical purpose and preparation method with bionical surface structure

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WO2000001716A2 (en) * 1998-07-06 2000-01-13 Karo Bio Ab Vasculoprotector
WO2000001716A3 (en) * 1998-07-06 2000-10-05 Karobio Ab Vasculoprotector
US9572654B2 (en) 2004-08-31 2017-02-21 C.R. Bard, Inc. Self-sealing PTFE graft with kink resistance
US10582997B2 (en) 2004-08-31 2020-03-10 C. R. Bard, Inc. Self-sealing PTFE graft with kink resistance
EP1887968A2 (en) * 2005-06-08 2008-02-20 C.R.Bard, Inc. Grafts and stents having inorganic bio-compatible calcium salt
EP1887968A4 (en) * 2005-06-08 2013-01-23 Bard Inc C R Grafts and stents having inorganic bio-compatible calcium salt
US8652284B2 (en) 2005-06-17 2014-02-18 C. R. Bard, Inc. Vascular graft with kink resistance after clamping
US8636794B2 (en) 2005-11-09 2014-01-28 C. R. Bard, Inc. Grafts and stent grafts having a radiopaque marker
US9155491B2 (en) 2005-11-09 2015-10-13 C.R. Bard, Inc. Grafts and stent grafts having a radiopaque marker
US9198749B2 (en) 2006-10-12 2015-12-01 C. R. Bard, Inc. Vascular grafts with multiple channels and methods for making
CN107661538A (en) * 2017-11-09 2018-02-06 四川大学 Biomaterial for medical purpose and preparation method with bionical surface structure

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