JPS60203264A - Synthetic vessel transplantation tissue coated with collagen - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) This invention relates to synthetic vascular grafts, particularly a series of RJff
plasticized = a vascular graft tissue having a plasticized layer, even if there is no pre-coagulation step (1preCIO1), the transplanted tissue IIR can be made blood-free (blood-free). It is technically sufficient to replace the human blood vessel VJ with @Kin blood vessel transplantation tissue. Accepted.

＠The shape of the ruts has become widespread.

It is also made of various materials. Acceptable and successful vascular grafts are constructed from biochemically compatible materials that, after implantation, maintain an open cavity that allows blood to flow through the synthetic graft. The graft tissue can be made from biochemically compatible fibers such as Dacron and 'l'eflon, and may be knitted or woven, and may be made of monofilament, multifilament or staple yarns. But that's fine.

An important factor in selecting a particular graft matrix is the porosity of the fibrous walls that make up the graft. Porosity is important because it controls the tendency for bleeding during or after implantation and also controls the growth of tissue into the wall of the implant. The vascular graft tissue matrix provides sufficient blood sealing to prevent blood loss during implantation, yet has a sufficiently porous structure to allow fibroblast ingrowth and to bind the graft to the host tissue (
Smooth muscle cells are desirable for attachment to the host tissue. U.S. Patent 3,805,
301 and 4,047,252 are elongated flexible tubular bodies constructed from threads such as Dacron. In the former patent, the implant is a warp-woven tube, and in the latter patent, the implant is a warp-woven tube, and the latter patent uses the trademark Mic.
It is a double velor synthetic graft marketed under the trademark Rovel. These artificial implants have a sufficiently porous structure to allow ingrowth of host tissue.

A common procedure for transplantation involves a precoagulation step in which the transplanted tissue is immersed in the patient's blood and allowed to survive for a sufficient period of time to ensure clotting. After precoagulation, no bleeding occurs when implantation occurs and tissue growth is unrestricted. However, since the precoagulation step takes a considerable amount of time during the surgical procedure, it is desirable to avoid this precoagulation step.

A non-bleedable and absorbable collagen-reinforced implant has already been proposed in US Pat. No. 3,272,204. Collagen of the type disclosed in that patent is obtained from the deep flexor muscles of livestock. The collagen obtained from the flexor vaginalis is generally highly cross-linked and is produced by the enzyme digestion method described in the U.S. patent.
tion procedure) is difficult.

Other Reinforced Vascular Proteasers, Zehohiro U.S. Pat. No. 3.47
No. 9,670, which includes an open-mesh cylindrical tube wrapped with an outer helical wrapping material of fused polypropylene monofilaments, which prevents the prosthetic method from being exposed to bacteria and liquids. Filled with collagen fibrils required to make it impermeable. The collagen fibrils used are US Pat. No. 3,272,204
It is the same as that described in .

Synthetic vascular grafts suggested by the prior art are required to be suitable for many applications. However, it would be desirable to obtain a flexible vascular graft that exhibits essentially zero porosity, which is sufficiently susceptible to host tissue ingrowth, and which is sufficiently susceptible to prior art techniques. It is easier to manufacture than the one shown in .

(Structure of the Invention) A collagen-coated synthetic vascular graft tissue, which is mixed with a plasticizer that makes the vascular graft non-leakage without a step of pre-coagulating blood: y
A biochemically compatible (biocompa
tible), filimentary
) is made from a tube-shaped material with a porous structure. The porous vascular graft substrate may be a tubular vascular graft made from Dacron material and may be woven.
It may also be knitted.

The raw material for the collagen is a highly pure dispersion of fibrils (X-ray, dispersion).
acid temperature 9 so as to obtain
ion ) (Preferably, those obtained from D-treated horse skin.

An aqueous, purified collagen slurry containing a plasticizer is applied to the synthetic vascular tissue by pine surge, which successfully yields a flexible vascular graft. Make sure that it is applied over the entire surface area so that it is visible. After coating and drying the collagen at least three times, the collagen is cross-linked by application of formaldehyde vapor, increasing the porosity of the vascular graft.
The porosity has been reduced to about 1% or less compared to the one before being coated with collagen.

(Problems to be Solved by the Invention) Therefore, it is an object of the present invention to obtain an improved synthetic vascular graft tissue.

Another object of the present invention is to provide an improved non-leakage synthetic vascular graft tissue.

It is a further object of the present invention to provide an improved collagen-coated synthetic vascular graft.

Another object of the invention is to provide an improved collagen coating obtained from bovine hide.

A further object of the present invention is to provide an improved method for producing ff2-gen coated synthetic vascular grafts.

Another object of the present invention is to provide an improved method of manufacturing vascular grafts to coat collagen in a manner that makes them less leaky.

Still other objects and advantages of the invention will be partly apparent from, and partly inherit from, the specification.

SUMMARY OF THE INVENTION Accordingly, the present invention includes laterals and various means having a characteristic and elemental relationship and the relationship of one or more such means to each other, These are exemplified in the detailed disclosure below, and the scope of the invention is set forth in the claims.

A synthetic vascular graft IO constructed and arranged in accordance with the present invention is shown in FIG. The implant IO includes a tubular matrix portion 12 constructed of a biochemically compatible fibrous synthetic material, preferably polyethylene terephthalate such as tiDacrom. Substrate 12 is a porous Dacron warp knit with internal and external velor surfaces as described in US Pat. No. 4,047,252. Tubular portion 12 is constructed of Dacron, but may be made of any biocompatible material that can be made into a porous structure that allows tissue ingrowth and maintains an open cavity for blood flow. Certain fibrous materials can be used for the substrate.

The inner surface of the tubular 11μ section 12 is coated with a collagen coating shown as 16. Collagen cover 16 is
It consists of at least three layers of aqueous collagen fibrils and a dispersion of plasticizer, which are cross-bridged by exposure to formaldehyde vapor.

FIG. 2 shows a bifurcated collagen-covered implant 20. Implant 20 includes a main tubular portion 22 and two branches 24 . The main tubular section 22 and the bifurcated section 24 are constructed from 1) an acron braided matrix 26; The inner surface of the matrix 26 is coated with a collagen coating 28, which is also composed of at least three layers of collagen fibrils.

Porous graft matrices suitable for use in accordance with the present invention are preferably made from Dacron multifilament yarns by knitting or weaving processes commonly used in the manufacture of these products. The porosity of a typical KDacron substrate is approximately 2,000
0 to 3.0001114'/min -ad (12
(purified water at 0 mmHH). The cross-linked collagen inner coating is applied by filling the tubular matrix with a slurry of collagen and plasticizer, hand pine-surging, removing excess and drying the deposited dispersion. After the final application, the collagen coating is
Cross-linked by formaldehyde vaporization,
Air dry and then vacuum dry to remove excess moisture and excess formaldehyde. Implants coated according to the present invention have essentially zero porosity.

EXAMPLES The following examples will be set forth to illustrate the method of preparing purified collagen from bovine skin and coated implants according to the present invention. The examples are given for illustrative purposes and are not intended to be in a limiting sense.

Example 1 Fresh cowhide is mechanically stripped from young calves, fetuses or stillborn calves and washed under cold running water in a rotating container until the water is clear of surface dirt, blood and/or tissue. The subcutaneous tissue is mechanically cleaned to remove contaminated tissue such as fat and blood vessels. Next, cut the skin lengthwise about 12 (M)
It is cut into strips 1.5 liters wide and placed in wooden or plastic containers such as those customarily used in the leather industry.

The skin was washed with a water sink solution of IM Ca (OH Ca) at 25
Removes hair over time. Alternatively, the skin may be depilated by mechanical means or by a combination of chemical and mechanical means. Following dehairing, the skin is cut into small pieces of approximately 111 x 11 dimensions and washed in cold water. - Following cleaning, 120k
li+ cowhide, 260L of water, 2L of NaOH (5o
%) and 0.4 L of HtOt (35%). The ingredients are mixed for 12-15 hours at 4° C. and washed with excess tap water for 30 minutes to provide a partially clarified skin. 26 pieces of partially purified skin
Process for 95 minutes at slow mixing speed in a solution of 0 L water, 1.2 L NaOH (50 g) and 1.4 U CaO. This treatment was continued twice a day for 25 days. Following this treatment, the solution was decanted and the skins washed with excess tap water for 90 minutes with constant stirring.

The skin is heated to 14kl while being subjected to strong agitation. MCI of.

(35%) and acidified by treatment with 70 L of water. The acid was allowed to penetrate the skin for approximately 6 hours. The skin is acidified and then soaked in excess tap water for about 4 hours or -5
．． It was washed until it became 0. The - of the skin was readjusted to 3.3-3.4 using acetic acid containing 0.5 T of preservative. The purified skins were then pressed through a grinder and through a series of filter sieves of constantly decreasing mesh size.

The final product was a white homogeneous smooth paste of collagen derived from pure cowhide.

A plasticizer is added to the collagen slurry prior to application in order to give the implant proper flexibility in the dry state. Suitable plasticizers include glycerin, sorbitol or other biochemically acceptable plasticizers. Approximately 0
．． In the Collagen slurry containing 5 to 5.0 weight percent collagen, the plasticizer is present in an amount of about 4 and 12 weight percent.

According to the present invention, synthetic vascular graft tissue can be synthesized with collagen fibrils (
Among the most important properties obtained when coating with collagen fibrila) is the reduction of the porosity of the porous substrate to almost zero. 2 randomly selected
The porosity of the uncoated Microvel Dacron synthetic vasculature of 0 is 12 with a standard deviation of 130.
It has an average porosity for purified water of 17961 M/m1n-di at 0 mmHg. After applying several collagen coats, the porosity lines were reduced to zero.

The following example describes a method of coating a graft matrix.

A Komata 50CC syringe is filled with two volumes of an aqueous slurry of purified calfskin collagen prepared according to Example 1. Collagen slurry is 8 tiglycerol.

Contains 17% ethanol and residual water, 30,000e
It has a viscosity of pH. The syringe is a Meadox Medical syringe with a diameter of 8 mm and a length of approximately 12 crIL.
Microvel Dacron implants are placed in m-. The slurry is injected into the cavity of the Microvel implant and manually mussed to cover the entire inner surface area with the collagen slurry. Excess collagen slurry is removed through one of the open ends. The graft can be dried for about 1/2 hour at room temperature. The coating and drying procedure was repeated three more times.

Following the fourth coating application, the collagen coating was cross-linked by exposure to formaldehyde vapor for 5 minutes. The crosslinked grafts were then dried for 15 minutes to remove moisture and excess formaldehyde and then vacuum dried for 24 hours.

Example 3 The hemorrhea of the collagen-coated vascular graft prepared according to Example 2 was tested as follows.

Microvel graft 8 m x 12 crn was attached to the blood container at a pressure of 120 m Hg due to the height of the container. Blood stabilized with heparin (eparin, ) was passed through the graft and the blood collected through the graft was determined and expressed as rtt per m1n-d. Porosity over 5 runs was 0. 04,0
．． It was determined to be 0, 0.0, 0.04 and 0.03. This showed an average porosity of 0.22111 Vmin-, which was considered zero as the value was within the experimental error of the study.

To compare this result with blood loss for uncoated Microvel implants, the experiment was repeated using uncoated implants. Average porosity is 36''/m1
It was n-crl.

The porosity of knitted implants coated with flat collagen was determined after three coatings (of the uncoated implants), as described below.
reduced to less than about 1 percent. The standard water porosity test used to measure the water porosity of implants is as follows. A column of water equivalent to a pressure of 120 van 14 g is allowed to flow through a 1/26 rl orifice with a swatch of implant tissue over the oriice in 1 minute. The amount of water collected was measured. The milliliter of water collected per minute was calculated as the area squared. Separate readings were taken for each specimen. The porosity is reported as:
Porosity = 4/min/di The water porosity of the Microvol graft knit is approximately 1.90
It was 0ψ'min/ffl. The porosity after coating was as follows.

No. of Coating Porosity 0 1.900 1 266 2 146 3 14 5 2 0 In each case - the collagen coating was a plastic slurry derived from cowhide prepared according to the composition mentioned in Example 2; The results are shown in Figure 3. Based on these results, it is desirable to have at least three (or four) layers of fibrils.
Most desirable are four or five layer collagen coatings with drying between each application and cross-linking to anchor the coating to the substrate.

In addition to reduced porosity, implants coated with co2-gen according to the invention exhibit reduced thrombogenicity compared to uncoated implants.

The example below shows that vascular grafts impregnated with collagen have a higher thrombogenicity than normal grafts.
icity) is small.

Example 5 Imai and Nok (J, Biomed, Mate
Res, 6°165, 1972).
ty) was evaluated in a test tube test. In this test method, an amount of 0.25 rat of ACD blood is
．． 25u of 1m calcium chloride! Collagen-coated Microve prepared according to Example 2 above, mixed with
1 placed on the inner wall of the tube of the vascular graft tissue. As a standard means of comparison (control standard) in this type of test, an identical amount of the sample was prepared using M without collagen coating.
It was placed on the inner wall of the tube of the icrovel vascular graft tissue. 5 seconds.

After 10 and 15 seconds, blood spots were seen appearing in the same location. This blood coagulation reaction was stopped by adding 5-distilled water to the test piece. A surprising difference appeared between the two vascular grafts, which was confirmed by the semi-quantitative parameters described below.

Thoroughly impregnated with ordinary collagen (control standard) A specimen of vascular graft tissue is immersed in blood Rapidly Slow rate Thrombus formation 5 seconds 0 ++ 10 seconds + +++ 15 seconds ++ ++++ +++ Gen A comparison of thrombus formation on the inner wall surface of the tube between the Microvel vascular graft tissue sufficiently impregnated with the following will be described below and a control vascular graft tissue.

For 5 seconds, the one soaked with collagen will absorb the fibrous proteins (fab) that are formed during blood coagulation.
No coagulation of rinphapurin occurred.

Both the one fully soaked with collagen and the control one had a much smaller amount of fapurine coagulation.

When blood was dropped onto the surface of the Microvel vascular graft, it exhibited an almost hydrophobic state.

It took approximately 10 to 15 seconds for the blood to soak into the Dacron woven vascular graft fabric. Vascular graft tissue matrix (
The contrast between blood-filled, collagen-soaked vascular grafts immersed in matrix and the control is clear, one slow and the other fast.

After 5 seconds, no residual thrombus was found in the one that had been fully soaked with collagen. In contrast,
In the normal control, a thin but distinct thrombus was observed after the same 5 seconds. After 10 seconds and after 15 seconds, there was a significant difference in the total amount of thrombi on the inner wall surface of the tube of the vascular graft between the collagen-coated tissue and the normal control. There are significantly fewer of them.

According to the observation in the above-mentioned test tube test, the collagen-coated [acron] membrane was rapidly immersed in blood without blood flowing through the vascular graft tissue.
In the arovel vascular graft tissue, no thrombus forms within 5 seconds. In contrast, thrombi were observed in the control vascular graft tissue. 10
After seconds to 15 seconds, the amount of blood clots was lower in the collagen-impregnated product than in the regular Dacron product.

Example 6 Microvel impregnated with collagen
) Vascular grafts were tested in vivo (dogs) as follows. femoral artery and vein
) (AV) minute Rf, (5hunt) was attached to the gray bound under deep anesthesia. A length of 5 crIL of prosthetic material was applied at both ends with 2 stiff conical tubing materials for better handling. As a result, the test vascular graft could be easily inserted into the arterial branch. After insertion, the venous forceps were gently removed and the arterial end was then gently released. Blood was allowed to circulate through the graft for 10 or 30 minutes. Next, both ends of the shunt were clamped again and the inserted prosthesis was removed. Excess blood was removed and weighed.

Adhesion of thrombi to the surface of the vascular graft tissue was observed with the naked eye. The vascular grafts were then washed with excess water (3 times) and weighed again.

As a control, a standard 6 m diameter Dacr
On) Micropel vascular graft tissue was used.

This vascular graft is pre-coagulated (
pre-clot). Therefore, this test revealed thrombus formation on the test surface visually and objectively. The weight of blood oozing through the vascular graft was also measured to document differences between the samples tested.

No bleeding was observed in the collagen-impregnated vascular graft tissue.

When a pre-coagulated control vascular graft was inserted into the AV branch, an average of 30 g of blood was lost in the first 5 minutes with a 5 crIL length of vascular graft. Blood loss over the next 5 minutes was only 3-5 d. In one of the control vascular grafts tested for 30 minutes, minimal bleeding of 1 d/min 15 cIL through the pre-coagulated vascular graft continued throughout the entire study.

Collagen-impregnated vascular grafts inserted for 10 or 30 minutes showed the same pattern of resistance to macroscopic thrombus formation. A smooth thin layer of shimmering protein material covered the collagen layer. After repeated washing with distilled water, a continuous film of protein (fibrin) was found in most of the prostheses. No apothecary-like blood clots were observed in the prosthesis samples.

Of the five pre-coagulated plain Dacron vascular grafts tested, three had distinct multiple thrombi. These occurred across the circumference 173 to 172 and across the direction of blood flow. The two remaining prostheses had a similar thin protein layer covering their inner surfaces. Each control vascular graft had a large thrombus due to continuous bleeding from the wall.

These observations showed that collagen-impregnated Dacron vascular grafts had significantly less thrombus formation than pre-coagulated control vascular grafts.

This is thought to be because thrombus formation was reduced in the collagen-coated tissue, or because thrombi were formed in the control vascular graft tissue because precoagulation was required. Blood clots are caused by excess cells and fibre-replacement bodies (fib
(rotic replacement), thereby reducing thrombus formation within the matrix of Dacron vascular grafts;
It has the advantage of lowering the risk of embolism.

In accordance with the present invention, by coating a plasticizer layer and at least three layers of collagen fibrils onto a synthetic porous vascular graft material, the vascular graft can be surgically applied to a human patient as a blood vessel. If you include it, you will get the desired improvement. A further, non-limiting advantage of the present invention is that it eliminates the need for precoagulation.

Conventional porous vascular grafts require long-term pate
However, in order to prevent excessive blood loss during transplantation, it is necessary for the surgeon to precoagulate the vascular graft with the patient's blood. In many cases, precoagulation is time consuming and requires skill. Therefore, the main purpose of collagen coating is to
There is a need to completely eliminate the need for pre-coagulation of synthetic vascular grafts.

Porous synthetic vascular graft tissue materials provide an ideal matrix for tissue ingrowth and can eliminate the need for precoagulation.

Additionally, collagen-impregnated synthetic vascular grafts exhibit significantly less thrombus formation, thereby reducing the risk of embolism. Coating a synthetic vascular graft material with a slurry of collagen and plasticizer in accordance with the present invention to form a series of coatings can result in a vascular graft that retains its plasticity.

It is therefore seen that the foregoing objectives, those of which are made clear from the foregoing description, are effectively achieved, as set forth herein and without departing from the spirit and scope of this invention. Since certain modifications may be made to the apparatus, all matter contained in the above description and shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense.

It goes without saying that the claims are intended to cover all the general and specific features of the invention described herein and the full scope of the claimed invention contained therebetween as a matter of language. Nor.

In particular, references to components or compounds recited in the singular in the claims above are, of course, intended to include compatible mixtures of such components, wherever the meaning permits.

Examples of the present invention will be listed below for the sake of clarity.

(1) A synthetic vascular graft consisting of a tubular, flexible, porous graft substrate, the graft substrate having at least three layers of collagen on at least the inner wall of the tube. The cross-linked coating of the fibril layer (crosu+ −
1 inked coating), and the collagen fibrils are coated with a sufficient amount of plasticize to render the implant non-bleeding and flexible.
Synthetic vascular graft tissue (2) characterized in that the porous graft tissue substrate is a mixture of polyethylene and
(3) The synthetic vascular graft tissue according to item 2, wherein the porous graft tissue substrate is knitted (4) The porous graft tissue is terephthalate. (5) The synthetic vascular graft tissue according to item 2, wherein the tissue substrate is plain-woven. (5) The synthetic vascular graft tissue according to item 1, wherein both the inner and outer surfaces of the graft tissue substrate are velor surfaces. Vascular transplant tissue (6) The collagen fibril
) The synthetic vascular graft tissue of claim 1, which has been cross-linked by exposure to formaldehyde vapor (where the plasticizer is biochemically compatible). (8) The synthetic vascular graft tissue according to item 1, wherein the plasticizer is polyhydric (9) The plasticizer Synthetic vascular graft tissue OQ according to paragraph 1, wherein the agent is glycerin.
0% (by weight) collagen fibrils and about 4 to 1
Synthetic vascular graft tissue according to claim 1, wherein said synthetic vascular graft consists of a deposited aqueous slurry of 2 g (by weight) of plasticizer; and wherein said collagen fibrils are obtained from bovine hide. Synthetic vascular graft tissue (13) Synthetic vascular graft tissue u3 according to item 1 above, in which both the inner and outer surfaces of the tube of the vascular graft tissue are coated Production of a non-blood leakage synthetic vascular graft tissue with collagen nuclide The method includes preparing a porous, tubular, flexible synthetic vascular graft tissue substrate, and applying an aqueous slurry of collagen fibrils and a plasticizer to at least the inner wall surface of the tube of the graft substrate. the collagen fibrils to ensure a tight bond with the collagen fibrils within the porous tissue, dry the collagen, and then A second layer of collagen and a plasticizer is placed on top of the first layer of the transplant tissue substrate, which is then dried; Once there is a third layer, this is dried and the collagen coating is then cross-linked by exposure to formaldehyde vapor to remove excess formaldehyde. , a method for producing a synthetic vascular graft tissue, characterized in that it is removed by vacuum drying ■ about 0.4 to 5.0% collagen fapril;
A slurry of collagen fabrils for forming a non-leak synthetic vascular graft consisting of 4.0 to 12.0% biochemically compatible plasticizer and water for balance ( +51 Slurry 1G according to item 14, wherein the collagen fabrils are obtained by acid digestion of bovine skin.+ The plasticizer is selected from the group consisting of umbitol and glycerin. Slurry (17) according to item 14 above: A synthetic vascular graft tissue consisting of a tubular, flexible, porous terephthalate graft substrate, the tube inner wall surface being cross-linked and mixed with a plasticizer. coating of at least five layers of collagen fibrils, said at least five layers comprising about 1.5 to 4.0% by weight collagen fibrils and about 6 to 10% by weight plasticizer. A synthetic vascular graft made from an aqueous slurry containing a

[Brief explanation of drawings]

For a better understanding of the invention, reference to the accompanying drawings is provided.
I will explain the following. That is, FIG. 1 is a front view, partially cut away, of a collagen-coated synthetic vascular graft fabricated according to the present invention, and FIG. 2 is a cross-sectional front view of a branch branch of the type shown in FIG. FIG. 3 is a front view showing a partially cutaway cross-section of a certain tubular vascular graft tissue, and FIG.
3 is a graph showing that the porosity decreases as the porosity increases. (IQI is a synthetic vascular graft tissue (121 is the tubular matrix portion 141 is the velor outer surface (16) is collagen coated; Medtux Medicals, Inc. 1, "No changes to the soup 1\inside" FIG, / FIG, 2 1'21 "1 s i 15; 0? IOd No V procedural amendment (voluntary) ) November 1, 1985 Director-General Gakudon Shiga 1, Indication of the incident 1985 Patent a@/da S9 Ko No. 2, Name of the invention Collagen-coated synthetic vascular graft tissue Medtux Medical Zu-Incoholated 4, Agent 2-9-5 Shinbashi, Minato-ku, Tokyo, Amended Order No. 1, 1925, Month, and Day Attached Sheet P Procedural Amendments (9 Issues) Showa 1.a, α On February 2nd, Mr. Manabu Shiga, Commissioner of the Japanese Patent Office1, Indication of the 1985 Patent 11II@/DaS?-2, Name of the Invention: Collagen ν4ia Synthetic Vascular Graft Tissue Medx Medicals, Inc. 4. Agent 5, date of amendment order 7, contents of the amendment attached to the OAR, and supplemented the specification signed by I Eve (there is no epicenter in the contents). Procedural amendment (spontaneous) Patent dated Q.30, 1985 Mr. Manabu Shiga, Commissioner of the Agency, Indication of the case 1985 Patent No. 1 Da S9-2, Name of the invention: Collagen nuclide synthetic vascular transplant tissue Medx Medicals, Inc. 4, Agent Attachment 1% FF Claim (1) A synthetic vascular graft tissue comprising a tubular, continuous, porous graft matrix. There is a cross-linked NFC coating of three collagen fibril layers, and the collagen fibrils make the transplanted tissue non-bleeding and 1'.
Synthetic vascular graft tissue whose flexibility is achieved by a complete mixture of optical lfr plasticizers and agents (2) A method for producing a collagen-type synthetic vascular graft tissue that is non-subdish-like, In this step, a porous, tubular synthetic vascular graft tissue substrate is prepared, and at least the inner wall surface of the tube is coated with collagen fibrils and IfJ! The iU agent is placed in an aqueous slurry, applied to the transplant tissue substrate, and pine surged to maintain a tight bond with the collagen fibrils within the porous tissue, and the collagen is dried. 1. Next, a second layer of collagen and plasticizer is applied on top of the first layer of the graft matrix and then dried;
Furthermore, a third layer of collagen and plasticizer is applied on the transplant tissue substrate, and then this is dried for 11i. A method for producing a synthetic vascular graft tissue, characterized in that the tissue is cross-linked by exposure to the vapor of the Kolaken Hinoki & YK, 7-olmaldehyde, and the formaldehyde and all the formaldehyde are removed by drying. (1) Akira at page g, line 6, coq, negative line 2, line 15, line 77, @page 25, line 6, i. Row, @l1 row, C] λth row, 7th row, 3rd row, and 4th row
Line 7 “Blood coagulation” Let’s say “Coagulation” 〇(2) 5th e4th q
Set the row's "persistence" to "keep". (3) 7th negative qth line and 3rd line ``Prosthesis method'' total 170 theses''. (41Fgff 6th line, 1i negative 1st o line, 1st/Sada line S, 3rd line, q negative q line, 17th line, 0th first line, 12th line, 75th line Line, 37th Liao, 12th line, 75th
1 to 16 lines, silk 77 lines 1. The [Kolaken fibrils] in lines 7 and 70 of ig3λ are all referred to as ``collagen fibrils''. (5) "Porous" in the 7th line of gro AA', the 70th line, the 1st column of the 1st page, the silk/S line, the 1st g line, and the 30th 1st + line of "Porous". "porous". (6) Change the “porosity” of the 9th negative 7th line and the g to 9th lines to “
"porosity". (7) In the 1st O negative rows 10 to 11, "element...-has" is changed to "regarded by the element." (8) Same last line, 1st/Sada line S and 12th negative first line “
``Porousness'' is changed to ``porosity''. (9) Change "according to the present invention" in the first column to "of the present invention". (Iu same number, line 3 and 13th negative line 10 “usually 1”
is "normal". [11 12th corner @S to 6th line, @16th line, 1st S negative @l
Co row, 13th row, 1f row, 77th negative row 5-6, 3rd row, 12th row, is row, 1g row, 1q row and 19th row [porosity] J? [-r porosity]. +121 Page 12, line 7, line 13, 16th negative line “Crosslinking” (131g/3 “Water” in line 6 is changed to “water”. u418g/j, II No. S Let “lλ” in the line be “between 12”.b “Porous…porous” in the same line 7
"porosity". (181, page 21, line 1O ← plaster ÷ and the 22nd negative line g, "taste J'krmmi". a9 23rd negative line 12, @2tavsax line, 6th line, 2S negative @ λ row, "Control vascular graft tissue" t [Control standard vascular transplant f211 2nd 5 negative 7th row "Significant" in row λ, 6th row and 9th row is "clear". "Matric" in C12m2t, 7A11iLiq row ``Matrix.'' Mu @Kokukaku Lines 12-13, ``Includes 1n...cover'' t ``Includes 100'' complete description of the scope of the invention t
"Cover". 24+ In the same line 75, "by the way" is tr. 1251 FIB page 29 line 6 [1inke J f
r 1inkJ and 3-ru. 4 Same number? 1 of the rows is ``polyvalent'' and ``polyhydroxyl''. c! 71 N430*a, line 9) r hole x-・T J
? r "porous and tubular". (2) During the brief explanation of the drawings, the ``porosity'' of the 33rd negative first ladle will be referred to as the ``shoulder porosity''. Procedural amendments (9) 1985 6θ≠Mon 30 Manabu Shiga, Director General of the Patent Office 1, Indication of the case 1985 Patent specification Mida S9 Ko No. 2, Name of the invention Synthetic blood vessel of collagen nuclide #I! Organization Medtux Medicals, Inc. 4, Agent 2-9-5-5 Shinbashi, Minato-ku, Tokyo Date of amendment order: Month, Day 6, 1939, Subject of amendment

Claims (1)

[Scope of Claims] A composite dish/θ graft tissue consisting of (II tube-shaped, flexible, porous graft tissue substrate + graft 5 substrate), wherein the graft vessel 1 green. At least the inner wall 1111 of the tube is coated with σ and at least three collagen-fibril layers.
s-11nkelcoating) is meji. RTN force)'%) The collagen fibrils are a general term for the transplant, non-bleeding, sterile, and extremely light.
(Plasticizer) 1 & Transplant Kumijo (2) It is a method of manufacturing a non-nematotic, Phragesi-grade plate @Adulting Nurse $ 1 tissue, and its process. a. A porous tube-shaped '5J flexible vascular graft tissue base was prepared. An aqueous slurry of % collagen fibrils and an agent is applied to at least the inner wall surface of the tube of the skeleton transplanted tissue base, and the collagen fibrils are tightly bonded within the porous tissue to the transplanted tissue base). Then, dry the kolaken by massaging it so that the kjii stand is preserved. The first oil layer of the transplanted M3 woven substrate was coated with Koshiken and -[
After cutting it into a second layer, dry it.
Furthermore. A third layer of Kolaken and a cleaning agent is applied on the #planted substrate, and this is dried to a temperature of 0 cK. The skeleton collagen ms't-, depending on exposure to formaldehyde vapor, is cross-linked (1 cross-1 ink). A patented method for producing synthetic vascular graft tissue that removes excess formaldehyde through vacuum drying.