JP2005124959A - Low blood permeable medical material - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a fiber medical material reducing blood leakage from fiber clearances. <P>SOLUTION: This medical material has ultrafine fibers of 0.5 dtex or less at least in a part of the fiber clearances inside the wall. This medical material has a value of a ratio Q=WP/BP of a coefficient of water permeability: WP (ml/cm<SP>2</SP>, 60sec.) to a coefficient of blood permeability: BP (ml/cm<SP>2</SP>, 30 sec.) is 6 or more. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a low blood permeability medical material. More particularly, the present invention relates to a low blood permeability medical material that is used in a case where a fiber cloth is in contact with blood, and blood leakage from the fiber gap is caused by easily forming a thrombus in the fiber gap. The present invention relates to a low blood leakage medical material that can reduce the amount. The medical material of the present invention can be suitably used particularly for patch materials and artificial blood vessels used for blood vessel walls or heart walls.

  Conventionally, as a design philosophy of a medical material that hardly leaks blood, “a method of preventing blood leakage by providing a structure that does not allow blood to penetrate into the cloth” has been adopted. However, in order to obtain a structure that does not easily soak in blood, it is naturally necessary to weave the fibers densely. Thus, when the fibers are densely woven, it is unavoidable that the individual fibers are in a finely packed state and the resulting cloth is hard like a tent cloth. When using such hard cloth artificial blood vessels, it is necessary to fix an artery that has been calcified due to arteriosclerosis or an arterial wall that has become thin and brittle due to an aneurysm. Is often difficult.

  Under such constraints, the development of artificial blood vessels that achieves as much flexibility as possible and reduces blood leakage by devising the way of weaving and knitting artificial blood vessels has been carried out. It was.

  The medical material made of fiber with only blood leaking less blood can be classified into “knitted” tissue and “woven” tissue from its basic structure. Among these, the former (knitted structure) has a feature that the manufacturing process is simple and has flexibility, but in addition to its weak shape maintaining ability, it tends to have a porous structure, and blood may leak from the fiber gap. Therefore, an artificial blood vessel of a knitted tissue is used as an artificial blood vessel or the like used for repairing an artery or the like at the periphery of a limb, which is a portion where life is not immediately jeopardized even when blood leaks.

  On the other hand, the latter (woven structure) can reduce the degree of the porous structure as compared with the former, and the fiber gap can be reduced to make it difficult for blood to leak. It is used. In addition to the woven structure and the knitted structure, a non-woven structure exists, but the non-woven structure is not used in a place where blood pressure is applied due to the non-uniformity of the structure and the instability of maintaining the shape.

  In order to estimate the degree of blood leakage of a medical material made of fiber, the total amount of fiber gap is used, and generally an index expressed as water permeability (porosity) or porosity (Void content) is used. It is done. Among these, the former (water permeability) is common, and the measurement method is also described in the American FDA artificial blood vessel guideline. (Guidance for Industry and FDA Staff. Guidance Document for Vascular prostheses 510 (k) Submissions, U.S. Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health, Document issue. On: November 26, 1999)

This water permeability is expressed by the amount of water applied with a pressure corresponding to 120 mmHg per minute through the fiber gap of a cloth having a width of 1 cm ² . For artificial blood vessels having a woven tissue, products having a water permeability of 50 ml to 500 ml are usually used. For artificial blood vessels having a knitted structure, the water permeability is usually between 800 ml to 2000 ml, especially 1200 ml to 1500 ml. Degree products are common. Therefore, since the fiber gap is narrower in an artificial blood vessel having a water permeability of 100 ml than that in an artificial blood vessel having a water permeability of 1500 ml, blood leakage is small. However, since the fiber gap is narrow, according to the knowledge of the present inventor, cell intrusion into the gap is also reduced, and the ease of integration of the fiber and the biological tissue, that is, the biocompatibility tends to decrease. is there.

  On the contrary, if the fiber gap is wide (that is, if the water permeability is high), it has a wide fiber gap. Therefore, when implanted into a living body, cells enter the fiber gap, and the tissue and fiber structure. Are easily integrated, and the fiber is expected to be stabilized in vivo for a long period of time. Therefore, such materials are used for medical materials that are implanted for a long period of time.

  As described above, a tissue with a high water permeability, that is, a cloth with a wide fiber gap is selected in an area where there is little risk of bleeding for the purpose of in vivo integration of a living tissue and a fibrous medical material. Yes. However, having a wide fiber gap also has the disadvantage that blood easily leaks. Therefore, an artificial blood vessel having an appropriate water permeability depending on the part of the body is used under the conflicting condition that the water permeability is low enough not to leak blood and the fiber gap is wide enough for cells to easily enter. Choosing to do has been done more commonly than before.

  However, in reality, no matter how low the water permeability is, blood pressure is somewhat high in the living body, so it is inevitable that blood leaks from the fiber gap. Therefore, when using a cloth artificial blood vessel for vascular surgery, the artificial blood vessel is brought into contact with blood immediately before implantation, and a blood clot is artificially created in the fiber gap, and the fiber gap is temporarily clogged by this thrombus. The preclotting of porous arterial is mostly done by so-called preclotting (Yates SG, Barros AAB, Berger K, Fernandez LG, Wood SJ, Rittenhouse EA, Davis CC, Mansfield PB, Sauvage LR. prostheses. Ann Surg 1978; 188: 611-622.)

  However, since recent vascular surgery often uses heparin to prevent blood clotting, clogging due to pre-clotting is often incomplete, and thus post-surgery due to blood leakage. A dangerous situation of massive bleeding can also occur. In addition, if fibrin produced by pre-clotting begins to dissolve due to the fibrinolysis phenomenon, which is a natural phenomenon after surgery, the thrombus tissue is easily dissolved, so that a large amount of hemorrhage that is life-threatening after surgery (Sauvage LR, Berger K, Wood SJ, Sameh AA, Wesolowski SA, Golaski WM, Dedomenico M, hartmann JR. A very thin, porous knitted arterial prosthesis: experimental data and early clinical assasement. Surgery 1963; 65: 78-88. (Wuerfein RC, Campbell GS. Analysis of preclotting technique for prosthetic arterial grafts. Ann Surg 1963; 29: 179-182.)

  In consideration of the above-mentioned tendency, in medical materials used for aortic or heart surgery that uses heparin in large quantities (in addition to the above-described methods of knitting and weaving the fibers themselves), blood leaks to some extent. Even if it is a cloth, by applying a substance such as collagen or gelatin that is decomposed and absorbed in vivo to the cloth, it has been devised to prevent blood leakage by preventing blood from penetrating into the medical material. It was. This is a so-called coated artificial blood vessel or coated patch, which has already been commercialized. (Scott SM, Gaddy LR, Sahmel R, Hoffman H. A collagen coated vascular prosthesis. J Cardiovasc Surg. 1978; 28: 498-504 (Non-patent Document 1); Noishiki Y. Chvapil M. Healing pattern of collagen-impregnated and preclotted vascular grafts in dogs. Vasc Surg., 1987; 21: 401-411 (non-patent document 2))

  In such an operation, the importance is placed on the safety that blood never leaks rather than the desire for stability by long-term integration of the fiber and the living body.

  However, since many of the collagen and gelatin used to clog these coated artificial blood vessels and coated patches are bovine-derived substances, their use is feared due to the impact of so-called BSE (mad cow disease) in recent years. It has been rigorously reviewed.

  As another problem, it has been pointed out that the cut end of the woven fabric is easily frayed. Compared to the knitted structure, in the woven structure, in particular, when it is cut in an oblique direction, when a suture needle is applied to the cut end, there is a high possibility that the portion will fray.

  Guidance for Industry and FDA Staff.Guidance Document for Vascular prostheses 510 (k) Submissions, US Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health, Document issue.on: November 26 , 1999. Usually, in accordance with this test method, a thread is pulled at a distance of 2 mm from the cut end, and the force required for fraying is measured as a Suture Retention Test (SR). A typical value is about 1.0 kg for a knitted fabric and about 0.3 kg for a woven structure.

  In order to improve the fray resistance, it is necessary to densely weave the fibers. In this case, as described above, the obtained fibers become as hard as a tent cloth, which causes a problem in handling. On the other hand, the disadvantage that loosely woven fibers tend to fray and blood easily leaks remains unresolved.

  That is, in the case of fiber-made medical materials, especially artificial blood vessels and patch materials that may come into contact with blood, blood leakage, fraying problems, fabric hardness, handling, compatibility with cells, that is, integration with living tissue However, it has different advantages and disadvantages depending on the weaving method, knitting method, fiber gap and the like.

  As described above, many dilemmas remain as unsolved problems in conventional artificial blood vessels and patch materials.

Scott SM, Gaddy LR, Sahmel R, Hoffman H. A collagen coated vascular prosthesis. J Cardiovasc Surg. 1978; 28: 498-504. , Noishiki Y. Chvapil M. Healing pattern of collagen-impregnated and preclotted vascular grafts in dogs. Vasc Surg. 1987; 21: 401-411.

  An object of the present invention is to provide a fiber-made medical material capable of eliminating the above-described drawbacks of the prior art.

  Another object of the present invention is to provide a medical material made of fiber having the characteristics of improving fraying resistance and maintaining cell affinity while minimizing blood leakage.

  As a result of diligent research, the present inventor has found that the use of the permeability of a specific liquid in a fiber structure as an index in combination with other specific physical properties is extremely useful for solving the above-described problems.

Based on the above findings, the present inventors have further studied, and as a result, by using a specific ultrafine fiber in a manner that satisfies the above-mentioned combination of physical properties, the blood permeability is kept constant while maintaining a certain degree of water permeability. It was found that it can be suppressed to a certain extent. The medical material of the present invention is based on the above knowledge. More specifically, at least the surface on the fluid contact side of an ultrafine fiber of 0.5 dtex (dtex) or less (in the case of a tubular structure, inside the wall) The ratio of water permeability: WP (ml / cm ² , 60 sec.) And blood permeability: BP (ml / cm ² , 30 sec.) Q = WP / BP is 6 It is the above, It is characterized by the above.

  Further, according to the present invention, in a fiber cloth having a woven structure as a basis, at least a surface on the fluid contact side of an ultrafine fiber of 0.5 detex or less (dtex) (in the case of a tubular structure, its wall (Inside) part of the fiber gap, and the following formula:

R = (N + M) ² /WP>8.0×10 ⁶
There is provided a medical material having the following relationship: (N: total number of weft fibers per square centimeter, M: total number of warp fibers per square centimeter, WP: fabric permeability).

In the present invention, it is sufficient that the predetermined ultrafine fiber is present at least on the fluid contact side of the medical material (for example, fluid existing in the living body such as blood, lymph, body fluid, electrolyte solution, etc.). This is because, as will be described later, the function of the medical material of the present invention is achieved mainly by the ultrafine fibers existing on the fluid contact side. Therefore, for example, in the aspect in which the medical material of the present invention has a tubular structure, it is sufficient that the predetermined ultrafine fiber exists in at least a part of the inside of the tubular wall.
In the medical material of the present invention having the above-described configuration, the reason why a preferable result is obtained is estimated as follows according to the knowledge of the present inventor.

  In other words, one point of the present invention is that there are two paths: a path where blood coagulation is initiated by fibrin deposition and a path initiated by platelet aggregation. In this case, the former fibrin deposition has the disadvantages that it is blocked by heparin and that the fibrin network that has been deposited is dissolved by the fibrinolysis phenomenon, but a large amount of huge thrombus is rapidly removed. This route has been empirically used in the prior art because it can be formed and blood clotting can be obtained. However, in the present invention, as a result, thrombus formation by platelets is mainly used as a result, so that the effects of heparin and fibrinolysis can be substantially avoided. In other words, since thrombus formation due to platelet aggregation is not affected by heparin or fibrinolysis, effective thrombus formation is achieved in the present invention by actively inducing platelet adhesion in fine fiber gaps. Can be promoted.

  In order to efficiently exhibit such a method that mainly uses thrombus formation, it is necessary to arrange even a very small amount of ultrafine fibers in a normal gap between fibers, or to make a medical material with ultrafine fibers. Thus, it can be realized by keeping the fiber gap narrow and attracting adhesion and aggregation of platelets into the fiber gap. As a result, in the present invention, it is presumed that stable thrombus formation and its maintenance are brought about.

As described above, according to the present invention, ultrafine fibers of 0.5 dtex or less are at least part of the fiber gap inside the wall, and water permeability: WP (ml / cm ² , 60 sec.) Blood permeability: ratio of BP (ml / cm ² , 30 sec.) Q = WP / BP has a value of 6 or more, and a medical material is provided.

  According to the present invention, in a fiber cloth having a woven structure as a basis, the fiber has an ultrafine fiber of 0.5 dtex or less in at least a part of the fiber gap inside the wall, and the following formula:

R = (N + M) ² /WP>8.0×10 ⁶
(Where N: total number of weft fibers per square centimeter, M: total number of warp fibers per square centimeter, WP: water permeability of fabric)

  According to the present invention, although the water permeability can be maintained at a relatively high level (the proportion of the material itself is relatively low), the blood permeability is suppressed to a relatively low level and the blood leakage is small. Safe medical materials can be made.

  According to the present invention, the blood leakage is positively measured in the fiber gap, the blood coagulation property of the infiltrated blood is increased, and the formed thrombus is stably retained, thereby reducing blood leakage. A material can be made.

  According to the present invention, since the water permeability can be made relatively high, a path through which host cells can enter the medical material in the living body is opened, and the total amount of fiber gaps is high, so that Since the cell can easily enter the cell, an integrated state of the fiber material and the living tissue can be easily formed in the living body.

  In the present invention, in an aspect in which ultrafine fibers having the same strength as ordinary fibers are in an entangled state, even if the water permeability is the same, a fiber product having high fraying resistance at the cut end is easily provided. Even if it is cut in any direction at the time of surgery, it is possible to provide a medical material in which the suture of the cut end is difficult to come off (that is, highly safe).

  In the present invention, since it is easy to narrow and increase the fiber gap, in the embodiment in which the bioabsorbable substance is combined, the bioabsorbable substance is easily retained in the fiber gap even if it is a trace amount. It is possible. Therefore, by providing such a bioabsorbable substance with the property of coagulating blood, a medical material with further reduced blood leakage can be easily produced.

  In the present invention, since it is easy to narrow and increase the fiber gap, it is possible to stably keep the bioabsorbable substance in the fiber gap in the aspect of combining the bioabsorbable substances. Therefore, even when a small amount of a bioabsorbable substance is used, a medical material having substantially complete hemostasis can be easily produced.

  Furthermore, in the present invention, in the embodiment in which the bioabsorbable substance is combined, the bioabsorbable substance can be stably retained even in a minute amount in the fiber gap. These physiologically active substances can be gradually released in vivo by a method such as adsorbing or retaining the physiologically active substances. Therefore, medical materials having various physiological activities (and having a slow release property) can be easily produced.

  Hereinafter, the present invention will be described more specifically with reference to the drawings as necessary. In the following description, “parts” and “%” representing the quantity ratio are based on mass unless otherwise specified.

(Medical materials)
The medical material of the present invention has ultrafine fibers of 0.5 decidex (dtex) or less in at least a part of the fiber gap inside the wall, and water permeability: WP (ml / cm ² , 60 sec.) And blood permeability. Ratio: Ratio of BP (ml / cm ² , 30 sec.) Q = WP / BP is 6 or more.

  According to another aspect of the present invention, in a fiber cloth having a woven structure as a basis, the fiber has an ultrafine fiber of 0.5 dtex or less in at least a part of a fiber gap inside the wall, and formula:

R = (N + M) ² /WP>8.0×10 ⁶
There is provided a medical material having the following relationship: (N: total number of weft fibers per square centimeter, M: total number of warp fibers per square centimeter, WP: fabric permeability).

(Estimated mechanism of thrombus formation)
As a premise for explaining the reason why the medical material of the present invention is effective, first, the estimation mechanism of thrombus formation (based on the knowledge of the present inventor) in the present invention will be described.

  In other words, as described above, thrombus formation starts from fibrin precipitation and platelet aggregation. However, once thrombus formation is started, both influence each other and entangle the thrombus one after another. These synergistic effects are used to create macroscopically recognized blood clots. Therefore, in the place where a thrombus is formed, it is rarely questioned which started first, and in the development of medical materials, no attention has been paid to which route is used. In the present invention, focusing on the starting point of thrombus formation, platelet adhesion and aggregation are induced in order to make maximum use of the platelet aggregation pathway, which is hardly affected by heparin administration and fibrinolysis. The device was devised to create an environment for the gap between the fibers.

  Platelets have the property of adhering to the surface when they come into contact with foreign substances other than the surface of vascular endothelial cells. When the degree of stimulation received from the foreign substance is large, the platelets are self-ruptured to release internal granules around them, and the platelet debris adheres to the original part. When this granule scatters, the other platelets to which it adheres are ruptured by stimulation by the granule and further release the granules in a chain. And leave those debris. Platelet thrombus grows in the state that those debris and granules gather and aggregate one after another. In this way, the remnants of platelets that are ruptured in a chained manner accumulate, and a thrombus can be formed without resorting to fibrin deposition.

  Since fibrin easily adheres to platelet aggregates, when fibrin adheres to the aggregate and begins to form a wide fibrin network rapidly, it grows into a huge thrombus. If platelets further adhere to the fibrin network and repeat rupture, the thrombus formation spreads at an accelerated rate and becomes suddenly huge.

  The platelet size is about 1-2 μm (micron), and the fiber gap of a commercially available artificial blood vessel made of cloth is usually about 50 μm. Therefore, even if platelets aggregate one after another to form a clump, the aggregate is 50 μm or more. A large amount of platelets is required to produce the product, and it takes time. However, fibrin deposition can easily form a thrombus of 50 μm or more efficiently in a short time because fibrin rapidly forms a network. Therefore, according to fibrin precipitation, hemostasis can be stopped by the above-described pre-clotting operation even for a fiber medical material having a fiber gap of 50 μm or more. This is because thrombus formation by preclotting causes rapid platelet aggregation and fibrin network formation.

  However, depending on hemostasis only on the fibrin network, there is a drawback that it is easily affected by heparin and fibrinolysis as described above. Thus, as much as possible, the new technique of the present invention has improved reliable hemostasis by utilizing thrombus formation mainly based on platelet aggregation.

  Naturally, when platelet aggregation is initiated, fibrin deposition is also naturally induced, so the state where fibrin adheres to the platelet thrombus is not excluded, and the thrombus adheres stably in this state. By doing so, it is expected that thrombus formation will proceed more efficiently. However, there is one feature of the present invention in that a thrombus can be formed by only platelet aggregation, and blood leakage can be reduced.

  In order to obtain such a state with a medical material made of cloth having a knitted structure, the present inventors have conducted intensive research focusing on what kind of state the fiber gap is desirable. A structure that closes the fiber gap and causes blood leakage even with agglomeration alone is extremely preferable. For this purpose, the fiber gap is 30 μm or less, more preferably 20 μm or less, and even more preferably 10 μm or less. It has been found preferable to have.

  However, even if complete hemostasis with only platelets is not achieved, blood platelets may actually adhere to platelet aggregates, making it difficult for blood to leak. It has also been found by the present inventor that it is substantially convenient to measure the value.

  In reality, it is almost impossible to measure countless fiber gaps. Therefore, in the present invention, a method has been developed that regulates the degree of blood permeation by inducing aggregation of the plasma plate by actually passing blood through the blood gap.

(Permeability)
In this way, in order to define the fiber gap by the actual blood permeation amount, how the blood passes through the fiber gap of the cloth is numerically expressed in the present invention. More specifically, blood is collected from an animal, and the amount of blood passing through a 1 cm ² cloth is measured under the same conditions as when measuring the water permeability, that is, applying a pressure corresponding to a pressure of 120 mmHg. In the present invention, a new evaluation method called blood permeability was developed in this way, and a fiber medical material was designed based on the evaluation method. More specifically, in the present invention, a method for measuring blood permeability as shown in “Examples” described later can be suitably used.

  When measuring blood permeability, the more fresh blood is, the more physiological data can be obtained. However, if fresh blood is used as it is, fibrin network formation occurs during measurement due to blood coagulation by fibrin. The fiber gap is clogged with thrombus caused by Therefore, when measuring the blood permeability, it is required to allow blood to pass through while causing only platelet adhesion, at least in a state where hemostasis due to fibrin network formation is substantially prevented.

  That is, in order to obtain hemostasis only by platelet aggregation, it is necessary to add heparin to the blood to obtain blood that does not precipitate fibrin. By observing blood leakage in this state and measuring the passage state, it is possible to express the blood leakage state under the fibrinolysis phenomenon.

  Then, the minimum amount of heparin necessary to obtain such a state becomes a problem. As an index for this, the present invention employs a method that is routinely performed in clinical practice. That is, in clinical practice, the activated clotting time (ACT) is measured as a method for measuring the coagulability of blood with heparin added. In general, fibrin deposition can be prevented in blood whose value is 400 seconds or more, and thus surgery for large blood vessels such as the heart and aorta is performed safely. Therefore, in the present invention, fresh blood was used for evaluation in the same manner, that is, in a state where heparin was added to blood and ACT was 400 seconds or longer.

  Compared to water, blood has higher viscous resistance. The flow of a medium having such a high viscous resistance depends on temperature. In this regard, there is the Hagen Poisjour's law, and the equation for the flow of the capillary sets the temperature dependence of the viscosity, the relationship with the pressure purchase of the osmotic flow, etc., and sets the permeability of the medium to the viscosity of the fluid. There is a method of calculating by rate.

  Dalceal's law is applied to the flow in a field that is filled with fine particles that are like a capillary aggregate. More specifically, when a viscous fluid is flowed by applying a pressure gradient Dp in a material having a gap such as fine particles or unglazed material, the average flow velocity v is expressed as v = −kDp. It is a law. k is a coefficient determined by the viscosity and the geometric properties of the gap, and is called a permeability coefficient (Permeability). This law is used in the analysis of groundwater flow.

  Therefore, in order to express the state of the blood flowing through the fiber gap of the present invention, the Hagen Poisjour's law and the Darseal law should be applied, but in reality, even if heparin is added to the blood, Since platelets are sticky and adhere to the fibers one after another, not only the geometrical conditions in the fiber gap change over time, but also the blood properties change and viscosity resistance decreases. Because they change, those laws cannot be applied as they are. Therefore, it is more realistic to actually flow blood and actually measure to obtain the most accurate value. Therefore, in the present invention, a method for measuring the blood permeability and comparing it with the water permeability is adopted. .

In the present invention, the water permeability is expressed as the amount of water that passes through a cloth of 1 cm ² per minute, as will be described later. However, the present inventors have found that when blood is flowed, the measurement for the first 30 seconds is convenient for observing a state in which blood is allowed to pass through while platelet adhesion and aggregation occur. This is because, when platelets come into contact with a foreign substance, it is generally caused by aggregation within 30 seconds, so that it is possible to most prominently show a state in which platelets adhere to and aggregate in fiber gaps. .

  If the amount of blood permeated for 30 seconds or more is measured, red blood cells will be deposited where platelets adhere to the fiber gap, and blood will begin to be blocked. It becomes difficult. Red blood cells do not have a mechanism for adhering to the periphery even if they are once laminated, and thus it has been found that they easily peel off when conditions change, and the hemostatic effect caused by clogging due to lamination is lost. Therefore, it has been found that it is appropriate to measure the blood permeability only with the amount of blood permeated for the first 30 seconds. Therefore, in the present invention, the blood permeability is measured with the amount of blood permeated for the first 30 seconds. Rate.

  The blood used for such evaluation is desirably fresh blood collected from horses, cows, pigs, dogs, sheep, goats and the like. Among them, it is preferable to use bovine, sheep, or goat blood from the viewpoint that blood can be always obtained from healthy young animals.

  In that case, heparin was injected into the animal after intravenously injecting heparin of 1000 international units or more per kg of body weight, and the blood ACT was measured. If the value was 400 seconds or less, heparin was further injected into the blood. And use it for evaluation after 400 seconds or more. At that time, the evaluation is performed to protect the platelets as much as possible so that the blood is handled as much as possible, and the blood storage bag is also a container that does not easily cause blood coagulation (that is, a blood collection bag for blood transfusion on the market). It is desirable to finish the evaluation within 2 hours after blood collection.

  By using such a method, blood permeability in a fiber cloth can be measured. However, if a fibrous fabric with low blood permeability is used, a structure in which the fiber gap is narrow and blood cannot permeate into the fabric will be extremely preferable. However, as a practical matter, as described above, such a densely woven cloth becomes hard like a tent cloth. Therefore, in the present invention, the fiber type and the arrangement thereof are designed so that the fiber gap is provided as much as possible and the cloth is given flexibility, and the blood leakage is minimized.

  In this case, it is extremely preferable to numerically grasp the state in which the fiber gap is provided to some extent and blood is difficult to pass through. Therefore, in the present invention, water is allowed to pass through with some fiber gaps. It has also been found that when this state is actually implanted in a living body, body fluids, electrolytes, and the like in the body can pass through and there is less adverse effect on substance metabolism.

  Therefore, in the present invention, a fiber product evaluation method having a high hemostatic property has been developed, in which even if the water permeability is high, the blood permeability is low, or even if the water permeability is the same, the blood permeability is low. Then, the present invention has found a method of designing a fiber structure with little blood leakage, that is, having excellent hemostasis, or obtaining basic design data using the evaluation method. In the present invention, the water permeability is preferably measured using a measurement method such as that used in Examples described later.

  Using this index, in the present invention, a cloth in a state in which a large amount of water passes but a small amount of blood permeates is designed. As a result of thorough examination of fabrics having various fiber structures as to how to design a fabric in such a state, the present invention has found that there is a law in the fabric. That is, when the ratio between the water permeability (Water Permeability, WP) and the blood permeability (Blood Permeability, BP), that is, the value of Q = WP / BP is 6 or more, even though water can pass, blood cannot pass easily. I found out that I can judge. The value of Q = WP / BP is more preferably 6.5 or more, and particularly preferably 7.0 or more.

  Conversely, when the value of Q = WP / BP is less than 6, the BP tends to increase as the WP increases. That is, it can be determined that the tissue is made of fibers in which water and blood are similarly permeated in a large amount. However, if the value of Q = WP / BP is 6 or more, the amount of blood permeation is relatively small compared to the amount of water permeation, even in a state where a large amount of water can permeate. It means to say.

  When commercially available artificial blood vessels were measured using such an evaluation method, it was found that all the values of the artificial blood vessels were less than 6 as described later. That is, it can be understood that a commercially available artificial blood vessel has a high water permeability and blood permeability, and blood leakage is remarkable.

(Narrow fiber gap)
The present inventor specifically examined what structure the organization has to obtain a state where the value of Q = WP / BP is 6 or more. As a result, it has been found that such a situation can be created by capturing a large amount of platelets by giving the tissue many narrow fiber gaps.

  Based on such an index, as a result of developing a cloth that satisfies the conditions in the present invention, in order to prevent the fiber cloth structure from being hardened while still having many narrow fiber gaps, thin fibers are used. This state was successfully achieved by using fabrics and / or mixing very thin fibers in a fiber gap of normal thickness.

  Therefore, when we actually made such a cloth using commercially available ultrafine fibers, in order to use them in living bodies, especially as artificial blood vessels or patch materials used for blood vessel walls or heart walls, However, it was found that even if the hemostasis was successful, it could not be used practically due to the problem of mechanical strength if it was not as strong as the fiber of normal thickness.

  At present, commercially available ultrafine fibers of 0.5 denier or less are produced by various production methods. And in order to make a fiber thin according to a manufacturing method or the composition in each fiber, even if it is the same polyester fiber, there are many fibers with weak intensity | strength. Therefore, in the present invention, even if the manufacturing method is not questioned, it is possible to use an ultrafine fiber having at least the same strength as that of a fiber having a normal thickness at a site that actually touches blood. It has been found that it is extremely preferable for producing a medical material.

  In the present invention, the method for producing ultrafine fibers is not particularly limited. On the other hand, there is a point to be noted with respect to the substance adhering to the microfiber.

  That is, many ultrafine fibers are currently made by the so-called sea-island structure or the split type manufacturing method, and the ultrafine fiber is an island part, and the sea part is dissolved, or a method of removing by splitting is taken. ing. At this time, a polyamide-based polymer, a polyolefin-based polymer, polystyrene, a soluble polyester-based polymer, or the like is used for the sea portion or the divided portion (for details of such a method for producing ultrafine fibers, see, for example, the document Okamoto M: Ultra-fine fiber and its application, Preprints Japan-China Bilated Symposium on Polymer Science and Technology, 256-262, Tokyo, October, 1981.).

  Among these ultrafine fibers produced by various methods, the present invention pays attention to the amount of S (sulfur content) adhering to the ultrafine fiber after removing the sea portion and the divided portion, and the use of the ultrafine fiber having a low value is used. I found it desirable.

  This is because recent ultrafine fiber production methods employ many ultrafine fiber production methods using soluble polyester in the sea. At this time, a sulfonic acid copolymer is often used for the soluble polymer. In this case, the sulfonic acid copolymer is eluted and removed with an alkaline solution, but if it remains in a very small amount, the sulfone group is negatively charged, so that calcium ions are adsorbed over a long period in vivo. There is a possibility to continue. As a result, the inventor has found that there is a high possibility that calcification will occur around the ultrafine fibers within one year.

  Ultrafine fibers have the same number of fibers as compared to normal-thickness fibers, and the number of fibers increases, which increases the total surface area. If so, the sulfone group may continue to be released from a large surface area. In order to measure this sulfone group, the value of S constituting it is generally quantified.

  Therefore, in the present invention, when selecting the ultrafine fiber to be used, the production method is not particularly limited. However, when the value of S adhering to the ultrafine fiber is high, the phenomenon of calcification was observed around the fiber in animal experiments. In order not to cause this phenomenon, the value of S adhering to the ultrafine fiber was 20 ppm or less. It is preferred to use fibers. The value of S is further preferably 10 ppm or less, and particularly preferably 5 ppm or less.

  Therefore, in the present invention, in ultrafine fibers produced using a polyamide-based polymer, a polyolefin-based polymer, polystyrene, or the like in the sea part or divided part, the sulfone group cannot theoretically remain, so that the adhering matter It is considered that the possibility of being 20 ppm or less is high in the S analysis. From the viewpoint of this S analysis, in the present invention, it is preferable to use a polyamide-based polymer, a polyolefin-based polymer, polystyrene or the like. In the case of an ultrafine fiber using a soluble polyester-based polymer, it is preferable to use a fiber that has been sufficiently washed with an alkaline solution and has a value of 20 ppm or less by S analysis of the deposit.

  Although any method can be used as the method of S analysis, an oxidation (combustion) method is common. A specific method is as follows.

First, a cloth whose S content is to be measured is collected as a sample, and its weight (for example, about 5 g) is measured. Next, the sample is burned and vaporized. At this time, if sulfur S is contained, it becomes an oxide gas in the form of SO ₃ . This is introduced into the electrolyte and dissolved, and the value of S dissolved in the solution is measured.

  As a measuring instrument, a total chlorine / sulfur analyzer TSX-10 manufactured by Mitsubishi Chemical Corporation is used, and the temperature of the electric furnace is set to 850 ° C. for oxidation.

(Fiber strength)
On the other hand, regarding the strength of the fiber, in the case of a fiber having a normal thickness, for example, the strength of a polyester fiber used for clothing is 4 to 5 g / dtex. However, many ultrafine fibers have a strength of 2-4 / dtex. Depending on how it is made, it is possible to make stronger fibers, while there are weaker fibers that are less than that. In the fiber manufacturing process, by strongly stretching the fiber, the degree of polymerization of the polymer constituting the fiber can be increased, and molecular orientation can be obtained regularly. And fiber strength becomes high. However, it becomes easy to cut in the process of stretching. Therefore, there is a method for producing ultrafine fibers that are thinly drawn with fibers having a low degree of orientation, in which case the fiber strength decreases.

  In the present invention, at least in the case of a medical material at a site that comes into contact with blood, even a very fine fiber of 0.5 dtex or less, at least a strength of 4 g / dtex or more, preferably 4.5 g / dtex or more, The use of ultrafine fibers having a strength of 5 g / dtex or more is preferred.

  The strength of the fiber can be sufficiently measured with a normal tensile tester, but in the present invention, the strength is analyzed by an analysis system (Factory Shikibu 2000) using a Shimadzu Corporation testing machine EZ-TEST.

  In particular, when an artificial blood vessel or a patch material is cut out in an oblique direction with respect to the weaving or knitting method of the cloth, the cut end tends to be easily frayed. If frayed, major bleeding may occur, and if there is an ultrafine fiber at such a cut end, the strength is often required even if it is thin, even if it is thin.

  More specifically, since the woven structure is easier to unravel than the knitted structure, even when the basic structure is woven, the fray resistance at the cut end is preferably 0.8 kg or more. The fraying resistance coefficient of a commercially available artificial blood vessel having a woven structure was measured to be about 0.3 kg, and even a strong cloth was 0.4 to 0.5 kg, both of which were 0.8 kg or less. In the present invention, the fiber-made medical material has a higher fray resistance coefficient value by mixing ultrafine fibers having the same fiber strength.

    On the other hand, in the case where the basic structure is a knitted structure, when a commercially available artificial blood vessel was examined, the fray resistance was about 1.0 kg to 1.5 kg, that is, all were less than 2.0 kg. Therefore, in the present invention, by mixing ultrafine fibers having fiber strength equivalent to that of normal fibers, the present inventors have succeeded in providing a strength exceeding that, that is, a fray resistance of 2.0 kg or more.

  This measurement of fraying resistance can also be analyzed by an analysis system (Factory Shikibu2000) using the Shimadzu Corporation test machine EZ-TEST.

(Aspect of woven structure)
In order to improve hemostasis, it is extremely preferable to have a large number of narrow fiber gaps. As a result of intensive studies by the inventor on whether or not the effective number of fiber gaps can be expressed by the number of fibers actually used, the following has been found when the fabric is basically a woven structure. .

That is, in the fabric made of fibers having a basic woven structure, when the total number of weft fibers per square centimeter: N, the total number of warp fibers per square centimeter: M, and the water permeability of the fabric: WP, It is preferable that R = (N + M) ² / WP> 8 × 10 ⁶ . The reason why the cloth having such a configuration is effective is estimated as follows according to the knowledge of the present inventor.

  In other words, in the present invention, an attempt was made to create an index for comparing and examining many medical materials made of fibers by simply expressing the number of gaps between fibers that actually constitute the cloth. The specific theory is as follows.

  For example, if there are n fibers, the number of fiber gaps with other fibers as seen from one of the fibers is n-1. Therefore, the total number of fiber gaps viewed from n fibers is n times that of n fibers, that is, n (n-1). However, as a result, it is supposed that the respective fibers are overlapped and the actual total number is half that number. That is, the total number of fiber gaps of the cloth composed of n fibers is represented by n (n-1) / 2.

Taking a fabric based on a woven structure as an example, the yarns constituting the fabric can be divided into warp yarns and weft yarns. For example, the total number of warp yarns per square centimeter is n and the total number of weft yarns is m. In the case of a book, the number of fiber gaps in the cloth made by crossing them is (m + n) (m + n-1) / 2. That is, (m + n) ² / 2- (m + n) / 2.

In reality, since both n and m are extremely large, (m + n) is relatively smaller than (m + n) ² , and (m + n) can be ignored.

  In this way of thinking, when comparing the number of fiber gaps of medical materials having various woven structures, it is concluded that it is practical to compare the number of fibers with the square of the total number of fibers.

  In consideration of the index of the number of fiber gaps obtained in this way and whether or not it creates a narrow fiber gap state, the present inventor has found the following further. That is, when the fiber gap becomes wider, the water permeability becomes higher. Therefore, the “water permeability” has an inversely proportional relationship to narrow the fiber gap. On the other hand, “the square of the total number of fibers used” is directly proportional to the total number of fiber gaps. That is, the numerical value represented by the function of “the square of the total number of fibers used” / “water permeability” represents a state having many narrow fiber gaps.

  That is, in the present invention, since the function of “the square of the total number of fibers to be used” / “water permeability” is used as an index, there are many narrow fiber gaps, and the efficiency of capturing, sticking, and aggregating platelets is high. It is presumed that it is easy to obtain fiber arrangement conditions.

  At this time, it is necessary to consider the thickness of the cloth, but it is considered that the thickness of the medical material is not substantially excessive due to the ease of use. In a medical material, since the thickness of a cloth is generally 1000 μm or less, it is considered that the thickness does not significantly affect the above “function”.

As a result of further research based on the above findings, the present inventor has found that a thrombus caused by the formed platelets can be used as long as the fiber gap is narrow enough to satisfy the condition of (m + n) ² / WP> 8 × 10 ^6. Has been found to be held stably. As will be described later, such a conclusion was proved by obtaining a coefficient ((m + n) ² / WP) based on actual measurement data in a commercially available artificial blood vessel having a woven structure.

  However, regardless of the woven structure or the knitted structure, it is difficult to capture a large amount of platelets because the fibers are bundled and the individual fibers are closely packed. Therefore, it is extremely preferable to separate the fibers from each other to produce a structure having many narrow fiber gaps.

  Thus, specifically, as a result of intensive studies on “a structure having many narrow fiber gaps”, the present inventor formed napped and / or looped shapes having irregular entangled states in which fibers exist in a dispersed state. It has been found that having at least a part of one or more states selected from the group, it is possible to create a situation where water can pass through a lot but blood cannot pass through. In the present invention, a loop is formed on the surface of a knitted fabric as disclosed in JP-A-50-117287, JP-A-52-94699, JP-A-52-113094 and JP-A-53-137599. The method of forming can also be utilized.

  Further, as a device for providing a gap between individual fibers, a part of multi-component fibers as shown in Japanese Patent Publication No. 48-22126, Japanese Patent Publication No. 53-22593, or the like is removed or separated. It is also effective as one means for achieving the object of the present invention to use a fiber bundle in which fibers are separated by such means as a part of the basic structure.

  In the present invention, by using ultrafine fibers, it is possible to easily satisfy the condition of securing as many extremely narrow fiber gaps as possible inside the medical material made of fibers. Among ultrafine fibers, if the fibers are extremely thin of 0.5 decidex or less, the total number of interstices can be increased by orders of magnitude compared to the total weight and volume of the fibers, and many platelet aggregates are captured. Thus, it has been found in the present invention that it is convenient to maintain stably.

  There are various production methods for ultrafine fibers. In the present invention, it is also possible to use ultrafine fibers produced with multicomponent fibers. The reason for this is that a slight gap is formed between the fibers produced by a multicomponent system by means such as removing or peeling a part of the multicomponent fiber. Can be used to promote adhesion and aggregation of platelets to the area to obtain stable thrombus formation, and the fiber gap can be expanded by using a technique such as water jet, which will be described later. Therefore, the effect can be improved dramatically. Therefore, it is different from JP 61-4546 A, JP 61-58190 A, US Pat. No. 4,6895,280, US Pat. No. 4,743,250, etc., which only aim to use ultrafine fibers. In the present invention, it is possible to use a multicomponent yarn in a state where the effect is exerted.

  In the present invention, by using an ultrafine fiber and spraying a fluid such as a water jet, the ultrafine fiber is entangled irregularly and further separated from the fiber bundle so as to protrude irregularly into the fiber gap. Alternatively, a state having a large number of narrow fiber gaps, which is the object of the present invention, can also be produced by, for example, causing disturbance in the arrangement of ultrafine fibers by using a bulky processed yarn.

  Furthermore, if heat-shrinkable yarn is used for some yarns in the fabric made of fiber, the shrinkable yarn portion shrinks after heating, resulting in loosening of the bundle of other yarns. In the present invention, it is preferable to use a part of the heat shrinkable yarn because the individual yarns of the bundle are dispersed.

  In order to produce such a state, an ultrafine fiber-forming composite fiber is temporarily processed to have latent crimping ability, a cloth is produced with this fiber, and after crimping is manifested, an ultrafine fiber is processed. It is more effective to have ultrafine fibers dispersed by the above.

(Fiber gap)
The following describes what phenomenon occurs in the fiber gap in such a mixed fabric of ultrafine fibers.

  Most of the fibers used in ordinary artificial blood vessels are polyester fibers, the thickness is about 1.2 decidex, and the cross-sectional diameter is about 16 to 20 μm. However, at this time, if very thin fibers, that is, thin fibers of 0.5 decidex or less are mixed in the gap between the fibers, the cross-sectional diameter becomes 3 μm or less, and the thin fibers are fibers of normal thickness. Since it is possible to create a state in which the thread exists as if the cocoon thread is stretched in the gap, it is possible to capture a large amount of platelets in this portion. At this time, the thinner the fibers are, the more flexible the fibers are, so that such irregular thread-like fiber arrangement is possible. That is, it is possible to easily produce an arrangement state of ultrafine fibers such as a string of cocoons in a fiber gap having a normal thickness. As a result, a large number of narrow fiber gaps can be provided.

  In order to create such a situation, it has been found that even when a very small amount of ultrafine fibers are present between normal fibers, it is possible to reliably construct a structure having a large number of narrow fiber gaps. Of course, it is obvious that the narrow fiber gap further increases when the cloth is made of only ultrafine fibers. In this state, once blood adheres, a thrombus with platelets attached to the site is formed, and when the fiber gap is clogged by the thrombus, heparin is used even if fibrinolysis occurs. It was also found that it was not easily removed. That is, it has been clarified in the present invention that a structure with excellent hemostasis can be obtained.

(Extra fine fiber)
Currently, many ultrafine fibers are commercially available, many of which have a strength of less than 4 g / dtex. If such a weak fiber is used in a place where blood pressure is applied, the blood pressure of the same pressure is applied to the ultrafine fiber holding the platelet aggregate and the fiber of normal thickness. If this happens, if weak fibers are used, the fibers in that part are stretched, and the platelet mass tends to come off, or the entire fiber structure breaks down, resulting in temporary hemostasis. However, the failure can cause blood leakage. Therefore, in order to exert the hemostatic effect due to platelet aggregation in the present invention, the ultrafine fiber has at least a strength of 4 g / dtex or more, further 4.5 g / dtex or more, particularly 5 g / dtex or more. It is preferable.

  In particular, the strength of ultrafine fibers is not so important in a fabric structure in which fibers are densely woven, but in a knitted structure with a wide fiber gap, strong tension may be applied to individual ultrafine fibers. Therefore, unless the strength of the ultrafine fibers is sufficient, the thrombus film formed by the aggregates of the captured platelets cannot be reliably retained. For that purpose, it is also desired for the ultrafine fiber to have the same strength as the normal thickness fiber used at the same time. That is, even a very thin fiber of 0.5 dtex or less preferably has a strength of at least 4 g / dtex, more preferably 4.5 g / dtex or more, particularly 5 g / dtex or more.

  With regard to the relationship between the degree of the presence of ultrafine fibers and the extent to which the fine fibers are projected into the gaps of the regular fibers like cocoon threads, in the present invention, even if the total number of the fine fibers is 1% For example, it is possible to overhang the fiber gaps in the form of cocoon fibers, but in order to cover the fiber gaps evenly, if 5% or more of ultrafine fibers are present, the cocoon threads are evenly distributed in the fiber gaps. This is preferable because it can be in a tangled state. In the present invention, it is preferable to mix at least 5% or more of fine fibers of 0.5 decidex or less in the total number of fibers (that is, the total number of fibers including the “ultrafine fibers”). The relationship between the degree of the presence of such ultrafine fibers and the degree to which the fibers are usually projected into the gaps of the fibers like a cocoon yarn is a basic experiment of the present invention on a knitted fabric using ordinary fibers. This can be confirmed by an experiment in which a non-woven fabric made of ultrafine fibers is covered, and a water jet having a water pressure of 80 atm is applied to the ultrafine fibers so that the ultrafine fibers are usually entangled with the fibers. At this time, what is necessary is just to observe the entanglement degree of an ultrafine fiber by changing the quantity of the nonwoven fabric of an ultrafine fiber.

  At least when measuring the number of ultrafine fibers, in the weaving structure, measuring the type and number of wefts and wefts makes it easy to measure the type and distribution of fibers inside the textile product, but the knitted structure It is not easy to measure the amount and ratio of fibers having different thicknesses inside a textile product having a thickness. Therefore, in the present invention, it is also possible to employ a method of observing the fiber distribution state of the cross section of the fibrous cloth cut by cutting in an arbitrary direction with an optical microscope or a scanning electron microscope.

  Specifically, the fiber product is cut in any direction with a sharp blade, and the cut surface is photographed with a scanning electron microscope at a magnification of 300 to 3000 times, and the width of the cut surface is about 5 mm. Determine whether there are at least 5% or more of the total number of fine fibers of 0.5 decidex or less by measuring the number and type of fibers in the range Can do.

  When using an optical microscope, cut the fiber product to a size of about 1.5 cm square, embed it with resin, make a section of the cut surface with a glass knife, and from 100 times with an optical microscope Taking a picture in the range of 1000 times, by measuring the type and thickness of the fiber in the range where the width of the cut surface is about 5 mm, the number of the thin fibers of 0.5 decidex or less, Judge whether there is at least 5% or more of the total number of fibers.

  According to the knowledge of the present inventor regarding the reason why hemostasis can be achieved even if blood with the same blood pressure is flowed if the ultrafine fibers are bulged into the fiber gaps to narrow the fiber gaps. It can be explained by Laplace's law. According to Laplace's law, it is clear from the calculation of the surface tension that the tension applied to the surface of the film is proportional to the radius and pressure of the spherical body and inversely proportional to the film thickness.

  Applying this rule to a clot that adheres to the fiber gap in the form of a film and exhibits an effect of preventing blood leakage, it is as follows.

  That is, it is assumed that thrombi having the same thickness and strength are formed in the thrombi formed in the fiber gaps having different sizes. Let's say that your blood pressure is 120mmHg. In such a state, if the fiber gap is wide, the film that stretches the gap is stretched to create an arc state. As a result, the radius of the arc naturally increases as the fiber gap increases, and the tension applied to the membrane naturally increases according to Laplace's law. Then, even if the same 120 mmHg pressure was applied, even if the membrane pressure due to the thrombus was the same, if the fiber gap was wide, the tension of the thrombus membrane was so strong that the membrane of the thrombus stuck in the fiber gap was easily torn. Become.

  However, when the fiber gap is narrow, since the radius is small, the tension applied to the membrane is small, and even if the same pressure, that is, 120 mmHg, is applied, only a small tension is applied according to Laplace's law, and it is difficult to break. Become. That is, if the fiber gap is narrow, the formed thrombus film is stable. Based on this principle, it can be explained that if the fiber gap is narrow, a fabric structure with less blood leakage is obtained.

  Let me explain it in another example. For example, when the gap between the crosspieces, which are the bones of the shoji, is wide and narrow, the paper with the wide shoji paper is torn in the case of the wide shoji and the narrow shoji with the same wind. easy. If the gap between the shoji paper bars is extremely narrow, the shoji paper will not be easily torn by the strong wind. Such a phenomenon is presumed to occur in a fiber gap in which ultrafine fibers are mixed.

  In this case, it can be seen that the formed thrombus film is formed between the ultrafine fiber and the fiber of normal thickness, or between the ultrafine fiber and the ultrafine fiber. At this time, if only the ultrafine fibers are mechanically weak in strength, the thrombus membrane cannot be retained. The ultrafine fiber has the same strength as that of a normal fiber, and must surely capture the thrombus membrane. In this respect, in order to exert the effect of the present invention, the presence of an ultrafine fiber having a strength of 4 g / dtex or more equivalent to a fiber having a normal thickness while having a fineness of 0.5 decidex (dtex) or less. is important.

  Conventional techniques using ultrafine fibers of 0.5 dtex or less include Japanese Patent Application Laid-Open Nos. 61-4546, 61-58190, US Pat. No. 4,6895,280, and US Pat. No. 4,743,250. . These techniques are made by the present inventor. In these techniques, by using ultrafine fibers, the artificial blood vessels are made flexible, and the stitches are stuffed to improve hemostasis and affinity with cells. It aims to improve.

  U.S. Pat. No. 4,695,280 describes that the use of ultrafine fibers improves the hemostasis, but in this regard, the use of ultrafine fibers provides the fabric with flexibility, resulting in anastomosis. In the part, it is described that hemostasis from the gap of the suture line is improved due to easy joining with the blood vessel of the living body. That is, it is different from the meaning of preventing bleeding from the gap between the artificial blood vessel wall and the living body blood vessel wall and preventing blood leakage inside the cloth, that is, blood leakage caused through the cloth.

  Assuming that an artificial blood vessel is actually created using the technique described in US Pat. No. 4,695,280, there is a concern that if the ultrafine fibers are not strong, the thrombus retention is weakened. In reality, at present, artificial blood vessels using this prior art are not used clinically.

  In the present invention, from a certain point of view, it is also related to techniques such as JP-A-64-1546, JP-A-61-58190, US Pat. No. 4,6895,280, and US Pat. No. 4,743,250. Have These prior arts stipulate that ultrafine fibers are present on a part of the inner wall and that the inner surface is raised, etc., but this demonstrates the hemostatic effect due to the capture of platelets inside the wall. There was a drawback that could not be done. In the present invention, by defining the presence of ultrafine fibers in the wall, particularly in the interstices, and the strength of the ultrafine fibers, the present invention can exhibit effects that were not obtained in the prior art. In a true sense, it has become possible to introduce ultrafine fibers into a medical material that can be used even in places where blood such as an artificial blood vessel is touched and mechanical strength such as blood pressure is required.

  In particular, vascular surgery and cardiac surgery in the era when technologies such as JP-A 61-4546, JP-A 61-58190, US Pat. No. 4,6895,280, and US Pat. No. 4,743,250 were developed. In this surgery, hemostasis was obtained by aggregation of platelets and fibrin network stuck in the fiber gap, and massive bleeding caused by fibrinolysis during and after surgery. Did not occur. However, since bold surgery has been performed since the development of the cardiopulmonary apparatus, etc., there are many surgeries that use heparin in large quantities. As a result of this, there has been a history of the development of artificial blood vessels covered with collagen and gelatin.

  That is, in the techniques such as JP-A-61-2546, JP-A-61-58190, US Pat. No. 4,6895,280, and US Pat. No. 4,743,250, the strength of the ultrafine fiber to be used is specified. Therefore, when used in a fiber material with a wide fiber gap such as a knitted structure, the platelet aggregate adhered to the folded ultrafine fiber may be peeled off if the fiber strength is weak, as described above. was there. In this regard, in the present invention, even if the ultrafine fibers to be used are thinned, it is recommended to use fibers having the same strength in terms of strength. The road was opened.

  This phenomenon has been clarified in the basic experiment of the present invention, particularly in the case of an artificial blood vessel having a high water permeability. In Japanese Patent Laid-Open Nos. 61-4546, 61-58190, US Pat. No. 4,6895,280, and US Pat. No. 4,743,250, the water permeability is in the range of 500 ml / min or less. A porous artificial blood vessel is assumed. In this case, even if the ultrafine fibers do not have sufficient strength, the normal gap between the fibers is also narrow. Therefore, even if fibrin dissolution occurs in the captured thrombus and the fibrin network disappears, platelets If the thrombus due to the aggregates of the blood stays in the interstices between the fibers, blood leakage is unlikely to occur. Therefore, even if the ultrafine fiber does not have sufficient strength in the prior art, it seems that there is no inconvenience within the range of the low-pore artificial blood vessel whose water permeability is in the range of 500 ml / min or less.

  However, when having a highly porous structure, especially when the basic structure is knitted, the fiber gap due to the normal fibers tends to be wide. At that time, platelet aggregates trapped in the fiber gaps must rely on adhesion to ultrafine fibers. At this time, if the ultrafine fiber does not have sufficient strength, at least as strong as normal fiber, it cannot be retained. In this sense, in the present invention, the higher the porosity, that is, the higher the water permeability in general expression, the more effective the presence of ultrafine fibers and the higher the required strength. Showed that.

In the present invention, the ratio of water permeability: WP (ml / cm ² , 60 sec.) To blood permeability: BP (ml / cm ² , 30 sec.) Q = from a textile product having a value of WP / BP of 6 or more. The higher the water permeability, the lower the blood permeability is 1/6 or less, so that the quantitative hemostatic effect is improved. Therefore, it can be seen that the present invention is particularly effective for a highly porous medical material. In the present invention, “highly porous” means that the water permeability: WP (ml / cm ² , 60 sec.) Is 800 ml / cm ² or more. The water permeability: WP is further preferably 1000 ml / cm ² or more, particularly preferably 1200 ml / cm ² or more. On the other hand, Toruchiritsu: (. 30 sec) BP is, 100 ml / cm ² or less, more 50 ml / cm ² or less, and particularly preferably 20 ml / cm ² or less.

  Therefore, the ultrafine fibers recommended in the present invention are present in a string shape in the fiber gap of the normal thickness, so that the fiber gap is narrowed by the interposition of the ultrafine fibers compared to the fiber gap of only the normal thickness, and hemostasis is achieved. Therefore, it becomes possible to provide a safe medical material. Nevertheless, the presence of ultrafine fibers is unlikely to affect the overall water permeability, and this technology has made it possible to design a medical material that has a high water permeability and a low blood permeability.

  Japanese Patent Laid-Open Nos. 61-4546, 61-58190, US Pat. No. 4,6895,280, US Pat. No. 4,743,250 and the like are characterized by using ultrafine fibers. Looking at these prior arts, it is shown that it is important that ultrafine fibers are present on the inner surface of the woven structure, and in particular, it is present on the inner surface in a raised state. This can provide an advantageous environment for attachment of vascular endothelial cells.

  Further, in detail, it can be seen that the water permeability is 500 ml or less, and a fabric structure in which the fiber gap is clogged with ultrafine fibers, that is, the fiber gap is filled. On the other hand, in the present invention, the presence of the ultrafine fibers is not limited to the inner surface, and even if it is very small in the fiber gap inside the cloth, if desired, the water permeability can be increased by including 5% or more of the total fiber. It has been shown that the object of the present invention of suppressing the permeation of blood is achieved even at a high level.

  Furthermore, in Japanese Patent Laid-Open Nos. 61-4546, 61-58190, US Pat. No. 4,6895,280, US Pat. No. 4,743,250, etc. It is considered to create a state in which blood is difficult to pass through the fiber gap by being placed in a packed state. Furthermore, it is important to have ultrafine fibers on the inner surface.

  In these prior arts, as described therein, the presence of ultrafine fibers on the inner surface, particularly in the raised state, is said to provide an advantageous environment for attachment of vascular endothelial cells. Indeed, the condition can be a good scaffold for endothelial cells. However, the use site of the low porosity artificial blood vessel having a water permeability of 500 ml or less shown in the prior art is the aorta, and in the area of vascular surgery, it is difficult for the artificial blood vessel used for the aorta to be covered with endothelial cells. It has been revealed. (Berger K, et al: Healing of arterial prostheses in man; Its incompleteness. Ann Surg 175; 118, 1972.)

  This is because vascular endothelial cells have a cellular senescence phenomenon, and if cell division is repeated to some extent, it becomes impossible to produce next-generation cells due to cell aging (Hoshi H. et al .: Long In Vitro Cell Dev. Biol 19; 661, 1983.) Therefore, in artificial blood vessels having a water permeability of 500 ml or less and used for the aorta, vascular endothelial cells are used with ultrafine fibers. Even if a good scaffold is provided, the endothelial cell coating is meaningless.

  In this sense, the prior art that promotes the coating of vascular endothelial cells by using ultrafine fibers is meaningless. However, in the present invention, since there is no limitation on the porosity, in high porosity, that is, in an artificial blood vessel having a high water permeability, hemostasis is enhanced by using ultrafine fibers, Regardless of the endothelial cell coating, the present invention has realized the advantage of providing safety in the sense of hemostasis.

  In particular, such a highly porous artificial blood vessel is used for arteries of limbs, and before use, the stitches are clogged by a pre-clotting operation. With an artificial blood vessel mixed with ultrafine fibers, a very advantageous result is obtained, and even if a fibrinolysis phenomenon occurs during or after the operation, a safe operation should be performed. I can do it.

  In particular, in a knitted structure, it is not a simple structure consisting only of weft and weft as in a woven structure, but because it is a knitted structure, the yarns in the oblique direction are three-dimensionally crossed very irregularly and three-dimensionally in the structure. "Extra fine exposed on the inner surface" shown in the prior arts such as the above-mentioned JP-A-64-1546, JP-A-61-58190, U.S. Pat. No. 4,6895,280, and U.S. Pat. No. 4,743,250. Unlike the “fiber”, in the present invention, the ultrafine fiber always enters the fiber gap inside the cloth no matter which part is used. In particular, when a knitted structure is used, it is possible to produce a structure having a space in the fiber gap, and therefore it is possible for ultrafine fibers to be always present in a dispersed state in the fiber gap inside the fabric. This is an advantage of the “ultrafine fibers existing in the fiber gap” of the present invention, unlike the “ultrafine fibers exposed on the inner surface” described in the prior art.

  At this time, if the ultrafine fibers are extremely thin fibers of 0.5 decidex or less, they are more flexible than ordinary fibers. Since the present invention has found that a fuzzy state can be created, it is confirmed that even if a small amount, that is, a very small amount of ultrafine fiber is mixed, if possible, the hemostatic effect can be improved with a knitted structure. did.

  Accordingly, considering that a part of the ultrafine fiber is used, the present invention is, in one aspect, disclosed in Japanese Patent Application Laid-Open Nos. 61-4546, 61-58190, US Pat. No. 4,6895,280, and US Although it can be considered to have relevance to Japanese Patent No. 4,743,250, it is possible to realize the advantage of utilizing the true characteristics of the ultrafine fiber by defining the strength of the ultrafine fiber in the present invention. It was.

  In the present invention, it is recommended to use ultrafine fibers in a dispersed state. Such a phenomenon occurs when a knitted structure is formed by using ultrafine fibers of 0.5 decidex or less, preferably 0.3 decidex or less, because the fibers are extremely flexible, that is, in a state where they are always scattered, that is, partly Distributed state.

  On the other hand, it is used for the weaving structure as seen in the prior arts such as JP 61-4546, JP 61-58190, US Pat. No. 4,6895,280, US Pat. No. 4,743,250, etc. When the water permeability is 500 ml or less, individual ultrafine fibers tend to clog in a finely packed manner, so that it is difficult to achieve the dispersion state aimed by the present invention.

  Therefore, it is desirable to adopt a method of making the ultrafine fibers more effectively dispersed. As a specific means, as described in JP-A-4-122252, an operation of hitting a fluid such as water at a high pressure, that is, a so-called water jet treatment is performed, so that even if a normal fiber does not become a dispersed state, it is extremely fine. It is possible to selectively disperse the fibers.

  Especially when using fibers produced by removing or exfoliating one component of a multi-component fiber, water jet treatment can effectively separate ultrafine fibers from each other. Only the ultrafine fibers can be selectively dispersed without breaking the knitting structure as the structure.

  In the prior art, as a method for numerically expressing the width of the fiber gap in this field, the state of the fiber gap is functionally expressed in the present invention. As a method for evaluating the degree of blood leakage, a measurement method called blood permeability was devised, and a structure for improving the blood permeability using the index was devised. As a result, an advancement that could not be achieved by the prior art was obtained. Furthermore, in order to obtain such a condition, it was possible to explain how it is theoretically applied by applying Laplace's law.

  In order to efficiently form a thrombus, it has long been known that promoting platelet aggregation is effective. As a method for promoting the aggregation of platelets, a method using a positively charged substance may be employed because the surface of platelets is negatively charged. Therefore, in the present invention, the method can be adopted.

  However, even when a positively charged substance is not used, platelets adhere when they come into contact with foreign substances. Therefore, in the present invention, a device other than positively charged is used to capture as much platelets as possible for hemostasis as much as possible. It was.

  When a water jet is applied, it varies depending on the water pressure applied, the nozzle diameter, the amount of water, the duration, the direction, etc., but the ultrafine fibers are more easily dispersed or entangled with each other than normal fibers.

  If it will be in such a state, compared with the structure only of a normal fiber, the form maintenance effect of a fiber structure will improve. For example, the tear strength is improved. Furthermore, the feature that the deformation | transformation of a fiber structure, etc. decreases is produced. Therefore, in the present invention, it is preferable that the used ultrafine fibers are in an entangled state.

  If the basic structure is woven due to such irregular entanglement of fibers, a fray resistance of 0.8 kg or more can be secured, and if the basic is a knitted structure, the fray resistance is 2.0 kg. The above is obtained. Such a high anti-fraying coefficient cannot be obtained with a woven or knitted fabric using only normal thickness fibers. In this respect, great progress has been made in the present invention. In particular, the effect that can be reliably obtained by using a strength of 4 g / dtex or more is important even for a thin fiber of 0.5 decidex or less.

  When using the fabric prepared in this way for medical materials such as artificial blood vessels, it is an effective means to perform bellows processing in order to maintain its form or to prevent kinks when it is made cylindrical. It is.

  Further, by wrapping a monofilament fiber having a thickness in the range of 30 to 10,000 decidex, preferably about 100 to 1,000 decidex, around the artificial blood vessel, it is possible to maintain the form and prevent kinks. This is a diversion of the prior art, but can also be used in the present invention as an effective means.

  At this time, if the monofilament has a core-sheath structure in which the sheath melting point is lower than the core melting point, the handling becomes easy. That is, heating is performed after the monofilament is attached by, for example, winding the monofilament around the fiber cloth. At this time, by applying a temperature such that the sheath part melts and the core part does not melt, the sheath part exerts the action of glue, and the fiber cloth and the monofilament core part can be fused. By this operation, the shape maintenance effect is exerted on the fiber cloth by the mechanical strength of the core portion of the monofilament after fusion.

(Fiber material)
The specific fiber material used in the present invention is not particularly limited as long as it satisfies the conditions defined in the present invention. The fiber material is preferably formed from a polymer of polyester, polyamide, polyolefin, or polytetrafluoroethylene. However, the fiber material is not limited to these, and many fiber materials may be used. Is possible.

  When the medical material in such a state is implanted in the living body, as it is clear from the high water permeability, the invasion of the cells is easy, so that blood is difficult to pass through, yet the invasion of the cells is made possible and is compatible with the living body. It has become possible to realize a medical material that has improved properties, that is, can be integrated with a living body.

(Maintaining morphology with monofilament)
Even in the case of e-PTFE artificial blood vessels made of polyester cloth or Teflon in the prior art, polyolefin monofilaments, specifically polypropylene monofilaments, are wound on the outside to resist pressure from bending or surrounding tissues. Thus, the shape of the artificial blood vessel is maintained. At this time, polyester and polypropylene, or Teflon and polypropylene are substantially incompatible with each other, and are difficult to adhere. Therefore, it is easy to peel off from each other.

  Advantages also arise in situations where they are easily peeled off. That is, when a portion that does not need reinforcement is locally generated, it can be easily peeled off as necessary. However, it is a problem if a peeling phenomenon occurs at a site where peeling is difficult. Therefore, welding that is difficult to peel off on the other side is also desired.

  In the present invention, it is recommended to divert the conventional technology that uses monofilaments to maintain the shape, but the monofilaments have a core-sheath structure, and the outer sheath part is at a temperature slightly lower than the inner core part. If it can be melted, welding becomes easy, and the strength can be maintained at the core portion that is difficult to melt for reinforcement. Therefore, in the present invention, it is recommended to use a monofilament having a core-sheath structure in which the monofilament has a core-sheath structure, and the sheath melting point is lower than the melting point of the core.

  At this time, if the same component is used for at least part of the polymer component constituting the monofilament and the polymer component of the fiber constituting the cloth, a part of the monofilament melted and welded constitutes the cloth. Since a part of the fibers to be bonded can be easily and strongly welded, the monofilament is thereby suddenly formed into a structure in which fine roots are stretched around in the structure of the cloth. By doing so, reinforcement with monofilament that is difficult to peel off can be obtained.

  The conventional technology has the feature and drawback of being easy to peel off, but in this technology, if the same component is used in at least a part of the polymer component constituting the monofilament and the polymer component of the fiber constituting the fabric. It can have the feature that it is difficult to peel off. However, it tends to be relatively difficult to peel off.

(Bioabsorbable substance)
It is also clear in the present invention that in a fibrous medical material designed in such a state, the hemostatic effect is further improved by impregnating a very small amount of a bioabsorbable substance into the fiber gap in advance. I made it.

  Conventionally, a technique for covering an artificial blood vessel using a bioabsorbable substance such as collagen or gelatin to prevent bleeding is conventionally used. However, complete coating is difficult unless a large amount of the bioabsorbable material is used for coating. This was due to the fact that these substances were easily peeled from the fiber gap.

  However, in the fabric medical material having a knitted structure manufactured according to the concept of the present invention, there are a lot of fine fibers in the fiber gap, or there are many fiber gaps and they are narrow. By simply impregnating the absorbable substance, it is possible to efficiently capture and hold the in vivo absorbable substance efficiently.

  This phenomenon can be easily understood by thinking of, for example, earthen wall painting. The mud wall is coated with mud in the place where split bamboo is assembled vertically and horizontally. At this time, the mud soil is firmly fixed to the split bamboo by cutting and mixing the mud in the mud soil. If there is no dredging, the mud form is difficult to maintain and the sticking to the split bamboo becomes unstable. In the present invention, considering that the split bamboo is a normal fiber, the cocoon is an ultrafine fiber, and the mud is a thrombus, the state is easily understood and the importance of the cocoon, that is, the ultrafine fiber You can understand the mixed effect.

  In the present invention, it has been found that at this time, it is possible to completely prevent blood leakage by increasing the amount of the bioabsorbable substance by a very small amount. This is also an effect obtained as a result of utilizing the fact that the fiber gap is large and narrow.

  The bioabsorbable substance to be impregnated can be insolubilized by a physical method such as heating, cooling, drying, ultraviolet irradiation, gamma ray irradiation, electron beam irradiation, or chemical means using various chemical crosslinking agents.

  In such a state, the bioabsorbable substance has the property of enhancing the hemostatic effect, and thereby, by impregnating a small amount of the substance, platelet aggregation is promoted more efficiently, thereby providing a medical material that is difficult to bleed. It becomes possible.

  The in vivo absorbable substance is desirably absorbed within 3 days or more and 3 months when implanted in the living body. By being present for 3 days or more, cells such as fibroblasts in the living body begin to invade into the interstices, and these cells form collagen fibers, resulting in a state in which blood does not leak. However, it is desirable that it be absorbed within 3 months since it will interfere with cell invasion if it is present forever.

  In many cases, the bioabsorbable substance is cured by drying when stored in a normal state. In order to prevent this, it is possible to prevent drying and maintain flexibility by impregnating with a polyhydric alcohol such as glycerin or sorbitol. This technique has already been used for artificial blood vessels coated with collagen or the like, and it is desirable to use it in the present invention.

  This bioabsorbable substance can have various properties as well as a hemostatic effect. In other words, it is possible to impregnate a substance having physiological activity.

  Bioabsorbable substances for that purpose include polyglycolic acid, polylactic acid, polyethylene glycol, polyvinyl alcohol, polyacrylic acid, polyvinylpyrrolidone, polylactic acid-polyglycolic acid copolymer, biodegradable (3-hydroxyl (Brate-4-hydroxylbutyrate) polyester polymer, polydioxane, collagen, gelatin, albumin, fibrin, chitosan, chitin, fibroin, cellulose, mucopolysaccharide, fibronectin, laminin, alginic acid, hyaluronic acid, chondroitin sulfate, polyamino acid, A small group selected from the group of dextran, dextrin, glucose, agarose, pectin, mannan, extracts from genetically engineered cells, substances produced from genetically engineered cells, and their derivatives. It is desirable, it characterized in having Kutomo one or more as a component.

(Bioactive substance)
The physiologically active substances to be adsorbed on these bioabsorbable substances include proteins, lipids, polysaccharides, enzymes, antibiotics, antibacterial substances, hormones, cytokines, heparin, protamine, urokinase, plasmin activator, blood anticoagulant Agents, blood coagulation promoters, cell growth factors, cell growth inhibitors, extracts from genetically engineered cells, substances produced from genetically engineered cells, vascular endothelial growth factor (VEGF), platelet-induced growth factor (PIGF), transforming growth factor beta 1 (TGF.beta.1), acid fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), transforming growth factor.alpha. (TGF.alph.), Epidermal growth factor, osteonectin, antipoietin 1 (Ang 1), Ang 2, insulin-like growth factor (IGF), pletelet-derived growth factor AA (PDGF-AA), PDGF-AB and PDGF-BB , Pletelet-derived endotherial growth factor (PD-ECGF) at least one selected from the group of bone transforming growth factor (BMP), hepatocyte growth factor (HGF), any complex or derivative thereof, etc. Although it is desirable, it is possible to have other physiologically active substances, without being limited thereto.

(Application examples)
The application site of the medical material of the present invention is not particularly limited as long as it is a site to be contacted with blood. The medical material of the present invention can be particularly suitably used at a site where blood leakage from the material may cause a problem.

  When the cloth produced in the present invention is cylindrical, for example, an artificial blood vessel, an artificial bile duct, an artificial ureter, an artificial urethra, an artificial trachea, an artificial bronchus, etc. It can be used as an alternative or a part thereof.

  Furthermore, if the fabric produced in the present invention is in a flat state, for example, artificial brain dura mater, artificial chest wall, artificial pleura, artificial pericardium, artificial heart wall, artificial diaphragm, artificial digestive tract wall, artificial peritoneum, artificial peritoneum As an abdominal wall, an artificial bladder, an artificial fascia, an artificial tendon, etc., it can be used in a patch form on an organ or tissue in a living body.

  Hereinafter, the present invention will be described more specifically with reference to examples. In the following examples, the following measuring methods were used.

(Measurement method of each physical property)
<Measurement method of blood permeability>
Create a device for measurement and prepare blood.
The device uses a blood bag and a vinyl chloride tube through which blood is introduced. This can be replaced by a tube used for blood transfusion. Next, an instrument for holding the cloth to be measured is required. For this purpose, holes are made in two acrylic plates having a thickness of about 2 mm. This hole has a width of 1 square centimeter or more. For example, a 1 cm square or a hole having a diameter of about 1.2 cm may be used. A tube of vinyl chloride is connected so that blood is guided to the hole. In this manner, the sample cloth is sandwiched and fixed between the two plates so as to coincide with the hole portion.
Next, blood is prepared. First, choose an animal that is easy to collect blood. Cattle and goats can collect blood without slaughtering animals. First, heparin is injected into a blood bag prepared from the jugular vein after intravenous injection of heparin into the animal at 1000 international units or more per kg body weight, and the ACT (Activated Clotting Time) of the blood is measured using a measuring device. At this time, if the ACT value of the blood is 400 seconds or less, heparin is further put in the blood bag to make it 400 seconds or more and used for evaluation. At that time, in order to minimize irritation to the platelets, the evaluation is carried out in a friendly manner as much as possible, and the evaluation is completed within 2 hours after blood collection. In blood collection from animals to be sacrificed, heparin is not injected into the animal's body, but heparin is added to the collected blood and mixed well, and ACT is measured and adjusted to 400 seconds or more.
The blood collected in this way is connected to the above-described apparatus, the blood is allowed to pass through the sample sample wall, and the permeation amount for the first 30 seconds is measured with a graduated cylinder. When the amount of permeation is small, it is possible to measure the weight of the permeated blood and convert the weight into volume. At this time, the difference in height between the blood bag and the sample is converted with the pressure of water corresponding to 120 mmHg, so that a difference of 162 cm is applied and the pressure at that height is applied to the sample.
Perform such measurement at least 5 times to obtain the average value, and further calculate the amount of blood permeation when the size of the hole opened in the acrylic plate is converted to 1 square centimeter, and use that value as the measurement sample. Of blood permeability. Its value is given in ml.

<Measurement method of water permeability>
As the apparatus, two acrylic plates with holes are prepared in the same manner as used in the blood permeability measurement method. Furthermore, a vinyl chloride tube is connected so that water is introduced into the hole. The size of the hole at this time is as wide as 1 square centimeter or more, as used in the blood permeability measurement method. For example, a 1 cm square or a hole having a diameter of about 1.2 cm may be used. A sample is sandwiched and fixed in the hole.
Next, prepare water. The water to be used is pure water that has been permeated through a microfilter. This is because water contamination does not cause measurement errors. The difference in height between the bag or tank containing water and the sample surface is 162 cm, as in the blood permeability measurement method.
Flowing water in this way, measuring the amount of water passing through the sample for 60 seconds with a graduated cylinder, calculating the amount of water permeated when the size of the hole opened in the acrylic plate is converted to 1 square centimeter, and that value Is the water permeability of the measurement sample. Its value is given in ml.
<Optical microscope observation sample preparation method and observation method>
If the sample to be observed is a cloth only, place it in the sample preparation process as it is.However, if the cloth is implanted in the living body, the cellular components are attached to it, so the physiological buffer solution makes it 10%. A cloth with cell components attached is put into the diluted formalin solution to fix biological components such as cells. After that, it is washed with water, and excess formalin is poured. After that, it is dehydrated using alcohol and placed on a sample preparation process cell. In that process, it was embedded in a hydrophilic resin of Technobit 7100 (manufactured by Heraeus Kulzer GmbH, Germany), solidified, and sliced to a thickness of 5 microns or less, preferably 4 microns, with a glass knife. Then, it is placed on a microscope slide glass and dried, it is stained using various staining methods, a cover glass is put on it, and it is observed with an optical microscope. Although there are various types of staining methods, hematoxylin / eosin staining is common. The observation magnification is about 40 to 200 times, mainly at 100 times. The observed photographs are saved on a computer each time and used for later analysis. Measurements such as fiber size are made by printing out an image.
<Scanning electron microscope observation sample preparation method and observation method>
If the sample to be observed is a cloth, it is put on the sample preparation process as it is. However, when the cloth is implanted in the living body, the cellular component is attached to it, so that the biological component such as the cell is physiological. Fix to formalin solution diluted to 10% with buffer or glutaraldehyde solution diluted to 2% with physiological buffer. After washing with water, excess formalin or glutaraldehyde is allowed to flow, followed by dehydration using alcohol, and final drying using a critical point drying device (HCP-2, manufactured by Hitachi, Ltd.). Place on the sample preparation process. In the process, a sample is adhered and fixed to a metal sample stage using a silver paste, and further deposited using platinum palladium under reduced pressure (about 10 ⁻³ Torr).
The sample prepared in this way is put into the body of a scanning electron microscope and observed at 10 to 3000 times with an acceleration voltage of 5 to 10 kv. The observed photographs are saved on a computer each time and used for later analysis. Measurements such as fiber size are made by printing out an image.

<Method for measuring the total number of weft yarns>
Since this measurement is limited to woven fabrics, this is a method used when counting the number of fibers of weft and weft.
The method includes measuring the cloth directly while observing it with a stereomicroscope, scratching the cloth with a resin, making a section from it, and observing it with transmitted light using an optical microscope, and metal cloth. There is a method of observing the cross section of the cloth with a scanning electron microscope.
When observing with a stereomicroscope, first fix the cloth to be inspected on a wooden cloth fixing base, and then observe with a binocular stereomicroscope from 100 to 400 times. At this time, the structure of the whole cloth is observed by observing in the longitudinal direction of the cloth and seeing how the fibers are bundled first. That is, it is first determined whether it is a simple plain weave, a weave weave, a twill weave, or a combination thereof. If this is the case, find out what kind of law the combination has, and whether each thread uses the same bundle of threads or whether the type of thread is changed. In the case of woven fabrics, wefts can be given various characteristics of the fabric structure, so observation of this structure is important. Next, the number of individual monofilament fibers contained in each bundle of fibers is measured while breaking the fibers with a sharp needle. Next, look at how many bundles measured in this way are gathered together to create one repeating structure, observe how many repetitions exist within a width of 1 cm, and multiply by these Calculate the total number of fibers.
Next, a measurement method using an optical microscope. In this case, the cloth of the sample to be observed is made of a hydrophilic resin technobit according to the method described in <Method for preparing and observing sample for optical microscope observation>. After embedding in 7100, a sample is placed with a glass knife at a right angle to the weft, that is, parallel to the weft, and the sample is sliced to a thickness of about 4 microns on that surface. This sample is placed on a slide glass like a mold, covered with a cover glass, and photographed with an optical microscope over a width of 1 cm. Thereafter, the photograph is enlarged and the total number of weft fibers included in the range is measured.
When measuring with a scanning electron microscope, as described in <Method for preparing and observing a sample for observation with a scanning electron microscope>, a sample is placed on a metal sample stage and covered with a silver paste, and a cross section of the fiber is photographed. To do. The magnification ranges from 100 times to 3000 times. The photograph taken in this way is printed out, and the number of fibers is counted on the photograph.

<Method for measuring the total number of weft yarns>
In woven fabrics, wefts are almost simple thread use. In many cases, the same yarn is often stretched straight. In order to observe this and measure the number of fibers, as in the case of a weft, when using a stereomicroscope, when creating and counting cross sections with an optical microscope, and using a scanning electron microscope, the number of fibers There is a way to measure. The same method as described in <Method for measuring the total number of wefts> is used for each.
When using a stereomicroscope, fix the fabric using the same fabric fixing tool used for observing the weft, and first place a mark at 1 cm in the lateral direction of the fabric. Within the range of the mark, observe how many bundles of fibers used for the weft are observed with a binocular stereo microscope at 100 to 400 times. Next, the number of monofilaments contained in each fiber bundle is observed while loosening the fibers with a sharp needle.
In the case of using an optical microscope or a scanning electron microscope, a sample is prepared in the same manner as the measurement of the total number of weft yarns, photographed, and counted on the photograph.

<Measurement method of fiber strength>
Two instruments for gripping and pulling the fibers were made with stainless steel bars. Hard rubber is used for the part that grips the thread, and the end of the fiber is wrapped and fixed so as not to come off. With these two instruments, a bundle of yarns, that is, many yarns are multifilaments. Then, the yarn was pulled gently, and the tension applied to it was expressed in a table on the coefficient of time to draw a so-called stress-strain curve. At this time, the degree of force applied to the fibers was measured by connecting directly to a computer via the Shimadzu Eztest apparatus and analyzed with the software of Factory SHIKIBU 2000. At this time, the elongation of the yarn and the tension immediately before breaking are measured, and the value is adjusted to the number of yarns contained in the bundle and their thickness (decidex), and the strength of the yarn per decidex is determined. Calculated.

<Method for measuring the number of ultrafine fibers>
Since ultrafine fibers are extremely thin and are often bent, the same yarn may be measured repeatedly. Therefore, measurement using a stereomicroscope or a scanning electron microscope is possible, but measurement using an optical microscope is most reliable. Specifically, as described above, a cloth is embedded in the hydrophilic resin techno bit 7100, and the slice is made by aligning it in the weft direction or the weft direction. In this case, since most of the ultrafine fibers have a fiber cross-sectional diameter of 3 microns or less, the thickness of the sections can be set to about 4 microns so that the individual fibers can be measured without overlapping each other. This method is used to take a photograph using an optical microscope and measure the thickness and number of ultrafine fibers.

<Method for measuring the thickness of ultrafine fibers>
This is measured by the same method as the above <Method for measuring the number of ultrafine fibers>, but on photography, 10 fibers showing the smallest fiber cross section are selected, and the average of the shortest cross section diameters is selected. The thickness is the value. When the fiber is cut in an oblique direction, the cross section appears large, so it is a secret to select and measure the smallest size part.

<Method for measuring sulfur content>
There are various methods for measuring sulfur. In the present invention, an oxidation (combustion) method is adopted as the most general quantitative method. First, take about 5 grams of sample. (In this case, it is convenient to use a large amount of sample in order to improve accuracy, but it is usually possible to measure even about 1 gram. In the present invention, about 5 gram is used). This is oxidized and burned by setting the temperature of the electric furnace to 850 degrees Celsius using the TSX-10, a total chlorine and sulfur literator manufactured by Mitsubishi Chemical Corporation. At this time, oxide gas is emitted, so it is introduced and dissolved in the electrolyte solution in the form of SO ₃ , and the concentration of sulfur contained in the solution is measured. The mass of the burned sample is input, and the amount of sulfur attached to the fiber is calculated using a computer. In general, polyester fiber, polyamide, and the like do not contain sulfur, so it is presumed that all the values obtained by this are sulfur adhering to the fiber.

<Measurement method of anti-fraying coefficient>
Guidance for Industry and FDA Staff. Guidance Document for Vascular prostheses 510 (k) Submissions, US Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health, Document issue. On: November 26, 1999 The test was performed according to the method.

<Measurement method of absorbability of bioabsorbable substance>
The sample to be examined is aseptically inserted into the rat subcutaneous tissue, this procedure is performed, and samples are taken at appropriate intervals from the third day to the third month and observed with an optical microscope. Observe the absorbance of the substance remaining in the sample. In general, polyester fiber has less foreign body reaction and can be a standard, so when a rat made of polyester fiber is impregnated with a substance to be evaluated and implanted in a rat, a sample exists in the fiber gap. The degree of absorption can be determined by observing whether the sample disappears from the fiber gap. The sample preparation method is in accordance with the method described in <Optical microscope observation sample preparation method and observation method>. Observation is performed between 40 times and 400 times. The staining is generally hematoxylin and eosin staining.

  First, an embodiment using an artificial blood vessel mainly having a knitted structure will be described. First, as a prototype, 90% 50D / 24F yarn (manufactured by Toray Industries, Inc. (Tokyo)), which is a fiber of normal thickness, and 300D / 3552F yarn (manufactured by Totobo Co., Ltd. (Taiwan)), which is an ultrafine fiber. ) Was used at a ratio of 10% to produce a cylinder having an inner diameter of 8 mm by a double denby knitting method. At this time, the fiber gap was narrowed by finely knitting the yarn. The details of the “knitting” method used at this time are as follows.

<Knitting method>
The knitting by the double denby method is performed by passing the yarn in an oblique direction through a normal knitting machine. This knitting method is less susceptible to fraying due to the presence of slanting yarns compared to a knitting method in which an ordinary sweater or the like is knitted by hand. This method was developed in the Denby region of Italy. Double denby is a technique in which yarns are knitted so as to overlap in two diagonal directions, and is more difficult to fray. For this reason, when the knitting is finished, there is a slight restriction on the stretchability, but the knitting structure is difficult to lose its shape, that is, a structure with high form-maintaining property.

  After a part of the prepared fabric was hardened with a hydrophilic resin, a section having a thickness of 4 μm was prepared with a glass knife, the total number of fibers present in the cross section was measured, and the ratio of the number of ultrafine fibers to ordinary fibers was calculated. However, although the ratio varies depending on the location to be selected, the number of fibers of 10% or more was occupied by ultrafine fibers at any part. The method for confirming the number of “ultrafine fibers” by region used at this time is as follows.

<Method for confirming the number of extra fine fibers>
The same method as described above in <Method for measuring the number of ultrafine fibers> is employed, embedded in a hydrophilic resin technobit 7100 to create a section, and the number is measured after photography. In this case, since many ultrafine fibers often exist in bundles, the error is eliminated by measuring the total number of fibers contained in each bundle in units of bundles. Can do. It was possible to confirm the number of photographs with such accuracy that no errors could occur.

  The ultrafine fiber used at this time is a fiber having a sea-island structure in which a soluble sulfonated isophthalic acid copolymer polyester is used as a sea component and an island component is used as an ultrafine fiber. It was washed 5 times with the solution, fully melted, and treated to expose the ultrafine fibers. The “alkaline solution cleaning” and “melting” treatments used at this time were performed as follows.

<Method of alkaline solution cleaning / melting>
Caustic soda is used as the alkali. First, a 0.25% NaOH solution is heated to 100 degrees Celsius, a sample is charged, and maintained for 60 minutes while stirring by high-pressure water jet. At this time, a sufficient alkaline solution having a ratio of the amount of the sample to the alkaline solution of 1: 100 or more is used. After performing this operation twice, wash with hot water at 100 degrees Celsius for 30 minutes, then add 0.05% acetic acid to neutralize the remaining alkali, and again wash with hot water at 100 degrees Celsius for 30 minutes. Repeat the washing procedure twice.

  The ultrafine fiber used for this was 0.4 dtex, and when the value of S adhering to it was examined, it was 0.3 ppm.

  It was 4.2 g / dtex when the tensile strength of the ultrafine fiber used for this was investigated by Shimadzu Corporation EZ-TEST.

  Guidance for Industry and FDA Staff.Guidance Document for Vascular prostheses 510 (k) Submissions, US Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health , Document issue. On: November 26, 1999. According to the Suture Retention Test method, the value was 2.42 kg.

  Next, an artificial blood vessel similar to that in Example 1 was prepared. At this time, the ultrafine fiber 70D / 480f of U company (Unitika) was used, and the ratio of the ultrafine fiber was 5% and the normal fiber was 95%. A similar double denby knitted artificial blood vessel was produced. At this time, alkali washing was performed three times.

  The ultrafine fiber used for this was 0.34 dtex, and the value of S adhering to it was 0.1 ppm or less.

  It was 4.0 g / dtex when the tensile strength of the ultrafine fiber used for this was investigated by Shimadzu Corporation EZ-TEST.

  The fray resistance of the cut end of this artificial blood vessel was 2.01 kg. That is, even when the strength of the ultrafine fiber is sufficient, it has been found that if the amount is small, the amount and ratio appearing at the cut end will be small and sufficient to improve fraying resistance. From this, it became clear that when the ratio of the ultrafine fibers decreases, the fray resistance also decreases.

  Next, an artificial blood vessel similar to that in Example 1 was prepared. At this time, the ultrafine fiber 105D / 700f of company A was used, the ultrafine fiber was used at a ratio of 20%, and the normal fiber was used at a ratio of 80%. An artificial blood vessel of double denby knitting was prepared. At this time, alkali washing was performed three times.

  The ultrafine fiber used for this was 0.15 dtex, and the value of S adhering to it was examined with a total chlorine / sulfur analyzer TSX-10 manufactured by Mitsubishi Chemical Corporation.

  It was 2.1 g / dtex when the tensile strength of the ultrafine fiber used for this was investigated by Shimadzu Corporation EZ-TEST.

  The fray resistance of the cut end of this artificial blood vessel was 1.25 kg. That is, it has been found that when the strength of the ultrafine fiber is weak, even if the amount is sufficient, the knitted structure is insufficient to improve the fray resistance. From this, it has been found that the strength of the ultrafine fibers used is required to be equal to or higher than 4.0 g / dtex of ordinary fibers.

  It was 550 ml when the water permeability of the cloth produced in Example 1 was measured. Furthermore, when the blood permeability was measured with blood collected from goats and with heparin added to increase the ACT to 400 seconds or longer (that is, blood that substantially suppressed thrombus formation based on the fibrin pathway), it was 53 ml. Therefore, the value of Q = WP / BP, which is the ratio between the water permeability and the blood permeability, was about 10.4.

(Implantation in dogs)
The tube produced in Example 1 was 6 cm in length, and was implanted as an artificial blood vessel into the descending aorta of the dog's chest. The cloth tube prepared before implantation was brought into contact with blood and pre-clotting was performed only once. He then implanted, but there was no bleeding from the walls. The pre-clotting and the implantation method as an artificial blood vessel used at this time were as follows.

<Pre-crotting and implantation method>
The method of Yates, SG (Yates SG, Barros AAB, Berger K, Fernandez LG, Wood SJ, Rittenhouse EA, Davis CC, Mansfield PB, Sauvage LR. The preclotting of porous arterial prostheses. Ann Surg 1978; 188: 611-622. ) Was performed as follows.
Basically, the blood of the host to be implanted is taken and poured into an artificial blood vessel. A blood clot is made in the fiber gap of the artificial blood vessel. Perform this operation several times, and then check that there is no thrombus in the artificial blood vessel, and finally flow physiological saline mixed with heparin into the artificial blood vessel to prevent excessive thrombus formation on the inner surface. To do. However, this operation, that is, the cleaning of the lumen with physiological saline mixed with heparin may be omitted.
Regarding the implantation, a blood vessel at a site where the implantation is performed is detached from the surroundings, an arterial forceps is applied to block the blood flow, and the blood vessel is excised. An artificial blood vessel suitable for the size of the lumen of the blood vessel at that site is selected and implanted. For anastomosis, 5-0 polyester multifilament thread is used for continuous stitching.

  Heparin was administered to the implanted animal immediately after implantation to bring the ACT into a state of 400 seconds or longer, but no bleeding from the wall of the artificial blood vessel was observed.

  When an artificial blood vessel implanted in the descending aorta of the dog was collected one year later, the inner surface was white and thrombus was not observed. There was no scar tissue or foreign body reaction around the artificial blood vessel, and it was in a calm state.

  An implantation experiment into the descending thoracic aorta of a dog was performed by changing the degree of washing of the ultrafine fibers with alkali (in Example 1). That is, in the operation of removing soluble polyester by washing with heated alkali, the number of washings is changed, and the amount of sulfone groups contained in the soluble polymer remaining on the fibers at that time is determined by quantitative determination of S. As a result, it was 125 ppm for the first washing, 3 ppm for the second washing, 1.5 ppm for the third washing, 0.6 ppm for the fourth washing, and 0.3 ppm for the fifth washing.

  These washed artificial blood vessels were implanted into the descending thoracic aorta of dogs and collected one year later. When each artificial blood vessel showed a value of 125 ppm for the first washing and 3 ppm for the second washing, the ultrafine fiber portion The calcification phenomenon was observed. Since the calcification appeared strongly in the order of the first washing and the second washing, it was found that the calcification was accelerated by the remaining amount of the sulfone group. At this time, the degree of “calcification” was determined by a method of observing the collected sample with an optical microscope. At this time, the sample is subjected to Von Kossa staining. This observation method is based on the method of the following literature. Ilse G, Ryan N, Kovacs K, Ilse D. Calcium deposition in human pituitary adenomas studied by histology, electron microscopy, electron diffraction and X-ray spectrometry. Exp Pathol (Jena). 1980; 18 (7-8): 377- 88.

  On the other hand, calcification was not observed in the artificial blood vessel of 1.5 ppm for 3 times washing, 0.6 ppm for 4 times washing, and 0.3 ppm for 5 times washing. Therefore, it was recognized that calcification occurs when the value of S attached to the ultrafine fibers increases. Therefore, in the following examples, an artificial blood vessel in which alkaline washing was performed 5 times and the S value was confirmed to be 2 ppm or less was used.

  As a prototype, a 50D / 24F yarn (made by Toray Industries, Inc.) 90% and a 300D / 3552F yarn (produced by Totobo Co., Ltd.) were used at a ratio of 10% to produce a cylinder having an inner diameter of 8 mm by a double denby knitting method. . At this time, the fiber gap was slightly narrowed by knitting the yarn with moderate tension (ie, tensioning the loom yarn and tensioning it as much as possible without breaking the yarn). After a part of the prepared fabric was hardened with a hydrophilic resin, a section having a thickness of 4 μm was prepared with a glass knife, the total number of fibers present in the cross section was measured, and the ratio of the number of ultrafine fibers to ordinary fibers was calculated. However, although the ratio varies depending on the place to be selected, the number of fibers of 30% or more was occupied by the ultrafine fibers at any part. The knitting method used at this time was as follows.

<Knitting method>
The knitting method by the double denby method as described in <Knitting method> is adopted. This method is carried out by passing diagonal yarns through a normal knitting machine so as to intersect two times. As described above, this knitting method is less susceptible to fraying due to the presence of two diagonal yarns. The Denby method is a method of knitting developed in the Denby region of Italy. Double denby is a technique in which yarns are knitted so as to overlap in two diagonal directions, and is more difficult to fray. For this reason, when the knitting is finished, there is a slight restriction on the stretchability, but the knitting structure is difficult to lose its shape, that is, a structure with high form-maintaining property.

  It was 1240 ml when the water permeability of the produced cloth was measured. Furthermore, when the blood permeability was measured with blood collected from goats, and heparin was added to make ACT more than 400 seconds, it was 96 ml. Therefore, the value of Q = WP / BP was about 14.0.

  The tube produced above was taken 6 cm in length, and was implanted as an artificial blood vessel into the descending thoracic aorta of a dog by the same method as in Example 2. The cloth tube prepared before implantation was brought into contact with blood and pre-clotting was performed only once. He then implanted, but there was no bleeding from the walls.

  Heparin was administered to the implanted animal immediately after implantation to bring the ACT into a state of 400 seconds or longer, but no bleeding from the wall of the artificial blood vessel was observed.

  As a prototype, 50D / 24F yarn (manufactured by Toray Industries, Inc.) 60% and 300D / 3552F yarn (manufactured by Totobo) are used in a ratio of 40% to produce a cylinder with an inner diameter of 8 mm by double denby knitting. did. At this time, the fiber gap was loosened by knitting the yarn without tension. After a part of the prepared fabric was hardened with a hydrophilic resin, a section having a thickness of 4 μm was prepared with a glass knife, the total number of fibers present in the cross section was measured, and the ratio of the number of ultrafine fibers to ordinary fibers was calculated. However, although the ratio varies depending on the location to be selected, the number of fibers of 50% or more was occupied by ultrafine fibers in any part.

  It was 1530 ml when the water permeability of the produced cloth was measured. Furthermore, when blood permeability was measured with blood collected from goats and heparin added to make ACT 400 seconds or longer, it was 67.8 ml. Therefore, the value of Q = WP / BP was about 22.1.

  The tube prepared above was 6 cm in length and was implanted as an artificial blood vessel into the descending thoracic aorta of a dog. The cloth tube prepared before implantation was brought into contact with blood and pre-clotting was performed only once. He then implanted, but there was no bleeding from the walls.

  When heparin was administered to the implanted animal immediately after implantation to bring the ACT to a state of 400 seconds or longer, bleeding from the wall of the artificial blood vessel was not observed.

(Comparative Example 1)
A commercially available artificial blood vessel with a knitted structure (manufactured by Inter Vascular, trade name: MICRON) was used as the target product. A portion of this fiber is present in the cross section after a section of 4 μm in thickness is prepared with a glass knife after being hardened with a hydrophilic resin in the same manner as described in the above-mentioned “Method for preparing optical microscope observation sample”. When the ratio of the number of ultrafine fibers to normal fibers was calculated, only normal thickness fibers were found, and no ultrafine fibers were present. Specific names of the commercially available artificial blood vessels having a knitted structure used at this time are as follows.

  The water permeability of this commercially available artificial blood vessel was measured and found to be 1200 ml. Further, when the blood permeability was measured with blood collected from goats and heparin added to make the ACT 400 seconds or longer, it was 206 ml. Therefore, the value of Q = WP / BP was about 5.8.

  The artificial blood vessel used above was 6 cm in length, and was implanted as an artificial blood vessel into the descending aorta of the dog's chest. The cloth tube prepared before implantation was brought into contact with blood and pre-clotting was performed only once. After implantation, there was a large amount of bleeding from the wall, and a compression and hemostasis operation for several minutes was necessary.

  When heparin was administered to an animal implanted immediately after implantation to bring the ACT to a state of 400 seconds or longer, there was a large amount of bleeding from the wall of the artificial blood vessel, and hemostasis was extremely difficult.

(Comparative Example 2)
As another target product, a commercially available artificial blood vessel having a knitted structure (manufactured by Bard, trade name: Bionit) was used. After a part of this was hardened with a hydrophilic resin, a 4 μm thick slice was prepared with a glass knife, the total number of fibers present in the cross section was measured, and the ratio of the number of ultrafine fibers to normal fibers was calculated. The fiber was only thick, and no ultrafine fiber was present.

  The water permeability of this artificial blood vessel was measured and found to be 1640 ml. Furthermore, when the blood permeability was measured with blood collected from goats and heparin was added to make the ACT more than 400 seconds, it was 320 ml. Therefore, the value of Q = WP / BP was about 5.1.

  The above-mentioned commercially available artificial blood vessel having a knitted structure was taken 6 cm in length, and was implanted as an artificial blood vessel into the descending aorta of the dog's chest. The cloth tube prepared before implantation was brought into contact with blood and pre-clotting was performed only once. After implantation, there was a large amount of bleeding from the wall, and a compression and hemostasis operation for several minutes was necessary.

  When heparin was administered to an animal implanted immediately after implantation to bring the ACT to a state of 400 seconds or longer, there was a large amount of bleeding from the wall of the artificial blood vessel, and hemostasis was extremely difficult. From this, it was proved that the artificial blood vessel produced by the technique of the present invention is more difficult to bleed and is safer.

  When the artificial blood vessel shown in Example 4 was prototyped as a prototype, a bulky processed yarn (obtained from Shindo Textile Co., Ltd.) was used as the normal thickness fiber at a rate of 10%. When a blood vessel was prepared and the obtained artificial blood vessel was evaluated in the same manner as in Example 4, good results could be obtained in the same manner.

  When the artificial blood vessel shown in Example 4 was prototyped as a prototype, raising operation was performed to make napped and loops in normal fibers, and the obtained artificial blood vessel was evaluated in the same manner as in Example 4, Similarly good results were obtained. The “raising operation” at this time was performed as follows.

<Raising operation>
Brushing is basically done by inserting a cloth between rollers with countless needles with small hooks and rotating them, and the needle pierces the fabric while the cloth passes through this narrow space. Raising of the fiber is caused to raise. Accordingly, the depth and degree of raising are changed according to the strength of the pinching between the cylinder having the needle and the roller, and further, the uniformity is made uniform by repeating this operation. However, if it is excessive, the fabric will be damaged.
This raising was repeated 10 to 15 times using a raising apparatus KU-50S manufactured by Kanai Important Industry Co., Ltd.

When the artificial blood vessel shown in Example 4 was made as a prototype, a multicomponent fiber (manufactured by Nanya Plastics (Taiwan)) made of polypropylene and polyester was used. An artificial blood vessel containing ultrafine fibers made only of polyester was prepared. And when the same evaluation was performed, the same good results could be obtained. The method of dissolving the polypropylene used in this case, using n- decane _{(n-Decane) C 10 H} 22 / CH 3 (CH 2) 8 CH 3, carried out by heating to 174 ° C..

When the value of S adhering to the ultrafine fiber used for this was investigated, it was 0.1 ppm or less.
It was 4.7 g / dtex when the tensile strength of the ultrafine fiber used for this was investigated by Shimadzu Corporation EZ-TEST.

  Further, when a water jet was jetted at a pressure of 70 atm to an artificial blood vessel using multicomponent ultrafine fibers in this way, an artificial blood vessel in which the fibers were entangled could be obtained. And when the same evaluation as other artificial blood vessels was performed, better results were obtained. The water jet injection method used at this time was as follows.

<Water jet injection method>
Insert a stainless steel rod into the artificial blood vessel. At this time, select a rod that is not too tight so that the difference between the size of the lumen of the artificial blood vessel and the size of the stainless steel rod is small. This rod is connected to a device capable of rotating about 5 to 10 revolutions per minute. Next, water with a pressure of 80 atm is made with a high-pressure water generator and sprayed from a nozzle to an artificial blood vessel from a close distance of 1 to 3 cm. At this time, the artificial blood vessel is rotated with a stainless steel rod. The nozzle is moved back and forth in the longitudinal direction of the artificial blood vessel. By this method, high-pressure water is uniformly applied to the artificial vascular cloth on the artificial vascular cloth, and the fibers raised on the outer surface are pushed into the interstices between the fibers. The fibers raised on the cavity surface also flow into the fiber gap and enter. As a result, a complicatedly entangled fiber entangled state is obtained.

  When making the artificial blood vessel shown in Example 4 as a prototype, a water jet was applied for 5 minutes at a water pressure of 80 kg. When the cloth was observed with a scanning electron microscope, the ultrafine fibers were entangled with each other and had an irregular and complicated structure.

  When the water permeability of the artificial blood vessel thus produced was measured, the state before applying the water jet was 1240 and that after the treatment was 1201. That is, although the water permeability slightly decreased, there was no significant change.

  Guidance for Industry and FDA Staff.Guidance Document for Vascular prostheses 510 (k) Submissions, US Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health, Document issue. on: November 26, 1999. The value before the treatment was 2.22 kg, and the value after the treatment was 2.41 kg. there were.

(Comparative Example 3)
When a Suture retention test was performed using a commercially available artificial blood vessel having a knitted structure (water permeability: 1200; manufactured by Inter Vascular, trade name: MICRON), the value was 1.75 kg. From this, even in an artificial blood vessel having substantially the same water permeability, the anti-fraying property is improved by mixing ultrafine fibers in the artificial blood vessel of the present invention, and the water jet treatment is performed to make the ultrafine fibers entangled. It has been found that further formation improves.

  When the artificial blood vessel shown in Example 4 was prototyped as a prototype, the bellows was processed, and kink prevention was possible even if it was bent. This bellows processing was performed by the following method.

<Bellows processing>
Prepare a stainless steel bar threaded to a width of 1 to 2 mm and its depth. For the relationship between the outer diameter of the rod and the inner diameter of the artificial blood vessel, a size that is not too loose and not too tight is selected as much as the relationship between the stainless steel rod used in the water jet and the artificial blood vessel.
First, a threaded stainless steel rod is passed through a tube of artificial blood vessel. At this time, do not insert too much, but insert it with a little space. Next, in accordance with the threaded portion, a stainless steel wire is wound from the outside so that the artificial blood vessel cloth is in close contact with the cut screw. At this time, looseness, wrinkles, over-tensioning, twisting, etc. are likely to occur in the cloth, so it is important to wind it while correcting it each time. In this way, it is wrapped around a stainless steel rod and made into a mold with a stainless steel wire, and then left in an oven kept at 180 degrees Celsius for 30 minutes to perform heat setting. Then, gradually cool the temperature, remove the stainless steel wire, and remove it from the stainless steel rod.
If the bellows state is not sufficient at this time, the same heating is performed again, but the second time, a simple round bar is used instead of a stainless steel bar with a thread cut. Then, without using a stainless steel wire, heating is performed in a state where the artificial blood vessels are brought close together and the bellows of the bellows is made dense. This completes a uniform and precise bellows processing.

  When the artificial blood vessel shown in Example 4 was prototyped as a prototype, a polypropylene monofilament (made by Chisso Corporation, trade name: ES fiber) having a thickness of 300 dedex was wound around the outer periphery in a spiral shape at intervals of 2 mm. (The fusing operation is a diversion of a conventional method of making a nonwoven paper diaper.) The monofilament used had a core-sheath structure, the melting temperature of the true part was 195 ° C., and the melting temperature of the sheath part was 170 ° C. Then, when it heated at 180 degreeC for 20 minute (s), the sheath part melt | dissolved and fuse | melted and it was in the state which was hard to peel from an artificial blood vessel. By this operation, kinking can be prevented even if bending is performed in the same manner as the bellows processing.

  When the artificial blood vessel shown in Example 4 was made as a prototype, it was neutralized after impregnating an acidic solution of 1% atelocollagen, and then manufactured by polyepoxy compound (Nagase Kasei Co., Ltd.) (trade name Denacol) Crosslinked with EX-313). For such atelocollagen impregnation, neutralization and crosslinking, see, for example, the document T. Miyata, T. Taira, Y. Noishiki: Clinical Materials 2., Collagen Engineering for Biomaterial Use., Jerome A. Werkmeister, John AM Ramshaw , Christina. Doyle, AU 'Dan' Daniels, H. Kawahara, DF Williams, P. 139-148, Elsevier Science Publishers Ltd, 1992.

  When this artificial blood vessel was implanted into the thoracic aorta of a dog in the same manner as in Example 6 without pre-clotting, blood soaked into the artificial blood vessel wall and turned red, but no bleeding from the artificial blood vessel wall was observed. It was. That is, it was proved that the need for pre-clotting was eliminated by a small amount of collagen, and the hemostatic effect was dramatically increased.

  When the artificial blood vessel shown in Example 4 was prototyped as a prototype, an acidic solution of 1% carbomethylcellulose was soaked and then naturally dried, and then thermally crosslinked at 120 ° C. for 6 hours under vacuum. Next, it was neutralized with 0.01N caustic soda, made into a 10% glycerin-containing alcohol solution, dried, and autoclaved. Regarding such impregnation, neutralization, drying and sterilization of carbomethylcellulose, reference can be made, for example, to US Pat. No. 4,521,594 and JP-A-58-104901.

  When this artificial blood vessel was implanted into the thoracic aorta of a dog in the same manner as in Example 6 without pre-clotting, blood soaked into the artificial blood vessel wall and turned red, but no bleeding from the artificial blood vessel wall was observed. It was. That is, it was proved that the need for pre-clotting was eliminated by a small amount of collagen, and the hemostatic effect was dramatically increased.

  When the artificial blood vessel shown in Example 6 was prototyped as a prototype, it was neutralized after impregnating an acidic solution of 1% atelocollagen and then crosslinked with a polyepoxy compound. The artificial blood vessel was impregnated with 10 ng of basic fibroblast growth factor. Regarding such atelocollagen impregnation, neutralization, cross-linking and fibroblast growth factor impregnation, see, for example, the document T. Miyata, T. Taira, Y. Noishiki: Clinical Materials 2., Collagen Engineering for Biomaterial Use. Jerome A. Werkmeister, John AM Ramshaw, Christina. Doyle, AU 'Dan'Daniels, H. Kawahara, DF Williams, P. 139-148, Elsevier Science Publishers Ltd, 1992.

  Thereafter, when this artificial blood vessel was implanted into the thoracic aorta of a dog in the same manner as in Example 14, fibroblasts actively invaded into the artificial blood vessel wall one week after implantation, and the effect of cell growth factor was clearly demonstrated. It became clear that it was out. “Invasion of fibroblasts” at this time was confirmed by a method in which a section having a thickness of 4 μm was prepared as a sample for an optical microscope, stained with hematoxylin and eosin, and observed at a magnification of 40 to 200 times.

  The examples described above are examples of an artificial blood vessel having a knitted structure, but a membrane-like material could be obtained by cutting a cylindrical medical material produced by the same method in the major axis direction.

  When this membrane is used on the heart wall of the animal (dog), pericardium, chest wall, abdominal wall, bladder wall, trachea wall, etc., it has little blood leakage as well as an artificial blood vessel, or has cytophilicity. The function as a good medical material was seen. At this time, the degree of “blood leakage” was confirmed by the weight of blood adhering to the gauze during the operation.

  As shown in the above examples, in the fabric having a knitted basic structure, it has been found that a safe medical material with low blood leakage and also good cell affinity can be obtained easily in the present invention. It has been clarified that the effect of the present invention is remarkably exhibited.

  Next, the Example regarding the medical material made from the fiber which has a woven structure is shown. First, 50D / 24F yarn (manufactured by Toray Industries, Inc.) is used as the weft, and 300D / 3552F yarn (manufactured by Totobo Co., Ltd.) and 150D / 108F yarn (manufactured by Toray Industries, Inc.) are used as the weft. The table was used to create a mixed weave and twill weave. (For details on how to make such a mixed fabric, refer to Bibliography of Dyeing, Tsuneo Yoshioka et al., Kyoto Shoin Publishing. Is possible). There were 78 wefts in a 1 cm width, and wefts were 31 300D / 3552F and 31 150D / 108F. This is Cloth A.

  The ultrafine fiber used for this was 0.4 dtex, and the value of S adhering to it was examined by Mitsubishi Chemical's total chlorine / sulfur analyzer TSX-10, and it was 0.3 ppm.

  It was 4.2 g / dtex when the tensile strength of the ultrafine fiber used for this was investigated by Shimadzu Corporation EZ-TEST.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. There was 2.1 kg.

The total number of wefts in this fabric is 1,872, the total number of wefts is 113,460, the water permeability (WP) is 33, and the blood permeability (BP) is 3.4. Therefore, the value of R = (N + M) ² / WP was 403, 078, 855, and the value of Q = WP / BP was 9.7.

  As prototypes, 50D / 24F yarn (made by Toray Industries, Inc.) is used for the weft, 300D / 3552F yarn (made by Totobo Co., Ltd.), and 150D / 108F yarn (made by Toray Industries, Inc.) as the weft. Used to prepare a mixed weave and twill weave. There were 78 wefts in a width of 1 cm, and wefts were 300D / 3552F and 30 150D / 108F. This is Cloth B. This fabric has the same structure as the fabric A, but when weaving, adjust the tension of the yarn (that is, loosely tension the yarn of the loom so that it does not sag) and slightly leave the yarn gap. did.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. There was 2.0 kg.

The total number of wefts in this fabric was 1,872, the total number of wefts was 113,460, the water permeability (WP) was 66, and the blood permeability (BP) was 5.3. Therefore, the value of R = (N + M) ² / WP was 403, 078, 855, and the value of Q = WP / BP was 12.5.

  As the next prototype, 50D / 36F yarn (made by Toray Industries, Inc.) is used as the weft, and 245D / 1440F yarn (made by Toray Industries, Inc.) and 150D / 108F yarn (made by Toray Industries, Inc.) are used as the weft. Were used in the table to prepare a mixed weave and twill weave. There were 78 wefts in a 1 cm width, and wefts were 245D / 1440F and 30 150D / 108F. This is Cloth C.

  The ultrafine fiber used for this was 0.3 dtex, and the value of S adhering to it was examined with a total chlorine / sulfur analyzer TSX-10 manufactured by Mitsubishi Chemical, and found to be 0.1 ppm or less.

  It was 4.5 g / dtex when the tensile strength of the ultrafine fiber used for this was investigated by Shimadzu Corporation EZ-TEST.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. 1.9 kg.

The total number of wefts in this fabric is 2,808, the total number of wefts is 44,316, the water permeability (WP) is 111, and the blood permeability (BP) is 5.2. Therefore, the value of R = (N + M) ² / WP was 20, 002, 652, and the value of Q = WP / BP was 21.3.

  As the next prototype, 50D / 36F yarn (made by Toray Industries, Inc.) is used as the weft, and 245D / 1440F yarn (made by Toray Industries, Inc.) and 150D / 108F yarn (made by Toray Industries, Inc.) are used as the weft. Were used in the table to prepare a mixed weave and twill weave. There were 78 wefts in a 1 cm width, and wefts were 245D / 1440F and 30 150D / 108F. This is cloth D. This fabric has the same configuration as the fabric C, but when weaving, the tension of the yarn was adjusted so that a slight gap between the yarns was produced.

The total number of wefts in this fabric is 2,808, the total number of wefts is 44,316, the water permeability (WP) is 111, and the blood permeability (BP) is 9.1. Therefore, the value of R = (N + M) ² / WP was 20, 002, 652, and the value of Q = WP / BP was 12.2.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. There was 1.8 kg.

  The fiber of the artificial blood vessel (trade name: UBE graft) of a commercially available artificial blood vessel (U company; Ube Industries, Ltd.) was analyzed. This was a plain weave structure, with 48 wefts at a spacing of 1 cm at 60D / 50F, and 40 wefts at the same 60D / 50F in 1 cm. This is called cloth E.

The total number of wefts in this fabric was 4,800, the total number of wefts was 8,640, the water permeability (WP) was 25, and the blood permeability (BP) was 10.8. Therefore, the value of R = (N + M) ² / WP was 7,225,344, and the value of Q = WP / BP was 2.3.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. It was 0.5 kg.

  After the cloth D examined with the artificial blood vessel of a commercially available artificial blood vessel (U company) was mechanically loosened to be soft and slightly deformed, the fiber was analyzed. This was of course a plain weave structure. Then, there were 48 wefts at a spacing of 1 cm at 60 D / 50 F, and there were 39 wefts at the same 60 D / 50 F in 1 cm. This is fabric F.

The total number of wefts in this fabric is 4,800, the total number of wefts is 8,640, the water permeability (WP) is 25, and the blood permeability (BP) is 16.2. Therefore, the value of R = (N + M) ² / WP was 7,225,344, and the value of Q = WP / BP was 1.5.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. It was 0.5 kg.

  Analysis of the fiber of the artificial blood vessel (trade name: ULP) of a commercially available artificial blood vessel (Company I; Inter Vascular) was performed. This was a plain weave structure, with wefts at 60D / 50F and 64 in 1 cm intervals, and wefts with 36 same 60D / 50F in 1 cm. This is called cloth G.

The total number of wefts in this fabric is 1,080, the total number of wefts is 10,336, the water permeability (WP) is 101, and the blood permeability (BP) is 19.3. Therefore, the value of R = (N + M) ² / WP was 1,291,251, and the value of Q = WP / BP was 5.2.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. It was 0.4 kg.

  Analysis of the fiber of the artificial blood vessel (trade name: LP) of a commercially available artificial blood vessel (Company I; Inter Vascular) was performed. This was a plain weave structure, with 45 wefts at a distance of 1 cm at 60 D / 50 F, and 29 wefts with the same 60 D / 50 F at a distance of 1 cm. This is called cloth H.

The total number of wefts in this fabric was 2,040, the total number of wefts was 4,480, the water permeability (WP) was 260, and the blood permeability (BP) was 47.7. Therefore, the value of R = (N + M) ² / WP was 7,225,344, and the value of Q = WP / BP was 5.5.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. It was 0.4 kg.

  The fiber of the artificial blood vessel (trade name: Meadox Double Verour) of a commercially available artificial blood vessel (M company; Meadox) was analyzed. This was a plain weave structure with 36 wefts at 60D / 50F at 1cm intervals and 36 wefts at the same 60D / 50F in 1cm. This is Cloth I.

The total number of wefts in this fabric was 3,672, the total number of wefts was 3,888, the water permeability (WP) was 390, and the blood permeability (BP) was 80.6. Therefore, the value of R = (N + M) ² / WP was 146, 548, and the value of Q = WP / BP was 4.8.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. It was 0.3 kg.

  The fiber of the artificial blood vessel (trade name: Meadox Cooley Low porosity) of a commercially available artificial blood vessel (Company M) was analyzed. This was a plain weave structure with 57 wefts at 60D / 50F at 1cm intervals and 36 wefts at the same 60D / 50F in 1cm. This is called cloth J.

The total number of wefts in this fabric is 1,998, the total number of wefts is 5,800, the water permeability (WP) is 68, and the blood permeability (BP) is 18.6. Therefore, the value of R = (N + M) ² / WP was 894, 247, and the value of Q = WP / BP was 3.7.

  When this cloth was cut at an angle of 45 degrees and pulled 2 mm away from the cut end with a thread, the force required to fray it was examined with Shimadzu EZ-TEST. It was 0.4 kg.

  Next, the dog blood subjected to a pressure corresponding to 120 mmHg was passed through the fabrics A to J obtained above. This blood was collected by administering heparin to an animal, and its ACT value was 400 seconds or more, which was blood that prevented thrombus formation by fibrin.

  The above results and the calculated values obtained from them are shown in the following table.

Among these, the fabrics exceeding 8 × 10 ⁶ with respect to the value represented by the formula of the reference value R = (N + M) ² / WP of the present invention were A, B, and C using ultrafine fibers.

  Next, about each sample (AJ) performed by 17 to 26, the sample after 24 hours dog implantation was observed by 3000 times with the scanning electron microscope (Hitachi Co., Ltd. brand name: H-800). However, in Samples A, B, C, and D, the fiber gap was narrow, and red blood cells and platelets entered the gap, and the fiber gap was completely bridged by these. However, in the samples from E to J, the fiber gap was wide and red blood cells and platelets were seen in the gap, but they were scattered, and there was no clogging that bridged the fiber gap.

  Next, in samples A, B, C, and D, the sample was repeatedly washed with physiological saline, and the sample after removing blood adhesion with the naked eye was again measured with a scanning electron microscope (3000 times). Observations were made. As a result, it was clarified that the erythrocytes seen in the above examples flowed away, platelets aggregated in the subsequent fiber gap, and the fiber gap became a bridging state.

From this example, in A, B, C, and D, which are fiber fabrics exceeding 8 × 10 ⁶ with respect to the value of R = (N + M) ² / WP of the present invention, the bridging state of the fiber gap between red blood cells and platelets is Turned out to be observed. Further, when the erythrocytes were washed away, it was found that there was aggregation of platelets and bridging of the interstices caused thereby.

  As is clear from these examples, in relation to the relationship between the high water permeability and the amount of blood leakage, A, B, C, and D exceeding the reference value of the present invention have a blood leakage as compared with the water permeability. It can be seen that the amount of is small. On the other hand, in other samples that did not exceed the reference value, it can be seen that a sample with a large amount of water permeation has a large amount of blood leakage almost in proportion thereto.

That is, in the fabric including ultrafine fibers based on a woven structure satisfying R = (N + M) ² / WP> 8 × 10 ⁶ and Q = WP / BP> 6 of the present invention, the knitting shown in Example 1 It shows that it is possible to provide a medical material made of fiber with less blood leakage, similar to a fabric of structure.

  The present invention will be described below with reference to the drawings.

FIG. 1 is a schematic perspective view showing a fabric structure (typical Denby knitting structure) knitted with fibers having a normal thickness. Unlike woven fabrics, it shows the relationship between yarns that are entangled with each other using complex yarns. FIG. 2 is a schematic perspective view showing a knitted fabric having a Denby structure knitted in the state of FIG. The ultrafine fibers run so as to be entangled with fibers having a normal thickness, but are very thin and tend to be separated from the fiber bundle. That is, it exists in a fuzzy state. This narrows the fiber gap. FIG. 3 is a schematic perspective view showing Denby knitting in which the ultrafine fiber is run along with the structure of FIG. 1 as shown in FIG. By applying a water jet of about 80 kg in this state, the ultrafine fibers are selectively separated from the running of the normal thickness fibers, and are in a state where the fibers are entangled in the form of cocoons. In this state, since the individual fiber gaps become extremely narrow, thrombotic tissues centered on platelets are easily captured in the fiber gaps, and are difficult to peel off. FIG. 4 is a schematic cross-sectional view for explaining Laplace's law with the tension applied to the thrombus membrane stretched between the fiber gaps. (A) is a thrombotic membrane stretched between fiber fibers of only normal thickness. On the right is a thrombosis membrane when ultrafine fibers are present in the normal gap between the fibers. When the same internal pressure, that is, blood pressure is applied in this state, the left thrombus film forms a large arc and spreads. (B) forms a small arc. At this time, according to Laplace's law, a tension proportional to the size of the arc, that is, its radius is applied to the film. In view of this, it can be seen that a greater tension is applied to the thrombosis membrane formed in the fiber gap of only the normal thickness fibers compared to the thrombosis membrane in the presence of ultrafine fibers. Then, it can be understood that the thrombosis membrane is easily broken in the left state and stable in the right state. FIG. 5 is a schematic plan view showing the basic structure of a plain weave fabric. Weft and weft are woven alternately. The fibers used are normal thickness fibers. FIG. 6 is a schematic plan view showing a basic structure in the case of a plain woven fabric using ultrafine fibers for the weft. Wefts of normal thickness and wefts of extra fine fibers are woven alternately. When the ultrafine fibers are simply woven, the individual fibers are in a bundled state as described above, so that the fiber gaps are extremely tight and easily fall into a densely packed state. FIG. 7 is a schematic perspective view showing a basic structure when a bulky processed yarn is used as the weft in a plain weave woven fabric. Wefts of normal weft and bulky processed yarn are woven alternately. In the bulky processed yarn, the fibers are separated from each other and the fiber gap is wide. Even if the fiber having the same thickness as that in FIG. 5 is used, a fiber gap that is not finely packed can be obtained by using the bulky processed yarn for the weft. FIG. 8 is a schematic perspective view showing a state in which a very fine fiber is used for a weft and a raised treatment is performed on a woven fabric having a plain weave structure. Even if the ultrafine fibers are bulky, it can be in this state, and the ultrafine fiber-forming composite fiber is processed temporarily to give it a latent crimping ability, and a fabric is produced with this fiber, resulting in crimping. Then, the state of the raised ultrafine fiber can be obtained also by subjecting to ultrafine fiber treatment. This conception can also be made by using heat-shrinking yarn in part. By using such a fiber for the weft, it is possible to have an infinite number of narrow fiber gaps due to ultrafine fibers that are not finely packed. FIG. 9 is a schematic cross-sectional view of a cloth made of fibers having a normal thickness. Individual fibers are evenly arranged. In both woven and knitted fabrics, the fiber gap is usually in this state. FIG. 10 is a schematic cross-sectional view of a cloth in which ultrafine fibers are mixed in a gap between fibers having a normal thickness. The individual normal-sized fibers are evenly arranged, and ultrafine fibers are scattered in the gaps. In this state, if there is no flow, the presence of ultrafine fibers does not have a significant effect on the water permeability, so there is only a slight difference in water permeability between the fabrics shown in FIGS. It is. FIG. 11 is a schematic cross-sectional view showing a thrombus film adhering to the fiber gap in a state where blood has started to flow through the cloth shown in FIG. Since the fiber gaps are separated, a thrombus film is difficult to form. Further, the formed film is easily broken. FIG. 12 is a schematic cross-sectional view showing a thrombus film adhering to the fiber gap in a state where blood has started to flow through the cloth shown in FIG. Since ultrafine fibers are interspersed between fibers having a normal thickness, the fiber gap is extremely narrow, and a thrombus membrane is easily formed. Moreover, the film is difficult to tear. FIG. 13 is a schematic cross-sectional view showing a thrombus film adhering to a fiber gap in a state where blood is continuously flowed through the cloth shown in FIG. Since the fiber gaps are separated, a thrombus film is formed, but it is formed only sparsely, and the formed film is easily broken. FIG. 14 is a schematic cross-sectional view showing a thrombus film adhering to a fiber gap in a state where blood is continuously flowed through the cloth shown in FIG. Since ultrafine fibers are interspersed between fibers of normal thickness, the fiber gap is extremely narrow, and a thrombus film is easily formed in a large amount. Since the total number of fibers of normal thickness and ultrafine fibers is increasing, the fiber gaps are extremely large, and fiber membranes are formed in the fiber gaps, and each fiber becomes like a hub. As a result, a high-density thrombosis film is formed, and since each thrombosis film has a short width, the formed individual films are hardly broken. This principle can be understood because it is difficult to break by Laplace's law shown in FIG. When this happens, the cloth will not leak blood. The result of the present invention, in which the ultrafine fibers are mixed in the fiber gaps of the normal fibers and the blood permeability is low even if the water permeability is high, can be clearly understood in this figure.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... The fiber of about 1.2 denier thickness which comprises a knitted structure 2 ... The thin fiber of 0.8 denier or less Exists in a fluffy state.
3 ... A thin fiber of 0.8 denier or less in an entangled state. In the gap between thick fibers of 1.2 denier or less, the yarn is in a state of being stretched.
4 ... Laplace's law is explained with a blood clot stretched between fibers, a fiber with a normal thickness of about 1.2 denier 5 ... A thin fiber with a diameter of less than 0.8 denier 6 ... A blood clot stretched between fibers Membrane 7 ... Tension applied to membrane 8 ... Blood pressure direction and force (vector)
9 ... Weft yarn of a plain weave structure 10 ... Weft yarn of a plain weave structure 11 ... Extra fine fiber 12 used in the weave yarn of a plain weave structure ... Bulky processed yarn 13 of normal thickness used in the plain weave structure ... Weft yarn of a plain weave structure 14 used for the above-mentioned, and raised fiber 14 ... The cross section 15 of the normal fiber when the cross section of the cloth using the normal thickness thread is viewed ... The cloth in which the normal thickness thread and the ultra fine fiber are mixed Cross section 16 of ultrafine fibers seen in the cross section of the thrombosis membrane stretched between the fibers

Claims (22)

It has ultrafine fibers of 0.5 dtex or less in at least a part of the fiber gap on the fluid contact side surface, water permeability: WP (ml / cm ² , 60 sec.) And blood permeability: BP ( ml / cm ² , 30 sec.) A medical material having a ratio Q = WP / BP of 6 or more. In a fabric made of a fiber having a woven structure as a basis, it has an ultrafine fiber of 0.5 dtex or less in at least a part of the fiber gap on the surface on the fluid contact side, and the following formula:
R = (N + M) ² /WP>8.0×10 ⁶
A medical material characterized by the following relationship: (where N is the total number of weft fibers per square centimeter, M is the total number of warp fibers per square centimeter, and WP is the water permeability of the fabric).   The medical material according to claim 1 or 2, wherein the ultrafine fibers have a fineness of 0.5 decitex (dtex) or less and a strength of 4 g / dtex or more.   The medical material according to claim 2, wherein a fray resistance coefficient is 0.8 kg or more.   The medical material according to claim 1 or 3, wherein the fabric is a textile fabric having a knitted structure and has a fray resistance of 2.0 kg or more.   At least a part of one or more states selected from the group consisting of a state in which the ultrafine fiber is present in a dispersed state, a state having an irregular entanglement state, and a state in which napped and / or looped are formed The medical material according to any one of claims 1 to 5.   The medical material according to any one of claims 1 to 6, which has at least a part of a bulky processed yarn and / or a heat-shrinkable yarn.   An ultrafine fiber-forming composite fiber is temporarily processed to have latent crimping ability, a fabric is produced with this fiber, and after crimping is expressed, a dispersed ultrafine fiber is characterized by being processed into ultrafine fibers. The medical material according to any one of claims 1 to 7.   Any one of the Claims 1-8 which have at least one part of the ultrafine fiber below 0.5 detex (dtex) manufactured by removing or exfoliating one component of the multicomponent fiber which is an ultrafine fiber-forming composite fiber Medical material according to crab.   The medical material according to claim 9, wherein the sulfonic acid copolymer adhering to the ultrafine fiber has a value of S (sulfur content) of 20 ppm or less.   The medical material according to any one of claims 1 to 10, wherein at least a part of fibers constituting the cloth is formed of any one of polyester, polyamide, polyolefin, and polytetrafluoroethylene.   The medical material according to any one of claims 1 to 11, which has been subjected to kink prevention processing by providing a bellows structure.   A monofilament having a thickness of 30 to 10,000 decidex formed from any one of polyester, polyamide, polyolefin, and polytetrafluoroethylene is disposed on the outer surface, and the shape is maintained. Item 13. A medical material according to any one of Items 1 to 12.   The medical material according to claim 13, wherein the monofilament has a core-sheath structure in which a sheath melting point is lower than a core melting point.   15. The medical material according to claim 13, wherein the polymer component constituting the monofilament is the same as at least a part of the polymer component constituting the fiber.   The fiber gap of the fiber cloth and / or the surface of the cloth is impregnated with a bioabsorbable substance having a property of being absorbed in the living body within 3 days to 3 months after being implanted in the living body, and The medical material according to any one of claims 1 to 15, which is attached.   The bioabsorbable substance is polyglycolic acid, polylactic acid, polyethylene glycol, polyvinyl alcohol, polyacrylic acid, polyvinyl pyrrolidone, polylactic acid-polyglycolic acid copolymer, biodegradable (3-hydroxyl brate-4 -Hydroxyl butyrate) Polyester polymer, polydioxane, collagen, gelatin, albumin, fibrin, chitosan, chitin, fibroin, cellulose, mucopolysaccharide, fibronectin, laminin, alginic acid, hyaluronic acid, chondroitin sulfate, polyamino acid, dextran, dextrin , Glucose, agarose, pectin, mannan, extracts from genetically engineered cells, substances produced from genetically engineered cells, and derivatives thereof, at least one The medical material of claim 16 having as a component of the above.   The medical material according to claim 16 or 17, wherein the bioabsorbable substance is insolubilized by chemical means and / or physical means.   The medical material according to any one of claims 15 to 18, wherein the bioabsorbable substance is impregnated with a polyhydric alcohol.   The medical material according to any one of claims 15 to 19, wherein the bioabsorbable substance can hold a physiologically active substance.   The physiologically active substance is protein, lipid, polysaccharide, enzyme, antibiotic, antibacterial substance, hormone, cytokine, heparin, protamine, urokinase, plasmin activator, blood anticoagulant, blood coagulation promoter, cell growth factor, cell Growth inhibitors, extracts from genetically engineered cells, substances produced from genetically engineered cells, vascular endothelial growth factor (VEGF), platelet-induced growth factor (PIGF), transforming growth factor beta 1 (TGF. beta.1), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), transforming growth factor.alpha. (TGF.alph.), Epidermal growth factor, osteonectin, antipoietin 1 (Ang 1), Ang2, insulin-like growth factor (IGF), pletelet-derived growth factor AA (PDGF-AA), PDGF-AB and PDGF-BB , Pletelet-derived endotherial growth factor (PD-ECGF) at least one selected from the group of bone transforming growth factor (BMP), hepatocyte growth factor (HGF), any complex or derivative thereof, etc. The medical material according to claim 20.   Artificial blood vessels to be used as a substitute for or a part of luminal organs and luminal tissues in the living body, and / or artificial pericardium, artificial heart wall, artificial vascular wall prosthesis in the form of patches on the in vivo organs and tissues The medical material according to any one of claims 1 to 20, which is to be used as an annulus and / or a leaflet of a heart valve.

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