Patent Description:
There are cases in which a tubular structure having a lumen is inserted into the human body for the purpose of treatment or prevention. Representative examples include a vascular conduit or a vascular access (hemodialysis access) for dialysis.

In general, vascular conduits are artificial blood vessels that may be used to replace living blood vessels when there is a vascular disease that is difficult to cure by surgery or pharmacological treatment. However, since the vascular conduit is not a natural structure of the human body, various problems may arise. Representative problems are stenosis at a connection site between a vascular conduit and blood vessels of the human body and surrounding sites, thrombosis with stenosis, and an inflammatory reaction at the site of the vascular conduit. In order to solve these problems, studies have been conducted to prevent vascular stenosis and inflammation by forming a physiologically active substance layer or a drug layer in a vascular conduit. <CIT> discloses porous multilayer polymeric tubular structures comprising a drug in the pores.

However, since the effect of the drug on the inside or outside of the vascular conduit may vary depending on the type of drug layer, it is necessary to control this variation by a preferred method. In addition, since the properties of the vascular conduit may vary depending on the method of forming the drug layer, the development of a new technology considering this variation is required.

The technical spirit of the present disclosure is intended to solve the above-described problems, and an object of the technical spirit of the present disclosure is to provide a technology for a tubular structure that may be appropriately controlled to show different effects on the inside and outside of the vascular conduit depending on the type of drug.

Another object of the technical spirit of the present disclosure is to provide a technology for a tubular structure that is capable of appropriately controlling the drug release rate.

Objects to be achieved by the present invention are not limited to the above-mentioned objects, and other objects not mentioned herein will be clearly understood by those skilled in the art from the following description.

To achieve the above objects, it is provided a porous multi-layered tubular structure according to claim <NUM>.

In addition, the amount of the physiologically active substance contained in at least one of the layers may be different from the amount of the physiologically active substance contained in the other layer.

In addition, at least one of the layers may be formed to be different from the other layer in terms of the shape of the pores, the size of the pores, the arrangement of the pores, or the number of pores per unit area of the layer, so that the content of the physiologically active substance in the pores of each of the layers and the release rate of the physiologically active substance may be set differently for each of the layers.

In addition, the physiologically active substance may be a substance that inhibits cell proliferation or cell migration.

In addition, the physiologically active substance may be at least one selected from the group consisting of paclitaxel, rapamycin, and everolimus.

In addition, the content of the physiologically active substance in each of the layers may decrease in the direction from the innermost layer to the outermost layer of the tubular structure.

In addition, the outermost layer of the tubular structure may not contain the physiologically active substance.

In addition, when the physiologically active substance is paclitaxel, the content of the physiologically active substance per area of the innermost layer of the tubular structure may be <NUM> to <NUM>µg/mm<NUM>.

In addition, when the physiologically active substance is paclitaxel, the content of the physiologically active substance per area of the layer positioned next to the innermost layer of the tubular structure may be <NUM> to <NUM>µg/mm<NUM>.

In addition, the outermost layer of the tubular structure may not contain the physiologically active substance, or when the physiologically active substance is paclitaxel, the content of the physiologically active substance per area of the outermost layer may be <NUM>µg/mm<NUM>.

In addition, the outermost layer of the tubular structure may have a porosity of less than <NUM> as measured according to International Standardization Organization (ISO) standard <NUM>:<NUM>.

The material of each of the layers is at least any one selected from the group consisting of expanded polytetrafluoroethylene, polytetrafluoroethylene, and polyurethane.

In addition, the content of the physiologically active substance in each of the layers may decrease in the direction from the outermost layer to the innermost layer of the tubular structure.

In addition, the tubular structure is formed of three or more layers, and the porosity of a layer positioned next to the outermost layer of the tubular structure is smaller than the porosities of the other layers, as measured according to International Standardization Organization (ISO) standard <NUM>:<NUM>.

In addition, the porosity of a layer positioned next to the outermost layer of the tubular structure may be less than <NUM> as measured according to International Standardization Organization (ISO) standard <NUM>:<NUM>.

In addition, all of the plurality of layers may be formed of the same material.

In addition, when the tubular structure is formed of three layers, the porosity of a layer positioned between the outermost layer and the innermost layer of the tubular structure is smaller than the porosities of the other layers.

As described above, according to various embodiments of the present invention, the content of the physiologically active substance may be set differently for each of the layers, and thus the release rate of the physiologically active substance in vivo may be appropriately controlled.

In addition, according to various embodiments of the present invention, the content of the physiologically active substance in each layer may decrease in the direction from the innermost layer to the outermost layer of the tubular structure, and the outermost layer may not contain the physiologically active substance, and thus it is possible to prevent the physiologically active substance from inhibiting proliferation of myofibroblasts outside of the vascular conduit.

In addition, according to various embodiments of the present invention, the size, number, shape, arrangement, etc. of pores may be different between layers, and thus the content of the physiologically active substance in the pores may be controlled differently for each of the layers. Thereby, it is possible to prevent a physiologically active substance that inhibits cell proliferation or cell migration from permeating from the inner circumferential surface to the outer circumferential surface of the tubular structure and reaching the outer circumferential surface.

In addition, according to the implementation, the content of the physiologically active substance in each layer may be controlled so that it decreases in the direction from the outermost layer to the innermost layer of the tubular structure and the innermost layer does not contain the physiologically active substance. Therefore, it is possible to selectively apply the physiologically active substance only to the outside of the tubular structure in consideration of the efficacy and type of physiologically active substance.

Effects according to various embodiments of the present invention are not limited to the above-mentioned effects, and other effects not mentioned herein will be clearly understood by those skilled in the art from the following description.

Preferred embodiments of the present invention will be described in more detail with reference to the accompanying drawings. The descriptions of already known technical features will be omitted or simplified for the sake of brevity.

It should be noted that references to "an" or "one" embodiment of the invention in this specification are not necessarily directed to the same embodiment, and they imply at least one.

In the following embodiments, terms such as "first" and "second" are not used in a limited sense, but are used for the purpose of distinguishing one component from another component.

In the following examples, singular expressions include plural expressions unless the context clearly indicates otherwise.

In the following embodiments, terms such as "include" and "have" are intended to denote the presence of mentioned features or components, but do not exclude the probability of presence or addition of one or more other features or components.

In the following embodiments, when a part, such as a layer, region, component, or the like, is referred to as being "on" or "above" another part, it not only refers to a case where the part may be directly above the other part, but also a case where a third part exists therebetween.

Sizes, heights, thicknesses, and the like in the drawings referred to when describing the embodiments of the present disclosure may be intentionally exaggerated and expressed for convenience of description and to facilitate understanding, and are not enlarged or shrunk according to any ratio. In addition, some elements illustrated in the drawings may be intentionally expressed as being smaller, and the other elements may be intentionally expressed as being larger.

<FIG> schematically shows a tubular structure according to a first embodiment, not according to the claims. Referring to <FIG>, the tubular structure <NUM> according to the first embodiment is a structure having a lumen and may be formed by stacking three layers. That is, a first layer <NUM> is the innermost layer of the tubular structure <NUM>, and a second layer <NUM> is attached to the outer circumferential surface of the first layer <NUM>. In addition, a third layer <NUM> is attached to the outer circumferential surface of the second layer <NUM> and is the outermost layer of the tubular structure <NUM>.

In the first embodiment, a plurality of pores may be formed in each of the layers constituting the tubular structure <NUM>. According to the first embodiment, a plurality of pores may be formed in the first layer <NUM>, the second layer <NUM>, and the third layer <NUM>. In addition, a physiologically active substance may be contained in at least one pore in at least one of the layers.

In the first embodiment, the physiologically active substance refers to a substance that inhibits cell proliferation or cell migration. For example, the physiologically active substance may be at least one selected from the group consisting of paclitaxel, rapamycin, and everolimus.

According to the first embodiment, the porosity of the pores <NUM> and <NUM> formed in the first layer <NUM> among the plurality of layers may be different from the porosity of the pores <NUM> formed in the second layer <NUM>. That is, by making the porosity different between the layers, it is possible to control the content of the physiologically active substance in the pores <NUM> and <NUM> of the first layer <NUM> so as to be different from the content of the physiologically active substance in the pores <NUM> of the second layer <NUM>. As used herein, the term "porosity" means a microscopic porosity value measured according to International Organization Standardization (ISO) standard <NUM>:<NUM>.

As a specific example, in the first embodiment, the porosity of the pores <NUM> and <NUM> formed in the first layer <NUM> among the three layers may be larger than that of the pores <NUM> formed in the second layer <NUM>, and the porosity of the pores <NUM> and <NUM> formed in the third layer <NUM> may be smaller than that of the pores <NUM> formed in the second layer <NUM>. Thus, the content of the physiologically active substance in each pore decreases in the direction from the first layer <NUM> to the third layer <NUM>. In addition, the porosity of each layer may be controlled so that the pores <NUM> and <NUM> of the third layer <NUM> do not contain the physiologically active substance, unlike the first layer <NUM> or the second layer <NUM>.

According to the first embodiment, the shape, size, or arrangement of the pores <NUM> and <NUM> formed in the first layer <NUM> among the plurality of layers constituting the tubular structure <NUM>, or the number of the pores <NUM> and <NUM> per unit area of the first layer, may be different from the shape, size, or arrangement of the pores <NUM> formed in the second layer <NUM>, or the number of pores <NUM> per unit area of the second layer. That is, when the shape, size, arrangement of pores or the number of pores per unit area of each layer is set differently for each of the layers, the content of the physiologically active substance in the pores <NUM> and <NUM> of the first layer <NUM> may be different from the content of the physiologically active substance in the pores <NUM> of the second layer <NUM>.

As a specific example, when <NUM> pores are formed in the first layer <NUM>, <NUM> pores are formed in the second layer <NUM>, and <NUM> pores are formed in the third layer <NUM>, the content of the physiologically active substance in the pores will be different between the layers. In addition, at least any one of the number, shape, and arrangement of the pores may be controlled so that the physiologically active substance is not contained in the pores <NUM> and <NUM> of the third layer <NUM>.

According to the first embodiment, the content of the physiologically active substance per area of the first layer <NUM>, which is the innermost layer of the tubular structure <NUM>, is <NUM> to <NUM>µg/mm<NUM>. regardless of the thickness of the layer, when the physiologically active substance is paclitaxel. As a specific example, the content of the physiologically active substance per area of the first layer <NUM> may be <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, or <NUM>µg/mm<NUM>. regardless of the thickness of the layer, when the physiologically active substance is paclitaxel. In addition, the content of the physiologically active substance per area of the first layer <NUM> may range from a value equal to or greater than any one of the above values to a value equal to or smaller than any one of the above values.

For example, the content of the physiologically active substance per area of the first layer <NUM> may be in the range of <NUM>µg/mm<NUM>. to <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>. to <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>. to <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>. to <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>. to <NUM>µg/mm<NUM>, or <NUM>µg/mm<NUM>. to <NUM>µg/mm<NUM>. regardless of the thickness of the layer, when the physiologically active substance is paclitaxel.

According to the first embodiment, the content of the physiologically active substance per area of the second layer <NUM> stacked on the outer circumferential surface of the first layer <NUM> may be <NUM> to <NUM>µg/mm<NUM>. regardless of the thickness of the layer, when the physiologically active substance is paclitaxel. As a specific example, the content of the physiologically active substance per area of the second layer <NUM> may be <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>. or <NUM>µg/mm<NUM>. regardless of the thickness of the layer, when the physiologically active substance is paclitaxel. In addition, the content of the physiologically active substance per area of the second layer <NUM> may range from a value equal to or greater than any one of the above values to a value equal to or smaller than any one of the above values.

For example, the content of the physiologically active substance per area of the second layer <NUM> may be in the range of <NUM>µg/mm<NUM>. to <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>. to <NUM>µg/mm<NUM>, or <NUM>µg/mm<NUM>. to <NUM>µg/mm<NUM>. regardless of the thickness of the layer, when the physiologically active substance is paclitaxel.

Meanwhile, according to the implementation, the third layer <NUM>, which is the outermost layer of the tubular structure <NUM>, may contain the physiologically active substance in a smaller amount than the first layer <NUM> or the second layer <NUM> (for example, when the physiologically active substance is paclitaxel, the content of the physiologically active substance in the third layer may be <NUM> to <NUM>µg/mm<NUM>. regardless of the thickness of the layer).

According to the first embodiment, the third layer <NUM>, which is the outermost layer of the tubular structure <NUM>, may be formed so that the porosity of the pores <NUM> and <NUM> is smaller than those of the other layers. In addition, the third layer <NUM> may be formed so that the number of pores <NUM> and <NUM> is smaller than those in the other layers. Thereby, the third layer <NUM> may not contain the physiologically active substance at all or may contain the physiologically active substance in a smaller amount than the other layers.

The tubular structure <NUM> according to the first embodiment has a plurality of layers, wherein the average size of pores formed in each of the layers may be <NUM> to less than <NUM> as measured according to International Standardization Organization (ISO) standard <NUM>.

In the first embodiment, the material of each of the layers constituting the tubular structure <NUM> may be at least one selected from the group consisting of expanded polytetrafluoroethylene, polytetrafluoroethylene, and polyurethane. Meanwhile, according to the implementation, all of the plurality of layers may be formed of the same material. In one embodiment, when all of the layers constituting the multi-layered tubular structure are formed of the same material, the elasticity and ductility of each layer may be equal between the layers, and it is possible to prevent the adjacent layers from falling off or cracking when the tubular structure is bent by an external force.

The tubular structure <NUM> according to the first embodiment may be manufactured by spraying a mixed solution of a polar solvent, a non-polar solvent and a physiologically active substance toward the inner circumferential surface of the first layer <NUM> in a state in which the first layer <NUM>, the second layer <NUM> and the third layer <NUM> are stacked in advance. That is, it may be manufactured by positioning a spraying device inside the tubular structure <NUM> and spraying the solution toward the inner circumferential surface of the first layer <NUM>.

<FIG> schematically shows a tubular structure according to a second embodiment, not according to the claims. Referring to <FIG>, the tubular structure <NUM> according to the second embodiment may be formed by stacking four layers. That is, a first layer <NUM> is the innermost layer of the tubular structure <NUM>. A second layer <NUM> is attached to the outer circumferential surface of the first layer <NUM>, and a third layer <NUM> is attached to the outer circumferential surface of the second layer <NUM>. A fourth layer <NUM> is attached to the outer circumferential surface of the third layer <NUM> and is the outermost layer of the tubular structure <NUM>.

In the second embodiment, a plurality of pores may be formed in each of the layers constituting the tubular structure <NUM>. According to the second embodiment, a plurality of pores may be formed in the first layer <NUM>, the second layer <NUM>, the third layer <NUM> and the fourth layer <NUM>. In addition, a physiologically active substance may be contained in at least one pore in at least one of the layers.

In the second embodiment, the physiologically active substance may be applied in the same way as in the first embodiment. According to the second embodiment, the porosity of the pores <NUM>, <NUM>, and <NUM> formed in the first layer <NUM> among the plurality of layers may be different from the porosity of the pores <NUM> formed in the second layer <NUM>. That is, by making the porosity of the pores different between the layers, it is possible to control the content of the physiologically active substance in the pores <NUM>, <NUM> and <NUM> of the first layer <NUM> so as to be different from the content of the physiologically active substance in the pores <NUM> of the second layer <NUM>.

As a specific example, in the second embodiment, the porosity of the pores <NUM>, <NUM> and <NUM> formed in the first layer <NUM> among the four layers may be larger than the porosity of the pores <NUM> formed in the second layer <NUM>, the porosity of the pores <NUM> formed in the second layer <NUM> may be larger than that of the pores <NUM> and <NUM> formed in the third layer <NUM>, and the porosity of the pores <NUM> and <NUM> formed in the third layer <NUM> may be larger than that of the pores <NUM> formed in the fourth layer <NUM>. Thus, the content of the physiologically active substance in each pore decreases in the direction from the first layer <NUM> toward the fourth layer <NUM>. In addition, it is possible to control the porosity of the pores so that the pores <NUM> of the fourth layer <NUM> do not contain the physiologically active substance, unlike the first layer <NUM>, the second layer <NUM> and the third layer <NUM>.

According to the second embodiment, the shape, size, or arrangement of the pores <NUM>, <NUM> and <NUM> formed in the first layer <NUM> among the plurality of layers constituting the tubular structure <NUM>, or the number of the pores <NUM>, <NUM> and <NUM> per unit area of the first layer, may be different from the shape, size, or arrangement of the pores <NUM> formed in the second layer <NUM>, or the number of pores <NUM> per unit area of the second layer. That is, when the shape, size, arrangement of pores or the number of pores per unit area of each layer is set differently for each of the layers, the content of the physiologically active substance in the pores <NUM>, <NUM> and <NUM> of the first layer <NUM> may be different from the content of the physiologically active substance in the pores <NUM> of the second layer <NUM>.

As a specific example, when <NUM> pores are formed in the first layer <NUM>, <NUM> pores are formed in the second layer <NUM>, <NUM> pores are formed in the third layer <NUM>, and <NUM> pores are formed in the fourth layer <NUM>, the content of the physiologically active substance in the pores will be different between the layers. In addition, at least any one of the number, shape, and arrangement of the pores may be controlled so that the physiologically active substance is not contained in the pores <NUM> of the fourth layer <NUM>.

According to the second embodiment, the content of the physiologically active substance per area of the first layer <NUM>, which is the innermost layer of the tubular structure <NUM>, may be <NUM> to <NUM>µg/mm<NUM>. As a specific example, the content of the physiologically active substance per area of the first layer <NUM> may be <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, or <NUM>µg/mm<NUM>. regardless of the thickness of the layer, when the physiologically active substance is paclitaxel. In addition, the content of the physiologically active substance per area of the first layer <NUM> may range from a value equal to or greater than any one of the above values to a value equal to or smaller than any one of the above values.

According to the second embodiment, the content of the physiologically active substance per area of the second layer <NUM> attached to the outer circumferential surface of the first layer <NUM> may be <NUM> to <NUM>µg/mm<NUM>. regardless of the thickness of the layer, when the physiologically active substance is paclitaxel. As a specific example, the content of the physiologically active substance per area of the second layer <NUM> may be <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>, <NUM>µg/mm<NUM>. or <NUM>µg/mm<NUM>. regardless of the thickness of the layer, when the physiologically active substance is paclitaxel. In addition, the content of the physiologically active substance per area of the second layer <NUM> may range from a value equal to or greater than any one of the above values to a value equal to or smaller than any one of the above values.

Meanwhile, according to the implementation, the fourth layer <NUM>, which is the outermost layer of the tubular structure <NUM>, may contain the physiologically active substance in a smaller amount than the other layers (for example, when the physiologically active substance is paclitaxel, the content of the physiologically active substance in the fourth layer may be <NUM> to <NUM>µg/mm<NUM>. regardless of the thickness of the layer).

According to the second embodiment, the fourth layer <NUM>, which is the outermost layer of the tubular structure <NUM>, may be formed so that the porosity of the pores <NUM> is smaller than those of the other layers. In addition, the fourth layer <NUM> may be formed so that the number of the pores <NUM> is smaller than those in the other layers. Thereby, the fourth layer <NUM> may not contain the physiologically active substance at all or may contain the physiologically active substance in a smaller amount than the other layers.

The tubular structure <NUM> according to the second embodiment has a plurality of layers, wherein the average size of pores formed in each of the layers may be <NUM> to less than <NUM> as measured according to International Standardization Organization (ISO) standard <NUM>.

In the second embodiment, the material of each of the layers constituting the tubular structure <NUM> may be as described above with respect to the first embodiment.

The tubular structure <NUM> according to the second embodiment may be manufactured by spraying a mixed solution of a polar solvent, a non-polar solvent and a physiologically active substance toward the inner circumferential surface of the first layer <NUM> in a state in which the first layer <NUM>, the second layer <NUM>, the third layer <NUM> and the fourth layer <NUM> are stacked in advance. That is, it may be manufactured by positioning a spraying device inside the tubular structure <NUM> and spraying the solution toward the inner circumferential surface of the first layer <NUM>.

<FIG> schematically shows a tubular structure according to a third embodiment, according to the present invention. Referring to <FIG>, the tubular structure <NUM> according to the third embodiment may be formed by stacking three layers. That is, a first layer <NUM> is the innermost layer of the tubular structure <NUM>. A second layer <NUM> is attached to the outer circumferential surface of the first layer <NUM>, and a third layer <NUM> is attached to the outer circumferential surface of the second layer <NUM>. The third layer <NUM> is the outermost layer of the tubular structure <NUM>.

In the third embodiment, a plurality of pores may be formed in each of the layers constituting the tubular structure <NUM>. According to the third embodiment, a plurality of pores may be formed in the first layer <NUM>, the second layer <NUM>, and the third layer <NUM>. In addition, a physiologically active substance may be contained in at least one pore in at least one of the layers.

In the third embodiment, the physiologically active substance may be of a type different from that in the first embodiment. For example, the physiologically active substance according to the third embodiment may be an anti-inflammatory agent. In the case in which it is preferable in terms of the efficacy of the physiologically active substance that the physiologically active substance be contained in an outer layer of the tubular structure <NUM> rather than contained in an inner layer of the tubular structure <NUM>, control may be made so that the physiologically active substance is selectively applied only to the outer layer without existing in the inner layer of the tubular structure <NUM>.

According to the third embodiment, the porosity of the pores <NUM> and <NUM> formed in the first layer <NUM> among the plurality of layers may be different from the porosity of the pores <NUM> formed in the second layer <NUM>. That is, by making the porosity of the pores different between the layers, it is possible to control the content of the physiologically active substance in the pores <NUM> and <NUM> of the first layer <NUM> so as to be different from the content of the physiologically active substance in the pores <NUM> of the second layer <NUM>.

As a specific example, in the third embodiment, the porosity of the pores <NUM> and <NUM> formed in the third layer <NUM> among the three layers is larger than that of the pores <NUM> formed in the second layer <NUM>, and the porosity of the pores <NUM> formed in the second layer <NUM> may be larger than that of the pores <NUM> and <NUM> in the first layer <NUM>. Thus, the content of the physiologically active substance in the pores of each layer decreases in the direction from the third layer <NUM>, which is the outermost layer of the tubular structure <NUM>, toward the first layer <NUM> which is the innermost layer. In addition, the porosity of the pores may be controlled so that the pores <NUM> and <NUM> of the first layer <NUM> do not contain the physiologically active substance, unlike the second layer <NUM> or the third layer <NUM>.

According to the third embodiment, the shape, size, or arrangement of the pores <NUM> and <NUM> formed in the first layer <NUM> among the plurality of layers constituting the tubular structure <NUM>, or the number of the pores <NUM> and <NUM> per unit area of the first layer, may be different from the shape, size, or arrangement of the pores <NUM> formed in the second layer <NUM>, or the number of the pores <NUM> per unit area of the second layer. That is, when the shape, size, arrangement of pores or the number of pores per unit area of each layer is set differently for each of the layers, the content of the physiologically active substance in the pores <NUM> and <NUM> of the first layer <NUM> may be different from the content of the physiologically active substance in the pores <NUM> of the second layer <NUM>.

According to the third embodiment, the first layer <NUM>, which is the innermost layer of the tubular structure <NUM>, may be formed so that the porosity of the pores <NUM> and <NUM> is smaller than those of the other layers. In addition, the first layer <NUM> may be formed so that the number of the pores <NUM> and <NUM> is smaller than those in the other layers. Thereby, the first layer <NUM> may not contain the physiologically active substance at all or may contain the physiologically active substance in a smaller amount than the other layers.

In the third embodiment, the material of each of the layers constituting the tubular structure <NUM> may be as described above with respect to the first embodiment.

The tubular structure <NUM> according to the third embodiment may be manufactured by spraying a mixed solution of a polar solvent, a non-polar solvent and a physiologically active substance toward the outer circumferential surface of the third layer <NUM> in a state in which the first layer <NUM>, the second layer <NUM> and the third layer <NUM> are stacked in advance. That is, it may be manufactured by positioning a spraying device outside the tubular structure <NUM> and spraying the solution toward the outer circumferential surface of the third layer.

<FIG> schematically shows a tubular structure according to a fourth embodiment, according to the present invention. Referring to <FIG>, the tubular structure <NUM> according to the fourth embodiment may be formed by stacking four layers. That is, a first layer <NUM> is the innermost layer of the tubular structure <NUM>. A second layer <NUM> is attached to the outer circumferential surface of the first layer <NUM>, a third layer <NUM> is attached to the outer circumferential surface of the second layer <NUM>, and a fourth layer <NUM> is attached to the outer circumferential surface of the third layer <NUM>. The fourth layer <NUM> is the outermost layer of the tubular structure <NUM>.

In the fourth embodiment, a plurality of pores may be formed in each of the layers constituting the tubular structure <NUM>. According to the fourth embodiment, a plurality of pores may be formed in the first layer <NUM>, the second layer <NUM>, the third layer <NUM> and the fourth layer <NUM>. In addition, a physiologically active substance may be contained in at least one pore in at least one of the layers.

In the fourth embodiment, the physiologically active substance may be of a type different from that in the first embodiment. For example, the physiologically active substance according to the fourth embodiment may be an anti-inflammatory agent. In the case in which it is preferable in terms of the efficacy of the physiologically active substance that the physiologically active substance be contained in an outer layer of the tubular structure <NUM> rather than contained in an inner layer of the tubular structure <NUM>, control may be made so that the physiologically active substance is selectively applied only to the outer layer without existing in the inner layer of the tubular structure <NUM>.

According to the fourth embodiment, the porosity of the pores <NUM> formed in the first layer <NUM> among the plurality of layers may be different from the porosity of the pores <NUM> formed in the second layer <NUM>. That is, by making the porosity of the pores different between the layers, it is possible to control the content of the physiologically active substance in the pores <NUM> of the first layer <NUM> so as to be different from the content of the physiologically active substance in the pores <NUM> of the second layer <NUM>.

As a specific example, in the fourth embodiment, the porosity of the pores <NUM> and <NUM> formed in the fourth layer <NUM> among the four layers is larger than the porosity of the pores <NUM> and <NUM> formed in the third layer <NUM>, the porosity of the pores <NUM> and <NUM> formed in the third layer <NUM> may be larger than the porosity of the pores <NUM> formed in the second layer <NUM>, and the porosity of the pores <NUM> formed in the second layer <NUM> may be larger than the porosity of the pores <NUM> formed in the first layer <NUM>. Thus, the content of the physiologically active substance in the pores of each layer decreases in the direction from the fourth layer <NUM>, which is the outermost layer of the tubular structure <NUM>, toward the first layer <NUM> which is the innermost layer. In addition, the porosity of the pores may be controlled so that the pores <NUM> of the first layer <NUM> do not contain the physiologically active substance, unlike the second layer <NUM>, the third layer <NUM> and the fourth layer <NUM>.

According to the fourth embodiment, the shape, size, or arrangement of the pores <NUM> formed in the first layer <NUM> among the plurality of layers constituting the tubular structure <NUM>, or the number of the pores <NUM> per unit area of the first layer, may be different from the shape, size, or arrangement of the pores <NUM> formed in the second layer <NUM>, or the number of the pores <NUM> per unit area of the second layer. That is, when the shape, size, arrangement of pores or the number of pores per unit area of each layer is set differently for each of the layers, the content of the physiologically active substance in the pores <NUM> of the first layer <NUM> may be different from the content of the physiologically active substance in the pores <NUM> of the second layer <NUM>.

Meanwhile, according to the implementation, the first layer <NUM>, which is the innermost layer of the tubular structure <NUM>, may also contain the physiologically active substance in a smaller amount than the other layers.

According to the fourth embodiment, the first layer <NUM>, which is the innermost layer of the tubular structure <NUM>, may be formed so that the porosity of the pores <NUM> is smaller than those of the other layers. In addition, the first layer <NUM> may be formed so that the number of the pores <NUM> is smaller than those in the other layers. Thereby, the first layer <NUM> may not contain the physiologically active substance at all or may contain the physiologically active substance in a smaller amount than the other layers.

In the fourth embodiment, the material of each of the layers constituting the tubular structure <NUM> may be as described above with respect to the first embodiment.

In another embodiment, when the tubular structure is formed of three or more layers, the porosity of a layer positioned next to the outermost layer of the tubular structure may be smaller than the porosities of the other layers. In another embodiment, when the tubular structure is formed of three or more layers, the porosity of a layer positioned next to the outermost layer of the tubular structure may be <NUM> to less than <NUM>. Accordingly, the innermost layer or the outermost layer of the tubular structure may not contain the physiologically active substance at all or may contain the physiologically active substance in very small amounts.

<FIG> schematically shows a tubular structure according to a fifth embodiment, according to the present invention. Referring to <FIG>, the tubular structure <NUM> according to the fifth embodiment may be formed by stacking three layers.

That is, a first layer <NUM> is the innermost layer of the tubular structure <NUM>. A second layer <NUM> is attached to the outer circumferential surface of the first layer <NUM>, and a third layer <NUM> is attached to the outer circumferential surface of the second layer <NUM>. The third layer <NUM> is the outermost layer of the tubular structure <NUM>.

In the fifth embodiment, a plurality of pores may be formed in each of the layers constituting the tubular structure <NUM>. According to the fifth embodiment, a plurality of pores may be formed in the first layer <NUM>, the second layer <NUM>, and the third layer <NUM>. In addition, a physiologically active substance may be contained in at least one pore in at least one of the layers. In the fifth embodiment, the physiologically active substance may be of the same or different type as that in the first embodiment.

According to the fifth embodiment, when the tubular structure <NUM> is formed of three layers, the second layer <NUM> positioned between the third layer <NUM>, which is the outermost layer of the tubular structure <NUM>, and the first layer <NUM> which is the innermost layer, may have the smallest porosity.

In the fifth embodiment, the material of each of the layers constituting the tubular structure <NUM> may be as described above with respect to the first embodiment.

<FIG> schematically shows a tubular structure according to a sixth embodiment, according to the present invention. Referring to <FIG>, the tubular structure <NUM> according to the sixth embodiment may be formed by stacking four layers.

That is, a first layer <NUM> is the innermost layer of the tubular structure <NUM>. A second layer <NUM> is attached to the outer circumferential surface of the first layer <NUM>, a third layer <NUM> is attached to the outer circumferential surface of the second layer <NUM>, and a fourth layer <NUM> is attached to the outer circumferential surface of the third layer <NUM>. The fourth layer <NUM> is the outermost layer of the tubular structure <NUM>.

In the sixth embodiment, a plurality of pores may be formed in each of the layers constituting the tubular structure <NUM>. According to the sixth embodiment, a plurality of pores may be formed in the first layer <NUM>, the second layer <NUM>, the third layer <NUM>, and the fourth layer <NUM>. In addition, a physiologically active substance may be contained in at least one pore in at least one of the layers. In the sixth embodiment, the physiologically active substance may be of the same or different type as that in the first embodiment.

In one embodiment, when the tubular structure is formed of four or more layers, any one of the layers excluding the outermost layer and the innermost layer of the tubular structure may have the smallest porosity.

According to the sixth embodiment, when the tubular structure <NUM> is formed of four layers, the second layer <NUM> positioned between the fourth layer <NUM>, which is the outermost layer of the tubular structure <NUM>, and the first layer <NUM> which is the innermost layer, may have the smallest porosity.

In the sixth embodiment, the material of each of the layers constituting the tubular structure <NUM> may be as described above with respect to the first embodiment.

<FIG> schematically shows a tubular structure according to a seventh embodiment, according to the present invention. Referring to <FIG>, the tubular structure <NUM> according to the seventh embodiment may be formed by stacking four layers.

In the seventh embodiment, a plurality of pores may be formed in each of the layers constituting the tubular structure <NUM>. According to the seventh embodiment, a plurality of pores may be formed in the first layer <NUM>, the second layer <NUM>, the third layer <NUM>, and the fourth layer <NUM>. In addition, a physiologically active substance may be contained in at least one pore in at least one of the layers. In the seventh embodiment, the physiologically active substance may be of the same or different type as that in the first embodiment.

According to the seventh embodiment, when the tubular structure <NUM> is formed of four layers, the third layer <NUM> positioned between the fourth layer <NUM>, which is the outermost layer of the tubular structure <NUM>, and the first layer <NUM> which is the innermost layer, may have the smallest porosity.

In the seventh embodiment, the material of each of the layers constituting the tubular structure <NUM> may be as described above with respect to the first embodiment.

According to one embodiment, in the case in which any one layer positioned between the outermost layer and the innermost layer of the tubular structure has the smallest porosity, when a syringe needle penetrates the surface of the tubular structure and then the needle is removed, the puncture point of the layer having the smallest porosity may easily shrink, thereby preventing leakage.

According to another embodiment, the outermost layer of the tubular structure may have a larger porosity than any one of the layers excluding the outermost layer and the innermost layer of the tubular structure. In this case, the outermost layer of the tubular structure may maintain a certain porosity, and thus skin tissue may easily penetrate into the pores of the outermost layer, which is in direct contact with the skin, and the tight coupling between the tubular structure and the skin may occur, so that the tubular structure may be stably maintained in vivo without departing from the initial placement position.

As described above, according to various embodiments of the present invention, the content of the physiologically active substance may be set differently between the layers, and thus the release rate of the physiologically active substance in vivo may be appropriately controlled.

In addition, according to various embodiments of the present invention, as the content of the physiologically active substance in each layer decreases in the direction from the innermost layer to the outermost layer of the tubular structure, and the outermost layer does not contain the physiologically active substance, it is easy for myofibroblasts to proliferate outside of the vascular conduit.

In addition, according to various embodiments of the present invention, as the size, number, shape, arrangement, etc. of pores are set differently for each of the layers, the content of the physiologically active substance in the pores and the release rate thereof may be controlled differently for each of the layers. Thereby, it is possible to prevent a physiologically active substance (e.g., paclitaxel, rapamycin, everolimus, etc.) that inhibit cell proliferation or cell migration from permeating from the inner circumferential surface to the outer circumferential surface of the tubular structure and reaching the outer circumferential surface. In addition, even when a liquid mixture of a physiologically active substance and an organic solvent is applied to the tubular structure, it is possible to prevent the organic solvent from reaching the outer circumferential surface of the tubular structure and deforming or damaging the outer circumferential surface of the tubular structure, thereby preventing unexpected side effects from occurring in vivo.

Claim 1:
A porous multi-layered tubular structure containing a physiologically active substance in pores, the tubular structure comprising a tubular structure in which a plurality of layers are stacked,
wherein a plurality of pores are formed in each of the layers, and the physiologically active substance is contained in the pores of at least one of the layers,
characterized in that,
each of the layers is made of at least one material selected from the group consisting of expanded polytetrafluoroethylene, polytetrafluoroethylene, and polyurethane,
the tubular structure is formed of three or more layers, and a porosity of a layer positioned next to an outermost layer of the tubular structure is smaller than porosities of the other layers, as measured according to International Standardization Organization (ISO) standard <NUM>:<NUM>.