KR102587534B1 - Biodegradable tube including radiographic materials - Google Patents

Abstract

The present invention includes a biodegradable fiber including a core portion formed of biodegradable monofilament and a sheath portion formed of a biodegradable polymer along the outer peripheral surface of the core portion, and at least one of the core portion and the sheath portion is radiopaque. It relates to a biodegradable tube comprising a material, wherein the core portion and the sheath portion have different hydrolysis rates (g/hr).

Description

BIODEGRADABLE TUBE INCLUDING RADIOGRAPHIC MATERIALS}

The present invention relates to a biodegradable tube endowed with a radiopaque function and capable of being inserted into a living body. Specifically, it includes biodegradable fibers including a core portion and a sheath portion with different hydrolysis rates (g/hr), and achieves desired decomposition. It is about a biodegradable tube that can maintain its performance for a long period of time and can accurately determine where it is inserted into the body.

Conventional biodegradable material-based tubes are made of radiolucent materials or, even if radiopaque, have a low radioopacity, making it difficult to confirm the exact location during the procedure, and the radiopaque materials are mixed unevenly. In this case, radiopacity may also appear unevenly, and excessive addition of radiopaque materials may cause problems that may reduce the biodegradability and mechanical properties of the biodegradable polymer.

In addition, technology that can effectively apply functional materials necessary for recovery of the treatment area while confirming whether a tube based on biodegradable materials, including radiopaque materials, has been inserted in the correct location has not yet been developed.

Accordingly, the present inventors completed the present invention as a result of efforts to solve the above-mentioned problems.

In order to solve the above-mentioned problems, the purpose of the present invention is to provide uniform fabrication by including a biodegradable fiber including a core portion formed of biodegradable monofilament or multifilament and a sheath portion formed of a biodegradable polymer along the outer peripheral surface of the core portion. The aim is to provide a biodegradable tube capable of imparting impermeability.

Another object of the present invention is to construct biodegradable materials of the core portion and sheath portion of the biodegradable polymer differently, thereby producing a difference in the decomposition rate (hydrolysis rate (g/hr)) of the core portion and the sheath portion, thereby improving biodegradability. The goal is to provide a biodegradable tube that can maintain its performance until the desired decomposition period or supplement its mechanical properties.

In order to achieve the above object, in one embodiment of the present invention, a biodegradable tube that can be inserted into a living body includes a core portion formed of biodegradable monofilament and a sheath portion formed of a biodegradable polymer along the outer peripheral surface of the core portion. May contain biodegradable fibers.

In one embodiment of the present invention, a biodegradable tube that can be inserted into a living body may include a biodegradable fiber including a core portion formed of biodegradable multifilament and a sheath portion formed of a biodegradable polymer along the outer peripheral surface of the core portion. there is.

In one embodiment of the present invention, the core portion and sheath portion of the biodegradable fiber included in the biodegradable tube insertable into the body may have different hydrolysis rates (g/hr).

In one embodiment of the present invention, the hydrolysis rate (g/hr) of the core portion of the biodegradable fiber contained in the biodegradable tube insertable in vivo may be relatively faster than the hydrolysis rate (g/hr) of the sheath portion. there is.

In one embodiment of the present invention, the biodegradable tube that can be inserted into the body is made up of fibrous collagen, gelatin, elastin, laminin, and integrin in the sheath portion of the biodegradable fiber. ), it may further include one or more fibrous proteins from the group consisting of fibronectin and proteoglycan.

In one embodiment of the present invention, the hydrolysis rate (g/hr) of the sheath portion of the biodegradable fiber contained in the biodegradable tube insertable in vivo may be relatively faster than the hydrolysis rate (g/hr) of the core portion. there is.

In one embodiment of the present invention, the biodegradable tube that can be inserted into the body is made of gold, silver, platinum, tantalum, tungsten, strontium, iridium, bismuth, bromine, iodine, barium sulfate, barium oxide, bismuth oxide, bismuth trioxide, At least one radiopaque material selected from the group consisting of sodium iodide, iohexol, ioversol, iobitridol, and ytterbium chloride is applied to either the core portion or the sheath portion of the biodegradable fiber. It can be included.

In one embodiment of the present invention, the radiopaque material included in the core portion or the sheath portion of the biodegradable fiber may be included in an amount of 10 to 35% by weight based on the weight of the biodegradable fiber.

In one embodiment of the present invention, the material of the biodegradable monofilament included in the biodegradable tube that can be inserted into the body is poly-L-lactide, poly-D-lactide, poly-D,L-lactide, poly Glycolide, polycaprolactone, poly-L-lactide-co-glycolide, poly-D-lactide-co-glycolide, poly-D,L-lactide-co-glycolide, poly-L-lac Tide-co-caprolactone, poly-D-lactide-co-caprolactone, poly-D,L-lactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone, polytrimethylene Carbonate, polyglycolide-co-dioxanone, polyamide ester, polypeptide, polyorthoester series, polymaleic acid, polyphosphazene, polyanhydride, polysebacic anhydride, polyhydroxyalkanoate, poly Hydroxyl butyrate, polycyanoacrylate, polydopamine, polygluconate, polyhydroxybutyrate, polyanhydride, polyphosphoester, polyalpha hydroxy acid, polyethylene glycol, polyvinyl acetate, polyiminocarbonate, poly Lactic acid, polylactic acid-polyethylene copolymer, polyesteramide, polyglycolic acid, cellulose, cellulose acetate butylate, cellulose triacetate, modified cellulose and their copolymers; and biodegradable magnesium or magnesium alloy.

In one embodiment of the present invention, the material of the biodegradable multifilament contained in the biodegradable tube that can be inserted into the body is poly-L-lactide, poly-D-lactide, poly-D,L-lactide, poly Glycolide, polycaprolactone, poly-L-lactide-co-glycolide, poly-D-lactide-co-glycolide, poly-D,L-lactide-co-glycolide, poly-L-lac Tide-co-caprolactone, poly-D-lactide-co-caprolactone, poly-D,L-lactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone, polytrimethylene Carbonate, polyglycolide-co-dioxanone, polyamide ester, polypeptide, polyorthoester series, polymaleic acid, polyphosphazene, polyanhydride, polysebacic anhydride, polyhydroxyalkanoate, poly Hydroxyl butyrate, polycyanoacrylate, polydopamine, polygluconate, polyhydroxybutyrate, polyanhydride, polyphosphoester, polyalpha hydroxy acid, polyethylene glycol, polyvinylacetate, polyiminocarbonate, polylactic acid. , polylactic acid-polyethylene copolymer, polyesteramide, cellulose, cellulose acetate butylate, cellulose triacetate, modified cellulose, and copolymers thereof.

In one embodiment of the present invention, the biodegradable fiber may further include polyoxalate copolymer (PVAX).

In one embodiment of the present invention, the polyoxalate copolymer (PVAX) may be included in an amount of 1 to 20% by weight based on the biodegradable tube.

In one embodiment of the present invention, the biodegradable fiber may further include magnesium hydroxide (Mg(OH) ₂ ).

In one embodiment of the present invention, the magnesium hydroxide (Mg(OH) ₂ ) may be included in an amount of 10 to 30% by weight based on the biodegradable tube.

The biodegradable tube according to the present invention can provide uniform impermeability by including biodegradable fibers including a core portion formed of biodegradable monofilament and a sheath portion formed of a biodegradable polymer along the outer peripheral surface of the core portion.

The biodegradable tube according to the present invention is manufactured so that the decomposition rate (hydrolysis rate (g/hr)) of the core portion and the sheath portion is different by composing biodegradable materials differently in the core portion and sheath portion of the biodegradable fiber, and is biodegradable. It has the effect of maintaining the performance of the tube until the desired decomposition period.

The biodegradable tube according to the present invention contains fibrous protein in the sheath, which has the effect of promoting wound recovery at the treatment site and confirming the exact location by radiopaque material.

Figure 1 is a schematic diagram showing a biodegradable fiber corresponding to an embodiment of the present invention.
Figure 2 is a photograph showing a cross section of a biodegradable fiber corresponding to an embodiment of the present invention.
Figure 3 is a schematic diagram showing the structure of a spinner for manufacturing biodegradable monofilament in the present invention.
Figure 4 is a schematic diagram showing the structure of a spinner for manufacturing biodegradable multifilament in the present invention.
Figure 5 is a schematic diagram of the spinning pack (nozzle pack) used in the present invention.
Figure 6 is a schematic diagram showing a device for forming a sheath portion in the present invention.
Figure 7 is a schematic diagram showing the form of biodegradable multifilament to be implemented in the present invention.
Figure 8 is a schematic diagram showing a cross section of a biodegradable fiber that can be implemented in the present invention.
Figure 9 is a photograph of the surface state of the biodegradable fiber that can be implemented in the present invention.
Figure 10 is a photograph of a biodegradable tube treated with sodium iodide (NaI) in the present invention analyzed by X-ray.

Embodiments of the present invention may be modified in various forms, and the scope of the present invention is not limited to the embodiments described below. Embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

The biodegradable tube that can be inserted into the body of the present invention may be a medical article such as a biodegradable polymer stent or scaffold.

There is no clear limit to the average diameter of the biodegradable tube that can be inserted into the body of the present invention, but in the present invention, it may be in the range of 2 mm or more.

If the average diameter of the biodegradable tube is less than 2 mm, it may be difficult to meet the mechanical properties of the biodegradable tube relative to the diameter.

The biodegradable tube that can be inserted into the body of the present invention may include a biodegradable fiber, and the polymer fiber includes a core portion formed of biodegradable monofilament or biodegradable multifilament; And it may include a sheath portion formed of a biodegradable polymer along the outer peripheral surface of the core portion, and the core portion and the sheath portion may have different hydrolysis rates (g/hr).

The biodegradable polymer of the present invention is poly-L-lactide, poly-D-lactide, poly-D,L-lactide, polyglycolide, polycaprolactone, poly-L-lactide-co-glycolide, poly-D-lactide-co-glycolide, poly-D,L-lactide-co-glycolide, poly-L-lactide-co-caprolactone, poly-D-lactide-co-caprolactone, Poly-D,L-lactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide-co-dioxanone, polyamide ester, polypeptide, poly Orthoester series, polymaleic acid, polyphosphazene, polyanhydride, polysebacianhydride, polyhydroxyalkanoate, polyhydroxybutyrate, polycyanoacrylate, polydopamine, polygluconate, polyhydroxy Butyrate, polyanhydride, polyphosphoester, polyalpha hydroxy acid, polyethylene glycol, polyvinyl acetate, polyiminocarbonate, polylactic acid, polylactic acid-polyethylene copolymer, polyesteramide, polyglycolic acid, cellulose, It may be one or more selected from the group consisting of cellulose acetate butylate, cellulose triacetate, modified cellulose, and copolymers thereof, and may be included in biodegradable monofilament or multifilament.

In the present invention, the core part is poly-L-lactide, poly-D-lactide, poly-D,L-lactide, polylactide-based polymer, polyglycolide-based polymer, polycaprolactone, poly(α-hydroxy) ester), polylactic acid, polyglycolide, polydioxanone, polytrimethylene carbonate, poly(oxaester), poly(oxamide), poly(lactide)-poly-L-lactide, poly(lactide/ glycolide), poly(glycolide/caprolactone) (75/25), poly(glycolide/trimethylene carbonate), tyrosine-derived polyamino acid, poly(DTH carbonate), poly(arylate), poly(imino -carbonate), phosphorus-containing polymers, poly(phosphoester) and poly(phosphazene), poly(ethylene glycol)-based block copolymer, polyethylene glycol-polylactic acid, polyethylene glycol-poly(propylene glycol), polyethylene glycol-poly (butylene terephthalate), poly(α-malic acid), poly(ester amide), polyalkanoate, poly(hydroxybutyrate)(HB), poly(hydroxyvalerate)(HV) copolymer, DL poly lactic acid; polylactic acid/polyglycolide copolymer (95/5; 85/15); It may include a biodegradable polymer selected from the group consisting of polylactic acid-polycaprolactone copolymer, which has a faster absorption time than poly-L-lactide, and copolymers and blends thereof.

In the present invention, the cis portion is polyglycolide, polydioxanone, poly(α-hydroxy ester), polyanhydride, poly(carboxyphenoxy hexane-sebacic acid), poly(fumaric acid-sebacic acid), and poly(carboxylic acid). Phenoxyhexane-sebacic acid), poly(imide-sebacic acid) (50-50), poly(imide-carboxyphenoxyhexane) (33-67), tyrosine-derived polyamino acid, polyortho ester (diketene acetal) based polymer), phosphorus-containing polymer, polyglycolide/polylactic acid (90/10); polyglycolide/polycaprolactone (75/25, 50/50, 65/35); polydioxanone and its derivatives, polyethylene glycol, which have a longer absorption time than polyglycolide; Biodegradable polymers selected from the group consisting of citrate esters and other water-soluble materials that dissolve to provide a high surface area for more rapid absorption, and copolymers and blends thereof.

In another embodiment of the present invention, the biodegradable monofilament or multifilament may be a biodegradable metal thread, and the biodegradable metal thread may be any one selected from magnesium or a magnesium alloy, but has high tensile strength, high tensile elongation, and high elastic modulus. It is desirable to use a magnesium alloy that has excellent mechanical properties, stable control of decomposition rate, and has little effect on cytotoxicity.

Here, the magnesium alloy may include aluminum, zinc, manganese, etc., but is not limited thereto, and the magnesium alloy is preferably made of 1 to 5% aluminum, 0.5 to 2% zinc, and 93 to 98% magnesium.

In the present invention, the average diameter of the core portion of the biodegradable fiber may be 40 to 80% of the average diameter of the biodegradable fiber. If it is less than 40% of the average diameter of the biodegradable fiber, the elasticity, which is the force that restores the biodegradable tube to its original form, There may be a problem in that it becomes difficult to maintain the shape due to reduced recovery, and if it exceeds 80%, it causes irregularities in the surface of the sheath, making it difficult to obtain stable physical properties of the yarn due to cracks, etc., making it difficult to control the speed of biodegradation. You can. At this time, the core part may be monofilament or multifilament.

In the present invention, when the core part of the biodegradable fiber is formed of multifilament, the average diameter of the filaments constituting the multifilament may range from 1 to 20% of the total multifilament. If it is less than 1%, the number of filaments that must be input is large. As a result, the bonding strength between filaments decreases, and it is difficult to obtain the desired physical properties related to the expansion force of the biodegradable tube due to the increase in pores and interfaces. If it exceeds 20%, an interface occurs between the input radiopaque material and the polymer that makes up the filament, making it difficult to obtain biodegradable properties. There may be problems that may cause the mechanical properties of the tube to deteriorate.

The biodegradable fiber included in the biodegradable tube of the present invention can be manufactured with a difference in the hydrolysis rate (g/hr) of the core portion and the sheath portion by composing the biodegradable materials of the core portion and the sheath portion differently. In this case, By controlling the decomposition rate, the biodegradable tube can maintain its performance until the desired decomposition period.

The biodegradable tube of the present invention can improve the overall mechanical properties of the biodegradable tube by complementing the relatively weak mechanical properties when different types of biodegradable polymers or metals are included. In this case, the overall mechanical properties of the biodegradable tube can be improved by adding poly- It may contain two or more biodegradable polymers or metals selected from the group consisting of L-lactide, poly-D-lactide, poly-D,L-lactide, polycaprolactone, polydioxanone, and biodegradable magnesium. You can.

In the case where the relatively weak mechanical properties are complemented as described above, the core portion preferably contains at least one biodegradable polymer or metal selected from the group consisting of poly-L-lactide, polycaprolactone, and biodegradable magnesium, and the cis portion. Polydioxanone and poly-L-lactide-co-glycolide can be applied. In particular, poly-L-lactide is brittle and difficult to manufacture when applied to the sheath part, so it is applied to the core part, and polydioxa Non- or poly-L-lactide-co-glycolide has excellent ductility and can be applied to the sheath portion.

As described above, the overall mechanical properties of the biodegradable tube can be improved by complementing the relatively weak physical properties of the core portion and the sheath portion.

By manufacturing the biodegradable polymer in the sheath portion at a relatively slower rate than the decomposition rate of the biodegradable polymer in the core portion, the biodegradable tube inserted into the body settles for a long time and maintains its physical properties and shape, preventing narrowing of the treatment area. Accurate location confirmation is possible through radiopaque materials.

In the present invention, if the biodegradable polymer of the sheath portion has a slower decomposition rate than the biodegradable material of the core portion, the sheath portion may further include a fibrous protein to treat wounds in the treatment area or control cell differentiation, and is included in the sheath portion. The fibrous protein is a group consisting of fibrous collagen, gelatin, elastin, laminin, integrin, fibronectin, and proteoglycan. There may be one or more from.

In order to maximize the effect of treating wounds or controlling cell differentiation and the radiopaque function by including the above fibrous proteins, biodegradable hydrolysis rate of the core part is 3 to 6 months and the hydrolysis rate of the sheath part is 18 to 24 months. It is preferable to include biodegradable fibers, and specifically, it may include biodegradable polymer fibers with a ratio of hydrolysis rate (g/hr) of the core portion to the sheath portion of 3:1 to 8:1.

In the present invention, the sheath portion of the biodegradable fiber may contain 5 to 30% by weight of the fibrous protein based on the weight of the biodegradable fiber, but when contained in less than 5% by weight, it has the function of healing wounds or regulating cell differentiation. This may be insufficient, and if it is included in excess of 30% by weight, the physical properties or radio-opacity function of the biodegradable fiber may be weakened, or manufacturing may become difficult due to the gelling nature of the protein fiber.

In the present invention, the decomposition rate of the biodegradable polymer in the core portion of the sheath portion is manufactured at a slower rate than that of the biodegradable polymer in the core portion, so that the biodegradable tube inserted into the body settles for a long time and causes wounds through the fibrous protein contained in the sheath portion. By treating or controlling cell differentiation, narrowing of the treatment area can be prevented, while radiopaque materials can be used to confirm whether the biodegradable tube has settled in the correct location.

In the present invention, the decomposition rate of the biodegradable tube in the body can be controlled by adjusting the weight average molecular weight of the biodegradable polymer in the core portion or the sheath portion, and through this, the decomposition rate of the biodegradable polymer in the sheath portion is increased compared to the biodegradable polymer in the core portion. It can be designed to be slow, and when inducing regeneration of human tissue through cell culture, it is also possible to accelerate tissue regeneration by accelerating the decomposition rate of the biodegradable tube.

Therefore, in the present invention, by appropriately controlling the weight average molecular weight of the biodegradable polymer in the core portion and the weight average molecular weight of the biodegradable polymer in the sheath portion, human tissue regeneration through the fibrous protein is maximized and the biodegradable tube is positioned at the correct location. You can check whether it has settled or not.

The radiopaque material of the present invention can be mixed or coated on one or more of the core portion and sheath portion of the biodegradable fiber included in the biodegradable tube that can be inserted into the body to form a layer.

Radiopaque materials are applied to one or more of the core and sheath portions of biodegradable fibers through post-process methods such as dip-coating, electrospinning, electrospray, and 3D printing. Can be coated.

Radiopaque materials usable in the present invention include gold, silver, platinum, tantalum, tungsten, strontium, iridium, bismuth, bromine, iodine, barium sulfate, barium oxide, bismuth oxide, bismuth trioxide, sodium iodide, and iohexol ( It may include one or more radiopaque materials selected from the group consisting of iohexol, ioversol, iobitridol, and ytterbium chloride.

Since the melting point must be taken into consideration during the manufacturing process of the biodegradable fiber in the present invention, it is preferable to select a radiopaque material of the present invention that has a melting point similar to or higher than the material of the sheath portion and the core portion.

In the present invention, the radiopaque material is preferably a hydrophilic material because the more hydrophilic groups such as hydroxyl (-OH) it contains, the lower its toxicity. Examples of radiopaque materials include iohexol, ioversol, and iobitridol. ) A hydrophilic iodine-based contrast agent such as ) can be preferably used.

In the present invention, by mixing barium sulfate, a radiopaque material, with a hydrophilic solvent such as ethanol, water, or methanol, the radiopaque material can be applied in the form of a hydrophilic material with low toxicity and high solubility in the body.

In the present invention, the average particle diameter of the radiopaque material must be smaller than the average particle diameter of the biodegradable fiber, and the smaller the average particle diameter is, the more the interface between the polymer constituting the filament and the radiopaque material is minimized, thereby forming a biodegradable tube. Deterioration of mechanical properties can be prevented.

In the present invention, the average particle diameter of the radiopaque material may range from 0.5 to 20㎛. If the average particle diameter of the radiopaque material is less than 0.5㎛, a larger amount of radiopaque material must be added to exhibit opacity. This may cause toxicity and a decrease in physical properties, and if it exceeds 20㎛, there may be a problem that the mechanical properties of the biodegradable fiber may deteriorate due to the occurrence of an interface between the input radiopaque material and the polymer that makes up the filament. .

The radiopaque material of the present invention may be included in an amount of 10 to 35% by weight based on the weight of the biodegradable fiber, preferably 10 to 20% by weight, and if contained in less than 10% by weight based on the weight of the biodegradable fiber, radiation The impermeability effect may be minimal, and if it exceeds 35% by weight based on the weight of biodegradable fiber, the surface of the biodegradable tube may become irregular and uneven, making it difficult to insert into the body.

The core portion or sheath portion of the biodegradable fiber of the present invention may further include polyoxalate copolymer (PVAX), which effectively removes hydrogen peroxide, a cause of cell damage, and protects against activated macrophages. Since it has the function of suppressing the production of reactive oxygen species, when a certain amount is injected into a biodegradable tube, it can suppress or prevent cell damage in biological tissues near the area where the catheter is inserted.

Polyoxalate copolymer (PVAX) can be formed by copolymerizing vanillyl alcohol and peroxalate ester.

In the present invention, polyoxalate copolymer (PVAX) may be included in an amount of 1 to 20% by weight based on the biodegradable tube. If it is included in less than 1% by weight, there may be a problem of lack of effect in preventing cell damage, and 20% by weight may be used. If it is exceeded, there may be a problem of deterioration of the physical properties of the biodegradable tube due to increased pores, etc.

The core portion or sheath portion of _{the biodegradable fiber of the present invention may additionally contain magnesium hydroxide (Mg(OH) 2 )} , which serves to neutralize the pH of the tissue around the inserted conduit. can do.

When inflammation occurs due to the decomposition of biodegradable tube polymers or the insertion of foreign substances, acidic substances are generated and the pH of surrounding tissues is lowered. The pH is neutralized through a chemical reaction of magnesium hydroxide (Mg(OH) ₂ ), a basic ingredient. It can reduce the inflammatory response of surrounding tissues by more than 90%.

Additional addition of a functional material such as magnesium hydroxide (Mg(OH) ₂ ) has the advantage of maximizing the in vivo utility and function of the biodegradable tube.

In the present invention, magnesium hydroxide (Mg(OH) ₂ ) may be included in an amount of 10 to 30% by weight based on the biodegradable tube. However, if it is included in less than 10% by weight based on the biodegradable tube, there may be a problem that the effect of reducing the inflammatory response is minimal. If it exceeds 30% by weight, it may become difficult to provide mechanical strength to the biodegradable tube, the dispersibility of the biodegradable resin may be greatly reduced, or crystallization of the filament being processed may be inhibited, making processing difficult.

Hereinafter, the biodegradable tube of the present invention will be described in detail through the attached drawings.

Figure 1 is a schematic diagram showing a biodegradable fiber corresponding to an embodiment of the present invention. The biodegradable fiber is largely divided into a core portion 10 and a sheath portion 20.

The biodegradable fiber 1 in FIG. 1 includes a core portion 10 made of biodegradable monofilament; It is composed of a sheath portion 20 made of a biodegradable polymer, and the sheath portion 20 may include a radiopaque material.

Figure 2 is a photograph showing a cross section of a biodegradable fiber corresponding to an embodiment of the present invention.

Hereinafter, in Figures 3 to 6, the manufacturing process of biodegradable monofilament, biodegradable multifilament, and biodegradable fibers containing the same will be described.

Figure 3 shows the structure of the spinning machine 30 for manufacturing biodegradable monofilament in the present invention, which includes an extruder 31 for melting the polymer, a die head 32 for extracting the extruded polymer in the form of a line, and A spin pack 33, a coolant 34 for cooling the polymer passing through the spin pack 33, a conventional stretching device 35 for improving the physical properties of the monofilament passing through the coolant 34, and a winder ( 36).

In the manufacturing process of the biodegradable monofilament, the radiopaque material may be applied. Methods of applying the above radiopaque material include dip-coating, electrospinning, electrospray, and 3D printing. However, electrospinning and electric Electrospray method is preferred.

The dip-coating method is performed by placing a storage unit (not shown) capable of storing the radiopaque material around the extruder 31 and adding the radiopaque material in the process of melting the polymer. .

In the electrospinning and electrospray methods, a spray device (not shown) is placed around the stretching device 35 to apply the radiopaque material to the biodegradable monofilament spun from the stretching device 35. This is done by coating.

Figure 4 shows the structure of the spinner 40 for manufacturing biodegradable multifilament in the present invention.

Looking at this in detail, composite spinning uses two extruders 41 to melt each polymer. The molten polymer is discharged in the desired amount through the metering pump 42, and by controlling this, the component ratio of each polymer can be adjusted during composite spinning.

As shown in FIGS. 5A and 5B, the molten polymer discharged through the metering pump 42 is combined and spun into a single strand of yarn 44 through the spinning block 43.

Although shown in Figure 4 as a simplified single filament, the spinneret can have any number of spinnerets, and the composite spun yarn 44 is solidified and crystallized in a cooling bath 45.

An air gap exists between the spinneret and the cooling tank, and may be preferably 0.5 to 100 cm, and more preferably about 1 to 30 cm.

The solidified yarn 44 is stretched through a conventional stretching device 46 to improve physical properties by orientation, and then wound on a winder 47.

In order to improve the physical properties of the suture, selectively, the solidified thread 44 is not stretched immediately, but is wound in the form of an undrawn yarn, aged under appropriate conditions, and then stretched through the stretching device 46 to form a stretched yarn. It can also be manufactured.

In order to improve the physical properties of the stretched suture, the stretched yarn 44 is sometimes heat treated under appropriate conditions. The solidified yarn 44 or drawn yarn 44 may be the biodegradable multifilament.

In the manufacturing process of the biodegradable multifilament, the radiopaque material may be applied.

Methods of applying the above radiopaque material include dip-coating, electrospinning, electrospray, and 3D printing. However, electrospinning and electric Electrospray method is preferred.

In the dip-coating method, a storage unit (not shown) capable of storing the radio-opaque material is disposed around the two extruders 41 inside the emitter to melt the radio-opaque material in the process of melting the polymer. This is done by adding .

In the electrospinning and electrospray methods, a spray device (not shown) is placed around the stretching device 46 to apply the radiopaque material to the biodegradable multifilament spun from the stretching device 46. This is done by coating.

Figures 5a and 5b show an embodiment of the spinning pack 50 consisting of a nozzle and a distribution plate that can be used in the spinning block 43 of the present invention, and each of the first polymer and the second polymer melted through the extruder is It flows into the nozzle 52 through the distribution plates 51 and 56, respectively, and generates the biodegradable multifilament through the nozzle.

Looking at this in detail, Figure 5a shows a spinning pack for obtaining a sea-island-type suture 70. To make the component of Figure 7a, the second polymer flows through the distribution plate 51 composed of a porous pin 53, and the distribution plate 51 ), the molten first polymer flowing out through the component flow path 54 surrounds the second polymer. The number of porous pins 53 of the distribution plate 51 may vary depending on the physical properties of the final filament to be obtained.

If the number of pins is 1, it becomes a sheath/core type suture 73 as shown in Figure 7b.

Figure 5b shows a method of making a sheath/core type suture 73, in which the second polymer for the core flows through the core pin 57 of the distribution plate 56 in the center, and the first polymer flows around the distribution plate 56. It flows through and merges into one strand at the nozzle 52.

In the suture obtained through the above manufacturing process, knot stability, knot strength, and flexibility can be adjusted by using polymers with different elastic modulus, strength, or melting point, and adjusting the component ratio of each polymer.

Figure 6 shows a general schematic diagram of the sheath forming device 60, showing the monofilament 62 constituting the core portion 10 and the multifilament 63 constituting the sheath 20. ) or installed by winding each on a bobbin, then supplying in a certain order and wrapping and weaving so that the core part 10 is at the center and the sheath part 20 is at the periphery to weave in the structure shown in Figures 1 and 2. You can. It is also possible for the multifilament 63 to constitute the core portion 10.

Figure 7 shows a biodegradable multifilament form that can be implemented in the present invention. Figure 7a shows a sea-island filament 70 that is compositely spun in the form of a sea-in-the-sea yarn, with the island component 71 surrounded by the sea component 72. Figure 7b shows a form in which the sheath component 75 surrounds the core component 74 with the sheath-shaped filament 73 spun compositely in a sheath shape.

Each filament 70, 73 has different characteristics from ordinary coatings in that its composition and structure affect the overall physical properties.

Figure 8 shows a cross section of a biodegradable fiber that can be implemented in the present invention.

Figure 8a shows a cross-section of a biodegradable fiber that forms a layer by coating a radio-opaque material on the core formed of monofilament, and then forms a biodegradable multifilament coated with a radio-opaque material along its outer peripheral surface.

Figure 8b shows a cross-section of a biodegradable fiber that forms a core portion made of monofilament that is not coated with a radiopaque material, and then forms a biodegradable multifilament coated with a radiopaque material along its outer peripheral surface.

Figure 8c shows a cross-section of a biodegradable fiber that forms a biodegradable multifilament coated with a radiopaque material along its outer circumferential surface after forming a layer by coating a radiopaque material on the core portion formed of multifilament.

Figure 8d shows a cross-section of a biodegradable fiber that forms a core portion made of multifilaments that are not coated with a radiopaque material, and then forms biodegradable multifilaments coated with a radiopaque material along its outer circumferential surface.

Preparation Example 1: Preparation of biodegradable fiber containing radiopaque function

Hereinafter, the present invention will be described in detail through production examples and test examples, but the present invention is not limited to these production examples and test examples.

1. According to the conventional method described in FIGS. 3 to 5 above, a monofilament with a diameter of 110 ㎛ composed of poly-L-lactide biodegradable polymer in the core portion, and polydioxanone in the sheath portion along the outer peripheral surface of the core portion. A biodegradable tube with a formed diameter of 380㎛ was manufactured.

2. Referring to the solubility of sodium iodide (NaI) in water, 84 g of sodium iodide (NaI) powder and 100 g of distilled water were stirred at 25°C and dissolved in water to prepare a sodium iodide (NaI) solution.

3. The biodegradable fiber prepared in Process 1 was dip-coated with the sodium iodide (NaI) solution prepared in Process 2, and then dried for 24 hours to complete a radiopaque biodegradable fiber. .

Preparation Example 2: Preparation of biodegradable tube containing radiopaque function

1. A design within a biodegradable tube was designed by adjusting the spacing of metal pins in a cylindrical metal jig.

2. The biodegradable fiber completed through Preparation Example 1 was placed in the designed tube design.

3. The design was heat treated considering the melting point and glass transition temperature of the biodegradable fiber material fixed to the metal jig.

4. After cooling the temperature of the metal jig to room temperature or with a fan, the metal pin was removed to detach the biodegradable tube from the cylindrical metal jig.

Test example: Confirmation of radiopaque function

In the above production example, radiopacity was confirmed through X-ray analysis through the biodegradable tube treated with sodium iodide (NaI) solution and the biodegradable tube not treated with sodium iodide (NaI) solution.

The results of the Biodegradable tube, represents NiTinol metal that has not been treated with sodium iodide (NaI) solution.

1: Biodegradable fiber
10: Core part
20: Sis part
30: Spinner for producing biodegradable monofilament
31: Extruder
32: Die head
33: Spinpack
34: Coolant
35: stretching device
36: Winder
40: Spinner for manufacturing biodegradable multifilament
41: Two extruders
42: Metering pump
43: Radiation block
44: solidified thread
46: stretching device
50: Radiation pack
51: distribution board
52: nozzle
53: perforated pin
54: Euro for sea ingredients
55: Radiation pack body
56: distribution plate
57: core pin
60: Multifilament injection device
61: carrier
62: monofilament
63: Multifilament
70: Island-shaped filament
71: Doseongbun
72: Sea ingredients
73: Siscore type filament
74: Core ingredients
75: Cis component
80a, 80b, 80c, 80d: Core
81a, 81b, 81c, 81d: cis
82a, 82b, 82c, 82d: layer of radiopaque material

Claims (13)

In a biodegradable tube that can be inserted into the body,
A biodegradable fiber comprising a core portion formed of biodegradable monofilament and a sheath portion formed of a biodegradable polymer along the outer peripheral surface of the core portion,
The cis portion is one from the group consisting of fibrous collagen, gelatin, elastin, laminin, integrin, fibronectin, and proteoglycan. It further contains the above fibrous proteins,
The fibrous protein is contained in an amount of 5 to 30% by weight based on the weight of the biodegradable fiber,
At least one of the core portion and the sheath portion contains 10 to 35% by weight of a radiopaque material based on the weight of the biodegradable fiber,
The biodegradable monofilament materials include poly-L-lactide, poly-D-lactide, poly-D,L-lactide, polyglycolide, polycaprolactone, and poly-L-lactide-co-glycolide. , poly-D-lactide-co-glycolide, poly-D,L-lactide-co-glycolide, poly-L-lactide-co-caprolactone, poly-D-lactide-co-caprolactone , poly-D,L-lactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide-co-dioxanone, polyamide ester, polypeptide, Polyorthoester, polymaleic acid, polyphosphazene, polyanhydride, polysebacianhydride, polyhydroxyalkanoate, polyhydroxybutyrate, polycyanoacrylate, polydopamine, polygluconate, polyhydride Roxybutyrate, polyanhydride, polyphosphoester, polyalpha hydroxy acid, polyethylene glycol, polyvinyl acetate, polyiminocarbonate, polylactic acid, polylactic acid-polyethylene copolymer, polyesteramide, polyglycolic acid, cellulose , cellulose acetate butylate, cellulose triacetate, modified cellulose and their copolymers; and at least one selected from the group consisting of biodegradable magnesium or magnesium alloy,
A biodegradable tube in which the core portion and the sheath portion are made of different materials and have different hydrolysis rates (g/hr). delete delete delete delete According to paragraph 1,
The radiopaque materials include gold, silver, platinum, tantalum, tungsten, strontium, iridium, bismuth, bromine, iodine, barium sulfate, barium oxide, bismuth oxide, bismuth trioxide, sodium iodide, iohexol, and ioversol. A biodegradable tube comprising at least one selected from the group consisting of (ioversol), iobitridol, and ytterbium chloride. delete delete delete According to paragraph 1,
The biodegradable fiber is a biodegradable tube further comprising polyoxalate copolymer (PVAX). According to clause 10,
The polyoxalate copolymer (PVAX) is a biodegradable tube containing 1 to 20% by weight based on the biodegradable tube. According to paragraph 1,
The biodegradable fiber is a biodegradable tube further comprising magnesium hydroxide (Mg(OH) ₂ ). According to clause 12,
A biodegradable tube containing 10 to 30% by weight of magnesium hydroxide (Mg(OH) ₂ ) based on the biodegradable tube.