KR102394776B1 - Stent for angioplasty - Google Patents

Abstract

The present invention relates to a stent for angioplasty, and the stent for angioplasty according to an embodiment of the present invention includes an expandable member; and a drug delivery film formed on the inflatable member.

Description

Stent for angioplasty

The present invention relates to a stent for angioplasty.

Coronary artery stenosis is often treated by a procedure known as stenting, in which a medical device (stent) is percutaneously implanted in the affected artery to prevent occlusion after the procedure. Complications such as restenosis are problems in which stenosis occurs again in the treated area in patients who have been treated for atherosclerosis in the form of medical procedures such as Percutaneous Transluminal Coronary Angioplasty (PTCA). The site of restenosis is usually treated with additional stenting or drug release balloons.

A stent is typically cylindrical in shape and is mainly made of a biocompatible metal such as cobalt chromium or surgical steel. Most stents are collapsible and are delivered through a cervical catheter into an obstructed artery. The stent is attached to a catheter and can be self-expanding or expanded by inflation of a balloon inside the stent that is later removed along with the catheter once the stent is in place.

Complications that may occur with stent therapy include restenosis and thrombosis. In an effort to overcome these complications, stents may include a layer or coating of anti-restenosis drug that is released in a controlled manner at the stent-implantation site. Typically, the drug is contained in, for example, a permanent or biodegradable polymeric carrier. Examples of conventional therapeutic agents proposed to be delivered in this manner include antiproliferative (anti-cancer agents: taoxol series) drugs, and anti-inflammatory agents (immunosuppressive agents: ex. sirolimus). It has been proposed that a polymeric carrier with a drug can be covered by a porous biodegradable layer that functions to modulate the controlled release of the drug into the body.

More recently, stents have been proposed in which an anti-restenosis drug is delivered into a channel, groove or pore for release in "polymer-free", ie, pure drug form. A stent with a roughened surface intended to immobilize a drug layer on the surface of the stent for release in pure drug form has been proposed. However, none of these indicate or suggest that, together with a particular class of anti-restenosis compounds, the anti-restenosis activity of the compounds can be enhanced by the selection of surface roughness characteristics within a certain range on the stent surface.

Most of the site where the stent is fixed includes a site where the vascular endothelium is already damaged. In addition, technically, the stent is implanted in the blood vessel to dig into the vascular endothelium. Damage to the endothelium cannot be avoided, and an initial inflammatory reaction is bound to occur accordingly.

Since the inflammatory reaction that occurs during this process responds to platelet activation as an initial mechanism, in general, patients undergoing stenting must maintain two antiplatelet drugs for about 6 months to 1 year in order to suppress this reaction, and thereafter, one treatment for the rest of their life. Maintenance of antiplatelet agents is recommended, and failure to do so has been reported to lead to an increased risk of thrombosis and restenosis.

However, initially strong antiplatelet therapy and maintaining one for life is associated with a significant increase in bleeding, and the most fatal hemorrhage is cerebral hemorrhage.

Therefore, from the viewpoint of complications related to stent therapy and the use of antiplatelet agents, it minimizes the inflammatory reaction after placement of the stent at the site of vascular injury and prevents the use of antiplatelet agents by leaving foreign metals in the blood vessels in the long term while minimizing the risk of thrombotic complications. The development of a stent having a lowering structure and drug component is required.

In this background, various stents have been developed and developed, and a bioresorbable stent has been developed and clinical research has been conducted.

The present invention is to solve the above-mentioned problems, and an object of the present invention is to use a bioresorbable polymer to maintain the shape by making the structure thinner and more dense, containing the drug and mammalian blood To provide a stent for angioplasty in which recurrent stenosis is prevented by adhering to the blood vessel of the subject, the biodegradation rate is shortened to several days to several weeks, and the decomposition dispersion can be bioabsorbed or excreted through a natural route in the body there is.

However, the problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

Angioplasty stent according to an embodiment of the present invention, an expandable member; and a drug delivery film formed on the inflatable member.

In one embodiment, the inflatable member may be in the form of a tubular network structure.

In one embodiment, the inflatable member may have pores formed on its surface, and the pore size may be 20 μm to 40 μm.

In one embodiment, the inflatable member may include a balloon catheter.

In an embodiment, the inflatable member may expand in a radial direction of an inserted blood vessel.

In an embodiment, the inflatable member may expand by 2 mm to 30 mm depending on the size of the blood vessel in the radial direction.

In one embodiment, the expandable member, the radial direction, the longitudinal direction of the blood vessel to be inserted may be one that can contract and expand in both directions.

In one embodiment, the drug delivery film may include a biodegradable material.

In one embodiment, the biodegradable material may be one comprising a natural polymer, a synthetic polymer, or both.

In one embodiment, the natural polymer is hyaluronic acid, chitosan, collagen, alginic acid, albumin, gelatin, silk fibroin. , polypeptide, heparin, alginate, dextran, chondroitin sulfate, dextran sulfate, acacia gum, tragacanthin ), pectin, guar gum, sodium carboxymethyl dextran, carboxymethyl cellulose, peptide, oligopeptide, agar, carrageenan ( carrageenan), Galactomannans, Xanthan, Beta-Cyclodextrin, Amylose (water-soluble starch), fibrin, pullulan and tertiary amine It may include at least one selected from the group consisting of starch ether).

In one embodiment, the synthetic polymer is polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), poly(D,L-lactic acid-co-glycolic acid) (poly(D,L) -lactide-co-glycolide; PLGA), poly(caprolactone), poly(valerolactone), poly(hydroxybutyrate), poly(hydroxyvalerate), poly[(3-hydroxybutyrate)-co- (3-hydroxyvalerate) (PHBV), polydioxanone (PDO), poly[(L-lactide)-co-(caprolactone)], poly(ester urethane) (PEUU), poly[(L-) group consisting of lactide)-co-(D-lactide)], poly[ethylene-co-(vinyl alcohol)](PVOH), hydroxyapatite (HA) and βtricalcium phosphate (βphosphate; β) It may be to include at least any one selected from.

In one embodiment, the drug delivery film, p-isononyl phenoxypolyglycidol, PEG laurate, PEG oleate, PEG stearate, PEG glyceryl laurate, Tween 20, Tween 40, Tween 60, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate, polyglyceryl-6 laurate, polyglyceryl-6 oleate Eate, polyglyceryl-6 myristate, polyglyceryl-6 palmitate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyglyceryl-10 myristate, polyglyceryl-10 palmitate, PEG sorbitan monolaurate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG oleyl ether, PEG lauryl ether, octocinol, monoxynol, tyloxapol, sucrose Monopalmitate, sucrose monolaurate, decanoyl-N-methylglucamide, n-decyl-β-D-glucopyranoside, n-decyl-β-D-maltopyranoside, n-dodecyl -β-D-glucopyranoside, n-dodecyl-β-D-maltoside, heptanoyl-N-methylglucamide, n-heptyl-β-D-glucopyranoside, n-heptyl-β -D-thioglucoside, n-hexyl-β-D-glucopyranoside, nonanoyl-N-methylglucamide, n-noyl-β-D-glucopyranoside, octanoyl-N-methylgyl lucamide, n-octyl-β-D-glucopyranoside, octyl-β-D-thioglucopyranoside; cystine, tyrosine, tryptophan, leucine, isoleucine, phenylalanine, asparagine, aspartic acid, glutamic acid, and methionine; acetic anhydride, benzoic anhydride, ascorbic acid, 2-pyrrolidone-5-carboxylic acid, sodium pyrrolidone carboxylate, ethylenediaminetetraacetic dianhydride, maleic anhydride; Succinic anhydride, diglycolic anhydride, glutaric anhydride, acetylamine, benfotiamine, pantothenic acid, cetothiamine, cyclothiamine, dexpanthenol, niacinamide, nicotinic acid, pyridoxal 5-phosphate, nicotinamide ascorbate, riboflavin, riboflavin phosphate, thiamine, folic acid, menadiol diphosphate, menadione sodium bisulfite, menadoxime, vitamin B12, vitamin K5, vitamin K6, vitamin K6 and vitamin U (S-methylmethionine); Albumin, immunoglobulin, casein, hemoglobin, lysozyme, immunoglobin, α-2-macroglobulin, fibronectin, vitronectin, fibrinogen, lipase, benzalkonium chloride, benzethonium chloride, dodecyltrimethylammonium bromide, dodecyl dialkyl esters of sodium sulfate, dialkyl methylbenzyl ammonium chloride, and sodium sulfosuccinate; L-ascorbic acid and its salts, D-glucoascorbic acid and its salts, tromethamine, triethanolamine, diethanolamine, meglumine, glucamine, amine alcohol, glucoheptonic acid, gluconic acid, hydroxyl ketone, hydride Loxyl lactone, gluconolactone, glucoheptonolactone, glucooctanoic acid lactone, gulonic acid lactone, mannonic acid lactone, ribonate lactone, lactobionic acid, glucosamine, glutamic acid, benzyl alcohol, benzoic acid, hydroxybenzoic acid, propyl-4- Hydroxybenzoate, lysine acetate, gentic acid, lactobionic acid, lactitol, cinapic acid, vanillic acid, vanillin, methyl paraben, propyl paraben, sorbitol, xylitol, cyclodextrin, (2-hydroxypropyl) cyclodextrin, Acetaminophen, ibuprofen, retinoic acid, lysine acetate, gentic acid, catechin, catechin gallate, tiletamine, ketamine, propofol, lactic acid, acetic acid, salts of any organic acid with organic amines, polyglycidol, glycerol, polyglycerol , galactitol, di(ethylene glycol), tri(ethylene glycol), tetra(ethylene glycol), penta(ethylene glycol), poly(ethylene glycol) oligomer, di(propylene glycol), tri(propylene glycol), tetra(propylene) glycol), penta (propylene glycol), poly (propylene glycol) oligomers, and at least one selected from the group consisting of derivatives thereof may be further included.

In one embodiment, the drug delivery film may have a thickness of 20 μm to 50 μm.

In one embodiment, the drug delivery film may include an anti-inflammatory drug in the vascular endothelium, and a platelet inhibitory drug in the vascular inner diameter direction.

In one embodiment, the anti-inflammatory drug is cilostazol, everolimus, dicoumarol, zotarolimus, carvedilol, antithrombotic agent, heparin, heparin derivative, urokinase, and dextrophenylalanine proline arginine chloromethyl ketone; anti-inflammatory agents, dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine and mesalamine, sirolimus and everolimus, anti-neoplastic/antiproliferative/antimitotic agents, major taxane domain-binding drugs, paclitaxel and its Analogs, epothilone, discordermolide, docetaxel, paclitaxel protein binding particles, ABRAXANE® (ABRAXANE is a registered trademark of ABRAXIS BIOSCIENCE, LLC), cyclodextrins (or cyclodextrin-like molecules) Paclitaxel synthesized with rapamycin and its analogues, rapamycin (or rapamycin analogue) synthesized with cyclodextrin (or cyclodextrin-like molecule), 17β-estradiol, 17β-estradiol synthesized with cyclodextrin, dicoumarol , dicoumarol synthesized with cyclodextrin, β-rapacon and its analogs, 5-fluorouracil, cisplatin, vinblastine, cladribine, vincristine, epothilone, endostatin, angiostatin, angiopeptin, smooth muscle cells monoclonal antibodies capable of blocking proliferation, and thymidine kinase inhibitors; cytolytic agents; It may include at least one selected from the group consisting of anesthetics, lidocaine, bupivacaine, and ropivacaine.

In one embodiment, the platelet inhibitory drug includes a P2Y1 receptor antagonist, a P2Y12 inhibitor, or an antagonist including a P2Y12 receptor antagonist, and the P2Y12 antagonist is clopidogrel, ticlopidine ), prasugrel (prasugrel), AR-C67085MX, cangrelor, C1330-7, MRS 2395 and 2-methylthioadenosine-5'-monophosphate may be one comprising at least one selected from the group consisting of.

In one embodiment, the stent for angioplasty may be for treatment of vascular stenosis or occlusion.

Since the stent for angioplasty according to an embodiment of the present invention is very thin and almost in the form of a film, the degree of penetrating into the vascular endothelium is very small, so that the inflammatory reaction after placement of the stent at the site of vascular damage is minimized, and stent therapy and stent therapy In view of associated complications, it is possible to reduce the incidence of inflammatory response and restenosis after stent placement at the site of vascular injury. Additionally, a drug delivery film that slowly dissolves over days to weeks may minimize the use of antiplatelet agents while maximizing the drug loading capacity and ability to deliver the drug to the vessel wall in a therapeutically enhanced manner. In addition, since there is no need to expand and maintain the balloon for a long period of time (40 to 80 seconds) like the conventional drug release balloon, it is possible to safely perform the operation even on a relatively large blood vessel from the point of view of a procedure using the drug release balloon.

1 is a schematic diagram of a stent for angioplasty according to an embodiment of the present invention.
2 is a schematic diagram of a stent for angioplasty according to another embodiment of the present invention.
3 is a cross-sectional view of a portion A of FIG. 1 .
4 shows an exemplary cross-sectional view of an inflatable member in a blood vessel in accordance with an embodiment of the present invention.
5 shows an exemplary perspective view of an inflatable member in a blood vessel in accordance with an embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. In describing the present invention, if it is determined that a detailed description of a related known function or configuration may unnecessarily obscure the gist of the present invention, the detailed description thereof will be omitted. In addition, the terms used in this specification are terms used to properly express a preferred embodiment of the present invention, which may vary depending on the intention of a user or operator or a custom in the field to which the present invention belongs. Accordingly, definitions of these terms should be made based on the content throughout this specification. Like reference numerals in each figure indicate like elements.

Throughout the specification, when a member is said to be located "on" another member, this includes not only a case in which a member is in contact with another member but also a case in which another member exists between the two members.

Throughout the specification, when a part "includes" a certain component, it means that other components may be further included, rather than excluding other components, unless otherwise stated.

Hereinafter, the stent for angioplasty of the present invention will be described in detail with reference to Examples and drawings. However, the present invention is not limited to these examples and drawings.

Angioplasty stent according to an embodiment of the present invention, an expandable member; and a drug delivery film formed on the inflatable member.

The stent for angioplasty according to an embodiment of the present invention can be used as a medium for delivering drugs, for example, anti-inflammatory and anti-platelet substances, and is biodegraded over several days or months to breathe or urine It may be made of a material that is decomposed into a substance that is emitted as As the porosity is increased by the pores formed on the surface of the stent body and contains more drugs compared to the smooth surface, it is possible to reduce restenosis and thrombosis of the stenosis site due to the action of the drug after the procedure.

1 is a schematic diagram of a stent for angioplasty according to an embodiment of the present invention, FIG. 1 is a schematic diagram of a stent for angioplasty according to another embodiment of the present invention, and FIG. 3 is a cross-sectional view of part A of FIG. 1 .

Referring to FIG. 1 , the stent 100 for angioplasty according to an embodiment of the present invention consists of only the expandable member 110, and referring to FIG. 2 , an angioplasty stent according to another embodiment of the present invention 100 includes an inflatable member 110 and an inlet 120 . Referring to FIG. 3 , the inflatable member 110 includes a balloon catheter 112 and a drug delivery film 114 . When the inflatable member 110 expands, an internal space 116 is created. In one embodiment, the inflatable member 110 may be in the form of a tubular mesh structure.

In one embodiment, the inflatable member 110 may have pores formed on its surface, and the pore size may be in a range of 20 μm to 40 μm. Innumerable pores can be formed on the surface of the expandable member 110, so that the porosity increases and contains more drugs compared to the smooth surface. can

In an embodiment, the inflatable member 110 may include a balloon catheter 112 .

In an embodiment, the inflatable member 110 may expand in a radial direction of an inserted blood vessel. Therefore, when performing angioplasty using the stent 100 for angioplasty, the balloon is expanded and adhered to the blood vessel while leaving the drug delivery film 114 that slowly melts in the blood vessel over several days to several weeks and comes out of the living body. can

In one embodiment, the balloon catheter 112 may include, for example, an amorphous elastomeric polymer. The balloon catheter 112 may be, for example, a polyurethane elastomer.

In one embodiment, the inflatable member 110 is expandable under inflation pressure by at least 2 times or more and to a diameter greater than, for example, 5 times the unexpanded diameter of the inflatable member 110 . It can be stretched/strained and, upon retraction, recover most or all of its unexpanded shape.

In the expansion process of the inflatable member according to an embodiment of the present invention, first, the inflatable member is maintained in an uninflated state at normal temperature and then inserted into a blood vessel, the balloon 112 self-inflates due to a temperature change. (self-expanding), it can be seated on the inner wall of the blood vessel or maintained in an expanded state by the gas injected into the balloon.

In an embodiment, the inflatable member 110 may expand to 2 mm to 30 mm according to the size of the blood vessel in the radial direction.

4 is an exemplary cross-sectional view of an intravascular inflatable member according to an embodiment of the present invention, and FIG. 5 is an exemplary perspective view of an intravascular inflatable member according to an embodiment of the present invention. 4 and 5, the expandable member 110 can be expanded to facilitate occupying the lumen of the blood vessel 200, and the drug delivery film 114 on the balloon catheter 112 is transferred to the blood vessel 200. In close contact with the drug delivery film 114 can be attached to the blood vessel (200).

In one embodiment, the expandable member 110, the radial direction, the longitudinal direction of the blood vessel to be inserted may be one that can contract and expand in both directions. In one embodiment, the inflatable member 110 may be radially compliant to allow expansion in both the radial and longitudinal directions of the blood vessel.

In an embodiment, the drug delivery film 114 may be separable from the expandable member 110 . The inflatable member 110 is inflated to bring the drug delivery film 114 into close contact with the blood vessel, leaving the drug delivery film 114 and the inflatable member 110 out of the living body.

In one embodiment, the drug delivery film 114 may include a biodegradable material. The biodegradable material has a short decomposition time in the living body, so it is good to utilize it in the living body.

In one embodiment, the biodegradable material may be one comprising a natural polymer, a synthetic polymer, or both.

In one embodiment, the natural polymer is hyaluronic acid, chitosan, collagen, alginic acid, albumin, gelatin, silk fibroin. , polypeptide, heparin, alginate, dextran, chondroitin sulfate, dextran sulfate, acacia gum, tragacanthin ), pectin, guar gum, sodium carboxymethyl dextran, carboxymethyl cellulose, peptide, oligopeptide, agar, carrageenan ( carrageenan), Galactomannans, Xanthan, Beta-Cyclodextrin, Amylose (water-soluble starch), fibrin, pullulan and tertiary amine It may include at least one selected from the group consisting of starch ether).

In one embodiment, the synthetic polymer is polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), poly(D,L-lactic acid-co-glycolic acid) (poly(D,L) -lactide-co-glycolide; PLGA), poly(caprolactone), poly(valerolactone), poly(hydroxybutyrate), poly(hydroxyvalerate), poly[(3-hydroxybutyrate)-co- (3-hydroxyvalerate) (PHBV), polydioxanone (PDO), poly[(L-lactide)-co-(caprolactone)], poly(ester urethane) (PEUU), poly[(L-) group consisting of lactide)-co-(D-lactide)], poly[ethylene-co-(vinyl alcohol)](PVOH), hydroxyapatite (HA) and βtricalcium phosphate (βphosphate; β) Preferably, the synthetic polymer may include polylactic acid/polyglycolic acid (PLA/PGA).

In one embodiment, the drug delivery film 114, p-isononyl phenoxypolyglycidol, PEG laurate, PEG oleate, PEG stearate, PEG glyceryl laurate, Tween 20, Tween 40, Tween 60, PEG Glyceryl Oleate, PEG Glyceryl Stearate, Polyglyceryl Laurate, Polyglyceryl Oleate, Polyglyceryl Myristate, Polyglyceryl Palmitate, Polyglyceryl-6 Laurate, Polyglyceryl -6 Oleate, Polyglyceryl-6 Myristate, Polyglyceryl-6 Palmitate, Polyglyceryl-10 Laurate, Polyglyceryl-10 Oleate, Polyglyceryl-10 Myristate, Polyglyceryl-10 palmitate, PEG sorbitan monolaurate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG oleyl ether, PEG lauryl ether, octocinol, monoxynol, tyloxapol , sucrose monopalmitate, sucrose monolaurate, decanoyl-N-methylglucamide, n-decyl-β-D-glucopyranoside, n-decyl-β-D-maltopyranoside, n -dodecyl-β-D-glucopyranoside, n-dodecyl-β-D-maltoside, heptanoyl-N-methylglucamide, n-heptyl-β-D-glucopyranoside, n- Heptyl-β-D-thioglucoside, n-hexyl-β-D-glucopyranoside, nonanoyl-N-methylglucamide, n-noyl-β-D-glucopyranoside, octanoyl-N -methylglucamide, n-octyl-β-D-glucopyranoside, octyl-β-D-thioglucopyranoside; cystine, tyrosine, tryptophan, leucine, isoleucine, phenylalanine, asparagine, aspartic acid, glutamic acid, and methionine; acetic anhydride, benzoic anhydride, ascorbic acid, 2-pyrrolidone-5-carboxylic acid, sodium pyrrolidone carboxylate, ethylenediaminetetraacetic dianhydride, maleic anhydride; Succinic anhydride, diglycolic anhydride, glutaric anhydride, acetylamine, benfotiamine, pantothenic acid, cetothiamine, cyclothiamine, dexpanthenol, niacinamide, nicotinic acid, pyridoxal 5-phosphate, nicotinamide ascorbate, riboflavin, riboflavin phosphate, thiamine, folic acid, menadiol diphosphate, menadione sodium bisulfite, menadoxime, vitamin B12, vitamin K5, vitamin K6, vitamin K6 and vitamin U (S-methylmethionine); Albumin, immunoglobulin, casein, hemoglobin, lysozyme, immunoglobin, α-2-macroglobulin, fibronectin, vitronectin, fibrinogen, lipase, benzalkonium chloride, benzethonium chloride, dodecyltrimethylammonium bromide, dodecyl dialkyl esters of sodium sulfate, dialkyl methylbenzyl ammonium chloride, and sodium sulfosuccinate; L-ascorbic acid and its salts, D-glucoascorbic acid and its salts, tromethamine, triethanolamine, diethanolamine, meglumine, glucamine, amine alcohol, glucoheptonic acid, gluconic acid, hydroxyl ketone, hydro Loxyl lactone, gluconolactone, glucoheptonolactone, glucooctanoate lactone, gulonic acid lactone, mannonate lactone, ribonate lactone, lactobionic acid, glucosamine, glutamic acid, benzyl alcohol, benzoic acid, hydroxybenzoic acid, propyl-4- Hydroxybenzoate, lysine acetate, gentic acid, lactobionic acid, lactitol, cinapic acid, vanillic acid, vanillin, methyl paraben, propyl paraben, sorbitol, xylitol, cyclodextrin, (2-hydroxypropyl) cyclodextrin, Acetaminophen, ibuprofen, retinoic acid, lysine acetate, gentic acid, catechin, catechin gallate, tiletamine, ketamine, propofol, lactic acid, acetic acid, salts of any organic acid with organic amines, polyglycidol, glycerol, polyglycerol , galactitol, di(ethylene glycol), tri(ethylene glycol), tetra(ethylene glycol), penta(ethylene glycol), poly(ethylene glycol) oligomer, di(propylene glycol), tri(propylene glycol), tetra(propylene) glycol), penta (propylene glycol), poly (propylene glycol) oligomers, and at least one selected from the group consisting of derivatives thereof may be further included.

In one embodiment, the drug delivery film may have a thickness of 20 μm to 50 μm. Preferably, it may be 20 μm to 40 μm. The structure of the drug delivery film takes the form of a very thin and dense stent, but the size of the pores between the struts is 2 mm, which is the minimum diameter, and is 20 μm or more when expanded to allow red blood cells to pass through. Also, the hardness of the stent is very low, so that the wire can easily pass through. The drug used takes the form of being coated on the stent and then released.

In one embodiment, the drug delivery film may include an anti-inflammatory drug (sirolimus) on the vascular endothelium, and a platelet inhibitory drug (clopidogrel) on the vascular inner diameter direction. Therefore, restenosis and thrombosis do not occur at the stenosis site where the stent is inserted.

In one embodiment, the anti-inflammatory drug is cilostazol, everolimus, dicoumarol, zotarolimus, carvedilol, antithrombotic agent, heparin, heparin derivative, urokinase, and dextrophenylalanine proline arginine chloromethyl ketone; anti-inflammatory agents, dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine and mesalamine, sirolimus and everolimus, anti-neoplastic/antiproliferative/antimitotic agents, major taxane domain-binding drugs, paclitaxel and its Analogs, epothilone, discordermolide, docetaxel, paclitaxel protein binding particles, ABRAXANE (ABRAXANE is a registered trademark of ABRAXIS BIOSCIENCE, LLC), cyclodextrins (or cyclodextrin-like molecules); Synthesized paclitaxel, rapamycin and its analogues, rapamycin (or rapamycin analogue) synthesized with cyclodextrin (or cyclodextrin-like molecule), 17β-estradiol, 17β-estradiol synthesized with cyclodextrin, dicoumarol; Dicoumarol synthesized with cyclodextrin, β-rapacon and analogs thereof, 5-fluorouracil, cisplatin, vinblastine, cladribine, vincristine, epothilone, endostatin, angiostatin, angiopeptin, smooth muscle cell proliferation monoclonal antibodies capable of blocking , and thymidine kinase inhibitors; cytolytic agents; It may include at least one selected from the group consisting of anesthetics, lidocaine, bupivacaine, and ropivacaine.

In one embodiment, the platelet inhibitory drug includes a P2Y1 receptor antagonist, a P2Y12 inhibitor, or an antagonist including a P2Y12 receptor antagonist, and the P2Y12 antagonist is clopidogrel, ticlopidine ), prasugrel (prasugrel), AR-C67085MX, cangrelor, C1330-7, MRS 2395 and 2-methylthioadenosine-5'-monophosphate may be one comprising at least one selected from the group consisting of.

In an embodiment, the drug delivery film 114 may be protein-free. When the drug delivery film 114 is a protein, it may be adsorbed in the blood vessel.

In one embodiment, the stent for angioplasty may be for treatment of vascular stenosis or occlusion. In addition, it can be modified to cause a thrombolytic action, and can be inserted into a tissue or vascular system requiring a thrombolytic reaction.

Since the stent for angioplasty according to an embodiment of the present invention is very thin and almost in the form of a film, the degree of penetrating into the vascular endothelium is very small, so that the inflammatory reaction after placement of the stent at the site of vascular damage is minimized, and stent therapy and stent therapy In view of associated complications, it is possible to reduce the incidence of inflammatory response and restenosis after stent placement at the site of vascular injury. Additionally, a drug delivery film that slowly dissolves over days to weeks may minimize the use of antiplatelet agents while maximizing the drug loading capacity and ability to deliver the drug to the vessel wall in a therapeutically enhanced manner. In addition, since there is no need to expand and maintain the balloon for a long period of time (40 to 80 seconds) like the conventional drug release balloon, it is possible to safely operate even a relatively large blood vessel.

Hereinafter, the present invention will be described in detail with reference to the following examples. However, the technical spirit of the present invention is not limited or limited thereto.

[Example]

It is a dense and thin stent-type film made of 20 nm polylactic acid or a copolymer of polyglycolic acid (PLA/PGA) with pores of about 20 μm in size. and P2Y1 receptor antagonist as a platelet inhibitory drug in the inner diameter direction of blood vessels.

In vitro drug release from the stent

In vitro drug release was performed at 37° C. in PBS pH 7.4/Tween medium using the stent of Example. Sampling was performed regularly and the total amount of cilostazol was measured by HPLC.

animal transplant test

The stent from the example was implanted into outbred immature pigs. The porcine target vessels were pre-dilated by known angiogenesis techniques prior to stent placement.

After 28 days, the animals were euthanized according to the approved protocol, and the heart and surrounding tissues were removed from the animals.

As described above, although the present invention has been described with reference to limited embodiments and drawings, the present invention is not limited to the above embodiments, and various modifications and variations from these descriptions are provided by those skilled in the art to which the present invention pertains. This is possible. Therefore, the scope of the present invention should not be limited to the described embodiments, but should be defined by the following claims as well as the claims and equivalents.

100: stent for angioplasty
110: inflatable member
112: balloon catheter
114: drug delivery film
116: inner space
200: blood vessels

Claims (17)

an inflatable member; and
a drug delivery film formed on the inflatable member;
including,
The inflatable member is in the form of a tubular network structure,
The inflatable member comprises a balloon catheter,
The drug delivery film, p-isononyl phenoxypolyglycidol, PEG laurate, PEG oleate, PEG stearate, PEG glyceryl laurate, Tween 20, Tween 40, Tween 60, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate, polyglyceryl-6 laurate, polyglyceryl-6 oleate, polyglyceryl- 6 Myristate, Polyglyceryl-6 Palmitate, Polyglyceryl-10 Laurate, Polyglyceryl-10 Oleate, Polyglyceryl-10 Myristate, Polyglyceryl-10 Palmitate, PEG Sorbitan Monolaurate , PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG oleyl ether, PEG lauryl ether, octocinol, monoxynol, tyloxapol, sucrose monopalmitate, sucrose Monolaurate, decanoyl-N-methylglucamide, n-decyl-β-D-glucopyranoside, n-decyl-β-D-maltopyranoside, n-dodecyl-β-D-glu Copyranoside, n-dodecyl-β-D-maltoside, heptanoyl-N-methylglucamide, n-heptyl-β-D-glucopyranoside, n-heptyl-β-D-thioglucoside , n-hexyl-β-D-glucopyranoside, nonanoyl-N-methylglucamide, n-noyl-β-D-glucopyranoside, octanoyl-N-methylglucamide, n-octyl -β-D-glucopyranoside, octyl-β-D-thioglucopyranoside; cystine, tyrosine, tryptophan, leucine, isoleucine, phenylalanine, asparagine, aspartic acid, glutamic acid, and methionine; acetic anhydride, benzoic acid anhydride, ascorbic acid, 2-pyrrolidone-5-carboxylic acid, sodium pyrrolidone carboxylate, ethylenediaminetetraacetic dianhydride, maleic anhydride; Succinic anhydride, diglycolic anhydride, glutaric anhydride, acetylamine, benfotiamine, pantothenic acid, cetothiamine, cyclothiamine, dexpanthenol, niacinamide, nicotinic acid, pyridoxal 5-phosphate, nicotinamide ascorbate, riboflavin, riboflavin phosphate, thiamine, folic acid, menadiol diphosphate, menadione sodium bisulfite, menadoxime, vitamin B12, vitamin K5, vitamin K6, vitamin K6 and vitamin U (S-methylmethionine); Albumin, immunoglobulin, casein, hemoglobin, lysozyme, immunoglobin, α-2-macroglobulin, fibronectin, vitronectin, fibrinogen, lipase, benzalkonium chloride, benzethonium chloride, dodecyltrimethylammonium bromide, dodecyl dialkyl esters of sodium sulfate, dialkyl methylbenzyl ammonium chloride, and sodium sulfosuccinate; L-ascorbic acid and its salts, D-glucoascorbic acid and its salts, tromethamine, triethanolamine, diethanolamine, meglumine, glucamine, amine alcohol, glucoheptonic acid, gluconic acid, hydroxyl ketone, hydro Loxyl lactone, gluconolactone, glucoheptonolactone, glucooctanoate lactone, gulonic acid lactone, mannonate lactone, ribonate lactone, lactobionic acid, glucosamine, glutamic acid, benzyl alcohol, benzoic acid, hydroxybenzoic acid, propyl-4- Hydroxybenzoate, lysine acetate, gentic acid, lactobionic acid, lactitol, cinapic acid, vanillic acid, vanillin, methyl paraben, propyl paraben, sorbitol, xylitol, cyclodextrin, (2-hydroxypropyl) cyclodextrin, Acetaminophen, ibuprofen, retinoic acid, lysine acetate, gentic acid, catechin, catechin gallate, tiletamine, ketamine, propofol, lactic acid, acetic acid, salts of any organic acid with organic amines, polyglycidol, glycerol, polyglycerol , galactitol, di(ethylene glycol), tri(ethylene glycol), tetra(ethylene glycol), penta(ethylene glycol), poly(ethylene glycol) oligomer, di(propylene glycol), tri(propylene glycol), tetra(propylene) glycol), penta (propylene glycol), poly (propylene glycol) oligomers, and at least one selected from the group consisting of derivatives thereof,
The drug delivery film, the endothelial side of the blood vessel contains an anti-inflammatory drug, and the inner diameter direction of the blood vessel contains a platelet inhibitory drug,
Stents for angioplasty.
delete According to claim 1,
The inflatable member has pores formed on its surface,
The pore size is 20 μm to 40 μm,
Stents for angioplasty.
delete According to claim 1,
wherein the inflatable member expands in a radial direction of a blood vessel to be inserted,
Stents for angioplasty.
6. The method of claim 5,
wherein the inflatable member expands from 2 mm to 30 mm in the radial direction,
Stents for angioplasty.
According to claim 1,
The inflatable member is capable of contracting and expanding in the radial direction, the longitudinal direction, and both directions of the blood vessel to be inserted,
Stents for angioplasty.
According to claim 1,
The drug delivery film, comprising a biodegradable material,
Stents for angioplasty.
9. The method of claim 8,
The biodegradable material, which comprises a natural polymer, a synthetic polymer, or both,
Stents for angioplasty.
10. The method of claim 9,
The natural polymer is, hyaluronic acid, chitosan, collagen, alginic acid, albumin, gelatin, silk fibroin, polypeptide (polypeptide) , heparin, alginate, dextran, chondroitin sulfate, dextran sulfate, acacia gum, tragacanthin, pectin , guar gum, sodium carboxymethyl dextran, carboxymethyl cellulose, peptide, oligopeptide, agar, carrageenan, galactomannan Group consisting of (Galactomannans), Xanthan, Beta-Cyclodextrin, Amylose (water-soluble starch), fibrin, pullulan, and tertiary amine starch ether Which comprises at least any one selected from
Stents for angioplasty.
10. The method of claim 9,
The synthetic polymer is polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), poly(D,L-lactic acid-co-glycolic acid) (poly(D,L-lactide-co-glycolide) PLGA), poly(caprolactone), poly(valerolactone), poly(hydroxybutyrate), poly(hydroxyvalerate), poly[(3-hydroxybutyrate)-co-(3-hydroxyvalerate) rate) (PHBV), polydioxanone (PDO), poly[(L-lactide)-co-(caprolactone)], poly(ester urethane) (PEUU), poly[(L-lactide)-co- (D-lactide)], poly [ethylene-co- (vinyl alcohol)] (PVOH), hydroxyapatite (Hydroxyapatite; HA) and β tricalcium phosphate (β phosphate; β) at least one selected from the group consisting of which includes,
Stents for angioplasty.
delete According to claim 1,
The drug delivery film has a thickness of 20 μm to 50 μm,
Stents for angioplasty.
delete According to claim 1,
The anti-inflammatory drugs include cilostazol, everolimus, dicoumarol, zotarolimus, carvedilol, antithrombotic agents, heparin, heparin derivatives, urokinase, and dextrophenylalanine proline arginine chloromethylketone; anti-inflammatory agents, dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine and mesalamine, sirolimus and everolimus, antineoplastic/antiproliferative/antimitotic agents, major taxane domain-binding drugs, paclitaxel and its Analogs, epothilone, discordermolide, docetaxel, paclitaxel protein binding particles, ABRAXANE® (ABRAXANE is a registered trademark of ABRAXIS BIOSCIENCE, LLC), cyclodextrins (or cyclodextrin-like molecules) Paclitaxel synthesized with rapamycin and its analogues, rapamycin (or rapamycin analogue) synthesized with cyclodextrin (or cyclodextrin-like molecule), 17β-estradiol, 17β-estradiol synthesized with cyclodextrin, dicoumarol , dicoumarol synthesized with cyclodextrin, β-rapacon and its analogs, 5-fluorouracil, cisplatin, vinblastine, cladribine, vincristine, epothilone, endostatin, angiostatin, angiopeptin, smooth muscle cells monoclonal antibodies capable of blocking proliferation, and thymidine kinase inhibitors; cytolytic agents; Anesthetics, lidocaine, bupivacaine and ropivacaine; which includes at least one selected from the group consisting of
Stents for angioplasty.
According to claim 1,
The platelet inhibitory drug includes antagonists including P2Y1 receptor antagonists, P2Y12 inhibitors or P2Y12 receptor antagonists,
The P2Y12 antagonist, clopidogrel, ticlopidine, prasugrel, AR-C67085MX, cangrelor, C1330-7, MRS 2395 and 2-methylthioadenosine-5'-monophosphate consisting of Which comprises at least any one selected from the group,
Stents for angioplasty.
According to claim 1,
The stent for angioplasty is for treatment of vascular stenosis or occlusion,
Stents for angioplasty.

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