WO2007119423A1 - Substance to be placed in the living body - Google Patents

Substance to be placed in the living body Download PDF

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Publication number
WO2007119423A1
WO2007119423A1 PCT/JP2007/055518 JP2007055518W WO2007119423A1 WO 2007119423 A1 WO2007119423 A1 WO 2007119423A1 JP 2007055518 W JP2007055518 W JP 2007055518W WO 2007119423 A1 WO2007119423 A1 WO 2007119423A1
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WO
WIPO (PCT)
Prior art keywords
polylactic acid
device according
vivo indwelling
vivo
stent
Prior art date
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PCT/JP2007/055518
Other languages
French (fr)
Japanese (ja)
Inventor
Yotaro Fujita
Keiko Yamashita
Original Assignee
Terumo Kabushiki Kaisha
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Priority to JP2006095211 priority Critical
Priority to JP2006-095211 priority
Application filed by Terumo Kabushiki Kaisha filed Critical Terumo Kabushiki Kaisha
Publication of WO2007119423A1 publication Critical patent/WO2007119423A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds

Abstract

It is intended to provide a substance to be placed in the living body which is made of a biodegradable material, causes neither mechanical stress nor chronic inflammation in the living body after placing in the living body, sustains a required strength and elongation in the living body and scarcely suffers from breakage or cracking due to an external force. The above problem is solved by providing a substance to be placed in the living body which has the main body made of a biodegradable material comprising, as the main component, a polylactic acid complex wherein D-polylactic acid and L-polylactic acid form together a complex of a stereo complex structure at a ratio by mass of from 45:55 to 55:45.

Description

Specification

Vivo indwelling

Technical field

[0001] The present invention relates vivo indwelling.

BACKGROUND

[0002] As vivo indwelling of the present invention, stents, catheters, artificial blood vessel, a stent graft or the like, in the following forces include various ones will be described as a stent as an example.

[0003] First, a description will be given Angioplasty applied to an ischemic heart disease.

Westernization of eating habits in Japan, ischemic heart disease (angina, myocardial infarction) sharply by increasing Caro the number of patients undergoing the Ru, transdermally via a method of reducing the their coronary lesions is enforced through a blood vessel coronary angioplasty (PTCA) has been dramatically spread. In currently, due to technical developments have increased also applicable cases, or not PTCA is began at the time localized (lesions with stenosis in only one site) Kazue lesions (the short lesion length) et al., such as those eccentrically calcifications more distal section, and the application of PTCA to multivessel lesion (lesion with stenosis in two or more parts position) is enlarged, Ru.

[0004] The PTCA, indwelling introducer Sashi one scan (introducer) is subjected to a small incision in the artery of the patient's leg or arm, through the lumen of the introducer sheath, while prior to the guide wire, the guide catheter long hollow tube, called inserted into a blood vessel withdrawn guide wire was placed at the entrance of the coronary shape artery and insert another guidewire and balloon catheter one ether into the lumen of the guide catheter, prior to the guide wire the balloon catheter while advancing to the lesion of the coronary artery of the patient under X-ray contrast, the balloon is positioned in the lesion portion, 30 to 60 seconds physician balloon at a predetermined pressure at that position, once forces more it is a procedure to inflate times.

Thus, the blood vessel lumen lesion blood flow through the expanded vessel lumen is increased. However, vessel wall when or damaged at a rate of occurs 30 to 40% growth of the healing response Der Ru intimal of the vessel wall have been reported restenosis by the catheter.

[0005] Stents are methods for preventing such restenosis Nio, are considered as being used Te, and with some success. The stent here, in order to treat a variety of diseases caused by blood vessel or other lumen stenosis also is properly closes, there to extend that stenosis or occlusion site, ensuring that the lumen a medical device tubular can be placed in. And many of them, Ri medical device der made of a metal material or a polymeric material, for example metal material or and those having a pore More made tubular body polymeric material, a metal material wire or polymeric material various shapes such as those formed into a cylindrical shape with braided fibers has been proposed. The purpose of stenting, have not been able to significantly suppress those aimed at preventing and reducing I spoon of restenosis force such narrowing the only placement of the stent that occurs after performing procedures of PTCA or the like the was the actual situation.

[0006] In recent years, by supporting the biological physiologically active substance of immunosuppressive agents and anti-cancer agent such as a stent, is released locally the biological physiologically active substance over a long period of time in a placement site of the lumen , and how to achieve a reduction of restenosis rates have been proposed! , Ru.

For example, Patent Document 1, metal (such as tantalum) or biostable or bioabsorbable port Rimmer (poly rata tick acid, etc.) force becomes the surface of the stent body, substances for the treatment and biodegradable polymer It describes a coated stent a mixture of.

Further, Patent Document 2, a metal (stainless steel) or the drug layer is provided on the front surface of the stent body is also high molecular force, describes a further stent in which a biodegradable polymer layer on the surface of the drug layer there.

While [0007] is a force, a metallic stent described in Patent Documents 1, 2 will permanently the stent body is placed into the body. Therefore, after the biodegradable polymer of the surface is decomposed by the drug is released in vivo, mechanical to the vessel wall of the stent body - there is a possibility that chronic inflammation caused by local stress occurs. This Patent Document 1,

2 is not limited to Ru metal stent is described in a problem in all stents using a metal material or hardly biodegradable polymers such as tantalum or stainless steel.

In this connection, Non-Patent Document 1, by the polymer layer is placed in semi-permanently in a living body, on which may persist chronically inflammation, restenosis by deterioration of the polymer but not only there is a risk that is induced, it has been reported that there is even a possibility that complicated by thrombosis.

[0008] On the other hand, is described in Patent Document 1, Ru stent comprising a biostable or biodegradable polymer poly rata ticks acid, etc. and, as described in Patent Document 3, in so that bioabsorbable port Rimmer and poly-L-lactic acid strength becomes stent, since the decomposed 'disappears in vivo, mechanical detained long time to live the body to the vessel wall - chronic inflammation giving local stress rarely occurs. Further, the vessel is gradually meandering with age, a layer of the remaining endothelial cells if loss stent can satisfactorily follow the meandering movement. Therefore, invasive such ヽ or small to the living body, to provide a stent.

Patent Document 1: JP-8- 33718 JP

Patent Document 2: JP 9 - 56807 JP

Patent Document 3: WO01 / 067990 pamphlet

Tokuhi literature 1:. Renu Virmani ect, Mechanism of Late In- Stent Restenosis After Impl antation of a Paclitaxel Derivate- Eluting Polymer Stent System in Humans, "Circul ation", 2002, VOL106, p2649- 2651

Disclosure of the Invention

Problems that the Invention is to you'll solve

[0009] However, as described in Patent Document 1, Ru poly rata tick acid such as force or becomes stent, is described in Patent Document 3, so that poly-L-lactic acid strength becomes stent strength and elongation low ingredients lesions be placed in part there may be damaged by some external force. Further, the stent had the potential to fall off lesion force after deployment for radial force is low. Furthermore, the force tightening force against Bruno lanes catheter into the stent (Clean Bing force) is low, the stent had the potential to fall off balloon catheter force during delivery of the lesion.

[0010] Problems of forces such as such strength reduction of the mentioned stents in the above is not limited to the stent

, It is a common problem in-vivo indwelling having biodegradability.

[0011] Accordingly, an object of the present invention, the material strength of the biodegradable becomes, without causing mechanical stress and chronic inflammation vivo after placement in the body, and the required strength 及 beauty elongation in vivo ( has a elongation), flame 1 caused damage and cracking due to an external force, in Rukoto to provide vivo indwelling.

Moreover, even in such a vivo indwelling further comprises a clinker Bing force or radians Rufosu required, hardly like dropout dropout Ya distillate After incubation from the balloon catheter during delivery to the lesion occurs live indwelling product (inserted at the site in order to expand the stenosis or occlusion, etc. generated in the living body, on an extension, stent placement to the portion position to hold that state, the catheter, artificial vessels, is to provide an in-vivo indwelling) such stent grafts.

Means for Solving the Problems

[0012] The present inventors have conducted intensive studies for solving the above problems, and a D-polylactic acid and L-form polylactic acid contained in a specific range, further to form them particular structure vivo indwelling having a body portion formed of a biodegradable material mainly comprising polylactic acid multilayer polymer there are found to solve the above problems.

[0013] Namely, the present invention is the following (1) to (21).

(1) D body polylactic acid and L-form polylactic acid and force 5: 55-55: Stereo complexity Tsu task structure 45 mass ratio of biodegradable mainly composed of polylactic acid complex to form a complex vivo indwelling having a body portion formed of a material.

(2) the biodegradable material-vivo indwelling device according to the above (1) containing a biologically physiologically active substance.

(3) at least a portion of the biological physiologically active substance is a powder, the raw described in (2) above biological physiologically active substance of the powder is dispersed in the biodegradable substance indwelling products.

(4) at least partially engages the polylactic acid complex chemical binding, Ru (2) or vivo indwelling device according to (3) of the biological physiologically active substance.

[0014] (5) on the surface of the body portion, the having a drug release layer containing the biological physiologically active substance (1) to (4), in-vivo indwelling device according to any misalignment.

(6) vivo indwelling device according to the above (5), wherein the drug release layer further contains a biodegradable polymer.

(7) the drug-releasing layer is made of two or more layers, the implanted device according to the the layers comprises a layer comprising a layer and the biodegradable polymer containing the biological physiologically active substance (6) Stuff.

[0015] (8) weight-average molecular weight of the polylactic acid complex is 1, 000-1, 000, 000 and the above (1) to (7), in-vivo indwelling device according to any misalignment.

(9) The polylactic acid complex, said a stretched polylactic acid complex (1) to (8), in-vivo indwelling device according to any misalignment.

(10) The polylactic acid complex has a first melting peak between 65 to 75 ° C in differential scanning calorimetry, polylactic acid composite having a second melting peak between 200 to 250 ° C a body above (1) to (9), in-vivo indwelling device according to any misalignment.

(11) The polylactic acid complex is the breaking strength defined in JIS K7113 is 70MPa or more, elongation at break of 15% or more, the (1 a Young's modulus of the polylactic acid complex is more lOOMPa ) vivo indwelling device according to any one of the - (10).

[0016] (12) The polylactic acid complex is a polylactic acid complex produced by the alternate lamination method described above (1) to (11)?-Vivo indwelling device according to any misalignment.

(13) the alternate lamination method is, in-vivo indwelling device according to (12) is an alternating lamination method performed by forming a micro-order films.

(14) the in-vivo indwelling device according to the thickness of the micro-order film is 1 πι~500 / ζ m (13).

(15) the between the micro orders thin-vivo indwelling device according to the above (13) or (14) containing the biological physiologically active substance.

[0017] (16) the shape of the body portion is tubular, tubular, reticulated, fibrous, nonwoven fabric, woven fabric-like or filamentary a above (1) to (15) in vivo according to any one of indwelling.

(17) wherein the biological bioactive agent, anticancer, immunosuppressants, antibiotics, antirheumatic, antithrombotic agents, HMG CoA reductase inhibitors, ACE inhibitors, calcium antagonists, anti-hyperlipidemic medicine, integrin inhibitor, antiallergic agents, antioxidants, GPIIbllla antagonists, Les Chinoido, flavonoids, carotenoids, lipid improver, DNA synthesis inhibitor, tyrosine kinase inhibitor, antiplatelet agents, anti-inflammatory agents, biological material-vivo indwelling device according to any one of the least is one above the group force consisting interferon, and NO production accelerator material force also selected (2) to (16).

(18) the biodegradable polymer force polylactic acid, Poridarikoru acid, polyhydroxybutyric acid, Po Riringo acid, poly one a- amino acid, collagen, laminin, heparan sulfate, fibronectin, vitronectin, chondroitin sulfate, hyaluronic acid, poly force Purorataton and vivo indwelling placement serial to one of at least is one the selected copolymerized physical group consisting forces of (6) to (17).

(19) in-vivo indwelling device described above SL (18) a copolymer of the biodegradable polymers forces polylactic and Poridarikoru acid.

[0018] (20) above a stent (1) to (19), in-vivo indwelling device according to any misalignment.

(21) after expanding the outer diameter of 2. 1mm to 3. Omm, stent according to the above (20) radial follower Ichisu is 130~500gf per stent length 10mm when the 1mm compression. Effect of the invention

According to [0019] the present invention, it consists of a biodegradable material, a living body without generating mechanical two callus Torres and chronic inflammation after placement in the body, and have a necessary strength and elongation in vivo and, difficulties occur breakage and cracking due to an external force, can provide vivo indwelling.

Moreover, even in such a vivo indwelling further comprises a clinker Bing force or radians Rufosu required, hardly like dropout dropout Ya distillate After incubation from the balloon catheter during delivery to the lesion occurs live indwelling product (inserted at the site in order to expand the stenosis or occlusion, etc. generated in the living body, on an extension, stent placement to the portion position to hold that state, the catheter, artificial vessels, it is possible to provide an in-vivo indwelling) such stent grafts.

BRIEF DESCRIPTION OF THE DRAWINGS

[0020] [FIG. 1] FIG. 1 is a side view showing an embodiment of the stent of the present invention.

FIG. 2 is an enlarged cross-sectional view taken along the A- A line of FIG.

[3] Figure 3 is another enlarged cross-sectional view taken along the A- A line of FIG.

[4] Figure 4 is another enlarged cross-sectional view taken along the A- A line of FIG.

FIG. 5 is an enlarged cross-sectional view taken along B- B line in FIG.

[6] Figure 6 is another enlarged cross-sectional view taken along B- B line in FIG. [7] FIG. 7 is an enlarged photograph showing a pathological image after implantation porcine coronary stents of Example 5 (4 0-fold).

圆 8] FIG. 8 is an enlarged photograph showing a pathological image after implantation porcine intracoronary stent of Comparative Example 9 (4 0-fold).

圆 9] FIG. 9 is an enlarged photograph showing a pathological image after implantation porcine intracoronary stent of Comparative Example 11 (40 times).

DESCRIPTION OF SYMBOLS

1 stent (stent body)

2 linear member

11 elements

12 annular units

13 connecting member

10 stent body

20 polylactic acid complex

30 Biological physiologically active substance powder

Layer containing 32 biological physiologically active substance

40 biodegradable polymer

Layer containing 42 biodegradable polymer

BEST MODE FOR CARRYING OUT THE INVENTION

[0022] One of the present invention hereinafter, Te be described in detail.

The present invention, D body polylactic acid and L-form polylactic acid and 45: 55-55: biodegradability 45 mass ratio Sutereoko simplex complex formation to have polylactic acid complex structure of the main component an in vivo indwelling having a body portion comprising material force.

[0023] Here, vivo indwelling of the present invention may be one having no other parts a force main unit itself and has a main body portion. That is, in-vivo indwelling of the present invention, D body polylactic acid and L-form polylactic acid and force 5: 55-55: polylactic acid complex to form a complex stereo Comp REC scan structure 45 weight ratio of it may be vivo indwelling ing from a biodegradable material mainly composed of. A such a case is also within the scope of the present invention. Therefore, the in-vivo indwelling of the present invention, for example, a stent or consisting of the biodegradable materials include stents coated cloth drug or the like on the surface of the biodegradable material force becomes stent body (main body) . Aspects of other vivo indwelling of the present invention is discussed later.

[0024] First, a description will be given polylactic acid complexes used in the present invention.

Polylactic acid complexes used in the present invention is a complex of D form polylactic acid and L-form polylactic acid. Then, in the complex, these polylactic acid forms a stereocomplex structure.

Here, the stereocomplex structure can interact polymer with each other by van der Waals forces in a relationship of enantiomers such as D form and L-form, a three-dimensional structure composed occurring structural fitting.

[0025] stereocomplex structure can be formed even per cent ヽ the polymer having a stereoregularity such as an Aisotakuchikku and syndiotactic.

As an example of forming a stereocomplex, in addition to polylactic acid, poly - gamma - Benjirugu Rutameto, poly - gamma - methyl Dal data formate, poly - tert butylene oxide, poly - tert Bed chill ethylene sulfates id, poly - alpha - methylbenzyl meth Tari, poly - alpha - methyl - alpha - Echiru - j8 - Puropiorataton, beta -1,1-dichloro propyl - beta - Puropiorataton like are known.

[0026] Further, the polylactic acid complex used in the present invention per cent Te, the quality quantitative ratio between the D-polylactic acid and L-form polylactic acid from 45:55 to 55:45. This mass ratio is 50:! It is preferably a 50 /,.

A such weight ratio, and in-vivo indwelling polylactic acid complex that strength and elongation becomes noticeably Kogu using the same having a stereocomplex structure as described above is hard to break a live body . Moreover, such polylactic acid complexes, since the holding strength even after extended by an external force, the in-vivo indwelling device such as a stent made by using a polylactic acid complex (stenosis occurring in vivo and inserting an occlusion or the like at the site in order to extend, on an extension, stent placement at the site to hold that state, the catheter, artificial blood vessel, in-vivo indwelling device such as stent-graft) is for example the lesion with Roh lane catheter or the like inserted, even after extended extended to placement at the site, with the radial force required to hold the shape.

The mass ratio of the D-polylactic acid and L-form polylactic acid as referred to herein means a weight ratio of each used in the manufacture of the polylactic acid complex.

[0027] The weight average molecular weight of the polylactic acid complex is 1, 000-1, 000, that force S preferably 000, 2, 000-700, more preferably it force S is 000, 5, 000 400, more preferably 000.

Further, the polylactic acid complex is between 65 to 75 ° C in differential scanning calorimetry has a first melting peak (i.e. glass transition temperature), a second melting peak between 200 to 250 ° C (i.e., melting point) is preferably one having a. Here, differential scanning calorimetry N

Under 2 gas flow shall be measured at a heating rate of 5 ° CZmin. It can be preferably used Shimadzu DT- 5 0.

The polylactic acid complex, and if the weight average molecular weight of such a range, when it has such a melting peak strength and elongation of the polylactic acid complex is further increased, comprising using the same vivo indwelling further hardly damaged in vivo. Moreover, in-vivo indwelling device such as a stent made by using such a polylactic acid complex, a higher, will have a radial force.

[0028] Further, the polylactic acid complex, breaking strength as defined in JIS K7113 is at least 70 MPa, elongation at break is 15% or more, Young's modulus of the polylactic acid complex is more lOOMPa It is preferred.

Here, the breaking strength is more preferably not less than 75MPa is more preferred instrument 80MPa or more. Upper limit Do particularly limited, but is preferably not more than 500 MPa,. The elongation at break is more preferably to be 20% or more is more preferred device 30% or more. The upper limit is not particularly limited Do, but preferably not more than 200%.

The Young's modulus is more preferably not less than 500MPa is more preferable device 1, OOOMPa more. Arbitrary preferred that the upper limit is not particularly limited is 50, OOOMPa below.

Vivo indwelling these values ​​obtained by using the polylactic acid complex of such a range is preferable since further hardly damaged in vivo. Further, arbitrary preferred because vivo indwelling stent or the like formed by using such a polylactic acid complexes will have a higher radial force.

Incidentally, "breaking strength" in the following, "elongation at break" as marked "Young's modulus" refers to those measured in all method defined in JIS K7113 (1Z5 using No. 2 test piece of scale) to.

[0029] Further, the polylactic acid complex is preferred that a stretched polylactic acid complex.

This is the polylactic acid complex its glass transition temperature or higher, stretched at a temperature below the melting point Then, with molecules stretched in the stretching direction crystallinity increases the amorphous portion, because the molecule is oriented in the stretching direction, tensile strength and tensile modulus in the stretching direction is because increases.

[0030] Further, the polylactic acid complex is preferably a polylactic acid complex produced by the alternate lamination method. In addition, the alternate lamination method is preferably alternating lamination method performed by forming a micro-order films. Furthermore, said thickness of the micro-order film is 1 m~50 0 μ more preferred tool 50 is that it is m is preferably tool 10 μ m~400 μ m μ m~3 00 μ m There further preferred.

The polylactic acid complex produced by the alternate lamination method, the strength and elongation is especially good good, vivo indwelling made using the polylactic acid complex is further hardly become corrupted in vivo. Moreover, in-vivo indwelling device such as a stent made by using such a polylactic acid complex, a higher, preferably so will have a radial force.

[0031] The herein alternate lamination method, a method of fabricating a thin film by immersing alternately substrate to D-polylactic acid solution and L-form polylactic acid solution. By applying such alternate lamination method, it is possible to form the polylactic acid complex efficiently stereocomplex structure than in Balta (solution).

Specifically, for example, D body polylactic acid was dissolved in Asetonitoriru solution, the L-form polylactic acid is prepared and a solution prepared by dissolving Asetonitoriru, PFA (tetrafluoroethylene modified styrene 'Pafuru O b alkoxide ether co dipping the substrate of the polymerization 榭脂) or the like alternately to each solution. method of repeating the drying.

The polylactic acid complex in the present invention can also Rukoto be produced by casting method or the like which is a conventional method. However, in this case, the probability of stereocomplex structure is formed becomes lower than that of the alternate lamination method. The extent have greens structure is stereocomplex structure in the case of casting, for example, single probability of crystals are formed resulting in summer relatively high, if there has manufactured by alternate lamination method, a stereocomplex structure usually 90% or more it can be formed at a rate of.

[0032] Biodegradable materials Te you, the present invention is mainly composed of such polylactic acid complex.

Here, "main component" means containing more than 60 wt% in mass%. In other words, you to the onset bright, Te biodegradable substance contains the polylactic acid complex of at least 60 wt%. The biodegradable material is preferably member 80 mass which contains the polylactic acid complex to 70 wt%

% And even more preferably contains more.

[0033] Further, the biodegradable material, ヽ preferred to contain biological physiologically active substance. After vivo indwelling of the present invention were placed in the body, in the course of decomposing in the organism, releases the raw Monogaku physiologically active substances, this organism the inflammatory response and restenosis due to the biodegradation This is because it is possible to suppress in academic physiologically active substance.

[0034] The content of definitive said biodegradable material wherein the biological physiologically active substance is not particularly limited, the more that it is contained preferably fixture 10 to 30 mass% containing 1 to 40 wt% preferable.

[0035] In addition, the biological physiologically active substance is preferably pile at least a portion of which is powder. The biological physiologically active substance of the powder is preferably dispersed in the biodegradable material. After vivo indwelling of the present invention is placed in the living body, and decomposed in the organism! / ヽ rather in the course, easily said biological physiologically active substance is released at a constant rate! It is the force.

[0036] Further, it is preferable that at least a part of said biological physiologically active substance is chemically bonded to the polylactic acid complex. After vivo indwelling of the present invention is placed in the living body, in the course of decomposing in vivo of their degradation at the same time biologically physiologically active substance of the polylactic acid complex is released at a more constant rate by easily be, as possible out is possible to suppress the inflammatory response.

[0037] Further, at least part of said biological bioactive agent, it is preferably contained between the micro orders thin film form shape by the alternate lamination method. Moreover, it is further preferable that at least part of the biological physiologically active substance is chemically bonded to the polylactic acid complex. After vivo indwelling of the present invention is placed in the living body, in the course of its going degraded in vivo degradation and at the same time biologically physiologically active substance of the polylactic acid complex, it is released in a more constant rate This is because easy.

[0038] Examples of such biological physiologically active substance, in vivo indwelling of the present invention were placed ill-varying portion of the body, in which effect of preventing the desired effect, for example, restenosis Oh Re if not particularly limited.

For example, anticancer, immunosuppressants, antibiotics, antirheumatic, antithrombotic agents, HMG-CoA reductase inhibitors, ACE inhibitors, calcium antagonists, hypolipidemic agents, integrin inhibition agents, antiallergic agents , antioxidants, GPIIbllla antagonists, retinoids, flavonoids, carotene maytansinoid, lipid improver, DNA synthesis inhibitor, tyrosine kinase inhibitor, antiplatelet agents, anti-inflammatory agents, biological material, interferon, and NO production accelerator substance preferably Ru can be exemplified. Wherein the biological physiologically active substance is at least 1 Tsudea Rukoto more preferably selected the group force consisting! /,.

[0039] Here, the anti-cancer agent, such as vincristine, vinblastine, vindesine, Irinote cans, pirarubicin, paclitaxel, docetaxel, methotrexate or the like. As the immunosuppressant, e.g., sirolimus, everolimus, biolimus, tacrolimus, Azachiopurin, cyclosporine, cyclophosphamide off amides, Mikofuenoru acid Mofuechi Le, Dasuperimusu, mizoribine and the like are preferable.

As the antibiotics, for example, mitomycin, adriamycin, doxorubicin, Akuchinomaishin, daunorubicin, idarubicin, pirarubicin, aclarubicin, E Pi Rubishin, Bae puromycin, zinostatin Lamar like.

[0040] Further, as the antirheumatic agent, for example, methotrexate, sodium thiomalate, Bae two Shiramin mouth Benzaritto like.

As the antithrombotic agents, for example, heparin, aspirin, antithrombin preparation, Chikuropi Jin, hirudin and the like are preferable to.

Further, HMG as the CoA reductase inhibitors, e.g., cerivastatin, Seribasuta Chin sodium, atorvastatin, Nisupasutachin, Itapasutachin, full pasta Chin, full pasta Chin sodium, sympathizers statins, mouth Pasutachin, pravastatin and the like is not preferable.

[0041] Further, as the ACE inhibitors, e.g., quinapril, Bae Lind prills Elp Min, Portland Rapuriru, cilazapril, temocapril, delapril, Enarapuriru maleic acid, Rishinopuri Le, captopril, and the like are preferable.

As the calcium antagonist, for example, Hifuejipin, Two Rubajipin, Jiruchiaze beam, base - adipic, two Sorujipin like.

As the anti-hyperlipidemia agents, for example, probucol is preferable.

As the antiallergic agents, for example, tigers - Last is preferred.

[0042] As the antioxidant, for example, catechins, Antoshianin, Puroantoshia - Gin

, Lycopene, j8 - carotene and the like are preferable. Among the catechins, E peak epigallocatechin gallate bets are particularly preferred.

As the retinoid, for example, all-trans retinoic acid. As the tyrosine kinase inhibitors, for example, genistein, Chinorefosuchin, § one Busutachin etc. preferable.

As the antiinflammatory agents, for example, dexamethasone, steroids prednisolone or the like.

[0043] Further, as the biological material, for example, EGF (epidermal growth factor), VE

jr (vascular endothelial growth factor), ir LjF (hepatocyte growth fac tor), PDGF (platelet derived growth factor), BFGF (basic nbrolast gro wth factor) and the like are preferable.

[0044] Component The said biodegradable material as is mainly composed of polylactic acid complexes, but preferably contains the biological physiologically active substance, in addition to these, you safe, biodegradable in vivo (hereinafter, also referred to as "the rest component".) may contain.

Such balance components, for example, the polylactic acid (D body single polylactic acid such no stereo complexity box structure as polylactic acid complex, a single L-form polylactic acid, the D-form and L-form (co) polymer, etc.), Poridarikoru acid, polyhydroxybutyric acid, polymalic acid, poly α- amino acid, collagen, laminin, heparan sulfate, fibronectin, vitronectin, chondroitin sulfate, hyaluronic acid, poly force Purorataton and copolymerization of these strength is also the group or al least is one mixture and I 匕合 was selected (copolymers) can be mentioned. Preferably used a copolymer of polylactic acid and Z or polylactic acid and Poridarikoru acid Among these leaves in the Rukoto.

[0045] The method for adjusting such a biodegradable material is particularly limited it! ヽ.

For example, if der lever this biodegradable material contains a biologically physiologically active substance powder, and the polylactic acid complex, a biological physiologically active substance of the powder, and the remainder component , a known method, for example, mixing methods and using the mixer, or a method of kneading by melting the components, the components can be prepared by mixing by applying a method in which kneading into a paste.

Further, for example, the biodegradable material containing a biological physiologically active substance, if if at least part of the said biology physiologically active substance is bound the polylactic acid complex chemical , for example, to create a polylactic acid complex of D form and L-form polylactic acid mosquito ゝ et the stereocomplex structure having a hydroxyl group or a carboxyl group in advance end, the biological the government functional group of the terminal as a micro initiator one how to Esuterui spoon or ami de a biologically active substances. In other features, the biological lactide were grown as a starting point a specific functional group of the physiologically active substance can be prepared by applying the method of forming the polylactic acid complex having a stereocomplex structure.

[0046] Further, for example, in the case where at least part of the biological physiologically active substance is contained between the micro orders thin film formed by the alternate lamination method, For example, D body polylactic acid It was prepared a solution dissolved in Asetonitoriru, a solution prepared by dissolving the L-form polylactic acid Asetonitoriru, and a solution prepared by dissolving the biological physiologically active substance, PFA (four French chemical styrene-Pafuruoro Arukokibi - Hitatsubushi the ether copolymer 榭脂) substrate such as sequentially to each solution can be prepared by a method of repeating the drying.

[0047] Further, for example, at least a portion of said biological bioactive agent, said being contained between the micro orders thin film formed by alternately laminating method, further, at least for the biological physiologically active substance in the case where some force has the polylactic acid chemically bonded to the composite of this micro-order films, for example, I and the and D-polylactic acid biological physiologically active substance in an ester bond or an amide bond 匕学preparation and those coupled to form dissolved in Asetonitoriru solution, a solution prepared by dissolving those is chemically bonded to Asetonitoriru and said the L-form polylactic biological physiologically active substance in an ester bond or an amide binding and, PFA - be prepared by (quartet France modified styrene per full O b Arco millet ether copolymer 榭脂.) was dipped a substrate such as a alternately to each solution method of repeating an operation of drying it can.

[0048] vivo indwelling of the present invention has a body portion made of such biodegradable materials.

The main body is a main part of the indwelling of the present invention described below. For example, in-vivo indwelling of the present invention, when a stent coated with a drug or the like on the front surface of the biodegradable material force becomes stent body, wherein the U stent body in the present invention, power sale to the body portion Equivalent to.

The shape of the body portion, the tubular, tubular, reticulated, fibrous, it is preferred nonwoven, a woven form or full Iramento shape. Reason is that it you to easily indwelled in a lumen in vivo such as a blood vessel.

[0049] Further, the manufacturing method of the main body is not particularly limited, can be produced, for example, by a known method.

For example, if a body of the body force ^ tents, after the biodegradable material and fiber 維状, a method of braiding a cylindrical, molding the tubular body from said biodegradable material, which method of providing pores are mentioned.

[0050] vivo indwelling of the present invention has a main body portion made of such biodegradable materials, further, the surface of the body portion of its, the drug release layer containing the biological physiologically active substance and this has is preferable.

Because, after vivo indwelling of the present invention is placed in the living body, in the course of this drug releasing layer in the organism is gradually decomposed, since biological physiologically active substance is released, restenosis the inflammatory response associated with and biodegradability which can be inhibited by this biological physiologically active substance.

Here, the biological physiologically active substance, the same type as those which may contain said biodegradable material, can be used as the properties and the like. [0051] In addition, the drug release layer preferably further contains a biodegradable polymer. Because, after vivo indwelling of the present invention is placed in the living body, in the course of in the organism the drug release layer is gradually decomposed, moderately the rate at which the biologically physiologically active substance is released This is because easier to adjust.

Here, the biodegradable polymer is the above polylactic acid was complex even Yogu other even polylactic acid Yogumata, the remainder component may contain the biodegradable material Choi.

In other words, this Biodegradable polymers include polylactic acid (including the polylactic acid complex, single of the other polylactic acid (D body polylactic acid, a single L-form polylactic acid, D-form and L-form and the (co ) polymer and the like) may be used), Poridarikoru acid, polyhydroxybutyric acid, polymalic acid, poly - a- Amino acids, collagen, laminin, heparan sulfate, fibronectin, vitronectin, chondroitin sulfate, hyaluronic acid, poly force Purorataton and their Ru can be exemplified preferably a copolymer of. It is preferred that these forces also group force is also a biodegradable polymer is at least one selected. Furthermore, it is more preferably a copolymer of the biodegradable polymers forces polylactic acid and Z or polylactic acid and polyglycolic Lumpur acid. Reason is the mosquito ゝ al capable of setting a desired strength and degradation rate.

[0052] In addition, the drug release layer is within a range not to impair the performance of the in-vivo indwelling of the present invention, as a pre-Symbol biodegradable polymer and the balance other than the biological physiologically active substance, contains other Ingredient and it may be (hereinafter also referred to as "other component".) o Examples of such other ingredients, for example, polyethylene succinate, polybutylene succinate, polybutylene succinate preparative 'adipate, polylactic acid over trimethylene carbonate copolymers, polyglycolic acid over preparative Li methylene carbonate copolymer, and the like.

[0053] Such agents wherein the release layer biological physiological content of active substance particularly limited Sarezu, be adjusted by considering the type of the biological physiologically active substance used and the state of the lesion but it is, more preferably to be 1 to 99 wt% is preferred tool 30 to 70 wt%.

Moreover, the drug release layer, in the case of further containing the biodegradable polymer, the ratio of the content of said biodegradable polymer and the biologically physiologically active substance, 99: 1 to 1: 99 in it is preferred tool 70: 30-30:! it is more preferably 70 /,.

Further, it is more preferable that the drug content of the other ingredients in the release layer is less preferred tool 30 wt% or less 40% by mass. Further, 0 wt%, i.e. may not contain.

[0054] In addition, the drug-releasing layer is made of two or more layers, it is preferable that the layers contain a layer comprising a layer and the biodegradable polymer containing the biological physiologically active substance. That is, the drug release layer is preferably comprised of two layers and other layers strength of the layer containing the layer and the biodegradable polymer one containing the biological physiologically active substance.

Moreover, the drug release layer preferably also two layers strength of the layer containing the layer and the biodegradable polymer containing the biological physiologically active substance.

Further, in the drug-releasing layer, a layer containing the biological physiologically active substance is present in the body unit side, it is preferable that the layer containing the biodegradable polymer to its upper surface are present. If the drug release layer is composed of two or more layers, after vivo indwelling of the present invention is placed in the living body, in the course of its the drug release layer in vivo is gradually decomposed, biological bioactive substance ease be released at a constant speed! / ヽ.

[0055] layer containing the biological physiologically active substance herein is a said biological physiologically active substance, a layer consisting of the biodegradable polymer and Z or the other component. Wherein said biological physiologically active substance, the weight ratio of the biodegradable polymer and Z or the other component is 10: 90 to 90: 10 it is preferably a /,.

Further, the layer containing said biodegradable polymer is a biodegradable polymer and the other is also component force layer. Here it is further preferable that the other content of the component is less than 30 mass% is preferably fixture 20 wt% or less.

[0056] The drug release layer, if having a layer other than the layer containing the layer and the biodegradable-mer containing the biological physiologically active substance, those layers are also layers der connexion comprising the other component good.

Incidentally, the order of lamination of these layers are not particularly limited.

These layers may each plurality exist.

[0057] The thickness of such a drug-releasing layer is not particularly limited, the amount of said biological physiologically active substance to be held on the surface of the body portion, the type of the type and in-vivo indwelling, etc., various it can be appropriately determined taking into account the conditions. For example, the stent-vivo indwelling of the present invention, artificial blood vessels, such as stent grafts, in the case the operation of delivering from outside the living body to the lesion in a living body is a living body indwelling necessary especially, the Ri reachability (deliverability) good der, and the biological physiologically active substance may be a thickness that can be contained the desired quantity. It is further preferred that the thickness is 1 to 100 / zeta is preferably tool 1~50 / ζ πι be Paiiota is more preferably tool 1~20 / ζ πι.

[0058] Furthermore, when the drug-releasing layer is composed of at least two layers is preferably in the range such as thickness force of the sum of all the layers. The thickness of the layer containing the biological physiologically active substance 1: that it is LOO m that is preferably tool 1~15 / ζ πι is more preferred instrument 3 to 7-m A further preferred. The thickness of the layer containing the biodegradable polymer is 1 to 75 m is that it is preferable instrument 1 to 25 / zeta and more preferably tool 1 is πι: LO / zm der Rukoto is A further preferred.

[0059] Methods of forming such drug-releasing layer on the surface of the body portion is not particularly limited, can be applied a known method if example embodiment.

For example, a ratio described above and the biological physiologically active substance and the biodegradable polymer, acetone, ethanol, black hole Holm, in a solvent such as tetrahydrofuran, a solution concentration of 0.001 to 20% by weight, preferably make a solution dissolved at a 01 to 10% by weight 0.1. Next, spray the solution, or applied by conventional method using a dispenser or the like on the surface of the body portion, or the solution said body portion was immersed in, thereafter the solvent is volatilized.

This method, solvents (such as acetone, ethanol, black hole Holm, tetrahydrofuran) to easily dissolve and the biodegradable polymer and the biologically physiologically active substance forces used surface of the main body portion can be readily wets If it is, it can be preferably applied.

[0060] Further, for example, Choi and coated cloth by melting the biological physiologically active substance on the surface of the body portion.

[0061] it is possible to form the drug-releasing layer in this way on the surface of the body portion. A case containing pre SL other components is the same. The thickness of each layer can be appropriately adjusted by the coating weight by the density Yasu play such a solution.

[0062] vivo indwelling Thus, the present invention is to have the said body portion is also the biodegradable material strength, preferably vivo indwelling having the drug releasing layer on the surface of the body portion.

[0063] Types of the in-vivo indwelling device such present invention is not particularly limited. May be a-vivo indwelling required Yogu strength and elongation disappeared after existing for a period of time in vivo. For example, stents, covered stents, coils, micro-coils, artificial blood vessels, artificial bones, shea one shield, a wire knit, clip, a plug.

Further, for example, those having a hollow organ and Z or tubing (ureter, bile duct, urethra, uterus, esophagus, bronchus) a lumen support functions within.

Further, for example, a hollow space connected, also the closing member as a closed system for the tubing, for example, a fixed or supporting device for temporary fixing of tissue implants or tissue transplant.

Further, for example, orthopedic implants (bolts, nails, wires, plates, joints, etc.) Ru der.

Further, for example, a stent graft, vascular anastomosis devices, vascular hemostatic devices, vascular Kobuchi care devices, and the like implantable medical device using a stent holding member.

These size and the like may be suitably be selected as depending on the application site.

[0064] Among these, inserted into the site for dilating strictures or occlusion occurs in a living body or the like, on an extension, such as a stent to be placed at the site in order to maintain their state vivo indwelling is preferably (stents, catheters, artificial blood vessel, the stent graft and the like). Furthermore, it is preferable that the stent among these. Is because the delivery and placement of the lesion can be performed easily.

[0065] In addition, the stent, balloon expandable type, may be either self-expanding type, may be suitably be selected as depending on the magnitude of the application site. For example, when used in the coronary arteries of the heart, the outer diameter before expansion 1. 0 to 3. Omm, length 5~50mm is not preferable. Also, the wall thickness of the stent has a radial force required to indwelled in a lesion is not particularly limited as long as it does not inhibit the blood flow in the range of 1 to 1000 mu m as the thickness of the stent body power S preferably, preferably from the range force S of 10 to 500 mu m, more preferably in the range of 40 to 200 mu m.

[0066] Further, the shape of the stent, for example, those illustrated in FIG.

In Figure 1, stent body 1, both ends are opened, a cylindrical body extending between the both ends in the longitudinal Direction. Side of the cylindrical body has a notch large number of communicating with its outer surface and an inner surface, by which the cut-out portion is deformed, has become a scaling available-structure in the radial direction of the cylindrical body, is detained in the target region, it maintains its shape.

In the embodiment shown in FIG. 1, the stent body 1 is made of a linear member 2, the substantially rhombic elements 11 having notches therein a basic unit. Elements 11 of a plurality of substantially rhombus, the shape of the substantially rhombic has an annular unit 12 by combining disposed in succession in the minor axis direction. Annular unit 12 is connected via the annular unit and the line-shaped connecting member 13 adjacent to each other. Thus it is arranged continuous to the axial direction by a plurality of annular units 12 guard portion bound state. Stent body (stent) 1 is by this arrangement, both ends are open mouth, said has a cylindrical body between the both ends extending in the longitudinal direction. Stent body (stent) 1 has a notch portion of the substantially rhombic, by the notch portion is deformed, and is collapsible structure in a radial direction of the cylindrical body.

[0067] When the stent main body 1 is composed of linear members 2, the length in the width direction of the linear member 2 constituting the stent body 1 so as to have a plurality of cutout portions are preferably 0. 01- 0.5 is 5 mm, more preferably 0.5 05-0. 2 mm.

[0068] Incidentally, only the stent 1 one embodiment shown above, consists of a linear member 2, both ends are opened, between the both ends and a cylindrical body extending in the longitudinal direction , on its side, it has a number of notch that communicates the outer surface and an inner surface, the notch Te cowpea that is deformed, broadly includes collapsible structure in a radial direction of the cylindrical body.

[0069] Further, when vivo indwelling of the present invention is a stent, after expanding the outer diameter of 2. 1mm to 3. Omm, radial force force the stent length 10mm per upon 1mm compression, 1 30~500Gf it is preferable that a stent is! /,.

Such stents with radial force, when the Ru can be reliably indwelled in a lesion, favored the exhibit starts selling effect.

Normally, the radial force is roughly directly proportional to the stent length.

[0070] Thus, the present invention has a main body portion comprising said biodegradable material strength, preferably vivo indwelling having the drug releasing layer on the surface of the front Stories body portion.

Therefore, when showing the cross section of the in-vivo indwelling of the present invention, good in Figures 2-6 shown below for example Uninaru.

[0071] vivo indwelling of the present invention is an example in a stent illustrated in Figure 1, the A- for A line cross-sectional view and a B- B line cross-sectional view, illustrating several embodiments.

Figure 2-4 is an enlarged cross-sectional view, cut along the A- A line of FIG. Figure 2 is a state that the stent 1 shown in FIG. 1, an in vivo indwelling which also biodegradable material force consisting of polylactic acid complex 20 comprising biologically physiologically active substance 30 of the powder in the dispersed state it is a cross-sectional view of a case of like.

Further, FIG. 3, the stent 1 shown in FIG. 1 has a stent body 10 is also the biodegradable material force, on the surface, comprises a layer 32 with a biodegradable polymer comprising biologically physiologically active substance Ru sectional view der in the case of embodiments in which vivo indwelling having drug release layer comprising a layer 42.

Further, FIG. 4, the stent 1 shown in FIG. 1 has a stent body 10 is also the biodegradable material force, on the surface, biodegradable polymer biologically physiologically active substance 30 of the powder are dispersed is a cross-sectional view of embodiment where vivo indwelling having drug release layer consisting of 40.

[0072] Next, FIG. 5, 6 is an enlarged cross-sectional view, cut along the B- B line in FIG.

Figure 5 shows the case of a similar embodiment to that shown in FIG.

Also, FIG. 6 shows a case of a similar embodiment to that shown in FIG. Example

[0073] Hereinafter is a description of the present invention embodiment, the present invention is not be to be limited thereto.

<Example 1>

L- polylactic acid (API Corporation, 100L0105) pellets (hereinafter, also referred to as "PLLA"), a synthesized D- polylactic acid by fermentation (hereinafter, also referred to as "PLDA") and the, previously adjusted 50 ° C the § cell Tonitoriru solution each was dissolved separately in, then 1 ^ 1 ^ \ :? 1 ^ eight = 50: so that the 50 proportion of was them mixed. Here, the total concentration of PLLA and PLDA was set to be 20 mg / m 1.

Next, place the solution PFA petri dish, to produce a cast film having a thickness of 0.99 m. Thereafter, the film was uniaxially stretched in a warm bath of 80 ° C. Draw ratio at this time was 4 times. The thickness of the resulting film by stretching was 100 m. The tensile subjected rupture strength test based on this was stretched film JIS K7113 (tensile test method of plastic), was determined breaking elongation. Here the film were used as had unplug out the No. 2 form test pieces of 1/5 scale.

The results are shown in Table 1.

[0074] <Example 2, 3>

In Example 2, it was 50:50 in Example 1! ^ 1 ^ \ :?] the ratio of ^ ^ and 45:55, the other of its was tested that were the same as all.

In Example 3, it was 50:50 in Example 1! ^ 1 ^ \ :?] the ratio of ^ ^ and 55:45, the other of its was tested that were the same as all.

The results are shown in Table 1.

[0075] [Table 1] Table 1 Example Tensile test value

[0076] <Comparative Example 1>

Copolymers of 0 polylactic acid 50 wt% of polylactic acid and 50% by weight (API Corporation 100 D065) pellets (hereinafter, "DL-PLA" also referred to), and acetone in a previously adjusted 23 ° C It was dissolved. Here, and as a copolymer concentration in the acetone to 5%. Next, place the solution PFA petri dish, to produce a cast film having a thickness of 0.99 m. Thereafter, the film was uniaxially stretched in a warm bath of 80 ° C. Draw ratio at this time was 4 times. The thickness of the resulting film by stretching was 100 m. The tensile subjected rupture strength test based on this was stretched film JIS K7113 (tensile test method of plastic), was determined breaking elongation. Here the film were used as had unplug out the No. 2 form test pieces of 1/5 scale.

The results are shown in Table 2.

[0077] <Comparative Example 2-7>

In Comparative Example 2-7, Example 1 to your /, Te 50: 50 and the PLLA: the ratio of PLDA 70: 30 (ratio Comparative Examples 2), 30: 70 (Comparative Example 3), 60: 40 ( Comparative example 4), 40: 60 (Comparative example 5), 100: 0 (Comparative example 6), 0: 100 and (Comparative example 7), others were subjected to tests similar all.

The results are shown in Table 2.

[0078] [Table 2] Table 2 Comparative Example Tensile test value

[0079] <Example 4>

Prepared in the same manner as in Example 1, a cast film was stretched cut to the size of the rectangle 50 mm X 7 mm, with rounded this diameter of about 2 mm, a cylindrical length 50 mm. Then, insert the Re this diameter 2. 4 mm, in polytetramethylene full O b ethylene made shrink tubing length 60 mm. Next, in a cylinder made of the cast film, further, the diameter 1. 5 m m, PTFE tube length 70mm (chukoh Co., AWG- 17) was inserted.

Thus tubes of three-layer structure was manufactured (inner force also PTFE tube, cast Fi Rumuka also cylindrical, shrink tube) and heated for 1 hour in an oven heated in advance 200 ° C, diameter 2. lmm, to obtain a pipe wall thickness 100 m (Note that this Caro heat is Aniru process in Pas Eve has been subjected).

Then, machining the pipe excimer laser (Shigeru Sumitomo Industries Ltd., SPL400H) by, a same shape as FIG. 1, the outer diameter 2. lmm, length 10 mm, the thickness (wall thickness) stent bets is 100 m did.

[0080] Next, rapamycin is an anticancer agent (hereinafter, also referred to as "RM") and, biodegradable polymers der Ru polylactic over polyglycolic acid (composition ratio (mass ratio): 85 - 15) copolymer ( hereinafter also "PLGA", U) and, the mass ratio of 1: tetrahydrofuran was dissolved to be 1 (hereinafter, "THF" and ¾, U) prepared solution (total concentration 1 wt%), of the It was sprayed by processed sPRAY to the surface of the stent (produced by micro-spray gun 11, NORDSON, Inc.) to. Then, after drying the THF as a solvent, to about 600 mu g of RM and PLGA and mixtures 10 mu m of the coating to the surface of the stent to a thickness in a scanning electron microscope that Ru of (SEM) and it confirmed Te, the stent outer diameter 3. Omm until the balloon catheter (Terumone earth manufactured, Arashi) expanded in, was then measured pushing force when pushed the stent to lmm inner (radial force).

As a result, the radial force was 198kgf.

[0081] <Example 5>

The stent of Example 4 percutaneously 1 month to month placed in the pig coronary arteries, pathological evaluation was rows summer.

As shown in FIG. 7, not observed less pronounced narrowing even after one month, 0 / oArea Stenosis (% AS ) for obtaining from the following equation was 5% 35..

[0082] <% Area Stenosis (% AS) calculation method>

% AS = (neointimal area) Z (internal elastic lamina area) X 100 (%)

[0083] <Comparative Example 8>

Using a cast film produced by the same method as Comparative Example 1, was prepared the same stent as in Example 4, it was subjected to the same measurement. As a result, the radial force was 103kgf.

[0084] <Comparative Example 9>

The stent of Comparative Example 8 percutaneously 1 month to month placed in the pig coronary arteries, pathological evaluation was rows summer.

As shown in FIG. 8, one month elapses when the value Gatineau yellowtail modeling seems to be due to a weak radial force is observed, 0/0 Area Stenosis (% AS) was also 97.3%.

[0085] <Comparative Example 10>

Using a cast film produced by the same method as Comparative Example 4, was prepared the same stent as in Example 4, it was subjected to the same measurement.

As a result, the radial force was 116kgf.

[0086] <Comparative Example 11>

The stent of Comparative Example 10 was 1 month indwelling percutaneously in pig coronary arteries, pathological evaluation was rows summer.

As shown in FIG. 9, one month elapses when the value Gatineau yellowtail modeling seems to be due to a weak radial force is observed, 0/0 Area Stenosis (% AS) also 95. was 1%.

Claims

The scope of the claims
[I] D body polylactic acid and L-form polylactic acid and force 5: 55-55: polylactic acid complex to form a complex of the stereocomplex structure from a biodegradable material mainly composed of 45 mass ratio of vivo indwelling having a body portion made.
[2] The biodegradable material-vivo indwelling device according to claim 1 containing biological physiologically active substance.
[3] wherein at least a portion of the biological physiologically active substance is a powder, in vivo according to claim 2 biological physiologically active substance of the powder is dispersed in the biodegradable substance indwelling.
[4] The biological bioactive least partially vivo indwelling device according to claim 2 or 3 are attached the polylactic acid complex and a chemical substance.
[5] on the surface of the body portion-vivo indwelling device according to claim 1 that have a drug release layer containing the biological physiologically active substance.
[6] In vivo cut ornament according to claim 5 wherein the drug release layer containing a further biodegradable polymer.
[7] The drug-releasing layer is made of two or more layers, in-vivo indwelling device according to claim 6 the layers comprises a layer comprising a layer and the biodegradable polymer containing the biological physiologically active substance .
[8] The weight-average molecular weight of the polylactic acid complex is 1, 000-1, 000, 000 is claim 1
To 7 in-vivo indwelling device according to any misalignment.
[9] The polylactic acid complex-vivo indwelling device according to any one of claims 1 to 8 is stretched polylactic acid complex.
[10] The polylactic acid complex has a first melting peak between 65 to 75 ° C in differential scanning calorimetry, polylactic acid composite having a second melting peak between 200 to 250 ° C vivo indwelling device according to any one of claims 1 to 9 is the body.
[II] The polylactic acid complex, breaking strength as defined in JIS K7113 is at least 70 MPa, elongation at break is 15% or more, claim a Young's modulus of Ru polylactic acid complex der is more lOOMPa vivo indwelling device according to any one of 1 to 10.
[12] The polylactic acid complex is a polylactic acid complex produced by the alternate lamination method according to claim 1: vivo indwelling device according to any one of L 1.
[13] the alternate lamination method is, in-vivo indwelling device according to claim 12 is an alternating lamination method performed by forming a micro-order films.
[14] Raw indwelling of claim 13 thickness of the micro-order film is 1 πι~500 / ζ m.
[15] during the micro-order thin-vivo indwelling device according to claim 13 or 14 containing the biological physiologically active substance.
[16] The shape of the body portion is tubular, tubular, reticulated, fibrous, nonwoven fabric, woven fabric-like or vivo indwelling device according to any one of claims 1 to 15 is filamentary.
[17] The biological bioactive agent, anticancer, immunosuppressants, antibiotics, antirheumatic, antithrombotic agents, HMG CoA reductase inhibitors, ACE inhibitors, calcium antagonists, anti-hyperlipidemia medicine, integrin inhibitor, antiallergic agents, antioxidants, GPIIbllla antagonists, retinyl maytansinoid, flavonoids, carotenoids, lipid improver, DNA synthesis inhibitor, tyrosine kinase inhibitor, antiplatelet agents, anti-inflammatory agents, biological material -vivo indwelling device according to any one of claims 2 to 16 is at least one selected the group forces also interferon and NO Sansei促 proceeds material force.
[18] The biodegradable polymer force polylactic acid, Poridarikoru acid, polyhydroxybutyric acid, polyphosphoric Gore acid, poly α amino acid, collagen, laminin, heparan sulfate, fibronectin, Vito Ronekuchin, chondroitin sulfate, hyaluronic acid, poly force Purorataton and raw indwelling product according to any one of claims 6 to 17 in which the group forces also these copolymerization stamina is also selected at least one.
[19] The biodegradable polymer according to claim 1, a copolymer of polylactic acid and Poridarikoru acid
Vivo indwelling device according to 8.
[20] vivo indwelling device according to any one of claims 1 to 19 is a stent.
[21] After extended outer diameter from 2. 1mm to 3. Omm, stent of claim 20 radial force is 130~500gf per stent length 10mm when the 1mm compression.
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