KR101217615B1 - A photo-functional self-cleaned stent and method for preparing the same - Google Patents

Abstract

The present invention relates to a photofunctional self-cleaning stent and a method of manufacturing the same. The present invention not only provides a photoactive stent capable of simultaneously performing a stent operation and photodynamic therapy, but also fully expresses the photoactivity of a photosensitive molecule using light in a visible or infrared region with high light transmittance in vivo. It is possible to efficiently perform photodynamic therapy.

Description

A photo-functional self-cleaned stent and method for preparing the same}

The present invention relates to a photofunctional self-cleaning stent and a method of manufacturing the same.

A stent is a general term for a medical device that is installed for the purpose of opening a narrowed or blocked lumen when blood vessels or non-vascular lumens in the human body are closed or narrowed due to cancer, tumor, or thrombus. Stents can be broadly divided into plastic stents (tube stents) and metal stents, depending on the material. The tube stent is mainly made of materials such as polyurethane, polyethylene, and polytetrafluoroethylene (PTFE). Tube stents have the advantage of easy operation, low cost and easy removal compared to metal stents, but there is a disadvantage that the restenosis of the lumen occurs earlier than the metal stent due to the sludge after the procedure. On the other hand, the metal stent is used a lot of stainless steel, cobalt alloy and nickel alloy, and the biggest advantage is that the long period (patency period). However, metal stents have the disadvantage of being difficult, expensive, and difficult to remove after the procedure.

Recently, photodynamic therapy (PDT) using photosensitive molecules has been performed. The photodynamic therapy (PDT) is a method of treating diseased cells or tissues by administering photosensitive molecules to lesions and irradiating light to generate reactive oxygen species (ROS). That is, when a photosensitive molecule absorbs light of an appropriate wavelength, the photosensitive molecule transitions to an excited singlet electron state and fluoresces as it becomes a ground state. In the case of the photosensitive molecules not subjected to the above process, the triplet may be in a triplet state and energy may be transferred to the oxygen molecules to generate singlet electron state oxygen ¹ O ₂ . In addition, the light-sensitive photosensitive molecules transfer energy to surrounding substrate molecules to generate reactive free radicals or radical ions, which react with oxygen molecules to form superoxide anion radicals (ex. O ₂ ⁻ ) and hydroxide radicals. (ex. OH ⁻ ) can be generated. The ¹ O ₂ , O ₂ ^- and OH ^- are reactive oxygen species, which are toxic and can be treated by destroying diseased cells and tissues.

Recently, one study demonstrated photodynamic therapy (PDT) with atherosclerosis for atherosclerotic plaque (Cather Cardio. Int. 2002. 57, 387-394).

Accordingly, US Patent Publication No. 2008/0262607 describes a structure in which a thin Ti layer is coated on an outer surface of a stent and a TiO ₂ layer is coated thereon in order to simultaneously perform the photodynamic therapy treatment and the stent procedure. The Ti layer is an intermediate layer serving as an adhesive, and the TiO ₂ layer is a surface layer capable of absorbing light in the ultraviolet region and having photoactivity. However, light in the ultraviolet region (wavelength of about 380 nm) is difficult to be transmitted into the body, and even a small amount of light may be transmitted even though it is transmitted. That is, US Patent Publication No. 2008/0262607 uses TiO ₂ as a photosensitive molecule, and the TiO ₂ The light absorbs light in the ultraviolet region and has photoactivity, but the light in the ultraviolet region has a low light transmittance in vivo, which makes it difficult to substantially use the photodynamic therapy.

In order to simultaneously perform photodynamic therapy and stent treatment, a stent in which photosensitive molecules are attached to a surface and fixed is required. In particular, a stent that absorbs light in a visible or near infrared region having high light transmittance in a living body There is a need for the development of a stent attached with a photosensitive molecule capable of expressing photoactivity.

An object of the present invention is to provide a photofunctional self-cleaning stent and a method of manufacturing the same.

The present invention as a means for solving the above problems, a stent; And it provides a photoactive stent comprising a photosensitive molecule attached to the outer surface of the stent.

The present invention as another means for solving the above problems, a stent; A metal oxide layer formed on an outer surface of the stent; And it provides a photoactive stent comprising a photosensitive molecule attached to the surface of the metal oxide layer.

As another means for solving the above problems, the present invention provides a method for producing a photoactive stent according to the invention, comprising the step of attaching a photosensitive molecule to the outer surface of the stent.

The present invention is another means for solving the above problems, the first step of forming a metal oxide layer on the outer surface of the stent; And a second step of attaching photosensitive molecules to the surface of the metal oxide layer.

The photofunctional self-cleaning stent of the present invention is a photodynamic therapy treatment by attaching photosensitive molecules to the outer surface of the stent, or forming a metal oxide layer on the outer surface of the stent, and then attaching the photosensitive molecules to the surface of the metal oxide layer And stent procedures can be performed simultaneously. In addition, the optical functional self-cleaning stent of the present invention includes photosensitive molecules capable of absorbing light in the visible or infrared region, and thus can use optical energy having high light transmittance in vivo. Efficient photodynamic therapy can be performed.

1 is a cross-sectional view showing the surface structure of a photoactive stent according to an aspect of the present invention.
2 is a cross-sectional view showing the surface structure of a photoactive stent according to another aspect of the present invention.
3 is a cross-sectional view showing the surface structure of a photoactive stent according to another aspect of the present invention.
4 is a view schematically illustrating a manufacturing process of a photoactive stent according to an aspect of the present invention.
5 is a view schematically illustrating a manufacturing process of a photoactive stent according to another aspect of the present invention.
FIG. 6 is an electron micrograph showing the photoactivity of hematopopirine (photosensitive molecules) against rat aortic smooth muscle cells (RAOSMC).
FIG. 7 is an electron micrograph showing the photoactivity of the photoactive stent according to Example 1 against rat aortic smooth muscle cells (RAOSMC).
FIG. 8 is an electron micrograph showing the photoactivity of the photoactive stent according to Example 2 with respect to rat aortic smooth muscle cells (RAOSMC).
9 is a graph of absorbance change of DPBF showing the photoactivity of the photoactive stent according to Example 3 for DPBF.
FIG. 10 is a graph of absorbance change of DPBF showing photoactivity of a photoactive stent according to Example 4 with respect to DPBF. FIG.

The present invention is a stent; And a photosensitive molecule attached to an outer surface of the stent.

Hereinafter, the photoactive stent of the present invention will be described in detail.

In the present invention, the photoactive stent may comprise a stent and photosensitizer attached to the outer surface of the stent.

The stent of the present invention may serve to expand a narrowed or blocked lumen when it is closed or narrowed by a blood vessel or non-vascular lumen in the human body due to cancer, tumor, or thrombus.

The kind of stent that can be used in the present invention is not particularly limited, and examples thereof include plastic stents (tube stents) such as polyurethane, polyethylene, polyethylene terephthalate and polytetrafluoroethylene; And metal stents such as stainless steel, cobalt alloy, nitinol (Ni-Ti alloy), and tantalum (Ta), but are preferably chromium-cobalt alloy (Cr-Co alloy) or nickel-titanium alloy (Ni-Ti). alloy) and one or more metal stents selected from the group consisting of stainless steel.

When the metal stent is used as the stent in the present invention, the outer surface of the stent may be oxidized. The oxidized stent surface may have -OH or the like, and the -OH or the like may form a covalent bond with a photosensitive molecule to be described later.

In the present invention, the photosensitive molecules may be attached to the outer surface of the stent.

The photosensitive molecules absorb light having an appropriate wavelength to generate reactive oxygen species (ex. ¹ O ₂ , O ₂ ^−, and OH ⁻ ), thereby necrosing the cells or tissues of the lesion, thereby causing photodynamic treatment, PDT). The mechanism by which the photosensitive molecules absorb light to generate reactive oxygen species is commonly known in the art.

In the present invention, the type of the photosensitive molecule is not particularly limited, and may be a porphyrin-based compound or a phthalocyanine-based compound, preferably 5,10,15-triphenyl-20- (4-carboxyphenyl) -porphyrin platinum ( 5,10,15-triphenyl-20- (4-carboxyphenyl) -porphyrin platinum, PtCP), 5,15-bisphenyl-10,20-bis (4-methoxycarbonylphenyl) -porphyrin platinum (5,15 -bisphenyl-10,20-bis (4-methoxycarbonylphenyl) -porphyrin platinum (t-PtCP), tetraphenyl porphyrin (H2TPP), hematoporphyrin (HP), proto porphyrin (PP) From indocyanin green (ICG), meso-tetrakis (p-sulfonatophenyl) porphyrin (TSPP) and pheophorbide A It may be one or more selected.

In the present invention, the wavelength of light that can be absorbed by the photosensitive molecules is not particularly limited, but may be preferably 450 nm to 1100 nm, more preferably 450 nm to 900 nm. In the present invention, when the wavelength range of light that the photosensitive molecules can absorb is less than 450 nm, the light transmittance in vivo is low, so that the amount of light energy that the photosensitive molecules can absorb is reduced, and thus sufficient photodynamic therapy cannot be performed. The wavelength of the strong UV region may cause necrosis of normal cells, and if it exceeds 1100 nm, the temperature may increase due to the stretching of water due to the long wavelength, thereby affecting the cells in the living body.

The light in the wavelength range corresponds to a visible light region or an infrared region, and in general, the visible light or the infrared light has a high light transmittance in vivo and thus can be easily transmitted into the living body, and the photosensitive molecule of the present invention is transmitted to the living body. By sufficiently absorbing light in the wavelength region, active oxygen species can be formed and photodynamic therapy can be performed more efficiently.

The photosensitive molecules of the present invention can be fixedly attached to the outer surface of the stent by forming a covalent bond with the outer surface of the stent.

If the stent used in the present invention is a plastic stent such as polyethylene terephthalate, polyurethane, etc., the outer surface of the stent is -OH, -COOH, -NH ₂ And -SH ₃ and the like can be present.

Thus, -OH, -COOH, -NH ₂ and -SH ₃ present on the stent outer surface And the like, by forming a covalent bond through an esterification reaction or an imine reaction with -COOH, -OH, and -SO ₃ and the like formed at the ends of the photosensitive molecule, the photosensitive molecule can be fixedly attached to the outer surface of the stent. .

When the stent used in the present invention is a metal stent, as described above, the outer surface of the metal stent may be oxidized, and the surface thereof may have -OH or the like.

Thus, -OH formed on the outer surface of the stent forms a covalent bond through esterification with -COOH formed at the end of the photosensitive molecule, whereby the photosensitive molecule can be fixedly attached to the outer surface of the stent. have.

In addition, when the stent used in the present invention is a metal stent, the outer surface of the oxidized stent may react with a functional group present at the end of the photosensitive molecule to form a metal-ligand coordination bond, such that the photosensitive molecule is stent. It may be attached to the outer surface of the fixed.

In the present invention, since the photosensitive molecules are fixed to the outer surface of the stent and are not separated from the outer surface of the stent, unlike the drug-release stent, continuous photodynamic therapy can be performed.

1 is a cross-sectional view showing a surface structure of a photoactive stent according to an aspect of the present invention. As shown in FIG. 1, the photoactive stent 10 may have a structure in which the photosensitive molecules 12 are attached to the outer surface 11a of the stent 11 through covalent or coordinating bonds 13.

2 is a cross-sectional view showing a surface structure of a photoactive stent according to another aspect of the present invention. As shown in FIG. 2, when the stent is a metal stent, the photoactive stent 20 is formed by oxidizing an outer surface 11a of the stent 11 to form an oxide 21 of the stent. The photosensitive molecule 12 may have a structure in which the photosensitive molecule 12 is attached via the covalent bond or the coordinative bond 13.

The invention also provides a stent; A metal oxide layer formed on an outer surface of the stent; And it relates to a photoactive stent comprising a photosensitive molecule attached to the surface of the metal oxide layer.

Hereinafter, the photoactive stent of the present invention will be described in detail with reference to FIG. 3.

3 is a cross-sectional view showing the surface structure of the photoactive stent according to another aspect of the present invention. As shown in FIG. 3, the photoactive stent 30 has a covalent or coordinating bond with the stent 11, the metal oxide layer 31 formed on the outer surface 11b of the stent, and the surface of the metal oxide layer 31. 13 may have a structure including the photosensitive molecules 12 attached through.

In the photoactive stent 30 of the present invention, descriptions related to the stent 11 and the photosensitive molecule 12 are the same as described above, and thus will be omitted.

The type of the metal oxide layer formed on the outer surface of the stent in the present invention is not particularly limited, but preferably at least one metal oxide selected from the group consisting of aluminum, iron, zinc, copper, silica titanium, zirconium, nickel and cobalt. have.

When the metal oxide layer is added to the outer surface of the stent in the present invention, the metal oxide layer may have irregularities on the surface, thereby increasing the specific surface area, thereby increasing the amount of photosensitive molecules that can be attached to the stent. You can.

The photosensitive molecules of the present invention can be fixedly attached to the outer surface of the metal oxide layer by forming covalent or coordinating bonds with the metal oxide layer surface.

The surface of the metal oxide layer of the present invention may have -OH or the like. Therefore, -OH formed on the surface of the metal oxide layer forms a covalent bond through an esterification reaction with -COOH formed at the end of the photosensitive molecule, whereby the photosensitive molecule can be fixedly attached to the surface of the metal oxide layer. .

In addition, the metal oxide layer of the present invention forms a metal-ligand coordination bond with a functional group such as -COOH, -OH, and -SO ₃ formed at the end of the photosensitive molecule, thereby leaving the photosensitive molecule fixed to the surface of the metal oxide layer. It may be attached.

In the present invention, since the photosensitive molecule is fixed to the outer surface of the metal oxide layer and is not separated from the outer surface of the metal oxide layer, unlike the drug release stent, continuous photodynamic therapy can be performed.

In the photoactive stent 30 of the present invention, since the photosensitive molecules are the same as described above, the wavelength of light that the photosensitive molecules can absorb is also the same as described above.

The invention also relates to a method of making a photoactive stent according to the invention, comprising attaching photosensitive molecules to the outer surface of the stent.

In the case where the stent used in the present invention is a plastic stent such as polyurethane or polyethylene terephthalate, photosensitive molecules may be attached to the outer surface through a covalent bond.

The outer surface of the plastic stent is -OH, -COOH, -NH ₂ and -SH ₃ When a photosensitive molecule having a functional group such as -COOH, -OH, and -SO _{3 at the} terminal is treated on the outer surface of the stent, esterification or imine reaction occurs between the functional groups to form a covalent bond. Can be formed.

If the stent used in the present invention is a metal stent, the step of oxidizing the outer surface of the stent may be performed before the step of attaching the photosensitive molecules to the outer surface of the stent.

The surface of the metal stent may be naturally oxidized by reacting with oxygen in the air, but in order to cause an oxidation reaction, the surface of the metal stent may be treated with hot water at a temperature of 80 ° C. to 100 ° C. or oxalic acid, sulfuric acid, phosphoric acid, nitric acid, and the like. Acid treatment such as hydrochloric acid can oxidize the outer surface of the metal stent.

The outer surface of the oxidized metal stent in the present invention is -COOH, -OH and -SO ₃ present at the end of the photosensitive molecule By forming a metal-ligand coordination bond with a functional group, such as, photosensitive molecules can be attached to the outer surface of the stent.

In addition, when the hydrogen peroxide (H ₂ O ₂ ) is treated on the surface of the oxidized metal stent in the present invention, it may have -OH on the surface of the metal oxide. The -OH on the surface of the metal oxide forms covalent bonds through the esterification reaction with -COOH formed at the ends of the photosensitive molecules, thereby attaching the photosensitive molecules to the outer surface of the stent.

4 is a view schematically illustrating a manufacturing process of a photoactive stent according to an aspect of the present invention.

As shown in FIG. 4, first, pretreatment may be performed to remove foreign matter present on the surface of the stent. When the stent from which the foreign substance is removed is a metal stent, the surface of the metal stent may be oxidized by treatment with hot water at 80 ° C. to 100 ° C. temperature or by acid treatment. In addition, hydrogen peroxide (H ₂ O ₂ ) may be treated on the surface of the oxidized metal stent to form -OH on the surface thereof. Then, photosensitive molecules (ex. Hemato porphyrin) are treated on the surface of the metal stent on which -OH is formed to form a covalent bond through an esterification reaction between -COOH formed at the end of the photosensitive molecule and -OH on the surface of the metal stent. By doing so, the photosensitive molecules can be attached to the outer surface of the stent.

The invention also includes a first step of forming a metal oxide layer on the outer surface of the stent; And a second step of attaching photosensitive molecules to the surface of the metal oxide layer.

In the present invention, the first step may include depositing a metal layer on an outer surface of the stent and oxidizing the deposited metal layer to form a metal oxide layer.

In the present invention, the method of depositing a metal layer on the outer surface of the stent may be by physical vapor deposition (Physical Vapor Deposition, PVD). The physical vapor deposition method is a method in which a material to be deposited is made into a gaseous state in a vacuum state and blown away, and when a vapor is deposited on a substrate, a physical change occurs in the gaseous state to a solid state and is deposited. Physical vapor deposition method that can be used in the present invention is not particularly limited, for example, sputtering, E-beam evaporation, Thermal evaporation, Laser Molecular Beam Epitaxy, L-MBE) and Pulsed Laser Deposition (PLD), and the like, but preferably sputtering.

In the present invention, the method of oxidizing the metal layer deposited on the outer surface of the stent is not particularly limited. For example, hot water at a temperature of 80 ° C to 100 ° C is oxidized by treating the metal layer, or oxalic acid, sulfuric acid, phosphoric acid, Acids, such as nitric acid and hydrochloric acid, can be treated by oxidizing the metal layer.

In the present invention, as described above, after the metal oxide layer is formed, hydrogen peroxide (H ₂ O ₂ ) may be additionally treated on the metal oxide layer. When hydrogen peroxide is treated on the metal oxide layer, -OH may be formed on the surface of the metal oxide layer.

In the present invention, the second step is attaching photosensitive molecules to the surface of the metal oxide layer. As described above, when the photosensitive molecules are treated in the metal oxide layer formed in the first step, the photosensitive molecules may be attached to the surface of the metal oxide layer through covalent or coordinating bonds.

That is, in the present invention, the metal oxide layer forms a metal-ligand coordination bond with a functional group such as -COOH, -OH, and -SO ₃ formed at the end of the photosensitive molecule, thereby fixing the photosensitive molecule to the surface of the metal oxide layer. May remain attached.

In addition, when hydrogen peroxide is treated to the metal oxide layer of the present invention, the photosensitive molecule has -OH on its surface, and esterification reaction with -COOH formed at the terminal of the photosensitive molecule to form a covalent bond, thereby forming the photosensitive molecule. It may be attached fixed to the surface of the metal oxide layer.

The metal oxide layer of the present invention is not particularly limited, but may preferably be an oxide of at least one metal selected from the group consisting of aluminum, iron, zinc, copper, silica titanium, zirconium, nickel and cobalt.

5 is a view schematically illustrating a manufacturing process of a photoactive stent according to another aspect of the present invention.

As shown in FIG. 5, a metal layer (eg, an aluminum layer) may be deposited on the outer surface of the stent by sputtering. Thereafter, the metal layer may be treated with hot water at a temperature of 80 ° C. to 100 ° C. or an acid such as oxalic acid, sulfuric acid, phosphoric acid, nitric acid and hydrochloric acid to oxidize the metal layer. In addition, hydrogen peroxide (H ₂ O ₂ ) may be treated on the surface of the oxidized metal oxide layer to form -OH on the surface thereof. Then, photosensitive molecules (ex. PtCP) are treated on the surface of the metal stent on which -OH is formed to form a covalent bond through an esterification reaction between -COOH formed at the end of the photosensitive molecule and -OH on the surface of the metal oxide layer. The photosensitive molecules can be attached to the surface of the metal oxide layer.

[ Example ]

Hereinafter, the present invention will be described in more detail with reference to the following examples and comparative examples, but the scope of the present invention is not limited by the following examples.

Example  One

As the stent, a circular polyethylene terephthalate film having a diameter of 10 mm and a thickness of 0.3 mm was used. A photoactive stent was prepared by treating hematopopirine (HP) as a photosensitive molecule on the polyethylene terephthalate film to attach 3.19 × 10 ⁻⁷ mol of hematopoietin to the outer surface of the stent through covalent bonds. .

Example  2

As the stent, a circular slide glass having a diameter of 10 mm and a thickness of 0.3 mm was used. A photoactive stent was prepared by treating hematopopirine as a photosensitive molecule on the glass to allow 4.06 × 10 ⁻⁸ mol of hematopoieline to adhere to the outer surface of the stent through covalent bonds.

Example  3

As the stent, a chromium-cobalt alloy was used. The chromium-cobalt alloy was immersed in hot water at 100 ° C. for 5 minutes to oxidize the surface. The oxidized chromium-cobalt alloy was then treated with hydrogen peroxide. Subsequently, a chromium-cobalt alloy oxide treated with hydrogen peroxide was produced in a circular form having a diameter of 10 mm and a thickness of 0.3 mm, and hematopophyrin was treated as a photosensitive molecule on the chromium-cobalt alloy oxide prepared as described above. A photoactive stent was prepared by covalently attaching 4.02 × 10 ⁻⁸ mol of hematopoietin to the outer surface of the stent.

Example  4

As the stent, a nickel-titanium alloy was used. An aluminum layer was deposited on the nickel-titanium alloy by sputtering. Thereafter, the aluminum layer was soaked in hot water at 100 ° C. for 5 minutes to oxidize the aluminum layer. Hydrogen peroxide was then treated on the oxidized aluminum layer. Thereafter, the laminate of the aluminum oxide layer / nickel-titanium alloy was produced in a circular form having a diameter of 10 mm and a thickness of 0.5 mm, and as a photosensitive molecule on the aluminum oxide layer of the laminate thus produced, Photoactive stents were prepared by treating porphyrin to allow 4.02 × 10 ⁻⁸ mol of hematopoietin to adhere to the outer surface of the stent through covalent bonds.

Test Example  One

To investigate the photoactive activity of hematopoietin against rat aortic smooth muscle cells (RAOSMC), 1 μg of hematopopirine, a photosensitive molecule, was added to a medium containing 1 × 10 ⁵ cell / well of RAOSMC. ML (1.67 × 10 −9 mol) was applied. Thereafter, the change of RAOSMC was observed while irradiating ns Nd-YAG OPO laser (wavelength 510 nm, intensity 14mW) as a light source for 10 minutes. As shown in FIG. 6, after irradiation with the laser, the smooth muscle cells were found to be necrotic. That is, the hematopoieline absorbed light having a wavelength of 510 nm to form reactive oxygen species, and it was confirmed that RAOSMC was necroticed by the reactive oxygen species.

Test Example  2

In order to examine the photoactive stent of the photoactive stent on rat aortic smooth muscle cell (RAOSMC), the photoactive stent prepared in Example 1 was laid on the bottom of the medium, and on top of the 1 × 10 ⁵ cell / well RAOSMC was cultured. Then, the change of RAOSMC was observed while irradiating ns Nd-YAG OPO laser (wavelength 510 nm, intensity 14mW) as a light source for 30 minutes. As shown in FIG. 7, after irradiating the laser, the smooth muscle cells were found to be necrotic. That is, the hematopoieline absorbed light having a wavelength of 510 nm to form reactive oxygen species, and it was confirmed that RAOSMC was necroticed by the reactive oxygen species.

Test Example  3

To investigate the photoactive stent photoactive stents against rat aortic smooth muscle cells (RAOSMC), the photoactive stents prepared in Example 2 were placed on the bottom of the medium, on top of 1 × 10 ⁵ cells / 48well. RAOSMC was cultured. Then, the change of RAOSMC was observed while irradiating ns Nd-YAG OPO laser (wavelength 510 nm, intensity 14mW) as a light source for 30 minutes. As shown in FIG. 8, after the laser irradiation, the smooth muscle cells were found to be necrotic. That is, the hematopoieline absorbed light having a wavelength of 510 nm to form reactive oxygen species, and it was confirmed that RAOSMC was necroticed by the reactive oxygen species.

Test Example  4

In order to investigate the photoactivity of the photoactive stent composed of the metal stent, as an indirect method, it was confirmed whether the photoactive stent prepared in Example 3 generates active oxygen species by light. To this end, the photoactive stent prepared in Example 3 was placed in a container containing a DPBF solution dissolved in THF, and irradiated with light to the container for 15 minutes using Xe-lamp (intensity 150W) as a light source, and having a wavelength of 415 nm. The absorbance change of DPBF for was observed. At this time, the wavelength of light irradiated from the Xe-lamp was filtered to remove light having a wavelength of less than 510 nm, thereby irradiating light having a wavelength of 510 nm or more. As shown in FIG. 9, it was found that the absorbance of DPBF with respect to the wavelength of 415 nm decreased with the irradiation time of light. That is, hematopophyrin of the photoactive stent absorbed light having a wavelength of 510 nm to form active oxygen species, and it was found that DPBF was decomposed by the active oxygen species.

Test Example  5

In order to investigate the photoactivity of the photoactive stent composed of the metal stent, as an indirect method, it was confirmed whether the photoactive stent prepared in Example 4 generates active oxygen species by light. To this end, the photoactive stent prepared in Example 4 was placed in a container containing a DPBF solution dissolved in THF, and the light was irradiated to the container for 15 minutes using Xe-lamp (intensity 150W) as a light source, and the wavelength was 415 nm. The absorbance change of DPBF for was observed. At this time, the wavelength of light irradiated from the Xe-lamp was filtered to remove light having a wavelength of less than 510 nm, thereby irradiating light having a wavelength of 510 nm or more. As shown in FIG. 10, it was found that the absorbance of DPBF with respect to the wavelength of 415 nm decreased with the irradiation time of light. That is, hematopophyrin of the photoactive stent absorbed light having a wavelength of 510 nm to form active oxygen species, and it was found that DPBF was decomposed by the active oxygen species.

As can be seen from the attached FIGS. 6 to 8, a photoactive stent including a photosensitive molecule attached to the stent and its outer surface is irradiated with light of a wavelength corresponding to a specific region, and is applied to smooth muscle cells on in-vitro. Cell activity was shown. That is, the photosensitive molecules attached to the stent absorb light of a wavelength corresponding to a specific region to form active oxygen species, and the reactive oxygen species have cytotoxicity, which can necrosis smoothly contacting smooth muscle cells. .

In addition, as can be seen from FIGS. 9 and 10, a photoactive stent comprising a metal stent and photosensitive molecules attached to an outer surface thereof is exposed to light of a wavelength corresponding to a specific region, and thus photoactive to DPBF. Indicated. That is, the photosensitive molecules attached to the stent absorb light of a wavelength corresponding to a specific region to form active oxygen species, and the active oxygen species have a decomposition ability with respect to DPBF, thereby decomposing DPBF.

As described above, when the photoactive stent of the present invention is attached to a narrowed vessel and irradiated with light having a specific wavelength, photosensitive molecules attached to the photoactive stent express photoactivity to form active oxygen species, Necrosis of vascular endothelial cells, such as smooth muscle cells, which grows again on the surface of the photoactive stent, confirmed that blood vessels could be restrained from restenosis.

That is, the photoactive stent according to the present invention has a self-cleaning function, and can be used for a long time without re-stenting due to restenosis of the lesion. Conventionally, if a restenosis occurs in the lesion after the stent operation, the stent installed in the lesion is removed and the stent is installed again, or the metal stent is not easy to remove. Corresponding to.

However, in the process of removing the stent installed on the lesion as described above or reinstall the stent may cause a secondary disease due to the blood vessels. In the present invention, the conventional problem was solved by developing a photoactive stent having a self-cleaning function.

10,20,30: Surface structure of the photoactive stent
11: stent 11a: outer surface of the stent
11b: internal surface of the stent 12: photosensitive molecules
13: covalent or coordinative bond 21: oxide of the stent
31: metal oxide layer

Claims (20)

Stents; And
Includes photosensitive molecules attached to the outer surface of the stent,
And the photosensitive molecule is attached to the outer surface of the stent through covalent or coordinating bonds. The method of claim 1,
Stents are photoactive stents that are plastic or metal stents. The method of claim 2,
The metal stent is at least one photoactive stent selected from the group consisting of chromium-cobalt (Cr-Co alloy), nickel-titanium alloy (Ni-Ti alloy), tantalum (Ta) and stainless steel (Stainless steel). The method of claim 1,
A photoactive stent in which the outer surface of the stent is oxidized. The method of claim 1,
The photosensitive molecule is a photoactive stent which is a porphyrin compound or a phthalocyanine compound. The method of claim 1,
Photosensitive molecules are 5,10,15-triphenyl-20- (4-carboxyphenyl) -porphyrin platinum (5,10,15-triphenyl-20- (4-carboxyphenyl) -porphyrin platinum (PtCP), 5,15 -Bisphenyl-10,20-bis (4-methoxycarbonylphenyl) -porphyrin platinum (5,15-bisphenyl-10,20-bis (4-methoxycarbonylphenyl) -porphyrin platinum, t-PtCP), tetraphenylporphyrin (tetraphenyl porphyrin, H ₂ TPP), hematopophyrin (HP), proto porphyrin (PP), indocyanin green (ICG), meso-tetrakis (p-sulfonatophenyl) At least one photoactive stent selected from the group consisting of meso-tetrakis (p-sulfonatophenyl) porphyrin (TSPP) and pheophorbide A. delete The method of claim 1,
The photosensitive molecule is a photoactive stent expressing photoactivity by light having a wavelength of 450 nm to 1100 nm. Stents;
A metal oxide layer formed on an outer surface of the stent; And
A photoactive stent comprising photosensitive molecules attached to a surface of the metal oxide layer. The method of claim 9,
Stents are photoactive stents that are plastic or metal stents. 11. The method of claim 10,
The metal stent is at least one photoactive stent selected from the group consisting of chromium-cobalt (Cr-Co alloy), nickel-titanium alloy (Ni-Ti alloy), tantalum (Ta) and stainless steel (Stainless steel). The method of claim 9,
The metal oxide layer is a photoactive stent which is an oxide of at least one metal selected from the group consisting of aluminum, iron, zinc, copper, silica titanium, zirconium, nickel and cobalt. The method of claim 9,
The photosensitive molecule is a photoactive stent which is a porphyrin compound or a phthalocyanine compound. The method of claim 9,
Photosensitive molecules are 5,10,15-triphenyl-20- (4-carboxyphenyl) -porphyrin platinum (5,10,15-triphenyl-20- (4-carboxyphenyl) -porphyrin platinum (PtCP), 5,15 -Bisphenyl-10,20-bis (4-methoxycarbonylphenyl) -porphyrin platinum (5,15-bisphenyl-10,20-bis (4-methoxycarbonylphenyl) -porphyrin platinum, t-PtCP), tetraphenylporphyrin (tetraphenyl porphyrin, H ₂ TPP), hematopophyrin (HP), proto porphyrin (PP), indocyanin green (ICG), meso-tetrakis (p-sulfonatophenyl) At least one photoactive stent selected from the group consisting of meso-tetrakis (p-sulfonatophenyl) porphyrin (TSPP) and pheophorbide A. The method of claim 9,
The photosensitive molecule is a photoactive stent attached to the surface of the metal oxide layer through covalent or coordinative bonds. The method of claim 9,
The photosensitive molecule is a photoactive stent expressing photoactivity by light having a wavelength of 450 nm to 1100 nm. Attaching photosensitive molecules to the outer surface of the stent,
A method for producing a photoactive stent according to any one of claims 1 to 6 or 8. The method of claim 17,
Prior to attaching the photosensitive molecules, further comprising oxidizing an outer surface of the stent. Forming a metal oxide layer on an outer surface of the stent; And
17. The method of producing a photoactive stent according to any one of claims 9 to 16, comprising a second step of attaching a photosensitive molecule to the surface of the metal oxide layer. The method of claim 19,
The first step includes depositing a metal layer on an outer surface of the stent; And
Oxidizing the deposited metal layer to form a metal oxide layer.

Images