JP7471119B2 - Medical long body - Google Patents

Description

The present invention relates to a medical elongated body.

Medical elongated bodies, such as guidewires, are introduced into body cavities for use. For example, guidewires are introduced into body cavities to safely and reliably guide medical instruments, such as catheters, to a specific target site in the human body. Guidewires used in this manner are required to have slidability, and also bendability so that they can pass through curved parts in the body cavities and bend for manual operation. In conventional guidewires, a polytetrafluoroethylene (PTFE) layer is sometimes provided as a surface layer since it is necessary to ensure slidability for introduction into the body cavity to the target site. However, guidewires with a PTFE layer have good slidability, but have problems with bendability because the PTFE layer is prone to cracking and detachment.

Japanese Patent No. 2575238

The present invention was made to solve the above-mentioned problems, and its purpose is to provide a medical elongated body that has sliding and bending properties.

式（１）中、Ｒ^１、Ｒ^２およびＲ^３はそれぞれ独立に水素原子、無置換若しくは置換基を有するアルキル基、または無置換若しくは置換基を有するアルケニル基を表し、Ｒ^１、Ｒ^２、Ｒ^３のいずれか１つは水素原子以外であり、ｎは正の整数である。
１つの実施形態においては、上記芯材が、ステンレス鋼から形成されている。
１つの実施形態においては、上記被覆層が形成された部分の長さが、４００ｍｍ～２８００ｍｍである。
１つの実施形態においては、上記被覆層の厚みが、２μｍ以下である。
１つの実施形態においては、上記芯材の一部に上記被覆層が形成され、該被覆層が形成されていない部分において、親水層が形成されている。 The medical elongated body of the present invention comprises a core material and a coating layer that covers at least a portion of the surface of the core material, and the coating layer contains an organic polysilazane.
In one embodiment, the organic polysilazane contains a constitutional unit represented by general formula (1).

In formula (1), R ¹ , R ² and R ³ each independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, or an unsubstituted or substituted alkenyl group, one of R ¹ , R ² and R ³ is other than a hydrogen atom, and n is a positive integer.
In one embodiment, the core is formed from stainless steel.
In one embodiment, the length of the portion on which the coating layer is formed is 400 mm to 2800 mm.
In one embodiment, the coating layer has a thickness of 2 μm or less.
In one embodiment, the coating layer is formed on a part of the core material, and a hydrophilic layer is formed in the part where the coating layer is not formed.

According to the present invention, by forming a coating layer containing organic polysilazane, it is possible to provide a medical elongated body that has both sliding properties and bendability.

1 is a schematic diagram illustrating a medical elongate body according to one embodiment of the present invention. FIG. 2 is a schematic partial longitudinal sectional view of a medical elongate body according to one embodiment of the present invention.

Figure 1 is a schematic diagram illustrating a medical elongated body according to one embodiment of the present invention. In Figure 1, a guidewire is shown as a representative example of a medical elongated body. Also, Figure 2 is a schematic partial longitudinal sectional view of a medical elongated body according to one embodiment of the present invention. Below, the medical elongated body will be described using a guidewire as an example. The guidewire 100 comprises a core material 10 and a coating layer 20 that covers at least a portion of the surface of the core material 10. The coating layer 20 contains organic polysilazane.

In one embodiment, the core material 10 may have a shape that tapers from the base end (proximal end) to the tip (distal end). In one embodiment, the guidewire 100 includes a coil body 30 disposed at the tip of the core material 10. The core material 10 may be inserted into the coil body 30 at its tip. By including the coil body 30, a guidewire that is easy to push into a body cavity and is less likely to buckle can be obtained. In this specification, the tip means the end that reaches the treatment area in the body cavity, and the base end means the end opposite the tip.

The guidewire of the present invention is not limited to the embodiment shown in FIG. 1 as long as the effects of the present invention can be obtained, and the shape of the core material, the shape of the tip including the presence or absence of a coil body, etc. can be any appropriate shape.

In one embodiment, a coating layer 20 is formed on the surface of the core material 10 in the portion of the core material 10 that is not inserted into the coil body 30.

The above-mentioned guidewire is inserted into a body cavity by the operator manipulating the proximal portion (near the base end of the core material). The inserted guidewire functions to guide a medical instrument such as a catheter to a predetermined position in the body cavity. The guidewire according to the present invention has excellent sliding properties, particularly with respect to medical instruments such as catheters, and the medical instrument can be guided with good workability by using the guidewire. In addition, when a coating layer is formed on the proximal portion, the guidewire can be made easier to handle by the person performing the insertion work. The medical elongated body of the present invention is not limited to the guidewire having the above-mentioned configuration, and can be suitably used for an elongated body having a sliding surface on the outer periphery. When the outer periphery surface slides against a medical instrument or biological tissue, frictional resistance is small, so that the medical elongated body of the present invention can be operated. At least a part of the coating layer is formed as the outermost layer and is formed in a state exposed to the outside.

Furthermore, in the present invention, since the coating layer is made of organic polysilazane, the bendability of the core material is unlikely to decrease, and a medical elongated body (e.g., a guidewire) with excellent bendability can be provided. The guidewire can be easily inserted along a desired path (e.g., a blood vessel). In addition, the coating layer made of organic polysilazane has the characteristic of having excellent adhesion to the core material and being difficult to come off. The medical elongated body of the present invention is also advantageous in that the coating layer is difficult to come off even when curved.

(Core material)
As the constituent material of the core material, a metal material is preferably used. Examples of the constituent material of the core material include stainless steel, Ni-Ti alloy, Cu-Zn alloy, cobalt alloy, etc. Among them, stainless steel is preferable. The core material may be formed by connecting a plurality of types of wires made of different materials.

The length of the core material is typically 1000 mm to 3000 mm. In one embodiment, the length of the core material may correspond to the length of the medical elongated body.

The diameter of the core material is typically 0.1 mm to 1.5 mm.

(Covering layer)
As described above, the coating layer is made of an organic polysilazane, which is a polymer having —Si—N— as a basic structural unit and having an organic group in the structural unit.

式（１）中、Ｒ^１、Ｒ^２及びＲ^３はそれぞれ独立に水素原子、無置換若しくは置換基を有するアルキル基、または無置換若しくは置換基を有するアルケニル基を表し、Ｒ^１、Ｒ^２、Ｒ^３のいずれか一つは水素原子以外である。ｎは正の整数である。 An example of the organic polysilazane is a polymer containing a structural unit represented by the general formula (1).

In formula (1), R ¹ , R ² and R ³ each independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, or an unsubstituted or substituted alkenyl group, and any one of R ¹ , R ² and R ³ is other than a hydrogen atom. n is a positive integer.

Examples of the alkyl group of the unsubstituted or substituted alkyl group include alkyl groups having 1 to 10 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl, and n-octyl.

Examples of the alkenyl group of the unsubstituted or substituted alkenyl group include alkenyl groups having 2 to 10 carbon atoms, such as vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, and 3-butenyl.

Examples of substituents for the alkyl and alkenyl groups include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, an alkoxysilyl group, a hydroxyl group, a thiol group, an epoxy group, a glycidoxy group, a (meth)acryloyloxy group, a phenyl group, a 4-methylphenyl group, and a 4-chlorophenyl group.

式（２－１）中、Ｒ^１－２は、無置換若しくは置換基を有するアルキル基である。
式（２－２）中、Ｒ^２－１およびＲ^２－２はそれぞれ独立して、無置換若しくは置換基を有するアルキル基である。
式（２－３）中、Ｒ^３－１は、水素原子または無置換若しくは置換基を有するアルキル基である。Ｒ^３－２は、無置換若しくは置換基を有するアルキル基である。Ｒ^３－３は、無置換若しくは置換基を有するアルキル基であり、良好な密着性を得るために、置換基として－Ｓｉ（ＯＲ）_３で表されるアルコキシシリル基（Ｒは１～２０）を含んでいてもよい。これらの官能基は、芯材を構成する金属材料に対応させて適宜選択することができる。 In one embodiment, the organic polysilazane contains a constitutional unit represented by the general formula (2-1), a constitutional unit represented by the general formula (2-2), and a constitutional unit represented by the general formula (2-3).

In formula (2-1), R ^1-2 is an unsubstituted or substituted alkyl group.
In formula (2-2), R ^2-1 and R ^2-2 each independently represent an unsubstituted or substituted alkyl group.
In formula (2-3), R ^3-1 is a hydrogen atom or an unsubstituted or substituted alkyl group. R ^3-2 is an unsubstituted or substituted alkyl group. R ^3-3 is an unsubstituted or substituted alkyl group, and may contain an alkoxysilyl group represented by -Si(OR) ₃ (R is 1 to 20) as a substituent in order to obtain good adhesion. These functional groups can be appropriately selected in accordance with the metal material constituting the core material.

In formulas (2-1) to (2-3), x, y, and z are positive integers. The ratio of x, y, and z is (5 to 90):(5 to 90):(5 to 90).

The organic polysilazane may be a random copolymer or a block copolymer.

The number average molecular weight of the organic polysilazane is preferably 500 to 4500. Within this range, a medical elongated body with excellent sliding properties and bendability can be obtained.

As long as the thickness of the coating layer satisfies various physical properties, it is preferable that the thickness be 10 μm or less, more preferably 5 μm or less, and even more preferably 2 μm or less, so that a medical elongated body with excellent bendability can be obtained. When the layer is formed by a known method, the thickness of the coating layer is, for example, preferably 0.1 μm to 10 μm, more preferably 0.5 μm to 5 μm, and even more preferably 1 μm to 2 μm. If it is within such a range, a medical elongated body with excellent bendability can be obtained.

The length of the portion where the coating layer is formed is preferably 400 mm to 2800 mm, more preferably 1300 mm to 2000 mm. The length of the portion where the coating layer is formed is preferably 8% to 100% of the length of the core material, more preferably 8% to 60%, even more preferably 10% to 50%, and particularly preferably 15% to 40%. In the portion where the coating layer is formed, it is preferable that the coating layer is formed over the entire circumference of the core material. In the portion where the coating layer is not formed, a hydrophilic layer may be formed on the surface of the core material. Details of the hydrophilic layer will be described later.

The coating layer can be formed by any suitable method. In one embodiment, a coating layer is formed by applying a coating layer-forming composition containing an organic polysilazane to a predetermined area of the core material. The coating layer-forming composition can be prepared by dissolving an organic polysilazane in a predetermined solvent.

As the above-mentioned solvent, any suitable solvent can be used as long as it can dissolve the organic polysilazane. Examples of the solvent include propane, butane, isobutane, pentane, 2-methylbutane, neopentane, cyclopentane, hexane, 2-methylpentane, 3-methylpentane, heptane, 2-methylhexane, 3-methylhexane, cyclohexane, octane, isooctane, nonane, isononane, decane, etc.

The concentration of the organic polysilazane in the coating layer-forming composition is preferably 5% to 40% by weight. Within this range, a coating layer of a uniform thickness can be formed.

The viscosity of the coating layer-forming composition is not particularly limited as long as it is a coating-compatible viscosity. By appropriately adjusting the viscosity of the coating layer-forming composition, a good coating layer can be formed.

Any suitable method may be used to apply the coating layer-forming composition. Typically, a dip coating method, a spray coating method, or a flow coating method may be used.

The medical elongated body is preferably subjected to a heat treatment after the coating layer forming composition is applied to the core material. The heat treatment causes the solvent to volatilize and the coating layer to harden, forming a coating layer that adheres closely to the core material.

The coating layer formed as described above can adhere to the core material by the action of a dehydration reaction between the OH groups of the core material and the SiH groups of the organic polysilazane; a deammonia reaction between the OH groups of the core material and the NH groups of the organic polysilazane; or, after the SiN groups of the organic polysilazane are hydrolyzed (for example, hydrolysis due to moisture in the atmosphere), a dehydration reaction between the OH groups of the core material and the silanol groups generated by hydrolysis.

When forming the coating layer, the core material may be subjected to any suitable surface treatment. For example, the core material may be subjected to a coupling treatment, and then the composition for forming the coating layer may be applied to the core material. Examples of coupling agents used in the coupling treatment include epoxy-terminated coupling agents, amino group-containing coupling agents, methacryl group-containing coupling agents, and thiol group-containing coupling agents.

When the above-mentioned coating layer forming composition is applied to a SUS304 plate to form a coating layer, the contact angle of the coating layer with pure water is preferably 100° to 120°, and more preferably 105° to 115°. If a coating layer is formed using a coating layer forming composition capable of forming such a coating layer, a medical elongated body with excellent sliding properties can be obtained.

When the above-mentioned coating layer forming composition is applied to a SUS304 plate to form a coating layer, the static friction coefficient of the coating layer is preferably 0.05 to 0.15. If a coating layer is formed using a coating layer forming composition capable of forming such a coating layer, a medical elongated body with excellent sliding properties can be obtained.

When the above-mentioned coating layer forming composition is applied to a SUS304 plate to form a coating layer, the coating layer preferably has a dynamic friction coefficient of 0.01 to 0.12. By forming a coating layer using a coating layer forming composition capable of forming such a coating layer, a medical elongated body with excellent sliding properties can be obtained.

When the coating layer is formed by applying the above-mentioned coating layer forming composition to a SUS304 plate, the pencil hardness of the coating layer is, for example, less than 6B. By having a good pencil hardness, a medical elongated body having excellent sliding properties can be obtained. Furthermore, a medical elongated body in which the coating layer is difficult to come off while maintaining sliding properties can be obtained.

(Hydrophilic Layer)
In one embodiment, as described above, a hydrophilic layer is formed on the surface of the core material in the portion where the coating layer is not formed. In addition, when the medical elongated body (e.g., guidewire) has a coil body, a hydrophilic layer may be formed on the surface of the coil body. By forming a hydrophilic layer, a medical elongated body (e.g., guidewire) having excellent slidability in a body cavity (especially slidability near a treatment area) can be obtained.

The hydrophilic layer can be formed by coating the core with any suitable hydrophilic material. Examples of hydrophilic materials include polymeric materials such as cellulose-based, polyethylene oxide-based, maleic anhydride-based, and acrylamide-based materials.

The length of the portion where the hydrophilic layer is formed is preferably 100 mm to 1000 mm, and more preferably 200 mm to 600 mm. The length of the portion where the hydrophilic layer is formed is preferably 40% to 92% of the length of the core material, more preferably 50% to 90%, and even more preferably 60% to 85%.

(Coil body)
The coil body may have any suitable structure. The coil body may be formed, for example, by winding any suitable wire. The material of the wire constituting the coil body is not particularly limited, and may be a radiopaque material or a non-radiopaque material. Examples of radiopaque materials include materials with good contrast properties to X-rays, such as platinum, platinum alloys (e.g., Pt/Ir=93/7), gold, gold-copper alloys, tungsten, and tantalum. Examples of non-radiopaque materials include stainless steel (e.g., SUS316, SUS304), and the like. The coil body may be subjected to a hydrophilic treatment.

The medical elongated body of the present invention can be used in medical devices with a metal surface, and is particularly suitable for medical devices with a curved or bendable internal insertion portion, such as guidewires and puncture needles, which require slidability and bendability.

The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. In the examples, "parts" and "%" are by weight unless otherwise specified.

＜防汚性＞
塗工層に油性インク（ＺＥＢＲＡ社製、商品名「ハイマッキー赤」）を連続５回塗り込み、インクの弾き性を目視及びマイクロスコープで確認した。
また、上記塗り込み後１分間経過した後に、ワイパーにより、インクが拭き取り可能であるかを確認した。
弾き性については、連続５回の重ね塗り後のインクの塗り跡に、塗布位置よりもインキが収縮するなどの、インキの弾きが見られたものを○とし、インキの弾きがないものを×とした。
＜鉛筆硬度＞
ＪＩＳ Ｋ ５４００－５－４に準じて、塗工層の鉛筆硬度を測定した。鉛筆硬度が６Ｂ以下のものを○とし、鉛筆硬度が６Ｂより硬いものを×とした。
＜折曲性＞
評価サンプル（１）を任意の一か所から折り曲げて、二つ折り状となるように、約１８０°に１回折り曲げた。折り曲げた状態で放置後、折り曲げた部位の被膜状態を市販のマイクロスコープで拡大して、被膜の割れや剥離の有無を目視により観察した。 [Example 1]
A wire made of SUS304 was used as a core material, and a coating layer-forming composition A (organic polysilazane concentration: about 20% by weight) was prepared by dissolving an organic polysilazane having structural units represented by the following structural formulas (3-1) to (3-3) in a hydrocarbon solvent. The core material was then coated with the coating layer-forming composition A and heated at about 110 to 130° C. for about 2 hours to form a coating layer having a thickness of 1 μm on the surface of the core material, thereby preparing an evaluation sample (1) intended as a guidewire. The evaluation sample (1) was evaluated for antifouling properties, pencil hardness, and bendability by the following evaluation methods. The results are shown in Table 1.

<Anti-stain properties>
An oil-based ink (manufactured by ZEBRA, product name "Hi-Mackie Red") was applied to the coating layer five times in succession, and the ink repellency was confirmed visually and with a microscope.
After one minute had elapsed since the ink was applied, it was confirmed whether the ink could be wiped off with a wiper.
Regarding repellency, a case in which the ink was repellent, such as the ink shrinking from the applied position at the ink application site after five consecutive applications, was marked with an ◯, and a case in which the ink was not repellent was marked with an ×.
<Pencil hardness>
The pencil hardness of the coating layer was measured according to JIS K 5400-5-4. Pencil hardness of 6B or less was marked as ◯, and pencil hardness of more than 6B was marked as ×.
<Bendability>
The evaluation sample (1) was folded at an arbitrary position, and folded once at about 180° so as to be folded in half. After leaving it in the folded state, the coating state of the folded portion was magnified with a commercially available microscope, and the presence or absence of cracks or peeling of the coating was visually observed.

In addition, the composition A for forming a coating layer used in Example 1 was applied to a SUS plate (commercially available product) to form a coating similar to that of the evaluation sample (1), to obtain an evaluation sample (2). The contact angle (pure water) and friction coefficient of the obtained evaluation sample (2) were measured by the following evaluation method. The results are shown in Table 2.
<Contact angle (pure water)>
The contact angle of pure water (liquid volume: 2 μL) was measured using a product name "DropMaster 500" manufactured by Kyowa Interface Science Co., Ltd.
<Coefficient of friction>
The static friction coefficient and dynamic friction coefficient of the coating layer were measured under the following conditions using a "Surface Property Measuring Instrument Tribostation Type: 32" manufactured by Shinto Chemical Co., Ltd.
(Friction coefficient measurement conditions)
Load: 100g
Indenter: flat indenter (10 mm x 10 mm)
Movement speed: 30 mm/min (static friction coefficient), 600 mm/min (dynamic friction coefficient)

Comparative Example
A commercially available guidewire having a PTFE layer as a coating layer was obtained, and the antifouling property, pencil hardness, and bendability were evaluated in the same manner as in the evaluation sample (1). The results are shown in Table 1.

[result]
When the bending portion of the evaluation sample (1) obtained in Example 1 was observed visually and with a microscope, no cracks or detachment of the coating layer was confirmed, and it was found that the coating layer was formed with excellent adhesion. In addition, the evaluation sample (1) also had good antifouling properties and pencil hardness. In contrast, the commercially available product of Comparative Example 1 had good antifouling properties and pencil hardness, but the coating layer at the bending portion peeled off, and the bending property was poor.
Regarding the composition A for forming a coating layer in Example 1, the evaluation sample (2) had excellent water repellency with a contact angle (pure water) of 108°, and had excellent sliding properties with a static friction coefficient of 0.095 and a dynamic friction coefficient of 0.057. In other words, it is found that the medical elongated body obtained from the composition A for forming a coating layer in Example 1 has excellent insertability in a body cavity.
By forming a coating layer using such a composition for forming a coating layer, a medical elongated body having excellent antifouling properties and pencil hardness, as well as excellent bendability, can be obtained. The medical elongated body of the present invention has the same or better sliding properties and antifouling properties as a medical elongated body coated with PTFE, and is advantageous in that it has excellent bendability without cracking or detachment of the coating layer, as shown in Example 1.

10 Core material 20 Covering layer 30 Coil body 100 Medical elongated body (guidewire)

Claims (8)

The core material has a coating layer that covers at least a part of a surface of the core material.
The coating layer comprises an organic polysilazane.
Guidewire . The guidewire of claim 1 , wherein the coating layer has a pencil hardness of less than 6B. The guide wire according to claim 1 or 2, wherein the contact angle of the coating layer is from 100° to 120°. 4. The guide wire according to claim 1, wherein the length of the portion on which the covering layer is formed is 400 mm to 2800 mm. 5. The guidewire according to claim 1, wherein the length of the portion where the covering layer is formed is 8% to 100% of the length of the core material. 6. The guidewire according to claim 1, wherein the coating layer is formed on a portion of the core material, and a hydrophilic layer is formed on a portion where the coating layer is not formed. The guidewire according to any one of claims 1 to 6 , wherein the organic polysilazane contains a constitutional unit represented by general formula (1):

In formula (1), R1, R2, and R3 each independently represent a hydrogen atom, an unsubstituted or substituted alkyl group, or an unsubstituted or substituted alkenyl group, one of R1, R2, and R3 is other than a hydrogen atom, and n is a positive integer. The guidewire according to claim 1 , wherein the core material is formed from stainless steel.

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