JP7003619B2 - Medical devices and manufacturing methods for medical devices - Google Patents

Description

The present invention relates to a medical device inserted or removed into a living body and a method for manufacturing the medical device.

For example, medical devices such as catheters and guide wires are inserted or removed into the living body. It is known that such a medical device is required to have good operability and good lubricity when it is inserted or removed into a living body. Operability is necessary for the medical device to reach the target site in the living body, and lubricity is required to damage the surrounding tissues or cause inflammation when the medical device is placed in an organ or tissue. Necessary to avoid doing.

As such a medical device, for example, as disclosed in Patent Document 1, a medical treatment in which a resin coating layer (coating layer) containing a maleic acid-based polymer (maleic acid-based resin) is provided on the surface of a base material. The equipment is known. In this medical device, as a maleic acid-based polymer, the ratio of the peak height of the carboxylic acid salt to the total peak height of the carboxylic acid ester and the carboxylic acid when measured by infrared spectroscopy (IR method) is specified. Those limited to the range are used. As a result, the medical device (medical device) can exhibit surface lubricity in water-based liquids such as body fluids, blood, and physiological saline, and contributes to improvement in operability.

International Publication No. 2015/029641

As described above, by forming a coating layer containing a maleic acid-based polymer on the surface of a medical device, it is possible to improve the operability and lubricity of the medical device. However, according to the studies by the present inventors, it has been clarified that the performance such as operability and lubricity due to such a coating layer deteriorates with time depending on the humidity in the storage environment before use.

In Patent Document 1, a maleic acid-based polymer in which the amount of carboxylate in the molecule is adjusted to a predetermined range is used as the resin coating layer, whereby lubrication is performed not only under normal environment but also under harsh conditions. We are evaluating the ability to exhibit properties and surface lubricity. Conditions such as high temperature, low temperature, and high humidity are assumed as the harsh environment in Patent Document 1, and in the example, a temperature / humidity cycle test in which the conditions of high temperature, low temperature, and high humidity are changed in 6 steps is performed. It has been. However, it is not assumed at all whether the performance of the coating layer deteriorates with time due to the humidity of the storage environment.

The present invention has been made to solve such a problem, and in a medical device inserted into a living body and formed with a coating layer containing a maleic acid-based polymer, the coating thereof depends on the humidity of the storage environment. The purpose is to effectively suppress the risk that the sliding performance of the layer will deteriorate over time.

The medical device according to the present invention is a medical device to be inserted into a living body in order to solve the above-mentioned problems, and a coating layer containing a maleic acid-based polymer is formed on at least a part of the surface thereof. Further, a water-soluble salt whose cation is a monovalent metal ion is attached to the surface of the coating layer.

According to the above configuration, the increase in the sliding resistance value of the coating layer is suppressed by adhering a water-soluble salt in which the cation is a monovalent metal ion to the surface of the coating layer containing the maleic acid-based polymer. It becomes possible. Moreover, even if the number of slidings increases or a long period of time elapses due to the acceleration test, the increase in the sliding resistance value can be satisfactorily suppressed. Therefore, deterioration of the sliding performance of the coating layer due to the humidity of the storage environment of the medical device can be effectively suppressed.

In the medical device having the above configuration, the water-soluble salt may be an alkali metal salt.

Further, in the medical device having the above configuration, the medical device may be configured to be a catheter or a guide wire.

The method for manufacturing a medical device according to the present invention is a medical device that is inserted into a living body and has a coating layer containing a maleic acid-based polymer formed on at least a part of the surface thereof in order to solve the above-mentioned problems. Is immersed in a salt aqueous solution containing a water-soluble salt in which the cation is a monovalent metal ion.

In the method for producing the medical device, the aqueous salt solution may contain an alkali metal salt as the water-soluble salt.

Further, in the method for manufacturing a medical device having the above configuration, the medical device may have a configuration of a catheter or a guide wire.

In the present invention, in a medical device inserted into a living body and having a coating layer containing a maleic acid-based polymer formed by the above configuration, the sliding performance of the coating layer deteriorates over time due to the humidity of the storage environment. It has the effect of being able to effectively suppress the risk of this.

It is a schematic plan view which shows the structural example of the balloon catheter for vasodilation which is an example of the medical device which concerns on embodiment of this invention. (A) and (B) are scanning electron microscope (SEM) photographs showing an example of deposits adhering to the surface of a medical device, which is a typical embodiment of the present invention. It is a graph which shows the evaluation result of the sliding performance of the medical device which is a typical example and comparative example of this invention. It is a graph which shows the evaluation result of the sliding performance of the medical device which is a typical example and comparative example of this invention. It is a graph which shows the evaluation result of the sliding performance of the medical device which is a typical example and comparative example of this invention.

Hereinafter, typical embodiments of the present invention will be described with reference to the drawings. In the following, the same or corresponding elements are designated by the same reference numerals throughout all the figures, and the overlapping description thereof will be omitted.

[Medical equipment]
The medical device according to the present disclosure is not particularly limited as long as it is configured to be inserted into a body cavity. Typical examples include catheters, guide wires, dilators, sheath introducers, stylets, needles and the like. In the present disclosure, a catheter or a guide wire can be mentioned as a particularly representative of these.

Specific examples of the catheter that is the medical device according to the present disclosure include those that are inserted into a blood vessel such as a balloon catheter for vasodilation, a catheter for angiography, a thermodilution catheter, and a central venous catheter; Oral or nasal insertion into the gastrointestinal tract such as tubing catheters and feeding catheters; oral or nasal insertion into the airway or trachea such as oxygen catheters and intratracheal suction catheters; urinary tract catheters and urinary conduction catheters , Those that are inserted into the urinary tract or urinary tract such as urinary tract balloon catheters; those that are inserted into body cavities, organs or tissues such as suction catheters, drainage catheters, and rectal catheters; and the like.

In the present disclosure, a catheter inserted into a blood vessel can be mentioned as a particularly representative of these catheters, and more specifically, a balloon catheter for vasodilation can be mentioned. A vasodilator balloon catheter is used, for example, to dilate a stenotic site by inserting it into a stenotic blood vessel and inflating the balloon within the blood vessel. In the following description, for convenience, the balloon catheter for vasodilation is simply abbreviated as "balloon catheter".

The specific configuration of the balloon catheter is not particularly limited, and any known one is provided with a balloon on the distal end side that inflates or contracts when a pressure fluid is supplied or discharged from the outside. As a typical balloon catheter, an RX (Rapid Exchange) type can be mentioned. The specific configuration of the RX-type balloon catheter is not particularly limited, but typically, the configuration shown in FIG. 1 can be exemplified.

As shown in FIG. 1, the RX-type balloon catheter 10 includes a catheter body 11 and a connector 12. The catheter body 11 is configured to be inserted into a tubular tissue in the body and the tip of the catheter body 11 to reach a target site. In the configuration shown in FIG. 1, the catheter main body 11 is formed in an elongated substantially cylindrical tube, and a connector 12 is provided at a base end portion thereof. The connector 12 has an opening at the base end, and is configured so that a pressure fluid such as physiological saline can be injected from the opening. Further, the connector 12 also serves as a gripping portion, and is formed in a shape that can be gripped by the practitioner.

The catheter body 11 includes an outer shaft 13, an inner shaft 14, a balloon 15, and the like. The outer shaft 13 is an elongated substantially cylindrical tube, and is configured by, for example, connecting a metal rear end side shaft and a resin (polymer material) front end side shaft. For example, a metal core wire is arranged on the tip end side portion of the outer shaft 13 in order to improve the rigidity of the tip end side portion.

The inner shaft 14 is, for example, an elongated substantially cylindrical tube made of a resin (polymer material), and is inserted so as to extend in the axial direction of the distal end side portion of the outer shaft 13. Further, the tip of the inner shaft 14 protrudes from the outer shaft 13. A balloon 15 is provided on the tip of the inner shaft 14 so as to cover it from the outside. The balloon 15 is a bag member having a substantially tubular shape, and is formed of a thin film made of a flexible or elastic resin (polymer material). The balloon 15 is configured to inflate by injecting a pressure fluid such as physiological saline into the balloon 15.

In the configuration shown in FIG. 1, the connector 12 is provided on the side of the proximal end portion of the catheter body 11. Further, although the connector 12 has a shape that also serves as a grip portion as described above, the shape of the connector 12 is not limited to this, and various known shapes can be adopted. Further, in the configuration shown in FIG. 1, an opening (guide wire port) for inserting a guide wire is provided in the middle of the outer shaft, but an OTW (over the wire) type that communicates with the connector 12 can be adopted. can.

The balloon catheter 10 having such a configuration is first inserted into the living body along the guide wire inserted into the living body. Then, by pushing the rear end side of the balloon catheter 10, the distal end side portion of the catheter can be pushed forward. A method of using the balloon catheter 10 for vasodilation will be described by taking, for example, a case of dilating a narrowed portion of a coronary vein as an example.

A contrast medium is injected into the coronary vein in advance, and the position of the stenosis is confirmed by a contrast device. Next, the balloon catheter 10 is inserted into the coronary artery along the guide wire. When the balloon 15 reaches the narrowed portion, the balloon 15 is inflated. This allows the stenosis of the coronary vein to be dilated. If the stenosis is well dilated, the balloon 15 is deflated and the balloon catheter 10 is removed. When the balloon catheter 10 is inserted into or removed from the living body in this way, the balloon 15 having a particularly large outer diameter is slid with an organ or tissue in the living body. Therefore, it is necessary to avoid damage to surrounding tissues and suppress the occurrence of inflammation.

Further, the guide wire which is a medical device according to the present disclosure may be, for example, any one used for inserting a catheter into a living body. Therefore, examples of the specific guide wire include those used when inserting the various catheters described above into the living body, and the specific type thereof is not particularly limited. Like the catheter, the guide wire slides with an organ or tissue in the living body at the time of insertion or removal. Therefore, it is necessary to avoid damage to surrounding tissues and suppress the occurrence of inflammation.

[Water-soluble salt adhering to the coating layer and surface]
In the present disclosure, the above-mentioned medical device has a coating layer containing a maleic acid-based polymer on its surface. The coating layer may be formed on at least a part of the surface of the medical device, but may be formed on the entire surface. Examples of the surface on which the coating layer is formed include a portion that is inserted into the living body and slides (possibly). For example, if the medical device is the balloon catheter described above, at least the coating layer may be formed on the outer surface of the balloon, and the coating layer may be formed on the entire outer surface of the balloon catheter including the balloon. In general, a maleic acid-based polymer can exhibit good lubricity in a wet state in contact with a body fluid such as blood.

The maleic acid-based polymer used in the coating layer in the present disclosure may include maleic acid or a salt thereof, or a derivative thereof (maleic acids) as a unit structure. Therefore, the maleic acid-based polymer in the present disclosure may be a homopolymer composed of only one type of maleic acid-derived unit structure, or may be composed of two or more types of maleic acid-derived unit structures. It may be a copolymer of maleic acids, or it may be a copolymer composed of one or more types of maleic acid-derived unit structures and other unit structures other than maleic acids.

When the maleic acid-based polymer is a copolymer, the arrangement of the unit structure is not particularly limited, and may be random copolymerization, alternate copolymerization, block copolymerization, graft copolymerization, or a combination thereof. .. Further, when the maleic acid-based polymer is a copolymer, the composition of each unit structure (monomer constituting the unit structure) is not particularly limited, and a known composition can be preferably adopted.

As a more specific maleic acid-based polymer, for example, a polymer having a unit structure represented by the following formula (1) can be mentioned. It should be noted that m and n in the equation (1) may be independently integers of 1 or more.

As a typical maleic acid-based polymer, those having m = 1 and n = 2 in the formula (1), that is, the ethyl ester of the methyl vinyl ether maleic anhydride copolymer can be mentioned. The ethyl ester is preferably a half ethyl ester (with an esterification degree of about 50%).

The molecular weight of the maleic acid-based polymer is not particularly limited, and a known range can be preferably used. Further, the physical properties of the maleic acid-based polymer other than the molecular weight are not particularly limited, and may be any physical properties that can exhibit good lubricity when used as a coating layer of a medical device.

In the present disclosure, the coating layer formed on the medical device may be composed of only the maleic acid-based polymer, but may contain components other than the maleic acid-based polymer. For example, it may contain other polymers that can be mixed with maleic acid-based polymers (capable of forming polymer alloys), or may contain various additives known in the field of resin materials for medical devices. good.

The composition of the coating layer is also not particularly limited, and any maleic acid-based polymer may be used as the main component of the coating layer. If the coating layer is composed of only a maleic acid-based polymer, the content (content rate) of the maleic acid-based polymer is 100% by weight, but if it contains a component other than the maleic acid-based polymer, the content (content ratio) is 100% by weight. The content of the maleic acid-based polymer may be more than 50% by weight. Alternatively, when the components of the coating layer can be classified into a maleic acid-based polymer and two or more other categories, the content of the maleic acid-based polymer may be the maximum. When two or more types of maleic acid-based polymers are used in combination, the content of the maleic acid-based polymers may be the total amount of the two or more types of maleic acid-based polymers.

The medical device according to the present disclosure includes the above-mentioned coating layer, and a water-soluble salt whose cation is a monovalent metal ion is attached to the surface of the coating layer. This water-soluble salt may adhere to the entire surface of the coating layer in a layered manner, but it may be finely crystalline and dispersed and adhered to the entire surface. The form of the water-soluble salt adhering to the surface of the coating layer is not particularly limited, and may be dendritic, particulate, or other. The state in which the water-soluble salt is attached to the surface of the coating layer can be visually observed, but can be confirmed more clearly by observing with an electron microscope. When the appearance of the medical device to which the water-soluble salt is attached (the medical device according to the present disclosure) is visually observed, the surface (the surface of the coating layer) thereof is compared with the medical device to which the water-soluble salt is not attached. White turbidity derived from the attached water-soluble salt can be confirmed.

Further, when the surface to which the water-soluble salt is attached is observed with, for example, a scanning electron microscope (SEM), as described in Examples described later, typically, dendritic or spherical (spherical particle-like) deposits are observed. Can be confirmed (see Fig. 2). When the components of these deposits are analyzed, the components of the water-soluble salt are detected particularly in the dendritic deposits, as described in Examples described later. Of course, the morphology of the attached water-soluble salt is not limited to the dendritic shape as described above, but a dendritic shape can be mentioned as a typical morphology. The method for analyzing the components of the deposit is not particularly limited, and a known method can be preferably used. Typical examples include Energy Dispersive X-ray Analysis (EDS).

Here, even when the weight of the medical device to which the water-soluble salt is attached is compared with the weight of the medical device to which the water-soluble salt is not attached, there is almost no difference in the total weight. Therefore, the weight of the water-soluble salt adhering to the coating layer in the medical device according to the present disclosure is very small. In other words, in the present disclosure, even a very small amount of the water-soluble salt adhering to the coating layer of the medical device can exert a good effect.

Further, in the medical device according to the present disclosure, it is difficult to determine whether or not a water-soluble salt is attached to the coating layer based on the weight change. Therefore, as described above, the white turbidity on the surface of the medical device may be visually observed, or the presence or absence of deposits on the surface of the medical device may be observed with an electron microscope in order to determine the clearer adhesion of the water-soluble salt. May perform component analysis of the deposit as described above.

In the medical device according to the present disclosure, it is possible to effectively suppress the possibility that the sliding performance of the coating layer deteriorates over time due to the humidity of the storage environment due to the adhesion of the water-soluble salt to the surface of the coating layer. .. Therefore, the water-soluble salt may be dispersed and adhered to the surface of the coating layer, but the water-soluble salt may be adhered to the surface of the medical device on which the coating layer is not formed. As described above, the coating layer may be formed on the entire surface of the medical device, or may be formed on at least a part of the surface. When the coating layer is partially formed, the water-soluble salt may be attached only to the coating layer, or the water-soluble salt may be attached to the surface of the medical device including the coating layer.

In the medical device according to the present disclosure, the specific type of the water-soluble salt adhering to the coating layer is not particularly limited, and the cation may be a monovalent metal ion. The anion is not particularly limited. As the water-soluble salt, a known one can be preferably used as long as it does not affect the use as a medical device in any way.

As a metal that can be used as a cation of a water-soluble salt, a salt of an alkali metal can be typically mentioned. Alkali metals are the elements of Group 1 of the periodic table excluding hydrogen, and specifically, lithium, sodium, potassium, rubidium, cesium, and francium. Examples of metals other than alkali metals that can be monovalent cations include silver and copper (copper ions include monovalent Cu ⁺ and divalent Cu ²⁺ ). Among these, lithium, sodium and potassium are preferable from the viewpoint of availability and the like, and sodium and potassium are more preferable from the viewpoint of being contained in the electrolyte component in the living body.

In addition, examples of the anion of the water-soluble salt include halide ion, hydroxide ion, nitrate ion, nitrite ion, acetate ion, hydrogen carbonate ion, hydrogen phosphate ion, hydrogen sulfate ion and the like. However, it is not particularly limited. Among these, halide ions such as fluoride ion, chloride ion, bromide ion, and iodide ion are preferable from the viewpoint of availability, and chloride ion is particularly preferable from the viewpoint of being contained in the electrolyte component in the living body. ..

More specific metal salts used as water-soluble salts in the present disclosure include sodium chloride or potassium chloride. Both sodium chloride and potassium chloride are contained in the electrolyte component together with cations (sodium ion, potassium ion) and anions (chloride ion), and are easily available and relatively inexpensive. As the water-soluble salt, only one type may be used, or two or more types may be appropriately combined and used.

[Manufacturing method of medical equipment]
The method for manufacturing a medical device according to the present disclosure may include a step of adhering the above-mentioned water-soluble salt to the above-mentioned coating layer of the medical device. The specific configuration is not particularly limited, but typically includes a step of immersing the medical device on which the coating layer is formed in a salt aqueous solution containing a water-soluble salt in which the cation is a monovalent metal ion. Any manufacturing method may be used. This step is referred to as a "immersion step" for convenience of explanation.

In the dipping step, the specific composition of the aqueous salt solution is not particularly limited, and the solute may be a water-soluble salt and the solvent may be water. Further, the aqueous salt solution may contain components other than the water-soluble salt. If necessary, a water-soluble solvent other than water can be used in combination as the solvent. The concentration of the water-soluble salt is also not particularly limited, but may be in the range of 0.5 to 10.0% by weight, preferably in the range of 0.8 to 1.0% by weight.

As the water-soluble salt, as described above, sodium chloride or potassium chloride, which is an electrolyte component of a living body, can be used. In medical treatment, a physiological saline solution, which is an aqueous solution of sodium chloride having an osmotic pressure equivalent to that of a body fluid, is used, and the concentration of sodium chloride in this physiological saline solution is about 0.9% by weight. Therefore, the preferable concentration of the water-soluble salt in the aqueous salt solution can be set based on the concentration of the physiological saline solution. However, depending on various conditions such as the type of water-soluble salt, the type of maleic acid-based polymer in the coating layer, the type, shape or material of medical equipment, the manufacturing efficiency of medical equipment, the manufacturing cost, etc., the concentration of the water-soluble salt Can be set to a higher or lower concentration than in the vicinity of saline solution.

In the dipping step, the dipping conditions such as the immersion time of the medical device in the salt aqueous solution, the immersion temperature, and the like are not particularly limited. These immersion conditions are appropriately set according to various conditions such as the type of water-soluble salt, the type of maleic acid-based polymer in the coating layer, the type, shape or material of the medical device, the manufacturing efficiency of the medical device, the manufacturing cost, and the like. can do.

The method for manufacturing a medical device according to the present disclosure may include a coating layer forming step in addition to the dipping step described above. That is, the method for manufacturing a medical device according to the present disclosure may have a configuration in which a water-soluble salt is attached to a medical device having a coating layer formed in advance, or a coating layer may be attached to a medical device having no coating layer formed. It may have a structure in which a water-soluble salt is attached after the formation.

The specific configuration of the coating layer forming step is not particularly limited, and for a medical device in which the coating layer is not formed, a coating layer is formed at a required site (entire surface or a part of the surface) by a known method. Just do it. The method for forming the coating layer is also not particularly limited, and a suitable method is appropriately selected according to the material of the medical device (particularly the material of the surface on which the coating layer is formed) and the type of maleic acid-based polymer used as the coating layer. can do.

As described above, the coating layer may be one containing a maleic acid-based polymer as a main component. Therefore, as a specific method for forming the coating layer, a resin solution in which a maleic acid-based polymer is dissolved in a solvent or a liquid resin composition containing a maleic acid-based polymer is immersed in the surface of a medical device. , Spraying, coating or printing methods. The solvent used for the dendritic solution of the maleic acid-based polymer or the resin composition is not particularly limited, and a known organic solvent capable of dissolving or dispersing the maleic acid-based polymer can be used. Specific examples of the organic solvent include tetrahydrofuran (THF), acetone, methyl ethyl ketone, dimethylformamide, dimethylacetamide, dimethyl sulfoxide and the like. Only one kind of these organic solvents may be used, or two or more kinds may be appropriately used in combination.

Here, when forming the coating layer, it is preferable to react the maleic acid-based polymer with a functional group existing on the surface of the medical device to form a covalent bond. This makes it possible to prevent the coating layer from peeling off from the surface of the medical device. Specific examples of the reactive functional group capable of reacting with the molecule of the maleic acid-based polymer include an acid anhydride group, a hydroxyl group, a carboxyl group, an amino group, an isocyanate group, an epoxy group, an aldehyde group and the like. However, it is not particularly limited.

Here, examples of the material of the medical device include metal, glass, resin (polymer), ceramics, etc. However, depending on the material of the medical device, the reactive functional group may not be present on the surface thereof. be. In this case, a reactive functional group may be introduced on the surface of the medical device. The specific introduction method is not particularly limited, and a reactive functional group may be introduced by a known surface treatment, or an underlayer made of a compound having the reactive functional group may be formed. The method for forming the base layer may be the same as the specific method for forming the coating layer described above. Further, the compound having a reactive functional group is not particularly limited, and a known compound can be preferably used.

In the method for manufacturing a medical device according to the present disclosure, in addition to the above-mentioned dipping step and coating layer forming step, an alkali treatment step for treating the coating layer with an alkali may be included. This alkali treatment step is carried out before the dipping step. By alkaline treatment, the carboxyl group of the maleic acid-based polymer contained in the coating layer and the ester of the carboxyl group are converted into a carboxylate. This makes it possible to further improve the lubricity of the coating layer. The specific method of alkaline treatment is not particularly limited, and the medical device may be immersed in a known alkaline aqueous solution for a predetermined time. Various conditions such as the composition of the alkaline aqueous solution and the immersion time are not particularly limited.

Further, after the dipping step, the medical device may be allowed to stand at room temperature to be naturally dried to remove water, but a drying step may be carried out if necessary. The drying method in the drying step is not particularly limited, and it may be dried at a predetermined temperature using a known dryer or the like. That is, in the method for manufacturing a medical device according to the present disclosure, at least one of a coating layer forming step, an alkali treatment step, and a drying step may be included in addition to the dipping step described above.

As described above, in the present disclosure, a water-soluble salt whose cation is a monovalent metal ion is attached to the surface of a coating layer containing a maleic acid-based polymer, which is formed in a medical device. This makes it possible to suppress an increase in the sliding resistance value of the coating layer. Moreover, even if the number of slidings increases or a long period of time elapses due to the acceleration test, the increase in the sliding resistance value can be satisfactorily suppressed. Therefore, deterioration of the sliding performance of the coating layer can be effectively suppressed due to the humidity of the storage environment.

The present invention will be described in more detail based on Examples and Comparative Examples, but the present invention is not limited thereto. One of ordinary skill in the art can make various changes, modifications, and modifications without departing from the scope of the present invention. The evaluation test of the sliding performance in the following Examples and Comparative Examples was carried out as shown below.

(Evaluation test of sliding performance)
The sliding performance of the balloon catheter, which is a medical device obtained in the examples or comparative examples, is the method described in the example of Japanese Patent No. 4254107 using the container A, the jig B, the weight C, and the tensile tester. Evaluated by. In the following evaluation test, a silicon rubber sheet is attached to the surface of the contact portion of the container A, a vinyl chloride resin resin plate is used as the resin plate of the jig B, and the weight C is 30 g. Weight was used. The sliding resistance value was measured until the number of slidings reached 21.

(Comparative Example 1)
As a medical device, a balloon catheter equipped with a balloon made of a polyether blockamide copolymer (trade name: PEBAX7033 (registered trademark), Alchema) was used. A coating layer of methyl vinyl ether maleic anhydride copolymer half ethyl ester (MVE) was formed on the surface of the balloon of this balloon catheter, and this was used as a reference balloon catheter. Using the balloon of this reference balloon catheter as the balloon of Comparative Example 1, an evaluation test of sliding performance was carried out as described above. The result is shown by the alternate long and short dash line in FIG.

(Comparative Example 2)
By the humidification acceleration test, the reference balloon catheter was placed in a state equivalent to one year. Using the balloon of this balloon catheter as the balloon of Comparative Example 2, an evaluation test of sliding performance was carried out as described above. The result is shown by the long broken line in FIG.

(Comparative Example 3)
As in Comparative Example 2, a humidification acceleration test was performed to bring the reference balloon catheter into a state equivalent to 3 years. Using the balloon of this balloon catheter as the balloon of Comparative Example 3, an evaluation test of sliding performance was carried out as described above. The result is shown by the short broken line in FIG.

(Example 1)
The reference balloon catheter was immersed in a 0.9% aqueous solution of sodium chloride (NaCl) (physiological saline) and dried to attach sodium chloride, which is a water-soluble salt, to the surface of the coating layer.

A part of the balloon of the obtained balloon catheter was collected and used as a sample for analysis. This analytical sample was observed with a scanning electron microscope (manufactured by JEOL Ltd., trade name: JSM-6360LA) at a magnification of 650 or 900 times. The results (SEM photographs) are shown in FIGS. 2 (A) (650 times) and 2 (B) (900 times). As shown in FIGS. 2A and 2B, dendritic deposits or spherical deposits were confirmed on the surface of the balloon.

Further, the analysis sample of these deposits was subjected to EDS analysis with an energy analysis type X-ray analyzer (manufactured by JEOL Ltd., trade name: EX-2300BU). As a result, carbon, oxygen, chlorine and sodium were detected in the dendritic deposits, and carbon and oxygen were mainly detected in the spherical deposits. In some spherical deposits, silicon was detected in addition to carbon and oxygen, and trace amounts of sodium were detected.

Further, the obtained balloon catheter was put into a state equivalent to one year by a humidification acceleration test in the same manner as in Comparative Example 2. Using the balloon of this balloon catheter as the balloon of Example 1, an evaluation test of sliding performance was carried out as described above. The result is shown by the solid line in FIG.

(Example 2)
Similar to Example 1, a balloon catheter having sodium chloride adhered to the surface of the coating layer was obtained. This balloon catheter was put into a state equivalent to 3 years by a humidification acceleration test in the same manner as in Comparative Example 3. Using the balloon of this balloon catheter as the balloon of Example 2, an evaluation test of sliding performance was carried out as described above. The result is shown by the white line in FIG.

(Comparison of Comparative Examples 1 to 3 and Examples 1 and 2)
In the graph shown in FIG. 3, the horizontal axis is the number of slides (unit: times) and the vertical axis is the sliding resistance value (unit: N) (the same applies to FIGS. 4 and 5). As shown in FIG. 3, in both Example 1 (solid line) and Example 2 (white line), Comparative Example 1 (dashed line), Comparative Example 2 (long dashed line), or Comparative Example 3 (short dashed line). ), The sliding resistance value was lower. Moreover, in both Examples 1 and 2, the sliding resistance value hardly increased even if the number of slidings increased.

(Comparative Example 4)
In the same manner as in Comparative Example 1, the balloon of the reference balloon catheter was used as the balloon of Comparative Example 4, and the evaluation test of the sliding performance was carried out as described above. The result is shown by the alternate long and short dash line in FIG.

(Example 3)
A balloon catheter having sodium chloride adhered to the surface of the coating layer was obtained in the same manner as in Example 1. Using the balloon of this balloon catheter as the balloon of Example 3, an evaluation test of sliding performance was carried out as described above. The result is shown by the solid line in FIG.

(Example 4)
A water-soluble salt, potassium chloride, was adhered to the surface of the coating layer by immersing the reference balloon catheter in a 0.9% aqueous solution of potassium chloride (KCl) and drying it. The balloon of the obtained balloon catheter was used as the balloon of Example 4, and the evaluation test of the sliding performance was carried out as described above. The result is shown by the dense dotted line in FIG.

(Comparative Example 5)
A water-soluble salt, magnesium chloride, was adhered to the surface of the coating layer by immersing the reference balloon catheter in a 0.9% aqueous solution of magnesium chloride (MgCl ₂ ) and drying it. Using the obtained balloon of the balloon catheter as the balloon of Comparative Example 5, an evaluation test of sliding performance was carried out as described above. The result is shown by the coarse dotted line in FIG.

(Comparative Example 6)
A water-soluble salt, calcium chloride, was adhered to the surface of the coating layer by immersing the reference balloon catheter in a 0.9% aqueous solution of calcium chloride (CaCl ₂ ) and drying it. Using the obtained balloon of the balloon catheter as the balloon of Comparative Example 6, an evaluation test of sliding performance was carried out as described above. The result is shown by the broken line in FIG.

(Comparison of Comparative Examples 4 to 6 and Examples 3 and 4)
None of the balloons of Comparative Examples 4 to 6 and Examples 3 and 4 was subjected to the humidification acceleration test (no acceleration). As shown in FIG. 4, in both Example 3 (solid line) and Example 4 (dense dotted line), the sliding resistance value was lower than that of Comparative Example 4 (dashed line) or Comparative Example 5 (coarse dotted line). rice field. Further, in both Example 3 and Example 4, almost no increase in the sliding resistance value was observed even if the number of slidings increased.

(Comparative Example 7)
In the same manner as in Comparative Example 2, the reference balloon catheter was brought into a state equivalent to 1 year of acceleration by the humidification acceleration test. Using the balloon of this balloon catheter as the balloon of Comparative Example 7, an evaluation test of sliding performance was carried out as described above. The result is shown by the alternate long and short dash line in FIG.

(Example 5)
A balloon catheter having sodium chloride adhered to the surface of the coating layer was obtained in the same manner as in Example 3. This balloon catheter was put into a state equivalent to one year of acceleration by the above-mentioned humidification acceleration test. Using the balloon of this balloon catheter as the balloon of Example 5, an evaluation test of sliding performance was carried out as described above. The result is shown by the solid line in FIG.

(Example 6)
A balloon catheter having potassium chloride adhered to the surface of the coating layer was obtained in the same manner as in Example 4. This balloon catheter was put into a state equivalent to one year of acceleration by the above-mentioned humidification acceleration test. Using the balloon of this balloon catheter as the balloon of Example 6, an evaluation test of sliding performance was carried out as described above. The result is shown by the dense dotted line in FIG.

(Comparative Example 8)
A balloon catheter having magnesium chloride adhered to the surface of the coating layer was obtained in the same manner as in Comparative Example 5. This balloon catheter was put into a state equivalent to one year of acceleration by the above-mentioned humidification acceleration test. Using the balloon of this balloon catheter as the balloon of Comparative Example 8, an evaluation test of sliding performance was carried out as described above. The result is shown by the coarse dotted line in FIG.

(Comparative Example 9)
A balloon catheter in which calcium chloride was attached to the surface of the coating layer was obtained in the same manner as in Comparative Example 6. This balloon catheter was put into a state equivalent to one year of acceleration by the above-mentioned humidification acceleration test. Using the balloon of this balloon catheter as the balloon of Comparative Example 9, an evaluation test of sliding performance was carried out as described above. The result is shown by the broken line in FIG.

(Comparison of Comparative Examples 7 to 9 and Examples 5 and 6)
The balloons of Comparative Examples 7 to 9 and Examples 5 and 6 are all in a state equivalent to one year of acceleration by the humidification acceleration test (no acceleration). As shown in FIG. 5, in both Example 5 (solid line) and Example 6 (dense dotted line), Comparative Example 7 (dashed line), Comparative Example 8 (coarse dotted line), or Comparative Example 9 (broken line). The sliding resistance value was lower than that. Further, in both Examples 5 and 6, almost no increase in the sliding resistance value was observed even if the number of slidings increased.

As described above, from the results of Examples and Comparative Examples, when a water-soluble salt whose cation is a monovalent metal ion is attached to the coating layer containing a maleic acid-based polymer, regardless of the presence or absence of an accelerated state. It can be seen that medical devices can achieve good sliding performance. On the other hand, if the water-soluble salt is a divalent metal ion, not only the sliding performance is lower than the standard state in which the water-soluble salt is not attached, but also the sliding resistance value changes depending on the presence or absence of the accelerated state. It turns out that the tendency is not stable.

It should be noted that the present invention is not limited to the description of the above-described embodiment, and various modifications can be made within the scope of the claims, and the present invention is disclosed in different embodiments and a plurality of modifications. Embodiments obtained by appropriately combining the above technical means are also included in the technical scope of the present invention.

INDUSTRIAL APPLICABILITY The present invention can be widely and suitably used in the field of medical devices that are inserted or removed into a living body, such as a catheter or a guide wire.

10: Balloon catheter 11: Catheter body 12: Connector 13: Outer shaft 14: Inner shaft 15: Balloon

Claims (6)

A medical device that is inserted into a living body
A coating layer containing a maleic acid-based polymer is formed on at least a part of the surface thereof.
Further, the surface of the coating layer is characterized in that a water-soluble salt in which a cation is a monovalent metal ion is crystalline and adheres to the entire surface .
Medical equipment. The water-soluble salt is an alkali metal salt.
The medical device according to claim 1. The medical device is characterized by being a catheter or a guide wire.
The medical device according to claim 1 or 2. A medical device that is inserted into a living body and has a coating layer containing a maleic acid-based polymer formed on at least a part of the surface thereof , a polymer containing a water-soluble salt whose cation is a monovalent metal ion. It is characterized by including a step of immersing it in a salt aqueous solution containing no polymer and then drying it .
How to manufacture medical devices. The aqueous salt solution contains an alkali metal salt as the water-soluble salt.
The method for manufacturing a medical device according to claim 4. The medical device is characterized by being a catheter or a guide wire.
The method for manufacturing a medical device according to claim 4 or 5.

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