JP2020028640A - Method for producing medical supply and medical supply - Google Patents

Abstract

To provide a method for producing a medical supply having a lubrication layer (coating layer) that exhibits excellent durability (particularly, slide durability).SOLUTION: The present invention relates to a method for producing a medical supply having a substrate layer, and a lubrication layer supported on at least part of the substrate layer. The method includes coating the substrate layer with a solution containing a block copolymer having a hydrophobic monomer-derived constitutional unit (A) and a hydrophilic monomer-derived constitutional unit (B), a carboxylic acid compound with a molecular weight of 80 or more to less than 1,000, and a solvent.SELECTED DRAWING: None

Description

  The present invention relates to a method for manufacturing a medical device and a medical device.

  Medical devices such as catheters and guide wires that are inserted into a living body are required to exhibit excellent lubricity in order to reduce damage to tissues such as blood vessels and improve operability for operators. For this reason, a method of coating a hydrophilic polymer having lubricity on the surface of a substrate layer of a medical device has been developed and put into practical use. On the other hand, in order to maintain the operability of the medical device, it is important that the hydrophilic polymer having lubricity can be maintained on the surface of the base material layer when the operator uses the medical device. For this reason, coating with a hydrophilic polymer is required to have not only excellent lubricity but also durability against loads such as abrasion and abrasion.

  From such a viewpoint, Patent Document 1 discloses that a water-soluble or water-swellable polymer is dissolved in a solvent in which a base material of a medical device swells to prepare a polymer solution. A medical device is disclosed in which a substrate is immersed and swollen, and the polymer is crosslinked or polymerized on the surface of the substrate layer to form a surface lubricating layer on the surface of the substrate layer.

  According to the technique disclosed in Patent Document 1, it is disclosed that a surface lubricating layer exhibiting good lubricity can be fixed to a substrate.

JP-A-8-33704

  Patent Document 1 discloses that it is preferable to use, as a water-soluble or water-swellable polymer, a block copolymer including a hydrophilic portion exhibiting lubricity and a portion having an epoxy group. When such a block copolymer is used, the epoxy group of the block copolymer can be crosslinked by a heating operation to form a surface lubricating layer that is relatively difficult to peel off. However, there is a trade-off between good lubricity and excellent durability, and there is a need for a technique that achieves both good lubricity and excellent durability.

  In particular, in recent years, medical devices have been remarkably reduced in size and diameter, and medical procedures for approaching medical devices to narrower lesions in a living body with higher flexibility have been spreading. Further, with the complication of medical procedures, operation of medical devices may take a long time. Therefore, in order to maintain the operability of the device satisfactorily even in a complicated lesion site, there is a demand for a technology for further improving the lubricity maintenance (durability) of the device surface as compared with the conventional technology. More specifically, there is a demand for a device that can maintain high lubricity and has excellent sliding durability even when sliding on the device surface is repeated.

  Therefore, there is a need for a technique capable of improving the durability (particularly, sliding durability) of a medical device and supporting a medical procedure that is becoming more sophisticated.

  The present invention has been made in view of the above circumstances, and has as its object to provide a method for manufacturing a medical device having a lubricating layer (coating layer) exhibiting excellent durability (particularly, sliding durability). I do.

  The present inventors have conducted intensive studies in order to solve the above problems, and as a result, together with a block copolymer of a hydrophobic monomer and a hydrophilic monomer, a carboxylic acid compound having a specific molecular weight, It has been found that the above object can be achieved by applying a solution containing the composition on the base material layer, and the present invention has been completed.

  That is, the object is to provide a method for manufacturing a medical device comprising a base material layer and a lubricating layer supported on at least a part of the base material layer, wherein the structural unit (A) is derived from a hydrophobic monomer. A solution containing a block copolymer having a structural unit (B) derived from a hydrophilic monomer, a carboxylic acid compound having a molecular weight of 80 or more and less than 1,000, and a solvent is applied on the base layer. This is achieved by a method for manufacturing a medical device, comprising:

  According to the present invention, there is provided a method for producing a medical device having a lubricating layer (coating layer) exhibiting excellent durability (particularly sliding durability). Further, according to the present invention, there is provided a medical device having a lubricating layer (coating layer) exhibiting excellent durability (particularly, sliding durability).

FIG. 2 is a partial cross-sectional view schematically illustrating a laminated configuration on the surface of a typical embodiment of a medical device manufactured by the method according to the present invention. FIG. 2 is a partial cross-sectional view schematically showing a configuration example having a different surface lamination configuration as an application example of the embodiment of FIG. 1.

  Hereinafter, embodiments of the present invention will be described. Note that the present invention is not limited to only the following embodiments.

  A method for manufacturing a medical device according to an embodiment of the present invention is a method for manufacturing a medical device, comprising: a base layer; and a lubricating layer supported on at least a part of the base layer, the method comprising: A solution comprising a block copolymer having a structural unit (A) derived from a body and a structural unit (B) derived from a hydrophilic monomer, a carboxylic acid compound having a molecular weight of 80 or more and less than 1,000, and a solvent. On the base material layer.

  Further, a medical device according to another aspect of the present invention is a medical device including a base layer and a lubricating layer supported on at least a part of the base layer, wherein the lubricating layer has a hydrophobic property. A block copolymer having a structural unit (A) derived from a monomer and a structural unit (B) derived from a hydrophilic monomer, and a carboxylic acid compound having a molecular weight of 80 or more and less than 1,000 are included.

  In addition, in this specification, the structural unit (A) derived from a hydrophobic monomer is also simply referred to as "structural unit derived from a hydrophobic monomer" or "structural unit (A)". Similarly, the structural unit (B) derived from a hydrophilic monomer is also simply referred to as “structural unit derived from a hydrophilic monomer” or “structural unit (B)”. In addition, a block copolymer having a structural unit (A) derived from a hydrophobic monomer and a structural unit (B) derived from a hydrophilic monomer is simply referred to as a “block copolymer”, and has a molecular weight of 80 to 1,000. A carboxylic acid compound that is less than is also simply referred to as “carboxylic acid compound”.

  In the method for producing a medical device according to the present invention, a block copolymer having a structural unit derived from a hydrophobic monomer and a structural unit derived from a hydrophilic monomer, a carboxylic acid compound having a molecular weight of 80 or more and less than 1,000 And a solution containing a solvent is applied onto the base material layer. Further, the medical device according to the present invention is a block copolymer having a structural unit derived from a hydrophobic monomer and a structural unit derived from a hydrophilic monomer in a lubricating layer supported on at least a part of a base material layer. And a carboxylic acid compound having a molecular weight of 80 or more and less than 1,000. With the above configuration, the medical device manufactured by the method of the present invention and the medical device according to the present invention can exhibit excellent durability (maintenance of surface lubrication and sliding durability).

  The mechanism by which the medical device manufactured by the method according to the present invention and the medical device according to the present invention can exhibit excellent durability (maintaining surface lubrication and sliding durability) is considered as follows. The present invention is not limited to the following estimation mechanism.

  In the method for producing a medical device according to the present invention, a block copolymer having a structural unit (A) derived from a hydrophobic monomer and a structural unit (B) derived from a hydrophilic monomer is applied on a base material layer. . Thereby, a lubricating layer is formed on the base material layer. The block copolymer that forms the lubricating layer exhibits swelling properties when it comes into contact with body fluids and aqueous solvents, thus imparting lubricating properties (surface lubricity) to medical devices and causing friction with luminal walls such as blood vessel walls. To reduce.

  Here, the block copolymer forming the lubricating layer includes a block formed of the structural unit (A) (hereinafter, also referred to as a “hydrophobic unit”) and a block formed of the structural unit (B) (hereinafter, referred to as “hydrophobic unit”). "Hydrophilic unit"). In such a block copolymer, in a solution, a hydrophobic unit has a property of aggregating close to a hydrophobic unit having a similar property. Similarly, hydrophilic units have the property of agglomerating close to hydrophilic units that also have similar properties. In addition to the above properties, the presence / absence of a carboxylic acid compound having a specific molecular weight promotes proximity / aggregation between the units. More specifically, a carboxylic acid compound interacts with a hydrophobic unit or a hydrophilic unit via a hydrogen bond or the like to increase the mobility of each unit (plasticization).

  It is considered that the coating (lubricating layer) obtained by applying the solution in such a state on the base material layer has a dense network structure (network) formed by aggregation of the units of the block copolymer, It is presumed that this network structure can maintain high lubricity (surface lubricity) even after sliding for a longer period of time (that is, maintain excellent surface lubricity and improve sliding durability). Therefore, the medical device manufactured by the method according to the present invention and the medical device according to the present invention have excellent durability (surface lubrication maintaining property, sliding durability).

  Hereinafter, embodiments of the present invention will be described. Note that the present invention is not limited to only the following embodiments. In addition, the dimensional ratios in the drawings are exaggerated for convenience of description, and may be different from the actual ratios.

  In this specification, the aggregation of each unit contained in the block copolymer described above and the formation of the network structure of the block copolymer by the aggregation are referred to as “aggregation of units and polymer of the block copolymer”. It may also be referred to as "conversion."

  In this specification, “X to Y” indicating a range includes X and Y, and means “X or more and Y or less”. Unless otherwise specified, the operation, physical properties, and the like are measured under conditions of room temperature (20 to 25 ° C.) / Relative humidity of 40 to 50% RH.

<Medical device manufacturing method>
The method for producing a medical device according to the present invention comprises: a block copolymer having a structural unit (A) derived from a hydrophobic monomer and a structural unit (B) derived from a hydrophilic monomer; The method includes applying a solution containing a carboxylic acid compound having a molecular weight of less than 000 and a solvent onto the base material layer ((I) a solution applying step and a coating layer forming step). Further, if necessary, a heat treatment may be further performed after the step (I) ((II) heat treatment step). Further, after the step (II), the coating layer (coating film) may be washed ((III) washing step). Thus, by applying a solution containing a carboxylic acid compound having a specific molecular weight together with the block copolymer, a medical device having a lubricating layer (coating layer) exhibiting excellent durability can be obtained.

(I) Solution coating step (coating layer forming step)
In the method for manufacturing a medical device according to the present invention, first, a solution containing the block copolymer, the carboxylic acid compound, and a solvent (hereinafter, also simply referred to as “block copolymer solution” or “coating solution”). Is applied onto the base material layer ((I) solution coating step, coating layer forming step). The solution coating step is performed for the purpose of carrying (or coating) a lubricating layer containing a block copolymer on at least a part of the surface of the base material layer. In addition, “supported” means a state in which the lubricating layer is fixed so as not to be easily released from the surface of the base material layer, and only when the entire surface of the base material layer is completely covered by the lubricating layer. However, the present invention also includes a form in which only a part of the base material surface is covered with the lubricating layer, that is, a form in which the lubricating layer is attached to only a part of the base material surface. Therefore, the method of applying the solution is not particularly limited except that a solution containing the block copolymer having the above structural units (A) and (B), the above carboxylic acid compound, and a solvent is used. The method can be applied in the same manner as in a known method or by appropriately modifying the method.

  In the solution coating step, specifically, a solution (coating solution) is prepared by dissolving the block copolymer and the carboxylic acid compound in a solvent, and coating the solution (coating solution) on a substrate. Form a layer.

  Hereinafter, preferred embodiments of the (I) solution application step (application layer formation step) will be described in detail.

≫Preparation of block copolymer solution (coating solution) ≫
As described above, in the solution coating step (coating layer forming step), first, a block copolymer solution (coating solution) is applied in order to apply a solution containing a block copolymer, a carboxylic acid compound and a solvent onto the base material layer. Prepare.

(Block copolymer)
In the present invention, the block copolymer forms a lubricating layer supported on at least a part of the base material layer. That is, in the medical device manufactured by the method according to the present invention, the lubricating layer contains a block copolymer.

  The block copolymer in the present invention has a structural unit (A) derived from a hydrophobic monomer and a structural unit (B) derived from a hydrophilic monomer.

  The hydrophobic monomer and the hydrophilic monomer constituting the block copolymer constitute a hydrophobic unit and a hydrophilic unit, respectively. Then, due to the similarity of the properties, the hydrophobic units and the hydrophilic units aggregate respectively. On the other hand, in the random copolymer of a hydrophobic monomer and a hydrophilic monomer, since the size of the hydrophobic unit and the hydrophilic unit is small, the properties (hydrophobic and hydrophilic) of the unit are hardly exhibited. Therefore, the property that the hydrophobic units and the hydrophilic units come close to each other and agglomerate is weak or not, and the network structure is hardly formed or not formed.

  The addition of the carboxylic acid compound according to the present invention to the solution containing the block copolymer promotes aggregation of the units and polymerization of the block copolymer, so that the strength of the lubricating layer can be improved. . Specifically, the carboxylic acid compound according to the present invention enhances the mobility of the block copolymer (plasticization) to promote aggregation of units having similar properties and formation of a network structure of the block copolymer. Is presumed to have contributed to Therefore, the medical device manufactured by the method according to the present invention has excellent sliding durability and can maintain good lubricity even after sliding.

  On the other hand, a random copolymer of a hydrophobic monomer and a hydrophilic monomer has small properties of the unit (hydrophobic and hydrophilic) because the size of the hydrophobic unit and the hydrophilic unit is small. Therefore, the property that the hydrophobic units and the hydrophilic units approach and agglomerate each other as described above is weak or not, and the network structure (network) is hardly formed or not formed. Therefore, it is difficult to achieve durability (maintenance of surface lubrication, sliding durability) as required by the above-mentioned complicated and sophisticated procedure.

<< hydrophobic monomer >>
The hydrophobic monomer constituting the block copolymer will be described. In the present specification, the term “hydrophobic monomer” means that when a homopolymer having a degree of polymerization of 10 or more is produced using the monomer, the amount of the homopolymer dissolved in 100 g of water at 20 ° C. is 0%. 0.1 g or less.

  The hydrophobic monomer constituting the block copolymer is not particularly limited as long as it satisfies the above definition, and a known compound can be used. As such a hydrophobic monomer, for example, glycidyl acrylate, glycidyl methacrylate (GMA), 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl acrylate, β-methylglycidyl methacrylate (Meth) acrylate having a glycidyl group (epoxy group) such as vinyl ether having a glycidyl group (epoxy group) such as allyl glycidyl ether; methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, isopropyl acrylate, isopropyl methacrylate; n-propyl acrylate, n-propyl methacrylate, n-butyl acrylate, n-butyl methacrylate (BuMA), 2- (Meth) acrylic acid esters having an alkyl group having 1 to 24 carbon atoms such as ethylhexyl acrylate and 2-ethylhexyl methacrylate; (meth) acrylic acid esters having an aryl group having 6 to 20 carbon atoms such as phenyl acrylate and phenyl methacrylate; (Meth) acrylic acid esters having an aralkyl group having 7 to 30 carbon atoms such as benzyl acrylate and benzyl methacrylate; N-alkylacrylamides such as N-tert-butylacrylamide and N-tert-butylmethacrylamide; ethylene, propylene and isobutylene Olefins such as vinyl chloride and vinylidene chloride; aromatic vinyls such as styrene and α-methylstyrene; vinyl esters such as vinyl propionate; and the like, but are not limited thereto.

  In addition, in this specification, "(meth) acrylic acid" includes both acrylic acid and methacrylic acid. Further, “(meth) acrylate” includes both acrylate and methacrylate, and “(meth) acryloyl” includes both acryloyl and methacryloyl.

  Among them, glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, and 3,4-epoxy are preferable because it is easy to control the aggregation of units and the polymerization of the block copolymer. Cyclohexylmethyl methacrylate, β-methylglycidyl acrylate, β-methylglycidyl methacrylate; allyl glycidyl ether; methyl acrylate, methyl methacrylate, n-butyl acrylate, n-butyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, benzyl acrylate, and It is preferable to include at least one selected from the group consisting of benzyl methacrylate.

  Further, from the viewpoints of improvement in durability, adhesion to a substrate layer, ease of aggregation, and the like, glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β More preferably, it contains at least one selected from the group consisting of -methyl glycidyl acrylate, β-methyl glycidyl methacrylate, and allyl glycidyl ether. These hydrophobic monomers have an epoxy group which is a reactive group, and a heat treatment step described below is performed using a block copolymer containing a hydrophobic unit obtained from such a hydrophobic monomer. It is considered that when the reaction is carried out, the aggregation of the units and the polymerization of the block copolymer are promoted, and the crosslinking reaction of the epoxy group also proceeds. Therefore, a stronger film (lubricating layer) is formed, and the durability (particularly, sliding durability) is further improved.

  It is particularly preferred that the hydrophobic monomer is glycidyl (meth) acrylate. Such a form also has the advantage that the network structure is easier to form and easier to manufacture.

  The above hydrophobic monomers may be used alone or in combination of two or more. That is, the hydrophobic unit (hydrophobic site) derived from the hydrophobic monomer may be a homopolymer type composed of a single type of hydrophobic monomer or two types of the above-mentioned hydrophobic monomers. It may be a copolymer type composed of the above. When two or more kinds of the above-mentioned hydrophobic monomers are used, the form of the hydrophobic portion may be a block copolymer, a random copolymer, or an alternating copolymer.

《Hydrophilic monomer》
The hydrophilic monomer will be described. In the present specification, the term "hydrophilic monomer" refers to a block copolymer having a hydrophilic monomer and a structural unit derived from the hydrophobic monomer. A compound in which a polymer has a swelling property upon contact with a body fluid or an aqueous solvent and can impart lubricity (surface lubricity). By introducing such a structural unit (B) derived from a hydrophilic monomer into the block copolymer, the medical device exhibits lubricity (surface lubricity) and the medical device exhibits a lumen such as a blood vessel wall. Friction at the time of contact with a wall can be reduced.

  The hydrophilic monomer constituting the block copolymer is not particularly limited as long as it satisfies the above definition, and a known compound can be used. Such a hydrophilic monomer may be any of an anionic hydrophilic monomer, a cationic hydrophilic monomer, and a nonionic hydrophilic monomer.

  Examples of the anionic hydrophilic monomer include a carboxylic acid group-containing monomer such as acrylic acid, methacrylic acid, and maleic acid; a sulfonic acid group-containing monomer such as 2-acrylamido-2-methylpropanesulfonic acid;

  Examples of the cationic hydrophilic monomer include quaternary base-containing monomers such as (meth) acryloyloxyethyltrimethylammonium salt, (3-acryloylaminopropyl) trimethylammonium salt, and (3-methacryloylaminopropyl) trimethylammonium salt; Is mentioned.

  Non-ionic hydrophilic monomers include N-methylacrylamide, N, N-dimethylacrylamide (DMAA), N-ethylacrylamide, N, N-diethylacrylamide (DEAA), N, N-dimethylaminopropylacrylamide, N, N-dimethylaminopropyl methacrylamide, acrylamide, N, N-dimethylaminoethyl acrylate, N, N-dimethylaminoethyl methacrylate, N-vinyl-2-pyrrolidone, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, 3-hydroxypropyl acrylate, 3-hydroxypropyl methacrylate, polyethylene glycol monoacrylate, polyethylene glycol monomethacrylate, alkoxypolyethylene glycol monoacrylate DOO, alkoxy polyethylene glycol monomethacrylate, and the like, but is not limited thereto.

  Among these, N, N-dimethylacrylamide, N, N-diethylacrylamide, acrylamide, and the like are preferred from the viewpoints of imparting excellent lubricity, easiness of synthesis and operability, and easy aggregation. , N-vinyl-2-pyrrolidone, 2-hydroxyethyl acrylate and 2-hydroxyethyl methacrylate. In light of imparting excellent lubricity and easiness of aggregation, the hydrophilic monomer is more preferably N, N-dimethylacrylamide or N, N-diethylacrylamide, and particularly preferably N, N-dimethylacrylamide. .

  The above hydrophilic monomers may be used alone or in a combination of two or more. That is, the hydrophilic unit (hydrophilic site) derived from the hydrophilic monomer may be a homopolymer type composed of one type of hydrophilic monomer alone, or two types of the above hydrophilic monomers. It may be a copolymer type composed of the above. When two or more kinds of the above hydrophilic monomers are used, the form of the hydrophilic portion may be a block copolymer, a random copolymer, or an alternating copolymer.

<< Ratio of structural units (composition ratio) >>
The ratio (composition ratio) between the structural unit (A) and the structural unit (B) in the block copolymer is not particularly limited as long as the above-mentioned effect is obtained. Considering good lubricity, lubricity maintenance property, slidability, sliding durability, strength of the coating layer, adhesion to the substrate layer, etc., the ratio of the structural unit (A) to the structural unit (B) ( The molar ratio of the structural unit (A): the structural unit (B)) is preferably 1: 2 to 1: 100, more preferably 1: 5 to 1:50, and 1:10 to 1: More preferably, it is 20. Within such a range, the lubricating layer can sufficiently exhibit lubricity by the structural unit (B), and the structural unit (A) can provide sufficient strength of the coating layer, adhesion to the base material layer, and durability. Can be demonstrated. The molar ratio of the structural unit (A) to the structural unit (B) can be controlled by adjusting the charge ratio (molar ratio) of each monomer in the step of producing the block copolymer. At this time, the charge ratio (molar ratio) of the hydrophobic monomer and the hydrophilic monomer in the step of producing the block copolymer is preferably 1: 2 to 1: 100, and is preferably 1: 5 to 1: 1. : 50, more preferably 1:10 to 1:20. Furthermore, the structural units (A): the molar ratio of the constituent unit (B), for example, the copolymer NMR measurement ⁽¹ H-NMR ^measurement, 13 C-NMR measurement and the like) can be confirmed by performing .

<< Weight average molecular weight (Mw) of block copolymer >>
The weight average molecular weight of the block copolymer is not particularly limited, but is preferably 10,000 to 10,000,000 from the viewpoint of solubility. The weight average molecular weight of the block copolymer is more preferably from 100,000 to 5,000,000 from the viewpoint of easy preparation of the block copolymer solution (coating solution). In the present specification, the “weight average molecular weight” is a value measured by gel permeation chromatography (GPC) using polystyrene as a standard substance.

<< Production method of block copolymer >>
The method for producing the block copolymer is not particularly limited, and the block copolymer can be produced by applying a conventionally known polymerization method such as a living radical polymerization method, a polymerization method using a macroinitiator, or a polycondensation method. Among these, the living radical polymerization method or the method of controlling the molecular weight and molecular weight distribution of the structural unit (site) derived from a hydrophobic monomer and the structural unit (site) derived from a hydrophilic monomer is easy. A polymerization method using a macroinitiator is preferably used. The living radical polymerization method is not particularly limited. For example, the methods described in JP-A-11-263819, JP-A-2002-145971, JP-A-2006-316169, etc., and atom transfer radical polymerization (ATRP) ) Method can be applied in the same manner or with appropriate modification. Further, in the polymerization method using a macroinitiator, for example, after preparing a macroinitiator having a hydrophobic portion having a hydrophobic functional group and a radical polymerizable group such as a peroxide group, the macroinitiator and To produce a block copolymer having a hydrophilic site (hydrophilic unit) and a hydrophobic site (hydrophobic unit) by polymerizing a monomer for forming a hydrophilic site (hydrophilic unit). Can be.

  In the polymerization of the block copolymer, known methods such as bulk polymerization, suspension polymerization, emulsion polymerization, and solution polymerization can be used. Specifically, in the production of the block copolymer, solution polymerization in which a hydrophobic monomer and a hydrophilic monomer are copolymerized by stirring and heating together with a polymerization initiator in a polymerization solvent can be applied. Here, the polymerization initiator is not particularly limited, and a known initiator may be used. Further, the polymerization solvent is not particularly limited, for example, n-hexane, n-heptane, n-octane, n-decane, cyclohexane, methylcyclohexane, aliphatic organic solvents such as liquid paraffin, tetrahydrofuran, dioxane and the like Ether solvents, aromatic organic solvents such as benzene, toluene, and xylene, halogen-based organic solvents such as 1,2-dichloroethane and chlorobenzene, and polar aprotic organic solvents such as N, N-dimethylformamide and dimethyl sulfoxide. Can be used. The polymerization solvent may be used alone or in combination of two or more.

  The concentration of the monomer in the polymerization solvent (the total concentration of the hydrophilic monomer and the hydrophobic monomer) is preferably from 3 to 90% by mass, more preferably from 5 to 80% by mass, and preferably from 8 to 80% by mass. It is particularly preferred that the content be 50% by mass.

  In the above polymerization, the polymerization conditions are also not particularly limited as long as the above copolymerization proceeds. For example, the polymerization temperature is preferably 30 to 150 ° C, more preferably 40 to 100 ° C, and the polymerization time is preferably 30 minutes to 30 hours, more preferably 3 to 24 hours.

  Further, at the time of copolymerization, if necessary, a chain transfer agent, a polymerization rate regulator, a surfactant, a water-soluble polymer, a water-soluble inorganic compound (alkali metal salt, alkali metal hydroxide, polyvalent metal salt) , And non-reducing alkali metal salts such as pH buffers), inorganic acids, inorganic acid salts, organic acids and organic acid salts, and other additives may be used as appropriate.

  The block copolymer after the copolymerization is preferably purified by a general purification method such as a reprecipitation method, a dialysis method, an ultrafiltration method, and an extraction method.

(Carboxylic acid compound)
In the present invention, the carboxylic acid compound enhances the mobility of each unit of the block copolymer, and facilitates aggregation of the units and polymerization of the block copolymer. As a result, a strong lubricating layer can be formed, and excellent durability (sliding durability) can be obtained.

  The carboxylic acid compound according to the present invention has a molecular weight of 80 or more and less than 1,000. In addition, in this specification, a "carboxylic acid compound" means the compound which has one or more carboxyl groups in a molecule | numerator, or its salt. When the molecular weight of the carboxylic acid compound is less than 80, the carboxylic acid compound volatilizes immediately from the lubricating layer during coating or during the heat treatment (II) described below, and the effect of improving the durability of the lubricating layer is not sufficient. Can not be obtained. On the other hand, when the molecular weight of the carboxylic acid compound is 1,000 or more, the effect of increasing the mobility of the block copolymer as described above is reduced, and the effect of improving the sliding durability of the coating film (lubricating layer) is sufficiently obtained. I can't get it. In the case of performing the washing step (III) described below, the carboxylic acid compound cannot be sufficiently removed, and the slidability of the lubricating layer in the initial stage (before repeated sliding) decreases.

  From the viewpoint of forming a lubricating layer having more excellent durability (sliding durability), the molecular weight of the carboxylic acid compound is preferably more than 80 and less than 500, more preferably 85 or more and 400 or less, It is particularly preferred that it is more than 85 and less than 300, most preferably 88 or more and 145 or less.

  The carboxylic acid compound according to the present invention is not particularly limited as long as it is a carboxylic acid having the above specific molecular weight and a salt thereof. As the carboxylic acid compound, aliphatic carboxylic acids (cyclic (alicyclic) aliphatic carboxylic acids, chain (acyclic) aliphatic carboxylic acids) and aromatic carboxylic acids and salts thereof can be used. . Among them, from the viewpoint of forming a lubricating layer having more excellent durability (sliding durability), the carboxylic acid compound is composed of a cyclic (alicyclic) aliphatic carboxylic acid and a chain (acyclic). And more preferably selected from linear (non-cyclic) aliphatic carboxylic acids and salts thereof.

  The linear (acyclic) aliphatic carboxylic acid may be a saturated carboxylic acid, an unsaturated carboxylic acid, or a linear (linear aliphatic carboxylic acid). Or a branched type (branched aliphatic carboxylic acid). Among them, from the viewpoint of forming a lubricating layer having more excellent durability (sliding durability), the carboxylic acid compound according to the present invention comprises a linear (linear aliphatic carboxylic acid) and a salt thereof. It is preferable to be selected.

  The carboxylic acid compound according to the present invention may have a substituent other than a carboxyl group. Examples of such a substituent include a hydroxy group, a nitro group, and a cyano group. Among them, the carboxylic acid compound preferably has a hydroxy group. That is, the carboxylic acid compound is preferably selected from compounds (hydroxy acids) each containing at least one hydroxy group and one or more carboxyl groups in the molecule, and salts thereof. It is presumed that such a carboxylic acid compound easily interacts with the block copolymer via a hydrogen bond or the like and easily improves the mobility of the hydrophobic unit / hydrophilic unit. Therefore, a dense network structure (network) is easily formed by agglomeration of each unit of the block copolymer, and a lubricating layer having more excellent durability (sliding durability) can be formed. The mechanism is based on a guess, and the technical scope of the present invention is not affected by the correctness.

  Regarding the carboxylic acid compound according to the present invention, the number of carboxyl groups contained in one molecule is not particularly limited, and any one of monocarboxylic acid, dicarboxylic acid, polycarboxylic acid having three or more carboxyl groups, and salts thereof. Can also be used. Among them, from the viewpoint of forming a lubricating layer having more excellent durability (sliding durability), the carboxylic acid compound is preferably selected from the group consisting of monocarboxylic acids and dicarboxylic acids and salts thereof, More preferably, it is selected from monocarboxylic acids and salts thereof. In particular, by using a monocarboxylic acid or a salt thereof, an effect of improving the slidability of the lubricating layer at an initial stage (before repeated sliding) can be obtained.

  The number of carbon atoms contained in the carboxylic acid compound is not particularly limited as long as the above-mentioned molecular weight is satisfied. For example, the number of carbon atoms contained in the carboxylic acid compound is preferably 2 to 30, more preferably 2 to 20, particularly preferably 3 to 15, and most preferably 3 to 5. Within such a range, the effect of increasing the mobility of the block copolymer as described above is further improved, and the effect of improving the sliding durability of the coating film (lubricating layer) is easily obtained.

Specific examples of the carboxylic acid compound include butyric acid, valeric acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, stearic acid, arachidic acid, behenic acid, cerotic acid, Saturated aliphatic monocarboxylic acids such as heptacosanoic acid, montanic acid, melicic acid, laccelic acid, tetracontanic acid, pentacontanic acid, cyclopentanecarboxylic acid and cyclohexanecarboxylic acid;
Unsaturated aliphatic monocarboxylic acids such as sorbic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid;
Saturated aliphatic dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, sebacic acid, brassic acid, fumaric acid, maleic acid, cyclohexanedicarboxylic acid, dicyclohexanedicarboxylic acid;
Unsaturated aliphatic dicarboxylic acids such as maleic acid, fumaric acid, citraconic acid, mesaconic acid;
Aromatic carboxylic acids such as benzoic acid, cinnamic acid, phthalic acid, terephthalic acid, isophthalic acid and naphthalenedicarboxylic acid;
Trivalent or higher polyvalent carboxylic acids such as trimellitic acid, pyromellitic acid, and melitic acid;
Aliphatic hydroxy acids such as lactic acid, tartronic acid, glyceric acid, hydroxybutyric acid, malic acid, tartaric acid, citric acid, isocitric acid, gluconic acid;
Aromatic hydroxy acids such as salicylic acid, vanillic acid, gallic acid, mandelic acid, benzylic acid, melilotic acid (3- (2-hydroxyphenyl) propanoic acid) and 4-hydroxymethylbenzoic acid;
And the like.

  Further, as described above, in the carboxylic acid compound, the carboxyl group of each of the above carboxylic acids may be in the form of a salt. Examples of the salt include alkali metal salts such as sodium salt and potassium salt, and salts of Group 2 elements such as calcium salt and magnesium salt.

  The above carboxylic acid compounds may be used alone or in combination of two or more. In addition, as the carboxylic acid compound, a synthetic product or a commercially available product may be used.

  Among the above-mentioned carboxylic acid compounds, it is preferable to be selected from the group consisting of hydroxy acids and aliphatic carboxylic acids and salts thereof from the viewpoint of improving the durability of the lubricating layer and biosafety. Further, from the same viewpoint, the aliphatic carboxylic acid is more preferably a fatty acid (monocarboxylic acid). That is, the carboxylic acid compound is preferably selected from the group consisting of hydroxy acids, fatty acids, and salts thereof. By using these carboxylic acid compounds, it becomes easier to form a dense network structure (network) due to aggregation of each unit of the block copolymer, and a lubricating layer having more excellent durability (sliding durability) is obtained. Can be formed.

  Further, the carboxylic acid compound according to the present invention is more preferably selected from the group consisting of hydroxy acids, unsaturated fatty acids, and salts thereof from the viewpoint of improving the durability of the lubricating layer and biosafety. Furthermore, the unsaturated fatty acid may be any of a short-chain fatty acid (4 or less carbon atoms), a medium-chain fatty acid (5 to 11 carbon atoms), and a long-chain fatty acid (12 or more carbon atoms). It is good, but from the viewpoint that the effects of the present invention can be more easily obtained, a long-chain fatty acid is preferable.

  Accordingly, the carboxylic acid compound in the present invention includes hydroxy acids such as lactic acid, glyceric acid, hydroxybutyric acid, malic acid, tartaric acid, citric acid and gluconic acid; long-chain unsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid; Are preferred.

  In particular, a lubricating layer that easily interacts with the block copolymer, facilitates formation of a dense network structure (network) by agglomeration of each unit of the block copolymer, and has better durability (sliding durability). From the viewpoint of forming carboxylic acid, the carboxylic acid compound is particularly preferably selected from hydroxy acids and salts thereof. From the viewpoint of improving the durability of the lubricating layer and biosafety, among the hydroxy acids, lactic acid, malic acid, tartaric acid, citric acid, gluconic acid and salts thereof are preferred, and lactic acid and salts thereof are particularly preferred.

(solvent)
In the present invention, for the purpose of uniformly supporting the block copolymer on the base material layer, a uniform solution containing the block copolymer and the carboxylic acid compound is prepared, and the solution (coating solution) is coated on the base material layer. Apply on top.

  The solvent used for dissolving the block copolymer and the carboxylic acid compound according to the present invention is not particularly limited as long as the solvent can dissolve the block copolymer and the carboxylic acid compound according to the present invention. Specifically, water, alcohols such as methanol, ethanol, isopropanol and ethylene glycol, ketones such as acetone, methyl ethyl ketone and cyclohexanone, esters such as ethyl acetate, halides such as chloroform, olefins such as hexane, tetrahydrofuran (THF), ethers such as butyl ether, aromatics such as benzene and toluene, amides such as N, N-dimethylformamide (DMF), and sulfoxides such as dimethylsulfoxide. There is no restriction. These may be used alone or in combination of two or more. Above all, from the viewpoint that the block copolymer and the carboxylic acid compound can be uniformly dissolved and the solution can be uniformly applied, ketones such as acetone and amides such as DMF are used as the solvent of the solution (coating solution). Acetone and DMF are particularly preferred.

(Other ingredients)
The block copolymer solution (coating solution) for forming the lubricating layer may contain other components in addition to the block copolymer, the carboxylic acid compound, and the solvent. Other components are not particularly limited, for example, when the medical device is intended to be inserted into a body cavity or lumen such as a catheter, an anticancer agent, an immunosuppressant, an antibiotic, an antirheumatic drug, an antithrombotic agent Drug, HMG-CoA reductase inhibitor, ACE inhibitor, calcium antagonist, antihyperlipidemic agent, integrin inhibitor, antiallergic agent, antioxidant, GPIIb / IIIa antagonist, retinoid, flavonoid, carotenoid, lipid Drugs (bioactive substances) such as ameliorating drugs, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet drugs, vascular smooth muscle growth inhibitors, anti-inflammatory drugs, biological materials, interferons, and NO production promoting substances Can be Here, the addition amount of the other components is not particularly limited, and the amount usually used is similarly applied. Ultimately, the amount of other components to be added is appropriately selected in consideration of the severity of the disease to be applied, the weight of the patient, and the like.

(Preparation of block copolymer solution (coating solution))
A block copolymer solution (coating solution) is prepared using the above-mentioned block copolymer, carboxylic acid compound and solvent. The order of addition of the above components and the method of addition are not particularly limited. The above components may be added all at once or separately, stepwise or continuously. The mixing method is not particularly limited, and a known method can be used. A preferred method for preparing a block copolymer solution (coating solution) includes sequentially adding a block copolymer and a carboxylic acid compound to a solvent, followed by stirring in the solvent.

  The concentration of the block copolymer in the block copolymer solution (coating solution) is not particularly limited. From the viewpoint of further improving coatability, lubricity and durability of the lubricating layer, the concentration of the block copolymer in the solution (coating solution) is preferably 0.01 to 20% by mass, and 0.1 to 20% by mass. It is more preferably from 0.5 to 15% by mass, and still more preferably from 1% by mass to less than 15% by mass. When the concentration of the block copolymer is within the above range, the lubricating layer obtained can exhibit sufficient lubricity and durability. In addition, a uniform lubricating layer having a desired thickness can be easily obtained by one coating, and the viscosity of the solution is within an appropriate range, so that operability (for example, ease of coating) and production efficiency are improved. It is preferred in that respect. However, even if it deviates from the above range, it can be sufficiently used as long as it does not affect the operation and effect of the present invention.

  The concentration of the carboxylic acid compound in the block copolymer solution (coating solution) is also not particularly limited. From the viewpoint that the aggregation of the units and the polymerization of the block copolymer sufficiently proceed, but not excessively (the aggregation and the polymerization can be appropriately promoted), the solution (coating solution) Is preferably 0.05 to 30% by mass, more preferably 0.1 to 20% by mass, still more preferably 1 to 15% by mass, more preferably 1.5 to 15% by mass. It is particularly preferable that the amount is at least 20% by mass and less than 15% by mass, and it is most preferable that the amount be 2 to 10% by mass. When the concentration of the carboxylic acid compound is in the above range, the lubrication and durability of the obtained lubricating layer can be sufficiently exhibited. However, even if it deviates from the above range, it can be sufficiently used as long as it does not affect the operation and effect of the present invention.

  Furthermore, the mixing ratio of the block copolymer and the carboxylic acid compound in the block copolymer solution (coating solution) is not particularly limited. From the viewpoint of further improving the applicability, the lubricity and durability of the lubricating layer, the solution (coating solution) contains the block copolymer and the carboxylic acid compound in an amount of 100: 0.5 or more and 100: 200 or less ( Block copolymer: carboxylic acid compound (by mass, hereinafter the same)), more preferably 100: 1 or more and 100: 200 or less (mass ratio), more preferably more than 100: 1 and 100: 110. It is more preferable that it is contained at less than (mass ratio), even more preferably it is contained at 100: 10 or more and 100: 105 or less (mass ratio), and is contained at 100: 20 or more and 100: 100 or less (mass ratio). Is particularly preferred, and most preferably 100: 50 or more and 100: 100 or less (mass ratio). When the mass ratio of the block copolymer and the carboxylic acid compound is in the above range, the lubricating layer obtained can sufficiently exhibit lubricity and durability. In addition, since the carboxylic acid compound can be efficiently removed in the washing step described later, the lubricity of the lubricating layer is also improved. In particular, by setting the mass ratio of the block copolymer to the carboxylic acid compound to be less than 100: 110, more preferably 100: 105 or less, and even more preferably 100: 100 or less, the mass ratio between the base material layer and the lubricating layer is reduced. The entry of the carboxylic acid compound can be suppressed, and the adhesion between the block copolymer and the base material layer can be further improved.

≫Application of block copolymer solution (coating solution) ≫
Next, as described above, a solution (coating solution) containing the block copolymer, the carboxylic acid compound, and the solvent is prepared, and the solution is applied onto the base material layer.

  The base layer may be made of any material, and examples thereof include a metal material, a polymer material (a resin material or an elastomer material), and ceramics.

  Among the materials constituting the base layer, the metal material is not particularly limited, and a metal material generally used for medical devices such as a catheter, a guide wire, and an indwelling needle is used. Specifically, various stainless steels such as SUS304, SUS314, SUS316, SUS316L, SUS420J2, SUS630, gold, platinum, silver, copper, nickel, cobalt, titanium, iron, aluminum, tin or nickel-titanium alloy, nickel-cobalt Alloys, various alloys such as a cobalt-chromium alloy and a zinc-tungsten alloy. These may be used alone or in combination of two or more. As the metal material, an optimum metal material may be appropriately selected as a base material layer for a catheter, a guide wire, an indwelling needle, and the like, which are used.

  Among the materials constituting the base layer, the polymer material (resin material or elastomer material) is not particularly limited, and is generally used for medical devices such as catheters, introducers, guide wires, and indwelling needles. A commonly used polymer material is used. Specifically, polyolefin resins such as polyamide resin, polyethylene resin and polypropylene resin, modified polyolefin resin, cyclic polyolefin resin, epoxy resin, polyurethane resin, diallyl phthalate resin (allyl resin), polycarbonate resin, fluorine resin, amino resin (urea Resin, melamine resin, benzoguanamine resin), polyester resin such as polyethylene terephthalate resin, polybutylene terephthalate resin, styrene resin, acrylic resin, polyacetal resin, vinyl acetate resin, phenol resin, vinyl chloride resin, silicone resin (silicon resin), poly Resins such as an ether resin and a polyimide resin are exemplified.

  In addition, thermoplastic elastomers such as polyurethane elastomer, polyester elastomer, and polyamide elastomer can also be used as the material of the base layer.

  These polymer materials may be used alone or as a mixture of two or more thereof or as a copolymer of two or more monomers constituting any of the above resins or elastomers. Among them, the polymer material is preferably a polyethylene resin, a polyurethane resin, a polyethylene terephthalate resin, a polyamide resin, or a polyamide elastomer. These polymer materials are relatively soft, and it can be said that the block copolymer constituting the lubricating layer easily permeates. Therefore, the interaction between the polymer material and the block copolymer is enhanced, and a more durable lubricating layer can be formed. As the above-mentioned polymer material, an optimum polymer material may be appropriately selected as a base material layer of a catheter, a guide wire, an indwelling needle, and the like, which are used.

  As described below, the method for manufacturing a medical device according to the present invention includes the steps of agglomerating units and block copolymerization even when a block copolymer solution (coating solution) is applied and then maintained at a relatively low temperature. The polymerization of the coalescence proceeds, and a lubricating layer having excellent sliding durability can be formed. In other words, the effect that the temperature at which the lubricating layer is fixed on the base material layer can be reduced is also exhibited. Therefore, in the method for manufacturing a medical device according to the present invention, a polymer material (a resin material or an elastomer material) is suitably used as a constituent material of the base layer. According to the present invention, since the lubricating layer can be fixed at a low temperature, even if the base material layer contains a polymer material that is easily deformed or plasticized by heat, deformation and plasticization of the base material layer are suppressed, and dimensional stability is improved. Is improved.

  Further, the shape of the base material layer is not particularly limited, and is appropriately selected depending on a use mode such as a sheet shape, a linear shape (wire), and a tubular shape.

  The method of applying (coating) the block copolymer solution (coating solution) on the surface of the base material layer is not particularly limited, and the application / printing method, the dipping method (dipping method, dip coating method), and the spraying method (spray method). Conventionally known methods such as spin coating, mixed solution impregnated sponge coating, bar coating, die coating, reverse coating, comma coating, gravure coating, and doctor knife can be applied.

  When a lubricating layer is formed on a thin and narrow inner surface of a catheter, injection needle, or the like, the base layer may be immersed in a coating solution, and the inside of the system may be depressurized and defoamed. By defoaming under reduced pressure, the solution can be quickly penetrated into the narrow and narrow inner surface, and the formation of a lubricating layer can be promoted.

  In addition, when forming a lubricating layer only on a part of the base material layer, only part of the base material layer is immersed in the coating liquid, and the coating liquid is coated on a part of the base material layer. A lubricating layer can be formed on a desired surface portion of the base material layer.

  When it is difficult to immerse only a part of the base material layer in the coating liquid, an appropriate member or material capable of attaching / detaching (attaching / detaching) the surface part of the base material layer which does not need to form a lubricant layer in advance. After protecting (coating, etc.) with the coating solution, the base material layer is immersed in the coating solution, and the coating solution is coated on the base material layer. The lubricating layer can be formed on a desired surface portion of the base material layer by removing the (material) and then causing the material to react by heat treatment or the like. However, in the present invention, the formation method is not limited at all, and a lubricating layer can be formed by appropriately using a conventionally known method. For example, when it is difficult to immerse only a part of the base material layer in the mixed solution, instead of the immersion method, another coating method (for example, a coating liquid is applied to a predetermined surface portion of a medical device, A coating method using a coating device such as a spray device, a bar coater, a die coater, a reverse coater, a comma coater, a gravure coater, a spray coater, or a doctor knife) may be applied. If both the outer surface and the inner surface of the cylindrical device need to have a lubricating layer due to the structure of the medical device, it is necessary to coat both the outer surface and the inner surface at once. In this respect, the dipping method (dipping method) is preferably used.

  The coating amount of the block copolymer solution (coating solution) is preferably such that the thickness of the resulting coating (lubricating layer) is 0.1 to 10 μm, and is preferably 0.5 to 5 μm. Is more preferable, and the amount is more preferably 1 to 3 μm. When the coating amount is such that the thickness of the coating (lubricating layer) is 0.1 μm or more, the durability of the obtained coating (lubricating layer) can be sufficiently achieved. If the coating amount is such that the thickness of the coating (lubricating layer) is 10 μm or less, the surface of the coating (lubricating layer) is less likely to be sticky, and handling during production becomes easier. Preferably, the amount is such that

(II) Heat Treatment Step In the method for producing a medical device according to the present invention, a heat treatment step may be performed after forming a coating layer by applying a block copolymer solution (coat liquid) on the base material layer. The heat treatment step can further promote aggregation of the units and polymerization of the block copolymer. That is, in the method for manufacturing a medical device according to the present invention, it is preferable to perform a heat treatment step.

  In addition, when a monomer having an epoxy group is used as the hydrophobic monomer constituting the hydrophobic unit of the block copolymer, it is considered that a crosslinking reaction of the epoxy group proceeds in this step. Therefore, a stronger film (lubricating layer) is formed, and the sliding durability is further improved.

  Hereinafter, a preferred embodiment of the heat treatment step (II) of the block copolymer solution (coating solution) will be described in detail.

  In the above (I) solution application step, it is preferable to perform a heat treatment after applying a solution (coating solution) containing the block copolymer and the carboxylic acid compound onto the base material layer.

  The temperature of the heat treatment is not particularly limited, but is preferably from 10 to 200 ° C. That is, after applying the block copolymer solution on the base material layer (after forming the coating layer), it is more preferable to maintain the coating layer at 10 to 200 ° C. By maintaining at such a temperature, aggregation of units and polymerization of the block copolymer are effectively promoted, and a strong coating layer (lubricating layer) is formed. Therefore, high lubricity (surface lubricity) can be maintained for a longer period. In addition, by maintaining the temperature at such a temperature, it is possible to suppress the aggregation of the units and the polymerization of the block copolymer from excessively progressing. Therefore, it is possible to suppress a decrease in swelling caused by the lubricating layer becoming too hard, and as a result, it is possible to maintain good lubricity (surface lubricity).

  Furthermore, after applying the block copolymer solution onto the base material layer (after forming the coating layer), it is more preferable to maintain the coating layer at 150 ° C or lower, more preferably to maintain the coating layer at 25 to 150 ° C, It is particularly preferable to maintain the temperature at 60 ° C. or more, and most preferably to maintain the temperature at 60 ° C. or more and less than 100 ° C. By maintaining at such a temperature, excellent lubricity can be exhibited and a lubricating layer having high durability can be formed. In particular, when the temperature is set to 100 ° C. or lower (further less than 100 ° C.), even if the heat treatment is performed for a long time, the aggregation of the units and the polymerization of the block copolymer are performed without giving an excessive heat load to the base material layer The lubricating property can be easily imparted and controlled even with a substrate having relatively low heat resistance. The temperature may be changed during the heat treatment.

  In the production method according to the present invention, as described above, after the block copolymer solution (coating solution) is applied, the temperature is maintained at a relatively low temperature, for example, 80 ° C. or lower, and more preferably 25 to 80 ° C. However, one of the features is that a lubricating layer having high durability can be formed. Thus, there is an advantage that even a polymer material which is easily deformed or plasticized by heat can be used as a base material layer. Therefore, according to the present invention, the selectivity of the material is further increased, and medical devices for various uses can be manufactured. Further, since a lubricating layer having excellent durability can be formed at a low temperature, it is preferable from the viewpoint of energy cost when manufacturing a medical device.

  The heat treatment time is not particularly limited, but is preferably 30 minutes to 30 hours, more preferably 1 to 25 hours, further preferably 2 to 24 hours, and particularly preferably 3 to 10 hours. By setting such a time, aggregation of the units and polymerization of the block copolymer are effectively promoted, and a strong coating layer (lubricating layer) is formed. Therefore, high lubricity (surface lubricity) can be maintained for a longer period. In addition, by setting the time as described above, it is possible to suppress the aggregation of the units and the polymerization of the block copolymer from excessively progressing. Therefore, it is possible to suppress a decrease in swelling caused by the lubricating layer becoming too hard, and as a result, it is possible to maintain good lubricity (surface lubricity).

  The pressure conditions during the heat treatment are not limited at all, and the heat treatment may be performed under normal pressure (atmospheric pressure), or may be performed under increased or reduced pressure.

  As the heating means (apparatus), if necessary, for example, an oven, a reduced pressure drier, or the like can be used.

(III) Cleaning Step In the method for manufacturing a medical device according to the present invention, after the above-mentioned (I) solution coating step or optional (II) heat treatment step, the coating (lubricating layer) provided on the base material layer is removed. Washing ((III) washing step). The cleaning step is performed for the purpose of efficiently removing the carboxylic acid compound contained in the film (lubricating layer) and imparting more excellent lubricity (low friction) to the film (lubricating layer).

  Hereinafter, a preferred embodiment of the washing step (III) will be described in detail.

  The washing method is not particularly limited, but a method of immersing the coating (lubricating layer) of the block copolymer in the washing solvent, a method of flowing the washing solvent, or a combination thereof may be used. The washing solvent used at this time is not particularly limited as long as it does not dissolve the film (lubricating layer) of the block copolymer and can efficiently remove the carboxylic acid compound. It is preferably used. The temperature of the washing water is not particularly limited, but is preferably from 20C to 100C, and more preferably from 25C to 80C. The washing time (the time for bringing the washing solvent into contact with the coating) is not particularly limited, but is preferably 30 seconds to 60 minutes, more preferably 1 to 30 minutes. According to the above conditions, the carboxylic acid compound can be efficiently removed. As a result, the lubricating layer formed on the base material layer can exhibit excellent lubricity.

  After the washing step, a drying step may be further performed. The drying method and drying conditions (temperature, time, etc.) are not particularly limited, and a conventionally known method can be used.

The medical device manufactured by the method according to the present invention is characterized in that a lubricating layer is formed by applying a solution (coating solution) containing a block copolymer and a carboxylic acid compound forming a lubricating layer onto the substrate layer. It has a configuration carried on it. Whether or not a carboxylic acid compound is contained in the lubricating layer can be confirmed by the following method. That is, was extracted lubricating layer using an organic solvent such as heavy chloroform, the resulting solution extracted ^NMR (1 H-NMR measurement, ^{13 C-NMR} measurement and the like) were analyzed by a peak derived from a carboxylic acid compound It can be confirmed by detecting.

<Medical equipment>
A film exhibiting excellent sliding durability by undergoing the (I) solution coating step (coating layer forming step) described above, (II) heat treatment step, and (III) washing step performed as necessary. A medical device having a (lubricating layer) can be manufactured.

  That is, according to the method according to the present invention, after forming a coating layer containing a block copolymer and a carboxylic acid compound on the surface of the base material layer, by aggregating the units and polymerizing the block copolymer, A strong lubricating layer that does not easily peel off from the base layer can be formed. Moreover, the medical device manufactured by the method according to the present invention can exhibit excellent lubricity and lubricity maintenance because the lubricating layer of the block copolymer is formed on the surface.

  Hereinafter, preferred embodiments of a medical device manufactured by the method according to the present invention will be described with reference to the accompanying drawings.

  FIG. 1 is a partial cross-sectional view schematically showing a laminated structure on a surface of a typical embodiment of a medical device (hereinafter, also abbreviated as “medical device”) manufactured by a method according to the present invention. is there. FIG. 2 is a partial cross-sectional view schematically showing a configuration example having a different laminated structure on the surface as an application example of the present embodiment. 1 and 2 represent the following, respectively. Reference numeral 1 denotes a substrate layer; reference numeral 1a denotes a substrate layer core portion; reference numeral 1b denotes a substrate surface layer; reference numeral 2 denotes a lubricating layer; and reference numeral 10 denotes a method according to the present invention. Medical devices to be used, respectively.

  As shown in FIGS. 1 and 2, in the medical device 10 of the present embodiment, the base material layer 1 and at least a part of the base material layer 1 are provided (in the drawings, the base material layer 1 in the drawings). A lubrication layer 2 containing a block copolymer (shown as an example provided on the entire surface (entire surface)). In FIGS. 1 and 2, the lubricating layer 2 is formed on both surfaces of the base material layer 1; however, the present invention is not limited to the above-described embodiment, and is formed on one surface of the base material layer 1; Any form such as a form formed on one or both surfaces of the material layer 1 may be used.

  Hereinafter, the medical device will be described in detail for each component.

≪Base layer (base) ≫
The substrate layer used in the present embodiment may be made of any material, and the material is not particularly limited. Specifically, the material forming the base material layer 1 includes a metal material, a polymer material, and ceramics. In addition, specific examples of the material constituting the base layer 1 are as described in the above {Application of block copolymer solution (coating solution)}.

  Here, as for the base material layer 1, the whole base material layer 1 may be composed of any of the above materials. The base material layer 1 may have a multilayer structure in which different materials are stacked in multiple layers, or a structure in which members made of different materials are connected to each other for each part of the medical device. Alternatively, as shown in FIG. 2, the surface of the base material layer core portion 1 a made of any of the above materials is coated with any of the above materials by an appropriate method to form the base material surface layer 1 b. It may have a structured structure. In the latter case, for example, a metal material is coated on the surface of a base material layer core portion 1a formed of a resin material or the like by an appropriate method (a conventionally known method such as plating, metal deposition, or sputtering). A surface layer 1b is formed; a polymer material which is more flexible than a reinforcing material such as a metal material is provided on the surface of a base layer core 1a formed of a hard reinforcing material such as a metal material or a ceramic material. It is coated by an appropriate method (a conventionally known method such as dipping (dipping), spraying (spraying), coating / printing, etc.), or the reinforcing material and the polymer material forming the base layer core 1a are composited. And those obtained by forming the substrate surface layer 1b. Further, the base layer core 1a may have a multilayer structure in which different materials are laminated in multiple layers, or a structure in which members made of different materials are connected to each other for each part of the medical device. Further, another middle layer (not shown) may be formed between the base layer core 1a and the base surface layer 1b. Further, the substrate surface layer 1b may have a multilayer structure in which different materials are laminated in multiple layers, or a structure in which members made of different materials are connected to each other for each part of the medical device.

≪Lubricating layer (surface lubricating layer, coating layer) ≫
The lubricating layer is supported on at least a part of the base layer 1. Here, the reason that the lubricating layer 2 is supported on at least a part of the surface of the base material layer 1 is that the medical devices such as catheters, guide wires, and indwelling needles are not necessarily used for these medical devices. It is not necessary that all surfaces (entire surfaces) have lubricity when wet, and a lubricating layer is applied only to the surface portions (sometimes all) that are required to have lubricity when wet. This is because it is only necessary to carry. For this reason, as described above, the lubricating layer is formed so as to cover both surfaces of the base material layer as shown in FIGS. 1 and 2; A form formed to cover a part of both surfaces of the base material layer in the same or different form; a form formed to cover a part of one surface of the base material layer; and the like.

<Use of medical equipment>
The medical device manufactured by the method of the present invention and the medical device according to the present invention are devices used in contact with bodily fluids, blood, or the like, and have a surface having lubricity in an aqueous liquid such as bodily fluid or physiological saline. It is possible to improve operability and reduce damage to tissue mucosa. Specific examples include catheters, guidewires, indwelling needles, and the like used in blood vessels. Other examples include the following medical devices.

  (A) Catheters that are inserted or placed in the digestive tract orally or nasally, such as a gastric tube catheter, a feeding catheter, and a tube for tube feeding.

  (B) Oxygen catheters, oxygen cannulas, endotracheal tube tubes and cuffs, tracheostomy tube tubes and cuffs, and catheters that are inserted or placed in the airway or trachea orally or nasally, such as intratracheal suction catheters.

  (C) Catheters to be inserted or placed in the urethra or ureter such as urethral catheters, urinary catheters, urethral balloon catheters and balloons.

  (D) Catheters inserted or placed in various body cavities, organs, and tissues such as suction catheters, drainage catheters, and rectal catheters.

  (E) Indwelling needles, IVH catheters, thermodilution catheters, angiographic catheters, vascular dilatation catheters and catheters to be inserted or indwelled in blood vessels such as dilators or introducers, or for these catheters Guide wire, stylet, etc.

  (F) Artificial trachea, artificial bronchi and the like.

  (G) Medical devices for extracorporeal circulation treatment (artificial lung, artificial heart, artificial kidney, etc.) and their circuits.

  The effects of the present invention will be described using the following examples and comparative examples. However, the technical scope of the present invention is not limited only to the following examples. In the following examples, operations were performed at room temperature (25 ° C.) unless otherwise specified. Unless otherwise specified, “%” and “parts” mean “% by mass” and “parts by mass”, respectively.

[Synthesis Example 1: Synthesis of Block Copolymer (1)]
The following reaction was carried out to produce a block copolymer (1).

  After 29.7 g of triethylene glycol was added dropwise to 72.3 g of adipic dichloride at 50 ° C., hydrochloric acid was removed at 50 ° C. for 3 hours under reduced pressure to obtain an oligoester. Next, 4.5 g of methyl ethyl ketone was added to 22.5 g of the obtained oligoester, which was added with 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of dioctyl phosphate as a surfactant, and 120 g of water. The resulting mixture was dropped into the resulting solution and reacted at -5 ° C for 20 minutes. The obtained product was repeatedly washed with water and methanol, and then dried to obtain a polyperoxide (PPO) having a plurality of peroxide groups in a molecule.

  Next, 0.5 g of this PPO, 9.5 g of glycidyl methacrylate (GMA) and 30 g of benzene were used as a solvent for polymerization at 80 ° C. for 2 hours while stirring under reduced pressure. The reaction product obtained after the polymerization was reprecipitated with diethyl ether to obtain polyglycidyl methacrylate (PPO-GMA) having a plurality of peroxide groups in the molecule.

  Subsequently, 1.0 g of the obtained PPO-GMA (equivalent to 7 mmol of GMA) was charged into 9.0 g of N, N-dimethylacrylamide (DMAA) (equivalent to 91 mmol of DMAA) and 90 g of dimethyl sulfoxide as a solvent, and the mixture was charged at 80 ° C. for 18 hours. And reacted. The reaction product obtained after the reaction is reprecipitated with hexane and recovered), and a block copolymer (1) having an epoxy group in the molecule and exhibiting lubricity when wetted (structural unit (A): structural unit (B) ) = GMA: DMAA = 1: 14 (molar ratio)). When the block copolymer (1) thus obtained was analyzed by NMR and ATR-IR, it was confirmed that an epoxy group was present in the molecule. The weight average molecular weight (Mw) of the block copolymer (1) measured by gel permeation chromatography (GPC, polystyrene conversion) was about 1.5 million.

  When a homopolymer having a degree of polymerization of 10 was prepared using glycidyl methacrylate (GMA), the amount of the homopolymer dissolved in 100 g of water was 0.1 g or less.

[Synthesis Example 2: Synthesis of block copolymer (2)]
In the same manner as in Synthesis Example 1, polyperoxide (PPO) having a plurality of peroxide groups in the molecule was obtained.

  Next, 0.5 g of this PPO, 9.5 g of n-butyl methacrylate (BuMA), and 30 g of benzene were used as a solvent for polymerization at 80 ° C. for 2 hours while stirring under reduced pressure. The reaction product obtained after the polymerization was reprecipitated with diethyl ether to obtain poly n-butyl methacrylate (PPO-BuMA) having a plurality of peroxide groups in the molecule.

  Subsequently, 1.0 g of the obtained PPO-BuMA (corresponding to 7 mmol of BuMA) was charged into 90 g of dimethyl sulfoxide as a solvent together with 9.0 g of N, N-dimethylacrylamide (DMAA), and reacted at 80 ° C. for 18 hours. Was. The reaction product obtained after the reaction is reprecipitated with hexane and recovered), and a block copolymer (2) having an epoxy group in the molecule and exhibiting lubricity when wetted (structural unit (A): structural unit (B) ) = BuMA: DMAA = 1: 14 (molar ratio)). When the block copolymer (2) thus obtained was analyzed by NMR and ATR-IR, it was confirmed that an epoxy group was present in the molecule. Further, the weight average molecular weight (Mw) of the block copolymer (2) measured by gel permeation chromatography (GPC, in terms of polystyrene) was about 1.4 million.

  When a homopolymer having a degree of polymerization of 10 was prepared using n-butyl methacrylate (BuMA), the amount of the homopolymer dissolved in 100 g of water was 0.1 g or less.

[Synthesis Example 3: Synthesis of block copolymer (3)]
A block copolymer (3) was prepared in the same manner as in Synthesis Example 1 except that 11.5 g (91 mmol) of N, N-diethylacrylamide (DEAA) was used instead of N, N-dimethylacrylamide (DMAA). (Structural unit (A): Structural unit (B) = GMA: DEAA = 1: 14 (molar ratio)) was obtained.

  When the block copolymer (3) thus obtained was analyzed by NMR and ATR-IR, it was confirmed that an epoxy group was present in the molecule. The weight average molecular weight (Mw) of the block copolymer (3) measured by gel permeation chromatography (GPC, converted to polystyrene) was about 1.6 million.

[Synthesis Example 4: Synthesis of random copolymer (r1)]
Using 0.035 g (0.21 mmol) of 2,2′-azobisisobutyronitrile (AIBN) as a polymerization initiator, 9.0 g (90 mmol) of N, N-dimethylacrylamide (DMAA) and glycidyl methacrylate (GMA) 1 0.0 g (7 mmol) was dissolved in dimethyl sulfoxide and polymerized at 80 ° C. for 7 hours under a nitrogen atmosphere. The reaction product obtained after the polymerization was recovered by reprecipitation with diethyl ether and recovered, and a random copolymer (r1) having N, N-dimethylacrylamide and glycidyl methacrylate as constituent units (DMAA: GMA = 1: 14 (mol Ratio)).

  When the random copolymer (r1) thus obtained was analyzed by NMR and ATR-IR, it was confirmed that an epoxy group was present in the molecule. The weight average molecular weight (Mw) of the random copolymer (r1) measured by gel permeation chromatography (GPC, polystyrene conversion) was about 46,000.

[Example 1]
The block copolymer (1) obtained in Synthesis Example 1 was dissolved in N, N-dimethylformamide (DMF) so as to have a concentration of 10% by mass, and lactic acid (molecular weight 90, manufactured by Tokyo Chemical Industry Co., Ltd.) was added thereto. ) Was added and dissolved in an amount (mass ratio) 0.7 times that of the block copolymer (1) to prepare a mixed solution (coating solution).

  The obtained mixed solution is applied on a surface of a polyethylene terephthalate (PET) film (Lumirror (registered trademark), manufactured by Toray Industries, Inc., thickness 250 μm) using a bar coater so that the thickness after drying becomes 2 μm. It was applied to form a coating film. Further, the film was stored in an oven at 80 ° C. for 5 hours to heat-treat the coating film. After cooling to room temperature, the coating was washed by immersing the film in water at room temperature (25 ° C.) for 1 minute. Thereafter, the film was dried at room temperature to prepare a coated film (1) having a coating layer (lubricating layer) containing a block copolymer (1) and lactic acid on the surface.

The coating layer (lubricating layer) of the coating film (1) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR. As a result, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

[Example 2]
A coating film (2) was produced in the same manner as in Example 1 except that eicosapentaenoic acid (EPA, molecular weight 302, manufactured by Tokyo Chemical Industry Co., Ltd.) was used instead of lactic acid.

The coating layer (lubricating layer) of the coating film (2) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR. As a result, a peak derived from EPA was detected, and the coating layer (lubricating layer) was detected. Contained EPA.

[Example 3]
A coated film (3) was produced in the same manner as in Example 1 except that the block copolymer (2) obtained in Synthesis Example 2 was used instead of the block copolymer (1).

When the coating layer (lubricating layer) of the coating film (3) was extracted with heavy chloroform and the obtained extraction solution was analyzed by ¹ H-NMR, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

[Example 4]
A coated film (4) was produced in the same manner as in Example 1 except that the block copolymer (3) obtained in Synthesis Example 3 was used instead of the block copolymer (1).

The coating layer (lubricating layer) of the coating film (4) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR. As a result, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

[Example 5]
Example 1 was repeated except that a sheet (thickness: 1 mm) obtained by hot pressing a polyamide elastomer (Vestamide (registered trademark) E47-S1, manufactured by Daicel Evonik Co., Ltd.) was used instead of the PET film. Similarly, a covering film (5) was produced.

The coating layer (lubricating layer) of the coating film (5) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR. As a result, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

[Example 6]
In the same manner as in Example 1 except that a sheet (film thickness: 1 mm μm) obtained by heating and pressing a polyethylene resin (Novatec (registered trademark) LD LF128, manufactured by Mitsubishi Chemical Corporation) was used instead of the PET film. Thus, a covering film (6) was produced.

The coating layer (lubricating layer) of the coating film (6) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR. As a result, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

[Example 7]
Example 1 was repeated except that a sheet (thickness: 1 mm μm) obtained by hot pressing a polyurethane resin (Pandex (registered trademark) T2180, manufactured by DC Covestro Polymer Co., Ltd.) was used instead of the PET film. Similarly, a covering film (7) was produced.

The coating layer (lubricating layer) of the coating film (7) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR. As a result, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

Example 8
Lactic acid was added and dissolved in an amount (mass ratio) 0.01 times the amount of the block copolymer (1) to prepare a mixed solution in the same manner as in Example 1 except that a mixed solution was prepared. ) Was prepared.

When the coating layer (lubricating layer) of the coating film (8) was extracted with heavy chloroform and the obtained extraction solution was analyzed by ¹ H-NMR, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

[Example 9]
Except that lactic acid was added and dissolved in an amount (mass ratio) 0.1 times the amount of the block copolymer (1) to prepare a mixed solution, a coating film (9) was prepared in the same manner as in Example 1. ) Was prepared.

The coating layer (lubricating layer) of the coating film (9) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR. As a result, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

[Example 10]
Except that lactic acid was added and dissolved in a 0.2-fold amount (mass ratio) with respect to the block copolymer (1) to prepare a mixed solution, a coating film (10) was prepared in the same manner as in Example 1. ) Was prepared.

When the coating layer (lubricating layer) of the coating film (10) was extracted with heavy chloroform and the obtained extraction solution was analyzed by ¹ H-NMR, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

[Example 11]
Lactic acid was added and dissolved in the same amount (1 time) (mass ratio) as that of the block copolymer (1), and a mixed solution was prepared in the same manner as in Example 1 except that a mixed solution was prepared. ) Was prepared.

The coating layer (lubricating layer) of the coating film (11) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR. As a result, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

[Example 12]
Lactic acid was added and dissolved in an amount (mass ratio) 1.1 times the amount of the block copolymer (1) to prepare a mixed solution in the same manner as in Example 1 except that a mixed solution was prepared. ) Was prepared.

The coating layer (lubricating layer) of the coating film (12) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR. As a result, a peak derived from lactic acid was detected, and the coating layer (lubricating layer) was detected. Contained lactic acid.

Example 13
A coated film (13) was produced in the same manner as in Example 1 except that adipic acid (molecular weight: 146, manufactured by Tokyo Chemical Industry Co., Ltd.) was used instead of lactic acid.

When the coating layer (lubricating layer) of the coating film (13) was extracted with deuterated chloroform, and the obtained extraction solution was analyzed by ¹ H-NMR, a peak derived from adipic acid was detected. ) Contained adipic acid.

[Comparative Example 1]
Comparative coating film (1) was produced in the same manner as in Example 1 except that lactic acid was not used.

[Comparative Example 2]
Comparative coating film (2) was produced in the same manner as in Example 1 except that polyacrylic acid (weight average molecular weight 25,000, manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) was used instead of lactic acid.

[Comparative Example 3]
Comparative coating film (3) was produced in the same manner as in Example 1 except that the random copolymer (r1) obtained in Synthesis Example 4 was used instead of the block copolymer (1).

[Comparative Example 4]
Comparative coating film (4) was produced in the same manner as in Example 1 except that acetic acid (molecular weight: 60, manufactured by Tokyo Chemical Industry Co., Ltd.) was used instead of lactic acid.

When the coating layer (lubricating layer) of the comparative coating film (4) was extracted with heavy chloroform and the obtained extraction solution was analyzed by ¹ H-NMR, no peak derived from acetic acid was detected.

[Comparative Example 5]
A comparative coating film (5) was produced in the same manner as in Example 3, except that lactic acid was not used.

[Comparative Example 6]
A comparative coating film (6) was produced in the same manner as in Example 4 except that lactic acid was not used.

[Evaluation of sliding properties and sliding durability]
For the coated films obtained in Examples 1 to 12 and Comparative Examples 1 to 6 and the comparative coated film (hereinafter, also simply referred to as “sample”), the slidability (the lubricating layer) was determined according to the following method. The sliding property) and the sliding durability (the durability of the lubricating layer) were evaluated.

(Evaluation method)
The sample was fixed in a Petri dish, and water was poured into the Petri dish until the whole sample was immersed, and the sample was immersed. This petri dish was placed on a moving table of a static friction measuring device (Handy Tribomaster TL201, manufactured by Trinity Lab Co., Ltd.).

  A stainless R-shaped terminal (R: 13 mm, semi-cylindrical terminal having a width of 10 mm) was brought into contact with the sample, and a load of 500 g was applied to the terminal. At a speed of 50 mm / sec and a moving distance of 25 mm, the horizontal stress applied to the terminal when the moving table was slid horizontally was measured as a sliding resistance value (unit: gf).

  The first sliding resistance value measured as described above was used as the sliding resistance evaluation result, and the number of sliding operations when the sliding resistance value exceeded 40 gf was used as the sliding durability evaluation result. . The evaluation results are shown in Table 1 below. As for the slidability, the smaller the value, the better the surface lubricating property. The larger the value for the sliding durability, the better the sliding durability. The description of “100 or more” in the item of “sliding durability” in Table 1 indicates that the sliding resistance does not exceed 40 gf even when the sample is slid at least 100 times, and the sliding durability is particularly excellent. To indicate that In the above evaluation, if it is 50 or more in the item of “sliding durability”, it can be said that it is a practical range.

  As is clear from the above Table 1, it was found that a medical device having a lubricating layer having excellent sliding properties and sliding durability can be obtained by using a mixed solution containing a specific carboxylic acid compound. In particular, from the comparison between Example 1 and Examples 8 to 12, when the mass ratio between the block copolymer and the carboxylic acid compound is 100: 20 to 100, it can sufficiently cope with complicated and sophisticated medical procedures. It is considered that possible sliding durability can be achieved. In addition, from the results of Example 1 and Examples 5 to 7, it was found that a medical device having excellent sliding durability was obtained according to the production method of the present invention regardless of the type of the base material layer. .

  In addition, it is considered that the hydrophilic monomer contributes to the initial slidability. From the comparison between Example 1 (GMA-DMAA copolymer) and Example 4 (GMA-DEAA copolymer), From the viewpoint of initial slidability, it is suggested that DMAA is preferable as the hydrophilic monomer. On the other hand, regarding the durability (sliding durability), it is presumed that the contribution of the hydrophobic monomer is large. From a comparison between Example 1 (GMA-DMAA copolymer) and Example 3 (BuMA-DMAA copolymer), from the viewpoint of durability (sliding durability), GMA was used as a hydrophobic monomer. It is suggested that it is preferable. Here, in Example 4 (GMA-DEAA copolymer), although GMA was used as the hydrophobic monomer, the durability (sliding durability) was lower than those in Examples 1 and 3. . The reason for this is that the initial slidability is lower than that of Examples 1 and 3 by including DEAA, so that the physical load in the initial sliding becomes relatively large, and the durability (sliding) is accordingly increased. This is considered to be due to a slight decrease in dynamic durability.

1 base material layer,
1a base material layer core,
1b substrate surface layer,
2 lubrication layer,
10 Medical tools.

Claims (8)

Base material layer, a lubricating layer carried on at least a part of the base material layer, a method for manufacturing a medical device comprising:
A block copolymer having a structural unit (A) derived from a hydrophobic monomer and a structural unit (B) derived from a hydrophilic monomer, a carboxylic acid compound having a molecular weight of 80 or more and less than 1,000, and a solvent. A method for producing a medical device, comprising applying a solution containing   The hydrophobic monomer includes glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl acrylate, β-methylglycidyl methacrylate; allyl glycidyl ether; methyl acrylate The medical device according to claim 1, comprising at least one selected from the group consisting of methyl methacrylate, n-butyl acrylate, n-butyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, benzyl acrylate, and benzyl methacrylate. Manufacturing method.   The hydrophobic monomer is composed of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl acrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether. The method for manufacturing a medical device according to claim 1, comprising at least one selected from the group.   The hydrophilic monomer is selected from the group consisting of N, N-dimethylacrylamide, N, N-diethylacrylamide, acrylamide, N-vinyl-2-pyrrolidone, 2-hydroxyethyl acrylate and 2-hydroxyethyl methacrylate. The method for producing a medical device according to any one of claims 1 to 3, comprising at least one kind.   The method for producing a medical device according to any one of claims 1 to 4, wherein the carboxylic acid compound is selected from the group consisting of hydroxy acids, fatty acids, and salts thereof.   The method for producing a medical device according to any one of claims 1 to 5, wherein the solution contains the block copolymer and the carboxylic acid compound in a mass ratio of 100: 1 to 100: 200.   The method for producing a medical device according to any one of claims 1 to 6, further comprising washing the coating film after forming the coating film by applying the solution on the base material layer. A medical device comprising a base material layer and a lubricating layer supported on at least a part of the base material layer,
A block copolymer having a structural unit (A) derived from a hydrophobic monomer and a structural unit (B) derived from a hydrophilic monomer, and a carboxylic acid having a molecular weight of 80 or more and less than 1,000 A medical device, comprising: a compound;