JP2019072103A - Medical appliance - Google Patents

Abstract

To provide a medical appliance that can exhibit excellent lubricity for a long time.SOLUTION: A medical appliance 1 has a resin mold part 2 containing silicone, which is inserted into a human body, an intermediate layer 3 formed on the surface 2a of the resin mold part, and a hydrophilic layer 4 formed on the surface 3a of the intermediate layer. The surface 2a of the resin mold part is irradiated with excimer UV.SELECTED DRAWING: Figure 1

Description

  The present invention relates to medical devices.

  Conventionally, it is required that the friction of the surface portion in contact with the human body is low in a medical instrument used by being inserted into the body such as a catheter, an endoscope and the like. To meet this demand, methods are known for forming a coating containing a hydrophilic compound that imparts lubricity to the surface of a catheter or an endoscope. For example, Patent Document 1 discloses a method of forming an interpolymer of polyvinyl pyrrolidone and polyurethane on the surface, and Patent Document 2 discloses a method of covalently bonding a hydrophilic polymer to unreacted isocyanate on the surface. Patent Document 3 discloses a method of forming a polyethylene oxide coating on a surface through a compound having an isocyanate group.

Japanese Patent Application Laid-Open No. 54-29343 JP-A-59-81341 Japanese Patent Application Laid-Open No. 58-193766

  Although the friction on the surface is reduced by the presence of the coating layer that imparts lubricity to the surface of the medical device inserted into the body, the lubricity is still not sufficient and further reduction of friction is required. There is. In addition, the catheter may be withdrawn after a certain period of time after it is placed in the body, and durability is also required to maintain the low friction without loss in the body.

  This invention is made in view of the said situation, and makes it a subject to provide the medical instrument which exhibits the outstanding lubricity over a long period of time.

[1] A medical device comprising: a resin-molded portion containing silicone to be inserted into the body, an intermediate layer formed on the surface of the resin-molded portion, and a hydrophilic layer formed on the surface of the intermediate layer The medical device is characterized in that the surface of the resin molded portion is irradiated with excimer UV.
[2] The medical device according to [1], wherein the intermediate layer contains a compound having one or more active groups selected from an isocyanate group, a vinyl group, an epoxy group and an amide group.
[3] The medical device according to [1] or [2], wherein the resin molding portion contains a silane coupling agent.
[4] The medical device according to [3], wherein the silane coupling agent has an isocyanurate group.
[5] The medical device according to any one of [1] to [4], wherein the hydrophilic layer contains one or more water-soluble polymers.
[6] The medical instrument according to any one of [1] to [5], wherein the wavelength of the excimer UV is 170 to 180 nm.
[7] The medical device according to any one of [1] to [6], wherein the resin molded portion is a resin layer covering a surface of a portion of the medical device to be inserted into at least the body.
[8] The medical device according to any one of [1] to [7], wherein the medical device is a tube or a catheter.

  Since the medical device of the present invention has at least a portion to be inserted into the body subjected to excimer treatment, the lubricity is improved and the friction on the surface is reduced. Furthermore, excellent lubricity can be maintained over a long period of time after being inserted into the body. As a result, the burden on the patient can be reduced not only when the medical device is inserted into the body but also when the medical device is moved or removed from the body after insertion.

1 is a partial cross-sectional view of a first embodiment of the present invention.

<< medical equipment >>
A medical device according to the present invention is a medical device in which at least a portion is inserted into a body, and a resin-molded portion containing silicone inserted into the body, an intermediate layer formed on the surface of the resin-molded portion, And a hydrophilic layer formed on the surface of the intermediate layer, wherein the surface of the resin molded portion is irradiated with excimer UV.
Specific types of medical instruments include, for example, catheters, tubes (for example, dialysis tubes, drain tubes, etc.), O-rings used in endoscopes, and the like.

  FIG. 1 shows a partial cross-sectional view of the first embodiment of the present invention. The medical device 1 of FIG. 1 includes a resin molded portion 2, an intermediate layer 3 formed on the surface 2 a of the resin molded portion 2, and a hydrophilic layer 4 formed on the surface 3 a of the intermediate layer 3.

  The resin molding portion 2 may be a base material forming the whole of the medical device 1 or may be a resin layer covering at least a part of the surface portion of the medical device 1. The thickness of the resin layer is not particularly limited, and can be, for example, about 10 μm to 10 mm.

  The resin molding portion 2 contains silicone. Silicone is a known polymer having a main chain formed by a siloxane bond, and its side chain is appropriately selected in accordance with the desired properties. For example, an aliphatic alkyl group such as a methyl group or an ethyl group, a phenyl group And aryl groups, such as halogen groups. It is preferable that silicone which comprises a catheter is silicone rubber. If the catheter is made of soft silicone rubber, it can be easily inserted into the body and the discomfort when it is placed in the body is reduced.

  The type of silicone contained in the resin molding portion 2 may be one, or two or more. As content of silicone with respect to the total mass of the resin molding part 2, 50 mass% or more is preferable, for example, 80% or more is more preferable, and 90% or more is more preferable. The upper limit value of the content is not particularly limited, and may be, for example, 99.9% or less.

  The resin molding portion 2 preferably contains a silane coupling agent. By including a silane coupling agent, the adhesion between the resin molded portion 2 and the intermediate layer 3 can be improved, and the durability of the hydrophilic layer 4 in the body can be further improved.

The silane coupling agent is an organosilicon compound having two or more different reactive groups in the molecule. Examples of the reactive group include vinyl group, epoxy group, styryl group, methacryl group, acrylic group, amino group, isocyanurate group, ureido group, mercapto group, isocyanate group and the like. Among them, a silane coupling agent having an isocyanurate group is preferable because the improvement of the lubricity and the durability by the excimer UV treatment is remarkable.
Specific silane coupling agents include, for example, vinyltrimethoxysilane, vinyltriethoxysilane, 2- (3,4-epoxycyclohexyl) ethyltrimethoxysilane, 3-glycidoxypropylmethyldimethoxysilane, 3-glyl. Cidoxypropyltrimethoxysilane, 3-glycidoxypropylmethyldiethoxysilane, 3-glycidoxypropyltriethoxysilane, p-styryltrimethoxysilane, 3-methacryloxypropylmethyl dimethoxysilane, 3-methacryloxypropyltrithiol Methoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, 3-acryloxypropyltrimethoxysilane, N-2- (aminoethyl) -3-aminopropylmethyldime Xylan, N-2- (aminoethyl) -3-aminopropyltrimethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-triethoxysilyl-N- (1,3-dimethyl-) Butylidene) propylamine, N-phenyl-3-aminopropyltrimethoxysilane, N- (vinylbenzyl) -2-aminoethyl-3-aminopropyltrimethoxysilane hydrochloride, tris- (trimethoxysilylpropyl) isocyanurate And 3-ureidopropyltrialkoxysilane, 3-mercaptopropylmethyldimethoxysilane, 3-mercaptopropyltrimethoxysilane, 3-isocyanatopropyltriethoxysilane and the like. Among these, tris- (trimethoxysilylpropyl) isocyanurate having an isocyanurate group is particularly preferable.

  The number of types of silane coupling agents contained in the resin molded portion 2 may be one, or two or more. Although content of the silane coupling agent with respect to the total mass of the resin molding part 2 is based also on the kind of silane coupling agent, 0.1-30 mass% is preferable, for example. Within this preferred range, the above-mentioned lubricity and durability can be further improved.

The middle layer 3 is a layer for bonding the resin molded portion 2 and the hydrophilic layer 4.
The thickness of the intermediate layer 3 can be, for example, about 0.1 μm to 500 μm.
The adhesive force of the resin molding part 2 and the hydrophilic layer 4 can be improved as it is the said range, and the durability in the body of the hydrophilic layer 4 can be improved more.

  The intermediate layer 3 preferably contains a compound having at least one active group selected from an isocyanate group, a vinyl group, an epoxy group and an amide group. By including these compounds, the adhesion between the resin molded portion 2 and the hydrophilic layer 4 can be improved, and the durability of the hydrophilic layer 4 in the body can be further improved. At least a part of the active group of the compound contained in the intermediate layer 3 is bonded to the surface 2 a of the resin molded portion 2 or the adhesive surface of the hydrophilic layer 4 to the intermediate layer 3.

The compound (isocyanate compound) which has the said isocyanate group is an organic compound which has one or more isocyanate groups in a molecule | numerator. The isocyanate compound preferably has two or more of the above-mentioned active groups including an isocyanate group in the molecule from the viewpoint of further improving the above-mentioned adhesiveness and durability.
Specific examples of the isocyanate compound include diisocyanates such as diphenylmethane diisocyanate, hexamethylene diisocyanate, toluene diisocyanate, xylene diisocyanate, naphthalene diisocyanate, triphenylmethane diisocyanate and the like.

  The number of types of isocyanate compounds contained in the intermediate layer 3 may be one, or two or more. Although content of the isocyanate compound with respect to the total mass of the intermediate | middle layer 3 is based also on the kind of isocyanate compound, 50-100 mass% is preferable, for example. The above-mentioned adhesiveness and endurance can be improved more as it is this suitable range.

The compound having a vinyl group (vinyl compound) is an organic compound having one or more vinyl groups in the molecule. It is preferable that the said vinyl compound has a 2 or more said active group including a vinyl group in a molecule | numerator from a viewpoint of improving said adhesiveness and durability more.
Specific vinyl compounds include, for example, epoxy group-containing vinyl compounds such as methyl glycidyl methacrylate, methyl glycidyl acrylate, allyl glycidyl ether, allyl phenol glycidyl ether, glycidyl methacrylate and the like.

  The number of types of vinyl compounds contained in the intermediate layer 3 may be one, or two or more. Although content of the vinyl compound with respect to the total mass of the intermediate | middle layer 3 is based also on the kind of vinyl compound, 50-100 mass% is preferable, for example. The above-mentioned adhesiveness and endurance can be improved more as it is this suitable range.

The compound (epoxide) which has the said epoxy group is an organic compound which has one or more epoxy groups in a molecule | numerator. From the viewpoint of further improving the above-mentioned adhesion and durability, the epoxide preferably has two or more of the above-mentioned active groups including an epoxy group in the molecule.
Specific epoxides include, in addition to the above-mentioned epoxy group-containing vinyl compounds, for example, glycidyl propionate, diglycidyl adipate, diglycidyl ether of 1,1-dimethylol-3-cyclohexane, triglycidyl ether of glycerol, 2,5 -Diglycidyl ether of bis (hydroxymethyl) tetrahydrofuran, butyl glycidyl ether, phenyl glycidyl ether, diglycidyl ether of bisphenol A, diglycidyl ether of resorcinol, triglycidyl ether of phloroglucinol, and the like.

  The number of types of epoxides contained in the intermediate layer 3 may be one, or two or more. Although content of the epoxide with respect to the total mass of the intermediate | middle layer 3 is based also on the kind of epoxide, 50-100 mass% is preferable, for example. The above-mentioned adhesiveness and endurance can be improved more as it is this suitable range.

The compound having an amide group (acid amide) is an organic compound having one or more amide groups in the molecule. The acid amide preferably has two or more of the above-mentioned active groups including an amide group in the molecule, from the viewpoint of further improving the above-mentioned adhesion and durability.
Specific acid amides include, for example, 4,4′-diaminodiphenyl ether, 3,4′-diaminodiphenyl ether, 2,4′-diaminodiphenyl ether, 4,4′-diaminodiphenylmethane, 2,4′-diaminodiphenylmethane, 3,4'-Diaminodiphenylmethane, 2,2-bis (4- (4-aminophenoxy) phenyl) propane, 2,2-bis (4- (4-aminophenoxy) phenyl) hexafluoropropane, 1,6- Hexamethylenediamine, 1,8-octamethylenediamine, azelaic acid dihydrazide, sebacic acid dihydrazide, 2,4'-diamino-3-methyl-stearyl phenyl ether, 2,4'-diamino-1-octyloxybenzene, 2, 2-Bis (4- (4-aminophenoxy) phenyl) octane Bis (4- (4-aminobenzoyl) benzoic acid) octane, diamino siloxane, 1,3-di (3-aminopropyl) -1,1,3,3 diamines such as tetramethyl disiloxane and the like.

  The number of types of acid amides contained in the intermediate layer 3 may be one, or two or more. Although content of the acid amide with respect to the total mass of the middle class 3 is based also on the kind of acid amide, 50-100 mass% is preferable, for example. The above-mentioned adhesiveness and endurance can be improved more as it is this suitable range.

The hydrophilic layer 4 is a hydrophilic coating layer that imparts lubricity to the outermost surface of the medical device 1.
The thickness of the hydrophilic layer 4 is, for example, about 0.1 μm to 1000 μm, preferably 1 μm to 100 μm, and more preferably 5 μm to 50 μm.
The effect of reducing the friction of the surface of the medical device 1 is enhanced and the adhesion of the hydrophilic layer 4 to the intermediate layer 3 is improved and the durability of the hydrophilic layer 4 in the body is further improved if it is in the above preferable range. it can.

The hydrophilic layer 4 preferably contains a water-soluble polymer.
The water-soluble polymer, for ^{_{example, -OH, -CONH 2, -COOH,}} -NH 2, -COO -, -SO 2 -, -NR 3 + ( where R is any organic group) a hydrophilic such And linear polymer compounds having a group.
Specifically, for example, starch-based polymers such as carboxymethyl starch and dialdehyde starch; cellulose-based polymers such as carboxymethyl cellulose (CMC), methyl cellulose (MC), hydroxyethyl cellulose (HEC) and hydroxypropyl cellulose (HPC) Wood-based polymers such as tannin and lignin; polysaccharide-based polymers such as alginic acid, gum arabic, guar gum, tragant gum and tamarint species; protein-based polymers such as gelatin, casein, glue and collagen; PVA-based polymers such as polyvinyl alcohol Polymers; polyethylene oxide-based polymers such as polyethylene oxide and polyethylene glycol; acrylic acid-based polymers such as sodium polyacrylate; maleic anhydride-based polymers such as methyl vinyl ether maleic anhydride copolymer; Phthalic acid-based polymers such as roxyethyl phthalate; water-soluble polyesters such as polydimethylol propionate; ketone aldehyde resins such as methyl isopropyl ketone formaldehyde; acrylamide resins such as polyacrylamide; polyvinyl pyrrolidone (PVP); Polyamines; polystyrene sulfonates; water soluble nylons; and the like.

  The number of types of water-soluble polymers contained in the hydrophilic layer 4 may be one, or two or more. Although the content of the water-soluble polymer with respect to the total mass of the hydrophilic layer 4 depends on the type of the water-soluble polymer, for example, 70 to 100% by mass is preferable. Within this preferred range, the above-mentioned lubricity and durability can be further improved.

  In the medical device 1, the surface of the surface 2 a of the resin molded portion 2 is modified by being irradiated with excimer UV before the intermediate layer 3 and the hydrophilic layer 4 are formed. As a result, the lubricity and durability of the hydrophilic layer 4 are improved. Hereinafter, the process of irradiating the surface with excimer UV is sometimes referred to as "excimer UV process".

<< Method of manufacturing medical instruments >>
Examples of the method for producing the medical device 1 according to the present invention include the following methods.
The resin molding portion 2 of the medical device 1 is a resin member formed by a known resin molding method such as extrusion molding or injection molding using a resin composition containing the silicone and the optional silane coupling agent as a raw material. It may be. Moreover, the resin layer formed by apply | coating and hardening the said resin composition on the surface of the base material which consists of glass, a metal, another resin molding part etc. may be sufficient.
The resin composition may optionally contain other optional components, and may contain, for example, a solvent, a known crosslinking agent that crosslinks and cures silicone, and a curing agent such as a catalyst. .

As a method of irradiating excimer UV to the surface 2a of the resin molding part 2, the method of irradiating using the irradiation apparatus provided with the well-known excimer lamp is mentioned. The atmosphere between the surface 2a of the resin-molded unit 2 to be excimer-processed and the excimer lamp may be filled with vacuum or any reactive gas using an apparatus provided with a vacuum chamber to irradiate excimer UV.
The irradiation distance between the excimer lamp and the surface 2 a of the resin molded portion 2 is not limited, and can be set to, for example, about 1 mm to 100 mm. The illuminance (unit: W / cm ² ) of the excimer lamp may be, for example, about 1 mW / cm ^{2 to} 100 W / cm ² , preferably 3 to ²⁰ mW / cm ² .

The wavelength of the excimer UV is, for example, 108 nm (NeF), 126 nm (Ar ₂ ), 146 nm (Kr ₂ ), 154 nm (F ₂ ), 161 nm (ArBr), 172 nm (Xe ₂ ), 175 nm and 184.9 nm (ArCl ₂ ) 191 nm (KrI), 193 nm (ArF), 207 nm (KrBr), 222 nm (KrCl), 248 nm (KrF), 253 nm and 253.7 nm (XeI), 258 nm (Cl ₂ ), 282 nm (XeBr), 291 nm (Br) ₂ ) 308 nm (XeCl), 341 nm (I ₂ ), 351 nm (XeF) can be mentioned. The above parenthesis is an excimer molecular species.
It is preferable that the wavelength of the excimer UV irradiated to the surface 2a of the resin molding part 2 is 170-180 nm. Within this preferred range, the above-mentioned lubricity and durability can be further improved.

Irradiation integrated light quantity (unit: J / ^{m 2)} of the excimer UV to the surface 2a of the resin molded section 2 includes, for example, it includes about 10~100,000mJ / cm ^2, preferably 25~10,000mJ / cm ² And 50 to 1000 mJ / cm ² are more preferable.
Within this preferred range, the above-mentioned lubricity and durability can be further improved.

"catheter"
A catheter will be described below as an example of the medical device according to the present invention.
The catheter is a medical instrument that has a tube portion that constitutes a conduit through which liquid or gas can flow, is inserted into the body, and is used for discharging body fluid, injecting a drug solution, and the like.
The specific dimensions and shape of the catheter are appropriately set according to the application. As an example of the dimension of the balloon catheter made of silicone resin, the total length of the tube part is about 20 to 60 mm, the outer diameter of the tube part is about 5 to 10 mm, the inner diameter of the duct of the tube part is about 2 to 7 mm, the balloon part is inflated The length in the longitudinal direction is about 10 to 20 mm, and the outer diameter of the largest part at the time of expansion is about 15 to 30 mm.

Example 1
First, using a silicone rubber (Shin-Etsu Chemical Co., Ltd., model number: KE-1950-30) whose viscosity is adjusted with a solvent as a raw material, a film-shaped test piece is formed by a known method, and the surface of the test piece is an excimer under the following conditions Hydrophilized by treatment.
Next, an MDI solution was applied to the surface of the hydrophilized test piece and dried to form an intermediate layer. As MDI solution, what melt | dissolved diphenylmethane diisocyanate (MDI) by density | concentration about 1 mass% in methyl ethyl ketone was used.
Subsequently, a PVP solution was applied to the surface of the intermediate layer and dried to form a hydrophilic layer. As the PVP solution, a solution of polyvinyl pyrrolidone (PVP) dissolved in methyl ethyl ketone at a concentration of about 1% by mass was used.
Test pieces in which an intermediate layer containing MDI and a hydrophilic layer containing PVP are sequentially coated on the excimer-treated surface of a film-shaped test piece made of silicone rubber by the above method (a test piece having a laminated structure shown in FIG. 1) I got three.

Example 2
A composition obtained by adding 30 parts by mass of a silane coupling agent (Shin-Etsu Silicone Co., model number: KBM-9659) as an additive to 100 parts by mass of the silicone rubber used in Example 1 is used as a raw material in Example 1 and Similarly, a film-like test piece was formed, and the surface of the test piece was hydrophilized by excimer treatment under the following conditions.
Next, a test piece in which an interlayer containing MDI and a hydrophilic layer containing PVP were sequentially coated on the excimer-treated surface of the film-like test piece in the same manner as in Example 1 (a laminated structure shown in FIG. Three test pieces were obtained.

(Excimer treatment)
As an excimer irradiation apparatus, an 8-inch unit manufactured by Ushio Inc. equipped with an excimer lamp with a UV wavelength of 172 nm and an illuminance of 20 mW / cm ² was used. The distance between the test piece and the lamp (irradiation distance) was set to 1 mm, and irradiation was performed for 30 seconds.

Comparative Example 1
A composition obtained by adding 30 parts by mass of a silane coupling agent (Shin-Etsu Silicone Co., model number: KBM-9659) as an additive to 100 parts by mass of the silicone rubber used in Example 1 is used as a raw material in Example 1 and A film-like test piece was similarly formed. No excimer treatment was performed on the surface of the test piece.
Next, an intermediate layer containing MDI and a hydrophilic layer containing PVP are sequentially coated on the surface of the film-like test piece by the same method as in Example 1 except that a film-like test piece not treated with excimer treatment is used. Three test pieces (the test pieces of the laminated configuration shown in FIG. 1) were obtained.

<Evaluation test of hydrophilicity>
The prepared test pieces (specimen) were immersed in warm water at 60 ° C. for 30 seconds, removed from the warm water, and the coefficient of static friction was measured using a portable tribometer (TYPE: 94i-II) manufactured by Shinto Scientific Co., Ltd. The results are shown in Table 1.

From the above results, the test pieces of Examples 1 and 2 subjected to the excimer treatment had a lower coefficient of friction than Comparative Example 1, and were excellent in lubricity and durability.
Example 2 in which the silicone surface containing a silane coupling agent was subjected to excimer treatment had a lower coefficient of friction than Example 1 in which the silicone surface not containing a silane coupling agent was subjected to excimer treatment, and was superior in lubricity and durability.

DESCRIPTION OF SYMBOLS 1 ... Medical instrument, 2 ... Resin molding part, 3 ... Intermediate layer, 4 ... Hydrophilic layer

Claims (8)

What is claimed is: 1. A medical device comprising: a resin-molded portion containing silicone inserted into a body, an intermediate layer formed on the surface of the resin-molded portion, and a hydrophilic layer formed on the surface of the intermediate layer,
The medical instrument characterized in that the surface of the resin molded portion is irradiated with excimer UV.   The medical device according to claim 1, wherein the intermediate layer comprises a compound having one or more active groups selected from an isocyanate group, a vinyl group, an epoxy group and an amide group.   The medical device according to claim 1, wherein the resin molding portion contains a silane coupling agent.   The medical device according to claim 3, wherein the silane coupling agent has an isocyanurate group.   The medical device according to any one of claims 1 to 4, wherein the hydrophilic layer contains one or more water-soluble polymers.   The medical instrument according to any one of claims 1 to 5, wherein the wavelength of the excimer UV is 170 to 180 nm.   The medical device according to any one of claims 1 to 6, wherein the resin molded portion is a resin layer covering a surface of a portion of the medical device to be inserted into at least the body.   The medical device according to any one of claims 1 to 7, wherein the medical device is a tube or a catheter.

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