JPS60259269A - Medical device and its production - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION ■ Background Technical Field of the Invention The present invention relates to a medical device and a surface treatment method thereof.

Prior art and its problems Medical instruments such as catheters inserted into the respiratory tract, trachea, gastrointestinal tract, urethra, JllIw-1 and other body cavities or tissues, as well as guide wires and stylets inserted into these Various medical devices, such as medical devices, must be smooth enough to be inserted to the target site without damaging tissue, and they also need to be smooth enough to avoid damaging mucous membranes due to friction while indwelling in tissue. It is required to exhibit excellent lubricity to avoid burning or causing irritation.

For this reason, the base materials for these medical devices have conventionally been made of general low-friction resistance materials such as fluororesin or polyethylene, or have surface coats such as fluororesin coats or silicone coats applied to the surface of the base material, or silicone Oil, olive oil, glycerin, xylocaine jelly, etc. are applied to the surface.

However, all of these conventional cases are insufficient in terms of effectiveness.

For example, when using low-friction resistance materials such as Teflon or high-density polyethylene, or applying a surface coating with them,
There are problems such as the coefficient of friction not being sufficiently low. Furthermore, although surface application of oil lowers the coefficient of dynamic friction, it has the disadvantage that the effect is not sustainable and the oil and the like are washed away. Alternatively, oil coating makes the surface sticky and difficult to store as a product, so the coating must be applied immediately before use, making handling cumbersome.

On the other hand, US Pat. No. 4,100,309 discloses the use of an interpolymer of polyvinylzorollidone and polyurethane as the coating layer.

This coating exceeds conventional coatings in terms of frictional resistance and durability.

However, it requires an isocyanate group as a reactive functional group, and polyurethane must be used as a base material or an underlayer formed on the base material, which is undesirable because it limits the usable base materials and the applications of medical devices.

For example, even if polyamide resin is treated with such a coating layer, it is difficult to directly introduce incyanate groups, and lower #! Even if polyurethane is used as a layer, the adhesion to the base material is low and a durable coating layer cannot be expected.

Also, polyvinylpyrrolidone is relatively expensive.

In addition, polyvinylpyrrolidone and incyanate group are
It is thought that ion complexes are formed, and therefore the bonding state is not stable in body fluids such as saliva, digestive juices, blood, etc., or in aqueous solutions such as physiological saline; It tends to dissolve in water, so it cannot be expected to have sufficient sustainability.

Furthermore, JP-A-53-108778 discloses a method for imparting fibrinolytic activity to the surface of polyurethane resin, which is characterized by immobilizing a fibrinolytic active substance on the surface of polyurethane resin; Polymers containing maleic acid units are used as an intermediate bonding layer to fix fibrinolytic active substances to the polyurethane resin surface, and these coating layers are eluted as the outer surface to improve the lubricity of medical devices. There is no disclosure or suggestion to that effect.

HObject of the invention The object of the invention is to reduce the frictional resistance during insertion when used in a wet state, that is, in a wet state with body fluids such as saliva, digestive juices, blood, and aqueous liquids such as physiological saline and water. It is an object of the present invention to provide a medical device that is small in size, has good durability, good storage stability, and has a coating layer that can be applied to a wide variety of base materials, and a method for manufacturing the same.

Such an object is achieved by the following first to third inventions.

That is, the first invention covalently bonds a reactive functional group present on at least the surface of a base material constituting a medical device with a water-soluble polymer substance or a derivative thereof, so that the surface has lubricity when wetted. This medical device is characterized by being configured as follows.

In addition, the second invention includes treating a base material constituting a medical device with a solution of a compound having a reactive functional group, and forming a base layer so that the reactive functional group is present on at least the surface of the base material, Then, treatment with a water-soluble polymeric substance or a derivative thereof to covalently bond the reactive functional group and the water-soluble polymeric substance to form a coating layer of the water-soluble polymeric substance on the base layer 1-; This is a method for manufacturing a medical device, characterized in that the surface has lubricity when wetted.

Furthermore, in a third invention, a base material constituting a medical device is treated with a solution of a compound having a reactive functional group, a base layer is formed so that the reactive functional group is present on at least the surface of the base material, and then treatment with a water-soluble polymeric substance or a derivative thereof to covalently bond the reactive functional group and the water-soluble polymeric substance to form a coating layer of the water-soluble polymeric substance on the base layer; This method of manufacturing a medical device is characterized in that a water treatment is then carried out so that the surface has lubricity when wet.

Water-soluble polymer substances include cellulose-based polymer substances, maleic anhydride-based polymer substances, acrylic acid-based polymer substances,
The polyethylene oxide polymer material, water-soluble nylon or cellulose polymer material is hydroxypropyl cellulose, the maleic anhydride polymer material is methyl vinyl ether maleic anhydride copolymer, and the acrylamide polymer material is polyacrylamide. ,
The medical device according to claim 2, wherein the polyethylene oxide polymer substance is polyethylene glycol. Further, it is preferable that the reactive functional group is an aldehyde group; an epoxy group, an isocyanate group, or an amino group. The medical device is a guide tool that is made of a rod-shaped body that can be inserted into a medical tube, and that allows the medical tube to be introduced into or removed from the body.

■Specific structure of the invention Hereinafter, a specific configuration of the present invention will be explained in detail.

The water-soluble polymeric substance used to form the lubricious surface coating layer of the medical device of the present invention is fixed to the medical device substrate 1- by covalent bonding. Such water-soluble polymer substances are
In principle, a chain-like, non-crosslinked polymer substance is 10I(,-
CONH2, -COOH.

Those with hydrophilic groups such as -NR2, -COO"-, -303-, and -NR3".

Natural water-soluble polymers 1) Starch-based carboxymethyl starch, dialdehyde starch 2) Cellulose-based CMC, MC, HEC, HPC 3) Tannin, nignin-based tannin, nignin 4) Polysaccharide-based alginic acid, gum arabic, guar gum, gum tragacanth, Tamarind seeds 5) Protein gelatin, casein, glue, collagen synthesis Water-soluble polymer 1) PVA-based polyvinyl alcohol 2) Polyethylene oxide-based polyethylene oxide, polyethylene glycol 3) Acrylic acid-based polyacrylic acid sodium 4) Maleic anhydride Methyl vinyl ether maleic anhydride copolymer 5) Phthalic acid-based polyhydroxyethyl phthalate ester 6) Water-soluble polyester polydimethylol propionate ester 7) Ketone aldehyde resin Methyl isopropyl ketone formaldehyde resin 8) Acrylamide-based polyacrylamide 9) Polyhydric Nilpyrrolidone VP 10) Polyamine polyethyleneimine 11) Polyelectrolyte polystyrene sulfonate 12) Others include water-soluble nylon.

In addition, the derivatives are not limited to water-soluble ones, and there are no particular restrictions as long as they have the basic composition of the water-soluble polymer substances mentioned above.
As for the insolubilized material, it is sufficient that the molecular chain has a degree of freedom and contains water as described below.

For example, condensation, addition, substitution of water-soluble polymeric substances to -,
Esterified products, salts, amidated products, anhydrides, halides, etherified products, hydrolyzed products, acetalized products, formalized products, alkylolated products, quaternized products, diazotized products, hydrazidized products, sulfones obtained by oxidation, reduction reactions, etc. compounds, nitrides, ion complexes, quesiazonium groups, azide groups, incyanate groups, acid chloride groups, acid anhydride groups, iminocarbonate groups, amino groups, carboxyl groups, epoxy groups, hydroxyl groups, aldehyde groups, etc. A crosslinked product with a substance having two or more functional groups.

Examples include copolymers with vinyl compounds, acrylic acid, methacrylic acid, diene compounds, maleic anhydride, and the like.

Such water-soluble polymer substances dissolve well in water, and when the solution is present between certain objects, the frictional resistance between the two can be significantly reduced, and it can be used as a lubricant. In addition, derivatives obtained by condensation, addition reactions, substitution reactions, etc. of these water-soluble polymer substances, as well as those that have been partially crosslinked, so-called insolubilized, are similarly effective as lubricants between two layers. It is.

By covalently bonding these with reactive functional groups present or introduced in the base material or on the base material surface, it is possible to obtain a lubricating layer supported on the base material, which does not dissolve in water and lasts for a long time. A lubricious surface can be obtained. The water-soluble polymeric material is not particularly limited, but the most representative ones include cellulose, fi-water mamalate, acrylamide, polyethylene oxide, and water-soluble nylon. Especially hydroxypropyl cellulose, methyl vinyl ether, maleic anhydride copolymer,
Polyacrylamide, polyethylene glycol, water-soluble nylon (AQ-nylon P-70 manufactured by Toshi Co., Ltd.)
) is a substance that is inexpensive, easily available, and has a good safety profile.

There is no particular limit to the average molecular weight of these water-soluble polymeric substances, but those of about 3 to 5 million have high lubricity and provide a lubricating layer with an appropriate thickness and a degree of swelling that is not significantly large when it contains water. It is suitable for this purpose.

Further, the degree of swelling when the substance is hydrated may be adjusted by using a substance that has been subjected to an insolubilization treatment as described above, or by carrying it on a substrate and then carrying out a similar treatment.

The reactive functional group present or introduced into the base material or on the base material surface -1- is not particularly limited as long as it reacts with the water-soluble polymeric substance and fixes it by bonding or crosslinking. , diazonium group, azide group, isocyanate group,
Possible examples include acid chloride groups, acid anhydride groups, iminocarbonate groups, amine groups, carboxyl groups, epoxy groups, hydroxyl groups, aldehyde groups, and particularly preferred are incyanate groups, amino groups, aldehyde groups, and epoxy groups.

Therefore, polyurethane, polyamide F, etc. are suitable as the base material containing a reactive functional group. Furthermore, base materials that do not contain these reactive functional groups are usually used as base materials constituting the outer walls, inner walls, etc. of various medical devices. As described above, such a substrate 5 is treated with a substance having a reactive functional group so that the reactive functional group is present in the base material, and a water-soluble polymeric substance is covalently bonded thereon as in the present invention. . There are various forms of bonding, such as covalent bonding, ionic bonding, and physical attachment, but covalent bonding is most preferable from the viewpoint of sustainability.

These methods are not limited to being applied directly to the surface of the base material, but can be applied to the outermost layer by the presence or introduction of a reactive functional group in the polymer layer or layer 1; Bonding and fixing may provide a permanently lubricated surface.

Examples of substances having such reactive functional groups include ethylene diisocyanate, hexamethylene diisocyanate, xylene diisocyanate, toluene diisocyanate, diphenylmethane diisocyanate, naphthalene diisocyanate, diphenylmethane diisocyanate, phenylene diisocyanate, cyclohexylene diisocyanate, and triphenylmethane diisocyanate. Isocyanates, polyisocyanates such as tolutriinocyanate, and adducts or prepolymers of these polyisocyanates and polyols, for example, low molecular weight polyamines such as ethylene diamine, trimethylene diamine, etc.

2-diaminopropane, tetramethylene diamine, 1.
3-diaminobutane, 2,3-diaminobutane, pentamethylenediamine, 2,4-diaminobencune, hexamethylenediamine, octamethylenediamine, nonamethylenediamine, decamethylenediamine, undecamethylenediamine, dodecamethylenediamine, tri Decamethylenediamine, octadecamethylenediamine, N,N-dimethylethylenediamine, N,N-diethyltrimethylenediamine, N,N-dimethyltrimethylenediamine, N
, N-dibutyltrimethylene diamine, N, N, N''
-Triethylethylenediamine, N-methyltrimethylenecyamine, N,N-dimethyl-P~phenylenediamine, N,N-dimethylhexamethylenediamine, diethylenetriamine, I.liethylenethiamine, tetraethylenepentamine, hebutaethylene Octamine, nonamethylene diamine, 1,3-bis(2'-aminoethylamino)propane, bis(3-aminopropal)amine, 1,3-bis(3'-aminopropylamino)propa7.1, 2, 3. − Triaminopropane, Tris (
2-aminoethyl)amine, tetra(aminomethyl)methane, methyliminobispropylamine.

Methyliminobisethylamine, ethyliminobisethylamine, N-ruaminopropyl 2,000luporine, N-aminopropyl-2-pipecoline, N-(2-hydroxyethyl)trimethylenediamine xylylenediamine,
Phenylenediamine, piperazine, N-methylbiperazine, tri(2-aminoethyl)ethanolamine, N-7
Minoethylpiperazine.

Examples include N,N,N''N'-tetramethylethylenediamine, N,N,N''N''-tetramethyltetramethylenediamine, and polymeric polyamines synthesized from (1) amine and alkylene civalide or epichlorohydrin. Poly(alkylene polyamine) [Encyclopedia φ of Polymer Science and Technology (Encyclopedia
of Polymer 5science and T
echn-ology) Volume 10, page 616], (
II) Alkylene imine polymers obtained by ring-opening polymerization of alkylene imines such as z-tylene imine and propylene imine [Ensaucropidia of Polymers and Science Ban and Kai Technology, vol. 1, page 734], (III) Others, Polyamines such as polyvinylamine and polylysine.

In addition, glutaraldehyde, terephthalaldehyde,
isophthalaldehyde, dialdehyde, starch, caroxal, malonaldehyde, succinic aldohyde,
Azibaldehyde, pimelindialdehyde, superingialdehyde, malealdehyde, 2-pentene-1,
Polyaldehydes such as 5-dialdehyde, and polyepoxides such as ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, propylene glycol diglycidyl ether, polypropylene diglycidyl ether, hexanediol diglycidyl ether, and trimethylolpropane triglycidyl ether be.

Among these, 4,4'-diphenylmethane diisocyanate, a 7-duct (adduct) of tolylene diisocyanate and trimethylolpropane, an adduct of hexamethylene diisocyanate and trimethylolpropane, a sonotrimer, and diethylenetriamine are particularly preferred. In the present invention, as the base material applied to the outermost layer, a particularly low frictional resistance base material is used, and a low frictional resistance treatment agent such as silicone oil, olive oil, glycerin, or xylofine jelly is not applied before use. However, when it comes into contact with an aqueous liquid such as the one described above, a low frictional resistance (lubricity) surface condition is immediately obtained, making it possible to use it as such a medical device. Furthermore, there are very few restrictions on the base material to be used. Therefore, the base materials to be used include polyamide, polyester, polyvinyl chloride, polystyrene, polyacrylic ester, polymethacrylic ester, polyacrylonitrile, polyacrylamide, polyacrylic acid, polymethacrylic acid, polyethylene, polypropylene, polyvinyl alcohol. , polymaleic anhydride, polyethyleneimine, polyurethane, polyvinyl acetate, silicone resins, various latexes, and various copolymers and blends of these materials;
Any of various inorganic or metal substrates such as glass, ceramics, and stainless steel may be used.

These base materials may contain various additives as necessary.

As a base material, organic polymer resins are particularly effective in maintaining lubricity, and among these, polyvinyl chloride, polyurethane, polyamide, latex, and polyester have the highest effect.

Therefore, when using these other resins, metals, glass, etc. as a base material, a layer made of various organic polymer resins similar to those used for the above-mentioned base materials is formed on the surface of the base material in advance to increase the reactivity. More favorable results can be obtained by providing a lubricating layer by introducing a functional group or blending the resin with a substance having a reactive functional group.

The coating layer of the present invention can be formed on such a base material in the following manner. .

When using an ordinary base material that does not contain reactive functional groups, 11 layers are first formed.

To form the base layer, the base material may be immersed in a solution containing the above-mentioned compound having a reactive functional group, and then dried.

In such a case, examples of solvents used include ketones such as methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone, esters such as butyl acetate, ethyl acetate, carpitol acetate, and butyl carpitol acetate, methyl cellosolve, ethyl cellosolve, and tetrahydrofuran. Any of ether systems such as ether systems, aromatic systems such as toluene and xylene, halogenated alkyl systems such as dichloroethane, alcohol systems, etc. may be used.

However, as a solvent, especially a resin base material (in some cases, a resin coating M pre-formed on the surface of the above-mentioned base material)
) is preferably one that dissolves or swells.

This is because the adhesion strength of the coating layer increases by -1, and the lasting effect becomes greater.

Particularly suitable solvents include methyl ethyl ketone, cyclohexanone, tetrahydrofuran, xylene, and methyl alcohol.

In addition to dipping treatment, brush painting, spinner coating, etc. are also possible.

The subsequent drying step is to evaporate the solvent, and is usually carried out at room temperature to about 80° C. for about 5 minutes to 48 hours.

Note that, as described above, when coating the surface of the base material with an adhesive layer in advance, a conventional method may be followed.

Next, the base material on which the base layer is formed (in some cases, the base material is
'I! ! water-soluble of the present invention (without forming a layer)? 1 is treated with a solution containing a polymeric substance.

The solvent used in this case is one that does not react with reactive functional groups present in the base material or adhesive layer, that is, one that does not react with isocyanate-1 groups and amine groups, and methyl ethyl ketone, THF, acetone, etc. are particularly preferred. . Particularly suitable are those that have solubility and swelling properties in the base material.

And its concentration is 0.1-15%, especially 0.5-10%
It is preferable to set it as approximately.

Further, the treatment is usually performed by dipping treatment as described above, but various coating methods can also be used.

The processing temperature is room temperature to 80°C, and the processing time is 1 second to 48°C.
It should be about an hour.

The subsequent drying process is performed at room temperature to about 80°C.
It may be done for about 5 minutes to 48 hours.

In this way, the water-soluble polymeric substance of the present invention is covalently bonded to the reactive functional group to form a coating layer.

In the present invention, when the coating layer formed in this manner is further subjected to water treatment, an even more favorable result can be obtained in that affinity with water can be obtained in a short time.

Water treatment usually involves immersing the material in water and then drying it.

In this case, the immersion time is about 10 minutes to 2 hours, the processing temperature is room temperature to 60℃, and the drying is 30 minutes at room temperature to 80℃.
Do this for about 48 hours.

In addition, as the water treatment, steam treatment or the like is also possible.

Although the detailed mechanism is not clear, the reason why the water-soluble polymer coating layer covalently fixed to the base material of the present invention maintains extremely excellent lubricity over a long period of time is as follows. Conceivable.

Water-soluble polymers are generally used in aqueous solution or gel form.
, -NH2, -Goof(, -OH, etc.).

Although the state of hydration is not fully understood, it is thought that there are two types of water: bound water, which is incorporated into the polymer and has relatively little movement, and water with a high degree of freedom.

It is thought that one of the reasons for the development of lubricity when wetted with water is the presence of this free water. Although they absorb water and swell very well, they have poor lubricity, and the reason why some materials with relatively low molecular weights have low lubricity is due to this lack of free water, and this is affected by the structure and polarity of the polymer. It is thought that

That is, materials with crystalline molecular structures such as cellulose-based polymers do not have much free water, and the movement of the entire molecule is not as smooth as in those with chain structures. Therefore, CMC, RPC, etc. do not have very good lubricity, and PVM/MA (Guntlets), P
This is considered to be the reason why VP, PAAm, etc. are good.

In addition, even if the chain structure has a hydrophilic group, those that are bonded to the base material at various places or those that have cross-linked molecules are 1
The molecules themselves lose their degree of freedom, resulting in poor lubricity.

Furthermore, a strong bond such as a covalent bond with the base material is very advantageous for maintaining lubricity.

Therefore, the best lubricity is achieved in a state in which the chain structure molecules that are covalently bonded to the base material and have a parent tree group extend relatively long.

In the present invention, the medical device having the base material subjected to the surface treatment as described above as its inner or outer surface is, as described above, wetted with the above-mentioned aqueous liquid when inserted. Or it has a surface that requires low frictional resistance when indwelling in the body.

Accordingly, one example of the medical device of the present invention is the following, the surface of which is provided with the coating layer of the present invention.

l) The outer or inner surface of catheters that are inserted or indwelled into the gastrointestinal tract orally or nasally, such as gastric tube catheters, feeding catheters, and EI) (enteral feeding) tubes.

For example, in FIG.
An example is shown in which the coating layer 1 of the present invention is formed on the outer surface of the olive 21 of the tube 2 and the main tube 22. At this time, insertion becomes easier, and the patient's own swallowing becomes easier.

2) Oxygen catheters, oxygen cameras, tubes and cuffs for endotracheal tubes, tubes and cuffs for tracheostomy tubes, endotracheal suction catheters, etc. (non-oral) and catheters that are inserted or placed in the airway or trachea through the nose. the outer or inner surface of

3) The outer surface or inner surface of catheters for insertion or indwelling into the urethra or ureter, such as urinary catheters, urinary catheters, and balloon catheters.

For example, FIG. 2 shows a side hole 31, a balloon 32, a main body tube 33, a balloon branch pipe 34, a main body connector 3
An example is shown in which the coating layer of the present invention is formed on the outer surfaces of the balloon 32 and the main body tube 33 of a balloon catheter 3 consisting of 5.

At this time, since the frictional resistance is low, insertion is easy and pain to the patient is reduced. Furthermore, during indwelling within tissue, frictional resistance with mucous membranes is low, reducing the risk of inflammation or damage. In addition, in the present invention, even when applied to an elastic body such as the balloon 32, its physical properties are not changed at all,
Moreover, since the balloon 32 is a part where resistance during insertion is extremely large, the effect is great.

4) The outer or inner surface of catheters for insertion or indwelling into various body cavities or tissues, such as suction catheters, drainage catheters, and rectal catheters.

In addition, by forming the coating layer of the present invention on the inner surface of these catheters 1) to 4), there are advantages such as reducing adhesion of nutrients, tissue fluids, etc. and not obstructing the lumen flow path.

5) Outer or inner surfaces of catheters for insertion or indwelling into blood vessels, such as indwelling needles, IVH catheters, thermodilution catheters, angiography catheters, dilators, and introducers.

Or the outer surface of the guidewire, squillent, etc. for these catheters.

For example, No. 314 shows an example in which the coating layer of the present invention is formed on the outer and inner surfaces of a Shadkins type coronary angiography catheter 5.

FIG. 4 also shows a guide wire 6 inserted into the catheter 5 and used to introduce the catheter 5 into a blood vessel site.
An example is shown in which the coating layer of the present invention is formed on the outer surface of.

This reduces the insertion resistance of the catheter into the blood vessel and the coronary insertion resistance of the guide wire.

6) Outer surface of endoscopes for insertion into various body cavities.

7) Other surfaces such as condoms and contact lenses.

(2) Specific effects of the invention According to the first invention, the frictional resistance on the surface of the medical device becomes extremely small. In particular, the frictional resistance is extremely low when wet, i.e. when wet with body fluids such as saliva, digestive juices, blood, or physiological saline or water.
It provides extremely great advantages such as ease of insertion, alleviation of patient pain, and prevention of damage to mucous membranes and vascular intima.

In addition, frictional resistance does not increase even after repeated use or storage under poor conditions, which is extremely advantageous in terms of long-lasting effect and shelf life.

And, since the coating layer can correspond to various reactive functional groups,
Since there are few restrictions on the base materials to which it can be applied, it can be used in various medical devices and has excellent versatility.

Furthermore, the coating layer can be manufactured at a lower cost than by conventional means.

According to the second invention, a coating layer that exhibits lubricity, that is, low frictional resistance in a wet state is obtained. Furthermore, when water treatment is carried out as in the third invention, water is incorporated into the new aqueous group of the water-soluble polymer substance in the coating layer as water contained or bound, and one end is fixed to the base material by a covalent bond. The polymeric substances are aligned to form an orderly water-containing coating layer.

When this is dried and first comes into contact with an aqueous system, the affinity for water has increased, so that it becomes a coating layer with lubricity in a short period of time.

Although the as-treated coating layer of the second invention tends to develop lubricity somewhat slower than the water-treated coating layer of the third invention, the difference in lubricity can be seen over time. Therefore, the device having the coating layer according to the second invention may be used in devices that do not require haste in developing lubricity.

[Example 1] Soft polyvinyl chloride 3 c+*X 5 c shoulder X O, 4
After adding 4.4'-diphenylmethane diisocyanate for 1 hour, methyl vinyl ether maleic anhydride copolymer (G
ANTREZ AN-139, MW=750,000GA
(manufactured by Company F) 1.25% MEK solution for 10 seconds, 6
It was dried at 0° C. for 2 hours to obtain a surface lubricity treated sample (1).

As a result of performing a frictional resistance and durability test to be described later on sample (1), the value of frictional resistance = 0.02 was maintained even after continuous water washing for 6 hours. However, the surface did not reach a low friction *resistance state immediately after the sample was wetted with water, but a good state was obtained after a while.

After preparing sample (1), it was immersed in water at room temperature for about 30 minutes, and
After drying at °C for 24 hours, sample (2) was obtained.

As a result of conducting the same test as (1) for Trial #I (2), this value was also maintained even after continuous water washing for 6 hours with Ru 0.02. Furthermore, in sample (2), sample (
Unlike 1), the surface lubricity developed relatively quickly after getting wet with water and was good.

After preparing sample (1), immerse it in water for about 1 hour or more at room temperature,
After drying at 60° C. for 24 hours, sample (3) was obtained.

Tests similar to those in (1) and (2) were conducted on sample (3), and as a result, the frictional resistance μ = 0.02 was able to maintain this value even after continuous water washing for 6 hours.

Furthermore, in comparison with samples (1) and (2), sample (3) exhibited very good surface lubricity immediately after getting wet with water.

[Example 2] Soft polyvinyl chloride 3 cmX 5 c■XO. , 4t
■■ in an aqueous solution of 5 wt% diethylenetriamine and 5 wt% tetra-n-butylammonium iosite.
After immersion at 0°C for 10 minutes and drying at 60°C for 30 minutes, methyl vinyl ether maleic anhydride copolymer (GANTREZ A
N-139) 2.5% immersed in EK solution for 10 seconds, 6
Dry at 0°C for 2 hours. After that, it was immersed in water for about 1 hour, and after water treatment, it was dried for 24 hours at 60°C. Surface lubricity treated sample (4)
I got it.

[Example 3] Polyethylene glycol (MW = 1000) lOg
, Penryerythritol 4g, Toluene diisocyanate 1B. A polyurethane resin having terminal incyanate groups was synthesized by reacting with g.

This polyurethane resin is 3cm x 5cm x 0.4tmm.
This sheet was immersed in a 1.25% MEK solution of methyl vinyl ether maleic anhydride copolymer for 10 seconds, dried at 60°C for 2 hours, immersed in water at room temperature for about 1 hour or more, and dried at 60°C for 24 hours. A surface lubricity treated sample (5) was obtained.

In the friction resistance test and durability test, like sample (3),
It was very good.

[Example 4] 7Fr (outer diameter 2.3 mm, inner diameter 1.411 m) nylon 6
Immerse a manufactured #■ tube imaging catheter in dilute hydrochloric acid at 30°C for 60 minutes, rinse thoroughly with water, then soak in a mixed solution of 1:2 of a 10% polyethyleneimine aqueous solution and a 5% methanol solution of dicyclohexyl carbonimide for 5 hours at 30°C, and then rinse with water. , methyl vinyl ether maleic anhydride copolymer 1.25%M
It was immersed in an EK solution for 10 minutes, dried at 80°C for 2 hours, immersed in water at room temperature for about 1 hour or more, and dried at 60°C for 24 hours to obtain a surface-lubricious catheter (6).

It showed very good lubricity and durability in friction resistance tests and durability tests.

[Example 5] A stainless steel rod with a diameter of 0.87 and a length of 100 cm was immersed in a 5% polyurethane n+Fm solution and a 4.4'-diphenylmethane diisocyanate diisocyanate solution, dried at 80°C for 1 hour, and then soaked in 2.5% methyl. Vinyl ether maleic anhydride copolymer (GANTR
EZ AN- 169 MW = 1.5 million manufactured by GAF)
After immersion in MEK solution for 1 minute and drying at 60°C for 30 minutes,
It was immersed in water for about 3 hours, and after water treatment, it was dried at 60°C for 24 hours to provide surface lubricity, and a catheter guide wire (7) was obtained.

When a guide wire (7) wetted with physiological saline was inserted into a 7Fr angiography catheter and operated, the dynamic resistance was very low and satisfactorily.

[Example 6] A balloon catheter made of 18Fr (outer diameter 6 + sm) made of natural rubber was treated with 4,4'-diphenylmethane diisocyanate and then treated with methyl vinyl ether maleic anhydride copolymer (G
ANTREZ AN-189 MIll= 1.5 million G
After dipping in 1% MEK solution (manufactured by AF) for 1 second and drying at 80°C for 30 minutes, immersing in water for about 3 hours, and after water treatment, at 60°C.
Dry for 24 hours and add surface lubricity to the balloon catheter (8
) was obtained.

The surface lubricity was good as in the previous example.

[Example 7] Soft polyvinyl chloride 3c layer X5c layer X O. 4tmm 4,4'-diphenylmethane diisocyanate 1YNE
After immersing in W solution for 1 minute and drying for 30 minutes at 60'0,
Methyl vinyl ether maleic anhydride copolymer (GAN
TREZ AN-170, MW=807j GAF
) Noethyl ester (degree of esterification 40-50%)
It was immersed in the solution for 10 seconds and dried at 60°C for 2 hours to obtain a surface lubricity treated sample (21).

As a result of performing frictional resistance and durability tests separately shown on sample (21), the value of frictional resistance JL = 0.02 was maintained even after continuous water washing for 6 hours. However, the surface did not reach a low frictional resistance state immediately after the sample was wetted with water, but the above-mentioned good state was obtained after some time had elapsed.

After preparing sample (21), immerse it in water at room temperature for about 30 minutes, and
After drying at 0° C. for 24 hours, a sample (22) was obtained.

As a result of conducting the same test as (21) on sample (22), it was found that this value was still maintained even after continuous water washing for 6 hours with = 0.02. Furthermore, unlike sample (21), sample (22) exhibited good surface lubricity relatively quickly after being wetted with water.

After preparing sample (1), immerse it in water for about 1 hour or more at room temperature,
After drying at 60° C. for 24 hours, a sample (23) was obtained.

Tests similar to those in (21) and (22) were conducted on sample (23), and the results showed that the frictional resistance was the same. = 6 at 0.02
This value could be maintained even after hours of continuous water washing.

Furthermore, in comparison with samples (21) and (22), sample (23) showed very good surface lubricity immediately after getting wet with water.

[Example 8] Soft polyvinyl chloride 3c Peng X5c intestine
n-Butylammonium iosite aqueous solution at 80℃ 1O
After being immersed for 10 minutes at 60°C and dried for 30 minutes, immersed in a methyl vinyl ether maleic anhydride copolymer ethyl ester 4% T) IF solution for 10 seconds and dried at 60°C for 2 hours.

Thereafter, it was immersed in water for about 1 hour, and after water treatment, it was dried at 60° C. for 24 hours to obtain a surface lubricity treated sample (24).

Similarly, a friction resistance test and a durability test were conducted, and the results were favorable.

[Example 9] Polyethylene lz7 clear: l-le (MW = 1000) 1
0 g of penry erythritol and 16 g of toluene diisocyanate to synthesize a polyurethane resin having terminal incyanate groups.

This polyurethane resin is molded into layers of 3c x 5c x 0.4, and this sheet is immersed in a 4% THF solution of half ethyl ester of methyl vinyl ether maleic anhydride copolymer (degree of esterification 40-50%) for 10 seconds. Soaking, 80
Dry for 2 hours at room temperature, soak in water for about 1 hour or more at 60℃
After drying at ℃ for 24 hours, a surface lubricity treated sample (25) was obtained.

Like sample (23), it performed very well in the friction resistance test and durability test.

[Example 10] A 7Fr (outer diameter 2.3 mm, inner diameter 1.4+u+) nylon 6 angiography catheter was immersed in dilute hydrochloric acid at 30°C for 60 minutes, and after thoroughly rinsing with water, a 10% aqueous solution of polyethyleneimine and 5% dicyclohexyl carbonimide were added. After immersing in a mixed solution of 1=2 methanol solution at 30°C for 5 hours and washing with water, it was immersed in a 4% THF solution of half ethyl ester of methyl vinyl ether maleic anhydride copolymer (degree of esterification 40-50%) for 20 minutes. , ElO'C! It was dried for 2 hours, immersed in water for about 1 hour or more at room temperature, and then dried at 60° C. for 24 hours to obtain a surface-lubricated catheter (26).

It showed very good lubricity and durability in friction resistance tests and durability tests.

[Example tB A stainless steel rod with a diameter of 0.871 and a length of 100 cm was immersed in a solution of polyurethane 5% THF and 4.4'-diphenylmethane diisocyanate 2, dried at 60°C for 1 hour, and then methyl vinyl ether anhydrous. Maleic copolymer ethyl ester (degree of esterification 40-50%) 4%T) Immersed in IF solution for 1 minute, dried at 80℃ for 30 minutes, immersed in water for about 3 hours, dried at 60℃ for 24 hours after water treatment A catheter guide wire (27) with surface lubricity was obtained.

When a guide wire (27) wetted with physiological saline was inserted into a 7Fr angiography catheter and operated, the dynamic resistance was very low and satisfactorily.

[Example 12] A 18Fr (outer diameter 6 mm) natural rubber balloon catheter was coated with 4,4'-diphenylmethane diisocyanate and then half ethyl ester of methyl vinyl ether maleic anhydride copolymer (degree of esterification 40-50%). 1%
After immersing in THF solution for 1 second and drying at 60°C for 30 minutes,
It was immersed in water for about 3 hours, treated with water, and then dried at 60° C. for 24 hours to obtain a balloon catheter (28) with surface lubricity.

The surface lubricity was good as in the previous example.

Examples 1 to 6 of the present invention (sample numbers (1) to (8)) and 1 Examples 7 to 12 of the present invention (sample numbers (21) to (2))
8)), there was no significant difference in the friction resistance and continuous water washing tests, but as a more severe test method, when the fingers were repeatedly squeezed under running water, Examples 7 to 12 showed no significant difference. The durability of surface lubricity was slightly better, and even better results were obtained.

(Example 13) Polyurethane resin 3c layer x 5 cm x O. A sheet of 4ts was soaked in 4,4'-diphenylmethane diisocyanate 0, θ% MEK# solution for 1 minute at 80℃30.
After drying for a minute, water-soluble nylon (AQ Nylon P-7
0) in 10% chloroform solution for 1 second at 60℃6
After drying and water treatment, a surface lubricity treated sample (31) was obtained.

Good results were observed in both wet lubricity and durability.

[Example 14] Polyurethane resin sheets similar to (13) were
- diphenylmethane diisocyanate o. ot%MEK
Immersed in solution for 1 minute, dried for 30 minutes at 60°C, then immersed in 0.75% chloroform solution of hydroxypropyl cellulose (HPC: Hercules H type) for 1 second, 6
After drying at 0°C for 6 hours and water treatment, the surface lubricity treated sample (32
) was obtained.

Good results were confirmed for both wet lubricity and durability.

[Comparative Example 1] Soft polyvinyl chloride 3c x 5 cm x O. 4tm
(12) low-density polyethylene, (13) high-density polyethylene, and (14) tetrafluoroethylene of the same size as the sample pieces whose m surfaces were (9) glycerin coated, (10) olive oil coated, and (11) uncoated. Prepare sample pieces and conduct friction resistance and durability tests with the invention examples (1) to (8).
As a result of conducting (2) as follows, it was found that the friction resistance was originally high on the side other than the side of the present invention, or the initial lubricity was lost after about 10 minutes of continuous water washing, and the effectiveness of the present invention was confirmed. Ta.

[Comparative Example 2] A nylon angiography catheter and sheet similar to those used in Example 4 were coated with a polyurethane resin having terminal isocyanate groups synthesized in Example 3, and polyvinylpyrrolidone (K-80, average molecular weight Mutsumi 360,000, G
Sample (15) (I
ff) was obtained.

Friction resistance test of present invention samples (1) to (5), sheet obtained in the same manner as Example 4) (81) and sample (15),
Although there was a slight difference in the latter test in the sustainability test (■), good surface lubricity was observed in all cases. However, in the sustainability test-H, sample (16) had a clear loss of lubricity, whereas the present invention (1) to (5) (61)
The lubricity was still observed. Furthermore, when both catheters were bent, peeling of the urethane layer occurred around the catheter side hole and at the boundary of the untreated portion only in sample (15), and no abnormality was observed in sample (6) prepared in Example 4.

Therefore, the effectiveness of the present invention was confirmed.

[Friction resistance test]

As shown in FIG. 5, polyvinyl chloride or polyurethane (polyvinyl chloride or polyurethane) 41 treated to have a coating according to the examples of the present invention and comparative examples is fixed on an inclined plate, and a polyamide resin sheet 43 is pasted on the bottom surface thereof. When an iron cylindrical weight 44 weighing approximately 100 g is placed on it and the inclination angle θ of the plate 41 is gradually increased, the angle θ at which the weight starts to move is determined, and the coefficient of friction is expressed as g-tan (+). The results are shown in Table 1.

Glycerin coat (8) and olive oil coat (9)
For this, a polyvinyl chloride sheet was immersed in the coating solution, and the sample surface was obtained by shaking it off to the extent that the solution would not drip.

[Durability test - Change in coefficient of friction over time] A sample having the coated surface, olive oil and glycerin coated surface described in the examples of the present invention was immersed in ice (ii) for 500 to 600 r.
The friction coefficient was determined by the test method shown in Figure 5, and its change over time was investigated. The results are shown in Table 1 and Figure 6.

[Persistence test-II (Change in lubricity due to severe friction)]

The surfaces of the samples as described in Example and Comparative Example 1 were strongly rubbed with fingers moistened with water to confirm whether or not the lubricity persisted. The results are shown in Table-1.

[Brief Description of the Drawings] Figures 1, 2, 3, and 4 show configuration examples of medical devices of the present invention, including an ED tube, a balloon catheter, a catheter for hepatic arteriography, and a guide, respectively. A side view of the wire, FIG. 5 is a diagram showing a method of measuring the coefficient of friction, and FIG. 6 is a graph showing changes in the coefficient of friction over time. Explanation of symbols ■...Coating layer of the present invention, 2...ED tube, 21
...Olive 22...Body tube, 24...
Connector, 31... Side hole, 32... Balloon,
33... Main body tube, 34... Branch tube for balloon, 35... Main body connector, 41... Sample plate, 42
... inclined plate, 43 ... bottom plate, 44 ... weight,
5... Hepatic artery contrast catheter, 6... Sword wire

Claims (1)

[Claims] (D A reactive functional group present on at least the surface of the base material constituting the medical mu is covalently bonded to a water-soluble polymer substance or a derivative thereof, and the surface has lubricity when wetted. A medical device characterized by being configured as follows. (2) The water-soluble polymeric substance is a cellulose-based polymeric substance,
The medical device according to claim 5, which is a maleic anhydride-based polymer material, an acrylamide-based polymer material, a polyethylene oxide-based polymer material, or a water-soluble nylon. (3) The medical device according to claim 2, wherein the cellulosic polymer material is hydroxypropyl cellulose. (4) Claim 2, wherein the maleic anhydride-based polymeric substance is a methyl vinyl ether maleic anhydride copolymer.
Medical equipment listed in section. (5) The medical device according to claim 2, wherein the acrylamide-based polymer material is polyacrylamide. (6) The medical device according to claim 2, wherein the polyethylene oxide polymeric substance is polyethylene glycol. (7) Claim 1 in which the reactive functional group is an aldehyde group, an epoxy group, an incyanate group, or an amine group.
Medical equipment listed in section. (8) The medical device according to claim 1, which comprises a rod-shaped body that can be inserted into a medical tube, and is a guide tool that allows the medical tube to be introduced into or removed from the body. (9) Treat a base material constituting a medical device with a solution of a compound having a reactive functional group so that the reactive functional group is present on at least the surface of the base material. A layer is formed and then treated with a water-soluble polymeric substance or a derivative thereof to covalently bond the reactive functional group and the water-soluble polymeric substance, and a coating layer of the water-soluble polymeric substance is formed on the base layer. A method for manufacturing a medical device, characterized in that the surface thereof has lubricity at S temperature. (lO) A base material constituting a medical device is treated with a solution of a compound having a reactive functional group, a base layer is formed so that a reactive functional group is present on at least the surface of the base material, and then a water-soluble highly Treatment with a molecular substance or a derivative thereof to covalently bond the reactive functional group and the water-soluble polymer substance to form a coating layer of the water-soluble polymer substance on the base layer, followed by water treatment. A method for manufacturing a medical device, characterized in that the surface thereof has lubricity when wetted.