JPH08280790A - Medical material and its production - Google Patents

Abstract

PURPOSE: To make it possible to obtain the elution rate and elution patterns of an antimicrobial agent which is easily producible and meets the purposes of use by incorporating a pyridone carbonic acid-base antimicrobial agent into an ethylene-vinyl alcohol copolymer or polyether-base block copolymer. CONSTITUTION: The ethylene-vinyl alcohol copolymer or polyether-base block copolymer and the pyridone carbonic acid-base antimicrobial agent are mixed in a molten state. The ethylene content of the ethylene-vinyl alcohol copolymer is set in a range of 10 to 80mol%, more preferably about 27 to 47mol%. The number average polymn. degree thereof is set at about 10,000 to 50,000. The strength and workability of the copolymer degrade if the content is below 10mol%. The elutability of the antimicrobial agent degrades at >=80mol%. On the other hand, for example, a polyether-polyurethane block copolymer consisting of soft segments having a polyether part and hard segments is used for the polyether-base block copolymer.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical material for forming a medical instrument or the like that comes into contact with a living body and a method for producing the same in the medical field. And a method for producing the same.

[0002]

2. Description of the Related Art In recent years, various medical materials have been developed with the progress of science and technology, and have been used as medical instruments for living bodies. On the other hand, the problem of infectious diseases caused by such medical devices is also becoming very large. For example,
Devices that connect the inside and outside of the body such as blood vessel catheters and urethral catheters are likely to be the entry route of bacteria from the outside,
The wound healing material has a problem that it easily becomes a breeding nest of bacteria. Also, in medical devices such as artificial blood vessels, artificial hearts, artificial lungs, and blood circuits, cases have been reported in which the light and darkness of treatment is influenced by bacterial infection from these devices themselves. In particular, patients who require such medical devices have a weakened immunity due to illness, and it is necessary to pay sufficient attention to the entry of bacteria.

Therefore, it has been studied to impart antibacterial activity to the medical material itself constituting the medical device, and as a method therefor, for example, a method of immobilizing an antibacterial agent on the medical material is used. The antibacterial agent has excellent antibacterial activity,
In addition, those having a broad antibacterial spectrum are preferable, and examples of such antibacterial agents include pyridonecarboxylic acid antibacterial agents.

Examples of the medical material to which the above-mentioned antibacterial agent is immobilized include, for example, (1) a material in which the surface of the medical material is modified to chemically bond the antibacterial agent (WO92 / 007).
47, etc.), (2) A material in which an organic solvent solution of an antibacterial agent is impregnated into a medical material (JP-A-62-11457, JP-A-63-43668, etc.), and (3) an antibacterial agent A material in which an organic solvent solution with a polymer is coated on the surface of a medical material (JP-A-2-17071), (4) A material obtained by dispersing an antibacterial agent in rubber or a general synthetic resin (special Kaisho 6
No. 2-161377) and the like.

[0005]

[Problems to be Solved by the Invention] However, the above (1)-
The medical material of (3) has a fatal drawback that it lacks the sustainability of antibacterial activity in addition to the drawbacks such as a complicated manufacturing process and the need to use an organic solvent harmful to the human body. There is. Although the medical material of (4) solves some of the above-mentioned drawbacks, it does not have sufficient sustaining antibacterial activity because it uses a mere general synthetic resin. Further, when rubber is used, the antibacterial agent may be decomposed during vulcanization of the rubber to generate a decomposed product harmful to the human body.

[0006] Further, although the elution amount of the antibacterial agent and the change over time (elution pattern) of the elution amount differ depending on the purpose of use of the medical material, they are adjusted in the medical materials of (1) to (4) above. It also has the drawback of being difficult to do.
For example, a pyridonecarboxylic acid antibacterial agent has a bacterial regrowth inhibitory effect even when the amount of elution is below the minimum inhibitory concentration of bacteria. In the case of using it for such purposes, it is preferable to control so that the antibacterial agent can be eluted continuously for a long period of time even if the elution concentration of the antibacterial agent is low in order to suppress the generation of resistant bacteria. On the other hand, when it is used as a wound treatment material, it is preferable that the antibacterial agent can be adjusted so that it can be continuously eluted at a relatively high concentration for a certain period.

However, as described above, the above (1)-
In the medical material of (4), the elution amount and elution pattern cannot be changed according to various applications, and it is difficult to optimize these for specific applications. The object of the present invention is to solve the above technical problems, easy to manufacture,
Further, the present invention provides a medical material capable of uniformly containing the antibacterial agent in the medical material, and capable of obtaining the elution amount and elution pattern of the antibacterial agent according to the purpose of use of the medical material, and a method for producing the same. That is.

[0008]

Means and Actions for Solving the Problems As a result of studies to solve the above problems, the present inventors have found that an ethylene-vinyl alcohol copolymer or a polyether block copolymer is a pyridonecarboxylic acid antibacterial agent. We have found a new fact that it is possible to contain the agent uniformly, and the elution rate of the antibacterial agent can be arbitrarily controlled depending on the type of these copolymers, the content of the antibacterial agent, the method of inclusion, etc. The present invention has been completed.

That is, the medical material of the present invention comprises an ethylene-vinyl alcohol copolymer or a polyether block copolymer containing a pyridonecarboxylic acid antibacterial agent. By using the above copolymer, the antibacterial agent can be uniformly contained in the medical material.
Furthermore, the elution amount and elution pattern of the antibacterial agent can be controlled by the kind and form of the antibacterial agent (whether it is a free form or a salt), the content and the containing method, the kind of the copolymer, the additive formulation and the like. Further, as will be described later, the elution rate can be controlled by changing the shape to be molded, especially the surface area.

The method for producing a medical material of the present invention is
It is characterized in that the ethylene-vinyl alcohol copolymer or the polyether block copolymer and the pyridonecarboxylic acid antibacterial agent are mixed in a molten state. By using the above manufacturing method, the medical material of the present invention can be easily manufactured.

The medical material of the present invention will be described in detail below. The ethylene-vinyl alcohol copolymer used in the present invention has an ethylene content of 10 to 80 mol%,
It is preferably in the range of 27 to 47 mol% and has a number average degree of polymerization of about 10,000 to 50,000. When the ethylene content is less than 10 mol%, the strength and processability of the copolymer are lowered, and when it exceeds 80 mol%, the elution property of the antibacterial agent is lowered, which is not preferable.

Specific examples of the ethylene-vinyl alcohol copolymer include Eval EP manufactured by Kuraray Co., Ltd.
-E105, ES-G110, EP-F101, ES-
H101; Soarnol D2958 manufactured by Nippon Synthetic Chemical Industry,
DT2903, DC3203, E3803, ET380
3, A4412, AT4403 and the like. As this ethylene-vinyl alcohol copolymer, those having various physical properties can be adopted depending on the purpose and application. That is, the degree of polymerization and the ethylene content of the copolymer can be appropriately set according to the desired physical properties. Furthermore, if necessary, an antioxidant, an ultraviolet absorber and other stabilizers, a lubricant and the like can be added and blended. It has already been confirmed that the ethylene-vinyl alcohol copolymer has safety and stability required for medical devices.

The polyether block copolymer used in the present invention is a block copolymer composed of a soft segment having a polyether portion and a hard segment. As the polyether portion contained in the soft segment, for example, a homopolymer or copolymer of glycol selected from the group consisting of ethylene glycol, propylene glycol and tetramethylene glycol is preferably used. As the hard segment, for example, polyurethane, polyamide, polyester, etc. are preferably used. That is, examples of the polyether block copolymer include polyether-polyurethane block copolymer, polyether-polyamide block copolymer, and polyether-polyester block copolymer.

Polyether-polyurethane block copolymers include prepolymers formed by the addition of 4,4'-diphenylmethane diisocyanate and / or 4,4'-dicyclohexylmethane diisocyanate and polyether glycol. In addition, chain extenders such as ethylene glycol, propylene glycol and tetramethylene glycol may be used. More specifically, for example, those having trade names such as Tecoflex (TherMedix), Peresen (Dow Chemical), and Angioflex (Abiomed) are listed.

As the polyether-polyamide block copolymer, the polyamide part is nylon 6, nylon 6
6, nylon 610, nylon 612, nylon 11,
An example is nylon 12 or the like. More specifically, for example, Pebax (Toray Industries, Inc.), UBE-PA
E (Ube Industries, Ltd.), Daiamide-PAE (Daicel Huls), polyether nylon 610 (Terumo Co., Ltd.) and the like.

As the polyether-polyester block copolymer, the polyester part is ethylene glycol,
Examples thereof include polycondensates of at least one glycol selected from the group consisting of propylene glycol and tetramethylene glycol, and terephthalic acid and / or isophthalic acid. More specifically, for example, Hytrel (Toray-Dupont), Perprene P (Toyobo Co., Ltd.), Perprene S (the same), Low Mod (Japan GE Plastics Co., Ltd.), Piviflex (Enimont-Nippon Synthetic Rubber Co., Ltd.) , Grelax E (Dainippon Ink Co., Ltd.) and the like.

The above polyether block copolymer is
Various physical properties can be adopted according to the purpose and application. That is, the degree of polymerization of each of the soft segment and the hard segment, the degree of polymerization of the entire copolymer, the content ratio of the soft segment and the hard segment, and the like can be set in a wide range according to desired physical properties. Furthermore, if necessary, an antioxidant, an ultraviolet absorber and other stabilizers, a lubricant and the like can be added and blended. These polyether block copolymers may be used alone, or two or more kinds may be mixed or laminated and used. It has already been confirmed that all of these copolymers have safety and stability required for medical devices.

Among the polyether block copolymers exemplified above, a polyether-polyurethane block copolymer is preferably used in the present invention. Further, those having a Shore hardness of 80A to 75D are particularly preferably used. As the antibacterial agent used in the present invention, any pyridonecarboxylic acid-based compound can be uniformly dispersed in the above copolymer and a desired drug elution ability can be realized. Examples of the pyridonecarboxylic acid-based antibacterial agent include grepafloxacin, nalidixic acid, pipemidic acid, pyromidic acid, sinoxacin, norfloxacin, enoxacin, ofloxacin, ciprofloxacin, levofloxacin, fleroxacin, sparfloxacin as common names. , Nadifloxacin,
Lomefloxacin, tosufloxacin, danofloxacin, rufloxacin, pefloxacin and the like, and 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7- (3-methylaminopiperidin-1-yl) -4- Oxoquinoline-3-carboxylic acid, 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7- (3-methyl-1-piperazinyl) -4-oxoquinoline-3-carboxylic acid, ( −)
-7-[(7S) -amino-5-azaspiro [2,4]
Heptan-5-yl] -8-chloro-6-fluoro-1
-[(1R, 2S) -cis-2-fluoro-1-cyclopropyl] 1,4-dihydro-4-oxoquinoline-3
-Carboxylic acid, (S)-(-)-10- (1-aminocyclopropyl) -9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-
De] [1,4] benzoxazine-6-carboxylic acid, 1-
Cyclopropyl-6-fluoro-8-difluoromethoxy-1,4-dihydro-7-[(3S) -methyl-1-
Piperazinyl] -4-oxo-3-quinolinecarboxylic acid, 7- [2- (aminomethyl) -4-morpholinyl]
Examples include -1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. These may be used alone or in combination of two or more. Among the above-exemplified antibacterial agents, grepafloxacin, ofloxacin, fleroxacin,
Levofloxacin, sparfloxacin and ciprofloxacin are preferably used.

A particularly preferred antibacterial agent in the present invention is grepafloxacin. Since grepafloxacin has excellent compatibility with the above-mentioned copolymer, it can be uniformly mixed. In particular, it has excellent compatibility with ethylene-vinyl alcohol copolymers and polyether-polyurethane block copolymers, and is suitable for use in combination with these copolymers.

The antibacterial agent may be contained in the copolymer in the form of a free form, or may be contained in the form of a pharmaceutically acceptable acid salt. As will be described later, the elution pattern differs depending on the form of the antibacterial agent, and therefore either one may be selected according to the purpose of use and the application. It is also possible to use a mixture of the educt and the acid salt. Examples of the acid salt include inorganic acid salts such as hydrochloride, hydrobromide, nitrate, sulfate and phosphate, methanesulfonate, p
-Toluene sulfonate, acetate, citrate, tartrate, maleate, fumarate, malate, lactate and other organic acid salts.

The compounding amount of the antibacterial agent may be set according to the desired elution amount and elution pattern. The range of blending amount is 0.001 to 60 parts by weight, preferably 0.01 to 50 parts by weight, more preferably 0.05 to 30 parts by weight, and especially 0.1 to 100 parts by weight of the copolymer. 20 parts by weight is preferable. When the content of the antibacterial agent is more than 60 parts by weight, the moldability is poor and the physical properties of the resulting molded article deteriorate, which is not practical. On the other hand, when the content of the antibacterial agent is less than 0.001 part by weight, it becomes difficult to control the elution of the antibacterial agent, and the effect of preventing the invasion of bacteria is reduced, so that the effect of adding the antibacterial agent is lost. As will be described later,
By changing the content of the antibacterial agent within the above range, the elution rate of the antibacterial agent can be controlled.

When an antibacterial agent is used as a free form, generally, the higher the content, the faster the elution rate of the antibacterial agent. However, there is an upper limit to the amount in which the antibacterial agent is uniformly dispersed in the polymer, and if the antibacterial agent is contained in excess of this upper limit, the dissolution rate will decrease. However, the duration of elution is considered to be extended. When an antibacterial agent is used as an acid salt, the elution rate increases as the content of the antibacterial agent increases. Therefore, it is preferable to determine the content and form of the antibacterial agent in accordance with the type, purpose, use, etc. of the medical material to be formed, and the free form and the acid salt may be mixed and used at an appropriate ratio. Since the acid salt of the pyridonecarboxylic acid antibacterial agent is extremely stable against ethylene oxide gas, there is an advantage that the content of the antibacterial agent does not decrease even when sterilized by such gas. is there.

The medical material of the present invention can be suitably used, for example, as a material for medical instruments. Examples of such medical devices include urethral catheters, blood vessel catheters, wound healing materials, sutures, cannulas, monitoring tubes, artificial kidneys, artificial hearts, artificial lungs, blood circuits for extracorporeal circulation, artificial kidney AV shunts, and artificial blood vessels. , Artificial heart valve, temporary blood bypass tube, blood circuit for artificial dialysis, vascular stent, urethral stent, endotracheal tube, intraocular lens, blood bag, disposable circuit for blood component separation device,
Examples include drains, aneurysm clips, nerve cuffs, cerebrospinal fluid shunts, dressings, peritoneal dialysis catheters, film-shaped or hollow dialysis membranes, and corneal protective materials.

Next, the method for producing the medical material of the present invention will be described in detail. The medical material of the present invention can be produced by mixing the above-mentioned ethylene-vinyl alcohol copolymer or polyether block copolymer with a pyridonecarboxylic acid antibacterial agent in a molten state. In the production of the medical material of the present invention, it is sufficient that the antibacterial agent can be uniformly dispersed with the polymer in a state where the antibacterial agent is not decomposed. The combination with the agent may be selected. Usually, melt molding is performed at 150 to 240 ° C.

If necessary, operations such as melting and molding can be carried out in an oxygen-free atmosphere to prevent oxidation of the antibacterial agent and the copolymer. Further, it is preferable to remove water in the polymer to be used as much as possible from the viewpoints of stability of the drug or copolymer and accuracy of the molded product. Various molding methods can be used for the melt molding, for example, a fibrous, tube-shaped or sheet-shaped molded product can be molded by extrusion molding, and a molded product having a complicated structure can be molded by injection molding. Also, by using a crosshead, etc.,
Coating on metal wire is also possible.

Regarding the elution control of the antibacterial agent from the molded article in the melt molding, the kind, form (form or salt) and content of the antibacterial agent in the copolymer, and further the kind of the copolymer to be used, etc. Can be changed. Further, the elution of the antibacterial agent can be controlled by blending additives such as a stabilizer and a lubricant. Furthermore, by performing multi-layer (multi-color) molding and changing the type, form (whether free form or salt) and content of the antibacterial agent in each layer (part), the physical properties required as a medical material are obtained, and It is possible to control anti-infective property and finer elution with only the necessary part.

Among the medical materials of the present invention, those formed into a tubular shape, especially those using a polyether-polyurethane block copolymer are, for example, catheters such as urethral catheters and vascular catheters, blood circuits for extracorporeal circulation. It is preferably used as a cannula, a bypass tube or the like. Also, by molding using a multi-layer die, it is possible to easily mold multi-layer tubes having different compositions. Specific examples thereof include a layer composed of a polyether-polyurethane block copolymer containing 1% of grepafloxacin hydrochloride, a layer composed of only a polyether polyurethane block copolymer, and grepafloxacin hydrochloride in order from the outer layer. An example is a tube having a three-layer structure of a layer made of a polyether polyurethane block copolymer containing 1% of.

From a metal wire whose surface is coated with the material of the present invention using a crosshead die,
Stents such as a vascular stent and a urethral stent can be produced. Furthermore, the material of the present invention formed into a film can be suitably used as a material for blood bags, dressings and the like.

Among the medical materials of the present invention, those using the ethylene-vinyl alcohol copolymer are particularly suitable for extrusion molding and injection molding, and in addition to fibrous, tubular or sheet-shaped moldings, This is advantageous for manufacturing a molded product having a complicated structure. For example, a suture can be produced from a fibrous product, and can be further spun into a wound treatment material or an artificial blood vessel, or directly processed into a non-woven fabric by a spun pond method, a melt blow method, a flash spinning method, or the like. it can. Further, examples of molded articles having a complicated structure include various cocks and various adapters.

As another example of the use of the medical material of the present invention, a method of using the material of the present invention molded in an arbitrary shape in a medical device as a member for exhibiting an anti-infective action is also used. It is possible. For example, a method of encapsulating a small piece of the material of the present invention in the form of a film or a granular material in an existing blood component storage bag, a method of fixing the small piece of the material of the present invention upstream in the extracorporeal circulation circuit, and the like can be mentioned.

[0031]

The present invention will be described below with reference to examples.
The invention is not limited to these examples only. Example 1 An ethylene-vinyl alcohol copolymer (manufactured by Kuraray Co., Ltd., "Eval EP-E105A, ethylene content 44 mol%) was pulverized with an analytical pulverizer to give a particle size of 50 to 125 µm.
The thing was collected. 45.0 g of the pulverized copolymer
And Grepafloxacin (Otsuka Pharmaceutical Co., Ltd.) 5.0 g
, And a super-small kneading extruder (made by CSI, MAXMIXING
EXTRUDER, CS-194A type) was kneaded and extruded at 180 ° C. using a strand die. Then, this was pelletized and hot-pressed at 180 ° C. with a test bench press (manufactured by Toyo Seiki) to obtain a slightly yellowish transparent film having a thickness of 100 μm. The grepafloxacin content of this film is 10% by weight. Example 2 An ethylene-vinyl alcohol copolymer (described above) was pulverized with an analytical pulverizer to obtain particles having a particle size of 50 to 125 μm. 49.5 g of this copolymer and 0.5 g of grepafloxacin (previously described) were mixed and kneaded and extruded at 180 ° C. using a strand die in an ultra-small kneading extruder (previously described) to give a slightly yellow color. A tinged transparent strand was obtained. Then, pelletize this and use a tabletop test press (described above) for 18
Hot pressing was performed at 0 ° C. to obtain a colorless and transparent film having a thickness of 100 μm. The grepafloxacin content of this film is 1% by weight. Example 3 An ethylene-vinyl alcohol copolymer (described above) was pulverized with an analytical pulverizer to obtain particles having a particle size of 50 to 125 μm. This copolymer (45.0 g) and grepafloxacin hydrochloride (Otsuka Pharmaceutical Co., Ltd.) (5.0 g) were mixed and kneaded and extruded at 180 ° C. using a strand tie in an ultra-small kneading extruder (described above). , A white strand was obtained. Then, this was pelletized, and hot pressed at 180 ° C. with a test bench press (described above) to obtain a white film having a thickness of 100 μm.
The grepafloxacin hydrochloride content of this film is 10
% By weight. Example 4 (Dissolution test) 100 mg of each of the films obtained in Examples 1 to 3 was placed in 10 ml of physiological saline having a pH of 7.4 that had been preheated to 37 ° C., and a constant temperature shaker was used. Shake at 37 ° C. for 1 hour. After shaking, remove the film from the physiological saline solution, and use another physiological saline solution (37 ° C, pH 7.4) 10 m.
Shaking was carried out in the same manner as above for 1 hour. Hereinafter, this operation was repeated for a total of 8 hours, and the concentration of grepafloxacin eluted in physiological saline was measured every hour. The result is shown in FIG.

As is clear from FIG. 1, continuous elution of grepafloxacin was observed in all the films of Examples 1 to 3. The film of Example 2 has a small amount of grepafloxacin and therefore has a small amount of elution, but sustained elution is observed, and such an elution amount may be preferable depending on the application. It can be fully used as a material. Example 5 The same as Example 2 except that 0.5 g of sparfloxacin (extracted and purified from 100 mg tablets of trade name “SPARA” manufactured by Dainippon Pharmaceutical Co., Ltd.) was used as the antibacterial agent instead of grepafloxacin. The operation was performed to obtain a yellow transparent film having a thickness of about 100 μm. The sparfloxacin content of this film is 1% by weight. Example 6 (Dissolution test) The film obtained in Example 5 was subjected to a dissolution test in the same manner as in Example 4. The result is shown in FIG.

As is apparent from FIG. 2, continuous elution of sparfloxacin was observed in the film of Example 5. Example 7 Polyether-polyurethane block copolymer [Tecoflex EG-65D (added product of polymer of tetramethylene glycol and 4,4′-dicyclohexylmethane diisocyanate, product of Thermedics, chain extender: tetra Methylene glycol)] 49.5 g and grepafloxacin (previously described) 0.5 g were mixed and kneaded and extruded at 180 ° C. using a strand die in an ultra-small kneading extruder (previously described). Then, pelletize this, heat-press at 180 ° C. with a tabletop test press (described above) to obtain a thickness of about 100.
A colorless transparent film having a thickness of μm was obtained. The grepafloxacin content of this film is 1% by weight. Example 8 Polyether-polyurethane block copolymer (supra)
49.5 g and grepafloxacin hydrochloride (supra) 0.5
g was mixed, and kneaded and extruded at 180 ° C. using a strand die in an ultra-small kneading extruder (described above). This is then pelletized and 180 ° C with a tabletop test press (described above).
The film was hot-pressed with to obtain a cloudy film having a thickness of about 100 μm. The grepafloxacin hydrochloride content of this film is 1% by weight. Example 9 (Dissolution test) 100 mg of each of the films obtained in Examples 7 and 8 was
Add each to 10 ml of pH 7.4 physiological saline that has been heated to 37 ° C in advance, and use 37
Shake at 1 ° C for 1 day. Then another saline solution (37
The mixture was shaken for 1 day in 10 ml of 10 ° C., pH 7.4) in the same manner as above. Hereinafter, this operation was repeated for a total of 30 days, and the concentration of grepafloxacin eluted in physiological saline was measured every day. The result is shown in FIG.

As is clear from FIG. 3, continuous elution of grepafloxacin is observed from the films of Examples 7 and 8. Example 10 Polyether-polyurethane block copolymer (Tecoflex EG-93A manufactured by Thermedix Co.) 49.
5 g and 0.5 g of grepafloxacin hydrochloride (previously described) were mixed and kneaded and extruded at 170 ° C. using a tube die in an ultra-small kneading extruder (previously described), inner diameter 0.8 mm, outer diameter 1 A 1 mm tube was made.

Since the obtained tube is flexible,
It can be suitably used as an indwelling venous catheter. Example 11 An ethylene-vinyl alcohol copolymer (described above) was pulverized with an analytical pulverizer to obtain particles having a particle size of 50 to 125 μm. 49.5 g of this pulverized copolymer and 0.5 g of grepafloxacin hydrochloride (previously described) were mixed and kneaded and extruded at 180 ° C. using a strand die in an ultra-small kneading extruder (previously described), It was drawn to obtain a yarn having a thickness of 25 μm.

Since the obtained thread has sufficient strength and flexibility, it can be suitably used as a suture thread. Example 12 49 g of polyether-polyurethane block copolymer (Tecoflex EG-80A manufactured by Thermedix Co., Ltd.)
And 1 g of grepafloxacin hydrochloride (above) were mixed and extruded at 165 ° C. in a nitrogen atmosphere with a T-die in a micro-kneading extruder (above), a white film with a thickness of about 30 μm. Got

Since the obtained film has flexibility, it can be suitably used as a wound dressing material. Example 13 Polyether-polyurethane block copolymer (Tecoflex EG-68D manufactured by Thermedix Co.) 49.
5 g and 0.5 g of grepafloxacin hydrochloride (supra) were mixed. This was applied to a stainless wire with a diameter of 0.12 mm at a temperature of 180 ° C. in a nitrogen atmosphere using a crosshead die in a micro kneading extruder (described above), and a stainless steel with a thickness of 0.17 mm was coated. A wire was produced. The obtained 24 wires were twisted together to prepare a self-expanding-wall type urethral stent having an outer diameter of 14 mm before insertion.

[0038]

As described above, in the medical material of the present invention, the antibacterial agent is uniformly dispersed in the medical material. Moreover, the antibacterial agent can be continuously eluted over a long period of time, and the elution amount and elution pattern of the antibacterial agent can be changed according to the intended use of the medical material.

Further, according to the method for producing a medical material of the present invention, there is an effect that the material can be easily produced. Therefore, the medical material of the present invention can be suitably used as a material for forming various medical devices.

[Brief description of drawings]

FIG. 1 is a graph showing changes over time in the elution concentration of grepafloxacin obtained using the films of Examples 1 to 3.

FIG. 2 is a graph showing the change over time in the elution concentration of sparfloxacin obtained using the film of Example 5.

FIG. 3 is a graph showing the elution concentration of grepafloxacin obtained using the films of Examples 7 and 8.

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Claims (10)

[Claims] 1. A medical material comprising an ethylene-vinyl alcohol copolymer or a polyether block copolymer containing a pyridonecarboxylic acid antibacterial agent. 2. The medical material according to claim 1, wherein the ethylene content in the ethylene-vinyl alcohol copolymer is 10 to 80 mol%. 3. The medical material according to claim 1, wherein the polyether block copolymer is a polyether-polyurethane block copolymer. 4. A polyether-polyurethane block copolymer wherein the prepolymer formed by addition of 4,4′-diphenylmethane diisocyanate and / or 4,4′-dicyclohexylmethane diisocyanate and polyether glycol. Polymer is ethylene glycol,
The medical material according to claim 3, which is chain-extended with a chain extender selected from the group consisting of propylene glycol and tetramethylene glycol. 5. The content of the pyridonecarboxylic acid antibacterial agent is
0.001 to 100 parts by weight of ethylene-vinyl alcohol copolymer or polyether block copolymer
To 60 parts by weight, The medical material according to any one of claims 1 to 4. 6. The medical material according to claim 1, wherein the pyridonecarboxylic acid antibacterial agent is grepafloxacin. 7. The medical material according to claim 1, wherein the medical material is a medical device material. 8. A method for producing a medical material, which comprises mixing an ethylene-vinyl alcohol copolymer or a polyether block copolymer and a pyridonecarboxylic acid antibacterial agent in a molten state. 9. The method for producing a medical material according to claim 8, wherein the polyether block copolymer is a polyether-polyurethane block copolymer. 10. The method for producing a medical material according to claim 8 or 9, wherein the pyridonecarboxylic acid antibacterial agent is grepafloxacin.