JPH08245389A - Granular resin material, medical material and medicinal preparation containing same resin material - Google Patents

Abstract

PURPOSE: To obtain a granular resin material capable of sustainedly releasing only the necessary amount of cilostazol over a long period into a living body without causing any adverse effect such as a headache by blending the specific amount of cilostazol with the copolymer of ethylene/vinyl alcohol. CONSTITUTION: This granular resin material having <=2000μm (especially preferably 75-105μm) particle diameter is prepared by blending (A) a ethylene/vinyl alcohol copolymer having a high safety and stability to a living body, 44-47mol% ethylene content, 12000-40000 number averaged molecular weight and 160-175 deg.C melting point with (B) 5-90wt.% (most preferably 60-85wt.%) cilostazol. Furthermore, cilostazol exhibits a high suppressing effect for platelet aggregation and also has an inhibiting effect to phosphodiesterase, an antiulcer effect, a hypotensive effect, an antiphlogistic effect, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a resin granule containing cilostazol as an active ingredient, a medical material, and a pharmaceutical preparation containing the resin granule and particularly used as an oral preparation.

[0002]

BACKGROUND OF THE INVENTION Cilostazol has a high inhibitory effect on platelet aggregation, a phosphodiesterase inhibitory effect, an anti-ulcer effect, an antihypertensive effect, and
Since it has an anti-inflammatory effect, it is widely used as an anti-thrombotic agent, a cerebral circulation improving agent, an anti-inflammatory agent, an anti-ulcer agent, an antihypertensive agent, an anti-asthma agent, and a phosphodiesterase inhibitor.

Cilostazol is usually used in the form of tablets, which are obtained by adding an excipient and other ingredients thereto, and is orally administered. However, since the tablet rapidly disintegrates in the living body, a large amount of cilostazol is released in the living body in a short time, which may cause side effects such as headache, heavy feeling of head, and pain.

The main object of the present invention is to solve the above-mentioned problems and to provide a resin granule capable of continuously releasing only a necessary amount of cilostazol into a living body for a long time.

[0005]

Means for Solving the Problems To solve the above problems, the present inventors have studied to combine cilostazol with a polymer material, and as a result, have found that ethylene-vinyl alcohol copolymers containing cilostazol in an amount of 5 to 90%. By controlling the particle size to 2000 μm or less by containing it in a weight percentage, the release rate of cilostazol into the body can be controlled arbitrarily, and as a result, sustained release of cilostazol into the body over a long period of time is possible. The present invention has been completed by discovering a new fact that

That is, the resin granules of the present invention contain ethylene-vinyl alcohol copolymer containing 5 to 5 parts of cilostazol.
90% by weight, the particle size is 2000 μm
It is characterized in that it is the following granular material. The above ethylene-
The vinyl alcohol copolymer has high safety and stability for living bodies, and is used in various medical materials and the like. On the other hand, cilostazol is excellent in dispersibility in the ethylene-vinyl alcohol copolymer, and thus can be compatible with each other at a high temperature, and by cooling this, a solid substance can be obtained at an arbitrary ratio.

Further, the same solid substance can be obtained by dissolving the both in a solvent and then removing the solvent. The medical material of the present invention is an ethylene-vinyl alcohol copolymer containing cilostazol in a proportion of 60 to 85% by weight. The resin granules of the present invention alone or by mixing with a conventional pharmaceutical carrier,
It can be used as a pharmaceutical formulation.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The ethylene content in an ethylene-vinyl alcohol copolymer can be appropriately determined according to the processing method of the resin granules, etc.
˜70 mol%, preferably 38 to 47 mol%, particularly preferably 44 to 47 mol%. The ethylene content is 2
If it is less than 7 mol%, the processability in the melting method described below will be reduced. On the other hand, when the ethylene content exceeds 70 mol%, the compatibility of cilostazol with the ethylene-vinyl alcohol copolymer becomes poor.

The ethylene-vinyl alcohol copolymer has a number average degree of polymerization of 5,000 to 10,000.
0, preferably 10,000 to 50,000, particularly preferably 12,000 to 40,000 is suitable. If necessary, various biosafe plasticizers, stabilizers, secondary plasticizers, lubricants and the like may be added. The melting point of the ethylene-vinyl alcohol copolymer is usually 120 to 200.
℃, preferably 140-191 ℃, particularly preferably 16
It is 0-175 degreeC. If the melting point is lower than 120 ° C, the solubility and dispersibility of cilostazol will deteriorate, and
If it exceeds, the cilostazol may be decomposed during the production by the melting method described later, the processability may be poor, and the ethylene-vinyl alcohol copolymer may be discolored during the production by the melting method.

The content of cilostazol is usually about 5
90% by weight, preferably 20 to 85% by weight, especially 30 to 85% by weight, particularly preferably 40 to 85% by weight, and further preferably about 60 to 85% by weight. If the content of cilostazol is lower than 5% by weight, the expected oral absorption cannot be obtained due to excessive sustained release. On the other hand, when the content of cilostazol exceeds 90% by weight, the sustained release effect is not observed, and the suppression of side effects such as headache cannot be expected.

The particle size of the resin granules containing cilostazol is 2000 μm or less, preferably 1000 μm.
It is particularly preferably 600 μm or less. Specifically, the particle size is 75 to 250 μm, preferably 75 to 15
0 μm, particularly preferably 75 to 105 μm. When the particle size exceeds 2000 μm, the release of cilostazol from the inside of the particle is excessively suppressed, and the desired oral absorption of cilostazol cannot be expected, which is not preferable.

Next, in order to produce the resin granules of the present invention, a so-called melting method, in which an ethylene-vinyl alcohol copolymer and cilostazol are mixed in a molten state and molded, is preferably adopted. The melt should allow the cilostazol to be uniformly dispersed in the ethylene-vinyl alcohol copolymer without decomposition. Therefore, the ethylene-vinyl alcohol copolymer is melted at a temperature below the decomposition temperature of cilostazol (about 240 ° C.), 14
The above resin is melted at 0 to 210 ° C, preferably 160 to 185 ° C, particularly preferably 165 to 180 ° C. It should be noted that, if necessary, operations such as melting and molding can be carried out in an oxygen-free atmosphere to prevent oxidation of cilostazol and the resin. Further, it is preferable to remove water in the ethylene-vinyl alcohol copolymer as much as possible from the viewpoint of the stability of cilostazol and the resin and the properties of the molded product.

Various molding methods can be used for the melt molding, and for example, a rod-shaped, droplet-shaped or sheet-shaped molded product can be obtained by extrusion molding. Also, an injection molding method can be used. After molding, crush the molded product with a crusher,
Then, if necessary, classification is performed to adjust to a predetermined particle size.
The pulverizer to be used, the pulverization conditions and the like can be appropriately determined according to the intended particle size and the like.

To control the release of cilostazol from a molded article in melt molding, the content of cilostazol in the ethylene-vinyl alcohol copolymer, the ethylene content of the ethylene-vinyl alcohol copolymer used, the degree of saponification, etc. are changed. Can be done by In addition, a plasticizer, a stabilizer, an ethylene-vinyl alcohol copolymer,
The release of cilostazol can also be controlled by appropriately adding additives such as secondary plasticizers and lubricants as needed.

A solution method can be adopted instead of the melting method. In the solution method, the ethylene-vinyl alcohol copolymer and cilostazol are uniformly dissolved in a solvent, the solvent is distilled off, and the resin granules of the present invention are obtained by pulverizing in the same manner as above. Examples of the solvent include dimethylformamide, dimethylacetamide, dimethylsulfoxide, cyclohexanone, tetrahydrofuran, chloroform, dichloromethane, acetone, 1,1,1,
Examples include 3,3,3-hexafluoro-2-propanol and a mixed solvent of two or more of these. Of these, particularly in the ethylene-vinyl alcohol copolymer, 1,1,1,3,3,3-hexafluoro-2-propanol, dimethylsulfoxide, etc. are highly soluble and easily distilled off. preferable.

It is preferable that the ethylene-vinyl alcohol copolymer used is thoroughly washed in advance by a method such as Soxhlet extraction to remove impurities and the like from the resin. In addition, it is preferable to sufficiently dry the resin to sufficiently remove water in the resin. Molding is carried out by casting a solution of the above components dissolved in a solvent on a glass plate or extruding it into a rod shape, and then removing the solvent. As a result, it is formed into a film shape, a rod shape, or the like. Removal of the solvent is, for example, air drying
It is carried out by heating and drying under reduced pressure, phase separation with a coagulating liquid, and the like. Examples of the coagulating liquid include poor solvents for ethylene-vinyl alcohol copolymers, such as water, alcohols such as methanol, ethanol, propanol and butanol, and ketones such as acetone. In this case, it is necessary to avoid elution of cilostazol into the coagulation liquid during the coagulation of the resin. Therefore, when the solubilizing power of cilostazol with respect to the poor solvent is large, it is preferable to use, as the coagulating liquid, a solvent that reduces the solubilizing power of cilostazol is mixed with the poor solvent.

In the solution method, the release rate of cilostazol from the molded article is controlled by controlling the content of cilostazol contained in the ethylene-vinyl alcohol copolymer,
It can be carried out by changing the ethylene content of the ethylene-vinyl alcohol copolymer, the method for removing the solvent (for example, drying under normal pressure or reduced pressure, or coagulation using a coagulating liquid). it can. Also,
The release rate can also be controlled by blending additives such as a plasticizer, a stabilizer, a secondary plasticizer, and a lubricant as needed.

The resin granules of the present invention containing cilostazol are mainly used as an oral preparation, and can be used in various forms such as capsules, tablets, granules and suspensions directly as granules or by mixing with a conventional pharmaceutical carrier. It can be administered to animals and humans in dosage forms. In addition to oral preparations, it can also be used in the form of suppositories. Oral preparations such as tablets and capsules are prepared according to a conventional method. That is, tablets are shaped by mixing the resin granules of the present invention with excipients such as gelatin, starch, lactose, magnesium stearate, talc, and gum arabic. Capsules are prepared by mixing the resin granules of the present invention with an inert formulation filler, diluent, etc. and filling them into hard gelatin capsules, soft capsules or the like.

The amount of the resin granules to be administered is not particularly limited and is appropriately selected from a wide range. However, in order to exert the initial effect of cilostazol, it can be calculated as 0. It is good to set it as 06-10 mg. In addition, 1 cilostazol was included in the dosage form.
It is advisable to mix the resin granules so as to contain ˜500 mg and to administer them once a day.

Further, the medical material of the present invention can be preferably used as a raw material of a medical preparation for continuously releasing cilostazol at an effective concentration or as a material for a medical device. In addition, a method of installing the material of the present invention in a medical device (for example, a platelet bag, an extracorporeal circulation circuit, etc.) as a member for exerting an antiplatelet effect can be mentioned.

As is apparent from the above detailed description, the present invention includes the following embodiments. (1) An ethylene-vinyl alcohol copolymer containing cilostazol in a proportion of 5 to 90% by weight, having a particle diameter of 2
Resin granules of 000 μm or less (2) The resin granules according to (1) above, wherein the content of cilostazol is 20 to 85% by weight.

(3) The content of cilostazol is 30 to 85
The resin granules according to (2) above, which are in weight%. (4) The resin granule according to the above (3), wherein the content of cilostazol is 40 to 85% by weight. (5) The resin granules according to (4) above, wherein the content of cilostazol is 60 to 85% by weight.

(6) The particle size is 600 μm or less
(5) The resin granules as described. (7) The resin granular material as described in (6) above, which has a particle diameter of 75 to 250 μm. (8) The resin granular material as described in (7) above, which has a particle diameter of 75 to 150 μm. (9) The resin granular material as described in (8) above, which has a particle diameter of 75 to 105 μm. (10) The resin granule according to any one of (1) to (4) above, which has a particle diameter of 600 μm or less.

(11) The above, wherein the particle size is 75 to 250 μm
(10) The resin granules as described above. (12) The resin granular material as described in (11) above, which has a particle diameter of 75 to 105 μm. (13) The resin granule according to any one of (1) to (12) above, wherein the ethylene-vinyl alcohol copolymer and cilostazol are mixed in a molten state. (14) The resin granules according to (13) above, which have a melting temperature of 165 to 180 ° C.

(15) The content of cilostazol is 60 to 85
The resin granules according to (14) above, which are in a weight percentage. (16) The resin granules according to (15) above, wherein the ethylene-vinyl alcohol copolymer has an ethylene content of 44 to 47 mol%. (17) The resin granules according to (16) above, wherein the ethylene-vinyl alcohol copolymer has a number average degree of polymerization of 12,000 to 40,000.

(18) A medical material comprising an ethylene-vinyl alcohol copolymer containing 60 to 85% by weight of cilostazol. (19) The medical material as described in (18) above, which has a melting temperature of 165 to 180 ° C. (20) The ethylene content in the ethylene-vinyl alcohol copolymer is 44 to 47 mol% (18) or
(19) The medical material as described above.

(21) The number average degree of polymerization of the ethylene-vinyl alcohol copolymer is 12,000 to 40,000.
The medical material according to any one of 8) to (20). (22) The above (18) to (21), wherein the ethylene content in the ethylene-vinyl alcohol copolymer is 38 to 47 mol%.
The medical material according to any one of 1. (23) A medical preparation comprising the resin granules according to claim 1 alone or mixed with a conventional preparation carrier.

[0028]

【Example】

Example 1 60 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 110 manufactured by Kuraray Co., Ltd.
A ", ethylene content: 47 mol%) crushed product (amount passed through 28 mesh) 60 g is mixed, and the mixture is kneaded into an extruder (Cu).
It was extruded at an extrusion temperature of 165 ° C. with a CS-194A type manufactured by stom Scientific Instruments Inc.). The molded product was crushed by a small crusher (SM-1 type manufactured by Inouchi Sakaeido) to obtain granules containing 50% by weight of cilostazol. Example 2 Granules obtained in Example 1 (50% by weight of cilostazol
Content) with a particle size range of 35 using various JIS standard sieves.
5 to 500 μm, 250 to 355 μm, 150 to 250
μm, 105-150 μm, 75-105 μm, 75 μ
The particles were classified into particles of m or less and other particle sizes. Example 3 48 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 110 manufactured by Kuraray Co., Ltd.
A ", ethylene content: 47 mol%) was mixed with 72 g of a pulverized product (amount passed through 28 mesh) and extruded at an extrusion temperature of 165 ° C, and 40% by weight of cilostazol was contained in the same manner as in Example 1. Granules were obtained. Example 4 Granules obtained in Example 3 (40% by weight of cilostazol
Particle size range of 105 to 150 μm, 75 to 1
The particles were classified into particles having a particle size of 05 μm, 75 μm or less and other particles. Example 5 36 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 110” manufactured by Kuraray Co., Ltd.
A ”, ethylene content: 47 mol%) was mixed in the same manner as in Example 1 except that 84 g of a pulverized product (amount passed through 28 mesh) was mixed and extrusion-molded at an extrusion temperature of 165 ° C., and 30% by weight of cilostazol was contained. Granules were obtained. Example 6 Granules obtained in Example 5 (30% by weight of cilostazol
Particle size range of 105 to 150 μm, 75 to 1
The particles were classified into particles having a particle size of 05 μm, 75 μm or less and other particles. Example 7 24 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 110 manufactured by Kuraray Co., Ltd.
A ”, ethylene content: 47 mol%) was mixed in the same manner as in Example 1 except that 96 g of a pulverized product (amount passed through 28 mesh) was mixed and extrusion-molded at an extrusion temperature of 165 ° C., and 20% by weight of cilostazol was contained. Granules were obtained. Example 8 12 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 110 manufactured by Kuraray Co., Ltd.
A ”, ethylene content: 47 mol%) was mixed with 108 g of a pulverized product (amount passed through 28 mesh) and extrusion-molded at an extrusion temperature of 165 ° C., except that 10% by weight of cilostazol was contained in the same manner as in Example 1. Granules were obtained. Example 9 6 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 110 manufactured by Kuraray Co., Ltd.
A ”, ethylene content: 47 mol%) was mixed in the same manner as in Example 1 except that 114 g of a crushed product (amount passed through 28 mesh) was mixed and extrusion-molded at an extrusion temperature of 165 ° C., and 5% by weight of cilostazol was contained. Granules were obtained. Example 10 72 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 110 manufactured by Kuraray Co., Ltd.
A ", ethylene content: 47 mol%) was mixed in the same manner as in Example 1 except that 48 g of a crushed product (amount passed through 28 mesh) was mixed and extrusion-molded at an extrusion temperature of 165 ° C, and 60% by weight of cilostazol was contained. Granules were obtained. Example 11 The granules obtained in Example 10 (containing 60% by weight of cilostazol) had a particle size range of 75 to 105 μm and 75 μm.
The particles were classified into the following and other particle sizes. Example 12 84 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 110 manufactured by Kuraray Co., Ltd.
A ", ethylene content: 47 mol%) was mixed with 36 g of a pulverized product (amount passed through 28 mesh) and extruded at an extrusion temperature of 170 ° C., and 70% by weight of cilostazol was contained in the same manner as in Example 1. Granules were obtained. Example 13 The particles obtained in Example 12 (containing 70% by weight of cilostazol) had a particle size range of 75 to 105 μm and 75 μm.
The particles were classified into the following and other particle sizes. Example 14 96 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 110 manufactured by Kuraray Co., Ltd.
A ", ethylene content: 47 mol%) was mixed with 24 g of a crushed product (amount passed through 28 mesh) and extruded at an extrusion temperature of 170 ° C, and 80% by weight of cilostazol was contained in the same manner as in Example 1. Granules were obtained. Example 15 The granules obtained in Example 14 (containing 80% by weight of cilostazol) have a particle size range of 75 to 105 μm and 75 μm.
The particles were classified into the following and other particle sizes. Example 16 108 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval ES-G 11 manufactured by Kuraray Co., Ltd.
0 A ", ethylene content: 47 mol%) was mixed with 12 g of a pulverized product (amount passed through 28 mesh), and extrusion molding was carried out at an extrusion temperature of 170 ° C, except that 90% by weight of cilostazol was contained in the same manner as in Example 1. Granules were obtained. Example 17 The granular material (containing 90% by weight of cilostazol) obtained in Example 16 was classified into particles having a particle size range of 75 μm or less and other particle sizes. Example 18 48 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval EP-E 105 manufactured by Kuraray Co., Ltd.
A ", ethylene content: 44 mol%) pulverized product (passing through 28 mesh) (72 g) was mixed, and extrusion molding was carried out at an extrusion temperature of 170 ° C, except that 40% by weight of cilostazol was contained in the same manner as in Example 1. Granules were obtained. Example 19 The granular material (containing 40% by weight of cilostazol) obtained in Example 18 was classified into particles having a particle size range of 75 to 105 μm and other particle sizes. Example 20 60 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval EP-E 105 manufactured by Kuraray Co., Ltd.
A ”, ethylene content: 44 mol%) was mixed in the same manner as in Example 1 except that 60 g of a pulverized product (amount passed through 28 mesh) was mixed and extrusion-molded at an extrusion temperature of 170 ° C., and 50% by weight of cilostazol was contained. Granules were obtained. Example 21 The granular material (containing 50% by weight of cilostazol) obtained in Example 20 was classified into particles having a particle size range of 75 to 105 μm and other particle sizes. Example 22 72 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval EP-E 105 manufactured by Kuraray Co., Ltd.”)
A ", ethylene content: 44 mol%) was mixed in the same manner as in Example 1 except that 48 g of a crushed product (amount passed through 28 mesh) was mixed and extrusion-molded at an extrusion temperature of 170 ° C, and 60% by weight of cilostazol was contained. Granules were obtained. Example 23 The granular material (containing 60% by weight of cilostazol) obtained in Example 22 was classified into particles having a particle size range of 75 to 105 μm and other particle sizes. Example 24 84 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval EP-E 105 manufactured by Kuraray Co., Ltd.
A ”, ethylene content: 44 mol%) was mixed with 36 g of a pulverized product (amount passed through 28 mesh) and extruded at an extrusion temperature of 175 ° C., and 70% by weight of cilostazol was contained in the same manner as in Example 1. Granules were obtained. Example 25 The granular material (containing 70% by weight of cilostazol) obtained in Example 24 was classified into particles having a particle size range of 75 to 105 μm and other particle sizes. Example 26 96 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval EP-E 105 manufactured by Kuraray Co., Ltd.”
A ", ethylene content: 44 mol%) was mixed with 24 g of a pulverized product (amount passed through 28 mesh) and extruded at an extrusion temperature of 175 ° C, and 80% by weight of cilostazol was contained in the same manner as in Example 1. Granules were obtained. Example 27 The granular material (containing 80% by weight cilostazol) obtained in Example 26 was classified into particles having a particle size range of 75 to 105 μm and other particle sizes. Example 28 108 g of cilostazol and an ethylene-vinyl alcohol copolymer (“Eval EP-E 10 manufactured by Kuraray Co., Ltd.
5A ", ethylene content: 44 mol%) was mixed with 12 g of a pulverized product (amount passed through 28 mesh) and extruded at an extrusion temperature of 175 ° C, and 90% by weight of cilostazol was contained in the same manner as in Example 1. Granules were obtained. Example 29 The granular material (containing 90% by weight of cilostazol) obtained in Example 28 was classified into particles having a particle size range of 75 to 105 μm and other particle sizes. (Dissolution test) The granular material obtained in each example was immersed in 500 ml of a test solution (0.3% sodium lauryl sulfate aqueous solution) in an amount such that the cilostazol content was 50 mg, and the cilostazol test solution was introduced into the test solution at predetermined intervals. Was measured. The amount of cilostazol eluted was quantified by the absorbance measurement method. Table 1 shows the results.

[0029]

[Table 1]

From Table 1, it is understood that the elution amount of cilostazol can be arbitrarily controlled by adjusting the content and particle size of cilostazol. (Absorbability test) An absorbency test was conducted using the following test formulations and controls. Test formulation 1: Granules having a particle size of 75 to 105 μm obtained in Example 2 Test formulation 2: Granules having a particle size of 75 to 105 μm obtained in Example 4 Test formulation 3: Granules having a particle size of 75 to 105 μm obtained in Example 19 105 μm
Granules of Test preparation 4: Particle size obtained in Example 21 is 75 to 105 μm
Granules Control: Hydroxypropylmethylcellulose (HPMC) suspension containing 10 mg cilostazol Each test formulation was used by filling it into minicapsules for rats at a dose of 10 mg as cilostazol. Male rats for each test formulation and control (32 per group)
, 0.5, 1, 2, 3, 4, 6,
Blood was collected from the inferior vena cava at each time point 8 and 10 hours later (n =
4), cilostazol in serum was quantified by high performance liquid chromatography to compare the absorbability. The results are shown in Table 2.

[0031]

[Table 2]

From Table 2, as compared with the control, all the test preparations showed that the rapid increase in the serum cilostazol concentration at the initial administration was suppressed, and the values were high even after 6 hours. It was confirmed that the suppression of (Cmax) and the sustained serum concentration were achieved.

Formulation Example 1 200 mg of the granular material (containing 50% by weight of cilostazol, particle size range: 75 to 105 μm) obtained in Example 2 was filled in a capsule to produce a capsule containing 100 mg of cilostazol. Formulation Example 2 To 125 mg of the granular material (containing 80% by weight of cilostazol, particle size range: 75 to 105 μm) obtained in Example 27, 40 g of crystalline cellulose, 34 g of corn starch and 1 g of magnesium stearate were added and mixed. Using the obtained mixed powder, a punch with a diameter of 9 mm and a tablet weight of 200 mg
Were tableted to give tablets containing 100 mg of cilostazol.

[0034]

EFFECT OF THE INVENTION Since the resin granules of the present invention are granules having a predetermined particle diameter in which a predetermined amount of cilostazol is contained in an ethylene-vinyl alcohol copolymer, the release amount of cilostazol into the living body is suppressed. , As a result, the blood concentration of cilostazol becomes constant and lasts for a long time, so that side effects such as pain and headache caused by the rapid release of cilostazol in the body can be significantly reduced. .

The medical material of the present invention has the effect of continuously releasing cilostazol at an effective concentration.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 31/47 ACL A61K 31/47 ACL AED AED 9/16 9/16 S U 47/32 47 / 32 C C07D 401/12 257 C07D 401/12 257 C08L 23/26 LDM C08L 23/26 LDM // (C07D 401/12 215: 22 257: 04) (72) Inventor Hiroaki Yamamoto Setocho Myojin, Naruto City, Tokushima Prefecture Character Narutani 104-4 (72) Inventor Yuzo Kimura 4-33-10 Minamisho-cho, Tokushima City, Tokushima Prefecture (72) Inventor Shinsuke Nakagawa 487 Sumiyoshi, Sumiyoshi, Matsushige-cho, Itano-gun, Tokushima Corp. Ras Kokufu 4-C (72) Inventor Keigo Yamada 4-9-15 Kitaokisu, Tokushima City, Tokushima Prefecture (72) Inventor Toshio Nakamura 1-115 Shinkirai, Kitajima-cho, Itano-gun, Tokushima Prefecture

Claims (3)

[Claims] 1. A resin granule having a particle diameter of 2000 μm or less, which is obtained by incorporating cilostazol in an ethylene-vinyl alcohol copolymer in a proportion of 5 to 90% by weight. 2. A medical material comprising an ethylene-vinyl alcohol copolymer containing cilostazol in a proportion of 60 to 85% by weight. 3. A medical preparation comprising the resin granules according to claim 1 alone or mixed with a conventional preparation carrier.