JP2003292438A - Pharmaceutical for treatment of nerve disorder - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a safe and effective agent for the prevention and treatment of peripheral neuropathy. <P>SOLUTION: A pharmaceutical composition composed of B complex vitamin, vitamin E, folic acid, etc., has high effectiveness for the prevention and treatment of peripheral neuropathy. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a medicament for preventing and treating neuropathy. More specifically, the present invention relates to a pharmaceutical composition for preventing and treating peripheral neuropathy using a vitamin complex.

[0002]

2. Description of the Related Art Peripheral neuropathy is ischemia, drug poisoning, trauma,
It is known to be caused by various causes such as viral infection, nutritional disorders, genetics, diabetes, tumors, allergies, and polydipsia. The site of the disorder may be local, multiple, or systemic. As a result, there are various symptoms such as general paralysis, muscle atrophy, muscle weakness, numbness, pain, edema, hearing loss, visual acuity, dyspnea, and skin ulcer depending on the site of neuropathy.

It has been reported that administration of vitamin B12 is effective for the above-mentioned peripheral neuropathy (medical treatment and new drugs, 22, 219-223, 1985).
Year). Further, Japanese Patent Laid-Open No. 22229/1990 discloses at least one of ginkgo biloba extract and folic acid or a derivative thereof, α-lipoic acid, a vitamin B group or a derivative thereof, which are used for preventing and preventing diseases of nerve cells and nerve fibers. The combination preparations containing are reported. JP-A-5-294968 and JP-A-7-18084 disclose that a folic acid derivative can be used for cancer treatment, specific anemia, autoimmune disease, and neuropathy. Japanese Patent Application Laid-Open No. 10-218775 describes that administration of a large amount of methylcobalamin is effective for treating amyotrophic lateral sclerosis. Furthermore, for patients with peripheral neuropathy who showed numbness and pain, vitamin B12 and vitamin E were used.
It is reported that coadministration of nicotinin improves the neuropathy more than that of vitamin B12 alone, which is based on the peripheral circulation promoting action of vitamin E (Suzuki, K., et al., Jp.
n. Pharmacol. Ther. , Vol. 13,
3061-3084, 1985).

[0004]

Folic acid is an essential vitamin that has long been known as an anti-anemia factor, and is involved in metabolism of purines and pyrimidines, and metabolism of glycine, serine, histidine and the like. JP 2001-238640 A
The publication describes a complex in which lactoferrin retains folic acid and / or vitamin B12 effective for improving anemia, but does not describe any nerve repair action. Therefore, an object of the present invention is to provide a nerve repair agent that is more effective than conventionally known ones.

[0005]

Means for Solving the Problems As a result of intensive studies in view of the above circumstances, the inventors of the present invention have found that medicines in which specific vitamins are combined are conventionally known, for example, vitamin B.
The inventors have found that it has a higher effect than that of a nerve repair agent containing 12 or folic acid alone, and completed the present invention.

That is, the present invention is a preventive / therapeutic agent for neuropathy, which comprises at least one vitamin B group and vitamin E as active ingredients. Further, the present invention is the above-mentioned prophylactic / therapeutic agent for neurological disorders, which further comprises folic acid. Furthermore, the present invention provides the above vitamin B
Is one or more selected from the group consisting of B1, B2, B6 and B12.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, a neurological disorder means an organic disorder or a functional disorder. That is, damage to nerve tissue due to neuropathy and accidents, dysfunction due to physical compression of tumors, ataxia of autonomic nerves induced by stress, and pain, numbness, numbness, malaise, muscle weakness resulting from these, It means various symptoms such as eye strain and headache. The composition according to the present invention is a food, a beverage,
It can be used as a feed, a drug, a quasi drug, or an additive thereof. The dosage form of the composition according to the present invention is a tablet, a fine granule, a granule, a powder, a capsule, a caplet, an orally-dissolving tablet, an injection, a liquid for internal use, etc., preferably a tablet or a capsule. is there.

In the present invention, the vitamin B group also includes derivatives. For example, vitamin B1 (thiamin, fursultiamine, etc.), vitamin B2 (riboflavin, riboflavin phosphate, riboflavin mononucleotide, etc.), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine, pyridoxal,
Pyridoxamine and the like) and vitamin B12 (cyanocobalamin, methylcobalamin, hydroxocobalamin, adenosylcobalamin) and the like. Preferably vitamin B
1, vitamin B6 and vitamin B12.

The daily dose of the vitamin B group is usually 0.05 to 250 mg / kg, preferably 0.1 to 1 for vitamin B1 and B6 when orally administered.
25 mg / kg, more preferably 0.5-5 mg / k
It is g. Also, with vitamin B12, it is usually 0.1 to 5
000 μg / kg, preferably 1-500 μg / kg,
More preferably, it is 15 to 45 μg / kg.

In the present invention, vitamin E means tocopherols and tocotrienols, and their salts and derivatives are also included. For example, α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocopherol acetate, α-tocopherol succinate, calcium tocopherol succinate,
It means α-tocopherol nicotinate, α-tocotrienol, γ-tocotrienol and the like. Preferred is d-α-tocopherol acetate.

The daily dose of vitamin E is not particularly limited, but is usually 0.05 to 250 mg / kg, preferably 0.1 to 125 mg / kg, and more preferably 0.5 to 5 mg / kg.

In the present invention, folic acid also includes pteroyl monoglutamate or an active substance, a salt or a derivative thereof. For example, dihydrofolic acid, tetrahydrofolic acid, 5-methyltetrahydrofolic acid, 5,10-methylenetetrahydrofolic acid, 10-formyltetrahydrofolic acid and the like.

Although the daily dose of folic acid is not particularly limited, it is usually 0.5 to 62.5 mg / kg, preferably 1 to 100 mg / kg, and more preferably 2.5 to 10 mg.
mg / kg.

In the formulation of the liquid composition according to the present invention, various commonly used additives can be added. Examples of additives include stabilizers, surfactants, solubilizers, buffers, sweeteners, corrigents, suspending agents, antioxidants, cooling agents, flavoring agents / fragrances, emulsifiers, pH adjusters. Agent, dispersant,
Examples include fragrances, preservatives, preservatives and the like.

Examples of the stabilizer include adipic acid, ascorbic acid, sodium L-ascorbate, L-aspartic acid, sodium L-aspartate, sodium sulfite, L-arginine, sodium benzoate, inositol, sodium edetate, Erythorbic acid, sodium erythorbate, sodium citrate, glycine, glycerin, glycerin fatty acid ester, light anhydrous silicic acid, tocopherol acetate, gelatin, soybean oil unsaponifiable matter, polyoxyethylene polyoxypropylene glycol, anhydrous sodium citrate, monostearin Acid glycerin, sodium hydrogen phosphate and the like can be mentioned.

As the surfactant, cholesterol, sucrose fatty acid ester, stearyl alcohol, sorbitan sesquioleate, cetanol, sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, polysorbate, macrogol, Sorbitan monooleate, glycerin monostearate, sorbitan monolaurate,
Examples thereof include sodium lauryl sulfate and lauromacrogol.

As the solubilizer, L-aspartic acid,
Examples include L-arginine, sodium benzoate, ethanol, sodium sorbitan chloride fatty acid ester, sodium hydrogen carbonate, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, polysorbate, polyvinyl alcohol, D-mannitol, anhydrous ethanol and the like. be able to.

As the buffering agent, ascorbic acid, magnesium L-aspartate, aminoethylsulfonic acid,
L-arginine, benzoic acid, sodium benzoate, citric acid, calcium citrate, sodium citrate, disodium citrate, glycine, sodium hydrogen carbonate, lactic acid, glucose, anhydrous citric acid, anhydrous sodium citrate, anhydrous phosphoric acid Sodium hydrogen, sodium metaphosphate, sodium hydrogenphosphate, dipotassium phosphate, potassium dihydrogenphosphate, sodium dihydrogenphosphate and the like can be used.

Examples of sweeteners include aspartame, armature, licorice, fructose, fructose glucose solution, glucose fructose syrup, reduced maltose syrup, dipotassium glycyrrhizinate,
Monoammonium glycyrrhizinate, high fructose syrup, glucose, starch syrup, lactose, sucrose, refined sucrose, honey, saccharin, sodium saccharin, stevia, sucralose, erythritol, xylitol, D-sorbitol, maltitol, maltose, D-mannitol, simple. Syrup etc. can be mentioned.

As corrigents, ascorbic acid, L-aspartic acid, DL-alanine, 5'-inosinic acid disodium, fennel, sodium chloride, orange oil,
Cocoa powder, camphor, glycine, glycerin, L-glutamic acid, saffron, tartaric acid, ginger, D-sorbitol, peppermint, adipic acid, fumaric acid, peppermint, borneol, menthol, rheumatoid, green tea powder,
Apple juice, cider vinegar, lemon oil, rose oil, royal jelly and the like can be used.

Examples of the suspending agent include gum arabic,
Carrageenan, carboxyvinyl polymer, agar,
Xanthan gum, glycerin fatty acid ester, titanium oxide, sucrose fatty acid ester, stearic alcohol, aluminum stearate, cetanol, purified gelatin,
Examples thereof include sorbitan fatty acid ester, soybean lecithin, propylene glycol fatty acid ester, pectin, propylene glycol, polyoxyethylene hydrogenated castor oil, polyethylene glycol, methyl cellulose, glyceryl monostearate, and liquid paraffin.

As antioxidants, ascorbic acid, L-
Ascorbic acid stearic acid ester, sodium hydrogen sulfite, sodium sulfite, erythorbic acid, cysteine hydrochloride, tocopherol acetate, soybean lecithin, butylhydroxyanisole, propyl gallate and the like can be exemplified.

Examples of the cooling agent include geraniol, peppermint water, peppermint oil, borneol, menthol and mint.

As the flavoring agent / fragrance, fennel, ethyl vanillin, ethyl maltol, orange, camphor,
Keihi, sugar flavor, cinnamaldehyde, cherry flavor, spruce tincture, peppermint, vanilla flavor, vanillin, bitter essence, fruit flavor, flavor GI, vermouth flavor, mix flavor, mint flavor, menthol, eucalyptus oil, ryuno, lemon powder, lemon oil , Rosin, rose oil and the like.

As the emulsifier, carrageenan, carboxyvinyl polymer, carmellose sodium, guar gum, glycerin fatty acid ester, polyethylene glycol distearate, sucrose fatty acid ester, stearyl alcohol, stearic acid, cetanol, gelatin, sorbitan fatty acid ester, soybean lecithin, Examples thereof include hydroxypropyl cellulose, propylene glycol, propylene glycol fatty acid ester, polyoxyethylene polyoxypropylene glycol, polysorbate, myristyl alcohol, glyceryl monostearate, sorbitan monolaurate, and sodium lauryl sulfate.

Examples of the pH adjusting agent include dilute hydrochloric acid, sodium citrate, glycine, succinic acid, acetic acid, tartaric acid, sodium hydroxide, sodium hydrogen carbonate, sodium carbonate, monosodium fumarate, phosphoric acid, trisodium phosphate and phosphoric acid. Examples thereof include sodium hydrogen, dipotassium phosphate, sodium dihydrogen phosphate and the like.

As the dispersant, aminoalkyl methacrylate polymer RS, gum arabic, oleic acid, carboxyvinyl polymer, carmellose sodium, glycerin, crystalline cellulose, choline phosphate, lecithin,
Sorbitan sesquioleate, dextrin, corn starch, sorbitan trioleate, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, glyceryl monostearate, sodium lauryl sulfate, liquid paraffin and the like can be used.

As the fragrance, fennel, ethyl vanillin, orange oil, camphor, cinnamon, ginger,
Examples thereof include ginkgo, clove, peppermint, vanilla, vanillin, borneol, maltol, menthol, eucalyptus, agate, lemon, rose water and the like.

Preservatives include aminoethyl sulfonic acid, benzoic acid, sodium benzoate, ethanol, sodium edetate, agar, sodium citrate, sodium salicylate, sorbic acid, isopropyl paraoxybenzoate, ethyl paraoxybenzoate, menthol and the like. Is mentioned.

Preservatives include sodium benzoate, ethanol, sodium edetate, glycerin, salicylic acid, sodium salicylate, D-sorbitol, sorbic acid, isobutyl paraoxybenzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate, paraoxybenzoic acid. Examples thereof include methyl and propylene glycol.

[0031]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited thereto.

Example 1 A neuropathy model was prepared using 10 male rats (Crj: Wistar) in each group, and the pharmaceutical composition of the present invention was administered to examine the effect. Each rat was anesthetized with sodium pentobarbital, the sciatic nerve of the right hind limb was exposed, and the rat was crushed for 5 seconds with a Kochel to create a neuropathy model. Then, for 6 or 8 consecutive weeks, vitamin B1 (V
B1), vitamin B6 (VB6), vitamin B12 (V
B12), vitamin E (VE), folic acid (FA) 1 a day
It was administered by oral gavage once (administered drug and dose: Table 1). The vehicle was administered to the control group. In addition, low folate (12 μg / 100 g) was used as the feed, and 250 m of sulfasacudine was added to eliminate the influence of intestinal bacteria.
g / head was orally administered daily.

[0033] A: VB1 2 mg / kg, VB6 2 mg / kg, V
B12 0.03 mg / kg and VE 2 mg / kg mixed solution (vehicle; Tween
80) B: Folic acid 0.02 mg / kg (water for vehicle injection) C: Folic acid 0.1 mg / kg (water for vehicle injection) VB1 Fursultiamine hydrochloride VB6 Pyridoxine hydrochloride VB12 Methylcobalamin VE Acetate d-α-tocopherol

Six and eight weeks after the start of administration, 10 rats in each group were exsanguinated and killed under ether anesthesia, sciatic nerve was collected, and a preparation for histopathological examination was prepared according to a conventional method. And an image analysis device (MacSCOP
E: trade name, Mitani co. ltd. Was used to measure the minor axis of the myelinated nerve for 500 nerve fibers for each individual.

FIG. 1 shows the distribution of nerve fiber diameter after 6 weeks, and FIG. 2 shows the distribution of nerve fiber diameter after 8 weeks. VB1 2 mg / kg, VB6
2 mg / kg, VB12 0.03 mg / kg, VE
In the first group administered 2 mg / kg, 6 weeks after the administration,
The proportion of nerve fibers having a diameter of 4.5 μm or more and the proportion of nerve fibers having a diameter of 4.0 μm or more increased after 8 weeks from the control group. Therefore, it was revealed that the administration of the vitamin B group and vitamin E promotes the repair action of peripheral nerves. In the second group further administered with folic acid 0.02 mg / kg, 4.5 μm both 6 and 8 weeks after administration.
The proportion of the above large nerve fibers was further increased as compared with the first group. In addition, the third dose of 0.1 mg / kg of folic acid
In the group, the proportion of large nerve fibers of 3.5 μm or more 6 weeks after the administration and the proportion of 4.0 μm or more after 8 weeks were further increased as compared with the second group. As described above, since the effectiveness of the second and third groups was higher than that of the first group, it is clear that a synergistic effect can be obtained by further adding folic acid to the vitamins B and E. Became. Further, it was confirmed that there was a clear Dose-Response between the compounding amount of folic acid and the effect of promoting recovery of peripheral nerves.

Example 2 The pharmaceutical composition of the present invention was administered to a patient having a neurological disease in the orthopedic region and the effect was examined. For 50 patients with muscle pain, arthralgia (stiff shoulders, low back pain, periarthritis of the shoulders, neck-shoulder arm syndrome, etc.), numbness of limbs, neuralgia, and stiff neck and neck muscles Divided into 3 times a day,
After oral administration after meals, the efficacy was examined after 4 weeks. VB12 Methylcobalamin VE Acetate d-α-tocopherol VB1 Fursultiamine hydrochloride VB6 Pyridoxine hydrochloride FA Folic acid

The degree of improvement by subjective symptom is as follows. Spontaneous back pain 53.3% (8/15) Low back pain after exercise 50.0% (7/14) Numbness (upper limbs) 69.2% (9/13) Rigid (neck) 54.5% (6/11) Rigid (waist, back) 80.0% (4/5) Muscle pain 62.5% (5/8) Weakness 66.7% (4/6) Fatigue 80.0% (8/10) Cold feeling 60.0% (3/5) Hot feeling 66.7% (2/3)

The degree of improvement by objective symptom findings is as follows. Abnormal perception (upper limbs) 62.5% (5/8) Hypoesthesia (lower limbs) 50.0% (2/4) Spinal motion restriction 40.0% (2/5) Abnormal perception (lower limbs) 37.5% ( 3/8)

The overall degree of improvement is as follows. Improvement rate% (number of cases) Significant improvement 20.5 (9) Improvement 20.5 (9) Mild improvement 31.8 (14) No change 27.3 (12) Deterioration 0.0 (0) Total (44) Effective In the sex evaluation example, the improvement rate of “mild improvement degree” or higher is 72.
It was 7% (32/44). From the above results, it was revealed that the pharmaceutical composition according to the present invention is effective for various symptoms such as muscle pain (stiff neck, low back pain, and fifty shoulders), numbness of limbs, stiffness of shoulder and neck muscle. .

Example 3 Forty-five patients with eye strain, the therapeutic agents having the components shown in Table 2 were divided into three times a day and orally administered after meal, and after 2 weeks and 4 weeks, The effectiveness was evaluated.

The degree of improvement by subjective symptom is as follows 4 weeks after administration. Eye fatigue 64.1% (25/39) Eye pain 79.2% (19/24) Eye symptoms other than the above 80.0% (20/25) (Tears, dazzling, eyelids tingling) Headache and heavy 63.0% (17/27) Muscle symptoms 78.4% (29/37) (Lower back pain, stiff shoulders, neck pain) Visual function 64.3% (18/28) ( Things look double, things in front of me flicker, things aren't clearly visible, and they seem blurry. Fatigue 63.6% (21/33) (whole body, yawning / sleeping, lack of patience) The degree of overall improvement in subjective symptoms, which is the main evaluation item, was 76.7% (33/43) as determined 2 weeks after administration. The determination 4 weeks after administration was 90.5% (38/42).

The overall degree of improvement is as follows. Improvement rate% (number of cases) Significant improvement 14.0 (6) Improvement 46.5 (20) Mild improvement 30.2 (13) No change 2.3 (1) Mild deterioration 7.0 (3) Undecidable 0.0 (0) Number of evaluation cases (43) The improvement rate of "slight improvement" in the effectiveness evaluation example was 90.7.
% (39).

From the above results, it became clear that the pharmaceutical composition according to the present invention is effective as a therapeutic agent for eye strain.

Example 4 An ectopic nerve firing model (a model for studying the analgesic effect of a drug) was prepared using 4 male rats (SD, Japan Charles River) of each group, and the pharmaceutical composition according to the present invention was prepared. The effect of the object was examined. Each rat was anesthetized with halothane and the left hind limb was incised to expose the saphenous nerve. About 5 mm of the saphenous nerve was excised, and the surgical wound was sutured. One week after that, the rat was anesthetized with urethane / α-chlorase, and a catheter for drug administration was inserted into the right jugular vein. Furthermore, the proximal end of the excised saphenous nerve was exposed, a platinum hook electrode was applied, and nerve firing was recorded using a memory oscilloscope. It was confirmed that ignition was stable, and 10 seconds of ignition was recorded as an initial value. Then, from the catheter, vitamin B1 (VB
1), Vitamin B6 (VB6), Vitamin B12 (VB
12), Vitamin E (VE) and folic acid (FA) were administered, and nerve firing was recorded and compared with the initial value (administered drug and dose: Table 3). As a result, no effect was seen in the first group administered with vitamin B12 alone, but the second group treated with vitamins B1, B6, B12 and vitamin E.
Group, the younger brother group 3 which received vitamins B1, B6, B12 and folic acid, had nerve firing of 67% and 79% of the initial values, respectively.
Fell to%. In addition, 31% was obtained in the 4th group, which was administered 5 agents of vitamins B1, B6, B12, vitamin E and folic acid.
It was revealed that the pharmaceutical composition according to the present invention exerts a great effect.

[0045] A: VB12 (methylcobalamin) 0.6 mg / kg B: VB1 (thiamine hydrochloride) 20 mg / kg, VB6
(Pyridoxine hydrochloride) 20 mg / kg C: VE (tocopherol acetate) 20 mg / kg D: FA (folic acid) 6 mg / kg

Example 5 Using PC12 cells, the protective effect of the pharmaceutical composition according to the present invention against cell damage caused by the addition of rotenone was examined. 10% FCS and 10% HS for culturing PC12 cells
The containing DMEM medium was used. PC12 cells were seeded (1.3 × 10 ⁵ / well) on a 24-well collagen-coated culture plate (Falkon) and cultured in a CO ₂ incubator (37 ° C., 5% CO ₂ ) for 3 days until reaching confluence. did. After removing the culture solution, vitamin B1
(VB1), Vitamin B6 (VB6), Vitamin B12
(VB12), Vitamin E (VE), Folic acid (FA) in various combinations (drug and dose: Table 4) 5% FCS
The DMEM medium containing was added, and after 6 hours of culture, rotenone (10 nM, manufactured by Sigma) was added. After 1 day of culture (21 hours), MTT assay, which is an index of the number of viable cells
I went. 1/10 volume of MTT solution (5m
(g / ml, manufactured by Sigma) was added, and the mixture was placed in a CO ₂ incubator, and after 3 hours, a 1.5-fold amount of 40 mM hydrochloric acid-isopropanol solution was added, and after standing overnight, the absorbance (OD550 nm) was measured. As a result, VB1, V
For the first group added with B6 and VB12, VB
The absorbance values of the second group to which 1, VB6, VB12 and VE were added and the third group to which VB1, VB6, VB12 and FA were added were higher than those of the first group. Furthermore, since the highest absorbance value was exhibited in the fourth group to which VB1, VB6, VB12, VE and FA were added, it was revealed that the pharmaceutical composition according to the present invention exerts a great effect.

[0047] A: VB1 (thiamine hydrochloride) 25 μg / ml + VB6
(Pyridoxine hydrochloride) 25 μg / ml + VB12 (methylcobalamin) 10 μg / ml B: VE (tocopherol acetate) 25 μg / ml C: FA (folic acid) 10 μg / ml

[0048]

INDUSTRIAL APPLICABILITY The drug according to the present invention is effective for the preventive treatment of peripheral neuropathy. The repair of organic disorders such as nerve crush was promoted, and the improvement of subjective symptoms such as pain, stiffness, and numbness in the orthopedic region and the symptoms associated with eye strain were observed. In addition, an analgesic effect and a protective effect against cell damage were observed.

[Brief description of drawings]

FIG. 1 is a diagram showing the nerve fiber diameter distribution of the control group in Example 1 and each group 6 weeks after the administration of the therapeutic agent of the present invention.

FIG. 2 is a view showing the nerve fiber diameter distribution of the control group and each group 8 weeks after the administration of the therapeutic agent of the present invention.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ Identification code FI Theme code (reference) A61P 3/02 104 A61P 3/02 104 4C063 105 105 105 4C086 106 106 106 109 109 7/10 7/10 11/00 11/00 17/02 17/02 21/00 21/00 25/00 25/00 25/02 25/02 101 101 103 103 103 25/06 25/06 27/02 27/02 27/16 27/16 35 / 00 35/00 43/00 121 43/00 121 // A23L 1/302 A23L 1/302 2/38 2/38 Z 2/52 C07D 213/67 C07D 213/67 311/72 101 311/72 101 415 / 00 415/00 475/04 475/04 475/14 475/14 C07H 23/00 C07H 23/00 A23L 2/00 F (72) Inventor Akira Shiroishi 4-6-10 Koishikawa, Bunkyo-ku, Tokyo Eisai Co., Ltd. (72) Inventor Manabu Matsunaga 5-1-3 Tokodai, Tsukuba City, Ibaraki Prefecture In the Tsukuba Research Institute, Zai Co., Ltd. (72) Hiroki Shimizu, 5-1-3 Tokodai, Tsukuba City, Ibaraki Prefecture In the Tsukuba Research Center, Eisa Co., Ltd. (72) Tatsuhiro Ono, 5-1-3 Tokodai, Tsukuba City, Ibaraki Prefecture Eisai Co., Ltd. Tsukuba Research Laboratory (72) Inventor Seiichi Araki 5-1-3 Tokodai, Tsukuba City, Ibaraki Prefecture Eisai Tsukuba Research Laboratory F Term (reference) 4B017 LC03 LK16 4B018 MD23 MD26 ME14 4C055 AA01 BA02 BA06 CA03 CA16 CA42 DA06 DA16 4C057 BB02 DD03 NN01 4C062 FF21 4C063 AA01 BB01 CC62 DD29 EE03 4C086 AA01 AA02 BA09 BC18 BC83 CB09 CB10 GA07 GA10 MA02 MA03 MA04 NA05 NA25 Z25C29 Z25C29 Z25C29 Z25C29Z25B29ZA25 ZA59 ZA34 ZA34 ZA33 ZA34 ZA33 ZA34 ZA33 ZA34 ZA33 ZA34 ZA34

Claims (3)

[Claims] 1. At least one vitamin B group and vitamin E
A prophylactic / therapeutic agent for neuropathy, which comprises: 2. The preventive / therapeutic agent for neuropathy according to claim 1, which contains folic acid. 3. Vitamin B is B1, B2, B6 and B1.
The preventive / therapeutic agent for neurological disorders according to claim 1 or 2, which is one or more selected from the group consisting of 2.