JP2009155334A - Medicine - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medicine containing, as an active ingredient, 6-methylsulfinylhexylisothiocyanate which is known to have functions such as a glycogen synthase kinase 3β-inhibiting action, an anti-obestic action, a skin ageing-inhibiting action and an anti-stress active and is also effective for other diseases. <P>SOLUTION: Provided are a hyperuricemia-preventing or improving agent containing 6-methylsulfinylhexylisothiocyanate as an active ingredient, an anti-osteoporosis agent containing 6-methylsulfinylhexylisothiocyanate as an active ingredient, a hypotensive agent containing 6-methylsulfinylhexylisothiocyanate as an active ingredient, and an anti-fatigue agent containing 6-methylsulfinylhexylisothiocyanate as an active ingredient. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a therapeutic agent useful for various diseases comprising 6-methylsulfinylhexyl isothiocyanate as an active ingredient.

6-methylsulfinylhexyl isothiocyanate has glycogen synthase kinase 3β inhibitory action (patent document 1), anti-obesity action (patent document 2), skin aging inhibitory action (patent document 3), anti-stress action (patent document 4) and the like. The function is known.
However, there is no view that 6-methylsulfinylhexyl isothiocyanate is effective with remarkable effects on various diseases applied in the present invention described below.

JP 2008-247805 A JP 2006-328056 A JP 2006-241005 A JP 2004-269415 A

  An object of the present invention is to provide various therapeutic agents that are effective with a particularly remarkable effect on various diseases applied in the present invention described below.

The invention according to claim 1 is a preventive or ameliorating agent for hyperuricemia comprising 6-methylsulfinylhexyl isothiocyanate as an active ingredient.
The invention according to claim 2 is an anti-osteoporosis agent containing 6-methylsulfinylhexyl isothiocyanate as an active ingredient.
The invention according to claim 3 is an antihypertensive agent comprising 6-methylsulfinylhexyl isothiocyanate as an active ingredient.
The invention according to claim 4 is an anti-fatigue agent comprising 6-methylsulfinylhexyl isothiocyanate as an active ingredient.

  According to the present invention, there are provided various therapeutic agents that are particularly effective for various diseases applied in the present invention described below with remarkable effects.

  Hereinafter, the present invention will be described in more detail.

  6-Methylsulfinylhexyl isothiocyanate used in the present invention is a known compound and can be prepared by a method of extraction from horseradish, a method of synthesis by a known chemical synthesis and purification method, etc. 1 and 2). Moreover, a commercial item can also be utilized.

  The dose of 6-methylsulfinylhexyl isothiocyanate varies depending on the patient's age, body weight, indication symptoms, etc., for example, adults one to several times a day, daily dose of about 5 mg to 10 g, preferably about 100 mg to 1 g It is better to administer.

  The therapeutic agent of the present invention can be appropriately prepared by a known method in the form of a solid or solution (hereinafter, also referred to as a preparation) such as a tablet, pill, capsule, granule, powder, powder, or liquid. That is, the solid preparation or liquid preparation useful in the present invention is produced by using a well-known preparation method that has been well established. Examples of additives include excipients, pH adjusting agents, cooling agents, suspending agents, diluents, antifoaming agents, thickeners, solubilizers, disintegrating agents, binders, lubricants, antioxidants. Agents, coating agents, coloring agents, flavoring agents, surfactants, plasticizers or fragrances.

  The therapeutic agent of the present invention can be taken as various health foods and functional foods. Examples of these include various products, but for the production of health foods and functional foods, in addition to commonly used food materials and food additives, excipients, extenders, binders, It can be used in the form of food and drink preparations using adjuvants such as disintegrants, lubricants, dispersants, preservatives, wetting agents, solubilizers, preservatives, stabilizers, capsule bases and the like. Specific examples of the adjuvant include lactose, fructose, glucose, starch, gelatin, magnesium carbonate, synthetic magnesium silicate, talc, magnesium stearate, calcium carbonate, methylcellulose, carboxymethylcellulose, or a salt thereof, gum arabic , Polyethylene glycol, syrup, petrolatum, glycerin, ethanol, propylene glycol, citric acid, sodium chloride, sodium sulfite, sodium phosphate, pullulan, carrageenan, dextrin, reduced palatinose, sorbitol, xylitol, stevia, synthetic sweetener, citric acid Ascorbic acid, acidulant, baking soda, sucrose ester, hardened vegetable oil, potassium chloride, safflower oil, beeswax, soybean lecithin, flavor, and the like can be blended. Regarding the production of such health foods and functional foods, reference books for pharmaceutical preparations such as “Japanese Pharmacopoeia Manual (General Rules for Preparations)” (Yodogawa Shoten) can be referred to.

  In addition to the above, the therapeutic agent of the present invention can be taken as a food or drink. Specifically, natto, thick fried, tofu, konjac, dumplings, pickles, boiled, croquettes, sandwiches, pizzas, hamburgers, dumplings, shumai, salads, etc., various powders (beef, pork, chicken and other livestock products) Marine products such as shrimp, scallops, sea bream, kelp, vegetables / fruits, plants, yeast, algae, etc.), pudding, cookies, crackers, bread, cakes, chocolate, potato chips, biscuits, donuts, jellies and other confectionery, Japanese rice crackers such as rice crackers, sheep crab, daifuku, ohagi, other buns, Japanese confectionery such as castella, frozen confectionery (rice cake etc.), bread and confectionery such as chewing gum, noodles such as udon, buckwheat and kishimen, kamaboko, ham, fish sausage, etc. Fish paste products, meat products such as ham, sausage, hamburger, corn beef, salt, pepper, miso, soy sauce, sauce, dressy Seasonings such as gyu, mayonnaise, ketchup, sweeteners, spices, teppanyaki foods such as Akashi-yaki, takoyaki, monja-yaki, okonomiyaki, yakisoba, fried udon, dairy products such as cheese, hard-type yogurt, and fats and oils Various foods such as powdered solids of flavors and fragrances (vanilla, citrus fruits, bonito etc.) and powdered foods and drinks (instant coffee, instant tea, instant milk, instant soup, miso soup, etc.) These are not particularly limited.

  Furthermore, in the present invention, for example, royal jelly, propolis, vitamins (A, C, D, E, K, folic acid, pantothenic acid, biotin, derivatives thereof, etc.), minerals (iron, magnesium, calcium, zinc, etc.), Selenium, lecithin, carotenoids (lycopene, astaxanthin, zeaxanthin, lutein, etc.), saponins (gymnemic acid, soybean saponin, ginseng saponins, etc.), fatty acids, proteins (collagen, elastin, etc.), oligosaccharides (isomalto-oligosaccharides, cyclic oligosaccharides, etc.) ), Phospholipids and derivatives thereof (phosphatidylcholine, sphingomyelin, ceramide, etc.), sulfur-containing compounds (eg, alliin, sepaene, taurine, glutathione, methylsulfonylmethane), sugar alcohols, lignans (sesamin, etc.), Contains animal and plant extracts Root vegetables (turmeric, ginger, etc.), may be used in combination and the like.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not limited to these. The therapeutic agent of the present invention is extremely useful as an agent for preventing or improving hyperuricemia, an anti-osteoporosis agent, a blood pressure lowering agent, and an anti-fatigue agent. Hereinafter, the various medicinal effects will be described with examples.

Example 1 (improvement effect of hyperuricemia)
6-methylsulfinylhexyl isothiocyanate powder (hereinafter referred to as powder 1) was used for the following experiment.

Experimental Method As test animals, Wistar rats (8 weeks old, body weight of about 180 g) were used in groups of 6 animals.
Adenine was added to the test feed at a concentration of 0.75% and fed to rats to cause inhibition of uric acid excretion into the urine from the kidney, thereby giving a model animal of hyperuricemia.
The control group was the above 0.75% adenine feed only, and the drug administration group was a feed containing 0.75% adenine and the above powder 1. Although the feed was freely consumed, the concentration of the powder 1 in the test diet of the drug administration group was adjusted so that the intake amount was 1 mg / kg body weight. The uric acid level in the blood was measured on the test start day and 24th day.
As a result, the blood uric acid concentration on the test start day of the control group was 0.57 mg / ml, and it was 2.33 mg / ml on the 24th day, whereas the blood uric acid concentration on the 24th day of the drug administration group was The uric acid concentration was 0.88 mg / ml.
As is clear from this result, the blood uric acid concentration in the control group was significantly increased, whereas in the drug administration group, the concentration was not increased. Therefore, 6-methylsulfinylhexyl isothiocyanate has been shown to be useful as a preventive or ameliorating agent for hyperuricemia.

Example 2 (Anti-osteoporosis effect)
Osteoporosis Improvement Effect Test SD rat (22 weeks old) Female ovaries were surgically removed to create osteoporosis model rats. Ovariectomized rats were divided into 6 groups of 7 animals, and physiological saline so that the intake of powder 1 of Example 1 was 1 mg / kg every other day (total 17 times) during the 35-day test period. 2 ml of water-dispersed liquid was orally administered. The feed was the solid feed CRF-1 for mice, rats and hamsters from Oriental Yeast Co., Ltd. There was no difference in food intake between groups during the study period. On the 35th day after the start of the test, the weight of the rat was measured, and then the femur was removed. The femur was used for analysis with the adhesive tissue and muscle removed. After measuring the volume of the femur, it was washed three times with ethanol, then washed three times with acetone, dried overnight, and then weighed to determine the dry weight of the femur. From the volume and dry weight, the bone density (dry weight g / volume mm ³ ) was measured. As a control experiment, Table 1 shows the results together with an example (comparative example) in which the above experiment was repeated except that physiological saline not containing the powder 1 was administered to rats.

  When Example 2 and the comparative example were compared, Example 2 showed a significant difference at a risk rate of p <0.05.

Example 3 (blood pressure lowering effect)
Powder 1 of Example 1 was added to a general commercial feed (Funabashi Farm, Funabashi SP), and the changes in the maximum blood pressure value and body weight were compared using stroke-prone spontaneously hypertensive rats (SHR-SP). As a control group, a general sample to which powder 1 was not added was used. The A group is the control group and the B group is the present invention group, and each group of 6-week-old male SHR-SPs is bred for 7 weeks, and changes in blood pressure and body weight when they reach 12 weeks of age. Investigated about. As shown in Table 2, in the change of blood pressure, significant suppression of blood pressure increase was observed in the present invention group. In the present invention group, the concentration of the powder 1 in the feed was adjusted so that the daily intake of the powder 1 was 5 mg / kg body weight.

Example 4 (Anti-fatigue effect)
STD DDY male mice (5 weeks old: each group n = 3 to 4) were orally ingested with the above powder 1. The intake is 10 mg / kg body weight. In addition, the test group mice were fed with pure water only.

Thirty minutes after the ingestion, the mouse was placed in an 80 cm deep water tank, and the time until immobility was measured. As an average value of the time until the mice of each test group (n = 3 to 4) reached immobility, the control group was about 100 seconds, whereas the powder 1 administration group was about 358 seconds. there were.
From the above, it was confirmed that the powder 1 has a high anti-fatigue effect.

Example 5 (anti-fatigue effect)
Twelve volunteer men (age 34-37) were grouped into a test meal group (Example) and a placebo group (Comparative Example). The test meal group (Example) is a group in which Powder 1 is processed into a soft capsule based on olive oil and 500 mg of Powder 1 is ingested daily. The placebo group (comparative example) is a group in which soft capsules containing olive oil without powder 1 are ingested daily.
Volunteer men were exercised with a bicycle ergometer at 5 and 9 weeks after ingestion. The exercise continues for 30 minutes at an exercise intensity of 80% load of the maximum heart rate.
The blood lactate levels of volunteer men immediately before and after exercise were measured with a commercially available simple blood lactate analyzer, and the amount of blood lactate increased was examined.
As a result, the increase after 5 weeks from the start of intake was about 5.31 mmol / l in the example compared to about 6 mmol / l in the comparative example.
The increase after 9 weeks from the start of ingestion was about 6 mmol / l in the comparative example, whereas it was about 4.9 mmol / l in the example.
From the above, the anti-fatigue action of the powder 1 was clarified.

Example 6
Juice preparation:
Frozen concentrated orange juice 5.0 parts by weight Fructose glucose liquid sugar 1.0 part by weight Citric acid 0.10 parts by weight L-ascorbic acid 0.09 parts by weight Powder 1 of Example 1 0.05 parts by weight

Candy preparation:
Sugar 50.0wt%
Minamata 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
The remaining amount of the therapeutic agent of the present invention 100.0 wt%

Yogurt preparation:
Milk 41.5wt%
Nonfat dry milk 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Therapeutic agent of the present invention 1.0
Perfume Trace Water Residue
Total 100.0wt%

Preparation of soft drinks:
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Therapeutic agent of the present invention 1.0
Perfume appropriate amount water remaining
Total 100.0wt%

Claims (4)

  An agent for preventing or improving hyperuricemia, comprising 6-methylsulfinylhexyl isothiocyanate as an active ingredient.   An anti-osteoporosis agent comprising 6-methylsulfinylhexyl isothiocyanate as an active ingredient.   An antihypertensive agent comprising 6-methylsulfinylhexyl isothiocyanate as an active ingredient.   An anti-fatigue agent comprising 6-methylsulfinylhexyl isothiocyanate as an active ingredient.