JP2003252776A - Xanthine oxidase inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an effective xanthine oxidase inhibitor of high safety. <P>SOLUTION: The xanthine oxidase inhibitor includes plant bodies and/or extracts from the plant bodies selected from Origanum vulgare, Mosla chinensis, Elsholtzia cilita, Melissa officinalis, Satureja Montana, Rosmarinus officinalis, Mentha spicata, Mentha piperita, Satureja Montana, Piper betle, and Ehretia microphylla. These plant bodies are excellent in safety because they are normally used for food. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a plant-derived xanthine oxidase inhibitor and a prophylactic or therapeutic agent for diseases caused by abnormal metabolism of uric acid.

[0002]

2. Description of the Related Art Currently, various diseases caused by disordered eating habits, lack of exercise, stress, etc. are becoming a problem. Among them, it is relatively neglected that hyperuricemia due to abnormal metabolism of uric acid. Or gout. Currently, the number of gout patients in Japan is about 300,000 to 500,000, and the number of people with "subclinical hyperuricemia (preliminary gout group)" with high uric acid level, although not gout, is about 50.
It is estimated to be 0,000. If hyperuricemia is left untreated, it may cause complications such as kidney damage, urinary tract stones, and arteriosclerosis, and the risk of severe gout attack with gout increases, so it can be said that its prevention and treatment are extremely important.

[0003] In vivo, hypoxanthine is produced as a nucleic acid metabolite, which is oxidized by xanthine oxidase to be metabolized to xanthine and further to uric acid, and excreted in urine. Uric acid is poorly soluble in water, and about 90% is reabsorbed by the renal tubules, so uric acid synthesis is accelerated in vivo,
The decrease in the excretion rate of uric acid induces hyperuricemia.

[0004] For the treatment of hyperuricemia, benzbromarone, probenecid or sulfinpyrazone that promotes the excretion of uric acid, allopurinol that inhibits the synthesis of uric acid, etc. are used. However, these may cause transient hyperuricemia and gout attacks, and side effects such as fulminant hepatitis, aplastic anemia, and dermatitis are also observed, so they are not satisfactory in terms of safety. Not profitable. From such a viewpoint, various xanthine oxidase inhibitors derived from natural products have been investigated. For example, perilla, artichoke and onion are disclosed in JP-A-3-77830, lichens are disclosed in JP-A-5-244963, and cafe de mat is disclosed in JP-A-9-2027.
33, Japanese Patent Laid-Open No.
No. 00-290188, and Hamamelis and Isomatsu are disclosed in JP 2001-258504 A, respectively.

[0005] However, many of these materials have little eating experience, are difficult to obtain, or have a weak xanthine oxidase inhibitory activity, and thus cannot be used for the prevention or treatment of diseases caused by abnormal metabolism of uric acid.

[0006]

DISCLOSURE OF THE INVENTION The present invention has found a plant component which is safe and has a high xanthine oxidase inhibitory activity, and provides a pharmaceutical or food or drink useful for the prevention or treatment of diseases caused by uric acid metabolism abnormality. With the goal.

[0007]

In view of such circumstances, the present inventors have investigated the xanthine oxidase inhibitory activity of various plants that have abundant eating habits, and as a result, we have found that the plant has a lot of experience. The inventors have found that extracts of spearmint, peppermint, winter savory, betel and fukumangi have a remarkable xanthine oxidase inhibitory action, and completed the present invention.

[0008] That is, the present invention is,
The present invention provides a xanthine oxidase inhibitor containing a plant and / or an extract of the plant selected from Naginata koju, lemon balm, rosemary, spearmint, peppermint, winter sabori, betel and fukumangi.

[0009] Further, the present invention is,
Providing a preventive or therapeutic agent for a disease caused by uric acid metabolism abnormality, which comprises a plant selected from Naginata koju, lemon balm, rosemary, spearmint, peppermint, winter sabori, betel and fukumangi, and / or an extract of the plant. To do.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION A prophylactic or therapeutic agent for a disease caused by an abnormal metabolism of xanthine oxidase and uric acid in the present invention, is Gypsophila, Gypsophila, Gypsophila, Lemon Balm, Rosemary, Spearmint, Peppermint, Wintersabori, Betel And a plant selected from Fukumangi and / or an extract of the plant. The term "comprising" as used herein means containing one or more kinds of the above-mentioned plant and / or an extract of the plant.

[0011] The xanthine oxidase inhibitor of the present invention refers to an agent that inhibits xanthine oxidase that oxidizes hypoxanthine to xanthine and oxidizes xanthine to uric acid.

[0012] Further, the preventive or therapeutic agent for diseases caused by uric acid metabolism abnormality in the present invention, by inhibiting the xanthine oxidase, suppresses the production of uric acid, diseases caused by uric acid metabolism abnormality, for example, Gout, hyperuricemia,
It refers to those that prevent or treat vascular disorders, renal disorders, joint disorders, gouty nodules or uroliths. The treatment in the present invention also includes symptomatic relief and ameliorating effects.

[0013] The plant in the present invention refers to all or a part of the elements constituting the above plant, for example, roots, leaves, stems,
Flowers, fruits, seeds, shoots, baskets and the like can be used.
If necessary, these plants may be processed by any means such as crushing, repairing, roasting, drying or fermentation.

[0014] Further, the extract in the present invention refers to one obtained by extracting the above-mentioned plant body with any solvent, preferably a polar solvent or edible oil, and if necessary, diluted, concentrated or dried. Can be used.

As the polar solvent, water or alcohols such as methanol, ethanol, 1-propanol, 2-propanol and 1-butanol, ethers such as 1,4-dioxane, ketones such as acetone, nitriles such as acetonitrile. Examples thereof include a mixture of these.
It is preferably water or a lower alcohol such as methanol or ethanol, or a mixture thereof, and more preferably water or ethanol or a mixture thereof.

[0016] These extracts are obtained by crushing, crushing or cutting the above-mentioned plant or a dried product thereof, and adding the above polar solvent to the mixture, and then at 0 ° C to 100 ° C, preferably at room temperature to 70 ° C, at 1 to 2
After standing for 4 hours, more preferably 2 to 10 hours, and removing insoluble matter by an operation such as filtration and centrifugation, if necessary, the solvent can be distilled off or concentrated for use.

Hereinafter, the plant used in the present invention will be described. Dokoju ( Origanum vulgare ) belongs to the Lamiaceae genus Hanahakka, from Europe to Southwest Asia, the Himalayas,
Distributed in China and Taiwan. In addition to being used as a spice, tinctures have a marked diuretic effect,
It is used as a sweating agent. Immersions are used to relax the intestine, increase appetite and improve digestion. It also has an expectorant effect.

[0018] Sekikoju ( Mosla chinensis ) is a plant that belongs to the Lamiaceae genus Amaranthaceae and is distributed from the Chugoku region of Japan to Korea, mainland China, and the like, and its whole plant can be used.
Used in China for colds, abdominal pain, diarrhea and eczema in China.

[0019] Nasushi ( Elsholtzia ciliata , E. p
atrini , E. splendens ) belongs to the genus Lamiaceae and belongs to the genus Rhinoceros and belongs to the Eurasian continent and North Africa. In China, it is used as an antipyretic and diuretic agent, as well as fever with chills and headache, vomiting, and diarrhea.

[0020] Lemon balm ( Melissa officinalis ) belongs to the family Lamiaceae genus Prunus vulgaris and is a plant distributed from the Mediterranean coast to the eastern part of the Eurasian continent, and the whole plant can be used. The whole plant has a fragrance and is used for flavoring salads and soups. Essential oil is a raw material for perfume, and in Europe, exudate of whole plant is called Balm Tea, which is said to be effective for sweating, headache and toothache. .

[0021] Winter sabori ( Satureja montana ) is a plant belonging to the genus Tobana of the Lamiaceae family and distributed from the Mediterranean Sea to Ukraine, and its whole grass can be used. In addition to being used for cooking, it is also used for treating chest infections and bronchitis.

[0022] Rosemary ( Rosmarinus officinalis ) belongs to the Lamiaceae genus Mannenrow and is a plant distributed from Southern Europe to the Mediterranean coast, and its whole plant can be used. In addition to using perfume oil as a material for flavors and soaps, it is also used as an herb in both meat and vegetable dishes. Used in Europe for the treatment of jaundice and abortion. It is also customary to chew the leaves to eliminate bad breath. Used in China for pain relief, sweating, and stomach ache.

[0023] Spearmint ( Mentha spicata ) belongs to the mint family of the Labiatae family and is a plant cultivated in the United States and Japan, and the whole plant can be used. In Europe, it is used as a flavoring agent for meat and fish, and essential oil is used as a flavoring agent for chewing gum, cocktails, toothpaste and confectionery.

[0024] Peppermint ( Mentha piperita ) is a plant that belongs to the mint family of the Lamiaceae family and is cultivated in various parts of Europe, and its whole plant can be used. It is used to chop raw leaves for lamb dishes and fish and meat sauces, to add a beautiful green color and aroma to cocktails and liqueurs, and for chewing gum flavors and confectionery such as cakes and mint jellies. Essential oils are used in spices and essences of Western confectionery, fragrances of toothpaste and cosmetics, as well as cardiotonics, stimulants and other medicinal products.

[0025] Winter Savory ( Satureja montana ) is a plant belonging to the genus Tobana of the Lamiaceae family and distributed from the Mediterranean Sea to Ukraine, and its whole plant can be used. In addition to being used for cooking, it is also used for treating chest infections and bronchitis.

[0026] Betel ( Piper betle ) is a plant belonging to the genus Pepper of the family Pepperidaceae and widely cultivated in India and Africa, and its plant body, preferably its leaves, can be used. In China, antispasmodic, antibacterial, antifungal, antiinflammatory, anthelmintic,
Used for cough, stomach pain, stomach ache, expectoration, toothache.

[0027] Fukumangi ( Ehretia microphylla, Carmona re
tusa ) is a plant belonging to the genus Cistanche or the genus Fukumangi, belonging to the family Orchidaceae, and is distributed in the Philippines, South India, etc., and its plant, preferably its leaves can be used. Known in the Philippines as Tsaang-gubat, which means wild tea, it is used for non-inflammatory diseases. Tea prepared from leaves is used as a stomachic agent, and decoction of leaves is used for cough, bleeding diarrhea, and dysentery. Tsaang-gubat tablets have been registered with the Philippine Food and Drug Administration and have been shown to relieve abdominal pain and suppress intestinal peristalsis. In South India, roots are used for cachexia and syphilis.

[0028] The above-mentioned prophylactic or therapeutic agent for diseases caused by xanthine oxidase inhibition and uric acid metabolism abnormality can be provided as a medicine or a food or drink by any means.

When the preventive or therapeutic agent for diseases caused by xanthine oxidase inhibition and uric acid metabolism abnormality according to the present invention is used as a medicine or food or drink, it is in the form of powder, granules, tablets, dragees, capsules, liquids and the like. Can be provided at. When it is used as a food, it can be provided in the form of gum, candy, jelly, tablet confectionery, beverage and the like. Any of these can be produced by a technique generally used in pharmaceutics. When used as a medicine, general administration routes such as oral administration, parenteral administration, rectal administration and transdermal administration can be mentioned. Parenteral administration includes subcutaneous administration, intravenous administration, intranasal administration, infusion and the like. The amount used is generally 1
Within the range of about 0.1 to 500 mg / kg body weight per dose,
It is usually administered 1 to 5 times a day. However, the exact capacity is
The patient's age, body weight, symptom, administration route, etc. are taken into consideration to determine from the above range.

[0030]

The present invention will be described below with reference to examples, but these do not limit the present invention. The following experiments were conducted to evaluate the xanthine oxidase inhibitory action of the plant of the present invention.

[0031] Example 1: Preparation of xanthine oxidase inhibitor Whole dokuju (obtained from Kunming Fukurindo, China), Sekikouju whole plant (obtained from Tochimoto Tenkaidou Co., Ltd.), Naginata koju whole plant (Nippon Powder Chemicals Co., Ltd.) ), Whole lemon balm, whole rosemary, whole spearmint, whole peppermint, whole winter sabori (obtained from Shin Nippon Kampo Co., Ltd.), betel leaf (obtained from Nippon Powder Chemicals Co., Ltd.) 30% (v / v) ethanol was added to the dried product of Fukumangi leaf (obtained from Nohara Farm, Okinawa Prefecture) and crushed with a blender. This was filtered, the solvent was distilled off under reduced pressure, and freeze-dried to obtain a 30% ethanol extract. The yield is
Dokojou (14.6%), Sekikoju (16.1%)
%), Naginatakouju (12.0%) Lemon Balm (22.4%), Rosemary (20.6%), Spearmint (32.0%), Peppermint (23.2%),
Winter Savory (24.6%), betel (21.3%)
%) And Fukumangi (15.3%).

[0032] Example 2: Measurement of xanthine oxidase inhibitory activity In a test tube, a 1/15 M phosphate buffer solution (pH 7.5) was added.
58 ml, 0.15 mM xanthine 0.4 ml, test substance solution or water 0.12 ml were taken and reacted at 25 ° C. for 15 minutes. To this, 0.1 ml of 20 unit / ml of bovine milk-derived xanthine oxidase manufactured by Boehringer Mannheim, which was dissolved in the above buffer, was added, and the reaction was further continued for 30 minutes. The reaction was stopped by adding 0.2 ml of 1M hydrochloric acid. Separately, xanthine oxidase, 1M hydrochloric acid, and xanthine were added in that order as a blank. The absorbance difference of these reaction solutions at 290 nm was measured, and the xanthine oxidase inhibitory activity was calculated from the calculation formula 1. The test substance concentration was 100 μg / ml, and the results are shown in Table 1. As can be seen from Table 1, a strong xanthine oxidase inhibitory action was observed in all the plants tested this time.

[Calculation formula 1]

[0033]

[Table 1]

[0034]

According to the present invention, a highly safe and effective xanthine oxidase inhibitor can be provided. Therefore, diseases caused by abnormal metabolism of uric acid, for example, gout, hyperuricemia, vascular disorders, renal disorders, joint disorders,
It can be widely applied to the prevention or treatment of gouty nodules or urinary tract stones.

Front page continuation (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 13/12 A61P 13/12 19/02 19/02 43/00 111 43/00 111 (72) Inventor Naoaki Morihara Hiroshima 1624 Shimodate, Koda-cho, Takada-gun, Yunaga Pharmaceutical Co., Ltd. (72) Inventor Toshinori Morita 1624 Shimodate-tachi, Koda-cho, Takada-gun, Hiroshima F-term (reference) 4C088 AB12 AB38 AC03 AC04 AC05 AC11 BA08 CA03 ZA36 ZA81 ZA96 ZC20

Claims (5)

[Claims] 1. A xanthine oxidase inhibitor comprising a plant and / or an extract of the plant selected from Rhododendron japonica, Sekikoju, Naginakokouju, lemon balm, rosemary, spearmint, peppermint, winter sabori, betel and Fukumangi. 2. Abnormal metabolism of uric acid containing a plant and / or an extract of the plant selected from Rhododendron japonica, Sekikoju, Naginatakouju, lemon balm, rosemary, spearmint, peppermint, winter sabori, betel and Fukumangi. A preventive or therapeutic agent for the resulting disease. 3. A disease caused by uric acid metabolism abnormality is gout,
The preventive or therapeutic agent according to claim 2, which is selected from hyperuricemia, vascular disorders, renal disorders, joint disorders, gout nodules, and uroliths. 4. The xanthine oxidase inhibitor according to claim 1, which is a medicine or a food or drink. 5. The preventive or therapeutic agent for a disease caused by abnormal metabolism of uric acid according to claim 2 or 3, which is a medicine or a food or drink.