JP2007197388A - Platelet coagulation inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a platelet coagulation inhibitor comprising a natural extract. <P>SOLUTION: The platelet coagulation inhibitor is provided, utilizing the fact that extract obtained by subjecting the following natural plants to extraction treatment with water, a hydrophilic organic solvent or a mixture thereof has platelet coagulation-inhibitory activity. The natural plants are as follows: Isodon japonicus, Centella asiatica, Thymus serphyllum, Thymus vulgaris and Ruscus aculeatus. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a platelet aggregation inhibitor.

   There are various causes and onset mechanisms of inflammatory diseases, such as contact dermatitis (rash), psoriasis, pemphigus vulgaris, and various other skin diseases associated with rough skin. Are known.

Platelet aggregation leads to the activation of phospholipase A _{2 in} the arachidonic acid cascade, whereby leukotriene B, prostaglandin E _{2 and the} like are released and become a flame-inducing substance. Therefore, attempts have been made to prevent / treat allergic diseases and inflammatory diseases by extracting substances that inhibit / suppress platelet aggregation from natural products. For example, an extract of a plant belonging to the genus Canalium (see Patent Document 1), an extract of Kusasanfu (see Patent Document 2), an extract of Fuji tea (see Patent Document 3), an extract of vine leaves (see Patent Document 4), an extract of Nogatei To ( Patent Document 5), duimo extract (see Patent Document 6) and the like have been reported.

   However, the demand of the natural anti-inflammatory agent having a high platelet aggregation inhibitory action while being excellent in safety and productivity, and at a low price is extremely strong, and there has not yet been provided a sufficiently satisfactory one. is the current situation.

JP 2002-53478 A JP 2002-53477 A JP 2001-97873 A JP 2005-220100 A Japanese Patent Laid-Open No. 2005-220101 Japanese Patent Application No. 2004-243001

  An object of the present invention is to find a natural product having an inhibitory action on platelet aggregation, and to provide a platelet aggregation inhibitor containing the same as an active ingredient.

  As a result of intensive studies by the present inventors in order to solve the above-mentioned problems, the extract of enamel, dextran, wild thyme, ginger and butcher's bloom has a platelet aggregation inhibitory action and is effective as a platelet aggregation inhibitor. I found out that there was.

  According to the present invention, a platelet aggregation inhibitor is provided. The platelet aggregation inhibitor of the present invention is useful for preventing and / or improving skin inflammation.

  In addition, according to the present invention, there are provided skin cosmetics and foods and drinks having a platelet aggregation inhibitory action and excellent in safety.

  In the present invention, Enmezo (scientific name: Isodon japonicus) belongs to the Labiatae family and is widely distributed in Japan and can be easily obtained. The constituent part of the enamel used as the extraction raw material is not particularly limited, but above all, it is preferable to use the above-ground part as the extraction raw material.

  Betula (scientific name: Centella asiatica) is a perennial plant that belongs to the ciraceae family and is distributed in the southwestern Honshu, Shikoku, Kyushu, Okinawa, Korean Peninsula, Taiwan, China, etc., and is easily available from these regions. There are no particular limitations on the constituent parts of gramum used as the extraction raw material, but it is particularly preferable to use leaves and stems as the extraction raw material.

  Wild time (scientific name: Thymus serpylum) belongs to the family Lamiaceae, is native to Europe and Northwest Asia, has been introduced to other regions, has become naturalized, and is easily available from these regions. The constituent part of the wild time used as the extraction raw material is not particularly limited, but it is preferable to use the above-ground part as the extraction raw material.

  Tachimusou (scientific name: Thymus vulgaris) belongs to the family Lamiaceae, and is native or cultivated in Spain, France, Germany and the Mediterranean coast, and is easily available from these regions. There are no particular restrictions on the constituent parts of the pearl millet used as the extraction raw material, but the above-mentioned part is preferably used as the extraction raw material.

  Butcher's Bloom (scientific name: Ruscus acculeatus) belongs to the lily family, is native to Europe, and is readily available from these regions. The constituent parts of Butcher's Bloom used as the extraction raw material are not particularly limited, but it is particularly preferable to use rhizome as the extraction raw material.

  The said plant used as an extraction raw material can be obtained by drying and grinding | pulverizing as it is using a crusher, and using for solvent extraction. Drying may be performed in the sun or using a commonly used dryer. Each extraction raw material may be used as an extraction raw material after pretreatment such as degreasing with a nonpolar solvent such as hexane or benzene. By performing a pretreatment such as degreasing, the extraction raw material can be efficiently extracted with a polar solvent.

  In the extraction process, it is preferable to use a polar solvent as the extraction solvent. The component showing the platelet aggregation inhibitory action contained in the extraction raw material can be easily extracted by an extraction process using a polar solvent as the extraction solvent.

  Specific examples of suitable extraction solvents include water, lower aliphatic alcohols, hydrous lower aliphatic alcohols, and the like, and these can be used alone or as a mixture of two or more thereof. Specific examples of suitable lower aliphatic alcohols include methanol, ethanol, propanol, 1,3-butylene glycol, glycerin, propylene glycol and the like.

  The water that can be used as the extraction solvent includes pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, as well as those subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like. Therefore, the water that can be used as the extraction solvent in the present invention includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

  When using the liquid mixture of 2 or more types of polar solvents as an extraction solvent, the mixing ratio can be adjusted suitably. For example, when using the liquid mixture of water and a lower aliphatic alcohol, the mixing ratio of water and a lower aliphatic alcohol can be set to 9: 1 to 1: 9 (mass ratio).

  The extraction treatment is not particularly limited as long as the soluble component contained in the extraction raw material can be eluted in the extraction solvent, and can be performed according to a conventional method. In the extraction process, it is not necessary to adopt a special extraction method, and any apparatus can be used at room temperature or under reflux heating.

  For example, the extraction raw material is put into a treatment tank filled with the extraction solvent, and the soluble components are eluted with occasional stirring. At this time, the extraction conditions can be appropriately adjusted according to the extraction raw material, etc., but the amount of the extraction solvent is usually 5 to 15 times (mass ratio) of the extraction raw material, the extraction time is usually 1 to 3 hours, and the extraction temperature is Usually, it is normal temperature to 95 ° C.

  An eluate can be obtained by eluting soluble components by extraction and then filtering to remove the extraction residue. The obtained extract is diluted, concentrated, dried, purified, etc. according to a conventional method in order to obtain a diluted or concentrated solution of the extract, a dried product of the extract, or a crude purified product or a purified product thereof. Processing may be performed.

  The obtained extract can be used as it is as a platelet aggregation inhibitor, but a concentrated solution or a dried product thereof is easier to use. In addition, since the plant that is the raw material for extraction has a unique odor, it can be purified for the purpose of decolorization, deodorization, etc. within a range that does not cause a decrease in its physiological activity. In this case, since it is not used in large quantities, there is no practical problem even if it is not purified.

  Specifically, purification can be performed by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like.

  Extracts from Enmezo, Sekisetsu, Wild Thyme, Ginger, Butcher's Bloom, and Reishi can be used as they are as platelet aggregation inhibitors, but can also be formulated and provided according to conventional methods. In the case of formulating, a pharmaceutically acceptable carrier such as dextrin and cyclodextrin and other optional auxiliaries can be added to facilitate storage and handling.

  The platelet aggregation inhibitor of the present invention can prevent and / or improve skin inflammation and is excellent in safety when applied to the skin, and is therefore suitable for blending into skin cosmetics. Only a platelet aggregation inhibitor may be blended in the skin cosmetic, or other effective materials may be blended in combination.

  Although the skin cosmetics which can mix | blend the platelet aggregation inhibitor of this invention are not specifically limited, As an example, ointment, cream, milky lotion, a lotion, a pack, a bath agent etc. can be illustrated.

  The compounding amount of the platelet aggregation inhibitor of the present invention can be adjusted as appropriate depending on the type of skin cosmetic, the physiological activity of the extract, etc., but a suitable compounding rate is about 0. 0 in terms of a standard extract. 01 to 10% by mass.

  The skin cosmetic containing the platelet aggregation inhibitor of the present invention is blended with various main agents and auxiliaries usually used in the production of skin cosmetics, and other optional auxiliaries, as long as the platelet aggregation inhibitory action is not hindered. However, regarding prevention and improvement of skin aging, the present invention is not limited to the use of only the platelet aggregation inhibitor of the present invention.

  Since the platelet aggregation inhibitor of the present invention can prevent and / or improve skin inflammation and is excellent in safety, it is suitable for blending into foods and drinks. In this case, it is appropriate that the amount of the extract per day for adults is about 1 to 1000 mg in consideration of the general intake of the food and drink to be added.

  The food and drink that can be mixed with the platelet aggregation inhibitor of the present invention is not particularly limited, and specific examples thereof include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks (concentrated concentrates of these drinks and Including ice cream, ice sherbet, shaved ice, etc .; noodles such as buckwheat, udon, harusame, gyoza peel, cucumber peel, Chinese noodles, instant noodles; rice cake, chewing gum, candy, gum, chocolate , Tablet confectionery, snack confectionery, biscuits, jelly, jam, cream, baked confectionery, etc .; fish and shellfish processed foods such as kamaboko, ham, sausage; dairy products such as processed milk, fermented milk; salad oil, tempura oil, margarine , Mayonnaise, shortening, whipped cream, dressing and other fats and oils and processed foods; sauces, sauces and other seasonings ; Soups, stews, salads, side dishes, pickles and the like.

  The platelet aggregation inhibitor of the present invention described above is suitably applied to humans, but can also be applied to animals other than humans as long as the effects are exhibited.

  Hereinafter, the present invention will be described in more detail with reference to examples. The scope of the present invention is not limited to these examples.

[Production Example 1]
Add 100 ml of water, 50% ethanol or ethanol as an extraction solvent to 100 g each of the above-ground part of Enmeiso, the leaves and stems of pheasants, the above-ground part of wild thyme, the above-ground part of Typhomycota and Butcher's bloom, and 80 ° C. with a reflux extractor. For 2 hours and filtered. The same extraction process was further performed on the residue. The obtained extracts were combined, concentrated under reduced pressure, and dried to obtain an extract. The yield of the extract is shown in Table 1.

[Table 1] Yield of extract
Raw material water (%) 50% ethanol (%) Ethanol (%)
Prunus 19.8 16.2 11.6
Sekisetsu 7.8 5.2 2.0
Wild time 8.6 5.5 3.2
Tachimusou 8.8 5.2 2.9
Butcher's Bloom 44.2 38.0 24.6

[Test Example 1] Platelet aggregation inhibitory action test 1/10 volume of 77 mM EDTA was added to the blood of Japanese white rabbits and centrifuged at 1000 rpm for 10 minutes to remove precipitates. The supernatant was centrifuged at 2100 rpm for 10 minutes, and the precipitated platelets were collected. The obtained platelets were suspended in a platelet washing solution and centrifuged at 2100 rpm for 10 minutes. The precipitated platelets were collected and suspended in a platelet suspension so that the platelet count was 300,000 / μL. 1 μL of calcium chloride solution was added to 223 μL of the washed platelet suspension prepared as described above, and incubated at 37 ° C. for 1 minute. 1 μL of the sample solution was added thereto, and the mixture was further incubated for 2 minutes, and then stirred for 1 minute. Next, 25 μL of a 10 ppm collagen solution was added as an aggregation inducer, incubated at 37 ° C. for 10 minutes, and then the aggregation rate A was measured using a platelet aggregation measuring device PAM12CL (manufactured by Mevanics Co., Ltd.). Separately, the solvent of the sample solution was added instead of the sample solution, and the same operation as described above was performed.
Platelet aggregation inhibition rate (%) = {(B−A) / B} × 100
However, A: Aggregation rate at the time of adding an aggregation initiator and adding a sample solution B: Aggregation rate at the time of adding an aggregation initiator and adding no sample solution The concentration of the sample solution was decreased stepwise to measure the platelet aggregation rate, The sample concentration IC ₅₀ (ppm) at which the inhibition rate was 50% was determined by interpolation (the smaller the IC ₅₀ value, the stronger the aggregation inhibition effect).

[Table 2] Inhibition of platelet aggregation
Test sample IC ₅₀ (ppm)
Enamel water extract 198
Enamel 50% ethanol extract 203
Nymphae ethanol extract 256
Gypsophila water extract 58
Budgerigar 50% ethanol extract 70
Exanthus ethanol extract 114
Wild Time Water Extract 76
Wild time 50% ethanol extract 90
Wild time ethanol extract 138
Tachikkosou water extract 156
Tachigasou 50% ethanol extract 209
Hachisou ethanol extract 255
Butchers Bloom Water Extract 37
Butcher's Bloom 50% ethanol extract 50
Butcher's Bloom ethanol extract 89

  As shown in Table 2, it was confirmed that the extract of enamel, budgerigar, wild thyme, ginger and butcher's bloom exhibits a platelet aggregation inhibitory effect in a concentration-dependent manner.

Claims (1)

  A platelet aggregation inhibitor characterized by containing at least one extract of enamel, gram, wild thyme, ginger and butcher's bloom as an active ingredient.