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WO2005092357A1 - Agent antiallergique et agent anti-inflammatoire - Google Patents

Agent antiallergique et agent anti-inflammatoire Download PDF

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Publication number
WO2005092357A1
WO2005092357A1 PCT/JP2005/005181 JP2005005181W WO2005092357A1 WO 2005092357 A1 WO2005092357 A1 WO 2005092357A1 JP 2005005181 W JP2005005181 W JP 2005005181W WO 2005092357 A1 WO2005092357 A1 WO 2005092357A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
lycium
agent according
antiallergic
agent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2005/005181
Other languages
English (en)
Japanese (ja)
Inventor
Hiroko Isoda
Shinichi Yokota
Yukuo Abe
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kaneka Corp
Original Assignee
Kaneka Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kaneka Corp filed Critical Kaneka Corp
Priority to JP2006511466A priority Critical patent/JPWO2005092357A1/ja
Publication of WO2005092357A1 publication Critical patent/WO2005092357A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an anti-allergy agent and an anti-inflammatory agent that can be used as foods and drinks for humans or animals, pharmaceuticals, and cosmetics.
  • Basophils present in blood and mast cells present around blood vessels and connective tissues have granules containing histamine and the like, and degranulation of these cells causes / 3-hexosaminidase and the like together with histamine. It has been known to release enzymes and induce immediate allergic reactions such as asthma and atopic eczema.
  • an allergic disease is not the same as an atopic disease. Allergy is involved in some atopic diseases, but microbial infections and genetic factors play a complex role in the onset of atopic diseases, as typified by atopic dermatitis .
  • mast cells and basophils can reduce allergy by inhibiting degranulation of these cells, which are strongly involved in immediate allergy. Therefore, an effective basophil cell degranulation inhibitor or mast cell degranulation inhibitor It is desirable to develop agents to provide useful antiallergic agents.
  • Anti-allergic agents include agents that suppress degranulation from mast cells and release of chemical mediators in type I allergic reactions that are immediate allergies, and agents that inhibit the binding of histamine to HI receptors.
  • Drugs that inhibit the lipid-type chemical mediator thromboxane A2 and drugs that suppress leukotriene have been developed, and have side effects such as central nervous system depression such as drowsiness and sedation, and cystitis-like symptoms such as hematuria. No drug is satisfactory enough.
  • the safety of antiallergic drugs is particularly important because they are often used not only for treatment but also for prophylactic purposes over a long period of time.
  • Lycium plants are plants of the Solanaceae family, the leaves of which are called licorice leaves, the fruits are licorice leaves, and the root bark is skeletal bark. It is said to have the effect of preventing presbyopia.
  • a wolfberry plant contains ⁇ -sitosterol, linolenic acid, zeaxanthin, betaine and fuesaliene, in addition to carotenes and vitamins.
  • betaine has an effect on lipid metabolism and anti-fatty liver, and an anti-fatty liver action of a water extract on the liver is known.
  • the present invention refers to the effect on the atopic dermatitis, which is reported to have an effect on the atopic disease of a wolfberry plant, and its basophil cell degranulation inhibitory activity or mast cell degranulation. No antiallergic effect due to inhibitory activity was found (Patent Document 2). In addition, there has been no report that basophil cell degranulation inhibitory activity, mast cell degranulation inhibitory activity, and / 3-hexosaminidase release inhibitory activity are caused by a wolfberry plant or a polar solvent thereof.
  • Patent Document 1 JP 2001-233778
  • Patent Document 2 JP 2004-67526
  • An object of the present invention is to provide a new antiallergic agent and an antiinflammatory agent which can be easily produced with high safety and can be blended in cosmetics and foods and drinks.
  • the present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, an extract obtained by extracting a Lycium plant with a polar solvent has a ⁇ -hexosaminidase inhibitory activity, The present inventors have found that they have a basophil cell degranulation inhibitory activity and a mast cell degranulation inhibitory activity, and have an antiallergic action and an anti-inflammatory action, thereby completing the present invention.
  • the present invention relates to an antiallergic agent comprising a Lycium plant or an extract thereof as an active ingredient.
  • the present invention also relates to a basophil cell degranulation inhibitor containing a Lycium plant or an extract thereof.
  • the present invention also relates to a mast cell degranulation inhibitor comprising a Lycium plant or an extract thereof.
  • the present invention also relates to a j3-hexosaminidase release inhibitor, which comprises an extract of a Lycium plant.
  • the antiallergic agent and the antiinflammatory agent of the present invention may be either a preventive agent or an ameliorating agent, or may be a combination of both.
  • the wolfberry extract described in the present specification is useful as an antiallergic agent and an antiinflammatory agent. Since the wolfberry extract of the present invention is highly safe and can be prepared by a simple method, it is highly applicable to pharmaceuticals, foods and drinks, cosmetics, bath preparations, etc., and its application range is extremely wide. Expected.
  • FIG. 1 is a graph showing a dilution ratio of a wolfberry hot water extract and an inhibition rate of ⁇ -hexosaminidase release of human basophils.
  • the genus Lycium is a plant belonging to the Solanaceae family, and is a species of Lycium chinense (also referred to as Lycium chmensis: 3 ⁇ 4 may be self-prone), Lycium barb arum Lycium turcomanicum, Lycium potaninii, Lycium dasystemum, etc.
  • Lycium chinense also referred to as Lycium chmensis: 3 ⁇ 4 may be self-prone
  • Lycium barb arum Lycium turcomanicum Lycium potaninii, Lycium dasystemum, etc.
  • the wolfberry plant used for the antiallergic agent, antibasophil cell degranulation inhibitor, mast cell degranulation inhibitor or ⁇ -hexosaminidase release inhibitor of the present invention is not particularly limited as long as it belongs to the genus Lycium.
  • chmense3; 7 lysium Lycium barbarum power is preferred, Lycmm chinense power is nun
  • the method for producing a Lycium plant used in the present invention is not particularly limited.
  • the wolfberry plant used in the present invention may be not only a naturally grown plant but also an artificially cultivated plant.
  • the wolfberry plant used in the present invention may be used by selecting only one kind from among various kinds of production methods, or may be used by combining a plurality of kinds.
  • An extract of a wolfberry plant is obtained by extracting various parts of a plant body (whole plant, flower, leaf, etc.) as they are or after pulverizing them and extracting them with an extraction solvent.
  • the portion used for extraction is not particularly limited, but is more preferably a fruit (Guyuko), which is favored by leaves (Gyugia leaves), fruits (Guyako), and root bark (skeletal bark).
  • a polar solvent can be used as the extraction solvent.
  • the polar solvent include polar organic solvents such as water and alcohols (eg, lower alcohols such as ethanol and methanol, and polyhydric alcohols such as propylene glycol). Any combination of more than one species can be used. Preferably, it is water alone or a mixed solvent of water and a polar organic solvent.
  • the mixing ratio of water and the polar organic solvent is not particularly limited, but it is preferable that the main component is water, that is, the volume ratio of water is 50% or more.
  • the polar organic solvent to be mixed with water methanol or ethanol is more preferable, since lower alcohols are preferable.
  • the components to be extracted are different because the polarity as the solvent is different as compared with the case of extracting mainly with an organic solvent.
  • the amount of extraction solvent used 0.5 weight to 50 weight is preferable to the genus plant, and 2 weight to 10 weight is more preferable.
  • the extraction method is not particularly limited. Usually, extraction may be performed at normal temperature and normal pressure using an extraction solvent. In this case, the extraction time is not particularly limited. 14 days is preferred. After extraction, it may be concentrated, dried, or made into a solution, paste, gel, or powder with oils and fats. In some cases, extraction can be performed under a condition of 30 to 120 ° C., or extraction can be performed under supercritical conditions using an autoclave, carbon dioxide, or the like. The extraction time may be appropriately set. If necessary, it can be further purified by an optional operation using an activated carbon column or an ion exchange resin.
  • an extract obtained by extracting a wolfberry plant with hot water can be used.
  • the amount of hot water used for the extraction is preferably an amount that can sufficiently dissolve the active ingredient contained in the wolfberry plant.
  • extraction of a wolfberry plant is carried out by washing the collected wolfberry plant to remove dirt and organisms attached to the surface, and then cutting, ball milling, ultrasonic treatment, a homogenizer and the like. It can be extracted after crushing. Prior to crushing, air drying or freeze drying may be performed. The crushed wolfberry plant is preferably extracted repeatedly several times with an extraction solvent such as hot water while stirring. This extract can be used as it is as a basophil cell degranulation inhibitor, mast cell degranulation inhibitor, -hexosaminidase release inhibitor, antiallergic agent or antiinflammatory agent.
  • the extract of the genus wolfberry of the present invention can be adjusted to an appropriate concentration by diluting or concentrating as necessary.
  • the extract of the present invention can be diluted with water or alcohol by adding it to be used as a water-soluble substance, or can be mixed with fats and oils to form a cream.
  • the extract is spray-dried to obtain a powdered basophil cell degranulation inhibitor, mast cell degranulation inhibitor, / 3-hexosaminidase release inhibitor, anti-allergic agent or anti-inflammatory agent You can also.
  • the concentration and shape of the extract of the present invention are not particularly limited, and can be appropriately determined according to the use.
  • the extract of the present invention may contain components other than an extract of a wolfberry plant. Since the extract of the present invention uses an extract of a wolfberry plant used for food as an active ingredient, the extract is highly safe for a living body. For this reason, the extract of the present invention is used for pharmaceuticals, functional foods, Products, quasi-drugs, cosmetics, bath preparations and a wide range of other products.
  • the wolfberry plant or the extract of the wolfberry plant of the present invention has ⁇ xosaminidase release inhibitory activity, it has an effect of inhibiting degranulation from basophils or mast cells. It can be used as a basophil cell degranulation inhibitor or a mast cell degranulation inhibitor, and is also useful as an antiallergic or antiinflammatory agent. That is, / 3 xosaminidase is one of the substances released from basophils or obesity cells upon degranulation. Therefore, anti-allergic and anti-inflammatory effects can be evaluated by measuring the / 3 xosaminidase released by degranulation from cells using the / 3 xosaminidase release assay.
  • basophil cell degranulation inhibitory activity or mast cell degranulation inhibitory activity is measured by the activity of -hexosaminidase released by degranulation.
  • ⁇ -Hexosaminidase activity was released by sensitizing cells with a mouse anti-DNP-IgE antibody using basophil cells such as KU812 shown in Example 3 below, and then using the antigen DNP-BSA.
  • the i3 xosaminidase activity is measured.
  • the enriched cells may be used for measuring i3_hexosaminidase activity. If wolfberry genus having high basophil cell degranulation inhibitory activity or mast cell degranulation inhibitory activity is used in combination, stronger antiallergic and anti-inflammatory effects can be expected.
  • the anti-allergic agent and anti-inflammatory agent of the present invention contain an active ingredient of a wolfberry plant or an extract of a wolfberry plant, and may be an extract solution or an extract itself, or a carrier or auxiliary agent known in the art. It may be a composition to which an agent, a food or drink material, another pharmaceutically acceptable formulation material, or the like is added.
  • the amount of the extract is not particularly specified, but the concentration of the extract of the present invention in these products can be appropriately selected within a range in which a desired effect is obtained.
  • it can be administered in one to several doses, for example, at a dose of 0.2 to 100 mg / Kg body weight per day.
  • the dosage form of the drug may be tablets, capsules, injections, drops, powders, suppositories, granules, ointments, suspensions, emulsions, syrups , Creams and the like.
  • binders such as agents, stabilizers, emulsifiers and buffers
  • Additives such as agents, stabilizers, emulsifiers and buffers
  • Preferred examples of the binder include starch, trehalose, dextrin, gum arabic powder, and the like.
  • Preferable examples of the lubricant include stearic acid, talc, sucrose fatty acid ester, polyethylene glycol and the like.
  • Preferred examples of the disintegrant include starch, carboxymethyl cellulose, corn starch and the like.
  • Preferable examples of the stabilizer include fats and oils, propylene glycol and the like.
  • Preferable examples of the emulsifier include an anionic surfactant, a nonionic surfactant, and polybutyl alcohol.
  • Preferred examples of the buffer include buffers such as phosphate, carbonate, and citrate.
  • the antiallergic agent or antiinflammatory agent of the present invention can be contained in foods and drinks, cosmetics and bath preparations, and the content thereof is not particularly limited, but is usually 0.0001% by weight or more, preferably 0.01% by weight or more. 100% by weight is good.
  • the extract of the present invention is contained in cosmetics and used as an antiallergic agent or an anti-inflammatory agent, the content can be adjusted to 0.01 to 10% by weight.
  • the food can be made a functional food for the purpose of preventing and / or improving allergy and inflammation.
  • the type of food to be targeted is not particularly limited as long as the extract does not inhibit the anti-allergic and anti-inflammatory effects.
  • beverages such as juice, soft drinks, tea, etc., processed foods such as bread and rice cake, sweets such as candy, instant foods such as cup ramen, fats and oils such as butter and salad oil, dressings, mayonnaise, sauces, and soy sauce
  • seasonings such as yamirin, sprinkles, and miso.
  • the extract it is possible to grind the wolfberry plant as it is, and ingest it directly into foods and the like.
  • Human immature basophils (KU812) cells were seeded on a medium prepared with 10% FBS, MEM 4.7 g / 500 ml, 200 mM L-gunorethamine 5 ml / 500 ml, 10% NaHCO (pH 7.0.7.4). Incubate at 37 ° C under 5% CO. Next, the cultured KU812 was peeled from the flask, and adjusted to a cell concentration of 5 ⁇ 10 5 cells / ml using the same medium as above, and finally 0.3 ml of lmg / ml mouse anti-DNP_IgE antibody was added. / ml.
  • the cells were seeded at 96 ⁇ / well in a 96-well plate, and incubated at 37 ° C under 5% CO in a carbon dioxide gas incubator to sensitize the cells.
  • the Itoda spores were washed twice with 200 / il PBS, and then-hexosaminidase release buffer (116.9 mM NaCl, 5.4 mM KC1, 0.8 mM MgSO-7H ⁇ , 5.6 mM gnorecose, 25 mM HEPES
  • the substrate solution 85.5 mg of p_nitrophenyto N-acetylb-D_glucosamide to 50 ml of 50 mM citrate buffer (pH 4.5; Add 80 ⁇ L of the solution (added to pH) with acid) and incubate at 37 ° C for 30 minutes. Then, the reaction stop solution (100 mM carbonate buffer; Na C03 1.06 g)
  • Inhibition rate (%) ⁇ 1- (S-B) / (C-b) ⁇ X100
  • the wolfberry extract of the present invention significantly inhibited the release of / 3 xosaminidase from basophils, which is an indicator of antiallergic action.
  • sucrose fatty acid ester 5 parts by weight of sucrose fatty acid ester
  • the above composition was mixed and tableted to produce a dietary tablet containing a wolfberry extract.
  • the above composition was mixed, pulverized, and filled into a gelatin capsule to produce a dietary power capsule containing a wolfberry extract.
  • a dressing containing wolfberry extract was prepared by the usual method with the above composition
  • Example 2 0.5 parts by weight of the wolfberry extract obtained in Example 2
  • a wolfberry extract-containing chewing gum having the above composition was prepared by a conventional method.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Botany (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
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  • Microbiology (AREA)
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  • Polymers & Plastics (AREA)
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  • Coloring Foods And Improving Nutritive Qualities (AREA)
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  • Medicines Containing Plant Substances (AREA)

Abstract

Un agent antiallergique et un agent anti-inflammatoire, un inhibiteur de dégranulation des basophiles, un inhibiteur de dégranulation de mastocyte ou un inhibiteur de libération de β-hexosaminidase contenant une plante appartenant au gène Lycium ou un solvant polaire extrait de ceux-ci. En utilisant la plante appartenant au gène Lycium qui est un matériau naturel ayant été pris par les êtres humains pendant longtemps, un agent antiallergique et un agent anti-inflammatoire présentant une sécurité élevée peuvent être fournis grâce à un procédé pratique. De plus, cet agent antiallergique et cet agent anti-inflammatoire peuvent être ajoutés à des nutriments, des boissons, des cosmétiques, des préparations de bain, des médicaments etc.
PCT/JP2005/005181 2004-03-29 2005-03-23 Agent antiallergique et agent anti-inflammatoire Ceased WO2005092357A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2006511466A JPWO2005092357A1 (ja) 2004-03-29 2005-03-23 抗アレルギー剤および抗炎症剤

Applications Claiming Priority (2)

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JP2004-094832 2004-03-29
JP2004094832 2004-03-29

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WO2005092357A1 true WO2005092357A1 (fr) 2005-10-06

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20170133561A (ko) * 2016-05-25 2017-12-06 주식회사 엘지생활건강 원지 또는 지골피 추출물을 유효성분으로 포함하는 항비듬용 화장료 조성물.
JPWO2018230733A1 (ja) * 2017-06-16 2020-07-27 マルホ株式会社 皮膚外用剤
CN118662572A (zh) * 2024-05-31 2024-09-20 北京工商大学 一种具有延缓皮肤光老化和抑制炎症功效的中华枸杞水提物制备与应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004067526A (ja) * 2002-08-02 2004-03-04 Noevir Co Ltd アトピー性疾患の症状の予防・緩和に有効な組成物

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004067526A (ja) * 2002-08-02 2004-03-04 Noevir Co Ltd アトピー性疾患の症状の予防・緩和に有効な組成物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SHIMANE-KEN ET AL: "Kakuso Nado no Saiba Gijutsu no Kakuritsu to Riyo Gijutsu no Kaihatsu.", pages 35, Retrieved from the Internet <URL:URL:http://www3.pref.shimane.jp/vritc/yakusou2.pdf> *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20170133561A (ko) * 2016-05-25 2017-12-06 주식회사 엘지생활건강 원지 또는 지골피 추출물을 유효성분으로 포함하는 항비듬용 화장료 조성물.
KR102429344B1 (ko) 2016-05-25 2022-08-05 주식회사 엘지생활건강 원지 또는 지골피 추출물을 유효성분으로 포함하는 항비듬용 화장료 조성물.
JPWO2018230733A1 (ja) * 2017-06-16 2020-07-27 マルホ株式会社 皮膚外用剤
JP2023054255A (ja) * 2017-06-16 2023-04-13 マルホ株式会社 皮膚外用剤
JP7473925B2 (ja) 2017-06-16 2024-04-24 マルホ株式会社 皮膚外用剤
CN118662572A (zh) * 2024-05-31 2024-09-20 北京工商大学 一种具有延缓皮肤光老化和抑制炎症功效的中华枸杞水提物制备与应用

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