JP2010070487A - Mif secretion inhibitor - Google Patents
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本発明は、マクロファージ遊走阻止因子（MIF）分泌抑制剤、炎症性疾患の改善剤に関するものである。 The present invention relates to a macrophage migration inhibitory factor (MIF) secretion inhibitor and an inflammatory disease ameliorating agent.
マクロファージ遊走阻止因子（以下、ＭＩＦと記載する）は、炎症・免疫のメディエーターの１つであり、マクロファージの遊走を制御し、炎症部位にマクロファージを集め、貪食能を高める液性因子である。ＭＩＦは慢性関節リウマチ(非特許文献１：Expert Opin Ther Targets, 7, 2, 153-164, 2003)、腎炎(非特許文献２：Expert Opin Ther Targets, 7, 2, 153-164, 2003)、アトピー性皮膚炎(非特許文献３：Biochem Biophys Res Commun, 240, 11, 173-8, 1997)、乾癬（非特許文献４：B J Dermatol, 141, 1061-66, 1999）、潰瘍性大腸炎、敗血症、接触性皮膚炎(非特許文献５：Eur J Immunol, 33, 1478-87, 2003)、紫外線による炎症(非特許文献６：J Invest Dermatol, 112, 2, 210-15, 1999)、遅延性アレルギー(非特許文献７：Pro Natl Acad Sci USA, 93, 7849-54, 1996)などの急性・慢性炎症疾患(J End, 179, 15-23, 2003)、関節炎、移植片拒絶反応、腫瘍成長、血管新生、貧血、脳脊髄炎等の炎症性疾患の病理過程に関与しており、ＭＩＦを阻害することにより、これら炎症性疾患を軽減させることが期待される。
ＭＩＦの活性阻害剤は種々開発されている（特許文献１：特表２００３−５１３０６５号公報、特許文献２：特表２００５−５００２６６号公報、特許文献３：特表２００６−５１７９７７号公報）が、ＭＩＦの分泌抑制剤は知られていない。
本発明者は、ＭＩＦの分泌抑制に着目し、ＭＩＦの分泌抑制剤に関する研究開発を継続しているが、先に本発明者は、ヒメジョオン又はその抽出物をＭＩＦの分泌抑制剤とする技術を特願２００８−０２２５８８号に提案した。
シナヤグルマカエデは民間薬として知られており、冠状動脈硬化や脳血管疾患への治療に使用されてきた。また、その抗酸化や抗炎症、脂肪酸合成酵素阻害活性が知られている（非特許文献８：J Chromato A, 1070, 211-214, 2006）。しかし、シナヤグルマカエデによるＭＩＦの分泌抑制効果は知られていない。なかでもシナヤグルマカエデの葉に優れたＭＩＦの分泌抑制効果があることは全く知られていない。
Macrophage migration inhibitory factor (hereinafter referred to as MIF) is one of the mediators of inflammation and immunity, and is a humoral factor that controls macrophage migration, collects macrophages at the site of inflammation, and enhances phagocytic ability. MIF is rheumatoid arthritis (Non-patent document 1: Expert Opin Ther Targets, 7, 2, 153-164, 2003), nephritis (Non-patent document 2: Expert Opin Ther Targets, 7, 2, 153-164, 2003), Atopic dermatitis (non-patent document 3: Biochem Biophys Res Commun, 240, 11, 173-8, 1997), psoriasis (non-patent document 4: BJ Dermatol, 141, 1061-66, 1999), ulcerative colitis, Sepsis, contact dermatitis (Non-patent document 5: Eur J Immunol, 33, 1478-87, 2003), inflammation caused by ultraviolet rays (Non-patent document 6: J Invest Dermatol, 112, 2, 210-15, 1999), delayed Acute / chronic inflammatory diseases (J End, 179, 15-23, 2003) such as sexual allergy (Non-patent Document 7: Pro Natl Acad Sci USA, 93, 7849-54, 1996), arthritis, graft rejection, tumor It is involved in the pathological processes of inflammatory diseases such as growth, angiogenesis, anemia, encephalomyelitis and the like, and it is expected to reduce these inflammatory diseases by inhibiting MIF.
Various active inhibitors of MIF have been developed (Patent Document 1: JP-T-2003-513065, Patent Document 2: JP-T-2005-500266, Patent Document 3: JP-T-2006-517777), MIF secretion inhibitors are not known.
The present inventor has focused on MIF secretion suppression and has continued research and development on MIF secretion inhibitors. However, the present inventor has previously proposed a technique that uses Himejoon or its extract as a MIF secretion inhibitor. Proposed in Japanese Patent Application No. 2008-022588.
Chinese maple is known as a folk medicine and has been used to treat coronary atherosclerosis and cerebrovascular diseases. Moreover, the antioxidant, anti-inflammatory, and fatty acid synthase inhibitory activity are known (nonpatent literature 8: J Chromato A, 1070, 211-214, 2006). However, the inhibitory effect of MIF secretion by Chinese maple is not known. Among them, it is not known at all that the leaves of Chinese maple maple have an excellent MIF secretion inhibitory effect.
本発明はＭIF分泌抑制剤の提供を目的とする。 An object of the present invention is to provide a MIF secretion inhibitor.
シナヤグルマカエデ（学名Acer truncatum）の葉抽出物が、マクロファージ遊走阻止因子分泌抑制作用に優れることを見出し、本発明を完成させた。
本発明の主な構成は、次のとおりである。
１．シナヤグルマカエデ（学名Acer truncatum）の葉の抽出物を含むマクロファージ遊走阻止因子分泌抑制剤。
２．１．記載のマクロファージ遊走阻止因子分泌抑制剤を含む皮膚外用剤。
３．１．記載のマクロファージ遊走阻止因子分泌抑制剤を含む炎症性疾患の改善剤。
The present inventors have found that a leaf extract of Acer truncatum (scientific name: Acer truncatum) has an excellent inhibitory effect on the secretion of macrophage migration inhibitory factor, thereby completing the present invention.
The main configuration of the present invention is as follows.
1. Macrophage migration inhibitory factor secretion inhibitor containing the leaf extract of Acer truncatum (scientific name: Acer truncatum).
2.1. A skin external preparation comprising the described macrophage migration inhibitory factor secretion inhibitor.
3.1. An ameliorating agent for inflammatory diseases comprising the described macrophage migration inhibitory factor secretion inhibitor.
本発明により、MIF異常分泌が認められるアトピー性皮膚炎への新たな治療剤または予防剤の提供が可能となった。
アトピー性皮膚炎以外にMIFの異常分泌や関与が示唆されている、乾癬や紫外線による皮膚炎症、血管腫、蕁麻疹、敗血症、呼吸器炎症、潰瘍性大腸炎、慢性関節リウマチ、腎炎、接触性皮膚炎、遅延性アレルギーなどの急性・慢性炎症疾患、関節炎、移植片拒絶反応、腫瘍成長、血管新生、貧血、脳脊髄炎、その他菌感染による炎症への治療や予防にも効果を期待できる。ＭIF分泌抑制剤を皮膚外用剤として局所に処方することにより、マクロファージ遊走阻止因子の働きを抑えて、皮膚の炎症部位におけるマクロファージの機能を抑制することができる。
According to the present invention, it is possible to provide a new therapeutic agent or preventive agent for atopic dermatitis in which abnormal secretion of MIF is observed.
In addition to atopic dermatitis, abnormal secretion and involvement of MIF have been suggested, skin inflammation caused by psoriasis and ultraviolet rays, hemangioma, urticaria, sepsis, respiratory inflammation, ulcerative colitis, rheumatoid arthritis, nephritis, contact It is also expected to be effective in treating and preventing acute and chronic inflammatory diseases such as dermatitis and delayed allergy, arthritis, graft rejection, tumor growth, angiogenesis, anemia, encephalomyelitis, and other inflammation caused by bacterial infection. By locally prescribing the MIF secretion inhibitor as an external preparation for skin, the function of macrophage migration inhibitory factor can be suppressed, and the function of macrophages in the inflammatory site of skin can be suppressed.
本発明で使用されるシナヤグルマカエデ（学名 Acer truncatum）は、ムクロジ科 カエデ属の植物である。本発明ではシナヤグルマカエデの葉を用いるが、特に枯葉が好ましい。枯葉とは落葉樹の葉が秋になり自然に落葉したものを指すが、落葉せず枝に残った葉の色が緑色ではない黄色や赤色、茶色に変色した葉でも構わない。すなわち、自然に老熟した葉であればよい。 The Chinese maple maple (scientific name: Acer truncatum) used in the present invention is a plant belonging to the genus Maple. In the present invention, leaves of Chinese maple maple are used, but dead leaves are particularly preferable. Dead leaves are those that fall naturally in the fall of deciduous trees, but leaves that have not fallen and the leaves remaining on the branches may be yellow, red, or brown that are not green. That is, any leaf that is naturally ripened may be used.
シナヤグルマカエデの葉の抽出物としてはシナヤグルマカエデの葉又は枯葉をそのまま粉砕し、あるいは乾燥させた後に粉砕して、水あるいはエタノール等のアルコール、エーテル、アセトン、1,3−ブチレングリコール、1,2−ペンタンジオール、プロピレングリコール、酢酸エチルなどの有機溶媒により抽出した粗抽出物、および粗抽出物を分配抽出やカラムクロマトなどの各種クロマトグラフィーなどで段階的に精製して得られた抽出物画分を含む。これらは単独で用いても良く、また２種以上混合して用いても良い。シナヤグルマカエデの葉又は枯葉を生のまま抽出操作に供しても良いが、細切、乾燥、粉砕等の処理を行なった後、抽出を行なう方が効率がよい。抽出は抽出溶媒に浸漬して行なうことができる。抽出効率を上げる為に、抽出溶媒を攪拌したり、抽出溶媒中で破砕均一化したり、抽出溶媒中で圧力をかけることもできる。抽出温度は５〜１００℃程度が適切であり、抽出時間は５分〜1ヶ月程度である。これらの条件は適宜設定することができる。
前記シナヤグルマカエデ抽出物はそのまま、また、水、エタノール等の有機溶媒にけんだくさせた状態で、ＭIF分泌抑制剤、炎症性疾患の改善剤、特に皮膚の炎症性疾患改善剤として使用できる。また、必要に応じて抽出溶媒を留去し、その乾燥物を用いてもよい。
As an extract of the leaves of Chinese corn maple, the leaves or dead leaves of Chinese corn maple are crushed as they are, or dried and then crushed, water or alcohol such as ethanol, ether, acetone, 1,3-butylene glycol, 1 , 2-Pentanediol, Propylene glycol, Ethyl acetate and other crude extracts, and extracts obtained by stepwise purification of the crude extract with various types of chromatography such as partition extraction and column chromatography Includes fractions. These may be used alone or in combination of two or more. Although the leaves or dead leaves of Sinaia maple may be subjected to the extraction operation as they are, it is more efficient to perform the extraction after processing such as chopping, drying, and pulverization. Extraction can be performed by immersing in an extraction solvent. In order to increase the extraction efficiency, the extraction solvent can be stirred, crushed and homogenized in the extraction solvent, or pressure can be applied in the extraction solvent. The extraction temperature is suitably about 5 to 100 ° C., and the extraction time is about 5 minutes to 1 month. These conditions can be set as appropriate.
The Sinaia maple extract can be used as it is or in a state of being dissolved in an organic solvent such as water or ethanol, as a MIF secretion inhibitor, an inflammatory disease ameliorating agent, particularly a skin inflammatory disease ameliorating agent. Further, if necessary, the extraction solvent may be distilled off and the dried product may be used.
シナヤグルマカエデ葉又は枯葉抽出物は、乾燥物として、0.0001〜1000mg／日の範囲で適用することができ、さらに、この範囲に限らず、対象、適用形態、症状に応じてその量を適宜設定することができる。
本発明のシナヤグルマカエデ葉又は枯葉抽出物の配合量としては、0.0001〜10重量％程度が好ましいが、用いる剤型、使用対象等の様々の条件に応じて、１００重量％までの広範囲でその配合量を適宜設定できる。
Sinaia maple leaf or dead leaf extract can be applied as a dry product in the range of 0.0001 to 1000 mg / day, and the amount is not limited to this range, and the amount is appropriately set according to the target, application form, and symptoms can do.
The blending amount of the Sinaia maple leaf or dead leaf extract of the present invention is preferably about 0.0001 to 10% by weight, but in a wide range up to 100% by weight depending on various conditions such as the dosage form to be used and the intended use. A compounding quantity can be set suitably.
本発明の製剤は、経口で又は非経口で投与することができる。
本発明の製剤は、例えば水溶液、油剤、乳液、けんだく液等の液剤、ゲル、クリーム等の半固形剤、粉末、顆粒、カプセル、マイクロカプセル、固形等の固形剤の形態で適用可能である。従来から公知の方法でこれらの形態に調製し、ローション剤、乳剤、ゲル剤、クリーム剤、軟膏、硬膏、ハップ剤、エアゾル剤、坐剤、注射剤、粉末剤、顆粒剤、錠剤、丸剤、シロップ剤、トローチ剤等の種々の剤型とすることができる。これらを身体に塗布、貼付、噴霧、飲用等により適用することができる。特にこれら剤型の中で、皮膚外用剤であるローション剤、乳剤、クリーム剤、軟膏剤、硬膏剤、ハップ剤、エアゾル剤等が適している。
通常、医薬において使用される製剤化方法にしたがって、これらの剤型、組成物として製造することができる。
以下、本発明を詳細に説明する。
The preparation of the present invention can be administered orally or parenterally.
The preparation of the present invention can be applied in the form of, for example, a solution such as an aqueous solution, an oil, an emulsion, and a liquid, a semi-solid such as a gel and a cream, and a solid such as a powder, granule, capsule, microcapsule, and solid. . It is prepared in these forms by conventionally known methods, and lotions, emulsions, gels, creams, ointments, plasters, haps, aerosols, suppositories, injections, powders, granules, tablets, pills , Various dosage forms such as syrups and lozenges. These can be applied to the body by applying, sticking, spraying, drinking and the like. Among these dosage forms, lotions, emulsions, creams, ointments, plasters, haps, aerosols and the like, which are external preparations for skin, are suitable.
Usually, these dosage forms and compositions can be produced according to the formulation method used in medicine.
Hereinafter, the present invention will be described in detail.
シナヤグルマカエデエタノール抽出物の調製
シナヤグルマカエデ葉乾燥物１００gを６Lの９９．５%エタノールに1週間浸漬し、得られたエタノール抽出液の溶媒を留去して、２gのシナヤグルマカエデ抽出物を得た。
Preparation of Sinaia maple maple ethanol extract 100 g of dried Syringa maple leaf was soaked in 6 L of 99.5% ethanol for 1 week, and the solvent of the obtained ethanol extract was distilled off to obtain 2 g of Saga maple maple extract. Got.
シナヤグルマカエデ熱水抽出物の調製
シナヤグルマカエデ葉乾燥物１００gを６Lの蒸留水に入れ100℃で10分煮沸した。得られた熱水抽出液を凍結乾燥し、９gのシナヤグルマカエデ抽出物を得た。
Preparation of Sinaia maple maple hot water extract 100 g of dried Sinaia maple leaf was placed in 6 L of distilled water and boiled at 100 ° C. for 10 minutes. The obtained hot water extract was freeze-dried to obtain 9 g of Chinese corn maple extract.
シナヤグルマカエデ枯葉エタノール抽出物の調製
シナヤグルマカエデ枯葉乾燥物１００ｇを６Ｌの９９．５％エタノールに１週間浸漬し、得られたエタノール抽出液の溶媒を留去して、1ｇのシナヤグルマカエデ枯葉抽出物を得た。
Preparation of Sinaia maple maple dead leaf ethanol extract 100 g of dry seasoner maple maple leaf extract was soaked in 6 L of 99.5% ethanol for 1 week, and the solvent of the obtained ethanol extract was distilled off to give 1 g of Sedalia maple maple leaf extract. An extract was obtained.
シナヤグルマカエデ枯葉熱水抽出物の調製
シナヤグルマカエデ枯葉乾燥物１００ｇを６Lの蒸留水に入れ100℃で10分煮沸した。得られた熱水抽出液を凍結乾燥し、４gのシナヤグルマカエデ抽出物を得た。
Preparation of Sinaia maple maple leaf hot water extract 100 g of dried Sinaia maple maple leaf extract was placed in 6 L of distilled water and boiled at 100 ° C. for 10 minutes. The obtained hot water extract was freeze-dried to obtain 4 g of Chinese corn maple extract.
シナヤグルマカエデ抽出物のＭＩＦ分泌抑制試験
１．ケラチノサイトを用いたＵＶＢ誘導性ＭＩＦ分泌抑制試験
ＭＩＦは皮膚の構成細胞の一つであるケラチノサイトで強く発現することが知られている。そして、ケラチノサイトにUVBを照射することにより、ＭＩＦの分泌が促進されることが知られている(J Invest Dermatol, 112, 2, 210-15, 1999)。そこで、ケラチノサイトにＵＶＢを照射したときのＭＩＦの分泌を、シナヤグルマカエデ抽出物が抑制するか調べた。
ヒトケラチノサイトを7.0×104cells/cm2でφ35mm dishに播種し、KBM・KGM培地（LONZA社製）で5日間培養した。各サンプルの入ったKBM・KGM培地（BPE(-)）に交換し、1晩培養後、HANKS(-)存在下で、UVBを1.0 W/m2、20 mJ/m2照射し、それぞれ各サンプルの入ったKBM・KGM培地（BPE(-)）に交換し、6時間培養した。培養上清を回収し、hMIF ELISA kitを用いて、定法に従い上清中MIF量を測定し、MIF分泌量を算出した。さらに、細胞をCell Lysis Bufferで溶解し、溶解液中の蛋白質をプロテインアッセイキットで測定し、dishあたりの蛋白量を算出した。サンプル無添加、UVB(-)処理を100%とし、サンプル添加時の単位蛋白質当たりのMIF分泌率の比較を行った。結果を表１に示す。又、表１の結果をグラフ化し図１に示す。なお、本試験におけるコントロールとサンプル添加の細胞のタンパク質量を比較した結果、両者におけるタンパク質量に差は認められず、各サンプルの細胞毒性は本試験系において認められなかった。
1. MIF secretion inhibition test of Chinese corn maple extract UVB-induced MIF secretion inhibition test using keratinocytes It is known that MIF is strongly expressed in keratinocytes, one of the constituent cells of the skin. It is known that MIF secretion is promoted by irradiating UVB to keratinocytes (J Invest Dermatol, 112, 2, 210-15, 1999). Therefore, it was examined whether or not the Sinaia maple extract extracts MIF secretion when keratinocytes are irradiated with UVB.
Human keratinocytes were seeded in a φ35 mm dish at 7.0 × 10 4 cells / cm 2 and cultured in KBM / KGM medium (manufactured by LONZA) for 5 days. Change to KBM / KGM medium (BPE (-)) containing each sample, and after overnight culture, UVB was irradiated at 1.0 W / m 2 and 20 mJ / m 2 in the presence of HANKS (-). The sample was replaced with KBM / KGM medium (BPE (-)) containing the sample and cultured for 6 hours. The culture supernatant was collected, and the amount of MIF in the supernatant was measured using the hMIF ELISA kit according to a conventional method, and the amount of MIF secretion was calculated. Furthermore, the cells were lysed with Cell Lysis Buffer, the protein in the lysate was measured with a protein assay kit, and the amount of protein per dish was calculated. The sample was not added and UVB (-) treatment was taken as 100%, and the MIF secretion rate per unit protein at the time of sample addition was compared. The results are shown in Table 1. The results of Table 1 are graphed and shown in FIG. In addition, as a result of comparing the protein amount of the control and the sample-added cells in this test, there was no difference in the protein amount between the two, and no cytotoxicity of each sample was observed in this test system.
このことから、シナヤグルマカエデにおいては、特に枯葉の抽出物の方がＭＩＦ分泌を抑制する効果に優れることが分かった。
From this, it was found that the extract of dead leaves was particularly effective in suppressing MIF secretion in Chinese maple maple.
ケラチノサイトにシナヤグルマカエデ枯葉抽出物を添加することにより、ＭＩＦの分泌が顕著に抑制された。ＭＩＦの発現が増加し、症状が悪化することが知られている紫外線による皮膚障害・炎症、アトピー性皮膚炎、乾癬、接触性皮膚炎等の皮膚の炎症性疾患に対して、シナヤグルマカエデ枯葉抽出物はより優れた改善効果が期待できる。 MIF secretion was remarkably suppressed by adding cinnamon maple maple leaf extract to keratinocytes. Sinaia maple dead leaves against skin inflammatory diseases such as UV-induced skin disorders / inflammation, atopic dermatitis, psoriasis, contact dermatitis, etc. The extract can be expected to have a better improvement effect.
２．THP-1細胞を用いたLPS誘導性ＭＩＦ分泌抑制試験
菌感染や異物などの刺激によりマクロファージからのＭＩＦ分泌が促進されることが知られている。マクロファージのモデル細胞であるヒト単球性白血病細胞であるTHP-1細胞は、菌感染モデルのLPSの刺激により、MIFを分泌する (FEBS Let 551, 78-88, 2003)。そこで、LPSで刺激したTHP-1細胞のMIF分泌を、シナヤグルマカエデ抽出物が抑制するか調べた。
2. LPS-induced MIF secretion inhibition test using THP-1 cells It is known that MIF secretion from macrophages is promoted by bacterial infection or stimulation of foreign substances. THP-1 cells, which are human monocytic leukemia cells, which are macrophage model cells, secrete MIF upon stimulation with LPS in a bacterial infection model (FEBS Let 551, 78-88, 2003). Therefore, it was examined whether or not the Sinaia maple extract suppressed MIF secretion of THP-1 cells stimulated with LPS.
THP-1細胞を1%血清・RPMI培地中で3時間培養後、同培地で1×106cells/well(12well plate)で播種し、各サンプルを添加した。各サンプル添加45分後に、LPSを終濃度10μg/mlで添加し、4時間培養した。培養後に400×gで遠心し、細胞上清を回収し、hMIF ELISA kitを用いて、定法に従い上清中MIF量を測定し、MIF分泌量を算出した。サンプル無添加、LPS(-)処理を100%とし、サンプル添加時のMIF分泌率の比較を行った。
実施例２および実施例４のサンプル添加時の結果を表２に示す。又、表２の結果をグラフ化し図２に示す。
THP-1 cells were cultured in 1% serum / RPMI medium for 3 hours, seeded at 1 × 10 6 cells / well (12 well plate) in the same medium, and each sample was added. 45 minutes after the addition of each sample, LPS was added at a final concentration of 10 μg / ml and cultured for 4 hours. After culturing, the cells were centrifuged at 400 × g, the cell supernatant was collected, the amount of MIF in the supernatant was measured according to a conventional method using hMIF ELISA kit, and the amount of MIF secretion was calculated. The sample was not added and LPS (-) treatment was taken as 100%, and the MIF secretion rate at the time of sample addition was compared.
Table 2 shows the results when the samples of Example 2 and Example 4 were added. The results of Table 2 are graphed and shown in FIG.
これに対し、シナヤグルマカエデ枯葉熱水抽出物（実施例４）を添加したwellでは、ＭＩＦ分泌率が６９％と抑えられ、実施例２と比べて著しいＭＩＦ分泌抑制効果が認められた。
On the other hand, in the well to which Sinaia maple dead leaf hot water extract (Example 4) was added, the MIF secretion rate was suppressed to 69%, and a remarkable MIF secretion inhibitory effect was observed compared to Example 2.
実施例１および実施例３の抽出物はＤＭＳＯ（ジメチルスルホキシド）に溶解して添加したので、同量のＤＭＳＯを添加し、サンプル無添加、ＬＰＳ（−）処理を１００％として、サンプル添加時のＭＩＦ分泌率の比較を行った。
実施例１および実施例３のサンプル添加時の結果を表３に示す。又、表３の結果をグラフ化し図３に示す。
Since the extracts of Example 1 and Example 3 were added after dissolved in DMSO (dimethyl sulfoxide), the same amount of DMSO was added, no sample was added, and LPS (−) treatment was set to 100%, and the sample was added at the time of sample addition. Comparison of MIF secretion rate was performed.
Table 3 shows the results when the samples of Example 1 and Example 3 were added. The results of Table 3 are graphed and shown in FIG.
これに対し、シナヤグルマカエデ枯葉エタノール抽出物（実施例３）を添加したwellでは、ＭＩＦ分泌率が４５％と抑えられ、実施例１と比べて著しいＭＩＦ分泌抑制効果が認められた。
On the other hand, in the wells to which Sinaia maple maple leaf ethanol extract (Example 3) was added, the MIF secretion rate was suppressed to 45%, and a remarkable MIF secretion inhibitory effect was observed compared to Example 1.
THP-1細胞にシナヤグルマカエデ枯葉抽出物を添加することにより、顕著にＭＩＦの分泌が抑制された。ニキビ、敗血症、などの菌感染による炎症や、浸潤性炎症、アレルギー、慢性関節リウマチなどの慢性炎症疾患に対して、シナヤグルマカエデ枯葉抽出物はより優れた予防や改善が期待できる。 MIF secretion was remarkably suppressed by adding Sinaia maple leaf extract to THP-1 cells. With respect to inflammation caused by bacterial infections such as acne and sepsis, and chronic inflammatory diseases such as invasive inflammation, allergies, and rheumatoid arthritis, Sinaia maple leaf extract can be expected to be more excellent in prevention and improvement.
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| CN102614232A (en) * | 2012-04-23 | 2012-08-01 | 昆明海之灵生物科技开发有限公司 | Acer truncatum health-care lozenge and preparation method thereof |
| CN103315289A (en) * | 2013-05-07 | 2013-09-25 | 江苏丹枫神源生物科技有限公司 | Mono maple pollen extract and application of the same as health care product |
| WO2018106009A1 (en) * | 2016-12-07 | 2018-06-14 | 한국한의학연구원 | Composition containing maple tree leaf extract or fractions thereof for preventing or treating inflammatory ocular diseases |
| CN109456948A (en) * | 2018-11-23 | 2019-03-12 | 遵义医学院附属医院 | MIF and TIPE2 double gene coexpression recombined adhenovirus and its preparation method and application |
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