TW202312990A - Composition containing 1'-acetoxychavicol acetate and acetyl eugenol - Google Patents
Composition containing 1'-acetoxychavicol acetate and acetyl eugenol Download PDFInfo
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Abstract
Description
本發明有關種含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之組成物。且本發明有關發炎之預防或發炎症狀之改善方法等。The present invention relates to a composition containing 1'-acetyloxygamrol acetate and acetyleugenol. Furthermore, the present invention relates to methods for preventing inflammation or improving symptoms of inflammation, and the like.
1’-乙醯氧基佳味酚乙酸酯(ACA)係薑科植物的大高良薑(學名：Alpinia galanga)中所含的化合物。ACA據報導可抑制負責發炎路徑之中心的NF kappaB(NF-κB)(非專利文獻1)。非專利文獻2中報導將大高良薑根莖進行水蒸氣蒸餾，以***萃取之餾分中，ACA及乙醯丁香酚以100：1.93含有(非專利文獻2)。 [先前技術文獻] [非專利文獻] 1'-Acetyloxygamicol acetate (ACA) is a compound contained in Galangal (scientific name: Alpinia galanga), a plant of the Zingiberaceae family. ACA is reported to inhibit NF kappaB (NF-κB), which is the center of the inflammatory pathway, which is responsible (Non-Patent Document 1). Non-Patent Document 2 reports that the rhizome of Galanga galanga is subjected to steam distillation, and in the fraction extracted with ether, ACA and acetyl eugenol are contained at a ratio of 100:1.93 (Non-Patent Document 2). [Prior Art Literature] [Non-patent literature]
非特許文獻1：Misawa et al., Bioorganic & Medicinal Chemistry 23 (2015) 2241-2246 非專利文獻2：森英己等人，日本食品科學工業會誌，第42卷，第12期，1995年12月，第989-995頁 Non-patented literature 1: Misawa et al., Bioorganic & Medicinal Chemistry 23 (2015) 2241-2246 Non-Patent Document 2: Eiki Mori et al., Journal of the Japan Food Science and Industry Association, Vol. 42, No. 12, December 1995, pp. 989-995
[發明欲解決之課題][Problem to be solved by the invention]
本發明之目的係提供含1’-乙醯氧基佳味酚乙酸酯，而可增強1’-乙醯氧基佳味酚乙酸酯之抗發炎作用之組成物。且本發明之目的係提供發炎之預防或發炎症狀之改善方法。 [用以解決課題之手段] The object of the present invention is to provide a composition containing 1'-acetyloxy gyrol acetate, which can enhance the anti-inflammatory effect of 1'-acetyloxy gyrol acetate. Furthermore, the object of the present invention is to provide a method for preventing inflammation or improving symptoms of inflammation. [Means to solve the problem]
本發明人等發現藉由將組成物中之1’-乙醯氧基佳味酚乙酸酯含量與乙醯丁香酚之含量的比率於特定範圍內，可增強1’-乙醯氧基佳味酚乙酸酯之抗發炎作用。The present inventors found that by setting the ratio of the content of 1'-acetyloxygamrol acetate to the content of acetyleugenol in the composition within a specific range, 1'-acetyloxygamrol can be enhanced. Anti-inflammatory effects of phenol acetate.
亦即本發明包含以下之組成物，但不限定於此。 [1] 一種組成物，其係含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚，相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.01~1.9重量份。 [2] 如上述[1]之組成物，其中相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.06~1.5重量份。 [3] 如上述[1]或[2]之組成物，其中相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.09~0.6重量份。 [4] 如上述[1]至[3]中任一項之組成物，其係抗發炎用組成物。 [5] 如上述[1]至[4]中任一項之組成物，其係使用於發炎之預防或發炎症狀之改善。 [6] 一種發炎之預防或發炎症狀之改善方法，其包含將1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚投予至對象，且相對於1’-乙醯氧基佳味酚乙酸酯之投予量100重量份，乙醯丁香酚之投予量為0.01~1.9重量份。 [7] 如上述[6]之方法，其中相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.01~1.9重量份。 [8] 一種1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之使用，其係用於發炎之預防及發炎症狀之改善，且相對於1’-乙醯氧基佳味酚乙酸酯100重量份，使用乙醯丁香酚0.01~1.9重量份。 [9] 如上述[8]之使用，其中上述使用係含1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之組成物之使用，前述組成物係相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.01~1.9重量份。 [發明效果] That is, the present invention includes the following compositions, but is not limited thereto. [1] A composition comprising 1'-acetyloxygaymol acetate and acetyleugenol, wherein acetyl The content of eugenol is 0.01-1.9 parts by weight. [2] The composition according to the above [1], wherein the content of acetyleugenol is 0.06 to 1.5 parts by weight relative to 100 parts by weight of 1'-acetyloxygamrol acetate. [3] The composition according to the above [1] or [2], wherein the content of acetyleugenol is 0.09 to 0.6 parts by weight relative to 100 parts by weight of 1'-acetyloxygamrol acetate. [4] The composition according to any one of the above-mentioned [1] to [3], which is an anti-inflammatory composition. [5] The composition according to any one of the above-mentioned [1] to [4], which is used for the prevention of inflammation or the improvement of inflammation symptoms. [6] A method for preventing inflammation or improving symptoms of inflammation, comprising administering 1'-acetyloxygamrol acetate and acetyleugenol to a subject, and relative to 1'-acetyloxy The dosage of jiaminol acetate is 100 parts by weight, and the dosage of acetyl eugenol is 0.01-1.9 parts by weight. [7] The method of [6] above, wherein the content of acetyleugenol is 0.01 to 1.9 parts by weight relative to 100 parts by weight of 1'-acetyloxygamrol acetate. [8] The use of 1'-acetyloxygaymol acetate and acetyleugenol for the prevention of inflammation and the improvement of inflammation symptoms, and compared with 1'-acetyloxygamicol For 100 parts by weight of phenol acetate, 0.01 to 1.9 parts by weight of acetyl eugenol is used. [9] Use as in the above [8], wherein the above use is the use of a composition containing 1'-acetyloxygamrol acetate and acetyl eugenol, and the above composition is relative to 1'-acetate For 100 parts by weight of acyloxy gamol acetate, the content of acetyl eugenol is 0.01-1.9 parts by weight. [Invention effect]
依據本發明可提供含1’-乙醯氧基佳味酚乙酸酯，而可增強1’-乙醯氧基佳味酚乙酸酯之抗發炎作用之組成物。且依據本發明可提供發炎之預防或發炎症狀之改善方法。According to the present invention, it is possible to provide a composition containing 1'-acetyloxy gyrol acetate, which can enhance the anti-inflammatory effect of 1'-acetyloxy gyrol acetate. And according to the present invention, a method for preventing inflammation or improving symptoms of inflammation can be provided.
本發明之組成物係含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚，且相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.01~1.9重量份之組成物。The composition of the present invention contains 1'-acetyloxy gaymol acetate and acetyl eugenol, and relative to 100 parts by weight of 1'-acetyloxy gaymol acetate, acetyl eugenol The content is 0.01-1.9 parts by weight of the composition.
本發明中，1’-乙醯氧基佳味酚乙酸酯可為D體、L體或該等之混合物之任一者。本發明中，關於1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之來源、製法未特別限制。1’-乙醯氧基佳味酚乙酸酯可源自天然物，亦可為合成品。乙醯丁香酚可源自天然品，亦可為合成品。1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚，例如可自大高良薑萃取而得。In the present invention, 1'-acetyloxygamrol acetate can be any one of D-form, L-form or a mixture thereof. In the present invention, the sources and production methods of 1'-acetyloxygamrol acetate and acetyleugenol are not particularly limited. 1’-Acetyloxygamrol acetate can be derived from natural or synthetic products. Acetyl eugenol can be derived from natural or synthetic products. 1'-Acetyloxygamicol acetate and acetyleugenol, for example, can be extracted from Galangal galanga.
本發明組成物中之1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之含有比率係相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.01~1.9重量份。 1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之含有比率若為上述範圍，則可增強1’-乙醯氧基佳味酚乙酸酯之抗發炎作用。藉由以上述比率使用1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚所得之抗發炎效果係比由單獨使用各成分所得之效果所預測之相加效果更優異之相乘效果。 本發明之組成物中，相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量較佳為0.06重量份以上，更佳為0.09重量份以上，又更佳為0.1重量份以上，且可為1.90重量份以下，較佳為1.5重量份以下，更佳為1.44重量份以下，又更佳為0.6重量份以下，特佳為0.5重量份以下。一態樣中，相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量較佳為0.06~1.5重量份，更佳為0.06~1.44重量份，又更佳為0.09~1.44重量份，再更佳為0.09~0.6重量份，特佳為0.1~0.5重量份。 The content ratio of 1'-acetyloxy gaymol acetate and acetyl eugenol in the composition of the present invention is relative to 100 parts by weight of 1'-acetyloxy gaymol acetate, acetyl clove The content of phenol is 0.01-1.9 parts by weight. When the content ratio of 1'-acetyloxygaymol acetate and acetyleugenol is in the above-mentioned range, the anti-inflammatory effect of 1'-acetyloxygaymol acetate can be enhanced. The anti-inflammatory effect obtained by using 1'-acetyloxygamrol acetate and acetyl eugenol in the above ratios is synergistically superior to the additive effect predicted from the effects obtained by using the ingredients alone Effect. In the composition of the present invention, the content of acetyl eugenol is preferably at least 0.06 parts by weight, more preferably at least 0.09 parts by weight, and more preferably Preferably at least 0.1 parts by weight, and may be at most 1.90 parts by weight, preferably at most 1.5 parts by weight, more preferably at most 1.44 parts by weight, still more preferably at most 0.6 parts by weight, particularly preferably at most 0.5 parts by weight. In one aspect, the content of acetyl eugenol is preferably 0.06-1.5 parts by weight, more preferably 0.06-1.44 parts by weight, and more preferably Preferably, it is 0.09-1.44 parts by weight, more preferably, it is 0.09-0.6 parts by weight, and most preferably, it is 0.1-0.5 parts by weight.
本發明組成物中之1’-乙醯氧基佳味酚乙酸酯之含量，若組成物中之1’-乙醯氧基佳味酚乙酸酯之含量與乙醯丁香酚之含量之比率滿足上述範圍，則可根據該組成物之形態、用途等適當設定。例如1’-乙醯氧基佳味酚乙酸酯之含量，於組成物中可為0.00001重量%以上，可為0.0001重量%以上，且可為80重量%以下，可為50重量%以下。一態樣中，1’-乙醯氧基佳味酚乙酸酯之含量，於本發明之組成物中可為0.00001~80重量%，可為0.0001~50重量%。The content of 1'-acetyloxygaymol acetate in the composition of the present invention, if the content of 1'-acetyloxygaymol acetate in the composition is equal to the content of acetyleugenol If the ratio satisfies the above-mentioned range, it can be appropriately set according to the form, use, etc. of the composition. For example, the content of 1'-acetyloxygamrol acetate in the composition may be 0.00001% by weight or more, may be 0.0001% by weight or more, and may be 80% by weight or less, and may be 50% by weight or less. In one aspect, the content of 1'-acetyloxygamrol acetate in the composition of the present invention may be 0.00001 to 80% by weight, or may be 0.0001 to 50% by weight.
本發明組成物中之乙醯丁香酚之含量，若組成物中之1’-乙醯氧基佳味酚乙酸酯之含量與乙醯丁香酚之含量之比率滿足上述範圍，則可根據該組成物之形態、用途等適當設定。例如乙醯丁香酚之含量，於組成物中可為0.00000001重量%以上，可為0.0000001重量%以上，且可為1.6重量%以下，可為1重量%以下。一態樣中，乙醯丁香酚之含量，於本發明之組成物中可為0.00000001~1.6重量%，可為0.0000001~1重量%。 1’-乙醯氧基佳味酚乙酸酯之含量可藉由高性能液相層析法(HPLC法)等之習知方法測定。乙醯丁香酚之含量可藉由氣相層析質譜法(GC/MS法)等之習知方法測定。 The content of acetyl eugenol in the composition of the present invention, if the ratio of the content of 1'-acetyloxygamisol acetate in the composition to the content of acetyl eugenol satisfies the above range, then it can be based on the Appropriately set the form, use, etc. of the composition. For example, the content of acetyl eugenol in the composition may be 0.00000001% by weight or more, 0.0000001% by weight or more, and may be 1.6% by weight or less, and may be 1% by weight or less. In one aspect, the content of acetyl eugenol in the composition of the present invention may be 0.00000001 to 1.6% by weight, or 0.0000001 to 1% by weight. The content of 1'-acetyloxygamrol acetate can be determined by conventional methods such as high performance liquid chromatography (HPLC method). The content of acetyl eugenol can be determined by conventional methods such as gas chromatography mass spectrometry (GC/MS method).
本發明之組成物例如可使用作為抗發炎組成物。一態樣中，本發明之組成物可使用於發炎之預防或發炎症狀之改善。一態樣中，本發明之組成物可使用作為NF-κB(核內因子κB)阻礙用組成物。NF-κB係調節編碼發炎促進性細胞素等之分子的基因轉錄之轉錄因子，於發炎反應中扮演重要角色。本發明之組成物可較佳地使用於藉由NF-κB阻礙而預防發炎或改善發炎症狀，更佳使用於預防發炎。本發明之組成物可含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚作為有效成分。 本發明之組成物可使用於例如發炎性大腸炎、支氣管哮喘、關節炎等之發炎性症狀或疾病之預防或改善。且，本發明之組成物可使用於NF-κB或其磷酸化引起之症狀或疾病(例如支氣管哮喘、關節炎)之預防或改善。 本說明書中所用之預防包含防止發病、延遲發病、降低發病率、減輕發病風險等。症狀或疾病之改善，包含使對象自該症狀或疾病中恢復，減輕症狀、使症狀好轉、或延遲或防止症狀的進展等。恢復包含部分恢復。 The composition of the present invention can be used, for example, as an anti-inflammatory composition. In one aspect, the composition of the present invention can be used for the prevention of inflammation or the improvement of inflammation symptoms. In one aspect, the composition of the present invention can be used as a composition for inhibiting NF-κB (nuclear factor κB). NF-κB is a transcription factor that regulates the transcription of genes encoding molecules such as inflammation-promoting cytokines, and plays an important role in inflammatory responses. The composition of the present invention can be preferably used to prevent inflammation or improve inflammation symptoms through NF-κB inhibition, more preferably used to prevent inflammation. The composition of the present invention may contain 1'-acetyloxygamrol acetate and acetyleugenol as active ingredients. The composition of the present invention can be used for the prevention or improvement of inflammatory symptoms or diseases such as inflammatory colitis, bronchial asthma, arthritis, etc. Moreover, the composition of the present invention can be used for the prevention or improvement of symptoms or diseases caused by NF-κB or its phosphorylation (such as bronchial asthma, arthritis). The prophylaxis used in this specification includes preventing the onset, delaying the onset, reducing the incidence rate, reducing the risk of onset, etc. The improvement of symptoms or diseases includes making the subject recover from the symptoms or diseases, alleviating the symptoms, making the symptoms better, or delaying or preventing the progress of the symptoms, etc. Recovery includes partial recovery.
本發明之組成物只要不損及本發明之效果，除了1’-乙醯氧佳味酚乙酸酯及乙醯丁香酚以外，可含有任意添加劑、任意成分。該等添加劑及成分可根據組成物之形態等進行選擇。又，本發明之組成物中不含大高良薑之植物體、大高良薑之粉碎物(例如大高良薑根莖之粉碎物)、該等之乾燥物。The composition of the present invention may contain any additives and components other than 1'-acetyloxygamicol acetate and acetyleugenol as long as the effect of the present invention is not impaired. These additives and components can be selected according to the form of the composition and the like. In addition, the composition of the present invention does not contain the plant body of Alpinia galanga, the ground material of Alpinia galanga (for example, the ground material of the rhizome of Alpinia galanga), and the dried material of these.
本發明之組成物可應用於任何治療用途(醫療用途)或非治療用途(非醫療用途)之任一者。所謂非治療係不含醫療行為，亦即人為手術、治療或診斷之概念。 本發明之組成物可以例如飲食品、醫藥、準醫藥、化妝品、飼料等形態提供，但不限於此。本發明之組成物本身可為飲食品、醫藥品、準醫藥、化妝品、飼料等，亦可為該等中使用之添加劑的製劑、材料。 一態樣中，本發明之組成物較佳為經口用組成物。作為經口用組成物，舉例為飲食品、經口用醫藥品、經口用準醫藥、該等之材料等，較佳為飲食品或其材料。 The compositions of the present invention may be used for either any therapeutic use (medical use) or non-therapeutic use (non-medical use). The so-called non-treatment does not include medical behavior, that is, the concept of artificial operation, treatment or diagnosis. The composition of the present invention can be provided in the form of, for example, food and drink, medicine, quasi-drug, cosmetic, feed, etc., but is not limited thereto. The composition itself of the present invention can be food and drink, pharmaceuticals, quasi-drugs, cosmetics, feed, etc., and can also be preparations and materials of additives used in these. In one aspect, the composition of the present invention is preferably a composition for oral use. Examples of the oral composition include food and beverages, oral pharmaceuticals, oral quasi-drugs, and materials thereof, and are preferably food and beverages or their materials.
本發明之組成物為飲食品時，可調配飲食品中可使用之成分(例如食品材料、根據需要使用之食品添加物等)，做成各種飲食品。飲食品未特別限制，舉例為例如一般飲食品、健康食品、健康飲料、顯示機能性之食品、特定保健用食品、保健輔助食品、病患飲食品等。上述健康食品、顯示機能性之食品、特定保健用食品、健康輔助食品等，可作為例如細粒劑、錠劑、顆粒劑、散劑、膠囊劑、可咀嚼劑、乾糖漿劑、糖漿劑、液劑、飲料、流質食品等之各種製劑形態使用。When the composition of the present invention is a food or drink, components usable in the food or drink (such as food materials, food additives used as needed, etc.) can be formulated to produce various food or drink. Food and drink are not particularly limited, and examples thereof include general food and drink, health food, health drink, food exhibiting functional properties, food for specific health use, health supplement food, food and drink for patients, and the like. The above-mentioned health food, food exhibiting functional properties, food for specific health use, health supplement food, etc., can be used as, for example, fine granules, lozenges, granules, powders, capsules, chewables, dry syrups, syrups, liquids, etc. It can be used in various preparation forms such as medicaments, beverages, and liquid foods.
本發明之組成物為醫藥品或準醫藥時，可調配藥理學上可接受之賦形劑等，做成各種劑型之醫藥品。醫藥品或準醫藥之投予形態較佳為經口投予形態。劑型只要為適於投予之劑型即可。作為經口投予之劑型，舉例為例如錠劑、被覆錠劑、細粒劑、顆粒劑、散劑、藥丸、膠囊劑、乾糖漿劑、可咀嚼劑等之經口投予用固形製劑；內服液劑、糖漿劑等之經口用液體製劑。作為非經口投予之劑型，舉例為注射劑、點滴劑、軟膏劑、乳液劑、貼敷劑、栓劑、經鼻劑、經肺劑(吸入劑)等。醫藥品亦可為非人類動物用醫藥。When the composition of the present invention is a medicine or a quasi-drug, pharmacologically acceptable excipients and the like can be formulated to make medicines in various dosage forms. The administration form of pharmaceuticals or quasi-drugs is preferably an oral administration form. The dosage form may be any dosage form suitable for administration. As the dosage form for oral administration, solid preparations for oral administration such as tablets, coated tablets, fine granules, granules, powders, pills, capsules, dry syrups, chewables, etc. are exemplified; oral administration Oral liquid preparations such as solutions and syrups. Examples of dosage forms for parenteral administration include injections, drips, ointments, emulsions, patch preparations, suppositories, nasal preparations, pulmonary preparations (inhalation preparations) and the like. Pharmaceuticals can also be pharmaceuticals for non-human animals.
本發明之組成物做成化妝品時，可調配化妝品可接受之載體、添加劑等。化妝品之製品形態未特別限制。When the composition of the present invention is made into cosmetics, cosmetically acceptable carriers, additives, etc. can be formulated. The product form of the cosmetic is not particularly limited.
本發明之組成物做成飼料時，可調配飼料可使用之成分做成飼料。作為飼料，舉例為例如牛、豬、雞、綿羊、馬等所用之家畜用飼料；兔子、豚鼠、大鼠、小鼠等所用之小動物用飼料；狗，貓、小鳥等之寵物食品等。When the composition of the present invention is made into feed, the ingredients that can be used in feed can be formulated to make feed. Examples of the feed include domestic animal feed for cattle, pigs, chickens, sheep, and horses; feed for small animals such as rabbits, guinea pigs, rats, and mice; and pet food for dogs, cats, and birds.
本發明之組成物可根據其形態以適當方法攝取或投予。本發明之組成物較佳為經口投予或經口攝取。本發明之組成物的攝取量(亦可稱為投予量)未特別限制，只要根據使用目的、投予形態、投予方法、對象等適當設定即可。一態樣中，本發明之組成物使用作為例如抗發炎用組成物或NF-κB阻礙用組成物時，較佳考慮其投予形態、投予方法等，以獲得所需效果之量，即有效量之1’-乙醯氧佳味酚乙酸酯及乙醯丁香酚予以攝取。例如以人類(成人)為對象經口投予或攝取時，本發明之組成物的攝取量，作為1’-乙醯氧基佳味酚乙酸酯之攝取量，每天較佳為0.1mg以上，更佳為1mg以上，且較佳為1000mg以下，更佳為100mg以下。作為一態樣，以人類(成人)為對象經口投予或攝取時，本發明之組成物的攝取量，作為1’-乙醯氧基佳味酚乙酸酯之攝取量，每天較佳為0.1~1000mg，更佳為1~100mg。上述量較佳以每天1次或分2~3次經口投予或攝取。上述之1’-乙醯氧佳味酚乙酸酯之攝取量可為每60公斤體重之攝取量。The composition of the present invention can be ingested or administered by an appropriate method according to its form. The composition of the present invention is preferably administered orally orally ingested. The ingestion amount (may also be referred to as the administration amount) of the composition of the present invention is not particularly limited, as long as it is appropriately set according to the purpose of use, administration form, administration method, target, and the like. In one aspect, when the composition of the present invention is used as, for example, an anti-inflammatory composition or a NF-κB inhibitory composition, it is preferable to consider its administration form, administration method, etc., so as to obtain the desired effect, that is, Effective amounts of 1'-acetyloxygamrol acetate and acetyl eugenol are ingested. For example, in the case of oral administration or ingestion to humans (adults), the intake of the composition of the present invention is preferably 0.1 mg or more per day as the intake of 1'-acetyloxygaymol acetate. , more preferably 1 mg or more, and preferably 1000 mg or less, more preferably 100 mg or less. In one aspect, when orally administered or ingested to humans (adults), the intake of the composition of the present invention is preferably the intake of 1'-acetyloxygaymol acetate per day. 0.1~1000mg, more preferably 1~100mg. The above amount is preferably orally administered or ingested once a day or divided into 2-3 times. The intake of the above-mentioned 1'-acetyloxygamicol acetate can be the intake per 60 kg of body weight.
投予或攝取本發明之組成物的對象(以下亦簡稱投予對象)較佳為哺乳動物(人類及非人類哺乳動物)，更佳為人類。且，作為本發明中之投予對象，較佳為需要或希望預防發炎或改善發炎症狀之對象、需要或希望預防或改善發炎性疾病之對象。作為本發明中之投予對象，亦舉例為需要或希望阻礙NF-κB之對象。本發明之組成物亦可對於例如以預防發炎等為目的之處於健康狀態的對象。The subject to administer or ingest the composition of the present invention (hereinafter also referred to as the administration subject) is preferably a mammal (human and non-human mammal), more preferably a human. Furthermore, as the subject of administration in the present invention, it is preferably a subject who needs or wants to prevent or improve inflammation symptoms, or a subject who needs or wants to prevent or improve inflammatory diseases. The subject of administration in the present invention also includes a subject that needs or desires to inhibit NF-κB. The composition of the present invention can also be administered to subjects in a healthy state for the purpose of preventing inflammation and the like, for example.
本發明之組成物的製造方法，只要使組成物中1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之比率在上述範圍內，調配該等即可，未特別限制。本發明之組成物例如可於習知之組成物製造中，於其原料中調配特定量之1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚而調製。亦可於含有1’-乙醯氧基佳味酚乙酸酯及/或乙醯丁香酚之原料中，添加1’-乙醯氧基佳味酚乙酸酯及/或乙醯丁香酚。製造本發明之組成物時，亦可使用大高良薑萃取物。例如，藉由以超臨界二氧化碳(為超臨界狀態下之二氧化碳)或液體二氧化碳萃取大高良薑原料，可獲得含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之大高良薑萃取物。如此所得之大高良薑萃取物中，根據需要調配1’-乙醯氧基佳味酚乙酸酯及/或乙醯丁香酚亦可獲得本發明之組成物。於習知之組成物製造中，添加含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之大高良薑萃取物，亦可製造本發明之組成物。The method for producing the composition of the present invention is not particularly limited as long as the ratio of 1'-acetyloxygamrol acetate and acetyleugenol in the composition is within the above-mentioned range and these are formulated. The composition of the present invention can be prepared, for example, by blending specific amounts of 1'-acetyloxygamrol acetate and acetyleugenol into the raw materials in the conventional manufacture of the composition. It is also possible to add 1'-acetyloxy gaymol acetate and/or acetyl eugenol to the raw material containing 1'-acetyloxy gaymol acetate and/or acetyl eugenol. When producing the composition of the present invention, galanga extract can also be used. For example, by extracting galanga raw materials with supercritical carbon dioxide (carbon dioxide in a supercritical state) or liquid carbon dioxide, galanga containing 1'-acetyloxygamicol acetate and acetyleugenol can be obtained. Ginger extract. The composition of the present invention can also be obtained by blending 1'-acetyloxy gaymol acetate and/or acetyl eugenol into the thus obtained galangal extract as required. The composition of the present invention can also be produced by adding the galanga extract containing 1'-acetyloxygamicol acetate and acetyleugenol to the conventional production of the composition.
關於將大高良薑原料以超臨界二氧化碳(為超臨界狀態之二氧化碳)或液體二氧化碳萃取獲得大高良薑萃取物之方法於以下說明。 上述大高良薑原料係萃取所用之大高良薑。本發明中，大高良薑係指薑科植物之大高良薑(學名Alpinia galanga)。大高良薑係東南亞原產的植物，亦稱為南薑(日本名)、卡(泰語)。 The method for extracting galanga raw material with supercritical carbon dioxide (carbon dioxide in a supercritical state) or liquid carbon dioxide to obtain galanga extract is described below. The above-mentioned galangal raw material is the galangal used for extraction. In the present invention, galangal refers to galangal (scientific name Alpinia galanga) of Zingiberaceae plant. Galangal is a plant native to Southeast Asia, also known as southern ginger (Japanese name) and card (Thai language).
大高良薑原料可使用大高良薑之任何部位，例如根莖、根、莖、葉、花、果實、種子、全草等，或該等之2種以上之組合。其中，較佳為選自大高良薑之根莖、根及葉所成之群中之至少1種。係因為該等部位1’-乙醯氧基佳味酚乙酸酯之含量較多。作為大高良薑原料，更佳為大高良薑之根莖及/或根，又更佳為根莖。The raw material of galanga can be any part of galanga, such as rhizome, root, stem, leaf, flower, fruit, seed, whole plant, etc., or a combination of two or more of them. Among them, at least one species selected from the group consisting of rhizomes, roots and leaves of Galangal galanga is preferred. It is because the content of 1'-acetyloxygamrol acetate in these parts is relatively high. As the raw material of galangal, more preferably the rhizome and/or root of galanga, and more preferably the rhizome.
作為大高良薑原料，可直接使用上述大高良薑之任意部位(生的狀態)，亦可使用經乾燥之乾燥物，亦可使用經粉碎或切斷者。較佳為乾燥物，更佳為將乾燥物粉碎或切斷者。As the raw material of galangal, any part of the above-mentioned galangal (raw state) can be used as it is, a dried product can be used, and a crushed or cut one can also be used. It is preferably a dry product, and more preferably a dried product that has been pulverized or cut.
利用超臨界二氧化碳或液體二氧化碳之萃取，係將大高良薑原料與超臨界二氧化碳或液體二氧化碳接觸，將目的物(萃取物)從大高良薑原料中萃取到超臨界二氧化碳或液體二氧化碳中(萃取步驟)。例如將大高良薑原料填充到容器中，升壓及/或升溫至特定壓力及溫度並與處於超臨界狀態或液體狀態之二氧化碳接觸，可將大高良薑原料以超臨界二氧化碳或液體二氧化碳萃取。The extraction using supercritical carbon dioxide or liquid carbon dioxide is to contact the raw material of galanga with supercritical carbon dioxide or liquid carbon dioxide, and extract the target substance (extract) from the raw material of galangal into supercritical carbon dioxide or liquid carbon dioxide (extraction step ). For example, the raw material of galanga is filled into a container, the pressure and/or temperature are increased to a specific pressure and temperature, and contacted with carbon dioxide in a supercritical or liquid state, the raw material of galangal can be extracted with supercritical carbon dioxide or liquid carbon dioxide.
以超臨界二氧化碳進行萃取時，超臨界二氧化碳較佳溫度為32~80℃，壓力為8~40MPa。本說明書中，二氧化碳之壓力為錶壓。超臨界二氧化碳之溫度更佳為35℃以上。超臨界二氧化碳之壓力更佳為10MPa以上。 一態樣中，超臨界二氧化碳更佳溫度為35~60℃，壓力為20~40 MPa。另一態樣中，超臨界二氧化碳更佳溫度為35℃以上未達60℃，壓力為10MPa以上未達20MPa。超臨界二氧化碳若溫度為35~60℃，壓力為20~40MPa，或溫度為35℃以上未達60℃，壓力為10MPa以上未達20MPa，則可迅速萃取1’-乙醯氧基佳味酚乙酸酯。且，1’-乙醯氧基佳味酚乙酸酯之收率變高。超臨界二氧化碳更佳溫度為35~60℃，壓力為20~40MPa，特佳溫度為35~60℃，壓力為20~35MPa。 When using supercritical carbon dioxide for extraction, the optimum temperature of supercritical carbon dioxide is 32~80°C, and the pressure is 8~40MPa. In this specification, the pressure of carbon dioxide is gauge pressure. The temperature of supercritical carbon dioxide is more preferably above 35°C. The pressure of supercritical carbon dioxide is more preferably 10 MPa or more. In one aspect, the optimum temperature of supercritical carbon dioxide is 35~60°C, and the pressure is 20~40 MPa. In another aspect, the more preferable temperature of supercritical carbon dioxide is not less than 35°C and not more than 60°C, and the pressure is not less than 10MPa and not more than 20MPa. If the temperature of supercritical carbon dioxide is 35~60°C, the pressure is 20~40MPa, or the temperature is above 35°C but not 60°C, and the pressure is above 10MPa but below 20MPa, then 1'-acetyloxygamiphenol can be extracted rapidly Acetate. Furthermore, the yield of 1'-acetyloxygamrol acetate became higher. The optimum temperature of supercritical carbon dioxide is 35-60°C and the pressure is 20-40MPa, and the optimum temperature is 35-60°C and the pressure is 20-35MPa.
以液體二氧化碳進行萃取時，液體二氧化碳較佳溫度為5~30℃，壓力為8~40MPa。液體二氧化碳更佳溫度為10~30℃，壓力為10~40MPa，又更佳溫度為15~30℃，壓力為10~35MPa，特佳溫度為18~25℃，壓力為10~35MPa。When using liquid carbon dioxide for extraction, the optimum temperature of liquid carbon dioxide is 5~30°C and the pressure is 8~40MPa. The best temperature of liquid carbon dioxide is 10~30°C, the pressure is 10~40MPa, the more preferable temperature is 15~30°C, the pressure is 10~35MPa, the most preferable temperature is 18~25°C, and the pressure is 10~35MPa.
萃取步驟中，超臨界二氧化碳或液體二氧化碳之使用量，相對於大高良薑原料(乾燥重量換算)1g，較佳為1~100mL，更佳為1.5~80mL。In the extraction step, the amount of supercritical carbon dioxide or liquid carbon dioxide used is preferably 1-100 mL, more preferably 1.5-80 mL, relative to 1 g of galanga raw material (dry weight conversion).
利用超臨界二氧化碳或液體二氧化碳之萃取時間較佳為5分鐘以上。一態樣中，萃取時間較佳為300分鐘以下，更佳為5~240分鐘，又更佳為5~120分鐘，再更佳為5~70分鐘，特佳為10~60分鐘。上述萃取時間係指大高良薑原料與超臨界二氧化碳或液體二氧化碳接觸之時間。The extraction time using supercritical carbon dioxide or liquid carbon dioxide is preferably more than 5 minutes. In one aspect, the extraction time is preferably less than 300 minutes, more preferably 5-240 minutes, more preferably 5-120 minutes, still more preferably 5-70 minutes, and particularly preferably 10-60 minutes. The above-mentioned extraction time refers to the time when the raw material of galanga is contacted with supercritical carbon dioxide or liquid carbon dioxide.
上述萃取步驟之後，較佳進行自大高良薑萃取物分離超臨界二氧化碳或液體二氧化碳之步驟(分離步驟)。上述分離可藉由降低含有大高良薑萃取物之超臨界二氧化碳或液體二氧化碳的壓力及/或提高溫度而進行。較佳藉由降低壓力自大高良薑萃取物分離二氧化碳。 藉由使大高良薑原料與超臨界二氧化碳或液體二氧化碳接觸進行目的物(大高良薑萃取物)之萃取，然後藉由降低超臨界二氧化碳或液體二氧化碳之壓力，可自包含大高良薑萃取物之超臨界二氧化碳或液體二氧化碳分離出目的物(大高良薑萃取物)。萃取步驟與分離步驟可於不同容器中進行，亦可在同一容器中進行。 自大高良薑萃取物分離超臨界二氧化碳或液體二氧化碳時，二氧化碳之壓力較佳為7MPa以下，更佳為0.1~ 1MPa。 After the extraction step described above, a step of separating supercritical carbon dioxide or liquid carbon dioxide from the galanga extract (separation step) is preferably performed. The above separation can be carried out by reducing the pressure and/or increasing the temperature of the supercritical carbon dioxide or liquid carbon dioxide containing the Alpinia galanga extract. Carbon dioxide is preferably separated from the galangal extract by reducing the pressure. Extraction of the target substance (galanga extract) is carried out by contacting the raw material of galanga with supercritical carbon dioxide or liquid carbon dioxide, and then by reducing the pressure of supercritical carbon dioxide or liquid carbon dioxide, it is possible to self-contain the galanga extract. Supercritical carbon dioxide or liquid carbon dioxide separates the target substance (Galangal galanga extract). The extraction step and the separation step can be carried out in different containers or in the same container. When separating supercritical carbon dioxide or liquid carbon dioxide from the galangal extract, the pressure of carbon dioxide is preferably below 7MPa, more preferably 0.1~1MPa.
獲得大高良薑萃取物時，根據需要，例如亦可進行自大高良薑原料萃取物去除萃取後之大高良薑原料(萃取殘渣)之步驟(殘渣去除步驟)。自萃取物去除萃取殘渣可藉由過濾等習知方法進行。When obtaining the galanga extract, for example, a step of removing the extracted galanga raw material (extraction residue) from the galanga raw material extract (residue removal step) may be performed as necessary. Removal of extraction residues from the extract can be performed by known methods such as filtration.
大高良薑根莖以超臨界二氧化碳或液體二氧化碳萃取所得之大高良薑萃取物含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚。所得之大高良薑萃取物含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚，相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚的含量為0.01~1.9重量份時，該萃取物亦可作為本發明之組成物使用。且，藉由於所得之大高良薑萃取物中添加1’-乙醯氧基佳味酚乙酸酯及/或乙醯丁香酚，亦可將該等之比率調整於上述範圍。The galangal extract obtained by extracting the rhizome of galanga with supercritical carbon dioxide or liquid carbon dioxide contains 1’-acetyloxy gamol acetate and acetyl eugenol. The resulting large galangal extract contains 1'-acetyloxy yammol acetate and acetyl eugenol, with respect to 100 parts by weight of 1'-acetyloxy yammol acetate, acetyl eugenol When the content is 0.01-1.9 parts by weight, the extract can also be used as the composition of the present invention. Furthermore, by adding 1'-acetyloxygamicol acetate and/or acetyleugenol to the obtained Alpinia galanga extract, these ratios can also be adjusted within the above-mentioned range.
本發明亦包含以下方法及使用。 一種發炎之預防或發炎症狀之改善方法，其包含將1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚投予至對象，且相對於1’-乙醯氧基佳味酚乙酸酯之投予量100重量份，乙醯丁香酚之投予量為0.01~1.9重量份。 一種1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之使用，其係用於發炎之預防及發炎症狀之改善，且相對於1’-乙醯氧基佳味酚乙酸酯100重量份，使用乙醯丁香酚0.01~1.9重量份。 The present invention also includes the following methods and uses. A method for preventing inflammation or improving symptoms of inflammation, comprising administering 1'-acetyloxygayrol acetate and acetyleugenol to a subject, and The dosage of acetate is 100 parts by weight, and the dosage of acetyl eugenol is 0.01-1.9 parts by weight. A use of 1'-acetyloxygayrol acetate and acetyleugenol, which is used for the prevention of inflammation and the improvement of inflammatory symptoms, For 100 parts by weight of the ester, 0.01 to 1.9 parts by weight of acetyl eugenol is used.
上述方法可為治療方法，亦可為非治療方法。 上述方法中，可投予包含1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之組成物，亦可將該等個別投予。上述方法中，較佳投予包含1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之組成物。上述方法中，更佳投予相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.01~1.9重量份之組成物。上述方法中，較佳投予上述本發明之組成物。 本發明亦包含一種發炎之預防或發炎症狀之改善方法，其包含將含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之組成物投予至對象，上述組成物係相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.01~1.9重量份。 The above method can be a therapeutic method or a non-therapeutic method. In the above-mentioned method, a composition containing 1'-acetyloxygamrol acetate and acetyl eugenol may be administered, or these may be administered separately. Among the above methods, it is preferable to administer a composition comprising 1'-acetyloxygamrol acetate and acetyleugenol. In the above method, it is more preferable to administer a composition in which the content of acetyl eugenol is 0.01 to 1.9 parts by weight relative to 100 parts by weight of 1'-acetyloxygamrol acetate. Among the above-mentioned methods, it is preferable to administer the above-mentioned composition of the present invention. The present invention also includes a method for preventing inflammation or improving symptoms of inflammation, which comprises administering to a subject a composition containing 1'-acetyloxygamrol acetate and acetyleugenol, the composition of which is relatively The content of acetyl eugenol is 0.01-1.9 parts by weight in 100 parts by weight of 1'-acetyloxygaymol acetate.
上述使用可為治療性使用，亦可為非治療性使用。 上述使用較佳係含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之組成物的使用，更佳為含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚，且相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.01~1.9重量份之組成物的使用。上述使用中，較佳使用上述本發明之組成物。 本發明亦包含含有1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚之組成物用於發炎之預防或發炎症狀之改善的使用，上述組成物係相對於1’-乙醯氧基佳味酚乙酸酯100重量份，乙醯丁香酚之含量為0.01~1.9重量份。 The above-mentioned uses may be therapeutic or non-therapeutic. The above-mentioned use is preferably the use of a composition containing 1'-acetyloxygamrol acetate and acetyl eugenol, more preferably a composition containing 1'-acetyloxygamrol acetate and acetyl Eugenol, and use of a composition in which the content of acetyl eugenol is 0.01 to 1.9 parts by weight relative to 100 parts by weight of 1'-acetyloxygamicol acetate. Among the above uses, the composition of the present invention described above is preferably used. The present invention also includes the use of a composition containing 1'-acetyloxygamrol acetate and acetyleugenol for the prevention of inflammation or the improvement of inflammatory symptoms. The above-mentioned composition is relative to 1'-acetyl For 100 parts by weight of oxygamicol acetate, the content of acetyl eugenol is 0.01-1.9 parts by weight.
上述方法或使用中，乙醯丁香酚之投予量(或使用量)，相對於1’-乙醯氧基佳味酚乙酸酯100重量份，可為0.01~1.90重量份，較佳為0.06~1.5重量份，更佳為0.09~1.44重量份，又更佳為0.09~0.6重量份，特佳為0.1~0.5重量份。較佳之投予對象、投予方法等與上述本發明之組成物相同。 本說明書中由下限值與上限值表示之數值範圍，即「下限值~上限值」包含該等下限值及上限值。例如，由「1~2」表示之範圍意指1以上2以下，包括1及2。本說明書中，亦可設為上限及下限經任何組合之範圍。 [實施例] In the above method or use, the dosage (or usage amount) of acetyl eugenol can be 0.01-1.90 parts by weight relative to 100 parts by weight of 1'-acetyloxy gaymol acetate, preferably 0.06-1.5 parts by weight, more preferably 0.09-1.44 parts by weight, more preferably 0.09-0.6 parts by weight, particularly preferably 0.1-0.5 parts by weight. Preferred administration objects, administration methods, etc. are the same as those of the above-mentioned composition of the present invention. The numerical range represented by the lower limit and the upper limit in this specification, that is, "lower limit ~ upper limit" includes the lower limit and the upper limit. For example, the range represented by "1~2" means 1 to 2, including 1 and 2. In this specification, any combination of the upper limit and the lower limit may be used. [Example]
以下藉由實施例更詳細說明本發明，但本發明之範圍不受該等之限制。The following examples illustrate the present invention in more detail, but the scope of the present invention is not limited thereto.
＜實施例1＞1’-乙醯氧基佳味酚乙酸酯(ACA)、乙醯丁香酚、ACA與乙醯丁香酚之組合產生之NF-kappaB(NF-κB)磷酸化抑制效果<Example 1> NF-kappaB (NF-κB) phosphorylation inhibitory effect produced by 1'-acetyloxygamicol acetate (ACA), acetyl eugenol, combination of ACA and acetyl eugenol
使用小鼠肌母細胞株(C2C12細胞，ATCC公司製)。將C2C12細胞在96孔盤中以2×10 4細胞/盤接種，以含有10%FBS(牛胎兒血清，Sigma-Aldrich公司製)、1%抗生素(Nacalai Tesque(股)製之抗生素-抗真菌劑混合溶液)之高葡萄糖正常DMEM(Sigma-Aldrich公司製)，在37℃下培養2天。確認C2C12細胞融合，進行以下實驗。 A mouse myoblast cell line (C2C12 cells, manufactured by ATCC) was used. C2C12 cells were inoculated in a 96-well dish with 2×10 4 cells/dish in a mixture containing 10% FBS (fetal bovine serum, manufactured by Sigma-Aldrich Company), 1% antibiotic (antibiotic-antifungal agent manufactured by Nacalai Tesque Co., Ltd.) DMEM (manufactured by Sigma-Aldrich) in high-glucose normal DMEM (manufactured by Sigma-Aldrich), and cultured at 37° C. for 2 days. To confirm the fusion of C2C12 cells, perform the following experiments.
於與細胞接種時相同組成的培養液中，以終濃度1ng/mL添加用以誘發NF-κB訊號之溶解於二甲基亞碸(DMSO)之TNFα(R&D公司製)，調製引起發炎用之培養基。To the culture medium with the same composition as that used for inoculation of cells, TNFα (manufactured by R&D Corporation) dissolved in dimethylsulfoxide (DMSO) to induce NF-κB signaling was added at a final concentration of 1ng/mL to prepare for inflammation. Medium.
藉由下述(I)~(III)記載之方法製備含有ACA及/或乙醯丁香酚之培養基。將ACA及乙醯丁香酚溶解於培養基時，將ACA及/或乙醯丁香酚溶解於DMSO中並添加到培養基中。 (I)為了測定ACA單獨之NF-κB磷酸化抑制率，於引起發炎用培養基中，以終濃度0.47μg/mL溶解ACA(abcam公司製)。 (II)為了測定乙醯丁香酚單獨之NF-κB磷酸化抑制率，將乙醯丁香酚溶解於引起發炎之培養基中。以將(I)之ACA的終濃度(0.47μg/mL)設為100時之乙醯丁香酚的濃度比率為0.06、0.09、0.12、0.18、0.36、0.72、1.44、5、10之終濃度(μg/mL)，將乙醯丁香酚溶解於引起發炎用培養基中。 (III)為了測定由ACA與乙醯丁香酚之組合所得之NF-κB磷酸化抑制率，將ACA及乙醯丁香酚溶解於引起發炎之培養基中。ACA以終濃度0.47μg/mL溶解於引起發炎之培養基中，將ACA之最終濃度設為100時之乙醯丁香酚之濃度(μg/mL)的比率為0.06、0.09、0.12、0.18、0.36、0.72、1.44、5、10之方式，調製溶解有乙醯丁香酚之培養基。 A medium containing ACA and/or acetyl eugenol was prepared by the method described in (I) to (III) below. When dissolving ACA and acetyl eugenol in the medium, ACA and/or acetyl eugenol were dissolved in DMSO and added to the medium. (I) In order to measure the inhibitory rate of NF-κB phosphorylation by ACA alone, ACA (manufactured by Abcam) was dissolved at a final concentration of 0.47 μg/mL in the medium for inducing inflammation. (II) In order to measure the inhibitory rate of NF-κB phosphorylation by acetyl eugenol alone, acetyl eugenol was dissolved in the inflammation-causing medium. The final concentrations of 0.06, 0.09, 0.12, 0.18, 0.36, 0.72, 1.44, 5, and 10 were determined by setting the final concentration of ACA (0.47 μg/mL) in (I) as 100. μg/mL), acetyl eugenol was dissolved in the medium for inducing inflammation. (III) In order to measure the inhibition rate of NF-κB phosphorylation obtained by the combination of ACA and acetyl eugenol, ACA and acetyl eugenol were dissolved in the inflammation-causing medium. ACA was dissolved in the medium causing inflammation at a final concentration of 0.47 μg/mL, and the ratios of the concentrations of acetyl eugenol (μg/mL) when the final concentration of ACA was set to 100 were 0.06, 0.09, 0.12, 0.18, 0.36, The methods of 0.72, 1.44, 5, and 10 were used to prepare the medium in which acetyl eugenol was dissolved.
(IV)作為不引起發炎之對照培養基，調製於與細胞接種時相同組成之培養液中添加DMSO之培養基。 所有培養基的DMSO終濃度為0.2%(v/v)。 (IV) As a control medium that does not cause inflammation, a medium in which DMSO was added to a culture medium having the same composition as that at the time of cell inoculation was prepared. The final concentration of DMSO in all media was 0.2% (v/v).
C2C12細胞之培養基更換為上述調製之任一培養基，30分鐘後去除培養基。以磷酸緩衝生理食鹽水(PBS，Nacalai Tesque(股)製)洗淨細胞後使用NF κB (pS536) ELISA套組(abcam公司製)所附之萃取溶液，製作細胞溶解液。 使用NF κB(pS536)ELISA套組測定細胞溶解液中之NF κB (pS536)。 The medium of C2C12 cells was replaced with any medium prepared above, and the medium was removed after 30 minutes. After the cells were washed with phosphate-buffered saline (PBS, manufactured by Nacalai Tesque Co., Ltd.), a cell lysate was prepared using the extraction solution attached to the NFκB (pS536) ELISA kit (manufactured by abcam). NF κB (pS536) in cell lysate was measured using NF κB(pS536) ELISA kit.
NF-κB之磷酸化抑制率(%)係使用以ELISA測定之細胞溶解液的吸光度(450nm)，由下述式算出。 NF-κB磷酸化抑制率(%)=100×(引起發炎之培養基的吸光度－樣品的吸光度)/(引起發炎之培養基的吸光度－對照樣品的吸光度) 上述式中，樣品係以含有ACA及/或乙醯丁香酚之培養基(上述(I)~(III))處理之細胞的細胞溶解液。對照樣品係以對照培養基(上述(IV))處理之細胞的細胞溶解液。 NF-κB之磷酸化抑制率越高，可說NF-κB抑制效果越高。 The phosphorylation inhibition rate (%) of NF-κB was calculated from the following formula using the absorbance (450 nm) of the cell lysate measured by ELISA. Inhibition rate of NF-κB phosphorylation (%)=100×(absorbance of medium causing inflammation-absorbance of sample)/(absorbance of medium causing inflammation-absorbance of control sample) In the above formula, the sample is a cell lysate of cells treated with a medium containing ACA and/or acetyl eugenol (above (I)-(III)). Control samples were cell lysates of cells treated with control medium ((IV) above). The higher the phosphorylation inhibition rate of NF-κB, the higher the NF-κB inhibitory effect.
表1中顯示(I)由ACA單獨(終濃度0.47μg/mL)，(II)由乙醯丁香酚(AE)單獨，(III)由ACA與乙醯丁香酚之組合所得之NF-κB之磷酸化抑制率(%)。 (II)AE單獨之結果係將(I)之ACA濃度(0.47μg/mL)設為100時之乙醯丁香酚的濃度比率為0.06、0.09、0.12、0.18、0.36、0.72、1.44、5或10時之NF-κB之磷酸化抑制率。 「(I)ACA單獨+(II)AE單獨(計算值)」係(I)ACA單獨時之NF-κB磷酸化抑制率與表1所示之濃度比(AE比率)之(II)AE單獨時之NF-κB磷酸化抑制率相加後的值。 (III)ACA+AE組合(實測值)係ACA與乙醯丁香酚以表1所示之濃度比(AE比率)使用時之NF-κB磷酸化抑制率之實測值。 表1中之「(III)/(I)+(II)」表示將ACA與乙醯丁香酚組合所得之NF-κB之磷酸化抑制率((III)ACA+AE組合(實測值))(%)除以將單獨添加ACA時之NF-κB的磷酸化抑制率(%)與單獨添加乙醯丁香酚時之NF-κB的磷酸化抑制率(%)相加後之數字(((I)+(II))(計算值))所得之值((III)/(I)+ (II))。該(III)/((I)+(II))的數字超過1時，認為確認到ACA與乙醯丁香酚之相乘的NF-κB之磷酸化抑制。乙醯丁香酚相對於ACA100的比率為0.06、0.09、0.12、0.18、0.36、0.72、1.44，(III)/((I)+(II))的值超過1，確認為相乘的NF-κB之磷酸化抑制(NF-κB阻礙)。1’-乙醯氧基佳味酚乙酸酯及乙醯丁香酚以特定比例組合，增強了NF-κB抑制作用。 Table 1 shows (I) from ACA alone (final concentration 0.47μg/mL), (II) from acetyl eugenol (AE) alone, (III) from the combination of ACA and acetyl eugenol NF-κB Phosphorylation inhibition rate (%). (II) The result of AE alone is that the concentration ratio of acetyl eugenol is 0.06, 0.09, 0.12, 0.18, 0.36, 0.72, 1.44, 5 or The phosphorylation inhibition rate of NF-κB at 10 o'clock. "(I) ACA alone + (II) AE alone (calculated value)" is the concentration ratio (AE ratio) of (II) AE alone between the NF-κB phosphorylation inhibition rate of (I) ACA alone and the concentration ratio (AE ratio) shown in Table 1 The value after adding the inhibition rate of NF-κB phosphorylation at time. (III) ACA+AE combination (measured value) is the measured value of the inhibition rate of NF-κB phosphorylation when ACA and acetyl eugenol are used at the concentration ratio (AE ratio) shown in Table 1. "(III)/(I)+(II)" in Table 1 represents the phosphorylation inhibition rate of NF-κB obtained by combining ACA and acetyl eugenol ((III) ACA+AE combination (measured value))( %) divided by the number obtained by adding the NF-κB phosphorylation inhibition rate (%) when ACA was added alone and the NF-κB phosphorylation inhibition rate (%) when acetyl eugenol was added alone (((I )+(II))(calculated value)) ((III)/(I)+(II)). When the number of (III)/((I)+(II)) exceeds 1, it is considered that the phosphorylation inhibition of NF-κB multiplied by ACA and acetyl eugenol was confirmed. The ratio of acetyleugenol to ACA100 was 0.06, 0.09, 0.12, 0.18, 0.36, 0.72, 1.44, and the value of (III)/((I)+(II)) exceeded 1, confirming multiplicative NF-κB Inhibition of phosphorylation (inhibition of NF-κB). The combination of 1'-acetyloxygamrol acetate and acetyl eugenol in a specific ratio enhanced the NF-κB inhibitory effect.
＜調製例1＞ 從乾燥大高良薑根莖以下述方法調製大高良薑超臨界CO 2萃取物。 將包含約3重量%之1’-乙醯氧基佳味酚乙酸酯(ACA)之乾燥大高良薑之根莖(市售品)予以粉碎，獲得大高良薑根莖粉碎物。調製例1中，壓力為錶壓。 <Preparation example 1> A supercritical CO 2 extract of galanga was prepared from dried rhizomes of galanga in the following manner. The dried rhizome (commercially available) of Alpinia galanga containing about 3% by weight of 1′-acetyloxycaymol acetate (ACA) was pulverized to obtain a pulverized rhizome of Galanga galanga. In Preparation Example 1, the pressure is gauge pressure.
將大高良薑根莖粉碎物(30g)饋入壓力容器中，以設定為40℃之水浴，對容器進行預熱。開始將二氧化碳(CO 2)導入壓力容器，升壓至25MPa，靜置10分鐘直到容器及預熱管穩定為相同溫度。在壓力25MPa下，二氧化碳在40℃時處於超臨界狀態。上述10分鐘靜置後於30分鐘後進行採樣，以兩段阱回收自背壓閥釋放之大高良薑CO 2超臨界萃取物(液體狀)。 The crushed galanga rhizome (30 g) was fed into a pressure vessel, and the vessel was preheated in a water bath set at 40°C. Start to introduce carbon dioxide (CO 2 ) into the pressure vessel, increase the pressure to 25MPa, and let it stand for 10 minutes until the vessel and the preheating tube are stabilized at the same temperature. At a pressure of 25MPa, carbon dioxide is in a supercritical state at 40°C. After the above-mentioned 10 minutes of standing, sampling was carried out 30 minutes later, and the CO 2 supercritical extract (liquid form) of Alpinia officinalis released from the back pressure valve was recovered with a two-stage trap.
＜ACA及AE之含量測定＞ 使用高速液體層析儀(HPLC法)，以下述條件測定上述所得之大高良薑超臨界CO 2萃取物中的ACA。 (分析條件) 高速液體層析儀：LC-2030C(島津製作所(股)製) PDA檢測器：SPD-M 30A(島津製作所(股)製) 檢測波長：220nm 管柱：5C18-AR-II(Nacalai Tesque(股)製，內徑4.6mm，長度150mm) 移動相(A液)：水 移動相(B液)：乙腈 流速：1.0mL/min 烘箱溫度：40℃ 檢測：220nm 梯度條件：B液濃度 10min 30vol% 30min 50vol% 31min 100vol% 40min 100vol% 41min 30vol% 50min 30vol% <Determination of ACA and AE content> Using high-speed liquid chromatography (HPLC method), ACA in the supercritical CO 2 extract of Alpinia galanga obtained above was measured under the following conditions. (Analysis conditions) High-speed liquid chromatography: LC-2030C (manufactured by Shimadzu Corporation) PDA detector: SPD-M 30A (manufactured by Shimadzu Corporation) Detection wavelength: 220 nm Column: 5C18-AR-II ( Manufactured by Nacalai Tesque Co., Ltd., inner diameter 4.6mm, length 150mm) Mobile phase (A solution): water Mobile phase (B solution): acetonitrile Flow rate: 1.0mL/min Oven temperature: 40°C Detection: 220nm Gradient condition: B solution Concentration 10min 30vol% 30min 50vol% 31min 100vol% 40min 100vol% 41min 30vol% 50min 30vol%
乙醯丁香酚(AE)之含量係以氣相層析質譜分析法(GC/MS法)，以下述條件測定。 氣相層析質譜分析 GC/MS裝置：Agilent公司製7890B(GC)、5977B(MS)、GESTEL公司製 MPS 載氣：He 管柱：DB-WAX UI(60m×0.32mm×0.25μm) 管柱溫度：50℃(5min)-8℃/min-250℃(3min) The content of acetyl eugenol (AE) was determined by gas chromatography mass spectrometry (GC/MS method) under the following conditions. Gas Chromatography Mass Spectrometry GC/MS apparatus: 7890B (GC), 5977B (MS) manufactured by Agilent, MPS manufactured by GESTEL Carrier gas: He Column: DB-WAX UI (60m×0.32mm×0.25μm) Column temperature: 50°C (5min)-8°C/min-250°C (3min)
調製例1所得之大高良薑超臨界CO 2萃取物中相對於ACA 100重量份之乙醯丁香酚含量為0.375重量份。 The content of acetyl eugenol relative to 100 parts by weight of ACA in the supercritical CO 2 extract of Alpinia officinalis obtained in preparation example 1 was 0.375 parts by weight.
＜實施例2＞ 包含ACA及乙醯丁香酚之大高良薑超臨界CO 2萃取物及ACA單獨之NF-κB磷酸化抑制效果 <Example 2> NF-κB Phosphorylation Inhibition Effect of Supercritical CO 2 Extract of Galangal officinalis Containing ACA and Acetyl Eugenol and ACA Alone
評價調製例1所得之大高良薑超臨界CO 2萃取物之NF-κB磷酸化抑制效果。為了比較，亦評價ACA(不含乙醯丁香酚)之NF-κB磷酸化抑制效果。 The NF-κB phosphorylation inhibitory effect of the supercritical CO 2 extract of Alpinia officinalis obtained in preparation example 1 was evaluated. For comparison, the NF-κB phosphorylation inhibitory effect of ACA (without acetyl eugenol) was also evaluated.
使用小鼠肌母細胞株(C2C12細胞，ATCC公司製)。將C2C12細胞在96孔盤中以2×10 4細胞/盤接種，以含有10%FBS(牛胎兒血清，Sigma-Aldrich公司製)、1%抗生素(Nacalai Tesque(股)製之抗生素-抗真菌劑混合溶液)之高葡萄糖正常DMEM(Sigma-Aldrich公司製)，在37℃下培養2天。確認C2C12細胞融合，進行以下實驗。 A mouse myoblast cell line (C2C12 cells, manufactured by ATCC) was used. C2C12 cells were inoculated in a 96-well dish with 2×10 4 cells/dish in a mixture containing 10% FBS (fetal bovine serum, manufactured by Sigma-Aldrich Company), 1% antibiotic (antibiotic-antifungal agent manufactured by Nacalai Tesque Co., Ltd.) DMEM (manufactured by Sigma-Aldrich) in high-glucose normal DMEM (manufactured by Sigma-Aldrich), and cultured at 37° C. for 2 days. To confirm the fusion of C2C12 cells, perform the following experiments.
於與細胞接種時相同組成的培養液中，以終濃度1ng/mL添加用以誘發NF-κB訊號之溶解於二甲基亞碸(DMSO)之TNFα(R&D公司製)，調製引起發炎用之培養基。調製於引起發炎用培養基中以終濃度1.41μg/mL添加溶解於DMSO之ACA(abcam公司製)之培養基與添加有終濃度1.76μg/mL(ACA含1.41μg/mL，乙醯丁香酚含0.0053 μg/mL)之大高良薑超臨界CO 2萃取物之培養基。作為不引起發炎之對照培養基，係調製於與細胞接種時同樣組成的培養液中添加有DMSO之培養基。所有培養基之DMSO終濃度為0.2%(v/v)。 To the culture medium with the same composition as that used for inoculation of cells, TNFα (manufactured by R&D Corporation) dissolved in dimethylsulfoxide (DMSO) to induce NF-κB signaling was added at a final concentration of 1ng/mL to prepare for inflammation. Medium. Prepare the medium for inducing inflammation by adding ACA (manufactured by Abcam) dissolved in DMSO at a final concentration of 1.41 μg/mL and the medium supplemented with a final concentration of 1.76 μg/mL (ACA containing 1.41 μg/mL, acetyl eugenol containing 0.0053 μg/mL) of supercritical CO 2 extract of Galanga galanga. As a control medium that does not cause inflammation, a medium in which DMSO was added to a culture medium having the same composition as that used for cell inoculation was prepared. The final concentration of DMSO in all media was 0.2% (v/v).
將C2C12細胞之培養基更換為所調製之培養基，30分鐘後去除培養基。以PBS(Nacalai Tesque(股)製)洗淨細胞後使用NF κB(pS536) ELISA套組(abcam公司製)所附之萃取溶液，製作細胞溶解液。 使用NF κB(pS536)ELISA套組測定細胞溶解液中之NF κB (pS536)。 以與實施例1相同方法求出NF-κB磷酸化抑制率。表2顯示NF-κB之磷酸化抑制率(%)。 The medium of C2C12 cells was replaced with the prepared medium, and the medium was removed after 30 minutes. After washing the cells with PBS (manufactured by Nacalai Tesque Co., Ltd.), a cell lysate was prepared using the extraction solution attached to the NFκB (pS536) ELISA kit (manufactured by abcam). NF κB (pS536) in cell lysate was measured using NF κB(pS536) ELISA kit. The NF-κB phosphorylation inhibition rate was determined in the same manner as in Example 1. Table 2 shows the phosphorylation inhibition rate (%) of NF-κB.
ACA與大高良薑超臨界CO 2萃取物均抑制了由TNFα誘發之NF-κB之磷酸化。上述使用之大高良薑超臨界CO 2萃取物係相對於ACA 100重量份含有0.375重量份AE。上述大高良薑超臨界CO 2萃取物所致之NF-κB之磷酸化抑制效果高於ACA單獨。可明瞭含有ACA及乙醯丁香酚之大高良薑超臨界CO 2萃取物顯示比ACA單獨更優異之抗發炎作用。 Both ACA and Galanga supercritical CO 2 extract inhibited the phosphorylation of NF-κB induced by TNFα. The galangal supercritical CO2 extract used above contains 0.375 parts by weight of AE relative to 100 parts by weight of ACA. The phosphorylation inhibitory effect of NF-κB induced by supercritical CO 2 extract of Alpinia officinalis above is higher than that of ACA alone. It can be seen that the supercritical CO 2 extract of galanga containing ACA and acetyl eugenol showed a superior anti-inflammatory effect than ACA alone.
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