JP5022403B2 - シマグワからの抽出物およびクワノンh化合物の抗菌用途 - Google Patents
シマグワからの抽出物およびクワノンh化合物の抗菌用途 Download PDFInfo
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- 239000012091 fetal bovine serum Substances 0.000 description 1
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- DKBPTKFKCCNXNH-QXGWMLRCSA-N kuwanone H Chemical compound CC(C)=CCC1=C(O)C=CC(C(=O)[C@@H]2[C@H](C=C(C)C[C@H]2C=2C(=CC(O)=CC=2)O)C=2C3=C(C(C(CC=C(C)C)=C(O3)C=3C(=CC(O)=CC=3)O)=O)C(O)=CC=2O)=C1O DKBPTKFKCCNXNH-QXGWMLRCSA-N 0.000 description 1
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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)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
- A61K36/605—Morus (mulberry)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Botany (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Pyrane Compounds (AREA)
Description
a)シマグワの根皮を極性溶剤で抽出する;
b)工程a)で得られた抽出溶液を濃縮する;
c)工程b)で得られた濃縮物を逆相クロマトグラフィカラムに導入し、順に、第一および第二の溶離液を用いてカラムを溶出する。この際、前記第一溶離液を約50wt%エタノール水溶液(たとえば、40〜70wt%、好ましくは45〜60wt%エタノール水溶液)の極性、および前記第二溶離液を約95wt%エタノール水溶液(たとえば、80〜98wt%、好ましくは85〜97wt%エタノール水溶液)の極性とする;並びに
d)第二溶離液を用いてカラムから溶出する第二溶出液を回収し、第二溶出液から第二溶離液を減圧除去する。
薄切りしたシマグワ(Moraceae)の乾燥根皮を細かく砕き、ふるいで選別した。得られた粉体100gを、丸底フラスコ中で95wt%エタノール水溶液1000mL(10:1(v/w))と混合し、得られた混合物を1時間還流沸騰させ、メッシュナンバー350のふるいおよびろ紙(#2)でろ過を行い、ろ液および残渣を得た。残渣を、前述した条件と同様にして、還流下で抽出し、ろ過を行った。得られた二つのろ液を混合し、その一部を減圧乾燥し、混合ろ液からの乾燥粉末重量を計算したところ、10.21gであり、粗抽出物の収率は10.21wt%であった。混合ろ液を元の重量の1/10に濃縮し、得られた濃縮物と同重量の水を添加した。混合ろ液の濃縮物の30倍の重量のポリスチレン吸収樹脂(Diaion HP20、三菱化学)を充填した逆相クロマトグラフィカラムに、得られた混合物を導入し、2ベッドボリューム(ベッドボリューム=600mL)の50wt%エタノール水溶液(1200mL)、続いて、2ベッドボリュームの95wt%エタノール水溶液(1200mL)を用いて溶出させた。95wt%エタノール水溶液の溶出液を回収し、真空で濃縮し乾燥させた。乾燥した抽出物EX−1(コードネーム)は2.73g得られ、混合ろ液の濃縮物の乾燥重量に対して、収率26.7%であり、乾燥根皮の重量に対して、収率2.73%であった。
2gのEX−1をメタノール10mLに溶解させた均一溶液に、純水10mLを添加し、この混合物を激しく振とうし、沈殿を促進させ、続いて15分間10000rpmで遠心分離を行った。遠心分離によって得られた固形分を溶解、沈殿および遠心分離を行い、このサイクルを総計6回実施した。
In Vitroの菌:黄色ブドウ球菌(スミス株)およびメチシリン耐性黄色ブドウ球菌(ATCC33591)
黄色ブドウ球菌(スミス株)およびメチシリン耐性ブドウ球菌(ATCC33591)のサンプルの最小発育阻止濃度(MIC)を、液体培地希釈法[Edwards J.R.et al.In vitro antibacterial activity of SM−7338,a carbapenem antibiotic with stability to dehydropeptidase I.Antimicrobial Agents Chemotherapy.33:pp.215−222,1989]により求めた。試験物質は(一般的には100%DMSOに)溶解させ、逐次、所定の濃度に溶媒中で希釈した。48ウェルプレートに、それぞれの試験濃度について0.01mL(最終DMSO濃度1%)を分取した後、1〜5×105CFU/mLの黄色ブドウ球菌(スミス株)またはメチシリン耐性黄色ブドウ球菌(ATCC33591)を含んだ0.99mLの培地(Mueller−Hinton Broth(DIFCO、USA))を添加した。以上のように、最終的なDMSO最大濃度は1%、初期の試験物質濃度は100μg/mLまたは30μMであった。プレートを37℃で20時間インキュベートした後、増殖すなわち濁度が抑制されたものを陽性(+)とし、増殖または濁度への影響がないものを陰性(−)として肉眼で評価を行った。媒体対照(Vehicle−control)および活性参照剤(active reference agents)をブランクおよびポジティブコントロールとして用いた。各濃度について二回ずつ評価を行った。結果は表1に示す。
肺炎連鎖球菌(ATCC6301)および肺炎連鎖球菌(エリスロマイシンおよびアンピシリン耐性、臨床分離株)のサンプルの最小発育阻止濃度(MIC)を、液体培地希釈法[Edwards J.R.et al.In vitro antibacterial activity of SM−7338,a carbapenem antibiotic with stability to dehydropeptidase I.Antimicrobial Agents Chemotherapy.33:pp.215−222,1989]により求めた。試験物質は(一般的に100%DMSOに)溶解させ、逐次、所定の濃度に溶媒中で希釈した。試験物質は(一般的には100%DMSOに)溶解させ、逐次、所定の濃度に溶媒に希釈した。48ウェルプレートに、それぞれの試験濃度について0.01mL(最終DMSO濃度1%)を分取した後、1〜5×105CFU/mLの肺炎連鎖球菌(ATCC6301)および肺炎連鎖球菌(エリスロマイシンおよびアンピシリン耐性臨床分離株)を含んだ7%ウシ胎児血清含有培地(Tryptic Soy Broth(DIFCO、USA))0.99mLを添加した。以上のように、最終的なDMSO最大濃度は1%、初期の試験物質濃度は100μg/mLまたは30μMであった。プレートを37℃で20時間インキュベートした後、増殖すなわち濁度が抑制されたものを陽性(+)とし、増殖または濁度への影響がないものを陰性(−)として肉眼で評価を行った。媒体対照(Vehicle−control)および活性参照剤(active reference agents)をブランクおよびポジティブコントロールとして用いた。各濃度について二回ずつ評価を行った。結果は表1に示す。
Claims (14)
- 以下の工程:
a)シマグワの根皮を極性溶剤で抽出する;
b)工程a)で得られた抽出溶液を濃縮する;
c)工程b)で得られた濃縮物を逆相クロマトグラフィカラムに導入し、第一溶離液および第二溶離液を順にカラムに充填し、この際、前記第一溶離液を約50wt%エタノール水溶液の極性、および前記第二溶離液を約95wt%エタノール水溶液の極性とする;並びに
d)第二溶離液を用いてカラムから溶出する第二溶出液を回収し、第二溶出液から第二溶離液を減圧除去する、
を含むプロセスによって、シマグワの根皮から調製される抽出物を含む、細菌感染の治療のための医薬組成物であって、
前記抽出物が、下記化学式(I)および化学式(II):
- 前記抽出物が、抽出物の重量に対して、前記化合物(I)を1〜5wt%、前記化合物(II)を1〜5wt%含有する、請求項2に記載の医薬組成物。
- 前記抽出物が、抽出物の重量に対して、前記化合物(I)を3.7wt%、前記化合物(II)を2.3wt%含有する、請求項3に記載の医薬組成物。
- 前記第一溶離液が50wt%エタノール水溶液であり、前記第二溶離液が95wt%エタノール水溶液である、請求項2〜4のいずれか1項に記載の医薬組成物。
- 工程a)における前記極性溶剤が、水または95wt%エタノール水溶液である、請求項2〜5のいずれか1項に記載の医薬組成物。
- 前記極性溶剤が95wt%エタノール水溶液である、請求項6に記載の医薬組成物。
- 前記シマグワの根皮の抽出が、還流下で行われる、請求項2〜7のいずれか1項に記載の医薬組成物。
- 前記細菌がグラム陽性菌である、請求項1〜8のいずれか1項に記載の医薬組成物。
- 前記細菌が黄色ブドウ球菌(スミス株)または肺炎連鎖球菌である、請求項9に記載の医薬組成物。
- 前記細菌が黄色ブドウ球菌(スミス株)である、請求項10に記載の医薬組成物。
- 前記細菌がメチシリン耐性黄色ブドウ球菌である、請求項11に記載の医薬組成物。
- 前記細菌が肺炎連鎖球菌である、請求項10に記載の医薬組成物。
- 前記細菌がエリスロマイシンおよびアンピシリン耐性肺炎連鎖球菌である、請求項13に記載の医薬組成物。
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