JP6778200B2 - Spiranthes sinensis抽出物を含有する組成物およびその薬学的適用 - Google Patents
Spiranthes sinensis抽出物を含有する組成物およびその薬学的適用 Download PDFInfo
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- CBEQULMOCCWAQT-WOJGMQOQSA-N triprolidine Chemical compound C1=CC(C)=CC=C1C(\C=1N=CC=CC=1)=C/CN1CCCC1 CBEQULMOCCWAQT-WOJGMQOQSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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- BDSYKGHYMJNPAB-LICBFIPMSA-N ulobetasol propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]2(C)C[C@@H]1O BDSYKGHYMJNPAB-LICBFIPMSA-N 0.000 description 1
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- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
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- 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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/898—Orchidaceae (Orchid family)
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- 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
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
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- 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]
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Description
炎症および自己免疫障害を処置するための試みの成功は限られている。これは、一部において、炎症および自己免疫障害の病因が、重複した機構によって炎症を引き出すと思われる種々の炎症誘導性分子ならびに多数の炎症媒介性分子および炎症感作性分子に一部基づく複雑な応答であるという事実に起因する。したがって、炎症、神経変性疾患、または自己免疫障害を処置することができる化合物、組成物、および方法が大いに望ましい。
参照による組み込み
組成物
抽出物
製剤
投薬単位
投与
医薬組成物
局所(例えば、経皮)送達のための医薬組成物
経口投与のための医薬組成物
注射用医薬組成物
吸入のための医薬組成物
他の医薬組成物
食物
処置
(実施例1)
シネチルカロールの精製
方法
(実施例2)
Spiranthes sinensisおよびシネチルカロールの細胞毒性
方法
細胞培養
細胞生存率
結果
(実施例3)
Spiranthes sinensis抽出物およびシネチルカロールのマウスにおけるCFA誘導炎症への効果
方法
動物
結果
(実施例4)
Spiranthes sinensis抽出物のマウスにおけるCFA誘導炎症の血液MMP2およびMMP9への効果
方法
動物
ゼラチンザイモグラフィー
結果
(実施例5)
RAW264.7細胞におけるLPS誘導IL−1β、IL−6、iNOsおよびTNF−α mRNA発現へのSpiranthes sinensis抽出物およびシネチルカロールの効果
方法
細胞培養
リアルタイムPCR
(実施例6)
Spiranthes sinensis抽出物およびシネチルカロールのLPS誘導RAW264.7細胞におけるCOX−2の発現、NFκBおよびphosphor ERK活性化への効果
方法
細胞培養
ウエスタンブロット
結果
(実施例7)
RAW264.7細胞におけるNO産生へのSpiranthes sinensis抽出物およびシネチルカロールの効果
方法
LPS誘導RAW264.7細胞において
方法
細胞培養
亜硝酸数量化
結果
(実施例8)
Spiranthes sinensis抽出物のin vivo抗酸化活性
方法
細胞培養
DPPHアッセイ
結果
(実施例9)
THSCおよびNHSC細胞培養ならびに生存率
NHCSおよびTHSC細胞培養
細胞生存率
MTTアッセイ
(実施例10)
脂質蓄積へのSpiranthes sinensis抽出物の効果
方法
オイルレッドO染色アッセイ
結果
AdipoRedアッセイ
結果
(実施例11)
コラーゲン蓄積へのSpiranthes sinensisの効果
方法
結果
(実施例12)
COL1 I、COL1 III、TGF−/3 R1、TGF−/3 R2、RXRα、NrF2およびPPARγの発現へのSpiranthes sinensis抽出物の効果
方法
結果
組織損傷/創傷治癒へのSpiranthes sinensisの効果
方法
結果
(実施例13)
Spiranthes sinensis抽出物の調製
(実施例14)
細胞生存率へのSpiranthes sinensis抽出物の効果
(実施例15)
細胞培養におけるMMP2へのSpiranthes sinensis抽出物の効果
Claims (34)
- 炎症応答を低減するための組成物であって、シネチルカロールを、炎症応答の低減に有効な量で含む組成物。
- 少なくとも4.4μgのシネチルカロールを含む、請求項1に記載の組成物。
- 前記シネチルカロールが、4.4μgから44μgの間の量である、請求項1に記載の組成物。
- 炎症応答の低減が、誘導性一酸化窒素合成酵素(iNOS)、シクロオキシゲナーゼ−2(COX−2)、腫瘍壊死因子−アルファ(TNF−α)、プロスタグランジンE2(PGE2)、インターロイキン−6(IL−6)、インターロイキン1β(IL−1β)、インターロイキン33(IL−33)、NLRP3、リン酸化ERK(pERK)、NFκB、マトリックスメタロプロテイナーゼ−2(MMP2)、およびマトリックスメタロプロテイナーゼ−9(MMP9)からなる群から選択される1つまたは複数の生物学的マーカーの発現または活性の低減によって証明される、請求項1に記載の組成物。
- 炎症応答の低減が、炎症応答における1つまたは複数のフリーラジカルのレベルの低減によって証明される、請求項1に記載の組成物。
- 前記1つまたは複数のフリーラジカルが、スーパーオキシドラジカルアニオン(O2 −.)、過酸化水素(H2O2)、ヒドロキシルラジカル(.OH)、一重項酸素(1O2)、ペルオキシナイトライト(ONOO−)、一酸化窒素(NO)、ニトロソニウムカチオン(NO+)、およびニトロキシルアニオン(NO−)からなる群から選択される、請求項5に記載の組成物。
- 炎症応答の低減が、組織腫脹の低減によって証明される、請求項1に記載の組成物。
- 前記組織が、皮膚、上皮、滑膜組織、腱、軟骨、靭帯、骨、筋肉、器官、硬膜、血管、骨髄、および細胞外マトリックスからなる群から選択される、請求項7に記載の組成物。
- 抗酸化物質産生の誘導、炎症応答の低減、及び創傷治癒の促進のうちの少なくとも1つのための剤形であって、有効量のシネチルカロールを含み、かつ対象に投与するために製剤化された、剤形。
- 静脈内投与、動脈内投与、経口投与、非経口投与、頬側投与、局所投与、経皮投与、直腸投与、筋肉内投与、皮下投与、骨内投与、経粘膜投与、または腹腔内投与のために製剤化されている、請求項9に記載の剤形。
- 局所投与のために製剤化されている、請求項9に記載の剤形。
- 液体形態、ゲル形態、半液体形態、半固体形態、または固体形態の単位投与量として製剤化されている、請求項9に記載の剤形。
- 少なくとも4.4μgのシネチルカロールを含む、請求項9に記載の剤形。
- シネチルカロールが4.4μgから44μgの間の量である、請求項9に記載の剤形。
- 単位投与量として製剤化されている、請求項9に記載の剤形。
- 前記単位投与量が、食物として製剤化されている、請求項15に記載の剤形。
- 前記単位投与量が、飲料として製剤化されている、請求項15に記載の剤形。
- 前記単位投与量が、栄養補助食品として製剤化されている、請求項15に記載の剤形。
- 炎症応答を低減するための医薬組成物であって、(a)炎症応答の低減に有効な量で存在する、ある量のSpiranthes sinensis抽出物(SSE)、および(b)薬学的に許容される担体を含み、前記SSEはSpiranthes sinensisを有機溶媒で抽出することによって取得され、かつ少なくとも0.1重量%のシネチルカロールを含む、医薬組成物。
- 炎症応答の低減が、誘導性一酸化窒素合成酵素(iNOS)、シクロオキシゲナーゼ−2(COX−2)、腫瘍壊死因子−アルファ(TNF−α)、プロスタグランジンE2(PGE2)、インターロイキン−6(IL−6)、インターロイキン1β(IL−1β)、インターロイキン33(IL−33)、NLRP3、リン酸化ERK(pERK)、NFκB、マトリックスメタロプロテイナーゼ−2(MMP2)、およびマトリックスメタロプロテイナーゼ−9(MMP9)からなる群から選択される1つまたは複数の生物学的マーカーの発現または活性の低減によって証明される、請求項19に記載の医薬組成物。
- 炎症応答の低減が、炎症応答における1つまたは複数のフリーラジカルのレベルの低減によって証明される、請求項19に記載の医薬組成物。
- 前記1つまたは複数のフリーラジカルが、スーパーオキシドラジカルアニオン(O2 −.)、過酸化水素(H2O2)、ヒドロキシルラジカル(.OH)、一重項酸素(1O2)、ペルオキシナイトライト(ONOO−)、一酸化窒素(NO)、ニトロソニウムカチオン(NO+)、およびニトロキシルアニオン(NO−)からなる群から選択される、請求項21に記載の医薬組成物。
- 炎症応答の低減が、組織腫脹の低減によって証明される、請求項19に記載の医薬組成物。
- 前記組織が、皮膚、上皮、滑膜組織、腱、軟骨、靭帯、骨、筋肉、器官、硬膜、血管、骨髄、および細胞外マトリックスからなる群から選択される、請求項23に記載の医薬組成物。
- 150gの前記SSEが少なくとも250mgのシネチルカロールを含む、請求項19に記載の医薬組成物。
- 局所投与のために製剤化されている、請求項19に記載の医薬組成物。
- 前記担体が、静脈内投与、動脈内投与、経口投与、非経口投与、頬側投与、局所投与、経皮投与、直腸投与、筋肉内投与、皮下投与、骨内投与、経粘膜投与、または腹腔内投与に適合している、請求項19に記載の医薬組成物。
- 液体形態、ゲル形態、半液体形態、半固体形態、または固体形態の単位投与量として製剤化されている、請求項19に記載の医薬組成物。
- 局所クリーム剤として製剤化されている、請求項19に記載の医薬組成物。
- 剤形の製造におけるシネチルカロールの使用であって、前記剤形は抗酸化物質産生を誘導するために使用される、使用。
- 剤形の製造におけるシネチルカロールの使用であって、前記剤形は炎症応答を低減するために使用される、使用。
- 剤形の製造におけるシネチルカロールの使用であって、前記剤形は創傷治癒を促進するために使用される、使用。
- 前記剤形が、薬学的に許容される担体を含む医薬組成物である、請求項30〜32のいずれか一項に記載の使用。
- 前記剤形が、Spiranthes sinensis抽出物を含む、請求項30〜32のいずれか一項に記載の使用。
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