JP6927884B2 - 創傷治癒調節のための製剤および方法 - Google Patents
創傷治癒調節のための製剤および方法 Download PDFInfo
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- JP6927884B2 JP6927884B2 JP2017553168A JP2017553168A JP6927884B2 JP 6927884 B2 JP6927884 B2 JP 6927884B2 JP 2017553168 A JP2017553168 A JP 2017553168A JP 2017553168 A JP2017553168 A JP 2017553168A JP 6927884 B2 JP6927884 B2 JP 6927884B2
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- JNXBNLHQYNWWGP-UHFFFAOYSA-N CC(C)(C=C1)C=[IH+][C@H]1[Cs] Chemical compound CC(C)(C=C1)C=[IH+][C@H]1[Cs] JNXBNLHQYNWWGP-UHFFFAOYSA-N 0.000 description 1
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Description
本発明は、概して細胞生物学の分野に関し、より詳細には、創傷または皮膚に関連する疾患または状態を治療するためにオートファジーを調節するための化合物、製剤、および方法に関する。オートファゴサイトーシスとしても知られる「オートファジー」という名称は、「食べる」と「自己」を意味するギリシャ語に由来する。オートファジーは、一般に自己消化と定義される。
例えば、角度、成分の量、ポリマー分子量、反応条件(pH、温度、電荷レベルなど)、物理的寸法など、本発明を特徴付けるために使用される数値範囲、測定値、およびパラメーターは、必然的に近似値であり、できるだけ正確に報告されているものの、それぞれの測定値に由来する不正確さを本質的に含む。したがって、明細書および特許請求の範囲で使用される大きさの範囲を表す全ての数字は、全ての場合において「約」という用語によって修飾されるものとして理解されるべきである。全ての数値範囲は、その範囲の外側境界内の全ての可能な漸増の部分範囲を含むと理解される。したがって、30〜90単位の範囲は、例えば、35〜50単位、45〜85単位、および40〜80単位などを開示する。他に定義されない限り、パーセンテージは、重量/重量(wt/wt)であり、処方は、概して、重量/容量(w/v)、100mLあたりのグラム数(密度1.0の水溶液ではwt/wtに相当)であり、創傷面積は、面積/面積(a/a)としてcm2で表されている。
化学的および生物学的定義
RaおよびRbは、独立して、H、または−(R3)pもしくは−(R4)qで置換されていてもよいフェニルであり、
R1〜R4は、独立して、フェニル環の任意の利用可能な位置の置換基であり、
m、n、p、およびqは、それぞれ独立して、環の置換基の数を表す0、1、2、または3であり、mまたはnの少なくとも1つは≧1でなければならず、
各R1、R2、R3、およびR4は、独立して、
(C1〜C6)アルキル、(C2〜C6)アルケニル、または(C2〜C6)アルキニルから選択され、−OH、−SH、−ハロ、−NH2、またはNO2から選択される1〜3個の置換基で置換されていてもよい−R5、
YがO、S、またはNHであり、R6がHまたはR5から選択される−YR6、
Zが−N(C=O)−または−O(C=O)−である−ZR5、
−ハロ、
−NO2、
−SO3Na、
−アジド、および
−グリコシド
−ならびにこれらの塩、
から選択され、
但し、FAMはレスベラトロールまたは4,4’−(エチン−1,2−ジイル)ジフェノール(TOLCINE)ではない。
第1のオートファジー調節剤(FAM)
補助的オートファジー調節剤(AAM)および製剤
ビタミン
アミノ酸
酸性糖
キノン誘導体
オートファジー調節におけるFAMおよびAAMの有用性
Claims (25)
- 4−ヒドロキシ−4'−メトキシトランまたは2,4,4'−トリメトキシトランである第1のオートファジー調節化合物を含む、慢性創傷または皮膚疾患を有する患者における創傷治癒を促進するための製剤。
- 補助的オートファジー調節化合物との併用投与用である、請求項1に記載の製剤。
- 前記補助的オートファジー調節化合物と同時に投与される、請求項2に記載の製剤。
- 前記補助的オートファジー調節化合物を投与した後に投与される、請求項2に記載の製剤。
- 前記補助的オートファジー調節化合物が、置換型または非置換型パラベンゾキノン、置換型または非置換型オルトベンゾキノン、および置換型または非置換型アントラキノンからなる群から選択される、請求項2に記載の製剤。
- 前記補助的オートファジー調節化合物が、アミノ酸、酸性単糖、およびビタミンまたはその塩からなる群から選択される、請求項2に記載の製剤。
- 前記ビタミンが酸素含有ビタミンである、請求項6に記載の製剤。
- 前記ビタミンがイソプレノイド含有ビタミンである、請求項6に記載の製剤。
- 前記第1のオートファジー調節化合物が、オートファジー活性をアップレギュレートする、請求項1に記載の製剤。
- 前記慢性創傷または皮膚疾患が、老化、炎症を伴う自己免疫疾患、無血管壊死、細菌感染、癌、糖尿病性神経障害、子宮内膜症、真菌感染症、感染性関節炎、炎症、炎症性腸疾患、虚血、ライム病、器官/組織移植、寄生虫感染、乾癬性関節炎、乾癬、偽痛風、関節リウマチ、強皮症、壊血病、敗血症、手術瘢痕、外科的癒着、トランスフェクション法、潰瘍性大腸炎、潰瘍、ウイルス感染、疣贅、手術創傷、切開、裂傷、切り傷および擦り傷、皮膚移植による供与部創傷、外傷性創傷、感染性創傷、虚血性創傷、火傷、水疱性創傷、非感染創傷、打撲傷、切創、裂傷、非貫通創、開いた創傷、貫通創、穿孔創、刺創、膿創、皮下創、慢性潰瘍、胃潰瘍、皮膚潰瘍、消化性潰瘍、十二指腸潰瘍、胃潰瘍、高血圧性虚血性潰瘍、鬱血性潰瘍、舌下潰瘍、粘膜下潰瘍、症候性潰瘍、栄養性潰瘍、熱帯性潰瘍、および性病性潰瘍から選択される1つ以上である、請求項1または9に記載の製剤。
- 慢性創傷または皮膚疾患が、角化症、光老化、乾癬、皮膚発疹、日焼け、および光反応過程などの1つ以上の皮膚病である、請求項1または9に記載の製剤。
- 慢性創傷または皮膚疾患が、口腔内のびらんおよび熱傷;抜歯後創傷;特に嚢胞および膿瘍の治療に関連する歯内創傷、細菌性、ウイルス性、または自己免疫性起源の潰瘍および病変;機械的、化学的、熱的、感染性、および苔癬状創傷;ヘルペス潰瘍;アフタ性口内炎;急性壊死性潰瘍性歯肉炎;および口腔内灼熱症などのうち1つ以上の損傷した口腔組織である、請求項1または9に記載の製剤。
- 慢性創傷または皮膚疾患が、角膜潰瘍、放射状角膜切開、角膜移植、エピケラトファキア、および他の手術により誘発された眼内の創傷のうち1つ以上である、請求項1または9に記載の製剤。
- 慢性創傷または皮膚疾患が、掻痒症、直腸炎、肛門裂傷、および痔核のうち1つ以上である、請求項1または9に記載の製剤。
- 慢性創傷または皮膚疾患が、乾いた割れた肌;他の疾患による重度の乾燥肌(静脈皮膚炎);UV光損傷を受けた皮膚;および脂漏性状態のうち1つ以上である、請求項1または9に記載の製剤。
- 慢性創傷または皮膚疾患が、熱傷、炭疽病、破傷風、ガス壊疽、猩紅熱(scalatina)、丹毒、ひげ毛瘡、毛嚢炎、伝染性膿痂疹、もしくは水疱性膿痂疹から選択される1つ以上の創傷またはびらんである、請求項1または9に記載の製剤。
- 慢性創傷または皮膚疾患が、皮膚における老化、および/または皮膚の非座瘡形成性炎症のうち1つ以上である、請求項1または9に記載の製剤。
- 慢性創傷または皮膚疾患が、放射線および/または化学療法から生じる口腔および口腔傍潰瘍のうち1つ以上である、請求項1または9に記載の製剤。
- 4−ヒドロキシ−4'−メトキシトランまたは2,4,4'−トリメトキシトランである第1のオートファジー調節化合物を、ヒドロゲル中に分散して含んでなる、慢性創傷または皮膚疾患を有する患者における創傷治癒を促進するための組成物。
- 前記ヒドロゲルが、前記第1のオートファジー調節化合物によって部分的に形成された液晶性ヒドロゲルである、請求項19に記載の組成物。
- 前記ヒドロゲルがアルギン酸塩である、請求項19に記載の組成物。
- 約1:1〜約1:10の第1のオートファジー調節化合物:シクロデキストリンの比でシクロデキストリンと組み合わされた前記第1のオートファジー調節化合物を含む、請求項1に記載の製剤。
- 前記第1のオートファジー調節化合物がアスコルビン酸およびカチオンとの複合体に組み込まれた、請求項1に記載の製剤。
- 4−ヒドロキシ−4'−メトキシトランまたは2,4,4'−トリメトキシトランである第1のオートファジー調節化合物を含む、オートファジー調節を必要とする患者におけるオートファジーを調節するための製剤。
- 前記患者がオートファジーアップレギュレーションを必要とする状態に罹患しており、前記状態が、創傷、毛髪再成長、細菌感染、炎症、ウイルス感染、パーキンソン病、老化、神経変性疾患、神経障害、循環器疾患、熱傷、心臓病、アルツハイマー病、アテローマ性動脈硬化症、動脈硬化症、慢性閉塞性肺疾患(COPD)、クローン病、炎症性腸疾患、大腸炎、糖尿病、I型およびII型糖尿病、アミロイドーシス、滑液包炎、皮膚炎、血管炎、炎症を伴う自己免疫疾患、血液疾患、再生不良性貧血、子宮内膜症、肝炎、ヘルペス感染症、HIV感染症、多発性硬化症、網膜剥離、老化性黄斑変性症、網膜色素変性、およびレーバー先天性黒内障、リソソーム蓄積症、関節炎、乾癬、骨減少症、骨粗鬆症、手術瘢痕、外科的癒着、宇宙旅行(骨密度障害)、腱炎、および潰瘍性大腸炎のうち1つ以上を含んでなる、前記オートファジーアップレギュレーションによって創傷治癒力を促進するための、請求項24に記載の製剤。
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AU2016246616B2 (en) | 2021-04-01 |
CA2982161A1 (en) | 2016-10-13 |
US11786481B2 (en) | 2023-10-17 |
IL254863B (en) | 2021-06-30 |
CN107847466A (zh) | 2018-03-27 |
EP3280402A2 (en) | 2018-02-14 |
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