telmicosin

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: telmicosin
• 英文别名: (5S,6S,7R,9R,11E,13E,15R,16R)-6-[(2R,3R,4S,5S,6R)-4-(dimethylamino)-3,5-dihydroxy-6-methyloxan-2-yl]oxy-7-[2-(3,5-dimethylpiperidin-1-yl)ethyl]-16-ethyl-4-hydroxy-15-[[(2R,3R,4R,5R,6R)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-5,9,13-trimethyl-1-oxacyclohexadeca-11,13-diene-2,10-dione
• 化学式: C₄₆H₈₀N₂O₁₃
• 分子量: 869.147
• InChiKey: JTSDBFGMPLKDCD-SWSPHLSKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  61
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  186
• 氢给体数：
  4
• 氢受体数：
  15

ADMET

代谢

Beulah杂交羔羊接受了一次皮下注射，剂量为每千克体重20毫克（14）C-蒂米科辛。肝脏、肾脏和尿液中主要的放射性成分是母药，以及较少量的T1和T2，还有少量其他未识别的物质。

Beulah cross lambs were administered a single subcutaneous dose of 20 mg/kg bw per day (14)C-tilmicosin. The major radioactive component in the liver, kidneys and urine was the parent drug, together with lesser amounts of T1 and T2, and minor amounts of other unidentified substances.

来源:Hazardous Substances Data Bank (HSDB)

代谢

费希尔-344大鼠（10只雄性和10只雌性）每天经口灌胃给予50毫克/千克体重的（14）C-蒂利霉素，持续5天。对粪便中硫酸盐代谢物的粪便放射性进行分析，发现猪粪便中存在类似的化合物，但未进行量化。

Fischer-344 rats (10 males and 10 females) were given gavage doses of 50 mg/kg bw per day (14)C-tilmicosin for 5 days. An analysis of fecal radioactivity for the presence of the sulfate metabolite that was found in the feces of pigs revealed the presence of a similar compound, but quantification was not undertaken.

来源:Hazardous Substances Data Bank (HSDB)

代谢

替米考星，在去甲基大环内酯环和哌啶环上均标记有（14）C，通过口服给与15只雄性和15只雌性Fischer-344大鼠。剂量为每天20毫克/千克体重，连续3天。在肝脏中，放射性标记物对应于替米考星和一个去甲基衍生物T1（在大环内酯环上脱甲基）。尿液中检测到的单一放射性物质是未改变的替米考星，而在粪便中，主要的放射性峰是母化合物，其次是较少量的去甲基替米考星和一个高分子量化合物，已知这是给药物质中的一个杂质，T2（由两个大环内酯环和一个哌啶环组成）。

Tilmicosin, labelled with (14)C in both the desmycosin macrolide ring and the piperidine ring, was given orally to 15 male and 15 female Fischer-344 rats. The dosage was 20 mg/kg bw per day for 3 days. In the liver, radiolabel corresponded to tilmicosin and a desmethyl derivative, T1 (demethylated in the mycaminose ring). The single radioactive substance identified in urine was unchanged tilmicosin, while in feces the major peak was parent compound with lesser amounts of desmethyl tilmicosin and a high molecular weight compound known to be present as an impurity in the administered substance, T2 (consisting of two macrolide rings and one piperidine ring).

来源:Hazardous Substances Data Bank (HSDB)

代谢

在给注射了(14)C-替米考星的结果概述中，报道称处理过的老鼠肝脏中的放射性活性轮廓与粪便中的相似。在使用高度纯化的替米考样品处理的动物中，在肝脏中未检测到代谢物T2，这表明其存在是作为药物物质组成部分直接给药的结果。肾脏中的放射性活性基本上以未改变的替米考星形式存在。

In a summary of results obtained in cattle injected with (14)C-tilmicosin, it was reported that the radioactivity profile in the liver of treated rats was similar to that in the feces. In animals treated with a highly purified sample of tilmicosin, metabolite T2 was not detected in the liver, suggesting that its presence was a result of direct administration as a component of the drug substance. Radioactivity in the kidneys was essentially in the form of unchanged tilmicosin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用卡马西平、环孢素、地高辛、己巴比妥、苯妥英或丙戊酸与大环内酯类抗生素，已与这些药物的血药浓度升高有关；建议监测同时给药的药物的血药浓度，以避免中毒。/大环内酯类抗生素/

Concurrent use /of carbamazepine, cyclosporine, digoxin, hexobarbital, phenytoin or valproic acid/ with macrolide antibiotics has been associated with increased serum concentration of these medications; monitoring of serum concentrations of medications administered concurrently is recommended to avoid toxicity. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

黄嘌呤类药物（除二羟丙茶碱外）与macrolides（大环内酯类抗生素）同时使用可能会减少黄嘌呤类药物的肝清除率，导致血清浓度升高和/或毒性增加；在macrolides治疗期间和治疗后，可能需要调整黄嘌呤类药物的剂量。/大环内酯类抗生素/

Concurrent use of the xanthines (except dyphylline) with macrolides may decrease hepatic clearance of xanthines, resulting in increased serum concentrations and/or toxicity; dosage adjustment of the xanthines may be necessary during and after therapy with macrolides. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用咪达唑仑或三唑仑与 macrolide 类抗生素可能会降低这些药物的清除率，增加咪达唑仑或三唑仑的药理作用。/Macrolide 类抗生素/

Concurrent use /of midazolam or triazolam/ with macrolide antibiotics may decrease the clearance of these medications, increasing the pharmacologic effect of midazolam or triazolam. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

与 macrolide 抗生素同时使用与增加抗凝血作用有关；在接受抗凝药物和 macrolides 同时治疗的患者中应仔细监测凝血酶原时间。/Macrolide 抗生素/

Concurrent administration with macrolide antibiotics has been associated with increased anticoagulant effects; prothrombin time should be monitored carefully in patients receiving anticoagulants and macrolides concurrently. /Macrolide antibiotics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，如有需要，进行辅助通气。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预防癫痫发作，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

猪在饮食中接受了154毫克或400毫克（14）C-蒂尔米科辛的剂量，这是在连续5天给予相似剂量后的情况。放射性物质的恢复在尿液中为4%到6%，在粪便中为62%到75%。胆汁中检测到放射性物质，但未进行量化。

Pigs were given a dose of 154 or 400 mg (14)C-tilmicosin in the diet following a similar dose given for 5 days. The recovery of radioactivity was 4 to 6% in urine and 62 to 75% in feces. Radioactivity was detected in the bile but was not quantified.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

猪在一天内通过饲料摄入了110毫克（14）C-蒂莫西辛。放射性物质的回收率在尿液中为15%，在粪便中为80%。

Pigs were administered a dose of 110 mg (14)C-tilmicosin in the diet over the course of one day. The recovery of radioactivity was 15% in the urine and 80% in the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

替米考星通过皮下注射给药。注射后吸收迅速...

Tilmicosin is administered SC. Absorption after injection is rapid ... .

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Beulah杂交羔羊单次皮下注射20 mg/kg bw/天的(14)C-替米考星。肝脏、肾脏和尿液中主要的放射性成分是母药，以及较少的T1和T2，还有少量的其他未识别物质。

Beulah cross lambs were administered a single subcutaneous dose of 20 mg/kg bw per day (14)C-tilmicosin. The major radioactive component in the liver, kidneys and urine was the parent drug, together with lesser amounts of T1 and T2, and minor amounts of other unidentified substances.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为产物：
  描述：

  3,5-二甲基哌啶 、 tylosin phosphate 在 盐酸 、 calcium sulfate 、 甲酸 作用下， 以 水 为溶剂， 以95.5 %的产率得到telmicosin
  参考文献：
  名称：

  CN115925772

  摘要：

  公开号：

文献信息

• SKIN PERMEABLE PEPTIDE AND METHOD FOR USING SAME
  申请人：IUCF-HYU (Industry-University Cooperation Foundation Hanyang University)

  公开号：EP3336098A1

  公开（公告）日：2018-06-20

  The present disclosure is directed to providing a new skin-penetrating peptide, a fusion product with a biologically active substance bound using the same, a cosmetic composition containing the same and a pharmaceutical composition for external application to skin containing the same. The skin-penetrating peptide of the present disclosure is less likely to cause an immune response as compared to existing skin-penetrating peptides and exhibits remarkably improved skin permeability. Therefore, the biologically active substance can be effectively delivered through the skin, particularly through the stratum corneum.

  本公开旨在提供一种新的皮肤穿透肽、使用该肽与生物活性物质结合的融合产品、含有该肽的化妆品组合物以及含有该肽的用于皮肤外用的药物组合物。与现有的皮肤穿透肽相比，本公开的皮肤穿透肽引起免疫反应的可能性更小，而且皮肤渗透性显著提高。因此，生物活性物质可以有效地通过皮肤，特别是角质层输送。
• Skin-penetrating peptide and method for using same
  申请人：IUCF-HYU (INDUSTRY-UNIVERSITY COOPERATION FOUNDATION HANYANG UNIVERSITY)

  公开号：US10858395B2

  公开（公告）日：2020-12-08

  The present disclosure is directed to providing a new skin-penetrating peptide, a fusion product with a biologically active substance bound using the same, a cosmetic composition containing the same and a pharmaceutical composition for external application to skin containing the same. The skin-penetrating peptide of the present disclosure is less likely to cause an immune response as compared to existing skin-penetrating peptides and exhibits remarkably improved skin permeability. Therefore, the biologically active substance can be effectively delivered through the skin, particularly through the stratum corneum.

  本公开旨在提供一种新的皮肤穿透肽、使用该肽与生物活性物质结合的融合产品、含有该肽的化妆品组合物以及含有该肽的用于皮肤外用的药物组合物。与现有的皮肤穿透肽相比，本公开的皮肤穿透肽引起免疫反应的可能性更小，而且皮肤渗透性显著提高。因此，生物活性物质可以有效地通过皮肤，特别是角质层输送。
• SKIN PERMEATING AND CELL ENTERING (SPACE) PEPTIDES AND METHODS OF USE THEREOF
  申请人：The Regents of the University of California

  公开号：EP2638162A2

  公开（公告）日：2013-09-18
• DELIVERY AND RETENTION OF ACTIVE AGENTS WITHIN THE SKIN
  申请人：Fount Bio, Inc.

  公开号：EP3955887A1

  公开（公告）日：2022-02-23
• SKIN PERMEATING AND CELL ENTERING (SPACE) PEPTIDES AND METHODS OF USE THEREFOR
  申请人：CONVOY THERAPEUTICS

  公开号：US20140227174A1

  公开（公告）日：2014-08-14

  Compositions that facilitate the delivery of an active agent or an active agent carrier wherein the compositions are capable of penetrating the stratum corneum (SC) and/or the cellular membranes of viable cells are provided. In some embodiments, the compositions include a peptide, an active agent, and a carrier that includes the active agent, wherein the peptide has an amino acid sequence set forth in any of SEQ ID NOs: 1-18; the peptide is associated with and/or conjugated to the active agent, the carrier, or both; the carrier is selected from the group consisting of a micelle, a liposome, an ethosome, and combinations thereof; and the composition is capable of penetrating a stratum corneum (SC) layer when contacted therewith or penetrating a cell when contacted therewith, and optionally wherein the composition further includes one or more free peptides having an amino acid sequence set forth in any of SEQ ID NOs: 1-18. Also provided are methods for delivering active agents to subjects, methods for treating subjects having dermatological diseases, and methods for attenuating expression of mRNAs of subjects in need thereof and/or for treating diseases and/or disorders thereby.