[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

CN110302204A - 一种用于糖尿病治疗的药物 - Google Patents

一种用于糖尿病治疗的药物 Download PDF

Info

Publication number
CN110302204A
CN110302204A CN201910620488.0A CN201910620488A CN110302204A CN 110302204 A CN110302204 A CN 110302204A CN 201910620488 A CN201910620488 A CN 201910620488A CN 110302204 A CN110302204 A CN 110302204A
Authority
CN
China
Prior art keywords
inhibitor
diabetes
treating diabetes
treatment
drug according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201910620488.0A
Other languages
English (en)
Inventor
王攀
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Peking University Third Hospital Peking University Third Clinical Medical College
Original Assignee
Peking University Third Hospital Peking University Third Clinical Medical College
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Peking University Third Hospital Peking University Third Clinical Medical College filed Critical Peking University Third Hospital Peking University Third Clinical Medical College
Priority to CN201910620488.0A priority Critical patent/CN110302204A/zh
Publication of CN110302204A publication Critical patent/CN110302204A/zh
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Landscapes

  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

本发明涉及一种用于糖尿病治疗的药物，具体指抑制剂CID755673在治疗糖尿病中的应用。通过使用抑制剂制备的药物对糖尿病的治疗，抑制剂能够显著降低2型糖尿病小鼠空腹血糖及体重，改善胰岛素耐量等，扩大了抑制剂的应用范围。

Description

一种用于糖尿病治疗的药物
技术领域
本发明属于医药技术领域，特别是指一种用于治疗糖尿病的药物。
背景技术
抑制剂CID755673的化学式为C12H11NO3，是一种具有细胞活性的泛蛋白激酶(PKD)1/2/3抑制剂，IC50值分别为180nM、280nM及227nM，选择性比其它CAMKs高大约200倍。
体外研究在前列腺癌细胞(LNCaP)中，CID755673直接抑制PKD1活性，在HeLa细胞中，CID755673显著阻断PMA诱导的HDAC5核输出，并阻断PKD介导的蛋白质转运。在前列腺癌细胞中，CID755673有效阻断细胞迁移和侵入，并对肿瘤细胞增殖和细胞周期分布表现出抑制活性。
此外，CID755673改变原代人NK细胞效应功能。在大鼠急性胰腺炎体内研究模型中，CID755673通过抑制PKD/PKD1，显著改善胰腺炎坏死的严重程度，并且在中短期使用CID755673能够改善心肌功能。
发明内容
本发明的目的是提供一种用于糖尿病治疗的药物，以扩大抑制剂CID755673的应用范围。
本发明是通过以下技术方案实现的：
一种用于糖尿病治疗的药物，抑制剂在治疗糖尿病药物中的应用。
所述抑制剂为CID755673，所述抑制剂CID755673的化学式为C12H11NO3，结构式为：
所述抑制剂通过降低血糖来治疗糖尿病。
所述抑制剂按每千克体重计的用量为10mg。
所述抑制剂在治疗糖尿病药物中的质量百分比含量为0.01-100％。
所述治疗糖尿病药物还包括所述抑制剂在药学上接受的载体和/或赋形剂。
所述治疗糖尿病药物为注射液。
所述治疗糖尿病药物的剂型还包括针剂、片剂、胶囊剂、滴丸剂或颗粒剂。
本技术方案的有益效果是：
本技术方案通过将原用于泛蛋白激酶的抑制剂，用于糖尿病治疗药物的研发上，扩大了该抑制剂的应用范围。
附图说明
图1为血液中丙氨酸氨基转移酶检测分析；
图2为血液中天冬氨酸氨基转移酶检测分析；
图3中为尾静脉血液中的空腹血糖检测分析；
图4为胰岛素耐量试验结果对比曲线；
图5为2型糖尿病小鼠体重随周龄变化的对比曲线。
具体实施方式
以下详细说明本发明的技术方案，以下的实施例仅是示例性的，仅能用来解释和说明本发明的技术方案，而不能解释为是对本发明技术方案的限制。
本发明涉及一种原用于泛蛋白激酶(PKD)1/2/3抑制剂的转用，用于治疗糖尿病药物的研发。
该抑制剂为CID755673，中文名称为7-羟基-2，3，4，5-四氢[1]苯并呋喃并[2，3-c]氮杂环-1-酮，化学式为C12H11NO3，结构式为：
本发明中，所述抑制剂通过降低血糖来治疗糖尿病。本发明中，所述抑制剂按每千克体重计的用量为10mg。本发明中，所述抑制剂在治疗糖尿病药物中的质量百分比含量为0.01-100％。本发明中，所述治疗糖尿病药物还包括所述抑制剂在药学上接受的载体和/或赋形剂。本发明中，所述治疗糖尿病药物为注射液。本发明中，所述治疗糖尿病药物的剂型还包括针剂、片剂、胶囊剂、滴丸剂或颗粒剂。
实施例
抑制剂为CID755673治疗糖尿病。
材料为7周龄db/db小鼠(2型糖尿病小鼠)共16只，购自江苏集萃耀康生物技术有限公司，饲养于北京大学医学部实验动物科学部。实验期间，小鼠单笼双只饲养，自由摄食饮水，房间保持温度为22±2℃，湿度为55±5％，光暗比12h/12h。将16只小鼠平均分为两组，每组8只，编号为A和B组。适应一周后开始试验。
一周后即8周龄开始，A组注射溶媒对照(2％DMSO+30％PEG300+2％tween-80+ddH2O)，B组注射CID755673(10mg/kg)(腹腔注射1次/天)，每天注射，连续注射12周。
第0周空腹12-16小时后(即8周龄小鼠)测尾静脉空腹血糖，第4周(即12周龄小鼠)、第8周(即16周龄小鼠)、第12周(即20周龄小鼠)分别测空腹血糖。
干预11周后一次胰岛素耐量实验。空腹6小时后，注射胰岛素(1U/kg)0min、15min、30min及60min后测尾静脉血糖。
在试验过程中，由于db/db小鼠体重会逐渐增加，所以需要每周测量和记录小鼠体重两次，根据动物体重计算药物用量。
干预结束后，尾静脉取血200μl，检测血清天冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)水平，并将B组(CID755673组)与A组(溶媒对照组)进行比较。结果显示，如图1和图2所示，CID755673组相比溶媒对照组，AST及ALT均有下降趋势，但无统计学差异，表明CID755673对肝脏功能无影响。
使用该抑制剂对治疗db/db糖尿病小鼠，如图3所示，与A组相比，B组空腹血糖明显降低。如图4所示，B组胰岛素耐量明显改善。与此同时，如图5所示，CID755673干预8周后，B组小鼠体重相比A组即有统计学差异。上述结果提示，CID755673对糖尿病小鼠有一定的治疗效果。
尽管已经示出和描述了本发明的实施例，对于本领域的普通技术人员而言，可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变形，本发明的范围由所附权利要求及其等同限定。

Claims (8)

1.一种用于糖尿病治疗的药物，其特征在于，抑制剂在治疗糖尿病药物中的应用。
2.根据权利要求1所述的用于糖尿病治疗的药物，其特征在于，所述抑制剂为CID755673，所述抑制剂CID755673的化学式为C12H11NO3，结构式为：
3.根据权利要求1所述的用于糖尿病治疗的药物，其特征在于，所述抑制剂通过降低血糖来治疗糖尿病。
4.根据权利要求1所述的用于糖尿病治疗的药物，其特征在于，所述抑制剂按每千克体重计的用量为10mg。
5.根据权利要求1所述的用于糖尿病治疗的药物，其特征在于，所述抑制剂在治疗糖尿病药物中的质量百分比含量为0.01-100％。
6.根据权利要求5所述的用于糖尿病治疗的药物，其特征在于，所述治疗糖尿病药物还包括所述抑制剂在药学上接受的载体和/或赋形剂。
7.根据权利要求5所述的用于糖尿病治疗的药物，其特征在于，所述治疗糖尿病药物为注射液。
8.根据权利要求5所述的用于糖尿病治疗的药物，其特征在于，所述治疗糖尿病药物的剂型还包括针剂、片剂、胶囊剂、滴丸剂或颗粒剂。
CN201910620488.0A 2019-07-10 2019-07-10 一种用于糖尿病治疗的药物 Pending CN110302204A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910620488.0A CN110302204A (zh) 2019-07-10 2019-07-10 一种用于糖尿病治疗的药物

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910620488.0A CN110302204A (zh) 2019-07-10 2019-07-10 一种用于糖尿病治疗的药物

Publications (1)

Publication Number Publication Date
CN110302204A true CN110302204A (zh) 2019-10-08

Family

ID=68079792

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910620488.0A Pending CN110302204A (zh) 2019-07-10 2019-07-10 一种用于糖尿病治疗的药物

Country Status (1)

Country Link
CN (1) CN110302204A (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4052700A1 (en) * 2021-03-03 2022-09-07 Instytut Biologii doswiadczalnej imienia Marcelego Nenckiego Polskiej Akademii Nauk Inhibitor of protein kinase d (pkd) for use in prevention or treatment of obesity and a pharmaceutical composition for such use
WO2022185253A1 (en) * 2021-03-03 2022-09-09 Instytut Biologii doswiadczalnej imienia Marcelego Nenckiego Polskiej Akademii Nauk Inhibitor of protein kinase d for use in prevention or treatment of hyperlipidemia

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999029324A1 (fr) * 1997-12-05 1999-06-17 Institute Of Medicinal Molecular Design. Inc. Agents preventifs/medicaments contre le diabete
CN104961742A (zh) * 2015-03-17 2015-10-07 丁新生 具有防治阿尔茨海默病作用的化合物及其应用
US20180289707A1 (en) * 2017-04-10 2018-10-11 Melior Pharmaceuticals I, Inc. Treatment Of Adipocytes

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999029324A1 (fr) * 1997-12-05 1999-06-17 Institute Of Medicinal Molecular Design. Inc. Agents preventifs/medicaments contre le diabete
CN104961742A (zh) * 2015-03-17 2015-10-07 丁新生 具有防治阿尔茨海默病作用的化合物及其应用
US20180289707A1 (en) * 2017-04-10 2018-10-11 Melior Pharmaceuticals I, Inc. Treatment Of Adipocytes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KYLIE VENARDOS ET AL.: "The PKD Inhibitor CID755673 Enhances Cardiac Function in Diabetic db/db Mice", 《PLOS ONE》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4052700A1 (en) * 2021-03-03 2022-09-07 Instytut Biologii doswiadczalnej imienia Marcelego Nenckiego Polskiej Akademii Nauk Inhibitor of protein kinase d (pkd) for use in prevention or treatment of obesity and a pharmaceutical composition for such use
WO2022185253A1 (en) * 2021-03-03 2022-09-09 Instytut Biologii doswiadczalnej imienia Marcelego Nenckiego Polskiej Akademii Nauk Inhibitor of protein kinase d for use in prevention or treatment of hyperlipidemia

Similar Documents

Publication Publication Date Title
EP1429602B1 (en) Methods for treating disorders using plant extracts
Xie et al. Effect of ethanolic extracts of Ananas comosus L. leaves on insulin sensitivity in rats and HepG2
Meezan et al. Contrasting effects of puerarin and daidzin on glucose homeostasis in mice
Wang et al. Glucose transporter inhibitor-conjugated insulin mitigates hypoglycemia
Blevins et al. Efficacy and safety of MYL‐1501D vs insulin glargine in patients with type 1 diabetes after 52 weeks: results of the INSTRIDE 1 phase III study
CN110302204A (zh) 一种用于糖尿病治疗的药物
Ginter et al. Hypocholesterolemic effect of ascorbic acid in maturity-onset diabetes mellitus.
Tian et al. Effect of docosahexaenoic acid on the recovery of motor function in rats with spinal cord injury: a meta-analysis
Bellin et al. Total pancreatectomy with islet auto-transplantation: surgical procedure, outcomes, and quality of life
Sabo et al. Pharmacodynamic action of a commercial preparation of the mushroom Coprinus comatus in rats
CN102895676B (zh) P53基因的新应用
CN110801456A (zh) 虫草素在制备保肝产品中的应用
CN109512820A (zh) iCRT14化合物在制备治疗I型糖尿病的药物中的应用
CN116531410A (zh) 白色葡萄球菌在制备组合物中的应用
Wang et al. Simultaneous Quantification of Pioglitazone and Omarigliptin in Rat Plasma by UHPLC‐MS/MS and Its Application to Pharmacokinetic Study after Coadministration of the Two Drugs
CN101695507B (zh) 一种治疗糖尿病的药物
CN105232541B (zh) 可皆霉素在制备治疗糖尿病药物中的应用
CN115813925B (zh) Acbi1的应用
CN103550222A (zh) 毛壳素在制备预防和治疗糖尿病药物中的应用
CN116077496B (zh) 紫草素联合cm-272在制备治疗肺癌药物中的应用
CN117797176B (zh) 双孢梭菌在制备治疗非酒精性脂肪性肝病药物中的应用和一种药物
CN103007296A (zh) 一种利拉鲁肽干预gk大鼠模型及其在制备干预治疗2型糖尿病药物中的应用
Reich et al. Brodalumab, a Human Anti-Interleukin-17 Receptor A Monoclonal Antibody, Shows Low Immunogenicity in Patients with Moderate-to-Severe Psoriasis
Karasawa et al. Effects of varying doses of methionine sulfoximine on liver glutamine synthetase activity and time courses of blood and urinary nitrogenous compounds in the chicken (Gallus domesticus).
CN108126055A (zh) 茶叶提取物组合物在缓解和治疗糖尿病中的应用

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20191008

RJ01 Rejection of invention patent application after publication