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Article(id=1236346590542221466, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236346588398932061, articleNumber=null, orderNo=null, doi=null, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=1670428800000, acceptedDateStr=2022-12-08, onlineDate=1772697597394, onlineDateStr=2026-03-05, pubDate=1685376000000, pubDateStr=2023-05-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1772697597394, onlineIssueDateStr=2026-03-05, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1772697597394, creator=13701087609, updateTime=1772697597394, updator=13701087609, issue=Issue{id=1236346588398932061, tenantId=1146029695717560320, journalId=1235980733773295621, year='2023', volume='32', issue='10', pageStart='969', pageEnd='1072', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1772697596882, creator=13701087609, updateTime=1772697715363, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1236347085411373506, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236346588398932061, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1236347085411373507, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236346588398932061, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1057, endPage=1063, ext={EN=ArticleExt(id=1236346590747742380, articleId=1236346590542221466, tenantId=1146029695717560320, journalId=1235980733773295621, language=EN, title=Pharmacokinetics of three new cocrystals of pioglitazone hydrochloride in rats, columnId=null, journalTitle=Chinese Journal of New Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective:

To evaluate the absorption of pioglitazone hydrochloride (PGH) cocrystals in SD rats and improve the problems of poor solubility and low bioavailability of PGH.

Methods:

Cocrystals of pioglitazone hydrochloride-para aminobenzoic acid, pioglitazone hydrochloride-para-aminosalicylic acid and pioglitazone hydrochloride-gallic acid were prepared by suspension method. PGH and 3 cocrystals were characterized by a variety of analytical techniques, and the concentration of PGH in rat plasma was determining by high performance liquid chromatography-mass spectrometry (HPLC-MS) to analyze the pharmacokinetic parameters of cocrystals.

Results:

The 3 cocrystals all showed good stability and solubility. Cocrystals of pioglitazone hydrochloride-para aminobenzoic acid and pioglitazone hydrochloride-gallic acid could significantly improve the bioavailability, peak concentration (Cmax), and area under the curve (AUC) of oral PGH in rats.

Conclusion:

Cocrystallization is an important method to change PGH solubility and absorption characteristics in vivo.

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目的：

评价3种盐酸吡格列酮（pioglitazone hydrochloride, PGH）共晶在SD大鼠体内的生物吸收过程，改善PGH水溶性差、生物利用度低等问题。

方法：

采用悬浮液法制备得到盐酸吡格列酮-对氨基苯甲酸、盐酸吡格列酮-对氨基水杨酸和盐酸吡格列酮-没食子酸3种新型共晶物质，通过多种分析检测技术进行表征，并采用HPLC-MS法测定大鼠血浆中PGH浓度，分析大鼠口服PGH共晶后的药动学参数。

结果：

3种共晶均具有良好的稳定性和溶解度，其中盐酸吡格列酮-对氨基苯甲酸和盐酸吡格列酮-没食子酸2个共晶能够改善大鼠口服PGH的生物利用度、达峰浓度（peak concentration，Cmax）和血药物浓度-时间曲线下面积（area under the cure, AUC）。

结论：

共晶技术是改变药物PGH溶解度和体内吸收特点的一种重要方法。

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杜冠华，男，博士生导师，教授，主要从事神经药理学研究。联系电话：(010)63165184，E-mail: 。
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孔德文，女，博士研究生，主要从事神经药理学及药动学研究。联系电话：(010)63165313，E-mail: 。

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孔德文，女，博士研究生，主要从事神经药理学及药动学研究。联系电话：(010)63165313，E-mail: 。

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孔德文，女，博士研究生，主要从事神经药理学及药动学研究。联系电话：(010)63165313，E-mail: 。

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3种新型盐酸吡格列酮共晶在大鼠体内的药动学
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孔德文 1 , 房政钰 2 , 龚宁波 2 , 王英 2 , 杜立达 3 , 张森 1 , 蒋楠 4 , 杨海光 1 , 方莲花 1 , 吕扬 2 , 杜冠华 1
中国新药杂志 | 实验研究 2023,32(10): 1057-1063
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中国新药杂志 | 实验研究 2023, 32(10): 1057-1063
3种新型盐酸吡格列酮共晶在大鼠体内的药动学
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孔德文1 , 房政钰2, 龚宁波2, 王英2, 杜立达3, 张森1, 蒋楠4, 杨海光1, 方莲花1, 吕扬2, 杜冠华1
作者信息
  • 1中国医学科学院北京协和医学院药物研究所国家药物筛选中心，药物靶点研究和新药筛选北京市重点实验室，北京 100050
  • 2中国医学科学院北京协和医学院药物研究所药物晶型中心，晶型药物研究北京市重点实验室，北京 100050
  • 3山东济世药业有限公司，济南 250101
  • 4河南大学药学院，开封 475004

    • 孔德文，女，博士研究生，主要从事神经药理学及药动学研究。联系电话：(010)63165313，E-mail: 。

通讯作者:

杜冠华，男，博士生导师，教授，主要从事神经药理学研究。联系电话：(010)63165184，E-mail: 。
Pharmacokinetics of three new cocrystals of pioglitazone hydrochloride in rats
De-wen KONG1 , Zheng-yu FANG2, Ning-bo GONG2, Ying WANG2, Li-da DU3, Sen ZHANG1, Nan JIANG4, Hai-guang YANG1, Lian-hua FANG1, Yang LV2, Guan-hua DU1
Affiliations
  • 1Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • 2Research Centre of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • 3Shandong Jishi Pharmaceutical Co., Ltd., Jinan 250101, China
  • 4School of Pharmacy, Henan University, Kaifeng 475004, China
出版时间: 2023-05-30
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摘要
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目的：

评价3种盐酸吡格列酮（pioglitazone hydrochloride, PGH）共晶在SD大鼠体内的生物吸收过程，改善PGH水溶性差、生物利用度低等问题。

方法：

采用悬浮液法制备得到盐酸吡格列酮-对氨基苯甲酸、盐酸吡格列酮-对氨基水杨酸和盐酸吡格列酮-没食子酸3种新型共晶物质，通过多种分析检测技术进行表征，并采用HPLC-MS法测定大鼠血浆中PGH浓度，分析大鼠口服PGH共晶后的药动学参数。

结果：

3种共晶均具有良好的稳定性和溶解度，其中盐酸吡格列酮-对氨基苯甲酸和盐酸吡格列酮-没食子酸2个共晶能够改善大鼠口服PGH的生物利用度、达峰浓度（peak concentration，Cmax）和血药物浓度-时间曲线下面积（area under the cure, AUC）。

结论：

共晶技术是改变药物PGH溶解度和体内吸收特点的一种重要方法。

盐酸吡格列酮  /  共晶化合物  /  高效液相质谱法  /  药动学  /  血药浓度
Objective:

To evaluate the absorption of pioglitazone hydrochloride (PGH) cocrystals in SD rats and improve the problems of poor solubility and low bioavailability of PGH.

Methods:

Cocrystals of pioglitazone hydrochloride-para aminobenzoic acid, pioglitazone hydrochloride-para-aminosalicylic acid and pioglitazone hydrochloride-gallic acid were prepared by suspension method. PGH and 3 cocrystals were characterized by a variety of analytical techniques, and the concentration of PGH in rat plasma was determining by high performance liquid chromatography-mass spectrometry (HPLC-MS) to analyze the pharmacokinetic parameters of cocrystals.

Results:

The 3 cocrystals all showed good stability and solubility. Cocrystals of pioglitazone hydrochloride-para aminobenzoic acid and pioglitazone hydrochloride-gallic acid could significantly improve the bioavailability, peak concentration (Cmax), and area under the curve (AUC) of oral PGH in rats.

Conclusion:

Cocrystallization is an important method to change PGH solubility and absorption characteristics in vivo.

pioglitazone hydrochloride  /  cocrystal  /  HPLC-MS  /  pharmacokinetics  /  plasma concentration
孔德文, 房政钰, 龚宁波, 王英, 杜立达, 张森, 蒋楠, 杨海光, 方莲花, 吕扬, 杜冠华. 3种新型盐酸吡格列酮共晶在大鼠体内的药动学. 中国新药杂志, 2023 , 32 (10) : 1057 -1063 .
De-wen KONG, Zheng-yu FANG, Ning-bo GONG, Ying WANG, Li-da DU, Sen ZHANG, Nan JIANG, Hai-guang YANG, Lian-hua FANG, Yang LV, Guan-hua DU. Pharmacokinetics of three new cocrystals of pioglitazone hydrochloride in rats[J]. Chinese Journal of New Drugs, 2023 , 32 (10) : 1057 -1063 .
基金
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  • 中国医学科学院医学与健康科技创新工程基金资助项目(2021-I2M-1-005)
  • 山东省重点研发计划资助项目(2019JZZY020909)
2023年第32卷第10期
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  • 首发时间：2026-03-05
  • 出版时间：2023-05-30
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  • 录用日期：2022-12-08
基金
中国医学科学院医学与健康科技创新工程基金资助项目(2021-I2M-1-005)
山东省重点研发计划资助项目(2019JZZY020909)
作者信息
    1中国医学科学院北京协和医学院药物研究所国家药物筛选中心，药物靶点研究和新药筛选北京市重点实验室，北京 100050
    2中国医学科学院北京协和医学院药物研究所药物晶型中心，晶型药物研究北京市重点实验室，北京 100050
    3山东济世药业有限公司，济南 250101
    4河南大学药学院，开封 475004

通讯作者:

杜冠华，男，博士生导师，教授，主要从事神经药理学研究。联系电话：(010)63165184，E-mail: 。
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2种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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