Title:
NOVEL POLYMER-ACTIVE DRUG CONJUGATE AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2020/105701
Kind Code:
A1
Abstract:
The present invention addresses the problem of providing a polymer-anticancer agent-nitric monoxide-releasing compound conjugate that, once administered intravitally, circulates continuously through the whole body and moves to a tumor tissue and accumulates there more efficiently than conventional polymer-anticancer agent conjugates, and that remains there for an extended period of time to release the anticancer agent in the low-pH environment around the tumor, thereby demonstrating excellent antitumor activity with fewer adverse effects. The present invention can provide a polymer compound, or a pharmaceutically-accepted salt thereof, that demonstrates excellent anti-cancer activity with few adverse effect, and that comprises: a constituent unit (1) represented by formula (1) [symbols in the formula are as defined in the specification]; a constituent unit (2) represented by formula (2) [symbols in the formula are as defined in the specification]; and a constituent unit (3) derived from N-(2-hydroxypropyl) methacrylamide.
Inventors:
TAKEDA SHIGEMITSU (JP)
MIIKE TOMOHIRO (JP)
OTAKE KAZUYA (JP)
TAKASHIMA SHUNSUKE (JP)
MIIKE TOMOHIRO (JP)
OTAKE KAZUYA (JP)
TAKASHIMA SHUNSUKE (JP)
Application Number:
PCT/JP2019/045604
Publication Date:
May 28, 2020
Filing Date:
November 21, 2019
Export Citation:
Assignee:
KYOTO PHARMA IND (JP)
International Classes:
A61K31/704; A61K31/785; A61K33/00; A61K47/58; A61P35/00; A61P35/02; A61P35/04; A61P43/00
Other References:
ISLAM,W. ET AL.: "Augmentation of the Enhanced Permiability and Retention Effect with Nitric Oxide-Generating Agents Improves the Therapeutic Effects of Nonomedicines", MOLECULAR CANCER THERAPEUTICS, vol. 17, no. 12, 1 September 2018 (2018-09-01), pages 2643 - 2653, XP055710965
RIHOVA,B. ET AL.: "Synergistic Action of Doxorubicin Bound to the Polymeric Carrier Based on N-(2-Hydroxypropyl)methacrylamide Copolymers through an Amide or Hydrazone Bond", MOLECULAR PHARMACEUTICS, vol. 7, no. 4, 2010, pages 1027 - 1040, XP008160783, DOI: 10.1021/mp100121g
ETRYCH,T. ET AL.: "Polymer conjugates of doxorubicin bound through an amide and hydrazone bond: Impact of the carrier structure onto synergistic action in the treatment of solid tumours", EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 58, 2014, pages 1 - 12, XP028650882, DOI: 10.1016/j.ejps.2014.02.016
FILIPPOV, K.S. ET AL.: "Macromolecular HPMA-Based Nanoparticles with Cholesterol for Solid-Tumor Targeting: Detailed Study of the Inner Structure of a Highly Efficient Drug Delivery System", BIOMACROMOLECULES, vol. 13, 2012, pages 2594 - 2604, XP055710962
RIHOVA,B. ET AL.: "Synergistic Action of Doxorubicin Bound to the Polymeric Carrier Based on N-(2-Hydroxypropyl)methacrylamide Copolymers through an Amide or Hydrazone Bond", MOLECULAR PHARMACEUTICS, vol. 7, no. 4, 2010, pages 1027 - 1040, XP008160783, DOI: 10.1021/mp100121g
ETRYCH,T. ET AL.: "Polymer conjugates of doxorubicin bound through an amide and hydrazone bond: Impact of the carrier structure onto synergistic action in the treatment of solid tumours", EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 58, 2014, pages 1 - 12, XP028650882, DOI: 10.1016/j.ejps.2014.02.016
FILIPPOV, K.S. ET AL.: "Macromolecular HPMA-Based Nanoparticles with Cholesterol for Solid-Tumor Targeting: Detailed Study of the Inner Structure of a Highly Efficient Drug Delivery System", BIOMACROMOLECULES, vol. 13, 2012, pages 2594 - 2604, XP055710962
Attorney, Agent or Firm:
TAKASHIMA, Hajime (JP)
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