METHOD FOR SCREENING TARGETING DDS PREPARATION

• Main Authors: SUZUKI, MANABU, KATO, MASAO, TABATA, TOMOYUKI, SATO, HARUYA, TAKAHARA, YOSHIYUKI, YUGIYAMA, YUICHI, HAYASHI, EIKO, TANAKA, YASUHIRO
• Format: Patent
• Language: English; French; German
• Published: 22.05.2002
• Edition: 7
• Subjects: CHEMISTRY; DERIVATIVES THEREOF; HUMAN NECESSITIES; HYGIENE; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; MEASURING; MEDICAL OR VETERINARY SCIENCE; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PHYSICS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SUGARS; TESTING

A method for screening an optimized ligand, which can avoid the internalization thereof in cell, with the guidance of a characteristic of the ligand of being capable of accumulating specifically in a target tissue by, after systemic administration, collecting the ligand around a specific receptor (ASGP-R, etc.) on the cell membrane due to the binding affinity to the receptor so as to minimize the internalization mediated by the receptor; and tissue-targeting DDS preparations which can be accumulated and retained around a receptor by binding an optimum ligand to a physiologically active protein via a covalent bond. Namely, a method for screening a ligand having a binding affinity to a protein such as a specific receptor or antigen present on the cell membrane of a target tissue or a substance modified with this ligand with the guidance of the ability to avoid the internalization mediated by the binding to the receptor, for example, the ratio of the constant of dissociation rate constant (Koff) to the constant of internalization rate constant (Kint) to the receptor (i.e., Koff/Kint) and the strength of the binding affinity; and medicinal preparations which can be accumulated and retained around a receptor, composed of the above-described ligand and a physiologically active protein or a low-molecular weight chemical bonded thereto.