Nanocarrier Co., Ltd.

The University of Tokyo

Riken Corporation

National Cancer Center

Tokyo Medical and Dental University

Nonocarrier Co., Ltd.

Yasuki Kato

Kazunori Kataoka

Nobuhiro Nishiyama

Atsushi Ishii

Kanjiro Miyata

Hiroyasu Takemoto

Shigeto Fukushima

Mitsunori Harada

Kensuke Osada

Hiroyuki Chaya

Sumiyo Watanabe

Miho Ohuchi

Akira Matsumoto

Takehiko Ishii

Hiroyuki Saito

Takahiro Nomoto

Yasuhiro Matsumura

Masahiro Yasunaga

Yutaka Miura

Shino Manabe

HyunJin Kim

Yu Matsumoto

Mitsuru Naito

Ryo Tsumura

Katsutoshi Kobayashi

Tatsuyuki Hayashi

Yuko Amano

Yoshiyuki Yamamoto

Ronald James Christie

Ryosuke Tanaka

Ryuta Sato

Yoshikatsu Koga

Kanjiiro Miyata

A unit structure-type pharmaceutical composition includes a single nucleic acid, such as an antisense nucleic acid, electrostatically bound to a single block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charges of the nucleic acid are counterbalanced, at least substantially, by the positive charges of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment. The block copolymer thereby improves the blood retention capability of the nucleic acids.

Unit structure-type pharmaceutical composition for nucleic acid delivery

Monoclonal antibodies against human and mouse tissue factor, and fragments thereof, are disclosed, as well as pharmaceutical compositions and compositions for drug delivery containing the same. Therapeutic methods using the same are also disclosed.

Anti-tissue factor monoclonal antibody

A unit structure-type pharmaceutical composition includes at least one nucleic acid, such as siRNA, electrostatically bound to at least one block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charge(s) of the nucleic acid are counterbalanced, at least substantially, by the positive charge(s) of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment(s). The at least one block copolymer thereby improves the blood retention capability of the nucleic acid(s).

The present invention provides a particulate pharmaceutical composition which has improved drug encapsulation stability and is suitable for a drug delivery system. The particulate pharmaceutical compositioncontains: a plurality of block copolymer unitarranged radially, each of which has a hydrophobic polymer-chain segment, which is arranged radially inside, and a hydrophilic polymer-chain segment, which is arranged radially outside; a drug, which includes a biomacromolecule; and a charged lipid, which has an electrical charge opposite to that of the drug; wherein the charged lipidis being attracted to the hydrophobic polymer-chain segment, and the drugis positioned radially inside the hydrophobic polymer-chain segment. The pharmaceutical compositioncan effectively prevent the drugfrom disengaging from the particle.

Particulate pharmaceutical composition

A pharmaceutical composition includes a block copolymer having a hydrophilic segment, a hydrophobic segment, and a boronic acid compound bound to a side chain of the hydrophobic segment via a linker moiety that includes a heterocyclic structure. The heterocyclic structure contains a cyclic skeleton that includes a boron atom of the boronic acid compound, one or two atom(s) X bound to the boron atom and selected from an oxygen atom and a nitrogen atom, and one or two carbon atom(s) (respectively) bound to the atom(s) X. The block copolymer further includes at least one organic group bound to the carbon atom(s). The organic group(s) contain(s) an aromatic group or cyclic alkyl group that sterically protects a boronic acid ester bond and/or a boron amide bond resulting from bonding between the boron atom and the atom(s) X.

Pharmaceutical composition containing a block copolymer bound to a boronic acid compound

The present invention provides a particulate composition containing: block copolymer units being arranged radially with hydrophobic polymer-chain segments radially inside and hydrophilic polymer-chain segments radially outside; and a charged lipid which carries a charge opposite to the charge of a drug to be encapsulated, the charged lipid being attracted to the hydrophobic polymer-chain segment. In this particulate composition, the drug is retained within the particle via electrostatic binding with the charged lipid, whereby the outer surface of the particle is prevented from being charged to attract a substance which has a charge opposite to that of the charged lipid.

Particulate composition and pharmaceutical composition containing the same

A composition of matter for use in encapsulating a drug is expressed by formula (1) or formula (2): wherein Rand Rare each independently a hydrogen atom or a substituted or unsubstituted, linear or branched alkyl group having 1 to 12 carbon atoms; A is a hydrophilic polymer chain; Land Lare each a linking group; B is a cation-containing group; Ris a side chain of an amino acid; z is an integer of 5 to 500; x is an integer of 40% or more of z; y is 0 or a positive integer; z-x-y is 0 or a positive integer; p is an integer of 1 to 10; and q is an integer of 1 to 10.

Particle composition and pharmaceutical composition using particle composition

A block copolymer includes a polyamino acid chain segment and a hydrophilic polymer chain segment. The polyamino acid chain segment includes at least one amino acid residue having a side chain that contains a cationic group and at least one amino acid residue having a side chain that contains a substituted phenylboronic acid group. In the substituted phenylboronic acid group, at least one hydrogen of the phenyl ring is substituted so that the phenylboronic acid group has a pKa of less than 8. Such a block copolymer serves as a carrier that simultaneously imparts stability to a biotechnology-based drug in blood and provides suitable drug-releasing properties of the drug at an affected area.

Block copolymer having phenylboronic acid group introduced therein, and use thereof

The present invention provides a cationic polyamino acid suitable for a carrier that can form a stable complex with a nucleic acid under a physiological condition and release the nucleic acid in cells suitably. The cationic polyamino acid can associate with a nucleic acid and includes a cationic amino acid residue having a cationic group in a side chain and a hydrophobic amino acid residue having a hydrophobic group in a side chain. The cationic polyamino acid includes 1 to 20 units of the cationic amino acid residue and is represented by the following formula (1). The meaning of each symbol in the formula is as shown in the description.

Short-chain cationic polyamino acid and use thereof

The present invention provides an active targeting polymer micelle encapsulating a drug, preventing an inappropriate release of a drug which may damage a normal cell. A polymer micelleincludes a backbone polymer unitthat has a target binding siteand a backbone polymer unitthat has a drugand is free from the target binding site, such polymer unitsandbeing disposed in a radial arrangement in a state where the target binding siteis directed outward and the drugis directed inward, in which: i) when the micelle is bound to a targetwhile maintaining the radial arrangement, the micelle is taken up into a cellsupplying the targetthrough endocytosis, and the drugis released into the cellby collapse of the radial arrangement in the cell; and ii) when the radial arrangement collapses in bloodbefore the micelle is bound to a target, the unitis excreted through metabolism, to thereby prevent a normal cell from being damaged by the drug

Active targeting polymer micelle encapsulating drug, and pharmaceutical composition

A pharmaceutical composition containing a drug encapsulated in a polymer micelle composition containing a first block copolymer having affinity with HDL and a second block copolymer having affinity with a lipoprotein excluding HDL, each block copolymer having a hydrophobic polymer chain segment and a hydrophilic polymer chain segment such that a plurality of block copolymers arrange radially with the hydrophobic segments directed inward and the hydrophilic segments directed outward. In the composition, a detachment of the first block copolymer is induced by HDL adhesion which forms a gap and promotes the release of a drug encapsulated, while the second block copolymer excluding an affinity with HDL controls a release speed of the drug encapsulated.

Sustained-release polymer micelle disruptable by HDL

The present invention relates to a block copolymer containing an uncharged hydrophilic polymer chain block and a cationic polyamino acid chain block, wherein the hydrophilic polymer chain block is covalently bound to one end of the main chain of the polyamino acid chain block, and the hydrophobic group is covalently bound to the side chains of not less than 10% and not greater than 70% of amino acid repeating units in the polyamino acid chain block. This block copolymer forms a stable aggregate with siRNA, a small-molecule nucleic acid, under a physiological condition.

Copolymer including uncharged hydrophilic block and cationic polyamino acid block having hydrophobic group in part of side chains, and use thereof

The invention provides a physiologically active polypeptide- or protein-encapsulating polymer micelle composition derived from a block copolymer comprising hydrophilic segments and hydrophobic segments.

Growing community of inventors

Kashiwa, Japan

Yasuki Kato