Chugai Seiyaku Kabushiki Kaisha

Tokyo Medical and Dental University

University of Washington

Tsuyoshi Shimoboji

Teruo Nakamura

Takashi Nakai

Tai Hirakura

Kenji Yasugi

Kazuo Hattori

Kazunari Akiyoshi

Tomoko Yasugi

Sei Kwang Hahn

Yoshihiro Tampo

Mika Sato

Allan Sachs Hoffman

Patrick S Stayton

Takashi Emura

Nobuyuki Morimoto

Noah Malmstadt

Sayan Chuanoi

Samarth Kulkarni

Hideyuki Togawa

The present invention provides a hyaluronic acid derivative containing a disaccharide unit represented by formula (I) or formula (I) and (II), and a complex containing the hyaluronic acid derivative and a drug.

Hyaluronic acid derivative having amino acid and steryl group introduced thereinto

The present invention provides hyaluronic acid derivatives including one or more of each of repeating units represented by the formulae (Ia), (Ib), and (Ic) in which certain cationic sites, certain hydrophobic sites, and certain hydrophilic sites have been introduced. In addition, the present invention provides complexes of the hyaluronic acid derivatives with a drug and pharmaceutical compositions including the hyaluronic acid derivatives, in particular, complexes of the hyaluronic acid derivatives with a drug.

Hyaluronic acid derivative modified with polyethylene glycol

The present invention provides hyaluronic acid derivatives into which a certain cationic group and a certain hydrophobic group are introduced, the hyaluronic acid derivatives including one or more repeating units represented by the formula (Ia) and one or more repeating units represented by the formula (Ib).

Hyaluronic acid derivatives into which cationic and hydrophobic groups are introduced

The present invention provides a water-soluble modified HA practically used as a drug carrier and a production method thereof. The present invention provides: a water-soluble modified hyaluronic acid, the residence time in blood of which is elongated to a practical level, which is produced by introducing a substituent into the carboxy group of the glucuronic acid of hyaluronic acid or a derivative thereof, via an amide bond, at a lower limit of an introduction ratio of 5 mole % or more, using a BOP condensing agent in an aprotic polar solvent; and a production method thereof. Moreover, by cross-linking the modified hyaluronic acid, the present invention provides a hyaluronic acid gel capable of extremely long drug sustained-release even at the same cross-linking functional group introduction ratio as that of the conventionally known gel.

Process for producing water-soluble hyaluronic acid modification

The present invention provides a hyaluronic acid derivative comprising disaccharide units of Formula (I), and a hyaluronic acid derivative/drug conjugate wherein one or more drugs are conjugated to the hyaluronic acid derivative.

Derivative of hyaluronic acid modified with amino-carboxylic acid

The present invention provides a composition comprising a hyaluronic acid derivative having a crosslinking group(s) and a hydrophilic polysaccharide derivative having a hydrophobic group(s), wherein the hyaluronic acid derivative having a crosslinking group(s) is prepared by crosslinkage formation reaction in hyaluronic acid or a derivative thereof having a crosslinkable group(s) in the presence of the hydrophilic polysaccharide derivative wherein the hydrophilic polysaccharide derivative may have a crosslinkable group(s).

Hybrid gel comprising chemically crosslinked hyaluronic acid derivative and  pharmaceutical composition comprising the same

The present invention provides a hydrophobic group-introduced hyaluronic acid derivative comprising at least one repeating unit represented by the formula (I): wherein R, R, R, R, Z, n, Ra, Y, and Xare as defined in the specification.

Hyaluronic acid derivative and pharmaceutical composition thereof

The present invention provides long-acting sustained-release formulations of drugs such as proteins or peptides, which are injectable, completely biodegradable and safe, as well as ensuring efficient encapsulation of the drugs such as proteins or peptides without inhibiting their biological activity. It is possible to achieve injectable sustained-release formulations that ensure efficient encapsulation and long-term sustained release of drugs such as proteins or peptides while retaining their biological activity, when a solution containing a drug and a polysaccharide derivative such as hyaluronic acid having a crosslinkable functional group(s) or a salt thereof is dehydrated in microparticulate form starting from a dilute state, where crosslinking proceeds slowly, to reach a concentration which facilitates crosslinking, to thereby cause crosslinking reaction during concentration, so that the drug is encapsulated into the crosslinked polysaccharide to give drug-carrying microparticles.

Crosslinked polysaccharide microparticles and method for their preparation

The present invention aims to provide completely biodegradable and biocompatible sustained-release carriers for proteins or peptides, which allow encapsulation of the proteins or peptides at high encapsulation rates without inhibiting their biological activity. The present invention provides a method for preparing a sustained-release carrier, wherein in a solution in the presence of a protein or a peptide, a hyaluronic acid derivative having an unsaturated bond(s) or a mercapto group(s) introduced into hyaluronic acid is chemically crosslinked with a mercapto group-containing compound or an unsaturated bond-containing compound, respectively, to give a hydrogel. The method of the present invention enables efficient encapsulation of proteins or peptides while retaining their biological activity.

Sustained release drug carrier

A hyaluronic acid modification product includes a polymer bonded to hyaluronic acid, the polymer being polylactic acid, polyglycolic acid or lactic acid-glycolic acid copolymer, providing a drug carrier which efficiently encapsulates low molecular weight drugs and provides sustained-release over a long term, control of blood residence, is well dispersible in an aqueous solution, and has excellent biocompatibility.

Hyaluronic acid modification products and drug carriers using them

Conjugates that include polymers that are reversibly self-associative in response to a stimulus and methods for using the conjugates.

Stimuli-responsive polymer devices

The present invention provides a safe hyaluronic acid base material that is suitable for use in practical hyaluronic acid pharmaceutical preparations capable of distribution at room temperature and having such a low viscosity that injection is easy. The hyaluronic acid pharmaceutical preparations can reside in a joint cavity for a prolonged period of time while exhibiting analgesic effects. More specfically, there is provide a hyaluronic acid modification product in which hyaluronic acid and/or a pharmaceutically acceptable salt thereof is bounded to a block polymer selected from PEO-PPO-PEO, PPO-PEO-PPO, PEO-PLGA-PEO, PLGA-PEO-PLGA, PEO-PLA-PEO and PLA-PEO-PLA. The hyaluronic acid modification product, despite capability of distribution at room temperature and ease in handling because of the low viscosity, can have its viscoelasticity rapidly increased after injection into a living body, so that it is highly useful in treatment of joint diseases, aid in surgical operation, repair of tissue, etc. as a main ingredient of novel and practical hyaluronic acid pharmaceutical preparations.

Growing community of inventors

Gotenba, Japan

Tsuyoshi Shimoboji