Daiichi Pharmaceutical Co., Ltd.

Other

Daiichi Sankyo Company, Limited

Drug Delivery System Institute, Ltd.

Hiroshi Susaki

Kazuhiro Inoue

Masahiro Ikeda

Hiroshi Kuga

Eiji Kumazawa

Akiko Togo

Makoto Takemura

Masashi Hasegawa

Yuichi Ochiai

Toshiyuki Nishi

Yumi Nakamoto

Takeshi Hayano

Tatsuya Nishi

Ryoko Kitazawa

Yoshinobu Shiose

Hiroko Koda

Youhei Ishida

A compound of the general formula (I): [wherein, Rrepresents a halogen atom, or the like, Rrepresents a hydrogen atom, or the like, Rand R, each independently, represent a hydrogen atom, a Calkyl group, or the like, Rrepresents a hydrogen atom, a halogen atom, or the like, Rrepresents a hydrogen atom, a halogen atom, or the like, Rand R, each independently, represent a hydrogen atom, a halogen atom, or the like, Rand R, each independently, represent a hydrogen atom, a Calkyl group, Rand R, each independently, represent a hydrogen atom, a Calkyl group, or the like, X represents an oxygen atom, a group &#x2014;CH&#x2014;, or the like, Y represents a nitrogen atom, a group &#x2550;CH&#x2014;, or the like, and Z represents a nitrogen atom, or the like] or a pharmacologically acceptable salt thereof, which has an excellent suppressive action on platelet aggregation, and is useful for prevention and/or treatment of thromboembolism.

3-(biaryloxy)propionic acid derivatives for prevention and/or treatment of thromboembolic diseases

A DDS compound comprising a carboxy(C)alkyldextran polyalcohol modified with a saccharide compound and a residue of drug compound bound to the carboxy(C)alkyldextran polyalcohol, and a method for measuring a DDS compound in which a polymer carrier and a residue of drug compound are bound to each other by means of a spacer comprising 2 to 8 amino acids linked by peptide bond(s), which comprises the steps of treating the DDS compound with a peptidase, and measuring the resulting hydrolysate.

DDS compound and method for measurement thereof

A drug complex characterized in that a residue of a drug compound such as antineoplastic agents and a carboxy(C)alkyldextran polyalcohol obtained by treating a dextran under conditions that enable substantially complete polyalcoholization are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Said complex is characterized in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.

Drug complex

A drug complex useful as a DDS compound, which is represented by the following formula: A-R&mdash;NH&mdash;Y&mdash;CH &mdash;O&mdash;CO-Q, wherein A is a polymer as a drug carrier; R is a spacer, wherein the spacer is an amino acid or an oligopeptide comprising 2 to 8 amino acids; Y is phenylene group which may be substituted; and Q is a residue of a drug compound such as antineoplastic agents. The complex provides rapid and site-selective release of a drug compound such as antineoplastic or anti-inflammatory agents and surely exhibits expected efficacy.

Drug complex and drug delivery system

A drug complex characterized in that a residue of a drug compound such as antineoplastic agents and a carboxy(C )alkyldextran polyalcohol obtained by treating a dextran under conditions that enable substantially complete polyalcoholization are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Said complex is characterized-in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.

Drug complexes

A method for preparing a drug complex in which a polysaccharide derivative having carboxyl groups and a residue of a drug compound are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids, or a drug complex in which a polysaccharide derivative having carboxyl groups and a residue of a drug compound are bound to each other without the spacer, characterized in that an organic amine salt of the polysaccharide derivative having carboxyl groups is reacted with the drug compound or the spacer bound to the drug compound in a non-aqueous system. The reaction between the polysaccharide derivative having carboxyl groups and the drug compound bound with the spacer or the like can be carried out in high yields, and when a drug compound having a lactone ring is subjected to the reaction, side reactions can be reduced.

Process for producing drug complexes

Carbapenem derivatives of formula (I): ##STR1## wherein (a) R.sub.1 is a hydrogen atom, an alkyl group of from 1 to 6 carbon atoms, a hydroxy-lower alkyl group or a protected hydroxy-lower alkyl group of from 1 to 6 carbon atoms in its alkyl moiety, (b) COOR.sub.2 is a carboxyl group, a carboxylate anion or a protected carboxyl group, (c) R.sub.3 is an alkyl group of from 1 to 6 carbon atoms and (d) R.sub.4 is a substituted or unsubstituted heterobicyclic group of formula (II): ##STR2## in which the partial structure ##STR3## is a 5- or 6-membered, saturated or unsaturated, nitrogen-containing heterocycle containing 1 to 4 hereto atoms each selected from the group consisting of oxygen, sulfur and nitrogen, at least one hetero atom being nitrogen, and is which R.sub.5 and R.sub.6 each is a hydrogen atom or an appropriate substituent, any isomeric form thereof, and pharmacologically acceptable salts thereof are potent and stable antimicrobial agents.

Carbapenem derivatives

Growing community of inventors

Tokyo, Japan

Hiroshi Susaki