Nippon Kayaku Kabushiki Kaisha

Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Keiichirou Yamamoto

Akira Masuda

Masatoshi Abe

Masayuki Kitagawa

Kazutoshi Takashio

Takeshi Onda

Yuki Kobayashi

Tsuyoshi Fukuda

Masaharu Nakamura

Masashi Nagai

Keizou Ishikawa

Kan Saiga

Chieko Seno

Yuki Kawano

Ken Yamakawa

Manami Okazaki

Hiroko Yamazaki

Dai Kawamura

Chihiro Nishimura

Hiroko Mashiba

Yuichi Akatsu

Nao Yoneki

Ayaka Mochizuki

Akihiro Sekiguchi

Kana Mizunuma

Junpei Konno

Masao Shibata

Dai Kurihara

Chisato Tomiyama

Yasushi Yoneta

Provided is a polymeric micelle type DDS preparation that may efficiently exhibit pharmacological activity effects by enhancing migration characteristics, penetrability, and retention characteristics toward a diseased target tissue such as a tumor tissue or an inflammation-affected tissue, and thereby enhancing the action of a pharmacologically active substance. Disclosed is a block copolymer (A) having a hydrophilic polymer segment linked to a hydrophobic polymer segment, the hydrophilic polymer segment containing a polyethylene glycol chain, and the hydrophobic polymer segment containing a polyamino acid chain having a hydrophobic substituent in a side chain, wherein the hydrophilic polymer segment has a target binding site bonded thereto, and the main chain polymer combining the polyethylene glycol chain and the polyamino acid chain has a molecular weight of not less than 2 kilodaltons and not more than 10 kilodaltons.

Active-targeting-type polymer derivative, composition containing said polymer derivative, and uses of said polymer derivative and said composition

An object of the invention is to obtain a preparation which shows enhanced effectiveness and safety compared to tacrolimus, has the concentration in blood maintained at a constant level without individual differences, whereby the control of the amount of administration depending on the blood kinetics (blood trough concentration) becomes unnecessary. The present invention relates to a polymeric derivative of tacrolimus, in which a polyethylene glycol segment and an alcoholic hydroxy group of tacrolimus are bonded to side-chain carboxy groups of a polyaspartic acid derivative.

Polymer derivative of macrolide immunosuppressant

Provided are a block copolymer having an enhanced effect of imaging the interior of a tumor compared to known block copolymers and imaging probes using the known block copolymers; and an imaging probe using the block copolymer. Specifically, for the purpose of enhancing penetrability into a diseased target tissue and efficiently enhancing an imaging effect compared to known block copolymers and imaging probes using the known block copolymers, disclosed is a block copolymer in which a hydrophilic polymer segment containing a polyethylene glycol chain is linked to a hydrophobic polymer segment containing a polyamino acid chain having a signal group and optionally a hydrophobic substituent in a side chain, wherein the main chain polymer combining the polyethylene glycol chain and the polyamino acid chain has an average molecular weight of not less than 2 kDa and not more than 10 kDa, and the mass content percentage of the signal group and the optional hydrophobic substituent is not less than 5% by mass and not more than 50% by mass; and also disclosed is a composition including the block copolymer.

Polymer derivatives, and novel polymer derivative imaging probe using same

A physiologically active substance-conjugated block copolymer having enhanced efficacy and/or safety is provided by enhancing the property of penetrating into a target diseased tissue and/or enhancing excretability, compared to known physiologically active substance-conjugated block copolymer, and suppressing sensitization of the physiologically active substance to normal tissues other than a target diseased tissue. Disclosed is a block copolymer including a polyethylene glycol segment connected with a polyamino acid derivative segment conjugated with a physiologically active substance, in which the molecular weight of the block copolymer is from 2 kilodaltons to 15 kilodaltons, and the light scattering intensity of a 1 mg/mL aqueous solution of the physiologically active substance-conjugated block copolymer as measured with a laser light scattering photometer is at least twice or more the light scattering intensity of toluene.

Block copolymer conjugate of physiologically active substance

Providing a method for producing a compound represented by formula (1) from a compound represented by formula (2), by which the additive amount of an aryl (C1-C8) alkyl alcohol which may have a substituent and the amount of residual carboxyl groups of pAsp (polyaspartic acid) are controlled. A production method including obtaining a compound represented by formula (1) by allowing a compound represented by formula (2) to react with an aryl (C1-C8) alkyl alcohol which may have a substituent, and a carbodiimide-based compound in an amount of 2(x+y) equivalents or more relative to the amount of carboxyl groups in formula (2) (sum of x and y), in a solvent at 15&#xb0; C. to 30&#xb0; C. for 2 hours to 48 hours, is used.

Method for manufacturing block copolymer

[Problem]To provide a novel polymer derivative of a cytidine metabolic antagonist which allows release of a medicament irrespective of enzymes of the living body and is expected to have high therapeutic effects. [Solution] The polymer derivative of a cytidine metabolic antagonist in which a substituent represented by the general formula (I) or the general formula (II) [wherein Rand Reach independently represent a hydrogen atom or an optionally substituted (C1-C6)alkyl group, Rrepresents a hydrogen atom, an optionally substituted (C1-C40)alkyl group, an optionally substituted (C1-C40)aralkyl group, an optionally substituted aromatic group, an amino acid residue in which the carboxy group is protected, or an optionally substituted sugar residue, CX&#x2014;CY represents CH&#x2014;CH or C&#x2550;C (double bond), and A represents the residue of the cytidine metabolic antagonist except the amino group at the position 4] is bonded to the side-chain carboxy group of a block copolymer of a polyethylene-glycol structural moiety and a polymer having 10 or more carboxy groups.

Polymer derivative of cytidine metabolic antagonist

A novel podophyllotoxin derivative, which is capable of releasing a drug without depending on biological enzymes and can be expected to have an effective therapeutic effect and is soluble in water has been demanded. A polymer having a polyethyleneglycol structural unit and two or more succinic monoamide structural units, particularly a polymer conjugate of a podophyllotoxin in which a carboxylic acid group of polyethyleneglycol/polyaspartic acid copolymer and a hydroxyl group of podophyllotoxin and linked via an ester bond is provided.

High-molecular weight conjugate of podophyllotoxins

A derivative of a cytidine metabolic antagonist which can exert a high therapeutic effect at a low dose. A polymeric derivative of a cytidine metabolic antagonist which comprises a polymeric compound having a polyethylene glycol moiety and a polymer moiety having a carboxyl group in a side chain and a cytidine metabolic antagonist, which has such a structure that the carboxyl group in the side chain of the polymeric compound and an amino group in the cytidine metabolic antagonist are bound together to form an amide bond.

Polymeric derivative of cytidine metabolic antagonist

A method for preparing a compound represented by the following general formula (5)   A method for preparing an optically active intermediate of sulphostin or an analogue thereof, which is an optically active amine salt of an optically active compound represented by the following general formula (8) where n is integer of 0 to 3; Y represents protecting group for the amino group; and each configuration at C* and P* may be the same or different and indicates S or R, the method including reacting a compound represented by the following general formula (7) where n and Y are as described above; and the configuration of C* indicates either of S or R, with an optically active amine, and resolving the formed diastereomeric salt by fractional crystallization.

Method for preparing sulphostin and analogue thereof or preparation intermediate thereof

There are disclosed a novel &#x3b1;-amino-N-(diaminophosphinyl)lactam derivative represented by general formula (1): wherein, for example, A is a hydrogen atom or a substituent such as a lower alkyl group or the like; W, X, Y and Z are independently a hydrogen atom or a substituent such as a lower alkyl group, aryl group, arylacyl group, arylaminocarbonyl group or the like; and Q is &#x2014;(CH)&#x2014; wherein n is 0 to 3, or its salt, and a therapeutic agent and a prophylactic agent for myelosuppression, a therapeutic agent for infectious diseases, an agent for increasing the number of leukocytes and a dipeptidyl peptidase IV inhibitor which comprise the above-mentioned derivative or salt thereof as an active ingredient.

&#x3b1;-Amino-N-(diaminophosphinyl)lactam derivatives

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Tokyo, Japan

Keiichirou Yamamoto