Toyo Jozo Kabushiki Kaisha

Toyo Jozo Company, Ltd.

Toyo Yozo Company, Ltd.

Satoshi Yaginuma

Naoki Muto

Tadashiro Fujii

Akira Asahi

Masaki Takada

Tetsu Saito

Mitsuo Hayashi

Masatoshi Tsujino

Yukio Suzuki

Masao Yaso

Masaru Otani

Kiyofumi Fukukawa

Kouichi Kuno

Motoshi Shoda

Takao Hirano

Kenya Ishizawa

Masashi Awata

Tooru Ueda

Kenji Kinoshita

Atsuki Morishita

An aldose reductase inhibitor, comprising a compound of the formula (I) ##STR1## or a pharmaceutically acceptable salt thereof as the effective component, in which R is lower alkyl or cyclohexylmethyl and n is 2 or 3. The compounds of formula (I) and salts thereof according to the invention exhibit a superior aldose reductase inhibiting activity with simultaneous high stability, so that they are useful for the prevention and therapy of diabetic complications.

Aldose reductase inhibitor

An aldose reductase inhibitor, comprising a compound of the formula ##STR1## or a pharmaceutically acceptable salt thereof as the effective component, in which R denotes an alkyl of C.sub.1-12, ##STR2## wherein X.sub.1 and X.sub.2 are same or different and are hydrogen or halogen, cyclohexylmethyl, cyclohexyl, tetra-hydro-2H-pyran-1-yl-methyl, carboxy-lower alkyl or cyclo-lower alkyl and n is 2 or 3. These compounds exhibit a superior aldose reductase inhibiting activity with simultaneous high stability, and are for use in the prevention and therapy of diabetic complications.

Biphenyl-5,5'-bis-alkanoic acid derivatives, their production and aldose

A antibiotic L53-18A and a pharmaceutically acceptable salt thereof which are useful for treatment of bacterial inventions are obtained by culturing, for example, Saccharopolyspora sp. L53-18 (FERM BP 2231) in a medium and the antibiotic accumulated therein is collected.

Antibiotic L53-18A and process for preparation thereof

A compound of the formula ##STR1## wherein R is .beta.-D-glucopyranosyl, .beta.-D-galactopyranosyl, 6'-O-acetyl-.beta.-D-glucopyranosy or 6'-O-acetyl-.beta.-D-galactopyranosyl, or a pharmaceutically acceptable salt thereof, has bronchodilator, cardiac activity, smooth muscle relaxant activity and hormone excretion stimulant activity. It can be produced by culturing a microorganism belonging to the genus Nodulisporium and adapted to produce the compound in a culture medium, and isolating the produced compound from the cultured medium. The microorganism can be Nodulisporium sp. M5220 FERM P-8133. The compounds have inhibitory activity on cyclic-adenosine-3',5'-monophosphate phosphodiesterase.

Physiologically active substance TPI and production thereof

A physiologically-active novel substance 'aldostatin' having an estimated molecular formula of C.sub.20 H.sub.20 N.sub.2 O.sub.8 is produced by culturing an aldostatin-producing microorganism of the Pseudeurotium, for example, the Pseudeurotium zonatum M4109 strain. Aldostatin inhibits the aldose reductase activity and as a consequence, avoids abnormal accumulation of sorbitol, galactitol, etc. It is therefore effective for the treatment of chronic complications such as cataract, retinopathy and neuropathy caused by diabetes renalis.

Physiologically-active novel substance 'Aldostatin' and production

A substance is provided which has strong enzyme inhibitory activity against thiol proteases such as papain, ficin, bromelain, etc. and which is represented by the following formula: ##STR1## (wherein R is a hydrogen atom or a hydroxyl group), its pharmaceutically acceptable salt or hydrate.

Enzyme Inhibiting substance

Neplanocin A derivatives of the formula ##STR1## wherein R.sub.1 and R.sub.2 are hydrogen or benzoyl, R.sub.3 is hydrogen or OR.sub.8, R.sub.5 is hydrogen or acetyl, R.sub.6 is hydrogen, acetyl or benzoyl, when R.sub.3 is hydrogen, R.sub.4 is hydrogen or halogen, hydroxy, acetoxy, acetylthio, amino or azide, and when R.sub.3 is OR.sub.8, R.sub.4 is hydrogen, R.sub.8 is hydrogen or acetyl, or R.sub.8 and R.sub.5 together form benzylidene, and at least one of R.sub.8, R.sub.5 and R.sub.6 is other than hydrogen. The compounds of the present invention have inhibitory action for the growth of L 5178 Y cells and have the same or superior activity as neplanocin A, and hence are useful as antitumor agents.

Neplanocin A derivatives

Antibiotic neplanocin A of the formula ##STR1## is produced by culturing Ampullariella sp. A 11079 FERM-P No. 4494 in a nutrient medium and then separating the neplanocin A thus produced from the culture medium.

Antibiotic neplanocin A

Neplanocin-B and -F of the formula ##STR1## in which Y is oxygen or a valence bond, are produced by culturing Ampullariella sp. A 11079 FERM-P No. 4494 in a nutrient medium and then separating the neplanocin-B and -F thus produced from the culture medium.

Neplanocin-B and -F

A group of sulfur-containing antibiotics, planothiocin-A, -B, -C, -D, -E, -F and -G, are produced by culturing Actinoplanes sp. A12526 in a nutrient medium, and separating the thus-produced planothiocins therefrom. The novel antibiotics have utility in therapeutic or prophylactic antibacterial compositions or feed additives for livestock, poultry or fish.

Growing community of inventors

Shizuoka, Japan

Satoshi Yaginuma