Takeda Chemical Industries, Inc.

Toshihiro Ishiguro

Ikuo Nogami

Takamasa Yamaguchi

Masahide Oka

Akira Nohara

Yasushi Sanno

Hiroaki Nomura

Takeshi Fugono

Kiyoshi Ukawa

Yasuhiko Kawano

Yoshiaki Uda

Takahiro Saraie

Yasushi Nakagawa

Takako Yamauchi

Kenya Kawashima

A composition is disclosed comprising a water-insoluble or slightly water-soluble compound and a branched cyclodextrin-carboxylic acid. The branched cyclodextrin-carboxylic acid significantly increases the water-solubility of the compound. Also disclosed is a method of enhancing water-solubility of the compound.

Composition containing a water-insoluble or slightly water-soluble

A process for producing a saccharide carboxylic acid or a salt thereof characterized in that a microorganism belonging to the genus Pseudogluconobacter and capable of oxidizing a hydroxymethyl group and/or hemiacetal hydroxyl-associated carbon atom to a carboxyl group, or an artifact derived from the microorganism, is permitted to act on a hydroxymethyl and/or hemiacetal hydroxyl-containing saccharide or saccharide derivative to produce and accumulate the corresponding carboxylic acid and the carboxylic acid so accumulated is harvested and novel saccharide carboxylic acids produced by the above production method, and by the process, from a broad range of saccharides, saccharic acids having carboxyl groups derived from hydroxymethyl and/or hemiacetal OH groups can be produced with high selectivity and in good yield, the resultant saccharide acids are resistant to enzymatic degradation and have improved water solubility, among other characteristics.

Production of saccharide carboxylic acids

Saccharide carboxylic acids of glycosides

Novel 1-azaxanthone-3-carboxylic acid derivatives, which are shown by the following formula (I) ##STR1## wherein R is hydrogen, alkyl, alkoxy or halogen; R.sub.1 and R.sub.2 are the same or different and each is hydrogen, alkyl or alkenyl; and m is 1 or 2; and their physiologically acceptable salts, are usable as effective medicines for preventing and/or treating allergic diseases. The compound of the formula (I) can be produced by reacting a compound of the formula: ##STR2## wherein R and m have the same meaning as defined above; R.sub.3 is carboxyl or group which is convertible into carboxyl through hydrolysis; X is alkyl phosphate radical or halogen, with a compound of the formula: ##STR3## wherein R.sub.1 and R.sub.2 have the same meaning as defined above, or its salt, and conducting hydrolysis, if necessary.

1-Azaxanthone-3-carboxylic acids and their production

Novel 3-(tetrazol-5-yl)-1-azaxanthone and its derivatives, which are shown by the following formula ##STR1## wherein R.sub.1 is hydrogen, amino or hydroxyl; R.sub.2 is alkyl, alkoxy, halogen, nitro, carboxyl, hydroxyl, butadienylene (--CH.dbd.CH--CH.dbd.CH--) which forms a benzene ring with any adjacent carbon atoms or amino group which may be unsubstituted or substituted by at least one alkyl; and m is 0, 1 or 2; and their physiologically acceptable salts, are usable as effective medicines for preventing and/or treating allergic diseases.

3-(Tetrazol-5-yl)-1-azaxanthones

Novel N-benzylpiperazine derivatives of the general formula ##STR1## wherein R.sup.1 and R.sup.2 are same or different and each stands for a hydrogen atom or an acyl group; R.sup.3 stands for a hydrogen atom, a carbamoyl group, an acyl group which is unsubstituted or substituted by mercapto or morpholino, or an alkyl group which is unsubstituted or substituted by hydroxy, aryl or aminocarbonyl represented by the formula ##STR2## wherein each of R.sup.4 and R.sup.5 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms or a cyclohexyl group, or R.sup.4 and R.sup.5 form a morpholino or piperidino ring together with the nitrogen atom adjacent thereto, and X stands for a halogen atom, and pharmaceutically acceptable acid addition salts thereof. These compounds and salts thereof have respiratory tract fluid secretion stimulatory properties and are useful as medicines such as respiratory tract fluid secretion stimulators.

N-Benzylpiperazines

Novel N-benzylpiperazine derivatives of the general formula ##STR1## wherein R.sup.1 and R.sup.2 are same or different and each stands for a hydrogen atom or an acyl group; R.sup.3 stands for a hydrogen atom; a carbamoyl group, an acyl group which is unsubstituted or substituted by mercapto or morpholino, or an alkyl group which is unsubstituted or substituted by hydroxy, aryl or aminocarbonyl represented by the formula ##STR2## wherein each of R.sup.4 and R.sup.5 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms or a cyclohexyl group, or R.sup.4 and R.sup.5 form a morpholino or piperidino ring together with the nitrogen atom adjacent thereto, and X stands for a halogen atom, and pharmaceutically acceptable acid addition salts thereof. These compounds and salts thereof have respiratory tract fluid secretion stimulatory properties and are useful as medicines such as respiratory track fluid secretion stimulators.

Morpholinocarbonyl alkyl N-benzylpiperazines

The present invention relates to novel chromone derivatives having effective antiallergic action with low toxicity, which are shown by the following formula (I) ##STR1## wherein R is hydrogen or lower alkyl and A is ##STR2## (R' is hydrogen or lower alkyl) or ##STR3## and their physiologically acceptable salts.

Novel chromone derivatives

Novel cephalosporanic acid derivatives which are active against both Gram positive and Gram negative pathogenic bacteria, particularly Pseudomonas, and which have .alpha.-sulfoacylamino group at 7-position. A few examples of the compounds are 7-(.alpha.-sulfophenylacetamido)-cephalosporanic acid, 7-(.alpha.-sulfopropionamido)-cephalosporanic acid, 7-(.alpha.-sulfocapronamido)-cephalosporanic acid. They are prepared by condensing 7-aminocephalosporanic acid or salts thereof with .alpha.-sulfocarboxylic acid or functional derivatives thereof in the presence of a solvent at -2.degree. - 10.degree. C.

7-(.alpha.-SULFOACYLAMIDO) CEPHALOSPORANIC ACIDS

1,1-Dichloro-1a, 10b-dihydrodibenzo(b,f)cycloprop(d)azepine-6(1H)-carboxaldehyde is produced in good yield through a reaction between a compound of the general formula ##SPC1## Wherein R stands for hydrogen or formyl group and chloroform. Thus obtained product can be used as a valuable intermediate for synthesizing medicines and is further convertible to known drugs, e.g. 6-(3-dimethylamino)propyl)-1, 1a, 6, 10b-tetrahydrodibenzo(b,f)cycloprop(d)azepine.

Novel cephalosporanic acid derivatives which are active against both Gram positive and Gram negative pathogenic bacteria, particularly Pseudomonas, and which have an .alpha.-sulfoacylamino group at 7-position. A few examples of the compounds are 7-(.alpha.-sulfophenylacetamido)-cephalosporanic acid, 7-(.alpha.-sulfopropionamido)-cephalosporanic acid, 7-(.alpha.-sulfocapronamido)-cephalosporanic acid. They are prepared by condensing 7-aminocephalosporanic acid or salts thereof with .alpha.-sulfocarboxylic acid or functional derivatives thereof in the presence of a solvent at -2.degree. - 10.degree. C.

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Toyono-cho, Japan

Toshihiro Ishiguro