Nippon Zoki Pharmaceutical Co., Ltd.

Kaoru Okamoto

Takayuki Kotani

Akira Ishii

Taisuke Hasegawa

Naoharu Nishimura

Yasuhiro Nagaki

Teikichi Kurosaki

Kiyoshi Fukuda

Akio Namimatsu

Toshio Goto

Shinji Morita

Hiroki Muramoto

Masaki Hamada

Conventional I-form crystals of 5-hydroxy-1-methylhydantoin contain, remaining therein in a considerable amount, the organic solvent used in a purification step. In contrast, in II-form crystals, the amount of the organic solvent remaining therein is smaller than the detection limit. Namely, the II-form crystals contain substantially no residual organic solvent. The novel II-form crystals of 5-hydroxy-1-methylhydantoin obtained through recrystallization from water not only contain substantially no residual organic solvent, but also have a high bulk density and are hence advantageous for pharmaceutical preparation. They further have properties advantageous for production, such as low adhesion. The crystals are significantly useful as a material for medicines required to have high safety, such as drugs for renal insufficiency.

Crystal form of 5-hydroxy-1-methylhydantoin

Crystal form of 5-hydroxy-1-methylimidazolidin-2,4-dione

Carboxyalkyl heterocyclic derivatives, pharmaceutically acceptable salts thereof, and therapeutic agents containing said compounds as an effective component are useful pharmaceuticals for the treatment of diabetic complications such as diabetic neuropathy, diabetic cataracts and retinopathy, diabetic nephropathy, diabetic dermopathy, and other diabetic microangiopathy. The compounds of the present invention are represented by the following general formula (A): ##STR1## The compounds of the present invention exhibit excellent inhibitory action towards aldose reductase with a high enzyme selectivity. Accordingly, they are useful as drugs for the therapy and prevention of various types of diabetic complications without substantially inhibiting aldehyde reductase.

Carboxyalkyl heterocyclic derivatives

Benzothiazole derivatives, pharmaceutically acceptable salts thereof, and therapeutic agents containing said compounds as an effective component possess a lipid lowering activity and are useful pharmaceuticals for the treatment of hyperlipemia. The lipid lowering agents are of the formula: ##STR1## wherein R.sub.1 is halogen, trifluoromethyl, acetamido or --OX.sub.1 ; X.sub.1 is hydrogen, alkyl or acyl; R.sub.2 is hydrogen, halogen, alkyl, hydroxyalkyl, trifluoromethyl, nitro, amino which may be substituted with alkyl or acyl, carboxy which may be esterified with alkyl, or --OX.sub.2 ; X.sub.2 is hydrogen, alkyl, acyl, carboxyalkyl which may be esterified with alkyl; n is an integer from 1 to 3 denoting the number of substituents R.sub.2 ; and plural R.sub.2 may be the same or different when n is 2 or 3; with the proviso that R.sub.1 is a group other than halogen when R.sub.2 is hydrogen. The benzothiazole derivatives and their pharmaceutically acceptable salts significantly decrease cholesterol, triglyceride and low-density lipoprotein in blood.

Benzothiazole derivatives

Parabanic acid derivatives, pharmaceutically acceptable salts thereof, and therapeutic agents containing said compounds as an effective component are useful pharmaceuticals for the treatment of diabetic complications such as diabetic neuropathy, diabetic cataracts and retinopathy, diabetic nephropathy, diabetic dermopathy, and other diabetic microangiopathy. The compounds of the present invention are represented by the following general formula (I): ##STR1## wherein R is hydrogen, lower alkyl or benzyl; X is substituted phenyl, optionally substituted benzothiazolyl, optionally substituted naphthyl, optionally substituted pyridyl, anthraquinonyl, phthalimide, or thienyl; and n is an integer from 1 to 3. The compounds of the present invention exhibit excellent inhibitory action towards aldose reductase with a high enzyme selectivity. Accordingly, they are useful as drugs for the therapy and prevention of various types of diabetic complications without substantially inhibitory aldehyde reductase.

Parabanic acid derivatives

The present invention provides purine derivatives and pharmaceutically acceptable salts thereof which exhibit an inhibitory action towards nasal mucus secretion and are useful as pharmaceuticals for treatment of nasal secretion and rhinitis. The purine derivatives are represented by the following general formula: ##STR1## wherein R is alkyl or cycloalkyl, or optionally-substituted phenyl or phenylalkyl; R' is hydrogen or --COOX; and X is alkyl, alkenyl, alkoxyalkyl, phenyl or phenylalkyl. The compounds are useful as therapeutic and preventive agents for various types of rhinitis accompanied by acceleration of nasal mucus secretion and by the sneezing reflex such as allergic rhinitis. The compounds may be administered orally and exhibit low toxicity, little side effect and high safety. Accordingly, continuous long term administration of the pharmaceutical compositions may be performed for highly effective treatment of rhinitis.

Purine-2,8-diones and pharmaceutically acceptable salts thereof

Sialic acid compounds of formula ##STR1## wherein X is hydrogen, a lower alkyl group or benzyl, Y is hydrogen or acetyl, Ac is acetyl, and the wavy line represents that the compound of the formula (I) includes both a .alpha.-anomer and .beta.-anomer, have excellent chemical and enzymatical stability and are useful in the treatment of central or peripheral nervous diseases.

Sialic acid derivatives

The present invention relates to novel luciferin derivatives and salts thereof represented by the following formula (I), which are useful as chemiluminescence reagents. ##STR1## wherein X is hydrogen, an amino-protecting group, R--, R--CO--, R--SO.sub.2 --, R--NHCO-- or R--NHCS--, R is a fluorescence probe, and n represents an integer of 1 to 4.

Luciferin derivatives

Heterocyclic compounds comprising the formula (I): ##STR1## wherein: R.sub.1, R.sub.2, R.sub.4 and R.sub.5 each are hydrogen or a lower alkyl group;

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Hyogo, Japan

Kaoru Okamoto