Takeda Chemical Industries, Inc.

Kyocera Corporation

Tachibana Textile Fabrics, Co., Ltd.

Fuji Sangyo Kaisha, Ltd.

Osami Aki

Akira Morimoto

Michihiko Ochiai

Taiiti Okada

Kenji Kawakita

Yoshihiro Matsushita

Masayoshi Matsuoka

Yoshinori Yamamoto

Atsunori Okada

Nakao Mikami

Kanji Nakatani

Hideki Tachibana

Rikujiro Kashi

Setsumi Tanase

Provided is a process for preparing a cephem compound of the formula: ##STR1## wherein R.sup.3 is hydrogen or methoxy, R.sup.4 is hydrogen or a residue of a nucleophilic compound, R.sup.5 is hydroxyl or a protected hydroxyl, and R.sup.8 is hydrogen or halogen, or a pharmaceutically acceptable salt or ester thereof, which comprises introducing an acyl group of the formula: ##STR2## wherein R.sup.5 and R.sup.8 are as defined above into the amino group of the molecule of the formula: ##STR3## wherein R.sup.3 and R.sup.4 are as defined above or a salt or ester thereof.

Methods for the manufacture of cephems

A composition of soap compounded with a garlic extract containing thiamine, a thiamine derivative having vitamin B.sub.1 activity or a salt thereof is disclosed. The soap is effective for improving atopic dermatitis.

Soap compounded with vitamin B.sub.1 -containing garlic extract

A molded article for skin contact medical treatment which comprises an integrally molded product of germanium and ceramic which irradiates far infrared rays by heating.

Molded germanium and ceramic article for skin contact medical treatment

A sheet material for skin contact medical treatment at least one part of which is a therapeutically effective part comprising germanium and ceramic which irradiates far infrared rays by heating, said germanium and ceramic being provided within a distance of 0 to 3 cm in said therapeutically effective part. A composition of therapeutically effective materials for skin contact medical treatment which comprises germanium powder and ceramic powder which irradiates far infrared rays by heating is also disclosed.

Sheet material of germanium and ceramic for skin contact medical

Novel cephem compounds of the formula: ##STR1## wherein R.sup.4 is a residue of a nucleophilic compound selected from hydroxyl, mercapto, cyano, azido, amino, carbamoyloxy, carbamoylthio and thiocarbamoyloxy, said group being unsubstituted or substituted by alkyl of up to three carbons, and R.sup.5 is hydroxyl or lower alkoxy, or a pharmaceutically acceptable ester thereof, have strong antibiotic properties against a wide variety of microorganisms.

Thiazolylacetamido cephalosporin compounds

3-Tertiary ammoniomethyl-7-beta-[alpha-(hydroxy or protected hydroxy)imino-alpha-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, pharmaceutically acceptable salt or 4-carboxy ester is provided which is a broad spectrum antibiotic.

Thiazolylacetamido cephalosphorin compounds

The present invention is directed to a compound having antibacterial activity of the formula ##STR1## wherein R.sup.1 represents amino, protected amino, hydroxy or protected hydroxy;

Thiazolylacetamido cephalosporin type compounds

Novel cephem compounds of the formula; ##STR1## wherein R.sup.1 represents amino or hydroxyl group which may be protected, R.sup.2 represents amino or hydroxyl group or a group convertible into these groups, R.sup.3 represents hydrogen or methoxy group or a group convertible into methoxy group, R.sup.4 represents hydrogen or a residue of a nucleophilic compound and R.sup.8 represents hydrogen or a halogen, or a pharmaceutically acceptable salt or ester thereof, have strong antibiotic properties against a wide variety of microorganisms including gram-positive bacteria as well as gram-negative ones, especially by oral administration and can be used as therapeutic agent for various bacterial infections of animals including human beings.

Thiazolylacetamido compounds

.alpha.-Alkoxyimino-.beta.-oxo-.gamma.-Bromobutyric acid

Novel cephem compounds of the formula; ##STR1## wherein R.sup.1 represents amino or hydroxyl group which may be protected, R.sup.2 represents amino or hydroxyl group or a group convertible into these groups, R.sup.3 represents hydrogen or methoxy group or a group convertible into methoxy group, R.sup.4 represents hydrogen or a residue of a nucleophilic compound and R.sup.8 represents hydrogen or a halogen, or a pharmaceutically acceptable salt or ester thereof, have strong antibiotic properties against a wide variety of microorganisms including gram-positive bacteria as well as gram-negative ones, especially by oral administration and can be used as therapeutic agent for various bacterial infections of animals including human beings. Also disclosed are novel thiazolylacetic acid compounds of the formula: ##STR2## wherein R.sup.1 represents amino, protected amino, hydroxyl or protected hydroxyl, R.sup.2 represents amino, protected amino, hydroxyl, protected hydroxyl or the group ##STR3## represents a group of the formula ##STR4## wherein R.sup.5 represents hydroxyl or lower alkoxy and R.sup.8 represents hydrogen or a halogen, or a salt, an ester or a reactive derivative thereof, and to processed for preparing these compounds. These latter compounds are useful as intermediates in the preparation of the novel cephem compounds.

A compound of the formula: ##STR1## wherein R.sup.2 is hydrogen or a halogen and R.sup.3 stands for methyl, acetoxymethyl, carbamoyloxymethyl, an alkoxymethyl, an alkylthiomethyl, 2-carboxy-1-ethenyl, or a heterocyclic thiomethyl, or a pharmaceutically acceptable salt thereof, is found to have a broad antimicrobial spectrum and, in particular, effective against Gram-negative bacteria including Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescense as well as Gram-positive ones including antibiotic resistant strains. Thus, these compounds may be used for antimicrobial agents in therapeutical purposes.

7-Methoxycephalosporin derivatives

Cephem and penam compounds having a partial structure of formula (II): ##STR1## wherein R.sup.1 and R.sup.2, respectively, represent a hydrocarbon group which is attached to P, either directly or through an oxygen atom, and which may optionally be substituted, and R.sup.3 is a hydrocarbon residue, are useful as intermediates for synthetic penicillins and cephalosporins, which in turn are useful as antibiotics or intermediates for some other synthetic penicillins and cephalosporins having antibiotic activity. To the 6- or 7-amino group of these penam or cephem compounds an objective acyl group can be introduced to give 6- or 7-acyl amino compound in a good yield, without isomerization of 6.alpha.-or 7.alpha.-substituent OR.sup.3 of the penam or cephem compounds.

7.beta.-Phosphoramido-7.alpha.-methoxycephalosporanic acid derivatives

A compound of the formula: ##STR1## wherein R.sup.1 represents mandeloyl or 2-(3-sydnone)-acetyl group and R.sup.2 represents a hydrogen atom, a halogen, an alkyl or an alkoxyl group, or a pharmaceutically accetable salt thereof, is found to have a broad antimicrobial spectrum and, in particular, effective against gram-negative bacteria as well as gram-positive ones. Examples thereof include 7-[D-(-)-mandelamido]-3-[6'-(3'-methylpyridazinyl)-thio-methyl]-3-cephem-4 -carboxylic acid 2'-oxide, 7-[D-(-)-mandelamido]-3-[6'-(3'-methoxypyridazinyl)-thiomethyl]-3-cephem-4 -carboxylic acid 1'-oxide, and 7-[2'-(3'-sydnone)acetamido]-3-[6'-(3'-methylpyridazinyl)-thiomethyl]-3-ce phem-4-carboxylic acid 2'-oxide.

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Kawanishi, Japan

Osami Aki