Gist-brocades N.v.

Dsm N.v.

Gist-brocades B.v.

Hong Sheng Tan

Jan Verweij

Jacobus Stark

Ferdinand Theodorus Van Rijn

Jan Verwey

Ben Rudolf De Haan

Willem J Van Zoest

Nicolaas Cornelis Barendse

Hermanus Jacobus Kooreman

Bernardus B Wegman

Luppo Edens

Johannes Wilhelmus Lambers

Dirk A Smink

Bertus Noordam

Martinus J Warmerdam

Sylvia Josefine De Jong

The present invention provides a method of preparing an improved antifungal composition containing an antifungal compound of the polyene type such as natamycin wherein the antifungal compound is incorporated into the composition in a form which shows an enhanced activity, e.g. in the form of a solution and/or being in a modified polymorphic form.

Antifungal composition

Use of compositions comprising stabilized biologically effective

Methods for long-term preservation of food products using a lactoperoxidase system. Long-term preservation is achieved by controlled generation of hydrogen peroxide as a substrate for the lactoperoxidase system. Controlled production of hydrogen peroxide is achieved by generating the hydrogen peroxide enzymatically form a system wherein the substrate for the enzyme generating the hydrogen peroxide is immobilized or is generated in situ from a precursor.

Longterm antimicrobial activity obtained by sustained release of

An antifungal composition is disclosed which comprises an antifungal agent of the polyene type, an acidific antifungal compound and an additional organic acid or its alkali or earth alkali salt. The use of this composition to treat food and agricultural products is disclosed.

Fungicide composition to prevent the growth of mould on foodstuff and

Concentrated suspensions of polyene fungicides such as natamycin are disclosed which exhibit good chemical, microbial and physical stability and which are thus particularly suitable as stock suspensions for the preparation of immersion liquids and coating emulsions for treatment of food, feed and agricultural products. Such suspensions have a pH in the range 3 to 4.8 and include a thickening agent.

Stable natamycin suspensions

Novel tablets comprising (a) 80 to 98% by weight of a mixture of trimethoprim and/or an acid addition salt thereof and a sulfonamide and/or a salt thereof in a weight ratio of 1:20 to 20:1 and (b) a pharmaceutically acceptable synthetic ion exchange resin having improved disintegration times and other properties and a process for their preparation.

Novel pharmaceutical tablets

Pharmaceutical tablets

A process for the treatment of fruits and vegetables to improve their shelf life and/or to decrease their loss of moisture and the fruits and vegetables treated by such a process and to compositions to be used in the said process wherein fruits and vegetables which are not over-ripe, i.e., to unripe fruits, to fruits which are just ripe or to partially ripened fruits are treated with an aqueous solution or suspension of sucrose esters of fatty acids.

Sucrose ester treatment of bananas

New azetidine derivatives of the formula: ##STR1## wherein R.sub.1 represents a penicillin- or cephalosporin-amido group, R.sub.2 represents one of the groups of the following formulae: ##STR2## wherein R.sub.4, R.sub.5 and R.sub.6 are the same or different and each represents a hydrogen atom or a lower alkyl or alkenyl group, n represents 2 or 3 and--in case formula IIB represents a phenyl group--this group may carry one to four further substituents selected from the group consisting of halogen atoms and lower alkyl, lower alkenyl and phenyl groups,

Process for the preparation of azetidines

Novel azetidine derivatives of the formula ##STR1## wherein R.sub.1 is an acylamido group, R.sub.2 is selected from the group consisting of ##STR2## wherein R.sub.4, R.sub.5 and R.sub.6 are individually selected from the group consisting of hydrogen, lower alkyl and lower alkenyl, n is 2 or 3 and -- in the case when formula IIB is a phenyl -- this group may carry 1 to 4 substituents selected from the group consisting of halogen, lower alkyl, lower alkenyl and phenyl, and R.sub.3 is lower alkyl optionally substituted with 1 or 2 phenyls which phenyl groups may be substituted with nitro and a process for their preparation and process for the preparation of cephalosporanic acid derivatives using the azetidines of formula I as intermediates.

Process for preparing cephalosporin derivatives

Novel 6-substituted amino-penicillanic acid anhydrides useful in the process for the preparation of 7-substituted amino-desacetoxycephalosporanic derivatives comprising converting a 6-substituted amino-penicillanic acid sulfoxide into an anhydride of a 6-substituted amino-penicillanic acid sulfoxide, heating the said acid anhydride intermediate at a temperature up to at most 160.degree. C in a dry inert organic solvent with an anhydrous acid which is capable of causing ring expansion of the penam ring to a .DELTA..sup.3 -cephem ring, in the presence of a silicon-containing compound capable of (a) removing water formed during the ring enlargement of the penam structure fast enough to prevent water hydrolysis of the acid anhydride moiety present and (b) forming neutral or basic products on hydrolysis, the aforesaid acid being strong enough not to be, or not to a substantial extent to be, silylated under the reaction conditions employed, and hydrolyzing the resulting compound in situ to form the .DELTA..sup.3 -7-substituted amino-desacetoxycephalosporanic acid as such or as a salt, such as alkali metal, alkaline earth metal or amine salt.

Preparation of 7-substituted amino-desacetoxycephalosporanic acid

Novel azetidine derivatives of the formula ##STR1## wherein R.sub.1 is an acylamido group, R.sub.2 is selected from the group consisting of ##STR2## wherein R.sub.4, R.sub.5 and R.sub.6 are individually selected from the group consisting of hydrogen, lower alkyl and lower alkenyl, n is 2 or 3 and -- in the case when formula IIB is a phenyl - this group may carry one to four substituents selected from the group consisting of halogen, lower alkyl, lower alkenyl and phenyl, and R.sub.3 is lower alkyl optionally substituted with 1 or 2 phenyls which phenyl groups may be substituted with nitro and the dotted lines of formula IIB indicate the optional presence of double bonds and a process for their preparation and process for the preparation of cephalosporanic acid derivatives using the azetidines of formula I as intermediates.

Azetidine derivatives

Process for the preparation of 7-substituted amino-desacetoxycephalosporanic derivatives comprising converting a 6-substituted amino-penicillanic acid sulfoxide into an anhydride of a 6-substituted amino-penicillanic acid sulfoxide, heating the said acid anhydride intermediate at a temperature up to at most 160.degree. C in a dry inert organic solvent with an anhydrous acid which is capable of causing ring expansion of the penam ring to a .DELTA..sup.3 -cephem ring, in the presence of a silicon-containing compound capable of (a) removing water formed during the ring enlargement of the penam structure fast enough to prevent water hydrolysis of the acid anhydride moiety present and (b) forming neutral or basic products on hydrolysis, the aforesaid acid being strong enough not to be, or not to a substantial extent to be, silylated under the reaction conditions employed, and hydrolyzing the resulting compound in situ to form the .DELTA..sup.3 -7-substituted amino-desacetoxycephalosporanic acid as such or as a salt, such as alkali metal, alkaline earth metal or amine salt and to the novel sulfoxide acid anhydrides formed therein.

New azetidine derivatives of the formula: ##EQU1## wherein R.sub.1 represents a penicillin- or cephalosporin-amido group, R.sub.2 represents one of the groups of the following formulae: ##EQU2## wherein R.sub.4, R.sub.5 and R.sub.6 are the same or different and each represents a hydrogen atom or a lower alkyl or alkenyl group, n represents 2 or 3 and - in case formula IIB represents a phenyl group - this group may carry one to four further substituents selected from the group consisting of halogen atoms and lower alkyl, lower alkenyl and phenyl groups, R.sub.3 represents an amino group of the formula ##EQU3## wherein R.sub.7 represents a hydrogen atom or a lower alkyl group and R.sub.8 represents a lower alkyl group, or R.sub.3 represents a N,N'-disubstituted hydrazino group wherein the substituents are lower alkyl groups, e.g. the N,N'-diisopropylhydrazino group, or R.sub.3 represents the group -OR.sub.9, wherein R.sub.9 represents a hydrogen atom, a lower alkyl group, which group may be substituted by 1 to 3 halogen atoms or by 1 or 2 phenyl groups, wherein the phenyl groups may be substituted by a methoxy or a nitro group, or R.sub.9 represents a phenacyl group or a salt-forming cation, and corresponding azetidine derivatives of formula 1 wherein the double bond in the propenyl side chain has been shifted from the 2- to the 1-position, which are versatile intermediates in the process of preparing cephalosporanic and penicillanic derivatives.

Growing community of inventors

Bleiswijk, Netherlands

Hong Sheng Tan