EMULSIFIABLE CONCENTRATES CONTAINING AZOLES

Abstract: Emulsifiable concentrates, being compatible with aqueous or non-aqueous mediums, containing from 1% to 60% w/v of a 1H-imidazole or 1H-1,2,4- triazole or an acid addition salt thereof; from 1% to 60%w/v of an emulsifying agent: and from 1% to 98% w/v of a solvent, and a process for preparing the said emulsifiable concentrates.

Description: EMULSIFIABLE CONCENTRATES CONTAINING AZOLES. Description of the invention: The present invention is concerned with azole-containing formulations which are highly compatible with any aqueous or non-aqueous medium lH-Imidazoles and lH-1,2,4-triazoles having attractive antimicrobial properties have been described in, for example, U.S. Patent Nos. 3,575,999; 3,717,655; 3,658,813; 3,927,017; 4,156,008; and 4,079,062, and in British Patent NOs. 2,026,486; 2,027,701 and 1,589,852. Due to their antimicrobial properties the hereinabove-mentioned azoles are very useful in the protection of living subjects and nonliving organic materials against decay caused by microorganisms. Living subjects are meant to include human and animal beings as well as plants. Non-living organic materials are meant to include any material which has a substantially organic nature such as, for example, wood, coatings, harvested fruits, foodstuffs, medicines and the like. The above-mentioned azoles are usually handled in the form of a suitable formulation which may be applied as such or after diluting with a suitable medium. Depending upon the nature of the azole incorporated and the nature of the subjects or materials where the formulation is applied to the said for formulations may have a predomi- nantly aqueous or organic nature. Furtherxore. in order to have sufficient protection it may be desirable to combine an azole with an additional active ingredient such as, for example, a pesticide, e.g., an additional fungicide, insecticide and the like. Said additional active ingredient may be incorporated in the initial formulation or the ultimate aixture may be prepared by adding at least two formulations to an appropriate medina, e.g. an aqueous or an organic medina. Since each active compound is preferably formulated in a medium appropriate for said compound it is not unusual that by combining two or more active ingredients the resulting formulation does not meet the requirements of stability and the like properties which are necessary or, at least, desirable for handling and/or applying the initial-, respectively the resulting formulation. The present invention is concerned with azole containing formulations which are highly compatible with any aqueous or non-aqueous medium, said azoles being selected from the group consisting of lH- imidazoles and lH-1,2,4-triazoles having the formula EMI2.1 or an acid addition salt thereof, wherein X is -N= or CH= and R1 is a radical of the formula EMI2.2 wherein Z is a group -CH2-CH2-, -CH2-CH2-CH2-, -CH(CH3)-CH(CH3)- or -CH2-CH(alkyl)-, wherein said alkyl is a 2 straight or branched C1-C10 alkyl radical; said Ar is a phenyl group which is optionally substituted with 1 to 3 halogens, C1-C6 alkyl radicals, C -C alkoxy radicals, cyano-, trifluoromethyl- or nitro groups, a thienyl-, halothienyl-, naphthalenyl- or fluorenyl group; and, said R is C1-C10 alkyl, cycloalkyl, cycloalkyllower alkyl, lower alkenyl, aryllower alkyl, aryloxylower alkyl or a radical of the formula -O-R . wherein said R is C1-C10 alkyl, lower 0 0 alkenyl, lower alkynyl or aryllower alkyl, wherein said aryl radical is phenyl, naphthalenyl or substituted phenyl, wherein said substituted phenyl has 1 to 3 substituents selected from the group consisting of halo, cyano, nitro, phenyl, lower alkyl and lower alkoxy, provided that when more than one substituent is present only one thereof may be cyano, nitro or phenyl. The subject formulations compatible with any aqueous or nonaqueous medium contain: i) from 1% to 60% w/v of an azole of formula (I); ii) from 1% to 60% w/v of an emulsifying agent; and iii) from 1% to 98% w/v of a solvent. Particularly interesting formulations contain an azole of formula EMI3.1 or an acid addition salt thereof, wherein X has the above-identified meaning and R1 is a radical of the formula EMI3.2 wherein Z is a group -CH2-CH2-, -CH2-CH2-CH2-, -CH(CH3)-CH2- -ai(c H )-CH -, -CH(C3H7)-CH2-, 25 2 3 2 -CH(CH3)-CH(CH3)- or -CH(CH3)-CH(C2H5)-; Ar is unsubstituted phenyl or phenyl substituted with 1 to 3 halogen atoms, preferably chloro atoms, C1-C6 alkyl radicals, C1-C6 alkoxy radicals, cyano or nitro groups: and R' is C1-C6 alkyl or C34 alkenyloxy. More particularly interesting formulations contain an azole of formula EMI4.1 or an acid addition salt thereof, wherein X has the above-identified meaning and R1" is a radical of the formula EMI4.2 wherein R" is C1-C4 alkyl or C3-C4 C C lower alkenyloxy, R3 is hydrogen or C1-C3 alkyl and n is 1 or 2. Preferred formulations in accordance with the present invention are those containing 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)- ethyll-lH-imidazole, generically designated as imazalil, or a suitable acid addition salt thereof. The solvent of the formulation is intended to fulfil the requirements of sufficiently solubilizing the azole and, if desired, any additional active ingredient. Furthermore, the solvent must be homogeneously miscible with the emulsifying agent used in the formulation. Due to their desirable solubilizing effect and their compatibility with a wide range of emulsifying agents alkanedioles such as, for example, 1,2-ethanediol, 1,2-propanediol and 1,3-propanediol, are particularly preferred. Even more particularly preferred is 1,2-propanediol since this solvent combines an excellent solubilizing effect with a desirably high flash-point. Since the subject formulations must be compatible with a wide range of mediums and/or additives the said formulations must contain a suitable amount of a non-ionic emulsifying agent. Due to their desirable solubilizing effect, their good solubility in a wide range of aqueous and non-aqueous mediums and their compatibility with the said mediums and a wide range of possible additives, e.g. co-emulsifying agents and additional active ingredients, the emulsifying agent is preferably selected from the group consisting of: i) addition products of 1 to 60 moles of ethylene oxide with 1 mole of a phenol which is further substituted with at least one Cl-Cl5 alkyl group; ii) addition products of 1 to 60 moles of ethylene oxide with 1 mole of ricinus oil; iii) addition products of 1 to 60 moles of ethylene oxide with 1 mole of a lanoline derivative: iv) addition products of 1 to 60 moles of ethylene oxide or propylene oxide with 1 mole of a fatty alcohol; and v) cobloc polymers consisting of polyethylene oxide and poly propylene oxide blocs. Because of their highly attractive properties cobloc polymers of polyethylene oxide and polypropylene oxide are particularly preferred. Where the selection of the cobloc polymer is less critical as concerns the compatibility of the subject formulations with an organic medium it has been found that the said selection is more critical as concerns the compatibility of the subject formulations with an aqueous medium. Therefore, the more preferred emulsifying agent is a cobloc polymer containing from 30% to 60% of ethylene oxide and having a molar mass of the polypropylene oxide block of 950 to 5000 g per mole. The most preferred cobloc polymer contains 50% of polyethylene oxide and has a molar mass of 3250 polypropylene oxide block per mole. In addition to the azole, a possible additional active ingredient, a solvent and an emulsifying agent the formulations may also contain one or more additives. Such additives may be added to the formulations in order to ameliorate the properties of the initial formulations or of the formulations finally applied. A suitable additive is, for example, a co-emulsifying agent which effects that by mixing the initial formulation with an aqueous or organic medium the resulting dilution is much more stable. Suitable co-emulsifying agents are, for example, (C634)alkyl benzenesulfonic acid. In the formulations of the present invention the azoles can also be used in combination with other compounds having a useful activity such as, biocidal compounds, e.g. antimicrobial agents, insecticides and the lie. As antimicrobial agents. which may be used in combination with the azoles there may be considered products of the following classes: Phenol derivatives such as 3,5-dichlorophenol, 2,5-dichlorophenol, 3,5-dibromophenol, 2,5-dibromophenol, 2,5-(resp. 3,5)-dichloro-4-broo- phenol, 3.4.5-trichlorophenol; chlorinated hydrodiphenylethers such as, for example, 2-hydroxy-3,2'4'-trichlorodiphenylether, phenylphenol, 4-chloro-2-phenylphenol. 4-chloro-2-benzylphenol. dichlorophene, hexachlorophene; aldehydes such as formaldehyde, glutaraldehyde; salicylaldehyde; alcohols such as phenoxyethanol; antimicrobially active carboxylic acids and their derivatives; organometallic compounds such as tributyltin compounds; iodine compounds such as iodophores, lodonium compounds; mono-, di and polyamines such as dodecylamine or l,l0-di(n-heptyl)-l,l0-diamino- decane; quaternary ammonium compounds such as benzyl-dimethyldode cylammonium chloride, dimethyldodecylamonium chloride, benzyldi(2-hydroxyethyl)dodecylamonium chloride; sulfonium and phosphonium compounds; mercapto compounds as -well as their alkali, earth alkaline and heavy metal salts such as 2-mercaptopyridine-N-oxide and its sodium and zinc salt, 3-mercaptopyridazin-2-oxide, 2mercapto- quinoxaline-l-oxide, 2-mercaptoquinoxalinedi-N-oxide, as well as the symmetrical disulfides of said mercapto compounds; ureas such as tribromo or trichlorocarbanilide, dichlorotrifluoromethyldiphenylurea; tribromosalicylanilide; 2-bromo-2-nitro-1,3-dihydroxypropane; dichlorobenzoxazolon; chlorohexidine; isothia- and benzisothiazolone derivatives. As insecticidal agents which may be used in combination with the azoles the following classes of products may be considered: insecticides having a natural origin, e.g., nicotine, rotenone, pyrethrum and the like; chloridinated hydrocarbons, e.g., lindane, chlordane, endosulfan and the like; organic phosphor compounds; carbamates, e.g., carbaryl, aldicarb, methiocarb, propoxur and the like: biological insecticides, e.g., products originating from Bacillus thuringiensis: synthetic pyrethroids, e.g., permethrin, allethrin, cypermethrin, halothrin and the like. Besides their high compatibility with aqueous and non-aqueous mediums the subject formulations are particularly attractive for incorporating relatively high doses of azoles and, if desired, other active ingredients. Preferred concentrated formulations contain from 20% to 60% w/v of an azole. By combining a high compatibility for aqueous and non-aqueous mediums with a capacity for incorporating relatively high doses of azoles and, if desired, other active ingredients the subject formulations are particularly attractive for handling concentrated azole containing mixtures which are usually applied to subjects or materials in relatively diluted mixtures. Diluted mixtures are meant to include for example tank-mixes for administering an azole and, if desired, an additional active ingredient to subjects or materials. Depending upon the application technique and the nature of the subject or material where the azole, optionally combined with an additional active ingredient, is applied to the diluted mixture may be any liquid, such as, for example, aqueous- or non-aqueous mixtures, e.g. aqueous or non-aqueous dilutions, aqueous- or non-aqueous waxes and the like liquids. The subject formulations have also the advantage that the activity of the azoles incorporated therein is positively influenced. As a consequence thereof analogous antimicrobial activities may be obtained with reduced concentrations of the azole in the mixture applied to the subject or material. Additionally. compared with the art-known formulations the subject formulations effect also a reduced fytotoxicity of the mixtures ultimately applied to, resulting in a very useful application-mixture with a desirable safety margin. The hereinabove-mentioned properties, combined with a substantial lack of irritation render the subject formulations particularly attractive, not only for their desirable safety margin for the subjects or materials applied to but also for the applicator. The subject formulations may be prepared by mixing the components together at a temperature comprised between 100C and 1000C, preferably between 150C and 60 c The following examples are intended to illustrate and not to limit the scope of the present invention. Unless otherwise stated herein all parts therein are by weight. Pluriol PEe, as used in the experimental part, is a Trade Mark for a cobloc polymer consisting of polyethylene oxide- and polypropylene oxide blocks wherein the molar mass of the polypropylene oxide block is 3250 g per mole and 50% of the cobloc-polymer consists of polyethylene oxide blocks. EXAMPLES ExamPle 1: Preparation of emulsifiable concentrates formulation 1: 50% w/v imazalil; 14 5% w/v Pluriol PEe; .l5% w/v dodecylbenzenesulfonic acid; and 1,2-propanediol ad volume. Preparation: 50 Parts of imazalil were mixed with 20 parts of 1,2-propanediol at 500C. Subsequently 14.5 parts of Pluriol PE and 7.15 parts of dodecylbenzenesulfonic acid were added and the mixture was stirred at 200C until the mixture was homogeneous. Finally, the mixture was diluted to 100 ml. formulation 2: 10% w/v imazalil; 1% w/v cypermethrin; 5% w/v Pluriol PE; and 1,2-propanediol ad 100 ml. Preparation: 10 Parts of imazalil were mixed with 50 parts of 1,2-propanediol. Subsequently 1 part of cypermethrin and 5 parts of Pluriol PEe were added and the mixture was stirred at 200C until the mixture was homogeneous. Finally, the mixture was diluted to 100 ml. Example 2: Antifunqal activity Young gherkin plants, about 10 days old, were sprayed with a mixture containing 10, 1 or 0.1 ppm of imazalil while controls were kept untreated. After drying of the plants artificial infection with spores of Erysiphe cichoracearum was carried out by slightly rubbing the plants with a heavily infected leaf. At the 15th day after artificial infection the degree of fungal attack was evaluated by counting the number of spots per plant. The results given in Table 1 are the percentages of fungal attack in comparison with the untreated plants. Dilution A was prepared by diluting a xylene-based emulsifiable concentrate containing 20% of imazalil with water. Dilution B was prepared by diluting formulation 1 (described hereinabove) with water. Table 1: percentage of fungal attack EMI10.1 <tb> <SEP> concentration <SEP> in <SEP> ppm <tb> <SEP> 10 <SEP> 1 <SEP> 0.1 <tb> dilution <SEP> A <SEP> 0 <SEP> 20 <SEP> 50 <tb> dilution <SEP> B <SEP> 0 <SEP> 0 <SEP> 1 <tb> Example 3: Pytotoxicity-tests Pears (Doyenne du Cornice and Conference) were immersed into an imazalil containing mixture during two minutes. After pears were leaked out during one minute they were stored on a glass petridish and stored during 5 days at 50C. As the apples and pears were not dried before storage a moistened ring is formed between the glass petridish and the contact-surface of the pear. Fytotoxicity was measured by determining the percent of the contact-surface which shows any form of decay or discoloration. The results given in Table 2 are the percentages of the contact-surface which shows any form of decay or discoloration at different concentrations of imazalil in the farmersemixture. Apples were immersed into an imazalil containing mixture during two minutes. After the apples were leaked out during one minute they were placed five together in a glass recipient of five liter and stored during 5 days at 20C. As the apples were not dried before storage a moistened ring was formed at the contact-surfaces of the apples and the contact-surfaces formed between the apples and the glass recipient. Fytotoxicity was measured by determining the percent of the contact-surface which shows any form of decay or discoloration. The results given in Table 3 are the percentages of the contact-surface which shows any form of decay or discoloration at different concentrations of imazalil in the immerse-mixture. The imazalil-containing mixtures under investigation were: - dilution C, prepared by diluting formulation 1 (described hereinabove) with water; - dilution D, prepared by diluting a water-soluble powder containing 75% of imazalil sulfate with water; and - dilution E, prepared by diluting a xylene-based emulsifiable concentrate containing 20% of imazalil with water. Table 2 : Fytotoxicity data on pears EMI11.1 <tb> <SEP> Percent <SEP> of <SEP> decay <SEP> or <SEP> discoloration <SEP> of <SEP> the <SEP> contact-surface <tb> <SEP> Doyenne <SEP> du <SEP> Comice <SEP> Conference <tb> dilution <SEP> C <tb> <SEP> 1000 <SEP> ppm <SEP> 2 <SEP> 0 <tb> <SEP> 1500 <SEP> ppm <SEP> 2 <SEP> 0 <tb> <SEP> 2000 <SEP> ppm <SEP> 2 <SEP> 0 <tb> dilution <SEP> E <tb> <SEP> 250 <SEP> ppm <SEP> 2 <SEP> 0 <tb> <SEP> 500 <SEP> ppm <SEP> 5 <SEP> 1 <tb> <SEP> 1000 <SEP> ppm <SEP> 6 <SEP> 2 <tb> Table 3: Fytotoxicity data on apples EMI11.2 <tb> <SEP> Percent <SEP> of <SEP> decay <SEP> or <SEP> discoloration <SEP> of <SEP> the <SEP> contact-surface <tb> <SEP> Golden <SEP> delicious <tb> dilution <SEP> C <tb> <SEP> 1000 <SEP> ppm <SEP> 0 <tb> <SEP> 2000 <SEP> ppm <SEP> 0.5 <tb> dilution <SEP> D <tb> <SEP> 1000 <SEP> ppm <SEP> 2 <tb> Example 4: Fysical compatibility Dilutions containing 500 ppm of imazalil and 500 ppm of a mixpesticide are prepared by diluting the initial mix-pesticide containing formulations with standard hard water (342 ppm) at 300C. adding a calculated amount of formulation 1 and, finally, diluting with standard hard water up to the desired concentration of imazalil and mix-pesticide containing formulations with standard hard water (342 ppm) at 300C. Blanco formulations containing only the mixpesticide were also prepared following the same procedure.The samples were inverted up to a homogeneous mixture was obtained (number of inversion-cycles: see Table 4, column 1 for blanco and column 2 for the combination) and, subsequently, up to twenty inversion-cycles. After an immobile storage of the samples at 300C the samples were inverted until the formed sedimentation or creaming had completely disappeared (number of inversion-cycles: see Table 4, column 3 for blanco and column 4 for the combination). Table 4 EMI12.1 <tb> <SEP> number <SEP> of <SEP> inversion-cycles <tb> mix-pesticide <SEP> containing <SEP> column <SEP> 1 <SEP> column <SEP> 2 <SEP> column <SEP> 3 <SEP> column <SEP> 4 <tb> <SEP> formulation <SEP> blanco <SEP> combination <SEP> blanco <SEP> combination <tb> Vinclozolin <SEP> 50% <SEP> UP+ <SEP> 2 <SEP> 2 <SEP> 1 <SEP> 1 <tb> Thiophanate <SEP> 70% <SEP> wP <SEP> 1 <SEP> 2 <SEP> 1 <SEP> 2 <tb> 3- <SEP> (3, <SEP> 5-dichlorophenyl <SEP> )- <SEP> <tb> 1-isopropylcarbaaoxyl- <SEP> 1 <SEP> 2 <SEP> 1 <SEP> 2 <tb> hydantoin <SEP> 50% <SEP> up <tb> Carbendazin <SEP> 50% <SEP> WP <SEP> 2 <SEP> 2 <SEP> 2 <SEP> 2 <tb> Triadimefon <SEP> 25% <SEP> VP <SEP> 3 <SEP> 3 <SEP> 2 <SEP> 3 <tb> Carbendazin <SEP> 50% <SEP> PL* <SEP> 3 <SEP> 3 <SEP> 6 <SEP> 7 <tb> Thiabendazol <SEP> 45% <SEP> FL <SEP> 3 <SEP> 8 <SEP> 2 <SEP> x <tb> * : WP is an abbreviation for wettable powder * : FL is an abbreviation for flowable

Claims: CLAIl4S 1. An emulsifiable concentrate containing i) from 1% to 60% w/v of an emulsifying agent; ii) from 1% to 98% w/v of a solvent: and iii) from 1% to 60% w/v of one azole having the formula EMI13.1 or an acid addition salt thereof, wherein X is -N or -CH= and R1 is a radical of the formula EMI13.2 wherein Z is a group -CH2-CH2 -, -CH2-CH2-CH2-, -CH(CH3)-CH(CH3)- or -CH2-CH(alkyl)-, wherein said alkyl is a straight or branched C1-C10 alkyl radical; said Ar is a phenyl group which is optionally substituted with 1 to 3 halogens, C1-C6 alkyl radicals, C1-C6 alkoxy radicals. cyano-, trifluoromethyl- or nitro groups, a thienyl-, halothienyl-. naphthalenyl- or fluorenyl group; and, said R is C1-C10 alkyl. cycloalkyl, cycloalkyllower alkyl. lower alkenyl. aryllower alkyl, aryloxylower alkyl or a radical of the formula -OR , wherein 0 said R is C1-C10 alkyl, lower alkenyl. lower alkynyl or 0 aryllower alkyl, wherein said aryl radical is phenyl. naphthalenyl or substituted phenyl, wherein said substituted phenyl has 1 to 3 substituents independantly selected from the group consisting of halo, cyano, nitro, phenyl, lower alkyl and lower alkoxy, provided that when more than one substituent is present only one thereof may be cyano. nitro or phenyl. 2. An emulsifiable concentrate according to claim 1 wherein the azole is selected from the compounds having the formula EMI14.1 or an acid addition salt thereof, wherein X is -N= or -CH= and R1' is a radical of the formula EMI14.2 wherein Z' is a group -CH2-CH2-, -CH2-CH2-CH2-, -CH(CH3)-CH2-, -CH(C2H5)-CH2-, -CH(C3H7)-CH2-, -CH(CH3)-CH(CH3)- or -CH(CH3)-CH(C2H5)-; Ar' is unsubstituted phenyl or phenyl substituted with 1 to 3 halogen atoms, preferably chloro atoms, C16 alkyl radicals, C1-C6 alkoxy radicals, cyano or nitro groups; and R' is C1-C6 alkyl or C3C4 alkenyloxy, 3. An emulsifiable concentrate according to claims 1 wherein the azole is selected from the compounds having the formula EMI14.3 or an acid addition salt thereof, wherein X is -N= or -CH- and R1" is a radical of the formula EMI15.1 wherein R" is C14 alkyl, C34 lower alkenyloxy, R3 is hydrogen or C1-C3 alkyl and n is 1 or 2. 4. An emulsifiable concentrate according to claim 1 wherein the azole is 1-[2-(2, 4-dichlorophenyl)-2-(2-propenyloxy)ethyl)-lH imidazole or an acid addition salt thereof. 5. An emulsifiable concentrate according to any of claim 1 to 4 wherein the emulsifying agent is selected from the group consisting of i) addition products of 1 to 60 moles of ethylene oxide with 1 mole of a phenol which is further substituted with at least one C1-C15 alkyl group; ii) addition products of 1 to 60 moles of ethylene oxide -with 1 mole of ricinus oil; iii) addition products of 1 to 60 moles of ethylene oxide with 1 mole of a lanoline derivative; iv) addition products of 1 to 60 moles of ethylene oxide or propylene oxide with 1 mole of a fatty alcohol; and v) cobloc polymers consisting of polyethylene oxide and polypropylene oxide blocs. 6.An emulsifiable concentrate according to any of claims 1 to 4 wherein the emulsifying agent is a cobloc polymer consisting of polyethylene oxide and polypropylene oxide blocs. 7. An emulsifiable concentrate according to any of claims 1 to 6 wherein the solvent is an alkanediol. 8. An emulsifiable concentrate according to any of claims 1 to 6 wherein the solvent is 1,2-ethanediol or 1,2-propanediol. 9. An emulsifiable concentrate according to claim 8 wherein the solvent is 1,2-propanediol. 10. An emulsifiable concentrate according to any of claims 1 to 9 containing additionally from 0.5% to 15% of a co-emulsifying agent. 11. An emulsifiable concentrate according to claim 10 wherein the co-emulsifying agent is selected from the group consisting oE (C6-C34) alkyl benzenesulfonic acids. 12. An emulsifiable concentrate containing i) from 10% to 20% w/v of a cobloc polymer consisting of polyethylene oxide and polypropylene oxide blocks; ii) from 45% to 55% w/v of (+)-l-(2-(2,4-dichlorophenyl)-2- (2-propenyloxy)ethyl)-lH-imidazole; and iii) 1,2-propanediol ad volume. 13. An emulsifiable concentrate according to claim 12 containing from 5% to 108 w/v of a co-emulsifying agent selected from the group consisting of (C634)alkyl benzenesulfonic acids. 14. An emulsifiable concentrate containing i) 50% w/v of (+)-l-(2-(214-dichlorophenyl)-2-(2-propenyl- oxy)ethylJrlH-imidazole; ii) 14.5% w/v of a cobloc polymer consisting of polyethylene oxide- and polypropylene oxide blocks wherein the molar mass of the polypropylene oxide block is 3250 g per mole and 50% of the cobloc polymer consists of polyethylene oxide blocks; iii) 7.15 8 w/v of dodecylbenzenesulfonic acid; and iv) 1,2-propanediol ad volume. 15. A mixture prepared by diluting an emulsifiable concentrate according to any of claims 1 to 14, for use in the protection of harvested fruits. vegetables and foodstuffs. 16. A process for preparing an emulsifiable concentrate according to claim 1, characterized by solubilizing the azole in part of the solvent at a temperature between 100C and 100 C, subsequently mixing the thus obtained mixture with the emulsifying agent at a temperature between lO0C and 100 C, if desired, adding a suitable additive and. finally. diluting the mixture with solvent ad volume at a temperature between 10çC and 100 C.

Inventors: LIGTVOET, THEO FRANS MARIA CORNELIS, RUELENS, PAUL FIRMIN MARC
Applicants: JANSSEN PHARMACEUTICA N.V.
Application year: 1985
Main classification: A01N25
IPC codes: A61P31, A23L3, A01N25, A61K9, A61K31, A01N43