CN102741327A - Method for solubilizing hydrophobic active ingredients in an aqueous solution - Google Patents
Method for solubilizing hydrophobic active ingredients in an aqueous solution Download PDFInfo
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- CN102741327A CN102741327A CN2011800082932A CN201180008293A CN102741327A CN 102741327 A CN102741327 A CN 102741327A CN 2011800082932 A CN2011800082932 A CN 2011800082932A CN 201180008293 A CN201180008293 A CN 201180008293A CN 102741327 A CN102741327 A CN 102741327A
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/002—Dendritic macromolecules
- C08G83/005—Hyperbranched macromolecules
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/30—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests characterised by the surfactants
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Abstract
The invention relates to a method for solubilizing hydrophobic active ingredients in an aqueous medium, characterized in that at least one hyperbranched polymer (A) is used as an auxiliary agent and can be obtained by reacting at least one hyperbranched polymer compound with at least one primary or secondary amino group per molecule (a), selected from (a1) hyperbranched polyamides and (a2) hyperbranched polyureas, having (b) at least one mono-, di-, or oligosaccharide.
Description
The present invention relates to a kind of in water-bearing media the method for solubilization hydrophobic active composition; This method comprises uses at least a hyperbranched polymer (A) as auxiliary agent; Said hyperbranched polymer (A) can through make at least a per molecule have at least one uncle or the hyperbranched polymerizable compound (a) of secondary amino group and (b) at least a list-, two-or the oligosaccharides reaction obtain, said hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
The invention further relates to hyperbranched polymer (A); It can through make at least a per molecule have at least one uncle or the hyperbranched polymerizable compound (a) of secondary amino group and (b) at least a list-, two-or oligosaccharides in liquid phase, react and obtains, said hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
The invention further relates to the mixture and a kind of method for preparing mixture of the present invention that comprise at least a hyperbranched polymer of the present invention and at least a hydrophobic active composition.The invention further relates to a kind of method for preparing hyperbranched polymer of the present invention.
In many cases need be in water solubilization lyophobic dust, for example hydrophobic active composition and the said activeconstituents of non-chemical modification itself.For this reason, for example can prepare emulsion, wherein said activeconstituents is present in the oil phase of this emulsion.Yet, for many active constituents of medicine or crop protection agents, especially to carry or in water, carry with body fluid those, this generic operation is impossible.Under the effect of high shear, emulsion maybe breakdown of emulsion.In addition, sterilization is impossible in many cases when keeping this emulsion.
But for example can be dissolved in the solvent mixture of second alcohol and water and Ucar 35 or polyoxyethylene glycol and can process and obtain the for example preparaton of parenteral admin by DE-A 33 16 510 known hydrophobic drug activeconstituentss.Such solvent mixture comprises 15-30 weight % ethanol usually.Yet, hope in patient's treatment, to avoid a large amount of like this alcohol in many cases.
The extra known phosphatide of in water, using is specially the solubilization of liposome phosphatide based on 1, the activeconstituents of 4-dihydropyridines; For example referring to EP 0 560 138 A.Yet liposome phosphatide stands the mechanism of degradation identical with the endogenous cell membrane lipid.Therefore, the liposome delivery system that produces in this way only has the limited storage time according to the pH and the ionic strength of this medium.Especially because the shearing force that in the intravenous administration process of activeconstituents, occurs possibly easily destroyed the liposome delivery system.
In addition, solubilizing agent and the activeconstituents of observing excessive concentrations in liver or spleen in many cases undesirably is transported in the surrounding tissue by blood vessel and even after the short period of time, observes the slow release of encapsulated active ingredients owing to the dynamic structure of double-layer of lipoid.The difficulty of sterilization is another reason why liposome is not suitable for the application of all conveying actives.
Other systems of solubilization hydrophobic active composition are for example known by WO 2007/125028.
WO 2007/060119 discloses hyperbranched poly Methionin, and has proposed its purposes as solubilizing agent.Yet it is not enough and can further improve for many purposes in the performance in the solubilization lyophobic dust.
WO 2006018125 discloses highly branched polymeric amide and the purposes in producing moulded product, film, fiber and foams thereof.
WO 2006/087227 discloses at least a hydrophobic active composition and hyperbranched polymer with nitrogen, the for example combination of polyureas.Yet it is not enough and can further improve for many purposes in the performance in the solubilization lyophobic dust.
D.Appelhans etc., Biomacromolecules 2009,10, and 1114 and D.Appelhans etc., Molecular Bioscience 2007,7,373 discloses and can use the hyperbranched polyethyleneimine that is connected with oligosaccharides to come the complexing drug substance.
The shortcoming of the known architectures of solubilization hydrophobic active composition is that they only can a small amount of activeconstituents of solubilization in water-bearing media.In addition, many used not functionalized hyperbranched polymers, for example many polymeric amide and polyureas itself be not water-soluble or for water dispersible usually, thereby they are not suitable for solubilization in water-bearing media.In addition, the shortcoming that contains the solubilizing agent of polymine be because even the amino of still a large amount of existence functionalized after, they have the too high polar structure that is not suitable for solubilization hydrophobic active composition.
Therefore, the purpose of this invention is to provide improving one's methods of a kind of solubilization hydrophobic active composition, it does not have by the known shortcoming of prior art.Another object of the present invention provides the delivery system of avoiding by the known shortcoming of prior art.
Therefore, found the defined method of beginning.
Solubilization is interpreted as referring in water-bearing media, being hydrophobicity, and in other words insoluble or sl. sol. activeconstituents own can distribute with molecular dispersion.This for example can or seal relevant hydrophobic active composition and realize through complexing.
In context of the present invention, water-bearing media is interpreted as referring to for example following: water, water and at least a organic solvent such as methyl alcohol, ethanol, terepthaloyl moietie, Ucar 35, polyoxyethylene glycol, Virahol, 1; 4-two
alkane or N; The solvent mixture of dinethylformamide, the aqueous solution of sugar, for example D/W; The aqueous solution of salt; For example sodium chloride aqueous solution or potassium chloride solution, aqueous solution of buffer agent, for example phosphate buffered saline buffer; Perhaps especially water or contain human or animal's body fluid of water, for example blood, urine and spleen liquid (splenic fluid).
Preferred water-bearing media is interpreted as referring to pure (distillation) water, sodium chloride aqueous solution, especially physiological salt soln, or the solvent mixture of water and at least a above-mentioned organic solvent, and wherein the ratio of organic solvent is no more than 10 weight % of said water-bearing media.
In context of the present invention; Activeconstituents also can be called effector substance and for for example as crop protection agents; For example Insecticides (tech) & Herbicides (tech) or mycocide; Preferred sterilant and acting that type material of mycocide are perhaps for effective as fluorescent agent or have a drug effect, for example as cardiovascular drug or anti-osteoporotic or as that type material of cytostatic.Pigment is not activeconstituents in context of the present invention.
Suitable cardiovascular drug embodiment is as being those of formula I:
In this formula, each variable defines with each group is following:
Y is NO
2, CN or COOR
1, wherein
R
1For not being substituted or by C
1-C
3Alkoxyl group such as methoxyl group, oxyethyl group, positive propoxy, isopropoxy replace the C of one or many
1-C
4Alkyl such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec.-butyl, the tertiary butyl; Substituted radicals R
1Embodiment as being methoxymethyl, ethoxyl methyl, 2-methoxy ethyl;
W is CO-NH-C
3-C
7Naphthenic base or COOR
2, wherein
R
2Be selected from and be not substituted or by C
1-C
3Alkoxyl group, trifluoromethyl, N-methyl-N-benzylamino or CH
2-C
6H
5The C that replaces one or many
1-C
10Alkyl such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec.-butyl, the tertiary butyl, n-pentyl, isopentyl, sec.-amyl sec-pentyl secondary amyl, neo-pentyl, 1; 2-dimethyl propyl, isopentyl, n-hexyl, isohexyl, Sec-Hexyl, n-heptyl, n-octyl, 2-ethylhexyl, n-nonyl, positive decyl, preferred especially C
1-C
4Alkyl such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec.-butyl and the tertiary butyl, especially methyl.Substituted radicals R
2Embodiment as being methoxymethyl, ethoxyl methyl, 2-methoxy ethyl, 2,2, the 2-trifluoroethyl;
R
3Be selected from CN, ω-hydroxyalkyl, preferred ω-hydroxyl-C
1-C
4Alkyl, especially methylol and 2-hydroxyethyl, or C
1-C
4Alkyl is like methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec.-butyl and the tertiary butyl;
X
1Identical or different in each case and be selected from NO
2, halogen, especially fluorine, chlorine or bromine, C
1-C
4Alkyl is like methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec.-butyl and the tertiary butyl, C
1-C
4Alkoxyl group is like methoxyl group, oxyethyl group, positive propoxy, isopropoxy, n-butoxy, isobutoxy, sec.-butoxy, tert.-butoxy; Benzoyl-, ethanoyl, O-CO-CH
3, trifluoromethyl or 2-(4-methyl benzyloxy);
M is selected from the integer of 0-2, and preferred 1 or 2.
The instance of specially suitable active constituents of medicine comprises nifedipine, nimodipine (1; 4-dihydro-2; 6-dimethyl--4-(3 '-nitrophenyl) pyridine-3-'beta '-methoxy ethyl ester 5-isopropyl esters, known by DE 28 15 278), nisoldipine, nitrendipine, felodipine and amlodipine.
With regard to activeconstituents, hydrophobicity is interpreted as referring to that the solubleness in zero(ppm) water is preferably below 1g/l, more preferably below 0.1g/l under 20 ° of C.
The instance of suitable cytostatic is Dx and taxol.
Other suitable active constituents of medicine be to osteoporosis, inflammation or rheumatosis effectively those.
Other active constituents of medicine suitable in context of the present invention are hormone, proton pump inhibitor, statin, proteasome inhibitor, anodyne and pravastatin.
Can comprise as follows according to the instance of the suitable Fungicidal active ingredient of the inventive method solubilization: acyl group L-Ala class, for example M 9834 (benalaxyl), metaxanin (metalaxyl), fenfuram (ofurace),
frost spirit (oxadixyl);
Sulfonamide derivatives; 4-dodecyl-2 for example, 6-thebaine (aldimorph), dodine (dodine), dodemorfe (dodemorph), fenpropimorph (fenpropimorph), fenpropidin (fenpropidin), Guanoctine (guazatine), biguanide spicy acid salt (iminoctadine), spiral shell
luxuriant amine (spiroxamin), tridemorph (tridemorph);
Anilino-pyrimidine, for example pyrimethanil (pyrimethanil), mepanipyrim (mepanipyrim) or encircle third pyrimidine (cyrodinyl);
Microbiotic, for example cycloheximide (cycloheximide), grisovin (griseofulvin), spring thunder plain (kasugamycin), myprozine (natamycin), Polyoxin (polyoxin) and Streptomycin sulphate (streptomycin);
Azole, for example Bitertanol (bitertanol), bromuconazole (bromoconazole), cyproconazole (cyproconazole),
ether azoles (difenoconazole), alkene azoles alcohol (diniconazole), oxole bacterium (epoxiconazole), RH-7592 (fenbuconazole), Fluquinconazole (fluquinconazole), fluzilazol (flusilazole), flutriafol (flutriafol), own azoles alcohol (hexaconazole), IMAZALIL (imazalil), cycltebuconazole (ipconazole), ring penta azoles bacterium (metconazole), nitrile bacterium azoles (myclobutanil), Topaze (penconazole), Wocosin 50TK (propiconazole), Prochloraz (prochloraz), prothioconazoles (prothioconazole), tebuconazole (tebuconazole), fluorine ether azoles (tetraconazole), triazolone (triadimefon), Triabimeno I (triadimenol), fluorine bacterium azoles (triflumizole), triticonazole (triticonazole);
The 2-methoxy benzophenone class of in EP 0 897 904, describing, for example metrafenone (metrafenone) with general formula I;
The dicarboximide class, for example different third fixed (iprodione), the myclozolin (myclozolin), sterilization sharp (procymidone), vinclozolin (vinclozolin);
Dithiocarbamate(s), for example Karbam Black (ferbam), Parzate (nabam), MANEB 20WP (maneb), zinc manganese ethylenebisdithiocarbamate (mancozeb), metamsodium (metam), Carbatene (metiram), propineb (propineb), polycarbamate (polycarbamate), thiram (thiram), ziram (ziram), zineb (zineb);
Heterogeneous ring compound, for example anilazine (anilazine), F-1991 (benomyl), boscalid amine (boscalid), derosal (carbendazim), DCMO (carboxin), oxycarboxin (oxycarboxin), cyanogen frost azoles (cyazofamid), dazomet (dazomet), Delan (dithianon),
famoxadone (famoxadon), fenamidone (fenamidon), fenarimol (fenarimol), fuberidazole (fuberidazole), fultolanil (flutolanil), the spirit of furan pyrazoles (furametpyr), isoprothiolane (isoprothiolane), third oxygen go out and embroider amine (mepronil), nuarimol (nuarimol), fluorine pyrrole bacterium amine (picobezamid), thiabendazole (probenazole), the third oxygen quinoline (proquinazid), pyrifenox (pyrifenox), pyroquilon (pyroquilon), quinoxyfen (quinoxyfen), silicon metsulfovax (silthiofam), Apl-Luster (thiabendazole), thifluzamide (thifluzamid), thiophanate methyl (thiophanate-methyl), tiadinil (tiadinil), tricyclazole (tricyclazole), triforine (triforine);
Nitrophenyl derivative is for example like Niagara 9044 (binapacryl), dinocap (dinocap), dinobuton (dinobuton), different third disappear (nitrophthal-isopropyl);
Phenylpyrrole class, for example fenpiclonil (fenpiclonil) and fluorine
bacterium (fludioxonil);
Non-classified mycocide, for example plain (acibenzolar-S-methyl), benzene metsulfovax (benthiavalicarb) of thiadiazoles, carpropamide (carpropamid), m-tetrachlorophthalodinitrile (chlorothalonil), cyflufenamid (cyflufenamid), cymoxanil (cymoxanil), diclomezine (diclomezin), two chlorine zarilamid (diclocymet), the mould prestige of second (diethofencarb), Hinosan (edifenphos), Guardian (ethaboxam), fenhexamid (fenhexamid), fentinacetate (fentin acetate), zarilamid (fenoxanil), ferimzone (ferimzone), PP-192 (fluazinam), fosetyl (fosetyl), ethyl phosphine aluminium (fosetyl aluminum), iprovalicarb (iprovalicarb), Perchlorobenzene (hexachlorobenzene), metrafenone (metrafenone), pencycuron (pencycuron), hundred dimension spirit (propamocarb), phthalides (phthalide), tolclofosmethyl (toloclofos-methyl), quintozene (q uintozene), zoxamide (zoxamid);
The strobilurins class of in WO 03/075663, describing with general formula I (strobilurins), instance are nitrile ICIA 5504 (azoxystrobin), ether bacterium amine (dimoxystrobin), fluoxastrobin (fluoxastrobin), imines bacterium (kresoxim-methyl), fork phenalgin acid amides (metominostrobin), orysastrobin (orysastrobin), ZEN 90160 (picoxystrobin), Strobilurin (pyraclostrobin) and oxime bacterium ester (trifloxystrobin);
The sulfenic acid verivate is like Difolatan (captafol), Vancide 89 (captan), Pecudin (dichlofluanid), Phaltan (folpet), tolylfluanid (tolylfluanid);
Cinnamide and similar compound are like HSDB 6915 (dimethomorph), fluorine biphenyl bacterium (flumetover), SYP-L190 (flumorp);
6-aryl-[1,2,4] triazolo [1,5-a] pyrimidine of for example in WO 98/46608, WO 99,41255 or WO 03/004465, describing with general formula I separately;
Amides mycocide such as cyflufenamid (cyclofenamid) and (Z)-N-[α-(cyclopropyl methoxyimino)-2,3-two fluoro-6-(difluoro-methoxy) benzyls]-2-phenyl-acetamides.
The instance of weedicide comprises following:
1,3, the 4-thiadiazole is like careless thiophene miaow (buthidazole) and ring cafenstrole (cyprazole);
Amides is like allidochlor (allidochlor), benzoylpropethyl (benzoylpropethyl), bromobutide (bromobutide), chlorothiamid (chlorthiamid), dimepiperate (dimepiperate), P DimethenamidP (dimethenamid), enide (diphenamid), diphenyl (etobenzanid), first FLAMPROP (flamprop-methyl), phosphine ammonium plain (fosamin), isoxaben (isoxaben), metazachlor (metazachlor), monalide (monalide), alanap (naptalam), pronamide (pronamide), Stam F-34 (propanil);
The phosphoramidic acid class is like bilanafos (bilanafos), special gram grass (buminafos), careless ammonium phosphine (glufosinate ammonium), Glyphosate 62 IPA Salt (glyphosate), sulphosate (sulfosate);
The aminotriazole class, like amerol (amitrole), the anilide class is like anilofos (anilofos), mefenacet (mefenacet);
Aryloxy alkane acids, as 2,4-D, 2; 4-DB, clomeprop (clomeprop), 2; 4-drips propionic acid (dichlorprop), high by 2, and 4-drips propionic acid (dichlorprop-P), high by 2, and 4-drips propionic acid, 2; 4,5-tears propionic acid (fenoprop), fluroxypyr (fluroxypyr), MCPA, MCPB, Vi par (mecoprop), mecopropP (mecoprop-P), R-7465 (napropamide), naproanilide (napropanilide), TRICLOPYR ACID (triclopyr);
Benzoic acids is like Amiben (chloramben), dicamba 98 (dicamba);
The benzothiadiazine ketone is like bentazon (bentazone);
SYNTHETIC OPTICAL WHITNER is like clomazone (clomazone), diflufenican (diflufenican), fluorochloridone (fluorochloridone), amine grass azoles (flupoxam), fluorine grass (fluridone), pyrazolate (pyrazolate), sulphur humulone (sulcotrione) together;
Amino formate is like carbetamide (carbetamid), Chlorophenocarb (chlorbufam), Y 3 (chlorpropham), different phenmedipham (desmedipham), phenmedipham (phenmedipham), vernolate (vernolate);
Quinoline acids is like quinclorac (q uinclorac), quinmerac (q uinmerac);
The Tripon class is like dalapon (dalapon);
The Dihydrobenzofuranes class is like ethofumesate (ethofumesate);
Dihydrofuran--3-ketone is like flurtamone (flurtamone);
Dinitroaniline; Like benfluralin (benefin), dibutalin (butralin), dinitramine (dinitramin), fourth fluchloralin (ethalfluralin), fluchloralin (fluchloralin), isopropaline,2,6-dinitroN,N-dipropylcumidine (isopropalin), nitralin (nitralin), oryzalin (oryzalin), pendimethalin (pendimethalin), prodiamine (prodiamine), profluralin (profluralin), trifluralin (trifluralin); Dinitrophenols is like Faneron (bromofenoxim), WSX-8365 (dinoseb), WSX-8365 acetic ester (dinoseb acetate), dinoseb acetate phenol (dinoterb), Sinox (DNOC), fourth nitre phenol acetic ester (minoterb acetate); Diphenylether is like acifluorfen (acifluorfen sodium), aclonifen (aclonifen), bifenox (bifenox), chlornitrofen (chlornitrofen), difenoxuron (difenoxuron), ethoxyfenethyl (ethoxyfen), fluorodifen (fluorodifen), fluoroglycofenethyl (fluoroglycofen ethyl), Fomesafen (fomesafen), fluorine furan grass ether (furyloxyfen), lactofen (lactofen), nitrofen (nitrofen), nitre AKH7088 (nitrofluorfen), oxyfluorfen (oxyfluorfen);
Bipyridyliums is like nutgrass flatsedge fast (cyperquat), benzene enemy fast (difenzoquat methyl sulfate), diquat (diquat), paraquat (paraquat dichloride);
Imidazoles is like fourth ring grand (isocarbamid);
Imidazolone type is like imazapic (imazamethapyr), weed eradication cigarette (imazapyr), weed eradication quinoline (imazaquin), miaow grass ester (imazethabenz methyl), Imazethapyr (imazethapyr), imazapic (imazapic), imazamox (imazamox);
Diazoles is like methazole (methazole), alkynes third
azoles grass (oxadiargyl), oxadiazon (oxadiazon);
Ethylene oxide is like tridiphane (tridiphane);
Phenols is like bromoxynil (bromoxynil), ioxynil (ioxynil);
The phenoxy phenoxypropionic acid ester is like alkynes grass ester (clodinafop), cyhalofopbutyl (cyhalofop butyl), diclofop-methyl (diclofop methyl),
azoles diclofop-methyl (fenoxaprop ethyl), high
azoles diclofop-methyl (fenoxaprop p-ethyl), diclofop-methyl thiazole (fenthiaprop ethyl), fluazifop (fluazifop butyl), efficient fluazifop (fluazifop p-butyl), pyrrole fluorine second standing grain spirit (haloxyfop ethoxyethyl), the spirit of pyrrole fluorine chlorine standing grain (haloxyfop methyl), haloxyfopPmethyl (haloxyfopp-methyl), dislike careless ether (isoxapyrifop), propaquizafop (propaquizafop), quizalofop (quizalofop ethyl), quizalofopPethyl (quizalofop p-ethyl), quizalofop (tetrahydro furfuryl ester) (quizalofop tefuryl);
The phenylacetic acid class is like Fenac (chlorfenac);
The phenylpropionic acid class is like chlorphenpropmethyl (chlorophenprop methyl);
Ppi (the ppi=kind is planted preceding soil treating) activeconstituents such as benzofenap (benzofenap); Imide phenoxy acetic acid pentyl ester (flumiclorac pentyl); Fluorine
piperazine ketone (flumioxazin); Flumipropyn; Butafenacil (flupropacil); Pyrazoxyfen (pyrazoxyfen); Sulfentrazone (sulfentrazone); Thiadiazoles amine (thidiazimin);
Pyrazoles is like pyrrole chlorine grass amine (nipyraclofen);
Pyridazine class is like pyrazon (chloridazon), maleic hydrazide (maleic hydrazide), monometflurazone (norflurazon), reach grass and end (pyridate);
The pyridine carboxylic acid class is like morpholine acid dichloride picoline (clopyralid), dithiopyr (dithiopyr), picloram (picloram), thiophene halozydine (thiazopyr);
The pyrimidyl ethers is like phonetic sulphur phenylformic acid (pyrithiobac acid), phonetic sulphur Sodium Benzoate (pyrithiobac sodium), KIH-2023, KIH-6127;
Sulfonamides is like fluorine ethofumesate (flumetsulam), azoles grass sulfanilamide (SN) (metosulam);
The triazole carboxyl acylamide is like triazofenamid;
Uracil is like bromacil (bromacil), lenacil (lenacil), terbacil (terbacil);
And extra benazolin (benazolin) in addition; Benfuresate (benfuresate); Bensulide (bensulide); Fluorine sulfanilamide (SN) grass (benzofluor); Bentazon (bentazone); Glufosinate ammonium (butamifos); Amine grass azoles (cafenstrole); Chlorthal dimethyl (chlorthal dimethyl); Cinmethylin (cinmethylin); Niagara 5006 (dichlobenil); Endothal (endothall); Fluorbentranil; Fluorine grass sulphur (mefluidide); Perfluidone (perfluidone); Piperophos (piperophos); Topramezone and Prohexadione calcium (prohexandione-calcium);
Sulfonylurea is like sulphur ammonia yellow grand (amidosulfuron), tetrazolium yellow grand (azimsulfuron), benzyl ethyl methyl (bensulfuron methyl), chlorimuron (chlorimuron ethyl), chlorsulfuron (chlorsulfuron), ether yellow grand (cinosulfuron), ring third yellow grand (cyclosulfamuron), the Ethanetsulfuron (ethametsulfuron methyl), pyridine ethyl methyl (flazasulfuron), pyrrole chlorsulfuron (halosulfuron methyl), pyridine miaow yellow grand (imazosulfuron), metsulfuron-methyl (metsulfuron methyl), nicoculsfuron (nicosulfuron), Fluoropyrimidinesulfuron (primisulfuron), fluorine third yellow grand (prosulfuron), the pyrazosulfuron (pyrazosulfuron ethyl), rimsulfuron (rimsulfuron), ethyl methyl (sulfometuron methyl), thiophene methyl (thifensulfuron methyl), triasulfuron (triasulfuron), tribenuron-methyl (tribenuron methyl), triflusulfuronmethyl (triflusulfuron methyl), tritosulfuron (tritosulfuron);
Cyclohexenone analog Crop protection activeconstituents is like withered (alloxydim), clethodim (clethodim), tetrahydrobenzene humulone (cloproxydim), cycloxydim (cycloxydim), sethoxydim (sethoxydim) and the tralkoxydim (tralkoxydim) of reaching extremely.
Preferred very especially cyclohexenone analog herbicidal active component is:
Quinone oximes grass (tepraloxydim) (referring to AGROW, the 243rd phase, 11.3.95, the 21st page, caloxydim) and
2-(1-[the 2-{4-chlorophenoxy } third oxyimino group] butyl)-3-hydroxyl-5-(2H-tetrahydric thiapyran-3-group)-2-tetrahydrobenzene-1-ketone
And sulfonylurea type: N-(((4-methoxyl group-6-[trifluoromethyl]-1,3,5-triazines-2-yl) amino) carbonyl)-2-(trifluoromethyl) benzsulfamide.
Suitable sterilant instance comprises following:
Organophosphorus compounds is like Ortho 12420 (acephate), R-1582 (azinphos-methyl), Chlorpyrifos 94 (chlorpyrifos), Zaprawa enolofos (chlorfenvinphos), diazinon (diazinon), SD-1750 (dichlorvos), dimethylvinphos (dimethylvinphos), salithion (dioxabenzofos), SD-3562 (dicrotophos), Rogor (dimethoate), thiodemeton (disulfoton), Nialate (ethion), EPN (EPN), Sumithion (fenitrothion), Tiguvon (fenthion), different
azoles phosphorus (isoxathion), Malathion (malathion), SRA-5172 (methamidophos), methidathion (methidathion), parathion-methyl (methyl-parathion), Phosdrin (mevinphos), SD-9129 (monocrotophos), R 2170 (oxydemeton-methyl), paraoxon (paraoxon), one six zero five (parathion), Tsidial (phenthoate), RP-11974 (phosalone), R-1504 (phosmet), phosphamidon (phosphamidon), phorate (phorate), Volaton (phoxim), PP-511 (pirimiphos-methyl), Tambo (profenofos), Toyodan (prothiofos), primiphos-ethyl, pyraclofos (pyraclofos), kill phosphorus (pyridaphenthion), demephion demephion_O demephion (sulprophos), triazophos (triazophos), Trichlorphon (trichlorfon), tetrachlorvinphos (tetrachlorvinphos), vamidothion (vamidothion) greatly;
Amino formate is like alanycarb (alanycarb), benfuracarb (benfuracarb),
worm prestige (bendiocarb), carbaryl (carbaryl), NIA-10242 (carbofuran), carbosulfan (carbosulfan), ABG-6215 (fenoxycarb), furathiocarb (furathiocarb),
diazole worm (indoxacarb), metmercapturon (methiocarb), methomyl (methomyl), thioxamyl (oxamyl), PP-062 (pirimicarb), Propoxur 97 (propoxur), the two prestige (thiodicarb) of sulphur, triaxamate (triazamate);
Pyrethroids: bifenthrin (bifenthrin); FCR-1272 (cyfluthrin); Cycloprothrin (cycloprothrin); PP-383 (cypermethrin); Deltamethrin (deltamethrin); Esfenvalerate (esfenvalerate); Ether chrysanthemum ester (ethofenprox); Fenvalerate (fenpropathrin); Kill chrysanthemum ester (fenvalerate); (RS) cyhalothrin (cyhalothrin); Cyhalothrin (lambda-cyhalothrin); WL 43479 (permethrin); Deinsectization silicon ether (silafluofen); Taufluvalinate (tau-fluvalinate); Tefluthrin (tefluthrin); Tralomethrin (tralomethrin); Nail body PP-383 (alpha-cypermethrin); Own body PP-383 (zeta-cypermethrin); WL 43479;
Arthropods growth regulator: a) chitin synthesis inhibitor; Benzoyl area kind for example is like UC 62644 (chlorfluazuron), TH-6040 (diflubenzuron), flucycloxuron (flucycloxuron), WL 115110 (flufenoxuron), fluorine bell urea (hexaflumuron), the fluorine third oxygen urea (lufenuron), Rimon (novaluron), Teflubenzuron (teflubenzuron), desinsection grand (triflumuron); PP618 (buprofezin);
luxuriant ether (diofenolan); Hexythiazox (hexythiazox); Special benzene
azoles (etoxazole); Four mite piperazines (clofentazine); B) moulting hormone antagonist is like RH 0345 (halofenozide), Runner (methoxyfenozide), RH-5992 (tebufenozide);
C) JHA is like SK 591 (pyriproxyfen), ZR-515 (methoprene), ABG-6215 (fenoxycarb); D) lipoid biosynthesis inhibitor is like spiral shell mite ester (spirodiclofen);
Anabasine is like flonicamid (flonicamid), thiophene worm amine (clothianidin), MTI-446 (dinotefuran), Provado (imidacloprid), thiophene worm piperazine (thiamethoxam), nitenpyram (nitenpyram), WL 35651 (nithiazin), pyrrole worm clear (acetamiprid), thiophene worm quinoline (thiacloprid);
Extra also have non-classified sterilant,, U-36059 (amitraz), Ai Zhading (azadirachtin), bensultap (bensultap), Bifenazate (bifenazate), cartap (cartap), fluorine azoles worm clear (chlorfenapyr), chlordimeform (chlordimeform), fly eradication amine (cyromazine) clear like avermectin (abamectin), the mite quinone (acequinocyl) that goes out, pyrrole worm, kills mite sulphur grand (diafenthiuron), dinetofuran,
luxuriant ether (diofenolan), Affirm (Merck Co.) (emamectin), 5a,6,9,9a-hexahydro-6,9-methano-2,4 (endosulfan), ethiprole (ethiprole), fenazaquin (fenazaquin), sharp strength special (fipronil), formetanate (formetanate), Formetanate monohydrochloride (formetanate hydrochloride), lindane (gamma-HCH), amdro (hydramethylnon), Provado,
diazole worm, isoprocarb (isoprocarb), MTMC (metolcarb), pyridaben (pyridaben), pymetrozine (pymetrozine), Tracer Naturalyte 105 (spinosad), tebufenpyrad (tebufenpyrad), thiophene worm piperazine, thiocyclarn (thiocyclam), XMC and xylylcarb (xylylcarb).
The N-phenylsemicarbazone, the particularly compound of general formula I I in EP-A 462 456, described with general formula I:
R wherein
5And R
6Be hydrogen, halogen, CN, C independently of each other
1-C
4Alkyl, C
1-C
4Alkoxyl group, C
1-C
4Haloalkyl or C
1-C
4Halogenated alkoxy and R
4Be C
1-C
4Alkoxyl group, C
1-C
4Haloalkyl or C
1-C
4Halogenated alkoxy, for example R wherein
5Be 3-CF
3, R
6Be 4-CN and R
4Be 4-OCF
3Compound IV:
The instance of operable growth regulator is choline dichloride (chlormequat chloride), help strong plain (mepiquat chloride), Prohexadione calcium (prohexadione-calcium) or be selected from those of Plant hormones regulators,gibberellins.These for example comprise Plant hormones regulators,gibberellins GA
1, GA
3, GA
4, GA
5And GA
7Deng and corresponding outer-16,17-dihydro Plant hormones regulators,gibberellins also has its verivate, instance is and C
1-C
4The ester of carboxylic acid.According to the present invention preferred outer-16,17 dihydros-GA
5The 13-acetic ester.
Preferred mycocide is strobilurins class especially for example, and azole and the 6-aryl triazoles in WO 98/46608, WO 99/41255 or WO 03/004465, described with general formula I be the activeconstituents of [1,5-a] pyrimidine, especially general formula III also:
Wherein
R
xBe group NR
7R
8, or optional by halogen, OH, C
1-C
4Alkoxyl group, phenyl or C
3-C
6The linearity of cycloalkyl substituted or branching C
1-C
8Alkyl perhaps is C
2-C
6Alkenyl, C
3-C
6Naphthenic base, C
3-C
6Cycloalkenyl group, phenyl or naphthyl, 4 groups mentioning after wherein can have 1,2,3 or 4 and be selected from halogen, OH, C
1-C
4Alkyl, C
1-C
4Halogenated alkoxy, C
1-C
4Alkoxyl group and C
1-C
4The substituting group of haloalkyl;
R
7And R
8Be hydrogen, C independently of each other
1-C
8Alkyl, C
1-C
8Haloalkyl, C
3-C
10Naphthenic base, C
3-C
6Halogenated cycloalkyl, C
2-C
8Alkenyl, C
4-C
10Alkadienyl, C
2-C
8Halogenated alkenyl, C
3-C
6Cycloalkenyl group, C
2-C
8Halo cycloalkenyl group, C
2-C
8Alkynyl, C
2-C
8Halo alkynyl or C
3-C
6Cycloalkynyl radical, perhaps
R
7And R
8Form 5-8 element heterocycle base with the nitrogen-atoms that they connected, it connects and can comprise 1,2 or 3 other heteroatoms that are selected from O, N and S as ring members and/or can have one or more halogen, C of being selected from via N
1-C
6Alkyl, C
1-C
6Haloalkyl, C
2-C
6Alkenyl, C
2-C
6Halogenated alkenyl, C
1-C
6Alkoxyl group, C
1-C
6Halogenated alkoxy, C
3-C
6Alkenyloxy, C
3-C
6Halo alkenyloxy, (outward)-C
1-C
6Alkylidene group and oxygen base-C
1-C
3The substituting group of alkylene oxide group;
L is selected from halogen, cyanic acid, C
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
6Alkoxyl group, C
1-C
4Halogenated alkoxy and C
1-C
6Carbalkoxy;
L
1Be halogen, C
1-C
6Alkyl or C
1-C
6Haloalkyl, especially fluorine or chlorine;
X
2Be halogen, C
1-C
4Alkyl, cyanic acid, C
1-C
4Alkoxyl group or C
1-C
4Haloalkyl, preferred halogen or methyl, especially chlorine.
The formula III examples for compounds is 5-chloro-7-(4-methyl piperidine-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-(4-N-METHYL PIPERAZINE-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-(morpholine-1-yl)-6-(2,4; The 6-trifluorophenyl)-[1,2,4] triazolo [1,5-a] pyrimidine, 5-chloro-7-(piperidines-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-(morpholine-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2; 4] triazolo [1,5-a] pyrimidine, 5-chloro-7-sec.-propyl amino-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-cyclopentyl amino-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine; 5-chloro-7-(2,2, the 2-trifluoroethyl is amino)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-(1,1,1-trifluoro propane-2-base is amino)-6-(2,4, the 6-trifluorophenyl)-[1; 2,4] triazolo [1,5-a] pyrimidine, 5-chloro-7-(3,3-dimethylbutane-2-base is amino)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-cyclohexyl methyl-6-(2,4, the 6-trifluorophenyl)-[1; 2,4] triazolo [1,5-a] pyrimidine, 5-chloro-7-cyclohexyl-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-(2-methylbutane-3-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2; 4] triazolo [1,5-a] pyrimidine, 5-chloro-7-(3-methylpropane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-(4-methylcyclohexane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolo [1; 5-a] pyrimidine, 5-chloro-7-(hexane-3-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-(2-methylbutane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine; 5-chloro-7-(3-methylbutane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-chloro-7-(1-methylpropane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-methyl-7-(4-methyl piperidine-1-yl)-6-(2; 4, the 6-trifluorophenyl)-[1,2,4] triazolo [1,5-a] pyrimidine, 5-methyl-7-(4-N-METHYL PIPERAZINE-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-methyl-7-(morpholine-1-yl)-6-(2,4; The 6-trifluorophenyl)-[1,2,4] triazolo [1,5-a] pyrimidine, 5-methyl-7-(piperidines-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-methyl-7-(morpholine-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1; 2,4] triazolo [1,5-a] pyrimidine, 5-methyl-7-sec.-propyl amino-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-methyl-7-cyclopentyl amino-6-(2,4, the 6-trifluorophenyl)-[1,2; 4] triazolo [1,5-a] pyrimidine, 5-methyl-7-(2,2, the 2-trifluoroethyl is amino)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-methyl-7-(1,1,1-trifluoro propane-2-base is amino)-6-(2; 4, the 6-trifluorophenyl)-[1,2,4] triazolo [1,5-a] pyrimidine, 5-methyl-7-(3,3-dimethylbutane-2-base is amino)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-methyl-7-cyclohexyl methyl-6-(2; 4, the 6-trifluorophenyl)-[1,2,4] triazolo [1,5-a] pyrimidine, 5-methyl-7-cyclohexyl-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-methyl-7-(2-methylbutane-3-yl)-6-(2,4; The 6-trifluorophenyl)-[1,2,4] triazolo [1,5-a] pyrimidine, 5-methyl-7-(3-methylpropane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-methyl-7-(4-methylcyclohexane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1; 2,4] triazolo [1,5-a] pyrimidine, 5-methyl-7-(hexane-3-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine, 5-methyl-7-(2-methylbutane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2; 4] triazolo [1,5-a] pyrimidine, 5-methyl-7-(3-methylbutane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolo [1,5-a] pyrimidine and 5-methyl-7-(1-methylpropane-1-yl)-6-(2,4, the 6-trifluorophenyl)-[1,2,4] triazolos [1,5-a] pyrimidine.
Suitable sterilant especially is:
-aryl pyrrolines, clear like fluorine azoles worm,
-pyrethroids; Like bifenthrin, FCR-1272, cycloprothrin, PP-383, Deltamethrin, esfenvalerate, ether chrysanthemum ester, Fenvalerate, kill chrysanthemum ester, (RS) cyhalothrin, cyhalothrin, WL 43479, deinsectization silicon ether, taufluvalinate, tefluthrin, tralomethrin, nail body PP-383, own body PP-383 and WL 43479
-sharp strength is special,
-anabasine, and
The semicarbazone class of-Shi II.
Suitable fluorescent agent for example is pyrene, uranine, rhodamine, resorcinolphthalein, tonka bean camphor, allophycocyanin, naphthalene, anthracene.
In one embodiment of the invention, the inventive method can be used at water-bearing media based on the whole aqueous formulation solubilization 0.01-1 weight % according to the present invention's preparation, preferably at least 0.1 weight % hydrophobic active composition.
For the embodiment of the present invention method; Use one or more auxiliary agents; Wherein at least a is hyperbranched polymer (A), and said hyperbranched polymer (A) is specific definition and in context of the present invention, also abbreviate hyperbranched polymer (A), polymkeric substance (A), hyperbranched polymer of the present invention (A) or polymkeric substance of the present invention (A) as below.
In one embodiment of the invention, the molecular-weight average M of hyperbranched polymer (A)
wBe 1000-100000g/mol, preferred 1500-50000g/mol.Molecular-weight average for example can pass through GPC (GPC) and measure.
In one embodiment of the invention, the polymolecularity (M of hyperbranched polymer (A)
w/ M
n) be 1-50, preferred 1.1-30, more preferably 2-15.
Polymkeric substance (A) can through make at least a per molecule have at least one uncle or the hyperbranched polymerizable compound (a) of secondary amino group-in context of the present invention, also abbreviate as hyperbranched compound (a)-with (b) at least a list-, two-or the oligosaccharides reaction obtain, said hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
Hyperbranched compound (a) and therefore to also have the hyperbranched polymer (A) by its preparation be uneven on molecule and structure.They for example are that with the different of branch-shape polymer its molecule ununiformity and they can be with significantly lower complexity preparations.Based on AB
2An embodiment of the molecular structure of the hyperbranched compound of molecule is as finding at WO 04/20503 page 2.For this structure (side chain distribute or the like), this is equally applicable to based on used A in the application's context for example
2+ B
yThe polymkeric substance of strategy (wherein y>=3); For example referring to J.-F.Stumb é etc., Macromol.Rapid Commun.2004,25,921.For the definition of branch-shape polymer and hyperbranched polymer, also referring to P.J.Flory, J.Am.Chem.Soc.1952,74,2718 and H.Frey etc., Chemistry-A European J.2000,6 (14), 2499.
In context of the present invention, hyperbranchedly be interpreted as preferably referring to that degree of branching DB is 10-99.9%, preferred 20-90%, more preferably 80% those polymerizable compounds (a) or polymkeric substance (A) at the most.
Degree of branching DB is defined as:
DB[%]=100·(T+Z)/(T+Z+L)
Wherein T is an end monomeric unit mean number, and Z representes that branched monomer cell-average number and L represent linear monomeric unit mean number, in each case based on per molecule polymerizable compound (a) or polymkeric substance (A).For the definition of DB, referring to H.Frey etc., Acta Polym.1997,48,30.
In context of the present invention, amino is interpreted as referring to primary amino, i.e. NH
2Group, or secondary amino group, preferred NHR
9Group, wherein R
9Be selected from C
1-C
6Alkyl, especially methyl or ethyl, or C
3-C
7Naphthenic base or C
1-C
6Alkylidene group-NH
2, preferred C
2-C
4Alkylidene group-NH
2Or C
2-C
4Alkylidene group-(NH-C
2-C
4Alkylidene group)
w-NH
2Or C
3-C
7Cycloalkylidene-NH
2, wherein w is 1-10, preferred 1-3, and preferred C
2Alkylidene group is (CH
2)
2, it can mix any position in ultrabranching polyamide (a1) or hyperbranched polyureas (a2).
R
9Instance be methyl, CH
2-NH
2, ethyl, CH
2-CH
2-NH
2, propyl group, (CH
2)
3-NH
2, butyl, (CH
2)
4-NH
2, n-hexyl, (CH
2)
6-NH
2, cyclohexyl and to cyclohexylidene-NH
2
Ultrabranching polyamide (a1) or hyperbranched polyureas (a2) can only have primary amino or only have secondary amino group or have primary and secondary amino.
In one embodiment of the invention, ultrabranching polyamide (a1) or hyperbranched polyureas (a2) per molecule have at least two uncles or secondary amino group.
In context of the present invention, ultrabranching polyamide (a1) is interpreted as referring to can be through making monomer A 2 and B
3Polycondensation and those ultrabranching polyamides of preparing, wherein
A
2Be appreciated that and be the list that refers to dicarboxylicacid for example or suitable verivate such as dicarboxylicacid-or two-C
1-C
4Alkyl ester or acid anhydrides, and B
3Be appreciated that to referring to trifunctional or high functionality amine-scheme (A) more, wherein above-mentioned trifunctional or more high functionality amine be selected from per molecule and have 3 or be selected from primary amino and secondary amino group greater than 3, be preferably selected from NH
2Group and NHR
9The compound of the amino of group.Except uncle or secondary amino group, trifunctional or more high functionality amine can also have other functional groups, for example uncle is amino.
Be preferably used as monomer A
2Dicarboxylicacid for example be oxalic acid, propanedioic acid, succsinic acid, pentanedioic acid, hexanodioic acid, pimelic acid, suberic acid, sebacic acid, undecane-α, ω-dioctyl phthalate, cis-with trans-hexanaphthene-1; The 2-dioctyl phthalate; Cis-and trans-hexanaphthene-1, the 3-dioctyl phthalate, cis-and trans-hexanaphthene-1; 4-dioctyl phthalate and verivate thereof, as single-with dialkyl, acyl chlorides or acid anhydrides.
Preferred trifunctional or more high functionality uncle or secondary amine for example are three (2-amino-ethyl) amine, three (2-aminopropyl) amine, NSC 446, Triethylenetetramine (TETA), tetren, two (hexa-methylene) triamine and verivate thereof; And alkoxylate and aminating more high functionality alcohol, for example
T product.
In another embodiment, A
2Be interpreted as referring to for example diamines and B
3Be interpreted as referring to trifunctional or high functionality poly carboxylic acid or derivatives thereof more, like trifunctional or the polycarboxylic acid anhydrides of high functionality more, single-, two-or three-C
1-C
4Alkyl ester-scheme (B).
Preferred diamines for example is quadrol, tn (1 and 1,3-diaminopropanes), 1,4-diaminobutane, 1,5-diamino-pentane, 1,1,8-diamino-octane and isophorone diamine.
Suitable trifunctional or more the high functionality carboxylic acid for example be trimesic acid, trimellitic acid, PMA, butane tricarboxylic acid and hexanaphthene-1,3,5-tricarboxylic acid and verivate thereof, as single-with dialkyl, acyl chlorides or acid anhydrides.
In another embodiment of the present invention, ultrabranching polyamide (a1) is interpreted as referring to can be through making functional carboxylic acid, for example AB
2Those ultrabranching polyamides that the functional carboxylic acid of type obtains from condensation, wherein A representes to have the carboxylic acid of two identical or different functional group B under the situation of ultrabranching polyamide (a1).B for example can be selected from OH, SH and NH thus
2B
2Two NH of preferred expression
2Group.Proper A B
2The instance of type functional carboxylic acid is halfcystine, Serine and especially Methionin.
In another embodiment of the present invention, ultrabranching polyamide (a1) is interpreted as referring to pass through functional carboxylic acid, for example AB
2Those ultrabranching polyamides that the functional carboxylic acid of type obtains from condensation, wherein B representes to have the carboxylic acid of other functional groups A beyond the COOH under the situation of ultrabranching polyamide (a1).A for example can be selected from OH, SH and NH thus
2Proper A B
2The instance of type functional carboxylic acid is L-glutamic acid and aspartic acid.
Amino acid can use with racemic modification or the pure form of enantiomorph in each case, especially uses with the L isomer.
Ultrabranching polyamide (a1) can comprise one or more other compounds of introducing through condensation, for example one or more aliphatic series or aromatics or alicyclic diamine under the situation of scheme (A), perhaps one or more dicarboxylicacid under the situation of scheme (B) for example.
In one embodiment of the invention, the molecular-weight average M of ultrabranching polyamide (a1)
wBe 800-100000g/mol, preferred 1000-75000g/mol.
Ultrabranching polyamide (a1) and preparation method thereof for example is disclosed in WO 2006/018125 and reaches in the document of wherein quoting.
In one embodiment of the invention, ultrabranching polyamide (a1) is selected from hyperbranched poly Methionin (a3).
In context of the present invention, hyperbranched poly Methionin (a3) is interpreted as referring to have the no cross-linked polymer of Methionin as monomeric unit.
In one embodiment of the invention, hyperbranched poly Methionin (a3) can have the monomeric unit beyond the 20mol% Methionin, for example aspartic acid or L-glutamic acid or one or more other dicarboxylicacid, for example hexanodioic acid or succsinic acid at the most.
In one embodiment of the invention, the molecular-weight average M of hyperbranched poly Methionin (a3)
wBe 1000-750 000g/mol, preferred 3000-100 000g/mol.
In one embodiment of the invention, hyperbranched poly Methionin (a3) can have 10-99.9%, preferred 20-99%, more preferably 95% the degree of branching at the most.
In context of the present invention, " uncrosslinked " with regard to hyperbranched poly Methionin (a3) is interpreted as referring to that its degree of crosslinking ratio has same molecular amount M
wAnd can be low through the polylysine that the polycondensation of free lysine alkali obtains.
A tolerance of degree of crosslinking for example is the comparison of the gel content of said polylysine, and this content promptly stores the ratio of insoluble part in 24 hours the process under water under the temperature of 23 ° of C, change into percentage ratio.
Hyperbranched poly Methionin (a3) and preparation method thereof for example is disclosed among the WO 2007/060119.
In context of the present invention, term " hyperbranched polyureas " (a2) also comprises except urea groups, having urethane groups and optional other functional groups, for example amino material.Urethane group is preferably O-alkyl-or O-alkenyl urethane group, and wherein alkyl or alkenyl have 1-18 carbon atom.Preferably can be through the O-alkyl urea groups that isocyanate groups and the monohydroxy-alcohol reaction that is used as encapsulant are obtained.
Hyperbranched polyureas (a2) can obtain by all means, for example through making isocyanic ester and polyamines direct reaction, makes urea and polyamines direct reaction, perhaps through making the reaction of dialkyl carbonate and polyamines.Yet in context of the present invention, hyperbranched polyureas (a2) preferably obtains through POLYMETHYLENE POLYPHENYLISOCYANATE and the polyamines reaction that makes sealing, as WO 03/066702.Other preparing methods have been described; For example WO 2005/044897 A1 has described by organic carbonate, for example diethyl carbonate (A
2And polyfunctional amine, for example triamine (B monomer),
3Monomer) synthetic suitable hyperbranched polyureas (a2).WO 2005/075541 has described by urea or urea derivatives (A
2Monomer) and polyfunctional amine, for example triamine (B
3Monomer) synthesis of super branched polyureas.
Hyperbranched polyureas (a2) preferably can through comprise make at least two functional sealings two-or POLYMETHYLENE POLYPHENYLISOCYANATE and at least a at least two senses uncle and/or secondary amine reaction and the method for eliminating encapsulant obtain.
As this at least two functional sealing two of ingredient requirement-or POLYMETHYLENE POLYPHENYLISOCYANATE for example can be through making two-or POLYMETHYLENE POLYPHENYLISOCYANATE and aliphatic series, araliphatic or aromatic alcohol, preferred monohydroxy-alcohol reaction and preparing.
Suitable monohydroxy-alcohol is preferably linearity or branched aliphatic monohydroxy-alcohol, like methyl alcohol, ethanol, propyl alcohol, butanols, amylalcohol, hexanol, enanthol, octanol, Virahol, isopropylcarbinol or 2-ethyl-1-hexanol or araliphatic monohydroxy-alcohol, like benzylalcohol or phenylethyl alcohol.Preferred especially linearity or branched aliphatic monohydroxy-alcohol, and also have benzylalcohol.Especially preferably have 1-18, the linear aliphatic monohydroxy-alcohol of preferred 1-6 carbon atom.
At least two functional amines that are used to prepare hyperbranched polyureas (a2) are selected from and have at least two compounds that urethane group are reactive amido.Have at least two compounds that urethane group is reactive amido and for example be quadrol, N-alkyl quadrol, tn, 2; 2-dimethyl--1; 3-tn, N-alkyl tn, tetramethylenediamine, N-alkyl tetramethylenediamine, hexamethylene-diamine, N-alkyl hexamethylene-diamine, tolylene diamine, diaminodiphenyl-methane, diamino-dicyclohexyl methane, phenylenediamine, cyclohexyl diamines, diamino diphenyl sulfone, isophorone diamine, 2-butyl-2-ethyl-1; 5-five methylene diamine, 2; 2; 4-or 2; 4; 4-trimethylammonium-1; 6-hexamethylene-diamine, 2-aminopropyl cyclo-hexylamine, 3 (4)-aminomethyl-1,2s-methylcyclohexyl amine, 1,4-diamino--4-methylpentane, the end capped polyoxyalkylene polyol of amine (for example from Huntsman Corporation
), amination polytetramethylene glycol, N-aminoalkyl group piperidines, ammonia, two (amino-ethyl) amine, two (aminopropyl) amine, two (amino butyl) amine, two (amino amyl group) amine, two (amino hexyl) amine, three (amino-ethyl) amine, three (aminopropyl) amine, three (amino hexyl) amine, triamino hexane, 4-aminomethyl-1,2,8-eight methylene diamine, N ' (3-aminopropyl)-N; N-dimethyl--1,3-tn, triaminononane or melamine.In addition, can also use any desired mixt of at least two kinds of said compounds.Preferably at least two senses uncle and/or secondary amine are at least two sense primary amine, more preferably two sense aliphatic primary amine, especially isophorone diamines.
Useful two-or POLYMETHYLENE POLYPHENYLISOCYANATE comprise known aliphatic series itself, alicyclic, araliphatic and aromatics two-and POLYMETHYLENE POLYPHENYLISOCYANATE.These preferably comprise 4,4 '-diphenylmethanediisocyanate, the mixture of haplotype diphenylmethanediisocyanate and oligomeric-type diphenylmethanediisocyanate (polymkeric substance MDI), tetramethylene diisocyanate; The tetramethylene diisocyanate tripolymer, hexamethylene diisocyanate, hexamethylene diisocyanate trimer, isophorone diisocyanate (IPDI); Isophorone diisocyanate trimer, and 2,4 toluene diisocyanate (2,4-TDI); 2,4 '-diphenylmethanediisocyanate (2,4 '-MDI); 2, and the 6-tolylene diisocyanate (2,6-TDI) or triisocyanate base toluene.
In order to form hyperbranched polyureas (a2); Especially preferably following: two-or POLYMETHYLENE POLYPHENYLISOCYANATE; Especially oligomeric-or POLYMETHYLENE POLYPHENYLISOCYANATE; It can be by aliphatic, alicyclic, araliphatic and aromatics; Aliphatic two-or POLYMETHYLENE POLYPHENYLISOCYANATE through by urethane, allophanate, urea, biuret, diazacyclo dimethyl diketone (uretdione), acid amides, isocyanuric acid ester, carbodiimide, diazacyclo butanone imines (uretonimine),
diazine triketone or imino-
diazine diketone structure, preferably connect and prepare by isocyanurate structure.These are oligomeric-or the average N CO functionality that POLYMETHYLENE POLYPHENYLISOCYANATE has usually be 2.1-4.9, preferred 2.9-4.4, especially 3.4-3.9.Average molar mass M
wBe preferably 300-3000g/mol, preferred 400-1500g/mol, especially 500-800g/mol.
In one embodiment of the invention, the hyperbranched polyureas (a2) of selection be in building-up process, added simple function aliphatic series, araliphatic or aromatic amine as chain terminator and synthetic those.Suitable monofunctional amines is a primary alkyl amine, preferred C
1-C
18Alkylamine, more preferably
M product (M1000 and M2010).
M product is the monofunctional polyethers polyvalent alcohol with uncle's end amino from Huntsman Corporation.They begin preparation by the monohydroxy-alcohol initiator, this initiator and ethylene oxide and/or propylene oxide are reacted and the terminal hydroxy group that will in this step, obtain subsequently changes into amino.
In one embodiment, ultrabranching polyamide (a1) and hyperbranched polyureas (a2) have makes they itself for water-soluble, promptly under 23 ° of C less than 1g/l, preferably less than the water-soluble structure of 0.1g/l.
Make above-mentioned polymerizable compound (a) and (b) at least a list-, two-or oligosaccharides-in context of the present invention, also abbreviate as separately monose (b), disaccharides (b) and oligosaccharides (b); Perhaps set abbreviates carbohydrate (b)-reaction as, selects those to make carbohydrate (b) be connected in the reaction of polymerizable compound (a).
In context of the present invention, monose (b) is interpreted as finger can have one or more blocking groups, for example natural the or synthetic monose of ethanoyl, benzyl or acetone solvate.Monose (b) does not preferably have any blocking group.
Preferred monose (b) is pentose, for example pectinose, wood sugar or ribose, and hexose, especially semi-lactosi, seminose or glucose, and extra tagatose such as fructose and sorbose in addition.
In context of the present invention, disaccharides (b) is interpreted as finger can have one or more blocking groups, for example natural the or synthetic disaccharides of ethanoyl, benzyl or acetone solvate.Disaccharides (b) does not preferably have any blocking group.
Preferred disaccharides is crystallised sugar, lactose and SANMALT-S.
In context of the present invention; Oligosaccharides (b) is interpreted as referring to that per molecule has 3-50, preferably at the most 25, and the more preferably natural or synthetic polysaccharide of 20 monosaccharide units at the most; It can have one or more blocking groups, for example ethanoyl, benzyl or acetone solvate.Oligosaccharides (b) does not preferably have any blocking group.
Oligosaccharides (b) is generally water miscible; 10g/l at least under 20 ° of C and standardpressure for example, preferred 20g/l at least, more preferably 100g/l is dissolved in the zero(ppm) water at least.
Carbohydrate (b) can preferably exist with hydrate.
Preferred especially carbohydrate (b) is the oligosaccharides (b) that monose (b), disaccharides (b) and per molecule have 3 sugar units, i.e. trisaccharide (b).
In disaccharides (b) and oligosaccharides (b), sugar unit separately can be identical or different.In oligosaccharides, sugar unit also can be basic identical, glucose unit for example, and more only, and 10mol% at the most for example, preferably 20mol% is not a glucose unit at the most.
In disaccharides (b) or oligosaccharides (b), sugar unit preferably interconnects through glycosidic link.
In one embodiment of the invention, single in polymkeric substance (A)-, two-or oligosaccharides (b) with the glucosides formal bond in hyperbranched polymerizable compound (a), especially via amino key in hyperbranched polymerizable compound (a).In context of the present invention, " glucosides " is meant aldehyde functional group or the ketone of this key via said carbohydrate (b).Glycosidic link can reversible or irreversibly form.
In one embodiment of the invention, different carbohydrate (b) keys are in identical hyperbranched polymer (a).Different carbohydrates for example can for disaccharides (b) be derived from identical sugar unit, the for example oligosaccharides of glucose or seminose (b), or monose (b) and the disaccharides that is derived from identical sugar unit (b), or monose (b) and the oligosaccharides that is derived from identical sugar unit (b).In a scheme, different carbohydrate (b), for example two kinds of different monose (b) or two kinds of different disaccharides (b) or two kinds of different polysaccharide (b) key are in identical hyperbranched polymer (a).
In one embodiment of the invention, the hyperbranched polymerizable compound of per molecule (a) on average the amino key of at least one end in a part carbohydrate (b); Preferred at least two amino of the hyperbranched polymerizable compound of per molecule (a) separately key in a part carbohydrate (b).
In one embodiment of the invention, the uncle or the secondary amino group of hyperbranched polymerizable compound (a) are quantitative, preferably are connected in carbohydrate (b) with the degree of 90mol% at least.
In another embodiment of the present invention, the uncle of the hyperbranched polymerizable compound of 10-90mol% (a) or secondary amino group are connected in carbohydrate (b).
Quantitatively be connected in the NH of carbohydrate (b)
2Each NH of group
2Group is connected in bimolecular carbohydrate (b).
Quantitatively be connected in the NHR of carbohydrate (b)
9Each NHR of group
9Group is connected in the carbohydrate (b) of a part.
When polymerizable compound (a) quantitatively was connected in carbohydrate (b), this was meant that bimolecular carbohydrate (b) is connected in each NH
2And the carbohydrate of a part (b) is connected in each NHR
9Group.
In one embodiment of the invention, hyperbranched polymer of the present invention (A) is contacted with one or more hydrophobic active compositions with water-bearing media, for example contact through mixing.For example mix and to carry out through stirring with conventional whisk or impeller.Other suitable methods are to apply UW or shaken.Mix preferably and in a more than step, carry out,, contact with one or more hydrophobic active compositions then and carry out for example through hyperbranched polymer of the present invention (A) is contacted with water-bearing media.
In one embodiment of the invention, hyperbranched polymer (A) and hydrophobic active composition are with 1:1-1000:1, and the mass ratio of preferred 1:1-100:1 uses.
In one embodiment, hyperbranched polymer (A) is stirred with water-bearing media, stir with one or more activeconstituentss then.
Mixing can be carried out under the temperature of 0-100 ° of C and if hope to use the temperature that raises, also can for example carry out under the temperature of 150 ° of C at the most.Preferably, operate under the temperature of preferred 20-50 ° of C at standardpressure and 15-70 ° of C.
In one embodiment of the invention, after mixing end, remove the hydrophobic active composition of not solubilization, for example through filtration or centrifugal.
The present invention further provides and has dissolved in the hyperbranched polymer (A) that maybe can be scattered in the water; It is water-soluble or water dispersible hyperbranched polymer (A); It can through make at least a hyperbranched polymerizable compound (a) and (b) at least a list-, two-or the oligosaccharides reaction obtain, said hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
The present invention adds dissolution method and can use polymkeric substance of the present invention (A) to carry out especially effectively.
With regard to polymkeric substance of the present invention (A), " water miscible " or " water soluble " is meant under 20 ° of C and standardpressure 10g/l at least, preferred 20g/l at least, and more preferably 100g/l is dissolved in the zero(ppm) water at least.
" water dispersible " polymkeric substance is interpreted as referring in water, not dissolve but can be processed into those polymkeric substance (A) of dispersion-s, and this dispersion-s did not at room temperature form the noticeable sedimentation of any bore hole at least 2 hours.Polymkeric substance (A) with the stationary phase bonding in post is not water dispersible within the scope of the present invention.
Remaining term as above defines separately.
In one embodiment of the invention, oligosaccharides (b) is selected from the compound that per molecule can identical or different monosaccharide unit be formed by 3-20.
In one embodiment of the invention, the molecular-weight average M of hyperbranched polymer of the present invention (A)
wBe 1000-100 000g/mol, preferred 1500-50 000g/mol.Molecular-weight average for example can pass through GPC (GPC) and measure.
In one embodiment of the invention, the polymolecularity (M of hyperbranched polymer of the present invention (A)
w/ M
n) be 1.1-30, more preferably 2-15.
In one embodiment of the invention, single-, two-or oligosaccharides (b) with the glucosides formal bond in hyperbranched polymerizable compound (a), especially via amino key in hyperbranched polymerizable compound (a).
In one embodiment of the invention, ultrabranching polyamide (a1) is selected from hyperbranched poly Methionin (a3).
The present invention further provides a kind of method for preparing hyperbranched polymer of the present invention (A), and it is also referred to as preparation method of the present invention in context of the present invention.In preparation method of the present invention, make the hyperbranched polymerizable compound (a) of at least a being selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas and (b) at least a list-, two-or oligosaccharides in liquid phase, under the reductive amination condition, react.
" in liquid phase " is interpreted as referring to the reaction of hyperbranched polymerizable compound (a) and carbohydrate (b) or is connected in the fused hyperbranched compound (a) or preferably in solution, carries out.
Suitable solvent for example is protic and non-proton organic solvent, for example THF, methylene dichloride, chloroform and alcohols, for example ethanol, Virahol and methyl alcohol.
Specially suitable solvent is a water.
Reductive amination itself is known.At this and be not intended to preferred particular theory; Reductive amination among the present invention can be interpreted as polystep reaction; Wherein in the first step, make the hyperbranched compound (a) with uncle or secondary amino group form the imines that is selected from aldimine and ketoimine with the aldehydes or ketones radical reaction of carbohydrate (b), it is reduced into amine subsequently in second step.
In one embodiment of the invention, used reductive agent is hydrogenate or complex hydride, especially LiBH
4Or NaBH
4Or NaBH
3CN.
In one embodiment of the invention, used reductive agent is borine-Lewis base title complex.Suitable Lewis base for example is a thioether, and ring-type and non-annularity ether and aliphatic series or aromatic amines also have assorted aromatic hydrocarbons.The instance of thioether is dimethyl sulphide and diethyl thioether.Suitable non-annularity ether instance is the different or preferred identical two-C of alkyl especially wherein
2-C
10Dialkyl ether, for example ether, DIPE and di-n-butyl ether.The instance of cyclic ether is THF (THF) and tetrahydropyrans.The instance of aliphatic amine is a TERTIARY BUTYL AMINE.The instance of tertiary amine is three-C especially
1-C
4Alkylamine, triethylamine for example, extra also have Wyovin, for example [2,2,2]-diazabicyclo octane (Dabco).The instance of aromatic amine especially is aromatic uncle amine such as N, accelerine and N, N-Diethyl Aniline.The instance of heteroaromatics especially is pyridine, 2-picoline and aldehydecollidine.
In one embodiment of the invention, the reductive agent of selection is the xitix in acetate/acetate buffer.
In another embodiment, selection does not have the acetate/acetate buffer of extra reductive agent between carbohydrate (b) and amino, also to reduce subsequently via imine intermediate and forms key, and this is by D.Bahdra; A.K.Yadav, S.Bhadra, N.K.Jain International Journal of Pharmaceutics 2005; 295,221-233 and P.V.Kumar etc., Journal of Drug Targeting 2006; 14,546-556 is known.
The following heteroaromatic amine of preferred especially selection is as Lewis base, and wherein at least one nitrogen-atoms is the part of heteroaromatic system such as pyridine, and it is for example by C
1-C
4Alkyl replaces, and perhaps more preferably is not substituted.Preferred very especially borine-Lewis base complex B H
3Pyridine also abbreviates BH as in document
3* Py.
In one embodiment of the invention, hyperbranched polymerizable compound (a) and carbohydrate (b) are so that the mol ratio of uncle or secondary amino group and carbohydrate (b) is 1:0.5-1:20, and the ratio of preferred 1:1-1:10 is used.
In one embodiment of the invention, carbohydrate (b) and reductive agent most preferably use with equimolar amount with the mol ratio of 1:1-1:3.
In this reaction, the amino that can will transform by the optional excessive control of using is with that what will transform is amino.If it is only will transform primary amino, then just much of that by stoichiometric ratio use carbohydrate (b) and reductive agent based on primary amino.If also will transform secondary amino group, then reductive agent and carbohydrate (b) are separately with respect to using with stoichiometric quantity from the amino summation of the primary and secondary of hyperbranched polymerizable compound (a).If also will transform all secondary amino groups, then require big excessive reductive agent.
In one embodiment of the invention, preparation method of the present invention carries out under the temperature of preferred 15-70 ° of C at 0-100 ° of C.
Have been found that the suitable reaction times be 1 hour to 2 weeks, the reaction times can be used as the function of temperature and selects.Temperature is low more, and the reaction times of selection is long more.
The reaction pressure itself of carrying out preparation method of the present invention is unimportant.Preferred choice criteria pressure.
In one embodiment of the invention, preparation method of the present invention is at 3-10, and preferred 6-9 more preferably carries out under the pH of 8-9.In order to produce this pH, can the known buffer reagent of use itself, for example acetate buffer or borate buffer.
In one embodiment of the invention,, the chemical reaction of preparation hyperbranched polymer of the present invention (A) omits purification after finishing.
In another embodiment of the present invention,, the chemical reaction of preparation hyperbranched polymer of the present invention (A) purifies after finishing.This purification for example can comprise the Lewis base of evaporating solvent and release.Purification can extraly comprise removes the inorganic salt that for example come from used buffer reagent.
Aftertreatment can be through known method itself, for example chromatography, redeposition, filtration, particle size dependence separation method such as ultrafiltration, or dialysis is carried out.
The present invention further provides the mixture that comprises at least a hyperbranched polymer of the present invention (A) and at least a hydrophobic active composition.Mixture is interpreted as not only referring to the mixture on the mixture theory significance, but also refers to inclusion compound or other aggregates of hydrophobic active composition and hyperbranched polymer of the present invention (A), and is not intended to preferred particular theory.
Mixture of the present invention for example can comprise a part or polymolecular hydrophobic active composition and a part or polymolecular hyperbranched polymer of the present invention (A), promptly need not to comprise hydrophobic active composition of a part just in time and the hyperbranched polymer of the present invention (A) of a part just in time.In addition, mixture of the present invention can comprise water or other the composition/additives that is present in this preparaton with infix form.
The present invention further provides a kind of method for preparing mixture of the present invention.The program of preparation mixture of the present invention can be that at least a hydrophobic active composition and at least a hyperbranched polymer of the present invention (A) are mixed each other, for example mixes through one of aforesaid method, preferably in the presence of water, mixes.
The present invention for example further provides with 0.01-400g/l, and more preferably the concentration of 0.015-100g/l comprises the aqueous formulation of at least a mixture of the present invention.
Mixture of the present invention and therefore also have aqueous formulation of the present invention for example to be used as crop protection agents or to be used to produce medicine according to used hydrophobic active composition.
Embodiment explains the present invention by work.
Term:
DBTL: di-n-butyltin dilaurate
Universal description:
Ultrabranching polyamide (a1) and hyperbranched polyureas (a2) are through having the GPC analysis of refractometer as detector.Used mobile phase is hexafluoroisopropanol (HFIP) or water; The standard substance that is used for determining molecular weight is polymethylmethacrylate (PMMA).
The amine value is measured according to DIN EN 13717.
Hyperbranched polymer of the present invention (A) is through having the GPC analysis of refractometer as detector.
Dialysis is used from Carl Roth GmbH & Co, and the ZelluTrans/Roth V series dialyzer of Karlsruhe/ Germany carries out.Unless otherwise, use the type of MWCO (molecular weight intercepting value) as 1000g/mol.
I. prepare ultrabranching polyamide (a1)
I.1 prepare ultrabranching polyamide (a1.1)
In the reaction vessel that whisking appliance, internal thermometer, reflux exchanger and nitrogen inlet tube are housed, at first add the 362g tetren.Under agitation in 1 hour, be metered into the 238g dimethyl adipate so that internal temperature is about 100 ° of C.In case reinforced the completion just is heated to 140 ° of C with reaction mixture and stirring 1 hour under 140 ° of C.Then reflux exchanger is exchanged for the descending condensing surface (descending condenser) with collection container and begins to distill the methyl alcohol of removing release in this reaction.The liquid measure that distillates of after 150 minutes, collecting is a 17.1g methyl alcohol.Make this reaction terminating through being cooled to room temperature then.The ultrabranching polyamide (a1.1) that is so obtained with the heavy-gravity yellow oil.
Analytical data (GPC in HFIP): M
n=6300g/mol; M
w=14300g/mol
Amine value: primary amine: 120mg KOH/g (a1.1), secondary amine: 381mg KOH/g (a1.1).
I.2 prepare ultrabranching polyamide (a1.2)
In the reaction vessel that whisking appliance, internal thermometer, reflux exchanger and nitrogen inlet tube are housed, at first add 343.9g three (2-amino-ethyl) amine.Under agitation in 2 hours, be metered into the 256.1g dimethyl adipate so that internal temperature is about 100 ° of C.In case reinforced the completion just is heated to 140 ° of C with reaction mixture and stirring 90 minutes under 140 ° of C.Then reflux exchanger is exchanged for the descending condensing surface with collection container and begins to distill the methyl alcohol of removing release in this reaction.The liquid measure that distillates of after 2 hours, collecting is a 14.3g methyl alcohol.Make this reaction terminating through being cooled to room temperature then.The ultrabranching polyamide (a1.2) that is so obtained with the heavy-gravity yellow oil.
Analytical data (GPC in HFIP): M
n=5400g/mol; M
w=10700g/mol;
Amine value: primary amine: 346mg KOH/g (a1.2), secondary amine: 50mg KOH/g (a1.2).
I.3 prepare hyperbranched polyureas (a2.1)
Step 1: at first in the drying nitrogen flushing, in the reaction vessel that whisking appliance, internal thermometer, reflux exchanger and nitrogen inlet tube are housed, add 1903.9g trimerization hexamethylene diisocyanate, and under agitation be heated to 80 ° of C.Under constant agitation, in 5 hours, add the 751.1g anhydrous normal butyl alcohol then, so that the temperature of reaction mixture is no more than 80 ° of C.After reinforced the end, this mixture was stirred 1 hour under 80 ° of C, be cooled to room temperature then.
Step 2: in the drying nitrogen flushing, whisking appliance is being housed; Internal thermometer; Have in the reaction vessel of descending condensing surface and nitrogen inlet tube of collection container reaction product and the 50.2g isophorone diamine of 255g from step 1; 294.8g
M-1000 and 0.1g DBTL mix.Under constant agitation, reaction mixture is heated to 170 ° of C and under 170 ° of C, stirred 90 minutes, in this process, steam and remove the propyl carbinol that in reaction, discharges.In reaction process, the amine consumption in the reaction mixture is through monitoring with 0.1N HCl titration aliquot and measuring transformation efficiency with the percentage ratio of the transformation efficiency possible with respect to theory thus.In case reach 68% transformation efficiency, just this mixture is cooled to room temperature, this stops this reaction.This obtains hyperbranched polyureas (a2.1) with HV yellow liquid form.
Analytical data (GPC in HFIP): M
n=10200g/mol; M
w=37700g/mol;
Amine value: primary amine 26mg KOH/g (a2.1).
I.4 prepare hyperbranched poly Methionin (a3.1)
Whisking appliance, internal thermometer are being housed, are having in the reaction vessel of descending condensing surface and nitrogen inlet tube of collection container 1000g L-Methionin mono-hydrochloric salts is mixed with 219.1g NaOH, 150g water and 0.1g DBTL.Under agitation reaction mixture is heated to 150 ° of C and under 150 ° of C, stirred 5.5 hours, in this process, the water that forms steamed from reaction mixture and remove.In case steam to remove 312g water, just the pressure in the reaction vessel reduced to 200 millibars and temperature risen to 170 ° of C, to steam except that further water.This mixture was stirred 30 minutes under 170 ° of C, be cooled to room temperature then, this stops this reaction.
Obtain hyperbranched poly Methionin (a3.1) with yellow solid.
Analytical data (GPC in water): M
n=14300g/mol, M
w=118000g/mol,
Amine value=n.d.
I.5 prepare hyperbranched poly Methionin (a3.2)
Whisking appliance, internal thermometer are being housed, are having in the reaction vessel of descending condensing surface and nitrogen inlet tube of collection container 1000g L-Methionin mono-hydrochloric salts is mixed with 219.1g NaOH, 150g water and 0.1g DBTL.Under agitation reaction mixture is heated to 150 ° of C and under 150 ° of C, stirred 5.5 hours, in this process, the water that forms steamed from reaction mixture and remove.In case steam to remove 230g water, just the pressure in the reaction vessel reduced to 200 millibars and temperature risen to 170 ° of C, to steam except that further water.This mixture was stirred 30 minutes under 170 ° of C, be cooled to room temperature then, this stops this reaction.
Analytical data (GPC in HFIP): M
n=1370g/mol, M
w=2800g/mol,
Amine value=378mg KOH/g (a3.2)
II. prepare hyperbranched polymer of the present invention (A)
II.1 prepares hyperbranched polymer of the present invention (A1.2-1-1)
In the 1L flask with 10g ultrabranching polyamide (a1.2)-in the moisture sodium borate buffer agent of 350ml 0.1M and this mixture was at room temperature stirred 1 hour corresponding to 61.8mmol NH2 group-be dissolved in.Under vigorous stirring, add 222.7g (618mmol) D (+)-SANMALT-S (b.1) then.Then with this mixture heating up to 50 ° C.In this process, realize the dissolving fully of D (+)-SANMALT-S (b.1).Adding the 8M solution (618mmol) of 77.3ml borine-pyridine complex in THF afterwards, reaction mixture was stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and with the product freeze-drying that obtains.Obtain hyperbranched polymer of the present invention (A1.2-1-1) with white amorphous products, yield is 20% (10g).
II.2 prepares hyperbranched polymer of the present invention (A1.2-1-2)
In the 1L flask with 10g ultrabranching polyamide (a1.2)-in the moisture sodium borate buffer agent of 100ml 0.1M and this mixture was at room temperature stirred 1 hour corresponding to 61.8mmol NH2 group-be dissolved in.Under vigorous stirring, add 22.3g (61.8mmol) D (+)-SANMALT-S (b.1) then.Then with this mixture heating up to 50 ° C.In this process, realize the dissolving fully of D (+)-SANMALT-S (b.1).Adding the 8M solution (61.8mmol) of 7.8ml borine-pyridine complex in THF afterwards, reaction mixture was stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and with the product freeze-drying that obtains.Obtain hyperbranched polymer of the present invention (A1.2-1-2) with white amorphous products, yield is 10% (3.2g).
II.3 prepares hyperbranched polymer of the present invention (A3.1-1-1)
In the 1L flask, 5g hyperbranched poly Methionin (a3.1) is dissolved in the moisture sodium borate buffer agent of 350ml 0.1M and this mixture is at room temperature stirred half a hour.Under vigorous stirring, add 277g (769mmol) D (+)-SANMALT-S (b.1) then.Then with this mixture heating up to 50 ° C.In this process, realize the dissolving fully of D (+)-SANMALT-S (b.1).Adding the 8M solution (769mmol) of 96ml borine-pyridine complex in THF afterwards, reaction mixture was stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and with the product freeze-drying that obtains.Obtain hyperbranched polymer of the present invention (A3.1-1-1) with white amorphous products, yield is 30% (18.1g).
II.4 prepares hyperbranched polymer of the present invention (A3.1-1-2)
In the 1L flask, 5g hyperbranched poly Methionin (a3.1) is dissolved in the moisture sodium borate buffer agent of 50ml 0.1M and this mixture is at room temperature stirred half a hour.Under vigorous stirring, add 27.7g (76.9mmol) D (+)-SANMALT-S (b.1) then.Then with this mixture heating up to 50 ° C.In this process, realize the dissolving fully of D (+)-SANMALT-S (b.1).Adding the 8M solution (76.9mmol) of 9.6ml borine-pyridine complex in THF afterwards, reaction mixture was stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and with the product freeze-drying that obtains.Obtain hyperbranched polymer of the present invention (A3.1-1-2) with white amorphous products, yield is 21% (7.0g).
II.5 prepares hyperbranched polymer of the present invention (A2.1-1-2)
In the 1L flask with the hyperbranched polyureas of 10g (a2.1)-in the moisture sodium borate buffer agent of 50ml 0.1M and this mixture was at room temperature stirred 1 hour corresponding to 4.64mmol NH2 group-be dissolved in.Under vigorous stirring, add 1.67g (4.64mmol) D (+)-SANMALT-S (b.1) then.Then with this mixture heating up to 50 ° C.In this process, realize the dissolving fully of D (+)-SANMALT-S (b.1).Adding the 8M solution (46.4mmol) of 0.58ml borine-pyridine complex in THF afterwards, reaction mixture was stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and with the product freeze-drying that obtains.Obtain hyperbranched polymer of the present invention (A2.1-1-2) with white amorphous products, yield is 30% (3.5g).
III. solubilization test-with the program of hyperbranched polymer of the present invention (A2.1-1-1) solubilization pyrene
100mg hyperbranched polymer of the present invention (A2.1-1-1) is weighed in the 50ml beaker and is dissolved in the 9.9g zero(ppm) water.Then the 100mg pyrene is weighed in this mixture to obtain supersaturated solution.By magnetic stirring apparatus this mixture was at room temperature stirred 24 hours then.After leaving standstill 1 hour, through the centrifugal activeconstituents of removing excessive (i.e. not solubilization).The active component content of the clear solution that so obtains by the UV analysis of spectral method then.The wavelength of UV spectral measurement is 334nm.
The solubilization test result is compiled in the table 1.
Table 1: having and do not having the solubleness [mg/l] of pyrene in water under the hyperbranched polymer (A)
| Hyperbranched polymer | Pyrene |
| Do not have | 0.1 |
| (A2.1-1-1) | 12.9 |
Claims (17)
1. the method for a solubilization hydrophobic active composition in water-bearing media; Comprise and use at least a hyperbranched polymer (A) as auxiliary agent; Said hyperbranched polymer (A) can through make at least a per molecule have at least one uncle or the hyperbranched polymerizable compound (a) of secondary amino group and (b) at least a list-, two-or the oligosaccharides reaction obtain, said hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
2. according to the process of claim 1 wherein the molecular-weight average M of said hyperbranched polymer (A)
wBe 1000-100000g/mol.
3. according to the method for claim 1 or 2, wherein said hydrophobic active composition is selected from crop protection agents and pharmaceutically active substance.
4. according to each method among the claim 1-3, wherein said hydrophobic active composition is selected from sterilant and mycocide.
5. according to each method among the claim 1-4, wherein said oligosaccharides is selected from per molecule by 3-20 compound that can identical or different monosaccharide unit forms.
6. according to each method among the claim 1-5, wherein said ultrabranching polyamide (a1) is selected from hyperbranched poly Methionin (a3).
7. water-soluble or water dispersible hyperbranched polymer (A); It can through make at least a per molecule have at least one uncle or the hyperbranched polymerizable compound (a) of secondary amino group and (b) at least a list-, two-or the oligosaccharides reaction obtain, said hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
8. according to the hyperbranched polymer (A) of claim 7, wherein said oligosaccharides is selected from per molecule by 3-20 compound that can identical or different monosaccharide unit forms.
9. according to the hyperbranched polymer (A) of claim 7 or 8, its molecular-weight average M
wBe 1000-100000g/mol.
10. according to each hyperbranched polymer (A) among the claim 7-9, wherein said list-, two-or oligosaccharides (b) with the glucosides formal bond in hyperbranched polymerizable compound (a).
11. according to each hyperbranched polymer (A) among the claim 7-10, wherein said ultrabranching polyamide (a1) is selected from hyperbranched poly Methionin (a3).
12. method for preparing according to each hyperbranched polymer (A) among the claim 7-11; It comprises make at least a per molecule have at least one uncle or the hyperbranched polymerizable compound (a) of secondary amino group and (b) at least a list-, two-or oligosaccharides in liquid phase, under the reductive amination condition, react, said hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
13. according to the method for claim 12, wherein said reductive amination is undertaken by borine-Lewis base title complex.
14. according to the method for claim 12 or 13, wherein said reductive amination is undertaken by borine-pyridine complex.
15. a mixture comprises at least a according to each hyperbranched polymer (A) and at least a hydrophobic active composition among the claim 7-11.
16. an aqueous formulation comprises at least a mixture according to claim 15.
17. a method for preparing according to the mixture of claim 15, it comprises at least a hyperbranched polymer (A) and at least a hydrophobic active composition is mixed each other.
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| EP10152726.5 | 2010-02-05 | ||
| EP10152726 | 2010-02-05 | ||
| PCT/EP2011/051292 WO2011095449A1 (en) | 2010-02-05 | 2011-01-31 | Method for solubilizing hydrophobic active ingredients in an aqueous solution |
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| CN110678498A (en) * | 2017-05-12 | 2020-01-10 | 巴斯夫欧洲公司 | Polylysine derivatives and their use in solid based compositions |
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| CN101163463A (en) * | 2005-02-21 | 2008-04-16 | 巴斯福股份公司 | Active substance composition comprising at least one nitrogen atom-containing, hyperbranched polymer |
| CN101316860A (en) * | 2005-11-25 | 2008-12-03 | 巴斯夫欧洲公司 | Production and use of highly functional, highly branched or hyperbranched polylysines |
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| DE3316510A1 (en) | 1983-05-06 | 1984-11-08 | Bayer Ag | PARENTERAL FORMULATION OF NIMODIPIN, A METHOD FOR THE PRODUCTION THEREOF AND THEIR USE IN THE FIGHT AGAINST DISEASES |
| ES2089056T3 (en) | 1990-06-16 | 1996-10-01 | Nihon Nohyaku Co Ltd | DERIVATIVES OF HYDRAZINCARBOXAMIDE, A PROCEDURE FOR THE PRODUCTION OF THE SAME, AND USES OF THE SAME. |
| DE4207481A1 (en) | 1992-03-10 | 1993-09-16 | Bayer Ag | LIPOSOMAL ACTIVE SUBSTANCE FORMULATIONS AND METHOD FOR THE PRODUCTION THEREOF |
| TW460476B (en) | 1997-04-14 | 2001-10-21 | American Cyanamid Co | Fungicidal trifluoromethylalkylamino-triazolopyrimidines |
| ATE213491T1 (en) | 1997-08-20 | 2002-03-15 | FUNGICIDE 2-METHOXYBENZOPHENONE | |
| HUP0100885A3 (en) | 1998-02-11 | 2002-12-28 | American Cyanamid Company Madi | Fungicidal 7-alkyl-triazolopyrimidines |
| ATE353901T1 (en) | 2001-07-05 | 2007-03-15 | Basf Ag | FUNGICIDAL TRIAZOLOPYRIMIDINES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE FOR CONTROLLING HARMFUL FUNGI AND AGENTS CONTAINING SAME |
| DE10204979A1 (en) | 2002-02-06 | 2003-08-14 | Basf Ag | Process for the production of highly functional highly branched polyureas |
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| DE102004039101A1 (en) | 2004-08-11 | 2006-02-23 | Basf Ag | Process for the preparation of hyperbranched polyamides |
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| CN101163463A (en) * | 2005-02-21 | 2008-04-16 | 巴斯福股份公司 | Active substance composition comprising at least one nitrogen atom-containing, hyperbranched polymer |
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| CN110678498A (en) * | 2017-05-12 | 2020-01-10 | 巴斯夫欧洲公司 | Polylysine derivatives and their use in solid based compositions |
| CN110678499A (en) * | 2017-05-12 | 2020-01-10 | 巴斯夫欧洲公司 | Polylysine derivatives stabilize solid-based compositions comprising one or more salts |
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| WO2011095449A1 (en) | 2011-08-11 |
| EP2531548A1 (en) | 2012-12-12 |
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