CN102741327B - Method for solubilizing hydrophobic active ingredients in an aqueous solution - Google Patents

Method for solubilizing hydrophobic active ingredients in an aqueous solution Download PDF

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Publication number
CN102741327B
CN102741327B CN201180008293.2A CN201180008293A CN102741327B CN 102741327 B CN102741327 B CN 102741327B CN 201180008293 A CN201180008293 A CN 201180008293A CN 102741327 B CN102741327 B CN 102741327B
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hyperbranched
hyperbranched polymer
hydrophobic active
methyl
active composition
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CN102741327A (en
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B·布鲁赫曼
H·蒂尔克
D·舍恩菲尔德
M·哈贝雷希特
D·阿佩尔汉斯
V·博伊科
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BASF SE
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BASF SE
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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
    • 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

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 method of solubilization hydrophobic active composition in the aqueous solution
The present invention relates to a kind of in water-bearing media the method for solubilization hydrophobic active composition, the method comprises uses at least one hyperbranched polymer (A) as auxiliary agent, described hyperbranched polymer (A) can by making at least one per molecule have at least one uncle or a hyperbranched polymerizable compound (a) and (b) of secondary amino group, at least one be single-, two-or oligosaccharides react and obtain, described hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
The invention further relates to hyperbranched polymer (A), it can by making at least one per molecule have at least one uncle or a hyperbranched polymerizable compound (a) and (b) of secondary amino group, at least one be single-, two-or oligosaccharides in liquid phase, react and obtain, described 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 of preparing mixture of the present invention that comprise at least one hyperbranched polymer of the present invention and at least one hydrophobic active composition.The invention further relates to a kind of method of preparing hyperbranched polymer of the present invention.
In many cases need to be in water solubilization lyophobic dust, for example hydrophobic active composition and activeconstituents itself described in non-chemical modification.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 carry in water with body fluid those, this generic operation is impossible.Under the effect of high shear force, emulsion may breakdown of emulsion.In addition, when maintaining this emulsion, sterilizing is impossible in many cases.
For example, in the solvent mixture that can be dissolved in second alcohol and water and propylene glycol or polyoxyethylene glycol by the known hydrophobic drug activeconstituents of DE-A 33 16 510 and can process and for example obtain can parenteral admin preparaton.Such solvent mixture comprises 15-30 % by weight ethanol conventionally.Yet, wish in many cases to avoid a large amount of like this alcohol in patient's treatment.
The extra known phosphatide of using in water, is specially the activeconstituents of liposome phosphatide solubilization based on Isosorbide-5-Nitrae-dihydropyridines; For example, referring to EP 0 560 138 A.Yet liposome phosphatide stands the mechanism of degradation identical with endogenous cell membrane lipid.Therefore the liposome delivery system, producing in this way only has the limited storage time according to the pH of this medium and ionic strength.Especially due to the shearing force occurring in the intravenous administration process at activeconstituents, may easily destroy liposome delivery system.
In addition, observe in many cases the solubilizing agent of excessive concentrations in liver or spleen and activeconstituents in blood vessel is undesirably transported to surrounding tissue and even after the short period of time, due to the dynamic structure of double-layer of lipoid, observe the slow release of encapsulated active ingredients.The difficulty of sterilizing 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, its performance in solubilization lyophobic dust for many objects not and can further improve.
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 one hydrophobic active composition and hyperbranched polymer with nitrogen, for example combination of polyureas.Yet, its performance in solubilization lyophobic dust for many objects not and can further improve.
D.Appelhans etc., Biomacromolecules 2009,10, and 1114 and D.Appelhans etc., Molecular Bioscience 2007,7,373 discloses and can carry out complexing drug substance with the hyperbranched polyethyleneimine being connected with oligosaccharides.
In water-bearing media, the shortcoming of the known architectures of solubilization hydrophobic active composition is that they only can a small amount of activeconstituents of solubilization.In addition, many unfunctionalized hyperbranched polymers used, for example many polymeric amide and polyureas, itself be not water-soluble or for water dispersible conventionally, thereby they are not suitable for solubilization in water-bearing media.In addition, the shortcoming that contains the solubilizing agent of polymine is the amino still existing in a large number after functionalized due to even, and they have the too high polar structure that is not suitable for solubilization hydrophobic active composition.
Therefore, the object 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 is to provide 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 to be 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 by complexing.
In the context of the invention, water-bearing media is interpreted as referring to for example following: water, water and at least one organic solvent are as methyl alcohol, ethanol, ethylene glycol, propylene glycol, polyoxyethylene glycol, Virahol, Isosorbide-5-Nitrae-bis- alkane or N, the solvent mixture of dinethylformamide, the aqueous solution of sugar, D/W for example, the aqueous solution of salt, for example sodium chloride aqueous solution or potassium chloride solution, aqueous solution of buffer agent, phosphate buffered saline buffer for example, or especially water or human or animal's body fluid of containing water, for example blood, urine and spleen liquid (splenic fluid).
Preferably water-bearing media is interpreted as referring to pure (distillation) water, sodium chloride aqueous solution, especially normal saline solution, or the solvent mixture of water and at least one above-mentioned organic solvent, and wherein the ratio of organic solvent is no more than 10 % by weight of described water-bearing media.
In the context of the invention; activeconstituents also can be called effector substance and for for example as crop protection agents; for example Insecticides (tech) & Herbicides (tech) or mycocide; that class material that preferably sterilant and mycocide work; or for as fluorescent agent effectively or there is drug effect, for example, as cardiovascular drug or anti-osteoporotic or as that class material of cytostatic.Pigment is not activeconstituents in the context of the invention.
Suitable cardiovascular drug example is for example those of formula I:
In the formula, the following institute of each variable and each group defines:
Y is NO 2, CN or COOR 1, wherein
R 1for not being substituted or by C 1-C 3alkoxyl group is as the C of methoxyl group, oxyethyl group, positive propoxy, isopropoxy replacement one or many 1-C 4alkyl is as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl; The radicals R replacing 1example be for example methoxymethyl, ethoxyl methyl, 2-methoxy ethyl;
W is CO-NH-C 3-C 7cycloalkyl 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 is 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, particularly preferably C 1-C 4alkyl is as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl and the tertiary butyl, especially methyl.The radicals R replacing 2example be for example methoxymethyl, ethoxyl methyl, 2-methoxy ethyl, 2,2,2-trifluoroethyl;
R 3be selected from CN, ω-hydroxyalkyl, preferably ω-hydroxyl-C 1-C 4alkyl, especially methylol and 2-hydroxyethyl, or C 1-C 4alkyl, as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl and the tertiary butyl;
X 1identical or different and be selected from NO in each case 2, halogen, especially fluorine, chlorine or bromine, C 1-C 4alkyl, as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl and the tertiary butyl, C 1-C 4alkoxyl group, as 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 preferably 1 or 2.
The example 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 distilled water is preferably below 1g/l, more preferably below 0.1g/l under 20 ° of C.
The example 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 the context of the invention are hormone, proton pump inhibitor, statin, proteasome inhibitor, anodyne and pravastatin.
Can comprise as follows according to the example 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 ring the third pyrimidine (cyrodinyl);
Antibiotic, for example cycloheximide (cycloheximide), grisovin (griseofulvin), spring thunder element (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), encircle 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 describing with general formula I in EP 0 897 904, for example metrafenone (metrafenone);
Dicarboximide class, for example fixed (iprodione), myclozolin (myclozolin) of isopropyl, sterilization profit (procymidone), vinclozolin (vinclozolin);
Dithiocarbamate(s), for example Karbam Black (ferbam), Parzate (nabam), maneb (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), carboxin (carboxin), oxycarboxin (oxycarboxin), cyazofamid (cyazofamid), dazomet (dazomet), Delan (dithianon), famoxadone (famoxadon), fenamidone (fenamidon), fenarimol (fenarimol), fuberidazole (fuberidazole), fultolanil (flutolanil), furan pyrazoles spirit (furametpyr), isoprothiolane (isoprothiolane), the third oxygen goes out and embroiders amine (mepronil), nuarimol (nuarimol), fluopicolide (picobezamid), thiabendazole (probenazole), the third oxygen quinoline (proquinazid), pyrifenox (pyrifenox), pyroquilon (pyroquilon), quinoxyfen (quinoxyfen), Silthiopham (silthiofam), Apl-Luster (thiabendazole), thifluzamide (thifluzamid), thiophanate methyl (thiophanate-methyl), tiadinil (tiadinil), tricyclazole (tricyclazole), triforine (triforine),
Nitrophenyl derivative, for example, as Niagara 9044 (binapacryl), dinocap (dinocap), dinobuton (dinobuton), isopropyl disappear (nitrophthal-isopropyl);
Phenylpyrrole class, for example fenpiclonil (fenpiclonil) and fluorine bacterium (fludioxonil);
Non-classified mycocide, for example thiadiazoles element (acibenzolar-S-methyl), benzene metsulfovax (benthiavalicarb), carpropamide (carpropamid), m-tetrachlorophthalodinitrile (chlorothalonil), cyflufenamid (cyflufenamid), cymoxanil (cymoxanil), diclomezine (diclomezin), two chlorine zarilamids (diclocymet), the mould prestige of second (diethofencarb), Hinosan (edifenphos), Guardian (ethaboxam), fenhexamid (fenhexamid), fentinacetate (fentin acetate), zarilamid (fenoxanil), ferimzone (ferimzone), fluazinam (fluazinam), fosetyl (fosetyl), fosetyl aluminium (fosetyl aluminum), iprovalicarb (iprovalicarb), Perchlorobenzene (hexachlorobenzene), metrafenone (metrafenone), pencycuron (pencycuron), hundred dimension spirits (propamocarb), phthalide (phthalide), tolclofosmethyl (toloclofos-methyl), quintozene (q uintozene), zoxamide (zoxamid),
The strobilurins class (strobilurins) of describing with general formula I in WO 03/075663, example is nitrile Azoxystrobin (azoxystrobin), dimoxystrobin (dimoxystrobin), fluoxastrobin (fluoxastrobin), imines bacterium (kresoxim-methyl), fork phenalgin acid amides (metominostrobin), orysastrobin (orysastrobin), ZEN 90160 (picoxystrobin), Strobilurin (pyraclostrobin) and oxime bacterium ester (trifloxystrobin);
Sulfenic acid derivative, as Difolatan (captafol), Vancide 89 (captan), Pecudin (dichlofluanid), Phaltan (folpet), tolylfluanid (tolylfluanid);
Cinnamide and similar compound, as dimethomorph (dimethomorph), fluorine biphenyl bacterium (flumetover), flumorph (flumorp);
For example, at WO98/46608, WO99,41255 or WO03/004465 in 6-aryl-[1,2,4] triazolos [1,5-a] pyrimidine of describing with general formula I separately;
Amides mycocide is as cyflufenamid (cyclofenamid) with (Z)-N-[α-(cyclopropyl methoxyimino)-2, the fluoro-6-of 3-bis-(difluoro-methoxy) benzyl]-2-phenyl-acetamides.
The example of weedicide comprises following:
1,3,4-thiadiazole, as careless thiophene miaow (buthidazole) and ring cafenstrole (cyprazole);
Amides, as allidochlor (allidochlor), benzoylpropethyl (benzoylpropethyl), bromobutide (bromobutide), chlorothiamid (chlorthiamid), dimepiperate (dimepiperate), P DimethenamidP (dimethenamid), enide (diphenamid), diphenyl (etobenzanid), first FLAMPROP (flamprop-methyl), phosphine ammonium element (fosamin), isoxaben (isoxaben), metazachlor (metazachlor), monalide (monalide), alanap (naptalam), pronamide (pronamide), Stam F-34 (propanil),
Phosphoramidic acid class, as bilanafos (bilanafos), special gram grass (buminafos), careless ammonium phosphine (glufosinate ammonium), glyphosate (glyphosate), sulphosate (sulfosate);
Aminotriazole class, as amerol (amitrole), anilide class, as anilofos (anilofos), mefenacet (mefenacet);
Aryloxy alkane acids, as 2,4-D, 2,4-DB, clomeprop (clomeprop), 2,4-drips propionic acid (dichlorprop), high by 2,4-drips propionic acid (dichlorprop-P), 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, as Amiben (chloramben), dicamba 98 (dicamba);
Benzothiadiazine ketone, as bentazon (bentazone);
SYNTHETIC OPTICAL WHITNER, if clomazone (clomazone), diflufenican (diflufenican), fluorochloridone (fluorochloridone), amine grass azoles (flupoxam), fluorine grass are with (fluridone), pyrazolate (pyrazolate), sulphur humulone (sulcotrione);
Amino formate, as carbetamide (carbetamid), Chlorophenocarb (chlorbufam), Y 3 (chlorpropham), different phenmedipham (desmedipham), phenmedipham (phenmedipham), vernolate (vernolate);
Quinoline acids, as quinclorac (q uinclorac), quinmerac (q uinmerac);
Tripon class, as dalapon (dalapon);
Dihydrobenzofuranes class, as ethofumesate (ethofumesate);
Dihydrofuran-3-ketone, as flurtamone (flurtamone);
Dinitroaniline, as 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, as Faneron (bromofenoxim), dinoseb (dinoseb), dinoseb acetic ester (dinoseb acetate), dinoseb acetate phenol (dinoterb), Sinox (DNOC), fourth nitre phenol acetic ester (minoterb acetate), diphenylether, as 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, as nutgrass flatsedge fast (cyperquat), benzene enemy fast (difenzoquat methyl sulfate), diquat (diquat), paraquat (paraquat dichloride);
Imidazoles, as grand in fourth ring (isocarbamid);
Imidazolone type, as imazapic (imazamethapyr), Arsenal (imazapyr), Scepter (imazaquin), miaow grass ester (imazethabenz methyl), Imazethapyr (imazethapyr), imazapic (imazapic), imazamox (imazamox);
Diazoles, as methazole (methazole), alkynes third azoles grass (oxadiargyl), oxadiazon (oxadiazon);
Ethylene oxide, as tridiphane (tridiphane);
Phenols, as bromoxynil (bromoxynil), ioxynil (ioxynil);
Phenoxy-phenoxy propionic ester, as clodinafop-propargyl (clodinafop), cyhalofop-butyl (cyhalofop butyl), diclofop-methyl (diclofop methyl), azoles diclofop-methyl (fenoxaprop ethyl), height 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), haloxyfop (haloxyfop methyl), haloxyfopPmethyl (haloxyfopp-methyl), dislike careless ether (isoxapyrifop), propaquizafop (propaquizafop), quizalofop (quizalofop ethyl), quizalofopPethyl (quizalofop p-ethyl), quizalofop (tetrahydro furfuryl ester) (quizalofop tefuryl),
Phenylacetic acid class, as Fenac (chlorfenac);
Phenylpropionic acid class, as chlorphenpropmethyl (chlorophenprop methyl);
Ppi (ppi=kind is planted front soil treatment) activeconstituents is 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, as pyrrole chlorine grass amine (nipyraclofen);
Pyridazine class, as pyrazon (chloridazon), maleic hydrazide (maleic hydrazide), monometflurazone (norflurazon), reach grass only (pyridate);
Pyridine carboxylic acid class, as morpholine acid dichloride picoline (clopyralid), dithiopyr (dithiopyr), picloram (picloram), thiophene halozydine (thiazopyr);
Pyrimidyl ethers, as phonetic sulphur phenylformic acid (pyrithiobac acid), phonetic sulphur Sodium Benzoate (pyrithiobac sodium), KIH-2023, KIH-6127;
Sulfonamides, as fluorine ethofumesate (flumetsulam), azoles grass sulfanilamide (SN) (metosulam);
Triazole carboxyl acylamide, as triazofenamid;
Uracil, as bromacil (bromacil), lenacil (lenacil), terbacil (terbacil);
And additionally also has benazolin (benazolin), 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, as grand in sulphur ammonia Huang (amidosulfuron), tetrazolium Huang grand (azimsulfuron), benzyl ethyl methyl (bensulfuron methyl), chlorimuron (chlorimuron ethyl), chlorsulfuron (chlorsulfuron), ether Huang grand (cinosulfuron), ring third yellow grand (cyclosulfamuron), Ethanetsulfuron (ethametsulfuron methyl), pyridine ethyl methyl (flazasulfuron), pyrrole chlorsulfuron (halosulfuron methyl), pyridine miaow Huang grand (imazosulfuron), metsulfuron-methyl (metsulfuron methyl), nicoculsfuron (nicosulfuron), Fluoropyrimidinesulfuron (primisulfuron), fluorine third yellow grand (prosulfuron), 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, kills as withered and reaches (alloxydim), clethodim (clethodim), tetrahydrobenzene humulone (cloproxydim), cycloxydim (cycloxydim), sethoxydim (sethoxydim) and tralkoxydim (tralkoxydim).
Cyclohexenone analog herbicidal active component is very particularly preferably:
Quinone oximes grass (tepraloxydim) (referring to AGROW, the 243rd phase, 11.3.95, the 21st page, caloxydim), and
2-(1-[2-{4-chlorophenoxy } the 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 example comprises following:
Organophosphorus compounds, as Ortho 12420 (acephate), R-1582 (azinphos-methyl), Chlorpyrifos 94 (chlorpyrifos), Zaprawa enolofos (chlorfenvinphos), diazinon (diazinon), SD-1750 (dichlorvos), dimethylvinphos (dimethylvinphos), salithion (dioxabenzofos), Carbicron (dicrotophos), Rogor (dimethoate), thiodemeton (disulfoton), Nialate (ethion), EPN (EPN), Sumithion (fenitrothion), Tiguvon (fenthion), different azoles phosphorus (isoxathion), Malathion (malathion), acephatemet (methamidophos), methidathion (methidathion), parathion-methyl (methyl-parathion), Phosdrin (mevinphos), monocrotophos (monocrotophos), oxydemeton methyl (oxydemeton-methyl), paraoxon (paraoxon), one six zero five (parathion), Tsidial (phenthoate), Phosalone (phosalone), R-1504 (phosmet), phosphamidon (phosphamidon), phorate (phorate), Volaton (phoxim), pirimiphosmethyl (pirimiphos-methyl), Profenofos (profenofos), Toyodan (prothiofos), primiphos-ethyl, pyraclofos (pyraclofos), kill greatly phosphorus (pyridaphenthion), demephion demephion_O demephion (sulprophos), triazophos (triazophos), Trichlorphon (trichlorfon), tetrachlorvinphos (tetrachlorvinphos), vamidothion (vamidothion),
Amino formate, as alanycarb (alanycarb), benfuracarb (benfuracarb), worm prestige (bendiocarb), carbaryl (carbaryl), carbofuran (carbofuran), carbosulfan (carbosulfan), ABG-6215 (fenoxycarb), furathiocarb (furathiocarb), diazole worm (indoxacarb), metmercapturon (methiocarb), methomyl (methomyl), thioxamyl (oxamyl), Aphox (pirimicarb), Propoxur (propoxur), thiodicarb (thiodicarb), triaxamate (triazamate);
Pyrethroids: bifenthrin (bifenthrin), cyfloxylate (cyfluthrin), cycloprothrin (cycloprothrin), Cypermethrin (cypermethrin), Deltamethrin (deltamethrin), esfenvalerate (esfenvalerate), ether chrysanthemum ester (ethofenprox), Fenvalerate (fenpropathrin), kill chrysanthemum ester (fenvalerate), (RS) cyhalothrin (cyhalothrin), cyhalothrin (lambda-cyhalothrin), permethrin (permethrin), deinsectization silicon ether (silafluofen), taufluvalinate (tau-fluvalinate), tefluthrin (tefluthrin), tralomethrin (tralomethrin), nail body Cypermethrin (alpha-cypermethrin), own body Cypermethrin (zeta-cypermethrin), permethrin,
Arthropods growth regulator: a) chitin synthesis inhibitor, benzoyl area kind for example, as UC 62644 (chlorfluazuron), TH-6040 (diflubenzuron), flucycloxuron (flucycloxuron), flufenoxuron (flufenoxuron), HEXAFLUMURON (hexaflumuron), fluorine the third oxygen urea (lufenuron), Rimon (novaluron), Teflubenzuron (teflubenzuron), desinsection grand (triflumuron); Buprofezin (buprofezin), luxuriant ether (diofenolan), hexythiazox (hexythiazox), special benzene azoles (etoxazole), clofentezine (clofentazine); B) moulting hormone antagonist, as RH 0345 (halofenozide), Runner (methoxyfenozide), RH-5992 (tebufenozide);
C) juvenile hormone analogue, as pyriproxyfen (pyriproxyfen), Entocon ZR 515 (methoprene), ABG-6215 (fenoxycarb); D) lipoid biosynthesis inhibitor, as spiral shell mite ester (spirodiclofen);
Anabasine, as flonicamid (flonicamid), clothianidin (clothianidin), MTI-446 (dinotefuran), Provado (imidacloprid), Diacloden (thiamethoxam), nitenpyram (nitenpyram), WL 35651 (nithiazin), pyrrole worm clear (acetamiprid), thiacloprid (thiacloprid);
Additionally also have non-classified sterilant, as avermectin (abamectin), acequinocyl (acequinocyl), pyrrole worm are clear, U-36059 (amitraz), Ai Zhading (azadirachtin), bensultap (bensultap), Bifenazate (bifenazate), cartap (cartap), fluorine azoles worm clear (chlorfenapyr), chlordimeform (chlordimeform), cyromazine (cyromazine), kill 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), Frontline (fipronil), formetanate (formetanate), Formetanate monohydrochloride (formetanate hydrochloride), lindane (gamma-HCH), amdro (hydramethylnon), Provado, diazole worm, isoprocarb (isoprocarb), meta-tolyl-N-methylcarbamate (MTMC) (metolcarb), pyridaben (pyridaben), pymetrozine (pymetrozine), spinosad (spinosad), tebufenpyrad (tebufenpyrad), Diacloden, thiocyclarn (thiocyclam), XMC and xylylcarb (xylylcarb).
The N-phenylsemicarbazone, the particularly compound of general formula I I in EP-A 462 456, with general formula I, described:
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 4for C 1-C 4alkoxyl group, C 1-C 4haloalkyl or C 1-C 4halogenated alkoxy, for example R wherein 5for 3-CF 3, R 6for 4-CN and R 4for 4-OCF 3compound IV:
The example of operable growth regulator is choline dichloride (chlormequat chloride), help strong element (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 have its derivative, example is and C 1-C 4the ester of carboxylic acid.Outside preferred according to the present invention-16,17 dihydros-GA 513-acetic ester.
Preferred mycocide is strobilurins class especially for example, and azole and the 6-aryl triazoles described with general formula I in WO 98/46608, WO 99/41255 or WO 03/004465 be the activeconstituents of [1,5-a] pyrimidine, especially general formula III also:
Wherein
R xfor group NR 7r 8, or optionally by halogen, OH, C 1-C 4alkoxyl group, phenyl or C 3-C 6the linearity of cycloalkyl substituted or branching C 1-C 8alkyl, or be C 2-C 6alkenyl, C 3-C 6cycloalkyl, C 3-C 6cycloalkenyl group, phenyl or naphthyl, 4 groups wherein mentioning afterwards 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 10cycloalkyl, 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, or
R 7and R 8together with the nitrogen-atoms connecting with them, form 5-8 element heterocycle base, 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 be with 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, cyano group, C 1-C 6alkyl, C 1-C 4haloalkyl, C 1-C 6alkoxyl group, C 1-C 4halogenated alkoxy and C 1-C 6carbalkoxy;
L 1for halogen, C 1-C 6alkyl or C 1-C 6haloalkyl, especially fluorine or chlorine;
X 2for halogen, C 1-C 4alkyl, cyano group, C 1-C 4alkoxyl group or C 1-C 4haloalkyl, preferably halogen or methyl, especially chlorine.
The example of formula III compound is the chloro-7-of 5-(4-methyl piperidine-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(4-methylpiperazine-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(morpholine-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(piperidin-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(morpholine-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-isopropylamino-6-(2 of 5-, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-cyclopentyl of 5-amino-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-(2 of 5-, 2, 2-trifluoroethyl is amino)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-(1 of 5-, 1, 1-trifluoro propane-2-base is amino)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-(3 of 5-, 3-dimethylbutane-2-base is amino)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-cyclohexyl methyl-6-(2 of 5-, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-cyclohexyl-6-(2 of 5-, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(2-methylbutane-3-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(3-methylpropane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(4-methylcyclohexane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(hexane-3-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(2-methylbutane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(3-methylbutane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, the chloro-7-of 5-(1-methylpropane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(4-methyl piperidine-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(4-methylpiperazine-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(morpholine-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(piperidin-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(morpholine-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-isopropylamino-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-cyclopentyl amino-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(2, 2, 2-trifluoroethyl is amino)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(1, 1, 1-trifluoro propane-2-base is amino)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(3, 3-dimethylbutane-2-base is amino)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-cyclohexyl methyl-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-cyclohexyl-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(2-methylbutane-3-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(3-methylpropane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(4-methylcyclohexane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(hexane-3-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(2-methylbutane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine, 5-methyl-7-(3-methylbutane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine and 5-methyl-7-(1-methylpropane-1-yl)-6-(2, 4, 6-trifluorophenyl)-[1, 2, 4] triazolo [1, 5-a] pyrimidine.
Suitable sterilant is especially:
-aryl pyrrolines, as clear in fluorine azoles worm,
-pyrethroids, as bifenthrin, cyfloxylate, cycloprothrin, Cypermethrin, Deltamethrin, esfenvalerate, ether chrysanthemum ester, Fenvalerate, kill chrysanthemum ester, (RS) cyhalothrin, cyhalothrin, permethrin, deinsectization silicon ether, taufluvalinate, tefluthrin, tralomethrin, nail body Cypermethrin, own body Cypermethrin and permethrin
-Frontline,
-anabasine, and
The semicarbazone class of-Shi II.
Suitable fluorescent agent is for example pyrene, uranine, rhodamine, fluorescein, tonka bean camphor, allophycocyanin, naphthalene, anthracene.
In one embodiment of the invention, the inventive method can be for the whole aqueous formulation solubilization 0.01-1 % by weight based on preparing according to the present invention, preferably at least 0.1 % by weight hydrophobic active composition in water-bearing media.
In order to implement the inventive method, use one or more auxiliary agents, wherein at least one is hyperbranched polymer (A), described hyperbranched polymer (A) below specific definition and in the context of the invention also referred to as hyperbranched polymer (A), polymkeric substance (A), hyperbranched polymer of the present invention (A) or polymkeric substance of the present invention (A).
In one embodiment of the invention, the molecular-weight average M of hyperbranched polymer (A) wfor 1000-100000g/mol, preferred 1500-50000g/mol.Molecular-weight average for example can pass through gel permeation chromatography (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 by make at least one per molecule have at least one uncle or the hyperbranched polymerizable compound (a) of secondary amino group-in the context of the invention also referred to as hyperbranched compound (a)-with (b) at least one is single-, two-or oligosaccharides react and obtain, described hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
Hyperbranched compound (a) and therefore to also have hyperbranched polymer prepared therefrom (A) be inhomogeneous in molecule and structure.They are for example that from branch-shape polymer different its molecule ununiformity and they can be with significantly lower complexity preparations.Based on AB 2an example of the molecular structure of the hyperbranched compound of molecule for example can find at WO 04/20503 page 2.For this structure (side chain distribute etc.), this is equally applicable to based on A used in the application's context for example 2+ B ythe polymkeric substance of strategy (wherein y>=3); Such as 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 the context of the invention, be hyperbranchedly preferably interpreted as referring to that degree of branching DB is 10-99.9%, preferred 20-90%, more preferably those polymerizable compounds (a) of 80% or polymkeric substance (A) at the most.
Degree of branching DB is defined as:
DB[%]=100·(T+Z)/(T+Z+L)
Wherein T is end monomeric unit mean number, and Z represents 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 the context of the invention, amino is interpreted as referring to primary amino, i.e. NH 2group, or secondary amino group, preferably NHR 9group, wherein R 9be selected from C 1-C 6alkyl, especially methyl or ethyl, or C 3-C 7cycloalkyl 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, preferably 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 9example 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 the context of the invention, ultrabranching polyamide (a1) is interpreted as referring to can be by making monomer A 2 and B 3polycondensation and those ultrabranching polyamides of preparing, wherein
A 2can be understood as and refer to that dicarboxylic acid for example or suitable derivative are as the list of dicarboxylic acid-or two-C 1-C 4alkyl ester or acid anhydrides, and B 3can be understood as and refer to trifunctional or high functionality amine-scheme (A) more, wherein above-mentioned trifunctional or more high functionality amine be selected from per molecule and there are 3 or be greater than 3 and be selected from primary amino and secondary amino group, be preferably selected from NH 2group and NHR 9the amino compound of group.Except uncle or secondary amino group, trifunctional or more high functionality amine can also have other functional groups, and for example uncle is amino.
Be preferably used as monomer A 2dicarboxylic acid be for example oxalic acid, propanedioic acid, succsinic acid, pentanedioic acid, hexanodioic acid, pimelic acid, suberic acid, sebacic acid, undecane-α, ω-dioctyl phthalate, cis-and trans-hexanaphthene-1,2-dioctyl phthalate, cis-and trans-hexanaphthene-1,3-dioctyl phthalate, cis-and trans-hexanaphthene-1,4-dioctyl phthalate and derivative thereof, as single-and dialkyl, acyl chlorides or acid anhydrides.
Preferred trifunctional or more high functionality uncle or secondary amine are for example three (2-amino-ethyl) amine, three (2-aminopropyl) amine, diethylenetriamine, Triethylenetetramine (TETA), tetren, two (hexa-methylene) triamine and derivative thereof, and the more high functionality alcohol of alkoxylate and amination, for example t product.
t is the trifunctional polyether glycol with uncle's end amino.They start preparation by trifunctional alcohol initiator, wherein make this initiator react with ethylene oxide and/or propylene oxide, then the terminal hydroxy group obtaining in this step are changed into amino.
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, as trifunctional or the polycarboxylic acid anhydrides of high functionality more, single-, two-or three-C 1-C 4alkyl ester-scheme (B).
Preferred diamines is for example quadrol, propylene diamine (1，2-diaminopropane and 1,3-diaminopropanes), 1,4-Diaminobutane, 1,5-1,5-DAP, 1，6-diaminohexane, 1,8-diamino-octane and isophorone diamine.
Suitable trifunctional or more high functionality carboxylic acid are for example trimesic acid, trimellitic acid, pyromellitic acid, butane tricarboxylic acid and hexanaphthene-1, and 3,5-tricarboxylic acid and derivative thereof, as single-and dialkyl, acyl chlorides or acid anhydrides.
In another embodiment of the present invention, ultrabranching polyamide (a1) is interpreted as referring to can be by making functional carboxylic acid, for example AB 2those ultrabranching polyamides that the functional carboxylic acid of type obtains from condensation, wherein ultrabranching polyamide (a1) in the situation that, A represents to have the carboxylic acid of two identical or different functional group B.B for example can be selected from OH, SH and NH thus 2.B 2preferably represent two NH 2group.Suitable AB 2the example 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 ultrabranching polyamide (a1) in the situation that, B represents to have the carboxylic acid of other functional groups A beyond COOH.A for example can be selected from OH, SH and NH thus 2.Suitable AB 2the example of type functional carboxylic acid is L-glutamic acid and aspartic acid.
Amino acid can be used with racemic modification or the pure form of enantiomorph in each case, especially with L isomer, uses.
Ultrabranching polyamide (a1) can comprise one or more other compounds of introducing by condensation, for example one or more aliphatic series or aromatics or alicyclic diamine scheme (A) in the situation that, or one or more dicarboxylic acid scheme (B) in the situation that for example.
In one embodiment of the invention, the molecular-weight average M of ultrabranching polyamide (a1) wfor 800-100000g/mol, preferred 1000-75000g/mol.
Ultrabranching polyamide (a1) and preparation method thereof be for example disclosed in WO 2006/018125 and the document wherein quoted in.
In one embodiment of the invention, ultrabranching polyamide (a1) is selected from hyperbranched poly Methionin (a3).
In the context of the invention, hyperbranched poly Methionin (a3) is interpreted as referring to have Methionin as the no cross-linked polymer of monomeric unit.
In one embodiment of the invention, hyperbranched poly Methionin (a3) can have 20mol% Methionin monomeric unit in addition, for example aspartic acid or L-glutamic acid or one or more other dicarboxylic acid, 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) wfor 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 the context of the 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 the polylysine that can obtain by the polycondensation of free lysine alkali is low.
A tolerance of degree of crosslinking is for example the comparison of the gel content of described polylysine, and this content store under water the ratio of insoluble part in the process of 24 hours at the temperature of 23 ° of C, changes into percentage ratio.
Hyperbranched poly Methionin (a3) and preparation method thereof is for example disclosed in WO 2007/060119.
In the context of the invention, term " hyperbranched polyureas " (a2) also comprises and except urea groups, can also have 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 by making isocyanate groups react with the monohydroxy-alcohol that is used as encapsulant the O-alkyl urea groups obtaining.
Hyperbranched polyureas (a2) can obtain by all means, for example, by making isocyanic ester and polyamines direct reaction, make urea and polyamines direct reaction, or by dialkyl carbonate is reacted with polyamines.Yet in the context of the invention, hyperbranched polyureas (a2) is preferably by making the polyisocyanates of sealing react and obtain with polyamines, as WO 03/066702.Other preparation 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 make by comprising that the sealing two of at least two senses-or polyisocyanates reacts with at least one at least two senses uncle and/or secondary amine and the method for eliminating encapsulant obtains.
As the sealing two of this at least two sense of ingredient requirement-or polyisocyanates for example can be by making two-or polyisocyanates and aliphatic series, araliphatic or aromatic alcohol, preferably monohydroxy-alcohol reaction and preparing.
Suitable monohydroxy-alcohol is preferably linearity or branched aliphatic monohydroxy-alcohol, as methyl alcohol, ethanol, propyl alcohol, butanols, amylalcohol, hexanol, enanthol, octanol, Virahol, isopropylcarbinol or 2-ethyl-1-hexanol or araliphatic monohydroxy-alcohol, as benzylalcohol or phenylethyl alcohol.Particularly preferably linearity or branched aliphatic monohydroxy-alcohol, and also have benzylalcohol.Especially preferably there is 1-18, preferably the linear aliphatic monohydroxy-alcohol of 1-6 carbon atom.
At least two functional amines for the preparation of hyperbranched polyureas (a2) are selected from the compound that urethane group is to reactive amido with at least two.Having at least two compounds that urethane group is to reactive amido is for example quadrol, N-alkyl quadrol, propylene diamine, 2, 2-dimethyl-1, 3-propylene diamine, N-alkyl propylene diamine, butanediamine, N-alkyl butanediamine, 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 polyoxyalkylene polyol of amine end-blocking is (for example, from Huntsman Corporation's ), amination polytetramethylene glycol, N-aminoalkyl group piperidines, ammonia, two (amino-ethyl) amine, two (aminopropyl) amine, two (aminobutyl) 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-propylene diamine, triaminononane or melamine.In addition can also use, any desired mixt of at least two kinds of described compounds.Preferably at least two sense uncles and/or secondary amine are at least two sense primary amine, more preferably two sense aliphatic primary amine, especially isophorone diamines.
Useful two-or polyisocyanates comprise known aliphatic series itself, alicyclic, araliphatic and aromatics two-and polyisocyanates.These preferably comprise 4, 4 '-diphenylmethanediisocyanate, the mixture of haplotype diphenylmethanediisocyanate and oligomeric-type diphenylmethanediisocyanate (polymkeric substance MDI), tetramethylene diisocyanate, tetramethylene diisocyanate tripolymer, hexamethylene diisocyanate, hexamethylene diisocyanate trimer, isophorone diisocyanate (IPDI), isophorone diisocyanate trimer, 2, 4-tolylene diisocyanate (2, 4-TDI), 2, 4 '-diphenylmethanediisocyanate (2, 4 '-MDI), 2, 6-tolylene diisocyanate (2, 6-TDI) or triisocyanate base toluene.
In order to form hyperbranched polyureas (a2), particularly preferably following: two-or polyisocyanates, especially oligomeric-or polyisocyanates, it can be by aliphatic, alicyclic, araliphatic and aromatics, preferred aliphatic series two-or polyisocyanates by 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 connects and prepares by isocyanurate structure.These are oligomeric-or the average N CO functionality that polyisocyanates has be conventionally 2.1-4.9, preferably 2.9-4.4, especially 3.4-3.9.Average molar mass M wbe preferably 300-3000g/mol, preferably 400-1500g/mol, especially 500-800g/mol.
In one embodiment of the invention, the hyperbranched polyureas (a2) of selection is in building-up process, to have added simple function aliphatic series, araliphatic or aromatic amine as chain terminator and synthetic those.Suitable monofunctional amines is primary alkyl amine, preferably 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 start preparation by monohydroxy-alcohol initiator, wherein make this initiator react with ethylene oxide and/or propylene oxide and subsequently the terminal hydroxy group obtaining is changed into amino in this step.
In one embodiment, ultrabranching polyamide (a1) and hyperbranched polyureas (a2) have make they itself for water-soluble, under 23 ° of C, be less than 1g/l, be preferably less than the water-soluble structure of 0.1g/l.
Make above-mentioned polymerizable compound (a) with (b) at least one is single-, two-or oligosaccharides-in the context of the invention is also separately referred to as monose (b), disaccharides (b) and oligosaccharides (b), or set, referred to as carbohydrate (b)-reaction, selects those to make carbohydrate (b) be connected in the reaction of polymerizable compound (a).
In the context of the 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 additionally also have tagatose as fructose and sorbose.
In the context of the 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 maltose.
In the context of the 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 standard pressure for example, preferred 20g/l at least, more preferably at least 100g/l is dissolved in distilled water.
Carbohydrate (b) can preferably exist with hydrate.
Particularly preferred 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 glucose unit at the most.
In disaccharides (b) or oligosaccharides (b), sugar unit preferably interconnects by glycosidic link.
In one embodiment of the invention, single in polymkeric substance (A)-, two-or oligosaccharides (b) with glucosides formal bond in hyperbranched polymerizable compound (a), especially via amino key in hyperbranched polymerizable compound (a).In the context of the invention, " glucosides " refers to that this key is via aldehyde functional group or the ketone of described carbohydrate (b).Glycosidic link can reversible or irreversibly form.
In one embodiment of the invention, different carbohydrate (b) key is in identical hyperbranched polymer (a).Different carbohydrates for example can and be derived from identical sugar unit for disaccharides (b), the oligosaccharides of glucose or seminose (b) for example, or monose (b) and be derived from the disaccharides (b) of identical sugar unit, or monose (b) and be derived from the oligosaccharides (b) of identical sugar unit.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); Preferably 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, uncle or the secondary amino group of hyperbranched polymerizable compound (a) are quantitative, preferably with the degree of 90mol% at least, are connected in carbohydrate (b).
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).
Quantitative continuous is connected to the NH of carbohydrate (b) 2each NH of group 2group is connected in bimolecular carbohydrate (b).
Quantitative continuous is connected to the NHR of carbohydrate (b) 9each NHR of group 9group is connected in the carbohydrate (b) of a part.
When polymerizable compound (a) quantitative continuous is connected to carbohydrate (b), this refers to 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, by mixing, contact.Mixing for example can be by stirring and carries out with conventional whisk or homogenizer.Other suitable methods are to apply ultrasonic wave or violent jolting.Mix and preferably in a more than step, carry out, for example, by first making hyperbranched polymer of the present invention (A) contact with water-bearing media, then contact and carry out with one or more hydrophobic active compositions.
In one embodiment of the invention, hyperbranched polymer (A) and hydrophobic active composition are with 1:1-1000:1, and preferably the mass ratio of 1:1-100:1 is used.
In one embodiment, hyperbranched polymer (A) is stirred together with water-bearing media, then stir together with one or more activeconstituentss.
If mixing can be carried out and wish using the temperature raising at the temperature of 0-100 ° of C, also can for example at the temperature of 150 ° of C, carry out at the most.Preferably, at standard pressure and 15-70 ° of C, preferably at the temperature of 20-50 ° of C, operate.
In one embodiment of the invention, after finishing, mixing removes the hydrophobic active composition of not solubilization, for example, by filtration or centrifugal.
The present invention further provides the hyperbranched polymer (A) that dissolves in or dispersible in water, it is water-soluble or water dispersible hyperbranched polymer (A), it can by making at least one hyperbranched polymerizable compound (a) and (b), at least one be single-, two-or oligosaccharides react and obtains, described hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
The present invention adds dissolution method and can especially effectively use polymkeric substance of the present invention (A) to carry out.
With regard to polymkeric substance of the present invention (A), " water miscible " or " water soluble " refers under 20 ° of C and standard pressure at least 10g/l, preferred 20g/l at least, and more preferably at least 100g/l is dissolved in distilled water.
" water dispersible " polymkeric substance is interpreted as referring to not dissolve in water but can be processed into those polymkeric substance (A) of dispersion, and this dispersion did not at room temperature form the noticeable sedimentation of any bore hole at least 2 hours.In post, not water dispersible within the scope of the present invention with the polymkeric substance (A) of stationary phase bonding.
Remaining term separately as defined above.
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) wfor 1000-100 000g/mol, preferred 1500-50 000g/mol.Molecular-weight average for example can pass through gel permeation chromatography (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 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 of preparing hyperbranched polymer of the present invention (A), its in the context of the invention also referred to as preparation method of the present invention.In preparation method of the present invention, make at least one be selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas hyperbranched polymerizable compound (a) and (b) at least one singly-, two-or oligosaccharides in liquid phase, under reductive amination condition, react.
" in liquid phase " is interpreted as referring in the hyperbranched compound that reacts or be connected to melting (a) of hyperbranched polymerizable compound (a) and carbohydrate (b) or preferably in solution, carries out.
Suitable solvent is for example protic and non-proton organic solvent, for example tetrahydrofuran (THF), methylene dichloride, chloroform and alcohols, for example ethanol, Virahol and methyl alcohol.
Specially suitable solvent is water.
Reductive amination itself is known.At this and be not intended to preferred particular theory, reductive amination in the present invention can be interpreted as polystep reaction, wherein in the first step, make to have uncle or the hyperbranched compound (a) of secondary amino group and the aldehydes or ketones radical reaction of carbohydrate (b) and form the imines that is selected from aldimine and ketoimine, it is reduced into amine subsequently in second step.
In one embodiment of the invention, reductive agent used is hydride or complex hydride, especially LiBH 4or NaBH 4or NaBH 3cN.
In one embodiment of the invention, reductive agent used is borine-Lewis base title complex.Suitable Lewis base is for example thioether, and ring-type and non-annularity ether and aliphatic series or aromatic amines also have assorted aromatic hydrocarbons.The example of thioether is dimethyl sulphide and diethyl thioether.Suitable non-annularity ether example especially wherein alkyl different or preferably identical two-C 2-C 10dialkyl ether, for example ether, diisopropyl ether and di-n-butyl ether.The example of cyclic ether is tetrahydrofuran (THF) (THF) and tetrahydropyrans.The example of aliphatic amine is TERTIARY BUTYL AMINE.The example of tertiary amine is three-C especially 1-C 4alkylamine, for example triethylamine, additionally also has Wyovin, for example [2,2,2]-diazabicyclo octane (Dabco).The example of aromatic amine be especially aromatic uncle amine as DMA and N, N-Diethyl Aniline.The example of heteroaromatics is especially pyridine, 2-picoline and aldehydecollidine.
In one embodiment of the invention, the reductive agent of selection is the xitix in acetic acid/acetate buffer.
In another embodiment, selection does not have the acetic acid/acetate buffer of extra reductive agent via imine intermediate, also to reduce subsequently between carbohydrate (b) and amino and forms key, 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.
Particularly preferably select following heteroaromatic amine as Lewis base, wherein at least one nitrogen-atoms be heteroaromatic system as a part for pyridine, it is for example by C 1-C 4alkyl replaces, or is not more preferably substituted.Borine-Lewis base complex B H very particularly preferably 3pyridine, in the literature also referred to as BH 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 preferably the ratio of 1:1-1:10 is used.
In one embodiment of the invention, carbohydrate (b) and reductive agent, with the mol ratio of 1:1-1:3, are most preferably used with equimolar amount.
In this reaction, the amino that can will transform by the excessive control of optional use and will transform how much amino.If only will transform primary amino, just much of that by stoichiometric ratio use carbohydrate (b) and reductive agent based on primary amino.If also will transform secondary amino group, reductive agent and carbohydrate (b) are used with stoichiometric quantity with respect to the summation of the primary and secondary amino from hyperbranched polymerizable compound (a) separately.If also will transform all secondary amino groups, require large excessive reductive agent.
In one embodiment of the invention, preparation method of the present invention, at 0-100 ° of C, preferably carries out at the temperature of 15-70 ° of C.
Have been found that the suitable reaction times is 1 hour to 2 weeks, the reaction times can be used as the function of temperature and selects.Temperature is lower, and the reaction times of selection is longer.
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 preferably 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, after the chemical reaction of preparation hyperbranched polymer of the present invention (A) finishes, omit and purify.
In another embodiment of the present invention, after finishing, the chemical reaction of preparation hyperbranched polymer of the present invention (A) purifies.This purification for example can comprise the Lewis base of evaporating solvent and release.Purification can additionally comprise removes the inorganic salt that for example come from buffer reagent used.
Aftertreatment can be by known method itself, and for example chromatography, redeposition, filtration, particle size dependence separation method be as ultrafiltration, or dialysis is carried out.
The present invention further provides the mixture that comprises at least one hyperbranched polymer of the present invention (A) and at least one hydrophobic active composition.Mixture is interpreted as not only referring to the mixture on 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), without the hydrophobic active composition that comprises 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 being present in this preparaton with infix form.
The present invention further provides a kind of method of preparing mixture of the present invention.The program of preparation mixture of the present invention can be that at least one hydrophobic active composition and at least one hyperbranched polymer of the present invention (A) are mixed mutually, for example, by one of aforesaid method, mix, and preferably under water exists, mixes.
For example the present invention further provides with 0.01-400g/l the aqueous formulation that more preferably concentration of 0.015-100g/l comprises at least one mixture of the present invention.
Mixture of the present invention and therefore also have aqueous formulation of the present invention to be for example used as crop protection agents or for the production of medicine according to hydrophobic active composition used.
By work, embodiment illustrates the present invention.
Term:
DBTL: di-n-butyltin dilaurate
m-1000: there is the monofunctional polyethers polyvalent alcohol of uncle's end amino, average molar mass M wabout 1000g/mol, Huntsman Corporation
Universal description:
Ultrabranching polyamide (a1) and hyperbranched polyureas (a2) are by analyzing as the gel permeation chromatography of detector with refractometer.Movement used is hexafluoroisopropanol (HFIP) or water mutually; Standard substance for determining molecular weight is polymethylmethacrylate (PMMA).
Amine value is measured according to DIN EN 13717.
Hyperbranched polymer of the present invention (A) is by analyzing as the gel permeation chromatography of detector with refractometer.
Dialysis is used from Carl Roth GmbH & Co, and the ZelluTrans/Roth V of Karlsruhe/ Germany series dialyzer carries out.Unless otherwise, using MWCO (molecular weight intercepting value) is the type of 1000g/mol.
I. prepare ultrabranching polyamide (a1)
I.1 prepare ultrabranching polyamide (a1.1)
In the reaction vessel that agitator, internal thermometer, reflux exchanger and nitrogen inlet tube are housed, first add 362g tetren.Under agitation in 1 hour, be metered into 238g dimethyl adipate so that internal temperature is approximately 100 ° of C.Once feed in raw material, just reaction mixture be heated to 140 ° of C and stir 1 hour under 140 ° of C.Then reflux exchanger is exchanged for to there is the descending condenser (descending condenser) of collection container and start distillation and removes the methyl alcohol discharging in this reaction.The liquid measure that distillates of collecting after 150 minutes is 17.1g methyl alcohol.Then by being cooled to room temperature, make this reaction terminating.Yellow oil with thickness obtains the ultrabranching polyamide (a1.1) so obtaining.
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 agitator, internal thermometer, reflux exchanger and nitrogen inlet tube are housed, first add 343.9g tri-(2-amino-ethyl) amine.Under agitation in 2 hours, be metered into 256.1g dimethyl adipate so that internal temperature is approximately 100 ° of C.Once feed in raw material, just reaction mixture be heated to 140 ° of C and stir 90 minutes under 140 ° of C.Then reflux exchanger is exchanged for to there is the descending condenser of collection container and start distillation and removes the methyl alcohol discharging in this reaction.The liquid measure that distillates of collecting after 2 hours is 14.3g methyl alcohol.Then by being cooled to room temperature, make this reaction terminating.Yellow oil with thickness obtains the ultrabranching polyamide (a1.2) so obtaining.
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: first add 1903.9g trimerization hexamethylene diisocyanate to being equipped with in the reaction vessel of agitator, internal thermometer, reflux exchanger and nitrogen inlet tube when rinsing with drying nitrogen, and be under agitation heated to 80 ° of C.Then under constant agitation, in 5 hours, add 751.1g anhydrous normal butyl alcohol, so that the temperature of reaction mixture is no more than 80 ° of C.After reinforced end, this mixture is stirred 1 hour under 80 ° of C, be then cooled to room temperature.
Step 2: when rinsing with drying nitrogen, agitator, internal thermometer are being housed, there is the descending condenser of collection container and the reaction vessel of nitrogen inlet tube in by 255g from the reaction product of step 1 and 50.2g isophorone diamine, 294.8g m-1000 and 0.1g DBTL mix.Reaction mixture be heated to 170 ° of C under constant agitation and stir 90 minutes under 170 ° of C, in this process, steaming except the propyl carbinol discharging in reaction.In reaction process, the amine consumption in reaction mixture is by monitoring with increments such as 0.1N HCl titration and measuring transformation efficiency with the percentage ratio of the transformation efficiency possible with respect to theory thus.Once reach 68% transformation efficiency, just this mixture is cooled to room temperature, this stops this reaction.This obtains hyperbranched polyureas (a2.1) with high viscosity 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)
In agitator, internal thermometer are housed, there is the descending condenser of collection container and the reaction vessel of nitrogen inlet tube, 1000g 1B mono-hydrochloric salts is mixed with 219.1g NaOH, 150g water and 0.1g DBTL.Under agitation reaction mixture be heated to 150 ° of C and stir 5.5 hours under 150 ° of C, in this process, the water of formation being steamed and removed from reaction mixture.Once steam except 312g water, just by the Pressure Drop to 200 in reaction vessel millibar and temperature is risen to 170 ° of C, remove further water to steam.This mixture is stirred 30 minutes under 170 ° of C, be then cooled to room temperature, this stops this reaction.
With yellow solid, obtain hyperbranched poly Methionin (a3.1).
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)
In agitator, internal thermometer are housed, there is the descending condenser of collection container and the reaction vessel of nitrogen inlet tube, 1000g 1B mono-hydrochloric salts is mixed with 219.1g NaOH, 150g water and 0.1g DBTL.Under agitation reaction mixture be heated to 150 ° of C and stir 5.5 hours under 150 ° of C, in this process, the water of formation being steamed and removed from reaction mixture.Once steam except 230g water, just by the Pressure Drop to 200 in reaction vessel millibar and temperature is risen to 170 ° of C, remove further water to steam.This mixture is stirred 30 minutes under 170 ° of C, be then cooled to room temperature, 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 1L flask by 10g ultrabranching polyamide (a1.2)-corresponding to 61.8mmol NH2 group-be dissolved in the moisture sodium borate buffer agent of 350ml 0.1M and this mixture is at room temperature stirred 1 hour.Then under vigorous stirring, add 222.7g (618mmol) D (+)-maltose (b.1).Then this mixture is heated to 50 ° of C.In this process, realize the dissolving completely of D (+)-maltose (b.1).At the 8M solution (618mmol) that adds 77.3ml borine-pyridine complex in THF afterwards, reaction mixture is stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and by the product freeze-drying obtaining.With white amorphous products, obtain hyperbranched polymer of the present invention (A1.2-1-1), yield is 20% (10g).
II.2 prepares hyperbranched polymer of the present invention (A1.2-1-2)
In 1L flask by 10g ultrabranching polyamide (a1.2)-corresponding to 61.8mmol NH2 group-be dissolved in the moisture sodium borate buffer agent of 100ml 0.1M and this mixture is at room temperature stirred 1 hour.Then under vigorous stirring, add 22.3g (61.8mmol) D (+)-maltose (b.1).Then this mixture is heated to 50 ° of C.In this process, realize the dissolving completely of D (+)-maltose (b.1).At the 8M solution (61.8mmol) that adds 7.8ml borine-pyridine complex in THF afterwards, reaction mixture is stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and by the product freeze-drying obtaining.With white amorphous products, obtain hyperbranched polymer of the present invention (A1.2-1-2), yield is 10% (3.2g).
II.3 prepares hyperbranched polymer of the present invention (A3.1-1-1)
5g hyperbranched poly Methionin (a3.1) is dissolved in the moisture sodium borate buffer agent of 350ml 0.1M in 1L flask and this mixture is at room temperature stirred half an hour.Then under vigorous stirring, add 277g (769mmol) D (+)-maltose (b.1).Then this mixture is heated to 50 ° of C.In this process, realize the dissolving completely of D (+)-maltose (b.1).At the 8M solution (769mmol) that adds 96ml borine-pyridine complex in THF afterwards, reaction mixture is stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and by the product freeze-drying obtaining.With white amorphous products, obtain hyperbranched polymer of the present invention (A3.1-1-1), yield is 30% (18.1g).
II.4 prepares hyperbranched polymer of the present invention (A3.1-1-2)
5g hyperbranched poly Methionin (a3.1) is dissolved in the moisture sodium borate buffer agent of 50ml 0.1M in 1L flask and this mixture is at room temperature stirred half an hour.Then under vigorous stirring, add 27.7g (76.9mmol) D (+)-maltose (b.1).Then this mixture is heated to 50 ° of C.In this process, realize the dissolving completely of D (+)-maltose (b.1).At the 8M solution (76.9mmol) that adds 9.6ml borine-pyridine complex in THF afterwards, reaction mixture is stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and by the product freeze-drying obtaining.With white amorphous products, obtain hyperbranched polymer of the present invention (A3.1-1-2), yield is 21% (7.0g).
II.5 prepares hyperbranched polymer of the present invention (A2.1-1-2)
In 1L flask by the hyperbranched polyureas of 10g (a2.1)-corresponding to 4.64mmol NH2 group-be dissolved in the moisture sodium borate buffer agent of 50ml 0.1M and this mixture is at room temperature stirred 1 hour.Then under vigorous stirring, add 1.67g (4.64mmol) D (+)-maltose (b.1).Then this mixture is heated to 50 ° of C.In this process, realize the dissolving completely of D (+)-maltose (b.1).At the 8M solution (46.4mmol) that adds 0.58ml borine-pyridine complex in THF afterwards, reaction mixture is stirred 7 days under 50 ° of C.Make reaction mixture to redistilled water dialysis 4 days, and by the product freeze-drying obtaining.With white amorphous products, obtain hyperbranched polymer of the present invention (A2.1-1-2), yield is 30% (3.5g).
III. the program of hyperbranched polymer of the present invention (A2.1-1-1) solubilization pyrene is tested-is used in solubilization
100mg hyperbranched polymer of the present invention (A2.1-1-1) is weighed in 50ml beaker and is dissolved in 9.9g distilled water.Then 100mg pyrene is weighed in this mixture to obtain supersaturated solution.Then by magnetic stirring apparatus, this mixture is at room temperature stirred 24 hours.After standing 1 hour, by the centrifugal activeconstituents of removing excessive (i.e. not solubilization).The active component content of the clear solution then so obtaining by UV analysis of spectral method.The wavelength of UV spectral measurement is 334nm.
Solubilization test result is compiled in table 1.
Table 1: having and do not having the solubleness [mg/l] of pyrene in water under hyperbranched polymer (A)
Hyperbranched polymer Pyrene
Nothing 0.1
(A2.1-1-1) 12.9

Claims (24)

1. the method for a solubilization hydrophobic active composition in water-bearing media, comprise and use at least one hyperbranched polymer (A) as auxiliary agent, described hyperbranched polymer (A) can by making at least one per molecule have at least one uncle or a hyperbranched polymerizable compound (a) and (b) of secondary amino group, at least one be single-, two-or oligosaccharides react and obtain, described 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 described hyperbranched polymer (A) wfor 1000-100000g/mol.
3. according to the process of claim 1 wherein that described hydrophobic active composition is selected from crop protection agents and pharmaceutically active substance.
4. according to the method for claim 2, wherein said hydrophobic active composition is selected from crop protection agents and pharmaceutically active substance.
5. according to the process of claim 1 wherein that described hydrophobic active composition is selected from sterilant and mycocide.
6. according to the method for claim 2, wherein said hydrophobic active composition is selected from sterilant and mycocide.
7. according to the method for claim 3, wherein said hydrophobic active composition is selected from sterilant and mycocide.
8. according to the method for claim 4, wherein said hydrophobic active composition is selected from sterilant and mycocide.
9. according to the method for any one in claim 1-8, wherein said oligosaccharides is selected from per molecule by 3-20 the compound can identical or different monosaccharide unit forming.
10. according to the method for any one in claim 1-8, wherein said ultrabranching polyamide (a1) is selected from hyperbranched poly Methionin (a3).
11. according to the method for claim 9, and wherein said ultrabranching polyamide (a1) is selected from hyperbranched poly Methionin (a3).
12. 1 kinds of molecules and the inhomogeneous water-soluble or water dispersible hyperbranched polymer (A) of structure, it can by making at least one per molecule have at least one uncle or the molecule of secondary amino group and structure inhomogeneous a hyperbranched polymerizable compound (a) and (b), at least one be single-, two-or oligosaccharides react and obtain, the inhomogeneous hyperbranched polymerizable compound (a) of described molecule and structure is selected from (a1) molecule and the inhomogeneous ultrabranching polyamide of structure and (a2) molecule and the inhomogeneous hyperbranched polyureas of structure.
13. according to the hyperbranched polymer of claim 12 (A), and wherein said oligosaccharides is selected from the compound that per molecule can identical or different monosaccharide unit be formed by 3-20.
14. according to the hyperbranched polymer of claim 12 (A), its molecular-weight average M wfor 1000-100000g/mol.
15. according to the hyperbranched polymer of claim 13 (A), its molecular-weight average M wfor 1000-100000g/mol.
16. according to the hyperbranched polymer (A) of any one in claim 12-15, wherein said list-, two-or oligosaccharides (b) with glucosides formal bond in hyperbranched polymerizable compound (a).
17. according to the hyperbranched polymer (A) of any one in claim 12-15, and wherein said ultrabranching polyamide (a1) is selected from hyperbranched poly Methionin (a3).
18. according to the hyperbranched polymer of claim 16 (A), and wherein said ultrabranching polyamide (a1) is selected from hyperbranched poly Methionin (a3).
Prepare the method for wanting the hyperbranched polymer (A) of any one in 12-18 according to right for 19. 1 kinds, it comprise make at least one per molecule there is at least one uncle or the hyperbranched polymerizable compound (a) and (b) of secondary amino group at least one is single-, two-or oligosaccharides in liquid phase, under reductive amination condition, react, described hyperbranched polymerizable compound (a) is selected from (a1) ultrabranching polyamide and (a2) hyperbranched polyureas.
20. according to the method for claim 19, and wherein said reductive amination is undertaken by borine-Lewis base title complex.
21. according to the method for claim 19 or 20, and wherein said reductive amination is undertaken by borine-pyridine complex.
22. 1 kinds of mixtures, comprise at least one according to the hyperbranched polymer (A) of any one in claim 12-18 and at least one hydrophobic active composition.
23. 1 kinds of aqueous formulations, comprise at least one according to the mixture of claim 22.
Prepare according to the method for the mixture of claim 22 for 24. 1 kinds, it comprises at least one hyperbranched polymer (A) and at least one hydrophobic active composition is mixed mutually.
CN201180008293.2A 2010-02-05 2011-01-31 Method for solubilizing hydrophobic active ingredients in an aqueous solution Expired - Fee Related CN102741327B (en)

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