WO2017207546A1 - Stabilized enzyme-containing washing and cleaning compositions - Google Patents
Stabilized enzyme-containing washing and cleaning compositions Download PDFInfo
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- WO2017207546A1 WO2017207546A1 PCT/EP2017/063000 EP2017063000W WO2017207546A1 WO 2017207546 A1 WO2017207546 A1 WO 2017207546A1 EP 2017063000 W EP2017063000 W EP 2017063000W WO 2017207546 A1 WO2017207546 A1 WO 2017207546A1
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- 230000004888 barrier function Effects 0.000 description 1
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 1
- OHJMTUPIZMNBFR-UHFFFAOYSA-N biuret Chemical compound NC(=O)NC(N)=O OHJMTUPIZMNBFR-UHFFFAOYSA-N 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 125000005619 boric acid group Chemical class 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
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- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 229940079919 digestives enzyme preparation Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 229940066758 endopeptidases Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000002979 fabric softener Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 229940059442 hemicellulase Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000013038 irreversible inhibitor Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 108010020132 microbial serine proteinases Proteins 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910052573 porcelain Inorganic materials 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 238000009991 scouring Methods 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38663—Stabilised liquid enzyme compositions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/02—Inorganic compounds ; Elemental compounds
- C11D3/04—Water-soluble compounds
- C11D3/046—Salts
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/26—Organic compounds containing nitrogen
- C11D3/32—Amides; Substituted amides
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/26—Organic compounds containing nitrogen
- C11D3/32—Amides; Substituted amides
- C11D3/323—Amides; Substituted amides urea or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/34—Organic compounds containing sulfur
- C11D3/349—Organic compounds containing sulfur additionally containing nitrogen atoms, e.g. nitro, nitroso, amino, imino, nitrilo, nitrile groups containing compounds or their derivatives or thio urea
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/36—Organic compounds containing phosphorus
- C11D3/364—Organic compounds containing phosphorus containing nitrogen
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/37—Polymers
- C11D3/3703—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- C11D3/3719—Polyamides or polyimides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
Definitions
- the present invention relates to detergents or cleaners, preferably liquid detergents containing at least one protease, at least one compound of formula (I) and / or of formula (II), which acts as a protease inhibitor and thus is a suitable enzyme stabilizer, and a salt of Formula (III), which enhances the action of the protease inhibitor. Also part of the invention are the corresponding washing and cleaning methods, the use of the agents described herein and the use of a salt to increase the effect of a peptide stabilizer in a protease-containing detergent or cleaning agent.
- enzymes in detergents and cleaners have been established in the art for decades. They serve to extend the range of services of the funds concerned according to their specific activities. These include in particular hydrolytic enzymes such as proteases, amylases, lipases and cellulases. The first three hydrolyze proteins, starches and fats and thus contribute directly to soil removal. Cellulases are used in particular because of their tissue effect.
- Another group of washing and cleaning agent enzymes are oxidative enzymes, in particular oxidases, which, if appropriate, in combination with other components, are preferably used to bleach soiling or to produce the bleaching agents in situ.
- enzymes which are subjected to constant optimization, further enzymes are constantly being made available for use in detergents and cleaners in order to be able to optimally address particular soiling, such as pectinases, ⁇ -glucanases, mannanases or other hemicellulases (glycosidases) Hydrolysis in particular of special vegetable polymers.
- soiling such as pectinases, ⁇ -glucanases, mannanases or other hemicellulases (glycosidases) Hydrolysis in particular of special vegetable polymers.
- the other many pathway is to add chemical compounds that inhibit the proteases and thus act collectively as stabilizers for proteases and the other proteins and enzymes contained. It must be reversible protease inhibitors, since the protease activity is only temporarily, especially during storage, but not be suppressed during the cleaning process.
- Polyols in particular glycerol and 1,2-propylene glycol, benzamidine hydrochloride, borax, boric acids, boronic acids or their salts or esters are established as reversible protease inhibitors in the prior art.
- These include, in particular, derivatives having aromatic groups, for example ortho, meta or para-substituted phenylboronic acids, in particular 4-formylphenylboronic acid, or the salts or esters of the abovementioned compounds.
- a particularly good protection results when boric acid derivatives are used together with polyols, since these can then form a complex stabilizing the enzyme.
- peptide aldehydes that is, oligopeptides with reduced C-terminus, especially those of 2 to 50 monomers are described for this purpose.
- peptidic reversible protease inhibitors include ovomucoid and leupeptin.
- specific, reversible peptide inhibitors and fusion proteins from proteases and specific peptide inhibitors are used for this purpose.
- enzyme stabilizers are amino alcohols such as mono-, di-, triethanol- and -propanolamine and mixtures thereof, aliphatic carboxylic acids up to C12, such as succinic acid, other dicarboxylic acids or salts of said acids. End-capped fatty acid amide alkoxylates are also established for this purpose. Certain organic acids used as builders are capable, as disclosed in WO 97/18287, of stabilizing an enzyme in addition to their builder function.
- subtilisin-type proteases subtilases, subtilopeptidases, EC 3.4.21.62
- subtilisin-type proteases subtilases, subtilopeptidases, EC 3.4.21.62
- serine proteases due to the catalytically active amino acids. They act as nonspecific endopeptidases, ie they hydrolyze any acid. Reamiditatien that lie inside of peptides or proteins. Their pH optimum is usually in the clearly alkaline range.
- Subtilases Subtilisin-like Proteases
- Subtilisin enzymes edited by R. Bott and C. Betzel, New York, 1996.
- Subtilases are naturally formed by microorganisms; Of these, in particular, the subtilisins formed and secreted by Bacillus species are to be mentioned as the most important group within the subtilases.
- polyols such as glycerol and 1, 2-propylene glycol have proved to be unfavorable due to their high levels of use necessary concentrations, because the other active ingredients of the respective agents can thus be contained only in correspondingly lower proportions.
- boric acid derivatives occupy an outstanding position among the serine protease inhibitors (stabilizers), which are effective at a comparatively low concentration.
- the boric acid derivatives have a significant disadvantage: many of them, such as borate, form undesirable by-products with some other detergent ingredients, so that they are no longer available in the agents concerned for the desired cleaning purpose, or even remain as an impurity on the laundry.
- Peptide-based protease stabilizers do not have the disadvantages mentioned for boric acid derivatives. However, peptide-based protease stabilizers, when used in moderate concentrations, exhibit significantly reduced protease stabilizer performance compared to the boric acid standard stabilizer (1 wt% boric acid based on the total weight of the agent).
- the object of the present invention was therefore to identify compounds which increase the protease stabilizer performance of peptide-based protease stabilizers and are suitable for use in detergents and cleaners.
- detergents or cleaners which contain at least one protease, at least one enzyme stabilizer and at least one salt, wherein the at least one enzyme stabilizer is selected from compounds
- A is an amino acid residue
- X is hydrogen
- Z is an N-capping residue selected from phosphoramidate [(R'O) 2 (O) P-], sulfenamide [(SR ') 2 -], sulfonamide [(R' (O) 2 S-], sulfonic acid re [SOsH], phosphinamide [(R ') 2 (0) P-], sulfamoyl derivatives [R'0 (0) 2 S-], thiourea [(R') 2 N (0) C-], thiocarbamate [ R'0 (S) C-], phosphonate [R'-P (0) OH], amidophosphate
- C is a cation selected from the group consisting of Al 3+ , Ca 2+ , Li + , Mg 2+ , Mn 2+ , Ni 2+ , K + , NR'V and Na + , where each R "is independently is H or a linear or branched, substituted or unsubstituted alkyl, aryl or alkenyl group, all of which may optionally contain one or more heteroatom (s), E is an integer from 1 to 3 and corresponds to the valency of the cation ; p is the number of cations in the salt corresponding to D is an anion selected from the group consisting of CH 3 COO ", Br, CO3 2 -, Cr, C 3 H 5 0 (COO) 3 3 -, HCOO-, HCOs", HS0 4 " , C2O4 2 -, S0 4 2” and S0 3 2 " ; F is an integer from 1 to 3 and corresponds to the valency of the anion;
- Preferred radicals R are selected from methyl, isopropyl, sec-butyl, isobutyl, -C6H5, -CH2-CeHs, and -CH2-CH2-C6H5, so that the part -NH-CH (R) -C ( 0) -X of the compound of formula (I) is derived from the amino acids Ala, Val, Ile, Leu, PGIy (phenylglycine), Phe and HPhe (homophenylalanine) by converting the carboxyl group to an aldehyde or trifluoromethyl ketone group.
- the aldehydes of the present invention can be prepared from the corresponding amino acids by converting the C-terminal carboxyl group of the amino acid into an aldehyde group.
- Such aldehydes may be prepared by known methods, e.g. in U.S. Pat. Pat. No. 5015627, EP 0 185 930, EP 0 583 534 and DE 3200812.
- the trifluoromethyl ketones can also be prepared from the corresponding amino acids by converting the C-terminal carboxyl group into a trifluoromethyl ketone group.
- Such trifluoromethyl ketones can be prepared by known methods, for example as described in EP 0 583 535.
- the substituent A is selected from Ala, Gly, Val, Ile, Leu, Phe and Lys.
- the N-terminal end of the enzyme stabilizers of formula (I), and optionally that of the enzyme stabilizers of formula (II) is protected by a protecting group capping the N-terminus, the group being selected from carbamates, ureas, sulfonamides, Phos - phonamides, thioureas, sulfenamides, sulfonic acids, phosphinamides, thiocarbamates, amidophosphates and phosphonamides.
- the N-terminal end is replaced by a methyl, ethyl or benzyl carbamate group [CH30- (O) C-;
- N-capping groups can be found in the following documents: Protective Groups in Organic Chemistry, Greene, T., Wuts, P., John Wiley & Sons, New York, 1991, pp 309-405; March, J, Advanced Organic Chemistry, Wiley Interscience, 1985, pp. 445, 469, Carey, F. Sundberg, R., Advanced Organic Chemistry, Part B, Plenum Press, New York, 1990, p. 686-89; Atherton, E., Sheppard, R., Solid Phase Peptide Synthesis, Pierce Chemical, 1989, pp. 3-4; Grant, G., Synthetic Peptides, WH Freeman & Co. 1992, pp.
- Bodansky, M. Principles of Peptide Synthesis, Springer-Verlag, 1988, pp. 62, 203, 59-69; Bodansky, M., Peptide Chemistry, Springer-Verlag, 1988, pp. 74-81, Bodansky, M., Bodansky, A., The Practice of Peptide Synthesis, Springer-Verlag, 1984, pp. 44-8. 9-32.
- the agents according to the invention include salts of the formula (III). These salts are in the agents described herein in a concentration of 50-2000 mM, preferably in a concentration of 70-1500 mM, more preferably in a concentration of 100-1000 mM, even more preferably in a concentration of 150-500 mM and further preferably in a concentration of 200 mM.
- the salt according to structural formula (III) is Na 2 S0 4 .
- alkyl refers to an aliphatic hydrocarbon group which may be straight or branched and comprises 1 to 20 carbon atoms in the chain
- aryl refers to an aromatic monocyclic or aromatic multicyclic ring system comprising 6 to 14 carbon atoms.
- alkenyl refers to an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and which may be straight or branched and comprises from 2 to 15 carbon atoms in the chain.
- the agents according to the invention may contain, alternatively or in addition to the enzyme stabilizer of the formula (I), an enzyme stabilizer of the formula Y-B1-B0-X (II), where X is hydrogen; B1 is a single D or L amino acid residue; Bo is an amino acid residue and Y consists of one or more, preferably one or two, amino acid residues and optionally an N-capping residue, wherein the N-capping residue is as defined above.
- Bo is a D or L amino acid residue selected from Tyr, m-tyrosine, 3,4-dihydroxyphenylalanine, Phe, Val, Met, Nva, Leu, Ile and Nie, and / or B1 is a D- or L-amino acid residue having an (optionally substituted) small aliphatic side group, preferably Ala, Cys, Gly, Pro, Ser, Thr, Val, Nva or Never.
- Y is B2, B3-B2, Z-B2, Z-B3-B2, wherein B2 and B3 are each independently an amino acid residue and Z is an N-capping residue, wherein the N-capping residue is as defined above ,
- B2 is selected from Val, Gly, Ala, Arg, Leu, Phe and Thr, and / or B3 is selected from Phe, Tyr, Trp, phenylglycine, Leu, Val, Nva, None and all.
- the amino acids in the abovementioned formulas are linked via peptide bonds and all peptides or peptide-like compounds are always shown from the N to the C terminus, unless stated otherwise.
- the agents according to the invention may contain the at least one enzyme stabilizer according to structural formula (I) and / or (II) in a concentration of 0.01-50 mM, preferably in a concentration of 0.05-5 mM, more preferably in a concentration of 0, 1-0.5 mM included. If several enzyme stabilizers of formulas (I) and / or (II) are included, this information refers to the total concentration.
- Exemplary enzyme stabilizers of formulas (I) and (II) which can be used in the present invention include, but are not limited to, Cbz-Arg-Ala-Tyr-H, Ac-Gly-Ala-Tyr-H, Cbz-Gly-Ala -Tyr-H, Cbz-Gly-Ala-Tyr-H, Cbz-Val-Ala-Tyr-H, Cbz-Gly-Ala-Phe-H, Cbz-Gly-Ala-Val-H, Cbz-Gly-Gly -Tyr-H, Cbz-Gly-Gly-Phe-H, Cbz-Arg-Val-Tyr-H, Cbz-Leu-Val-Tyr-H, Ac-Leu-Gly-Ala-Tyr-H, Ac-Phe Gly-Ala-Tyr-H, Ac-Tyr-Gly-Ala-Tyr-H, Ac-P
- Cbz refers to the benzyloxycarbonyl group having the empirical formula C7H7O which is used as a protecting group
- Other terminal groups in the enzyme stabilizers of the present invention may be: "Ph”: phenyl; “Ac”: acetyl and “Me”: methyl.
- urea as used herein is synonymous with urea.
- the invention also includes all stereoisomers, in particular enantiomers and diastereomers, tautomers and salts of the compounds described above.
- a detergent or cleaning agent under a detergent or cleaning agent according to the invention are all means that are suitable for washing or cleaning of particular textiles and / or solid surfaces. Other suitable ingredients are described in detail below.
- a protease is to be understood as meaning all enzymes which are capable of hydrolyzing acid amide linkages of proteins. The proteases are also described in detail below.
- the first advantage of the prior art compounds over the prior art is that the above-mentioned advantages of peptide stabilizers can be utilized (e.g., avoiding the formation of undesirable by-products in the composition of the invention by the unwanted reactions of the stabilizer with other ingredients of the composition).
- at least one salt of the formula (III) it is surprisingly possible to use the peptide stabilizers in moderate concentrations (0.01-50 mM) without the agent having a significantly reduced protease stabilizer performance in comparison to the standard stabilizer (boric acid) having.
- the protease and optionally other proteins contained, in particular other enzymes are protected in this way against proteolysis by this enzyme (stabilized against proteolysis) and are thus fully efficient even after storage.
- the compounds relevant to the invention have good solubility in water, so that they can easily be incorporated into corresponding agents and precipitation during storage is avoided.
- the said enzyme inhibitors presumably act as reversible inhibitors because they are structurally adapted to the conditions of the binding pocket, similar to the substrate of the proteases.
- washing or cleaning agent for washing and / or cleaning textiles and / or hard surfaces; such as the use of a protease and the compounds described above according to (A) formula (I) and / or (II) and (B) formula (III) for the preparation of a washing or cleaning agent.
- the enzyme i. the protease in an amount of 0.05-5% by weight, preferably 0.05-2% by weight, and the enzyme stabilizer in an amount of 0.05-15% by weight, preferably 0.05- 5 wt .-%, based on the total weight of the washing or cleaning agent contained in this.
- the enzyme and the enzyme stabilizer may be pre-formulated in an enzyme composition.
- the enzyme protein forms only a fraction of the total weight of conventional enzyme preparations.
- Preferably used protease preparations contain between 0, 1 and 40 wt .-%, preferably between 0.2 and 30 wt .-%, particularly preferably between 0.4 and 20 wt .-% and in particular between 0.8 and 10 wt .-% of the enzyme protein.
- the enzyme stabilizer may be contained in an amount of 0.05-35% by weight, preferably 0.05-10% by weight, based on the total weight in the enzyme composition.
- This enzyme composition which is also a constituent of the present invention, can then be used in detergents or cleaners according to the invention in amounts which lead to the above-mentioned final concentrations in the washing or cleaning agent.
- the protein concentration can be determined by known methods, for example the BCA method (bicinchoninic acid, 2,2'-biquinolyl-4,4'-dicarboxylic acid) or the biuret method.
- BCA method bicinchoninic acid, 2,2'-biquinolyl-4,4'-dicarboxylic acid
- the determination of the active protein concentration takes place via a titration of the active sites using a suitable irreversible inhibitor (for proteases, for example phenylmethylsulfonyl fluoride (PMSF)) and determination of the residual activity (compare M. Bender et al., J. Am. Chem. Soc , 24 (1966), pp. 5890-5913).
- PMSF phenylmethylsulfonyl fluoride
- an agent according to the invention may contain at least one further stabilizer, in particular a polyol, such as glycerol or 1,2-ethylene glycol, and / or an antioxidant.
- a further stabilizer in particular a polyol, such as glycerol or 1,2-ethylene glycol, and / or an antioxidant.
- the proteases used are alkaline serine proteases. They act as nonspecific endopepetases, that is, they hydrolyze any acid amide bonds that are located inside peptides or proteins, thereby causing degradation of proteinaceous soils on the items to be cleaned. Their pH optimum is usually in the clearly alkaline range.
- the protease stabilized or reversibly inhibited according to the invention is therefore preferably a serine protease, in particular a subtilase, more preferably a subtilisin.
- the subtilisin may be a wild-type enzyme or a subtilisin variant, wherein the wild-type enzyme or the starting enzyme of the variant is preferably selected from one of the following:
- alkaline protease from Bacillus lentus, preferably from Bacillus lentus (DSM 5483),
- alkaline protease from Bacillus sp. (DSM 14390) or an at least 98.5% identical alkaline protease, and
- alkaline protease from Bacillus sp. (DSM 14392) or an at least 98.1% identical alkaline protease.
- the protease stabilized according to the invention is a protease selected from the group of proteases according to SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3.
- SEQ ID NO: 1 / SEQ ID NO: 2; SEQ ID NO: 1 / SEQ ID NO: 3; SEQ ID NO: 2 / SEQ ID NO: 3 or SEQ ID NO: 1 / SEQ ID NO: 2 / SEQ ID NO: 3 stabilized according to the invention.
- protease Although reference will always be made hereinafter to a protease, it is of course also possible to use a combination of two or more proteases.
- Variant refers to naturally or artificially produced variations of a native protease that have an amino acid sequence that is modified from the reference form
- Such variant may be single or multiple point mutations, ie, substitutions of one naturally at the appropriate position one or more insertions (insertion of one or more amino acids) and / or deletions (removal of one or more amino acids), in particular one or more point mutations
- Such variants preferably have at least 50, preferably 60 or more, more preferably 70 , 80, 90, 100% or more of the enzyme activity of the reference form
- such variant has an amino acid sequence leading to the reference sequence over its total length of at least 70, preferably 75, 80, 85, 90, 95, 96 , 97, 98, or 99% is identical.
- the variants preferably have the same length as the reference sequence.
- Variants can be opposite the reference form characterized by improved properties, such as higher enzyme activity, higher stability, altered substrate specificity, etc ..
- sequence comparison is based on the BLAST algorithm established and commonly used in the prior art (see, for example, Altschul, SF, Gish, W., Miller, W., Myers, EW & Lipman, DJ. (1990) "Basic local alignment search Biol. 215: 403-410; and Altschul, Stephan F., Thomas L. Madden, Alejandro A. Schaffer, Jinghui Zhang, Hheng Zhang, Webb Miller, and David J.
- Lipman (1997): "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs"; Nucleic Acids Res., 25, pp.3389-3402) and is in principle effected by similar sequences of nucleotides or amino acids in the nucleic acid or nucleic acid sequences Amino acid sequences are assigned to each other. A tabular assignment of the respective positions is referred to as alignment.
- Another algorithm available in the prior art is the FASTA algorithm.
- Such a comparison also allows a statement about the similarity of the compared sequences to each other. It is usually given in percent identity, that is, the proportion of identical nucleotides or amino acid residues at the same or in an alignment corresponding positions.
- the broader concept of homology involves conserved amino acid substitutions in the consideration of amino acid sequences, that is, amino acids with similar chemical activity, as these usually perform similar chemical activities within the protein. Therefore, the similarity of the sequences compared may also be stated as percent homology or percent similarity.
- Identity and / or homology information can be made about whole polypeptides or genes or only over individual regions. Homologous or identical regions of different nucleic acid or amino acid sequences are therefore defined by matches in the sequences. Such areas often have identical functions.
- nucleic acid or amino acid sequence can be small and comprise only a few nucleotides or amino acids. Often, such small regions exert essential functions for the overall activity of the protein. It may therefore be useful to relate sequence matches only to individual, possibly small areas. Unless otherwise indicated, identity or homology information in the present application, however, refers to the total length of the particular nucleic acid or amino acid sequence indicated.
- “Functional fragments” as used herein refers to enzymatically active polypeptides which are truncated N- and / or C-terminally by at least one, preferably two or more, amino acids as compared to the reference sequence
- the activity of such fragments is at least 50%, preferably at least 60, 70, 80, 90, 95 or 100% of the activity of the reference enzyme.
- the measurement of the enzyme activity - matched to the particular type of enzyme - can be carried out in the customary manner. Methods for determining activity are familiar to the expert in the field of enzyme technology and are routinely used by him. Methods for determining protease activity are disclosed, for example, in Tenside, Vol. 7 (1970), pp. 125-132.
- the proteolytic activity can also be determined by the release of the chromophore para-nitroaniline (pNA) from the substrate suc-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide (suc-AAPF-pNA ).
- the protease cleaves the substrate and releases pNA.
- the release of pNA causes an increase in absorbance at 410 nm, the time course of which is a measure of enzymatic activity (see Del Mar et al., 1979).
- the measurement can be carried out at a temperature of 25 ° C, at pH 8.6 and a wavelength of 410 nm.
- the measuring time can be 5 min. amount to a measuring interval of 20s to 60s.
- the enzymes to be used may also be formulated together with adjuncts, such as from fermentation.
- the enzymes are preferably used as enzyme liquid formulation (s).
- the proteases are generally not provided in the form of the pure protein but rather in the form of stabilized, storage and transportable preparations.
- Such prefabricated preparations include, for example, the solid preparations obtained by granulation, extrusion or lyophilization or, especially in the case of liquid or gel-form detergents, solutions of the enzymes, advantageously as concentrated as possible, low in water and / or added with stabilizers or further auxiliaries.
- the enzymes may be encapsulated for both the solid and liquid dosage forms, for example by spray-drying or extruding the enzyme solution together with a preferably natural polymer or in the form of capsules, for example those in which the enzymes are entrapped as in a solidified gel or in those of the core-shell type in which an enzyme-containing core is coated with a water, air and / or chemical impermeable protective layer.
- a preferably natural polymer or in the form of capsules for example those in which the enzymes are entrapped as in a solidified gel or in those of the core-shell type in which an enzyme-containing core is coated with a water, air and / or chemical impermeable protective layer.
- further active ingredients for example stabilizers, emulsifiers, pigments, bleaches or dyes, may additionally be applied.
- Such capsules are applied by methods known per se, for example by shaking or rolling granulation or in fluid-bed processes.
- such granules for example by applying polymeric
- Agents according to the invention may contain, in addition to the protease, one or more further enzymes, in particular from the following group: amylases, hemicellulases, cellulases, lipases and oxidoreductases.
- the amylase (s) is preferably an ⁇ -amylase.
- the hemicellulase is preferably a ⁇ -glucanase, a pectinase, a pullulanase and / or a mannanase.
- the cellulase is preferably a cellulase mixture or a one-component cellulase, preferably or predominantly an endoglucanase and / or a cellobiohydrolase.
- the oxidoreductase is preferably an oxidase, in particular a choline oxidase, or a perhydrolase.
- compositions described herein include all conceivable types of detergents or cleaners, both concentrates and neat agents, for use on a commercial scale, in the washing machine or in hand washing or cleaning.
- detergents for textiles, carpets, or natural fibers, for which the term detergent is used.
- washing and cleaning agents in the invention also include washing aids which are added to the actual detergent in the manual or machine textile laundry to achieve a further effect.
- laundry detergents and cleaners in the context of the invention also include textile pre-treatment and post-treatment agents, ie those agents with which the laundry item is brought into contact before the actual laundry, for example to dissolve stubborn soiling, and also agents which are in one of the actual Textile laundry downstream step to give the laundry further desirable properties such as comfortable grip, crease resistance or low static charge. Among the latter, i.a. calculated the fabric softener.
- Embodiments of the present invention include all solid, powdered, liquid, gelatinous or pasty administration forms of agents described herein, which if appropriate can also consist of several phases and can be present in compressed or uncompressed form.
- the agent can be present as a free-flowing powder, in particular with a bulk density of 300 g / l to 1200 g / l, in particular 500 g / l to 900 g / l or 600 g / l to 850 g / l.
- the solid dosage forms of the composition also include extrudates, granules, tablets or pouches.
- the agent can also be liquid, gelatinous or pasty, for example in the form of a nonaqueous liquid washing or dishwashing detergent or a nonaqueous paste or in the form of an aqueous liquid washing or dishwashing detergent or a water-based dishwashing detergent. paste.
- the agent may be present as a one-component system. Such funds consist of one phase. Alternatively, an agent can also consist of several phases. Such an agent is therefore divided into several components.
- the detergents or cleaners described herein which may be in the form of powdered solids, in densified particulate form, as homogeneous solutions or suspensions, may further additionally contain all known ingredients customary in such compositions, preferably at least one further ingredient being present in the composition.
- the agents described herein may contain surfactants, builders, bleaches or bleach activators.
- they may contain water-miscible organic solvents, sequestering agents, electrolytes, pH regulators and / or further auxiliaries, such as optical brighteners, graying inhibitors, foam regulators, as well as dyes and fragrances, and combinations thereof.
- compositions described herein are disclosed in International Patent Application WO2009 / 121725, beginning on page 5, penultimate paragraph, and ending on page 13, after the second paragraph.
- Exemplary formulations of detergents or cleaners which may contain the protease, enzyme stabilizer and salt described herein are described in US6165966, Example 1, 2 and 3; WO20091 18375, Example 1 and WO2013004636, Table 1 and 3 discloses. This disclosure is incorporated herein by reference and the disclosure is incorporated herein by reference.
- a further subject of the invention is a method for the cleaning of textiles or hard surfaces, which is characterized in that in at least one method step a means described herein is used.
- Methods for cleaning textiles are generally distinguished by the fact that various cleaning-active substances are applied to the items to be cleaned and washed off after the contact time, or that the items to be cleaned are otherwise treated with a detergent or a solution or dilution of this product.
- Another subject of the invention is the use of an agent described herein for cleaning or washing textiles or for cleaning hard surfaces. All aspects, objects, and embodiments described for means described herein are also applicable to the aforementioned methods and uses. Therefore, reference is made at this point expressly to the disclosure in the appropriate place with the statement that this disclosure also applies to the above described methods and uses.
- the peptide-stabilizer / peptide inhibitor (PI) used is the peptide methoxycarbonyl-Val-Ala-leu-aldehyde, which was synthesized by Bachem (Bubendor, Switzerland).
- the proteolytic activity was determined by the release of the chromophore para-nitroaniline (pNA) from the substrate suc-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide (suc-AAPF-pNA).
- the protease cleaves the substrate and releases pNA.
- the release of pNA causes an increase in absorbance at 410 nm, the time course of which is a measure of enzymatic activity (see Del Mar et al., 1979).
- the measurement is carried out at a temperature of 25 ° C, at pH 8.6 and a wavelength of 410 nm.
- the measuring time is 5 min. at a measuring interval of 20s to 60s.
- the stabilizing effect of the peptide stabilizer / peptide inhibitor was measured in comparison to the effect of Na borate at various concentrations (by incubating the formulation at 30 ° C for the indicated number of days):
- the addition of salt causes increased stability of the enzyme in the presence of the peptide inhibitor to a level even greater than that observed with borate stabilization.
- Enzymes (amylase, protease, cel + + + + + + + + + + + + + + + + + + + + + + + + + + + lulase)
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Abstract
The present invention relates to washing or cleaning compositions, preferably liquid washing compositions, comprising at least one protease, at least one compound of the formula (I) and/or of the formula (II) that acts as a protease inhibitor and is thus a suitable enzyme stabilizer, and a salt of the formula (III) that boosts the action of the protease inhibitor. The invention likewise provides the corresponding washing and cleaning methods, for the use of the compositions described herein, and for the use of a salt for increasing the action of a peptide stabilizer in a protease-containing washing or cleaning composition.
Description
Stabilisierte Enzym-haltige Wasch- und Reinigungsmittel Stabilized enzyme-containing detergents and cleaners
Die vorliegende Erfindung betrifft Wasch- oder Reinigungsmittel, bevorzugt flüssige Waschmittel, enthaltend mindestens eine Protease, mindestens eine Verbindung der Formel (I) und/oder der Formel (II), die als Proteaseinhibitor wirkt und somit ein geeigneter Enzymstabilisator ist, sowie ein Salz der Formel (III), welches die Wirkung des Proteaseinhibitors verstärkt. Ebenfalls Bestandteil der Erfindung sind die entsprechenden Wasch- und Reinigungsverfahren, die Verwendung der hierin beschriebenen Mittel sowie die Verwendung eines Salzes zur Erhöhung der Wirkung eines Peptidstabilisators in einem Protease-haltigen Wasch- oder Reinigungsmittel. The present invention relates to detergents or cleaners, preferably liquid detergents containing at least one protease, at least one compound of formula (I) and / or of formula (II), which acts as a protease inhibitor and thus is a suitable enzyme stabilizer, and a salt of Formula (III), which enhances the action of the protease inhibitor. Also part of the invention are the corresponding washing and cleaning methods, the use of the agents described herein and the use of a salt to increase the effect of a peptide stabilizer in a protease-containing detergent or cleaning agent.
Der Einsatz von Enzymen in Wasch- und Reinigungsmitteln ist seit Jahrzehnten im Stand der Technik etabliert. Sie dienen dazu, das Leistungsspektrum der betreffenden Mittel entsprechend ihren speziellen Aktivitäten zu erweitern. Hierzu gehören insbesondere hydrolytische Enzyme wie Proteasen, Amylasen, Lipasen und Cellulasen. Die ersten drei genannten hydrolysieren Proteine, Stärke und Fette und tragen somit unmittelbar zur Schmutzentfernung bei. Cellulasen werden insbesondere wegen ihrer Gewebewirkung eingesetzt. Eine weitere Gruppe von Wasch- und Reinigungsmittelenzymen sind oxidative Enzyme, insbesondere Oxidasen, die ggf. im Zusammenspiel mit anderen Komponenten vorzugsweise dazu dienen, Anschmutzungen zu bleichen oder die bleichenden Agentien in situ zu erzeugen. Neben diesen Enzymen, die einer fortwährenden Optimierung unterworfen werden, werden laufend weitere Enzyme für den Einsatz in Wasch- und Reinigungsmitteln bereitgestellt, um insbesondere spezielle Anschmutzungen optimal angehen zu können, wie beispielsweise Pektinasen, ß-Glucanasen, Mannanasen oder weitere Hemicellulasen (Glykosidasen) zur Hydrolyse insbesondere spezieller pflanzlicher Polymere. The use of enzymes in detergents and cleaners has been established in the art for decades. They serve to extend the range of services of the funds concerned according to their specific activities. These include in particular hydrolytic enzymes such as proteases, amylases, lipases and cellulases. The first three hydrolyze proteins, starches and fats and thus contribute directly to soil removal. Cellulases are used in particular because of their tissue effect. Another group of washing and cleaning agent enzymes are oxidative enzymes, in particular oxidases, which, if appropriate, in combination with other components, are preferably used to bleach soiling or to produce the bleaching agents in situ. In addition to these enzymes, which are subjected to constant optimization, further enzymes are constantly being made available for use in detergents and cleaners in order to be able to optimally address particular soiling, such as pectinases, β-glucanases, mannanases or other hemicellulases (glycosidases) Hydrolysis in particular of special vegetable polymers.
Die am längsten etablierten und in praktisch allen modernen, leistungsfähigen Wasch- und Reinigungsmitteln enthaltenen Enzyme sind Proteasen und hierunter insbesondere Serin- Proteasen, zu denen erfindungsgemäß auch die Subtilasen gerechnet werden. Sie dienen dem Abbau proteinhal- tiger Anschmutzungen auf dem Reinigungsgut. Allerdings hydrolysieren sie auch sich selbst (Au- toproteolyse) und alle anderen in den betreffenden Mitteln enthaltenen Proteine, d.h. insbesondere Enzyme. Dies geschieht besonders während des Reinigungsvorgangs, d.h. in der wässrigen Waschflotte, wenn vergleichsweise günstige Reaktionsbedingungen vorliegen. Dies geschieht in geringerem Ausmaße aber auch während der Lagerung der betreffenden Mittel, weshalb mit einer langen Lagerung immer auch ein gewisser Verlust der Proteaseaktivität sowie der Aktivitäten der anderen Enzyme einhergeht. Besonders problematisch ist dies in gelförmigen oder flüssigen und insbesondere in wasserhaltigen Rezepturen, weil in diesem mit dem enthaltenen Wasser sowohl das Reaktionsmedium als auch das Hydrolyse-Reagenz zur Verfügung stellen.
Ein Ziel bei der Entwicklung von Wasch- und Reinigungsmittelrezepturen besteht darin, die enthaltenen Enzyme besonders während der Lagerung zu stabilisieren. Darunter wird der Schutz gegen verschiedene ungünstige Einflüsse verstanden, wie beispielsweise gegen Denaturierung oder Zerfall durch physikalische Einflüsse oder Oxidation. Ein Schwerpunkt dieser Entwicklungen besteht im Schutz der enthaltenen Proteine und/oder Enzyme gegen proteolytische Spaltung. Diese kann durch den Aufbau physikalischer Barrieren erfolgen, etwa durch Verkapselung der Enzyme in speziellen Enzymgranulaten oder durch Konfektionierung der Mittel in Zwei- oder Mehrkammersystemen. Der andere vielfach beschrittene Weg besteht darin, chemische Verbindungen zuzusetzen, die die Proteasen inhibieren und somit insgesamt als Stabilisatoren für Proteasen und die anderen enthaltenen Proteine und Enzyme wirken. Es muss sich dabei um reversible Proteaseinhibitoren handeln, da die Proteaseaktivität nur vorübergehend, insbesondere während der Lagerung, nicht aber mehr während des Reinigungsprozesses unterbunden werden soll. The enzymes which are the longest-established and are contained in virtually all modern, powerful detergents and cleaners are proteases and, in particular, serine proteases, to which the subtilases according to the invention are also calculated. They are used to break down proteinaceous soiling on the items to be cleaned. However, they also hydrolyze themselves (auto-proteolysis) and all other proteins contained in the agents concerned, ie in particular enzymes. This happens especially during the cleaning process, ie in the aqueous wash liquor, when comparatively favorable reaction conditions are present. This occurs to a lesser extent but also during storage of the agents concerned, which is why a long storage always accompanied by a certain loss of protease activity and the activities of other enzymes. This is particularly problematic in gel or liquid and especially in water-containing formulations, because in this with the water contained both the reaction medium and the hydrolysis reagent available. One goal in the development of detergent formulations is to stabilize the enzymes contained, especially during storage. This is understood as protection against various unfavorable influences, such as denaturation or decay by physical influences or oxidation. One focus of these developments is the protection of the contained proteins and / or enzymes against proteolytic cleavage. This can be done by the construction of physical barriers, such as by encapsulation of the enzymes in special enzyme granules or by packaging the means in two- or multi-chamber systems. The other many pathway is to add chemical compounds that inhibit the proteases and thus act collectively as stabilizers for proteases and the other proteins and enzymes contained. It must be reversible protease inhibitors, since the protease activity is only temporarily, especially during storage, but not be suppressed during the cleaning process.
Als reversible Proteaseinhibitoren sind im Stand der Technik Polyole, insbesondere Glycerin und 1 ,2-Propylenglycol, Benzamidin-Hydrochlorid, Borax, Borsäuren, Boronsäuren oder deren Salze oder Ester etabliert. Darunter sind vor allem Derivate mit aromatischen Gruppen, etwa ortho-, me- ta- oder para-substituierte Phenylboronsäuren zu erwähnen, insbesondere 4-Formylphenyl- Boron- säure, beziehungsweise die Salze oder Ester der genannten Verbindungen. Ein besonders guter Schutz ergibt sich, wenn Borsäurederivate zusammen mit Polyolen eingesetzt werden, da diese dann einen das Enzym stabilisierenden Komplex bilden können. Auch Peptidaldehyde, das heißt Oligopeptide mit reduziertem C-Terminus, insbesondere solche aus 2 bis 50 Monomeren sind zu diesem Zweck beschrieben. Zu den peptidischen reversiblen Proteaseinhibitoren gehören unter anderem Ovomucoid und Leupeptin. Auch spezifische, reversible Peptid-Inhibitoren sowie Fusionsproteine aus Proteasen und spezifischen Peptid-Inhibitoren werden hierfür eingesetzt. Polyols, in particular glycerol and 1,2-propylene glycol, benzamidine hydrochloride, borax, boric acids, boronic acids or their salts or esters are established as reversible protease inhibitors in the prior art. These include, in particular, derivatives having aromatic groups, for example ortho, meta or para-substituted phenylboronic acids, in particular 4-formylphenylboronic acid, or the salts or esters of the abovementioned compounds. A particularly good protection results when boric acid derivatives are used together with polyols, since these can then form a complex stabilizing the enzyme. Also peptide aldehydes, that is, oligopeptides with reduced C-terminus, especially those of 2 to 50 monomers are described for this purpose. Among the peptidic reversible protease inhibitors include ovomucoid and leupeptin. Also, specific, reversible peptide inhibitors and fusion proteins from proteases and specific peptide inhibitors are used for this purpose.
Weitere etablierte Enzymstabilisatoren sind Aminoalkohole wie Mono-, Di-, Triethanol- und -propanolamin und deren Mischungen, aliphatische Carbonsäuren bis zu C12, wie beispielsweise Bernsteinsäure, andere Dicarbonsäuren oder Salze der genannten Säuren. Auch endgruppenver- schlossene Fettsäureamidalkoxylate sind für diesen Zweck etabliert. Bestimmte als Builder eingesetzte organische Säuren vermögen, wie in WO 97/18287 offenbart, zusätzlich zu ihrer Builder- Funktion auch ein Enzym zu stabilisieren. Other established enzyme stabilizers are amino alcohols such as mono-, di-, triethanol- and -propanolamine and mixtures thereof, aliphatic carboxylic acids up to C12, such as succinic acid, other dicarboxylic acids or salts of said acids. End-capped fatty acid amide alkoxylates are also established for this purpose. Certain organic acids used as builders are capable, as disclosed in WO 97/18287, of stabilizing an enzyme in addition to their builder function.
Als Wasch- und Reinigungsmittelproteasen sind verschiedene Protease-Klassen etabliert, beispielsweise Metalloproteasen. Unter den Wasch- und Reinigungsmittelproteasen nehmen Proteasen vom Subtilisin-Typ (Subtilasen, Subtilopeptidasen, EC 3.4.21 .62) aufgrund ihrer günstigen enzymatischen Eigenschaften wie Stabilität oder pH-Optimum allerdings eine herausragende Stellung ein. Sie werden aufgrund der katalytisch wirksamen Aminosäuren den Serin-Proteasen zugerechnet. Sie wirken als unspezifische Endopeptidasen, das heißt, sie hydrolysieren beliebige Säu-
reamidbindungen, die im Inneren von Peptiden oder Proteinen liegen. Ihr pH-Optimum liegt meist im deutlich alkalischen Bereich. Einen Überblick über diese Familie bietet beispielsweise der Artikel „Subtilases: Subtilisin-like Proteases" von R. Siezen, Seite 75-95 in„Subtilisin enzymes", heraus- gegegeben von R. Bott und C. Betzel, New York, 1996. Subtilasen werden natürlicherweise von Mikroorganismen gebildet; hierunter sind insbesondere die von Bacillus-Spezies gebildeten und sekretierten Subtilisine als bedeutendste Gruppe innerhalb der Subtilasen zu erwähnen. As detergency and detergent proteases various protease classes are established, for example metalloproteases. However, among the detergent and detergent proteases, subtilisin-type proteases (subtilases, subtilopeptidases, EC 3.4.21.62) have a prominent position due to their favorable enzymatic properties such as stability or pH optimum. They are attributed to the serine proteases due to the catalytically active amino acids. They act as nonspecific endopeptidases, ie they hydrolyze any acid. Reamidbindungen that lie inside of peptides or proteins. Their pH optimum is usually in the clearly alkaline range. For an overview of this family, see for example the article "Subtilases: Subtilisin-like Proteases" by R. Siezen, pages 75-95 in "Subtilisin enzymes", edited by R. Bott and C. Betzel, New York, 1996. Subtilases are naturally formed by microorganisms; Of these, in particular, the subtilisins formed and secreted by Bacillus species are to be mentioned as the most important group within the subtilases.
Es wird deshalb besonders daran gearbeitet, reversible Inhibitoren gerade dieser Enzymklasse zur Verfügung zu stellen. Dabei haben sich Polyole wie Glycerin und 1 ,2-Propylenglycol aufgrund ihrer hohen notwendigen Einsatzkonzentrationen als unvorteilhaft erwiesen, weil die übrigen Wirkstoffe der betreffenden Mittel damit nur noch in entsprechend geringeren Anteilen enthalten sein können. It is therefore particularly worked to provide reversible inhibitors just this class of enzymes available. In this case, polyols such as glycerol and 1, 2-propylene glycol have proved to be unfavorable due to their high levels of use necessary concentrations, because the other active ingredients of the respective agents can thus be contained only in correspondingly lower proportions.
Unter den bereits in vergleichsweise niedriger Konzentration wirksamen Serin-Protease-Inhibitoren (Stabilisatoren) nehmen Borsäurederivate eine herausragende Stellung ein. Unabhängig von ihrer stabilisierenden Wirkung weisen die Borsäurederivate jedoch einen entscheidenden Nachteil auf: Viele davon, wie beispielsweise Borat, bilden mit einigen anderen Wasch- bzw. Reinigungsmittelinhaltsstoffen unerwünschte Nebenprodukte, so dass diese in den betreffenden Mitteln nicht mehr für den erwünschten Reinigungszweck zur Verfügung stehen oder sogar als Verunreinigung auf dem Waschgut zurückbleiben. Boric acid derivatives occupy an outstanding position among the serine protease inhibitors (stabilizers), which are effective at a comparatively low concentration. However, regardless of their stabilizing effect, the boric acid derivatives have a significant disadvantage: many of them, such as borate, form undesirable by-products with some other detergent ingredients, so that they are no longer available in the agents concerned for the desired cleaning purpose, or even remain as an impurity on the laundry.
Peptid-basierte Proteasestabilisatoren weisen die für Borsäurederivate genannten Nachteile nicht auf. Allerdings weisen Peptid-basierte Proteasestabilisatoren, wenn sie in moderaten Konzentrationen eingesetzt werden, im Vergleich zum Borsäure-Standardstabilisator (1 Gew.-% Borsäure bezogen auf das Gesamtgewicht des Mittels) eine signifikant verringerte Proteasestabilisator- Leistung auf. Peptide-based protease stabilizers do not have the disadvantages mentioned for boric acid derivatives. However, peptide-based protease stabilizers, when used in moderate concentrations, exhibit significantly reduced protease stabilizer performance compared to the boric acid standard stabilizer (1 wt% boric acid based on the total weight of the agent).
Aufgabe der vorliegenden Erfindung war es daher, Verbindungen zu identifizieren, die die Pro- teasestabilisator-Leistung von Peptid-basierten Proteasestabilisatoren steigern und für den Einsatz in Wasch- und Reinigungsmitteln geeignet sind. Hierbei war der Einsatz in insgesamt flüssigen, gelförmigen oder pastösen Wasch- und Reinigungsmitteln von besonderem Interesse, und darunter insbesondere in solchen, die Wasser enthalten. The object of the present invention was therefore to identify compounds which increase the protease stabilizer performance of peptide-based protease stabilizers and are suitable for use in detergents and cleaners. Here, the use in total liquid, gel or pasty detergents and cleaning agents of particular interest, and including in particular those containing water.
Diese Aufgabe wird durch Wasch- oder Reinigungsmittel gelöst, die mindestens eine Protease, mindestens einen Enzymstabilisator und mindestens ein Salz enthalten, wobei der mindestens eine Enzymstabilisator ausgewählt wird aus Verbindungen This object is achieved by detergents or cleaners which contain at least one protease, at least one enzyme stabilizer and at least one salt, wherein the at least one enzyme stabilizer is selected from compounds
(I) der allgemeinen Strukturformel (I) (I) the general structural formula (I)
Z-A-NH-CH(R)-C(0)-X (I), Z-A-NH-CH (R) -C (O) -X (I),
wobei A ein Aminosäurerest ist; X Wasserstoff ist; Z ein N-Verkappungsrest ausgewählt aus Phosphoramidat [(R'0)2(0)P-], Sulfenamid [(SR')2-], Sulfonamid [(R'(0)2S-], Sulfonsäu-
re [SOsH], Phosphinamid [(R')2(0)P-], Sulfamoyl Derivaten [R'0(0)2S-], Thioharnstoff [(R')2N(0)C-], Thiocarbamat [R'0(S)C-], Phosphonat [R'-P(0)OH], Amidophosphat wherein A is an amino acid residue; X is hydrogen; Z is an N-capping residue selected from phosphoramidate [(R'O) 2 (O) P-], sulfenamide [(SR ') 2 -], sulfonamide [(R' (O) 2 S-], sulfonic acid re [SOsH], phosphinamide [(R ') 2 (0) P-], sulfamoyl derivatives [R'0 (0) 2 S-], thiourea [(R') 2 N (0) C-], thiocarbamate [ R'0 (S) C-], phosphonate [R'-P (0) OH], amidophosphate
[R'0(OH)(0)P-], Carbamat (R'O(O)C-) und Harnstoff (R'NH(O)C-) ist, wobei jedes R' unabhängig ausgewählt wird aus geradkettigen oder verzweigten C1-C6 unsubstituierten Al- kyl-, Phenyl-, C7-C9 Alkylaryl- und Cycloalkyl-Resten, wobei der Cycloalkylring ein C4-C8 Cycloalkylring sein kann und ein oder mehrere Heteroatome enthalten kann, die ausgewählt werden aus O, N, und S; und R ausgewählt wird aus geradkettigen oder verzweigten C1-C6 unsubstituierten Alkyl-, Phenyl und C7-C9 Alkylarylresten; und Stereoisomeren, Tautomeren und Salzen davon; oder [R'0 (OH) (O) P-], carbamate (R'O (O) C-) and urea (R'NH (O) C-), where each R 'is independently selected from straight-chain or branched C1-C6 unsubstituted alkyl, phenyl, C7-C9 alkylaryl and cycloalkyl radicals, wherein the cycloalkyl ring may be a C4-C8 cycloalkyl ring and may contain one or more heteroatoms selected from O, N, and S ; and R is selected from C1 to C6 straight or branched unsubstituted alkyl, phenyl and C7 to C9 alkylaryl radicals; and stereoisomers, tautomers and salts thereof; or
(I I) der allgemeinen Strukturformel (I I) (I I) of the general structural formula (I I)
wobei X Wasserstoff ist; B1 ein einzelner D- oder L-Aminosäurerest ist; Bo ein Aminosäurerest ist und Y aus einem oder mehreren, bevorzugt ein oder zwei, Aminosäureresten und optional aus einem N-Verkappungsrest besteht, wobei der N-Verkappungsrest wie unter (I) definiert ist; und wherein X is hydrogen; B1 is a single D or L amino acid residue; Bo is an amino acid residue and Y is one or more, preferably one or two, amino acid residues and optionally an N-capping residue, wherein the N-capping residue is as defined under (I); and
wobei das mindestens eine Salz der allgemeinen Strukturformel (I I I) where the at least one salt of the general structural formula (I I I)
(CE+)P(DF )q (I II) entspricht, (C E + ) P (D F ) q (I II),
wobei C ein Kation ausgewählt aus der Gruppe bestehend aus Al3+, Ca2+, Li+, Mg2+, Mn2+, Ni2+, K+, NR'V und Na+ ist, wobei jedes R" unabhängig voneinander für H oder eine lineare oder verzweigte, substituierte oder unsubstituierte Alkyl-, Aryl- oder Alkenylgruppe steht, die alle optional ein oder mehrere Heteroatom(e) enthalten können; E eine ganze Zahl von 1 bis 3 ist und der Valenz/Wertigkeit des Kations entspricht; p der Anzahl an Kationen im Salz entspricht; D ein Anion ausgewählt aus der Gruppe bestehend aus CH3COO", Br, CO32-, Cr, C3H50(COO)33-, HCOO-, HCOs", HS04 ", C2O42-, S04 2" und S03 2" ist; F eine ganze Zahl von 1 bis 3 ist und der Valenz/Wertigkeit des Anions entspricht; q der Anzahl an Anionen im Salz entspricht; wobei die Nettoladung des Salzes 0 ist, d.h. es gilt ((E) p) - ((F) q) = 0. wherein C is a cation selected from the group consisting of Al 3+ , Ca 2+ , Li + , Mg 2+ , Mn 2+ , Ni 2+ , K + , NR'V and Na + , where each R "is independently is H or a linear or branched, substituted or unsubstituted alkyl, aryl or alkenyl group, all of which may optionally contain one or more heteroatom (s), E is an integer from 1 to 3 and corresponds to the valency of the cation ; p is the number of cations in the salt corresponding to D is an anion selected from the group consisting of CH 3 COO ", Br, CO3 2 -, Cr, C 3 H 5 0 (COO) 3 3 -, HCOO-, HCOs", HS0 4 " , C2O4 2 -, S0 4 2" and S0 3 2 " ; F is an integer from 1 to 3 and corresponds to the valency of the anion; q corresponds to the number of anions in the salt; where the net charge of the salt is 0, ie, ((E) p) - ((F) q) = 0.
Bevorzugte Reste R werden ausgewählt aus Methyl, iso-Propyl, sec-Butyl, iso-Butyl, -C6H5, -CH2- CeHs, und -CH2-CH2-C6H5, so dass der Teil -NH-CH(R)-C(0)-X der Verbindung der Formel (I) von den Aminosäuren Ala, Val, lle, Leu, PGIy (Phenylglycin), Phe und HPhe (Homophenylalanine) abgeleitet ist, indem die Carboxylgruppe in eine Aldehyd- oder Trifluoromethylketongruppe umgewandelt wird. Obwohl solche Reste daher keine Aminosäuren sind (obwohl sie aus einem Aminosäurevorläufer synthetisiert sein können), wird hierin bei den beispielhaft aufgelisteten Enzymstabilisatoren der Einfachheit halber der Aldehydteil der Inhibitoren, der von der entsprechenden Aminosäuren abgeleitet ist, durch den Zusatz "H" nach der analogen Aminosäure bezeichnet (z.B., steht "-AlaH" für den Rest "-NHCH(CH3)C(0)H"). Trifluoromethylketone werden in gleicher Weise durch den Zusatz "CF3" nach der analogen Aminosäure gekennzeichnet (z.B., steht "-AlaCF3M für den Rest "-NHCH(CH3)C(0)CF3").
Diese und weitere Aspekte, Merkmale und Vorteile der Erfindung werden für den Fachmann aus dem Studium der folgenden detaillierten Beschreibung und Ansprüche ersichtlich. Dabei kann jedes Merkmal aus einem Aspekt der Erfindung in jedem anderen Aspekt der Erfindung eingesetzt werden. Ferner ist es selbstverständlich, dass die hierin enthaltenen Beispiele die Erfindung beschreiben und veranschaulichen sollen, diese aber nicht einschränken und insbesondere die Erfindung nicht auf diese Beispiele beschränkt ist. Alle Prozentangaben sind, sofern nicht anders angegeben, Gewichts-%. Numerische Bereiche, die in dem Format„von x bis y" angegeben sind, schließen die genannten Werte ein. Wenn mehrere bevorzugte numerische Bereiche in diesem Format angegeben sind, ist es selbstverständlich, dass alle Bereiche, die durch die Kombination der verschiedenen Endpunkte entstehen, ebenfalls erfasst werden. Preferred radicals R are selected from methyl, isopropyl, sec-butyl, isobutyl, -C6H5, -CH2-CeHs, and -CH2-CH2-C6H5, so that the part -NH-CH (R) -C ( 0) -X of the compound of formula (I) is derived from the amino acids Ala, Val, Ile, Leu, PGIy (phenylglycine), Phe and HPhe (homophenylalanine) by converting the carboxyl group to an aldehyde or trifluoromethyl ketone group. Therefore, although such residues are not amino acids (although they may be synthesized from an amino acid precursor), in the case of the exemplified enzyme stabilizers, for convenience, the aldehyde portion of the inhibitors derived from the corresponding amino acids will be identified by the suffix "H" after the analogous Denotes amino acid (eg, "-AlaH" represents the radical "-NHCH (CH 3 ) C (O) H"). Trifluoromethylketone are likewise characterized by the additive "CF3" after the analogous amino acid (eg, standing "-AlaCF3 M for the rest" is -NHCH (CH 3) C (0) CF 3 "). These and other aspects, features, and advantages of the invention will become apparent to those skilled in the art from a study of the following detailed description and claims. Any feature of one aspect of the invention may be employed in any other aspect of the invention. Further, it is to be understood that the examples contained herein are intended to describe and illustrate the invention, but not to limit it, and in particular that the invention is not limited to these examples. All percentages are by weight unless otherwise specified. Numeric ranges specified in the format "from x to y" include the above values.If multiple preferred numeric ranges are specified in this format, it is understood that all ranges resulting from the combination of the various endpoints, also be recorded.
Die Aldehyde der vorliegenden Erfindung können aus den entsprechenden Aminosäuren hergestellt werden, wobei die C-terminale Carboxylgruppe der Aminosäure in eine Aldehydgruppe umgewandelt wird. Derartige Aldehyde können mittels bekannter Verfahren hergestellt werden, wie z.B. in U.S. Pat. Nr. 5015627, EP 0 185 930, EP 0 583 534 und DE 3200812 beschrieben. The aldehydes of the present invention can be prepared from the corresponding amino acids by converting the C-terminal carboxyl group of the amino acid into an aldehyde group. Such aldehydes may be prepared by known methods, e.g. in U.S. Pat. Pat. No. 5015627, EP 0 185 930, EP 0 583 534 and DE 3200812.
Die Trifluoromethylketone können ebenfalls aus den korrespondierenden Aminosäuren hergestellt werden, indem die C-terminale Carboxylgruppe in eine Trifluoromethylketongruppe umgewandelt wird. Solche Trifluoromethylketone können mittels bekannter Verfahren, wie beispielsweise in der EP 0 583 535 beschrieben, hergestellt werden. The trifluoromethyl ketones can also be prepared from the corresponding amino acids by converting the C-terminal carboxyl group into a trifluoromethyl ketone group. Such trifluoromethyl ketones can be prepared by known methods, for example as described in EP 0 583 535.
In bevorzugten Ausführungsformen ist der Substituent A ausgewählt aus Ala, Gly, Val, lle, Leu, Phe und Lys. In preferred embodiments, the substituent A is selected from Ala, Gly, Val, Ile, Leu, Phe and Lys.
Das N-terminale Ende der Enzymstabilisatoren gemäß Formel (I), und optional das der Enzymstabilisatoren gemäß Formel (II), wird durch eine Schutzgruppe, die den N-Terminus verkappt geschützt, wobei die Gruppe ausgewählt wird aus Carbamaten, Harnstoffen, Sulfonamiden, Phos- phonamiden, Thioharnstoffen, Sulfenamiden, Sulfonsäuren, Phosphinamiden, Thiocarbamaten, Amidophosphaten und Phosphonamiden. In einer bevorzugten Ausführungsform wird das N- terminale Ende jedoch durch eine Methyl-, Ethyl- oder Benzylcarbamatgruppe [CH30-(0)C-; The N-terminal end of the enzyme stabilizers of formula (I), and optionally that of the enzyme stabilizers of formula (II) is protected by a protecting group capping the N-terminus, the group being selected from carbamates, ureas, sulfonamides, Phos - phonamides, thioureas, sulfenamides, sulfonic acids, phosphinamides, thiocarbamates, amidophosphates and phosphonamides. In a preferred embodiment, however, the N-terminal end is replaced by a methyl, ethyl or benzyl carbamate group [CH30- (O) C-;
CH3CH20-(0)C-; oder C6H5CH20-(0)C-], eine Methyl-, Ethyl- oder Benzylharnstoffgruppe [CH3NH- (O)C-; CH3CH2NH-(0)C-; oder CeH5CH2NH-(0)C-], eine Methyl-, Ethyl- oder Benzylsulfonamid- gruppe [CH3S02-; CH3CH2S02-; oder CeHsChhSOH, oder eine Methyl-, Ethyl oder Benzylamido- phosphatgruppe [CH30(OH)(0)P-; CH3CH20(OH)(0)P-; oder C6H5CH20(OH)(0)P-] geschützt. CH 3 CH 2 O- (0) C-; or C 6 H 5 CH 2 O- (O) C-], a methyl, ethyl or benzyl urea group [CH 3 NH- (O) C-; CH 3 CH 2 NH- (O) C-; or CeH 5 CH 2 NH- (O) C-], a methyl, ethyl or Benzylsulfonamid- group [CH 3 S0 2 -; CH 3 CH 2 S0 2 -; or CeHsChhSOH, or a methyl, ethyl or benzylamido phosphate group [CH 3 O (OH) (O) P-; CH 3 CH 2 0 (OH) (0) P-; or C 6 H 5 CH 2 O (OH) (O) P-].
Die Synthese der N-Verkappungsgruppen kann beispielsweise den folgenden Dokumenten entnommen werden: Protective Groups in Organic Chemistry, Greene, T., Wuts, P., John Wiley & Sons, New York, 1991 , pp 309-405; March, J, Advanced Organic Chemistry, Wiley Interscience,
1985, pp. 445, 469, Carey, F. Sundberg, R., Advanced Organic Chemistry, Part B, Plenum Press, New York, 1990, pp. 686-89; Atherton, E., Sheppard, R., Solid Phase Peptide Synthesis, Pierce Chemical, 1989, pp. 3-4; Grant, G., Synthetic Peptides, W. H. Freeman & Co. 1992, pp. 77-103; Stewart, J., Young, J., Solid Phase Peptide Synthesis, 2nd Edition, IRL Press, 1984, pp. 3,5, 1 1 , 14- 18, 28-29. Bodansky, M., Principles of Peptide Synthesis, Springer-Verlag, 1988, pp. 62, 203, 59- 69; Bodansky, M., Peptide Chemistry, Springer- Verlag, 1988, pp. 74-81 , Bodansky, M., Bo- dansky,A., The Practice of Peptide Synthesis, Springer-Verlag, 1984, pp. 9-32. For example, the synthesis of the N-capping groups can be found in the following documents: Protective Groups in Organic Chemistry, Greene, T., Wuts, P., John Wiley & Sons, New York, 1991, pp 309-405; March, J, Advanced Organic Chemistry, Wiley Interscience, 1985, pp. 445, 469, Carey, F. Sundberg, R., Advanced Organic Chemistry, Part B, Plenum Press, New York, 1990, p. 686-89; Atherton, E., Sheppard, R., Solid Phase Peptide Synthesis, Pierce Chemical, 1989, pp. 3-4; Grant, G., Synthetic Peptides, WH Freeman & Co. 1992, pp. 77-103; Stewart, J., Young, J., Solid Phase Peptide Synthesis, 2nd Edition, IRL Press, 1984, pp. 3.5, 11, 14-18, 28-29. Bodansky, M., Principles of Peptide Synthesis, Springer-Verlag, 1988, pp. 62, 203, 59-69; Bodansky, M., Peptide Chemistry, Springer-Verlag, 1988, pp. 74-81, Bodansky, M., Bodansky, A., The Practice of Peptide Synthesis, Springer-Verlag, 1984, pp. 44-8. 9-32.
Die erfindungsgemäßen Mittel umfassen Salze der Formel (III). Diese Salze sind in den hierin beschriebenen Mittel einer Konzentration von 50-2000 mM, bevorzugt in einer Konzentration von 70- 1500 mM, weiter bevorzugt in einer Konzentration von 100-1000 mM, noch weiter bevorzugt in einer Konzentration von 150-500 mM und ferner bevorzugt in einer Konzentration von 200 mM enthalten. In weiteren Ausführungsformen der Erfindung ist das Salz nach Strukturformel (III) Na2S04. The agents according to the invention include salts of the formula (III). These salts are in the agents described herein in a concentration of 50-2000 mM, preferably in a concentration of 70-1500 mM, more preferably in a concentration of 100-1000 mM, even more preferably in a concentration of 150-500 mM and further preferably in a concentration of 200 mM. In further embodiments of the invention, the salt according to structural formula (III) is Na 2 S0 4 .
Der Begriff„Alkyl", wie hierin verwendet, bezieht sich auf eine aliphatische Kohlenwasserstoffgruppe, die gerade oder verzweigt sein kann und 1 bis 20 Kohlenstoffatome in der Kette umfasst. Der Begriff„Aryl", wie hierin verwendet, bezieht sich auf ein aromatisches monocyclisches oder multi- cyclisches Ringsystem, das 6 bis 14 Kohlenstoffatome umfasst. Der Begriff„Alke nyl", wie hierin verwendet, bezieht sich auf eine aliphatische Kohlenwasserstoffgruppe, die wenigstens eine Kohlenstoff-Kohlenstoff-Doppelbindung enthält und die gerade oder verzweigt sein kann und 2 bis 15 Kohlenstoffatome in der Kette umfasst. The term "alkyl" as used herein refers to an aliphatic hydrocarbon group which may be straight or branched and comprises 1 to 20 carbon atoms in the chain The term "aryl" as used herein refers to an aromatic monocyclic or aromatic multicyclic ring system comprising 6 to 14 carbon atoms. The term "alkenyl" as used herein refers to an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and which may be straight or branched and comprises from 2 to 15 carbon atoms in the chain.
Die erfindungsgemäßen Mittel können alternativ oder zusätzlich zum Enzymstabilisator der Formel (I) einen Enzymstabilisator der Formel Y-B1-B0-X (II) enthalten, wobei X Wasserstoff ist; B1 ein einzelner D- oder L-Aminosäurerest ist; Bo ein Aminosäurerest ist und Y aus einem oder mehreren, bevorzugt ein oder zwei, Aminosäureresten und optional aus einem N-Verkappungsrest besteht, wobei der N-Verkappungsrest wie oben definiert ist. The agents according to the invention may contain, alternatively or in addition to the enzyme stabilizer of the formula (I), an enzyme stabilizer of the formula Y-B1-B0-X (II), where X is hydrogen; B1 is a single D or L amino acid residue; Bo is an amino acid residue and Y consists of one or more, preferably one or two, amino acid residues and optionally an N-capping residue, wherein the N-capping residue is as defined above.
In bevorzugten Ausführungsformen ist Bo ein D- oder L-Aminosäurerest, ausgewählt aus Tyr, m- Tyrosin, 3,4-Dihydroxyphenylalanin, Phe, Val, Met, Nva, Leu, lle und Nie, und/oder B1 ist ein D- oder L-Aminosäurerest mit einer (optional substituierten) kleinen aliphatischen Seitengruppe, bevorzugt Ala, Cys, Gly, Pro, Ser, Thr, Val, Nva oder Nie. In weiteren bevorzugten Ausführungsformen ist Y B2, B3-B2, Z-B2, Z-B3-B2 ist, wobei B2 und B3 jeweils unabhängig voneinander ein Aminosäurerest sind und Z ein N-Verkappungsrest ist, wobei der N-Verkappungsrest wie oben definiert ist. In weiter bevorzugten Ausführungsformen ist B2 ausgewählt aus Val, Gly, Ala, Arg, Leu, Phe und Thr, und/oder ist B3 ausgewählt aus Phe, Tyr, Trp, Phenylglycin, Leu, Val, Nva, Nie und lle.
Sofern nicht anders angegeben, sind die Aminosäuren in den oben genannten Formeln über Pep- tidbindungen verknüpft und alle Peptide oder peptid-ähnlichen Verbindungen sind, sofern nicht anders angegeben, immer vom N- zum C-Terminus dargestellt. In preferred embodiments, Bo is a D or L amino acid residue selected from Tyr, m-tyrosine, 3,4-dihydroxyphenylalanine, Phe, Val, Met, Nva, Leu, Ile and Nie, and / or B1 is a D- or L-amino acid residue having an (optionally substituted) small aliphatic side group, preferably Ala, Cys, Gly, Pro, Ser, Thr, Val, Nva or Never. In further preferred embodiments Y is B2, B3-B2, Z-B2, Z-B3-B2, wherein B2 and B3 are each independently an amino acid residue and Z is an N-capping residue, wherein the N-capping residue is as defined above , In further preferred embodiments, B2 is selected from Val, Gly, Ala, Arg, Leu, Phe and Thr, and / or B3 is selected from Phe, Tyr, Trp, phenylglycine, Leu, Val, Nva, Never and all. Unless stated otherwise, the amino acids in the abovementioned formulas are linked via peptide bonds and all peptides or peptide-like compounds are always shown from the N to the C terminus, unless stated otherwise.
Die erfindungsgemäßen Mittel können den mindestens einen Enzymstabilisator nach Strukturformel (I) und/oder (II) in einer Konzentration von 0,01-50 mM, bevorzugt in einer Konzentration von 0,05-5 mM, weiter bevorzugt in einer Konzentration von 0,1-0,5 mM enthalten. Falls mehrere Enzymstabilisatoren der Formeln (I) und/oder (II) enthalten sind, beziehen sich diese Angaben auf die Gesamtkonzentration. The agents according to the invention may contain the at least one enzyme stabilizer according to structural formula (I) and / or (II) in a concentration of 0.01-50 mM, preferably in a concentration of 0.05-5 mM, more preferably in a concentration of 0, 1-0.5 mM included. If several enzyme stabilizers of formulas (I) and / or (II) are included, this information refers to the total concentration.
Beispielhafte Enzymstabilisatoren der Formeln (I) und (II), die erfindungsgemäß eingesetzt werden können, umfassen, sind aber nicht beschränkt auf Cbz-Arg-Ala-Tyr-H, Ac-Gly-Ala-Tyr-H, Cbz-Gly- Ala-Tyr-H, Cbz-Gly-Ala-Tyr-H, Cbz-Val-Ala-Tyr-H, Cbz-Gly-Ala-Phe-H, Cbz-Gly-Ala-Val-H, Cbz- Gly-Gly-Tyr-H, Cbz-Gly-Gly-Phe-H, Cbz-Arg-Val-Tyr-H, Cbz-Leu-Val-Tyr-H, Ac-Leu-Gly-Ala-Tyr- H, Ac-Phe-Gly-Ala-Tyr-H, Ac-Tyr-Gly-Ala-Tyr-H, Ac-Phe-Gly-Ala-Leu-H, Ac-Phe-Gly-Ala-Phe- H, Ac-Phe-Gly-Val-Tyr-H, Ac-Phe-Gly-Ala-Met-H, Ac-Trp-Leu-Val-Tyr-H, MeO-CO-Val-Ala-Leu- H, MeNCO-Val-Ala-Leu-H, MeO-CO-Phe-Gly-Ala-Leu-H, MeO-CO-Phe-Gly-Ala-Phe-H, MeS02- Phe-Gly-Ala-Leu-H, MeS02-Val-Ala-Leu-H, PhCH20(OH)(0)P-Val-Ala-Leu-H, EtS02-Phe-Gly-Ala- Leu-H, PhCH2S02-Val-Ala-Leu-H, PhCH20(OH)(0)P-Leu-Ala-Leu-H, PhCH20(OH)(0)P-Phe-Ala- Leu-H, MeO(OH)(0)P-Leu-Gly-Ala-Leu-H, a-MAPI, ß-MAPI, Phe-urea-Arg-Val-Tyr-H, Phe-urea- Gly-Gly-Tyr-H, Phe-urea-Gly-Ala-Phe-H, Phe-urea-Gly-Ala-Tyr-H, Phe-urea-Gly-Ala-Leu-H, Phe- urea-Gly-Ala-Nva-H, Phe-urea-Gly-Ala-Nle-H, Tyr-urea-Arg-Val-Tyr-H, Tyr-urea-Gly-Ala-Tyr-H, Phe-Cys-Ser-Arg-Val-Phe-H, Phe-Cys-Ser-Arg-Val-Tyr-H, Phe-Cys-Ser-Gly-Ala-Tyr-H, Antipain, GE20372A, GE20372B, Chymostatin A, Chymostatin B und Chymostatin C. Exemplary enzyme stabilizers of formulas (I) and (II) which can be used in the present invention include, but are not limited to, Cbz-Arg-Ala-Tyr-H, Ac-Gly-Ala-Tyr-H, Cbz-Gly-Ala -Tyr-H, Cbz-Gly-Ala-Tyr-H, Cbz-Val-Ala-Tyr-H, Cbz-Gly-Ala-Phe-H, Cbz-Gly-Ala-Val-H, Cbz-Gly-Gly -Tyr-H, Cbz-Gly-Gly-Phe-H, Cbz-Arg-Val-Tyr-H, Cbz-Leu-Val-Tyr-H, Ac-Leu-Gly-Ala-Tyr-H, Ac-Phe Gly-Ala-Tyr-H, Ac-Tyr-Gly-Ala-Tyr-H, Ac-Phe-Gly-Ala-Leu-H, Ac-Phe-Gly-Ala-Phe-H, Ac-Phe-Gly -Val-Tyr-H, Ac-Phe-Gly-Ala-Met-H, Ac-Trp-Leu-Val-Tyr-H, MeO-CO-Val-Ala-Leu-H, MeNCO-Val-Ala-Leu -H, MeO-CO-Phe-Gly-Ala-Leu-H, MeO-CO-Phe-Gly-Ala-Phe-H, MeSO 2 - Phe-Gly-Ala-Leu-H, MeSO 2 -Val-Ala -Leu-H, PhCH 2 O (OH) (0) P-Val-Ala-Leu-H, EtS0 2 -Phe-Gly-Ala-Leu-H, PhCH 2 S0 2 -Val-Ala-Leu-H, PhCH 2 O (OH) (0) P-Leu-Ala-Leu-H, PhCH 2 O (OH) (0) P-Phe-Ala-Leu-H, MeO (OH) (0) P-Leu-Gly -Ala-Leu-H, α-MAPI, β-MAPI, Phe-urea-Arg-Val-Tyr-H, Phe-urea-Gly-Gly-Tyr-H, Phe-urea-Gly-Ala-Phe-H , Phe-urea-Gly-Ala-Tyr-H, Phe-urea-Gly-Ala Leeu-H, pheurea-Gly-Ala-Nva-H, Phe-urea-Gly-Ala-Nle-H, Tyr-urea-Arg-Val-Tyr-H, Tyr-urea-Gly-Ala-Tyr -H, Phe-Cys-Ser-Arg-Val-Phe-H, Phe-Cys-Ser-Arg-Val-Tyr-H, Phe-Cys-Ser-Gly-Ala-Tyr-H, Antipain, GE20372A, GE20372B , Chymostatin A, Chymostatin B and Chymostatin C.
Wie hierin verwendet, bezieht sich der Ausdruck„Cbz" auf die Benzyloxycarbonyl-Gruppe mit der Summenformel C7H7O. Diese wird als Schutzgruppe verwendet. Weitere terminale Gruppen in den Enzymstabilisatoren der vorliegenden Erfindung können sein:„Ph": Phenyl;„Ac": Acetyl und„Me": Methyl. Der Ausdruck„urea", wie hierin verwendet, ist gleichbedeutend mit Harnstoff. As used herein, the term "Cbz" refers to the benzyloxycarbonyl group having the empirical formula C7H7O which is used as a protecting group Other terminal groups in the enzyme stabilizers of the present invention may be: "Ph": phenyl; "Ac": acetyl and "Me": methyl. The term "urea" as used herein is synonymous with urea.
In verschiedenen Ausführungsformen umfasst die Erfindung auch alle Stereoisomere, insbesondere Enantiomere und Diastereomere, Tautomere und Salze der vorstehend beschriebenen Verbindungen. In various embodiments, the invention also includes all stereoisomers, in particular enantiomers and diastereomers, tautomers and salts of the compounds described above.
Unter einem Wasch- oder Reinigungsmittel sind erfindungsgemäß alle Mittel zu verstehen, die sich zum Waschen oder Reinigen von insbesondere Textilien und/oder festen Oberflächen eignen. Weitere geeignete Inhaltsstoffe werden weiter unten detailliert beschrieben.
Unter einer Protease sind erfindungsgemäß alle Enzyme zu verstehen, die in der Lage sind, Säu- reamidverknüpfungen von Proteinen zu hydrolysieren. Auch die Proteasen werden weiter unten detailliert beschrieben. Under a detergent or cleaning agent according to the invention are all means that are suitable for washing or cleaning of particular textiles and / or solid surfaces. Other suitable ingredients are described in detail below. According to the invention, a protease is to be understood as meaning all enzymes which are capable of hydrolyzing acid amide linkages of proteins. The proteases are also described in detail below.
Ohne an eine Theorie gebunden sein zu wollen, wird erfindungsgemäß davon ausgegangen, dass die Zugabe eines Salzes der Formel (III) den Enzym-Peptidstabilisator-Komplex durch das Entfernen von freien reaktiven Wassermolekülen stabilisiert. Dies erhöht die Bindungseffizienz des Pep- tidstabilisators an das Enzym und/oder erhöht die lonenstärke, wodurch letztendlich der Enzym- Peptidstabilisator-Komplex stabilisiert wird. Without wishing to be bound by theory, it is believed that the addition of a salt of formula (III) stabilizes the enzyme-peptide stabilizer complex by removing free reactive water molecules. This increases the binding efficiency of the peptide stabilizer to the enzyme and / or increases the ionic strength, ultimately stabilizing the enzyme-peptide stabilizer complex.
Der erste Vorteil der erfindungsrelevanten Verbindungen gegenüber dem Stand der Technik besteht darin, dass die oben genannten Vorteile von Peptidstabilisatoren genutzt werden können (z.B. Vermeiden des Bildens von unerwünschten Nebenprodukten im erfindungsgemäßen Mittel durch die unerwünschte Reaktionen des Stabilisators mit anderen Inhaltsstoffen des Mittels). Durch die Verwendung mindestens eines Salzes der Formel (III) ist es überraschenderweise möglich, die Peptidstabilisatoren in moderaten Konzentrationen (0,01-50 mM) einzusetzen, ohne dass das Mittel im Vergleich zum Standardstabilisator (Borsäure) eine signifikant verringerte Protease- stabilisator-Leistung aufweist. Die Protease und ggf. weitere enthaltene Proteine, insbesondere weitere Enzyme werden auf diese Weise gegenüber einer Proteolyse durch dieses Enzym geschützt (gegen Proteolyse stabilisiert) und sind so auch nach einer Lagerung uneingeschränkt leistungsfähig. The first advantage of the prior art compounds over the prior art is that the above-mentioned advantages of peptide stabilizers can be utilized (e.g., avoiding the formation of undesirable by-products in the composition of the invention by the unwanted reactions of the stabilizer with other ingredients of the composition). By using at least one salt of the formula (III), it is surprisingly possible to use the peptide stabilizers in moderate concentrations (0.01-50 mM) without the agent having a significantly reduced protease stabilizer performance in comparison to the standard stabilizer (boric acid) having. The protease and optionally other proteins contained, in particular other enzymes are protected in this way against proteolysis by this enzyme (stabilized against proteolysis) and are thus fully efficient even after storage.
Ferner verfügen die erfindungsrelevanten Verbindungen über eine gute Wasserlöslichkeit, so dass sie in entsprechende Mittel einfach eingearbeitet werden können und ein Ausfallen während der Lagerung vermieden wird. Furthermore, the compounds relevant to the invention have good solubility in water, so that they can easily be incorporated into corresponding agents and precipitation during storage is avoided.
Die genannten Enzym-Inhibitoren (Stabilisatoren) wirken vermutlich deshalb als reversible Inhibitoren, weil sie ähnlich dem Substrat der Proteasen, strukturell an die Bedingungen der Bindungstasche angepasst sind. Dies gilt insbesondere für Serin-Proteasen, wie anhand der Beispiele zur vorliegenden Anmeldung mit der positiven Wirkung der dort experimentell beschriebenen Verbindungen anhand von Serin-Proteasen, konkret Subtilasen, noch spezieller Subtilisinen gezeigt worden ist. The said enzyme inhibitors (stabilizers) presumably act as reversible inhibitors because they are structurally adapted to the conditions of the binding pocket, similar to the substrate of the proteases. This applies in particular to serine proteases, as has been shown on the basis of the examples of the present application with the positive effect of the compounds experimentally described there on the basis of serine proteases, specifically subtilases, even more specific subtilisins.
Weitere Gegenstände der vorliegenden Erfindung betreffen: Further objects of the present invention relate to:
- Wasch- oder Reinigungsverfahren, in dem eine Protease zur Wirkung kommt, die mit den oben beschriebenen Verbindungen (A) der Formel (I) und/oder (II) und (B) der Formel (III) inhibiert und/oder stabilisiert ist; - Washing or cleaning method in which a protease comes into action, which is inhibited and / or stabilized with the above-described compounds (A) of the formula (I) and / or (II) and (B) of the formula (III);
- die Verwendung eines erfindungsgemäßen Wasch- oder Reinigungsmittels zum Waschen und/oder Reinigen von Textilien und/oder harten Oberflächen; sowie
- die Verwendung einer Protease und der oben beschriebenen Verbindungen nach (A) Formel (I) und/oder (II) und (B) Formel (III) zur Herstellung eines Wasch- oder Reinigungsmittels. the use of a washing or cleaning agent according to the invention for washing and / or cleaning textiles and / or hard surfaces; such as the use of a protease and the compounds described above according to (A) formula (I) and / or (II) and (B) formula (III) for the preparation of a washing or cleaning agent.
In erfindungsgemäßen Wasch- oder Reinigungsmitteln, die in einer Ausführungsform in überwiegend fester Form vorliegen und in einer anderen Ausführungsform in überwiegend flüssiger, pastö- ser oder Gelform vorliegen, ist das Enzym, d.h. die Protease, in einer Menge von 0,05-5 Gew.-%, vorzugsweise 0,05-2 Gew.-%, und der Enzymstabilisator in einer Menge von 0,05-15 Gew.-%, vorzugsweise 0,05-5 Gew.-%, bezogen auf das Gesamtgewicht des Wasch- oder Reinigungsmittels in diesem enthalten. In detergents or cleaners according to the invention, which in one embodiment are in predominantly solid form and in another embodiment in predominantly liquid, pasty or gel form, the enzyme, i. the protease in an amount of 0.05-5% by weight, preferably 0.05-2% by weight, and the enzyme stabilizer in an amount of 0.05-15% by weight, preferably 0.05- 5 wt .-%, based on the total weight of the washing or cleaning agent contained in this.
In verschiedenen Ausführungsformen können das Enzym und der Enzymstabilisator in einer Enzymzusammensetzung vorformuliert vorliegen. Wie aus der vorherigen Ausführungen ersichtlich, bildet das Enzym-Protein nur einen Bruchteil des Gesamtgewichts üblicher Enzym-Zubereitungen. Bevorzugt eingesetzte Protease-Zubereitungen enthalten zwischen 0, 1 und 40 Gew.-%, bevorzugt zwischen 0,2 und 30 Gew.-%, besonders bevorzugt zwischen 0,4 und 20 Gew.-% und insbesondere zwischen 0,8 und 10 Gew.-% des Enzymproteins. In solchen Zusammensetzungen kann der Enzymstabilisator in einer Menge von 0,05-35 Gew.-%, vorzugsweise 0,05-10 Gew.-% bezogen auf das Gesamtgewicht in der Enzymzusammensetzung enthalten sein. Diese Enzymzusammensetzung, die ebenfalls ein Bestandteil der vorliegenden Erfindung ist, kann dann in erfindungsgemäßen Wasch- oder Reinigungsmitteln eingesetzt werden und zwar in Mengen, die zu den oben angegeben Endkonzentrationen im Wasch- oder Reinigungsmittel führen. In various embodiments, the enzyme and the enzyme stabilizer may be pre-formulated in an enzyme composition. As can be seen from the previous comments, the enzyme protein forms only a fraction of the total weight of conventional enzyme preparations. Preferably used protease preparations contain between 0, 1 and 40 wt .-%, preferably between 0.2 and 30 wt .-%, particularly preferably between 0.4 and 20 wt .-% and in particular between 0.8 and 10 wt .-% of the enzyme protein. In such compositions, the enzyme stabilizer may be contained in an amount of 0.05-35% by weight, preferably 0.05-10% by weight, based on the total weight in the enzyme composition. This enzyme composition, which is also a constituent of the present invention, can then be used in detergents or cleaners according to the invention in amounts which lead to the above-mentioned final concentrations in the washing or cleaning agent.
Die Proteinkonzentration kann mit Hilfe bekannter Methoden, zum Beispiel dem BCA-Verfahren (Bicinchoninsäure; 2,2'-Bichinolyl-4,4'-dicarbonsäure) oder dem Biuret-Verfahren bestimmt werden. Die Bestimmung der Aktivproteinkonzentration erfolgt diesbezüglich über eine Titration der aktiven Zentren unter Verwendung eines geeigneten irreversiblen Inhibitors (für Proteasen beispielsweise Phenylmethylsulfonylfluorid (PMSF)) und Bestimmung der Restaktivität (vgl. M. Bender et al., J. Am. Chem. Soc. 88, 24 (1966), S. 5890-5913). The protein concentration can be determined by known methods, for example the BCA method (bicinchoninic acid, 2,2'-biquinolyl-4,4'-dicarboxylic acid) or the biuret method. In this regard, the determination of the active protein concentration takes place via a titration of the active sites using a suitable irreversible inhibitor (for proteases, for example phenylmethylsulfonyl fluoride (PMSF)) and determination of the residual activity (compare M. Bender et al., J. Am. Chem. Soc , 24 (1966), pp. 5890-5913).
Neben dem Enzymstabilisator gemäß der oben angegebenen allgemeinen Formel kann ein erfindungsgemäßes Mittel mindestens einen weiteren Stabilisator, insbesondere ein Polyol, wie Glyce- rin oder 1 ,2-Ethylenglycol, und/oder ein Antioxidans, enthalten. In addition to the enzyme stabilizer according to the abovementioned general formula, an agent according to the invention may contain at least one further stabilizer, in particular a polyol, such as glycerol or 1,2-ethylene glycol, and / or an antioxidant.
Die eingesetzten Proteasen sind alkalische Serin-Proteasen. Sie wirken als unspezifische Endop- eptidasen, das heißt, sie hydrolysieren beliebige Säureamidbindungen, die im Inneren von Peptiden oder Proteinen liegen und bewirken dadurch den Abbau proteinhaltiger Anschmutzungen auf dem Reinigungsgut. Ihr pH-Optimum liegt meist im deutlich alkalischen Bereich.
Bei der erfindungsgemäß stabilisierten, bzw. reversibel inhibierten Protease handelt es sich daher vorzugsweise um eine Serin-Protease, insbesondere um eine Subtilase, besonders bevorzugt um ein Subtilisin. Das Subtilisin kann dabei ein Wildtypenzym oder eine Subtilisin-Variante sein, wobei das Wildtypenzym bzw. das Ausgangsenzym der Variante vorzugsweise aus einer der folgenden ausgewählt ist: The proteases used are alkaline serine proteases. They act as nonspecific endopepetases, that is, they hydrolyze any acid amide bonds that are located inside peptides or proteins, thereby causing degradation of proteinaceous soils on the items to be cleaned. Their pH optimum is usually in the clearly alkaline range. The protease stabilized or reversibly inhibited according to the invention is therefore preferably a serine protease, in particular a subtilase, more preferably a subtilisin. The subtilisin may be a wild-type enzyme or a subtilisin variant, wherein the wild-type enzyme or the starting enzyme of the variant is preferably selected from one of the following:
- der Alkalischen Protease aus Bacillus amyloliquefaciens (ΒΡΝ'), the alkaline protease from Bacillus amyloliquefaciens (ΒΡΝ '),
- der Alkalischen Protease aus Bacillus licheniformis (Subtilisin Carlsberg), the alkaline protease from Bacillus licheniformis (subtilisin Carlsberg),
- der Alkalischen Protease PB92, the alkaline protease PB92,
- Subtilisin 147 und/oder 309 (Savinase) Subtilisin 147 and / or 309 (Savinase)
- der Alkalischen Protease aus Bacillus lentus, vorzugsweise aus Bacillus lentus (DSM 5483), the alkaline protease from Bacillus lentus, preferably from Bacillus lentus (DSM 5483),
- der Alkalischen Protease aus Bacillus alcalophilus (DSM 1 1233), the alkaline protease from Bacillus alcalophilus (DSM 1 1233),
- der Alkalischen Protease aus Bacillus gibsonii (DSM 14391 ) oder einer hierzu mindestens zu 70% identischen Alkalischen Protease, the alkaline protease from Bacillus gibsonii (DSM 14391) or an at least 70% identical alkaline protease,
- der Alkalischen Protease aus Bacillus sp. (DSM 14390) oder einer hierzu mindestens zu 98,5% identischen Alkalischen Protease, und the alkaline protease from Bacillus sp. (DSM 14390) or an at least 98.5% identical alkaline protease, and
- der Alkalischen Protease aus Bacillus sp. (DSM 14392) oder einer hierzu mindestens zu 98,1 % identischen Alkalischen Protease. the alkaline protease from Bacillus sp. (DSM 14392) or an at least 98.1% identical alkaline protease.
In verschiedenen Ausführungsformen der Erfindung ist die erfindungsgemäß stabilisierte Protease eine Protease ausgewählt aus der Gruppe aus Proteasen gemäß SEQ ID NO: 1 , SEQ ID NO:2 und SEQ ID NO:3. In alternativen Ausführungsformen werden Kombinationen zweier oder dreier Proteasen gemäß SEQ ID NO: 1 / SEQ ID NO:2; SEQ ID NO: 1 / SEQ ID NO:3; SEQ ID NO:2 / SEQ ID NO:3 oder SEQ ID NO:1 / SEQ ID NO:2 / SEQ ID NO:3 erfindungsgemäß stabilisiert. In various embodiments of the invention, the protease stabilized according to the invention is a protease selected from the group of proteases according to SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3. In alternative embodiments, combinations of two or three proteases according to SEQ ID NO: 1 / SEQ ID NO: 2; SEQ ID NO: 1 / SEQ ID NO: 3; SEQ ID NO: 2 / SEQ ID NO: 3 or SEQ ID NO: 1 / SEQ ID NO: 2 / SEQ ID NO: 3 stabilized according to the invention.
Obwohl im Folgenden immer auf eine Protease Bezug genommen wird, ist es selbstverständlich auch möglich eine Kombination von zwei oder mehr Proteasen einzusetzen. Although reference will always be made hereinafter to a protease, it is of course also possible to use a combination of two or more proteases.
„Variante", wie hierin in Zusammenhang mit Proteasen verwendet, bezieht sich auf natürliche oder artifiziell erzeugte Variationen einer nativen Protease, die eine gegenüber der Referenzform abgewandelte Aminosäuresequenz aufweisen. Eine solche Variante kann einzelne oder mehrere Punktmutationen, d.h. Substitutionen einer natürlicherweise an der entsprechenden Position vorkommenden Aminosäure durch eine andere, Insertionen (Einfügen von einer oder mehreren Aminosäuren) und/oder Deletionen (Entfernen von einer oder mehreren Aminosäuren) aufweisen, insbesondere eine oder mehrere Punktmutationen. Derartige Varianten haben vorzugsweise mindestens 50, vorzugsweise 60 oder mehr, noch bevorzugter 70, 80, 90, 100 % oder mehr der Enzymaktivität der Referenzform. In verschiedenen Ausführungsformen hat eine derartige Variante eine Aminosäuresequenz, die zu der als Referenz dienenden Sequenz über deren Gesamtlänge zu mindestens 70, vorzugsweise 75, 80, 85, 90, 95, 96, 97, 98, oder 99 % identisch ist. Die Varianten haben vorzugsweise dieselbe Länge wie die Referenzsequenz. Varianten können sich gegenüber
der Referenzform durch verbesserte Eigenschaften auszeichnen, wie beispielsweise höhere Enzymaktivität, höhere Stabilität, geänderte Substratspezifität, etc.. "Variant", as used herein in connection with proteases, refers to naturally or artificially produced variations of a native protease that have an amino acid sequence that is modified from the reference form Such variant may be single or multiple point mutations, ie, substitutions of one naturally at the appropriate position one or more insertions (insertion of one or more amino acids) and / or deletions (removal of one or more amino acids), in particular one or more point mutations, Such variants preferably have at least 50, preferably 60 or more, more preferably 70 , 80, 90, 100% or more of the enzyme activity of the reference form In various embodiments, such variant has an amino acid sequence leading to the reference sequence over its total length of at least 70, preferably 75, 80, 85, 90, 95, 96 , 97, 98, or 99% is identical. The variants preferably have the same length as the reference sequence. Variants can be opposite the reference form characterized by improved properties, such as higher enzyme activity, higher stability, altered substrate specificity, etc ..
Die Bestimmung der Identität von Nukleinsäure- oder Aminosäuresequenzen erfolgt durch einen Sequenzvergleich. Dieser Sequenzvergleich basiert auf dem im Stand der Technik etablierten und üblicherweise genutzten BLAST-Algorithmus (vgl. beispielsweise Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, DJ. (1990) "Basic local alignment search tool." J. Mol. Biol. 215:403- 410, und Altschul, Stephan F., Thomas L. Madden, Alejandro A. Schaffer, Jinghui Zhang, Hheng Zhang, Webb Miller, and David J. Lipman (1997): "Gapped BLAST and PSI-BLAST: a new genera- tion of protein database search programs"; Nucleic Acids Res., 25, S.3389-3402) und geschieht prinzipiell dadurch, dass ähnliche Abfolgen von Nukleotiden oder Aminosäuren in den Nukleinsäure- oder Aminosäuresequenzen einander zugeordnet werden. Eine tabellarische Zuordnung der betreffenden Positionen wird als Alignment bezeichnet. Ein weiterer im Stand der Technik verfügbarer Algorithmus ist der FASTA-Algorithmus. The identity of nucleic acid or amino acid sequences is determined by a sequence comparison. This sequence comparison is based on the BLAST algorithm established and commonly used in the prior art (see, for example, Altschul, SF, Gish, W., Miller, W., Myers, EW & Lipman, DJ. (1990) "Basic local alignment search Biol. 215: 403-410; and Altschul, Stephan F., Thomas L. Madden, Alejandro A. Schaffer, Jinghui Zhang, Hheng Zhang, Webb Miller, and David J. Lipman (1997): "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs"; Nucleic Acids Res., 25, pp.3389-3402) and is in principle effected by similar sequences of nucleotides or amino acids in the nucleic acid or nucleic acid sequences Amino acid sequences are assigned to each other. A tabular assignment of the respective positions is referred to as alignment. Another algorithm available in the prior art is the FASTA algorithm.
Solch ein Vergleich erlaubt auch eine Aussage über die Ähnlichkeit der verglichenen Sequenzen zueinander. Sie wird üblicherweise in Prozent Identität, das heißt dem Anteil der identischen Nukleotide oder Aminosäurereste an denselben oder in einem Alignment einander entsprechenden Positionen angegeben. Der weiter gefasste Begriff der Homologie bezieht bei Aminosäuresequenzen konservierte Aminosäure-Austausche in die Betrachtung mit ein, also Aminosäuren mit ähnlicher chemischer Aktivität, da diese innerhalb des Proteins meist ähnliche chemische Aktivitäten ausüben. Daher kann die Ähnlichkeit der verglichenen Sequenzen auch Prozent Homologie oder Prozent Ähnlichkeit angegeben sein. Identitäts- und/oder Homologieangaben können über ganze Polypeptide oder Gene oder nur über einzelne Bereiche getroffen werden. Homologe oder identische Bereiche von verschiedenen Nukleinsäure- oder Aminosäuresequenzen sind daher durch Übereinstimmungen in den Sequenzen definiert. Solche Bereiche weisen oftmals identische Funktionen auf. Sie können klein sein und nur wenige Nukleotide oder Aminosäuren umfassen. Oftmals üben solche kleinen Bereiche für die Gesamtaktivität des Proteins essentielle Funktionen aus. Es kann daher sinnvoll sein, Sequenzübereinstimmungen nur auf einzelne, gegebenenfalls kleine Bereiche zu beziehen. Soweit nicht anders angegeben beziehen sich Identitäts- oder Homologieangaben in der vorliegenden Anmeldung aber auf die Gesamtlänge der jeweils angegebenen Nukleinsäure- oder Aminosäuresäuresequenz. Such a comparison also allows a statement about the similarity of the compared sequences to each other. It is usually given in percent identity, that is, the proportion of identical nucleotides or amino acid residues at the same or in an alignment corresponding positions. The broader concept of homology involves conserved amino acid substitutions in the consideration of amino acid sequences, that is, amino acids with similar chemical activity, as these usually perform similar chemical activities within the protein. Therefore, the similarity of the sequences compared may also be stated as percent homology or percent similarity. Identity and / or homology information can be made about whole polypeptides or genes or only over individual regions. Homologous or identical regions of different nucleic acid or amino acid sequences are therefore defined by matches in the sequences. Such areas often have identical functions. They can be small and comprise only a few nucleotides or amino acids. Often, such small regions exert essential functions for the overall activity of the protein. It may therefore be useful to relate sequence matches only to individual, possibly small areas. Unless otherwise indicated, identity or homology information in the present application, however, refers to the total length of the particular nucleic acid or amino acid sequence indicated.
„Funktionale Fragmente", wie hierin verwendet, bezieht sich auf enzymatisch aktive Polypeptide, die im Vergleich zu der als Referenz dienenden Sequenz N- und/oder C-terminal um mindestens eine, vorzugsweise zwei oder mehr Aminosäuren verkürzt sind. Die Aktivität solcher Fragmente beträgt mindestens 50 %, vorzugsweise mindestens 60, 70, 80, 90, 95 oder 100 % der Aktivität des Referenzenzyms.
Im Allgemeinen kann die Messung der Enzymaktivität - abgestimmt auf den jeweiligen Enzymtyp - in fachüblicher Art und Weise erfolgen. Methoden zur Aktivitätsbestimmung sind dem Fachmann auf dem Gebiet der Enzymtechnologie geläufig und werden von ihm routinemäßig angewendet. Verfahren zur Bestimmung der Proteaseaktivität sind beispielsweise offenbart in Tenside, Band 7 (1970), S. 125-132. Die proteolytische Aktivität kann ferner bestimmt werden über die Freisetzung des Chromophors para-Nitroanilin (pNA) aus dem Substrat suc-L-Ala-L-Ala-L-Pro-L-Phe-p- Nitro- anilid (suc-AAPF-pNA). Die Protease spaltet das Substrat und setzt pNA frei. Die Freisetzung des pNA verursacht eine Zunahme der Extinktion bei 410 nm, deren zeitlicher Verlauf ein Maß für die enzymatische Aktivität ist (vgl. Del Mar et al., 1979). Die Messung kann bei einer Temperatur von 25°C, bei pH 8,6 und einer Wellenlänge von 410 nm erfolgen. Die Messzeit kann 5 min. betragen bei einem Messintervall von 20s bis 60s. "Functional fragments" as used herein refers to enzymatically active polypeptides which are truncated N- and / or C-terminally by at least one, preferably two or more, amino acids as compared to the reference sequence The activity of such fragments is at least 50%, preferably at least 60, 70, 80, 90, 95 or 100% of the activity of the reference enzyme. In general, the measurement of the enzyme activity - matched to the particular type of enzyme - can be carried out in the customary manner. Methods for determining activity are familiar to the expert in the field of enzyme technology and are routinely used by him. Methods for determining protease activity are disclosed, for example, in Tenside, Vol. 7 (1970), pp. 125-132. The proteolytic activity can also be determined by the release of the chromophore para-nitroaniline (pNA) from the substrate suc-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide (suc-AAPF-pNA ). The protease cleaves the substrate and releases pNA. The release of pNA causes an increase in absorbance at 410 nm, the time course of which is a measure of enzymatic activity (see Del Mar et al., 1979). The measurement can be carried out at a temperature of 25 ° C, at pH 8.6 and a wavelength of 410 nm. The measuring time can be 5 min. amount to a measuring interval of 20s to 60s.
In den hierin beschriebenen Mitteln können die einzusetzenden Enzyme ferner zusammen mit Begleitstoffen, etwa aus der Fermentation, konfektioniert sein. In flüssigen Formulierungen werden die Enzyme bevorzugt als Enzymflüssigformulierung(en) eingesetzt. In the agents described herein, the enzymes to be used may also be formulated together with adjuncts, such as from fermentation. In liquid formulations, the enzymes are preferably used as enzyme liquid formulation (s).
Die Proteasen werden in der Regel nicht in Form des reinen Proteins sondern vielmehr in Form stabilisierter, lager- und transportfähiger Zubereitungen bereitgestellt. Zu diesen vorkonfektionierten Zubereitungen zählen beispielsweise die durch Granulation, Extrusion oder Lyophilisierung erhaltenen festen Präparationen oder, insbesondere bei flüssigen oder gelförmigen Mitteln, Lösungen der Enzyme, vorteilhafterweise möglichst konzentriert, wasserarm und/oder mit Stabilisatoren oder weiteren Hilfsmitteln versetzt. The proteases are generally not provided in the form of the pure protein but rather in the form of stabilized, storage and transportable preparations. Such prefabricated preparations include, for example, the solid preparations obtained by granulation, extrusion or lyophilization or, especially in the case of liquid or gel-form detergents, solutions of the enzymes, advantageously as concentrated as possible, low in water and / or added with stabilizers or further auxiliaries.
Alternativ können die Enzyme sowohl für die feste als auch für die flüssige Darreichungsform verkapselt werden, beispielsweise durch Sprühtrocknung oder Extrusion der Enzymlösung zusammen mit einem vorzugsweise natürlichen Polymer oder in Form von Kapseln, beispielsweise solchen, bei denen die Enzyme wie in einem erstarrten Gel eingeschlossen sind oder in solchen vom Kern- Schale-Typ, bei dem ein enzymhaltiger Kern mit einer Wasser-, Luft- und/oder Chemikalienundurchlässigen Schutzschicht überzogen ist. In aufgelagerten Schichten können zusätzlich weitere Wirkstoffe, beispielsweise Stabilisatoren, Emulgatoren, Pigmente, Bleich- oder Farbstoffe aufgebracht werden. Derartige Kapseln werden nach an sich bekannten Methoden, beispielsweise durch Schüttel- oder Rollgranulation oder in Fluid-bed-Prozessen aufgebracht. Vorteilhafterweise sind derartige Granulate, beispielsweise durch Aufbringen polymerer Filmbildner, staubarm und aufgrund der Beschichtung lagerstabil. Alternatively, the enzymes may be encapsulated for both the solid and liquid dosage forms, for example by spray-drying or extruding the enzyme solution together with a preferably natural polymer or in the form of capsules, for example those in which the enzymes are entrapped as in a solidified gel or in those of the core-shell type in which an enzyme-containing core is coated with a water, air and / or chemical impermeable protective layer. In deposited layers, further active ingredients, for example stabilizers, emulsifiers, pigments, bleaches or dyes, may additionally be applied. Such capsules are applied by methods known per se, for example by shaking or rolling granulation or in fluid-bed processes. Advantageously, such granules, for example by applying polymeric film-forming agent, low in dust and storage stable due to the coating.
Weiterhin ist es möglich, zwei oder mehrere Enzyme zusammen zu konfektionieren, so dass ein einzelnes Granulat mehrere Enzymaktivitäten aufweist.
Erfindungsgemäße Mittel können neben der Protease ein oder mehrere weitere Enzyme enthalten, insbesondere aus folgender Gruppe: Amylasen, Hemicellulasen, Cellulasen, Lipasen und Oxidore- duktasen. Furthermore, it is possible to assemble two or more enzymes together so that a single granule has several enzyme activities. Agents according to the invention may contain, in addition to the protease, one or more further enzymes, in particular from the following group: amylases, hemicellulases, cellulases, lipases and oxidoreductases.
Bei der/den Amylase(n) handelt es sich vorzugsweise um eine a-Amylase. Bei der Hemicellulase handelt es sich vorzugsweise um eine ß- Glucanase, eine Pektinase, eine Pullulanase und/oder eine Mannanase. Bei der Cellulase handelt es sich vorzugsweise um ein Cellulase-Gemisch oder eine Einkomponenten-Cellulase, vorzugsweise bzw. überwiegend um eine Endoglucanase und/oder eine Cellobiohydrolase. Bei der Oxidoreduktase handelt es sich vorzugsweise um eine Oxidase, insbesondere eine Cholin-Oxidase, oder um eine Perhydrolase. The amylase (s) is preferably an α-amylase. The hemicellulase is preferably a β-glucanase, a pectinase, a pullulanase and / or a mannanase. The cellulase is preferably a cellulase mixture or a one-component cellulase, preferably or predominantly an endoglucanase and / or a cellobiohydrolase. The oxidoreductase is preferably an oxidase, in particular a choline oxidase, or a perhydrolase.
Die hierin beschriebenen Mittel umfassen alle denkbaren Wasch- oder Reinigungsmittelarten, sowohl Konzentrate als auch unverdünnt anzuwendende Mittel, zum Einsatz im kommerziellen Maßstab, in der Waschmaschine oder bei der Handwäsche beziehungsweise -reinigung. Dazu gehören beispielsweise Waschmittel für Textilien, Teppiche, oder Naturfasern, für die die Bezeichnung Waschmittel verwendet wird. Dazu gehören beispielsweise auch Geschirrspülmittel für Geschirrspülmaschinen oder manuelle Geschirrspülmittel oder Reiniger für harte Oberflächen wie Metall, Glas, Porzellan, Keramik, Kacheln, Stein, lackierte Oberflächen, Kunststoffe, Holz oder Leder, für die die Bezeichnung Reinigungsmittel verwendet wird, also neben manuellen und maschinellen Geschirrspülmitteln beispielsweise auch Scheuermittel, Glasreiniger, WC-Duftspüler, usw. Zu den Wasch- und Reinigungsmittel im Rahmen der Erfindung zählen ferner Waschhilfsmittel, die bei der manuellen oder maschinellen Textilwäsche zum eigentlichen Waschmittel hinzudosiert werden, um eine weitere Wirkung zu erzielen. Ferner zählen zu Wasch- und Reinigungsmittel im Rahmen der Erfindung auch Textilvor- und Nachbehandlungsmittel, also solche Mittel, mit denen das Wäschestück vor der eigentlichen Wäsche in Kontakt gebracht wird, beispielsweise zum Anlösen hartnäckiger Verschmutzungen, und auch solche Mittel, die in einem der eigentlichen Textilwäsche nachgeschalteten Schritt dem Waschgut weitere wünschenswerte Eigenschaften wie angenehmen Griff, Knitterfreiheit oder geringe statische Aufladung verleihen. Zu letztgenannten Mittel werden u.a. die Weichspüler gerechnet. The compositions described herein include all conceivable types of detergents or cleaners, both concentrates and neat agents, for use on a commercial scale, in the washing machine or in hand washing or cleaning. These include detergents for textiles, carpets, or natural fibers, for which the term detergent is used. These include, for example, dishwashing detergents for dishwashers or manual dishwashing detergents or cleaners for hard surfaces such as metal, glass, porcelain, ceramics, tiles, stone, painted surfaces, plastics, wood or leather, for which the term detergent is used, ie in addition to manual and machine Dishwashing agents, for example, scouring agents, glass cleaners, toilet scenters, etc. The washing and cleaning agents in the invention also include washing aids which are added to the actual detergent in the manual or machine textile laundry to achieve a further effect. Furthermore, laundry detergents and cleaners in the context of the invention also include textile pre-treatment and post-treatment agents, ie those agents with which the laundry item is brought into contact before the actual laundry, for example to dissolve stubborn soiling, and also agents which are in one of the actual Textile laundry downstream step to give the laundry further desirable properties such as comfortable grip, crease resistance or low static charge. Among the latter, i.a. calculated the fabric softener.
Ausführungsformen der vorliegenden Erfindung umfassen alle festen, pulverförmigen, flüssigen, gelförmigen oder pastösen Darreichungsformen hierin beschriebener Mittel, die gegebenenfalls auch aus mehreren Phasen bestehen können sowie in komprimierter oder nicht komprimierter Form vorliegen können. Das Mittel kann als rieselfähiges Pulver vorliegen, insbesondere mit einem Schüttgewicht von 300 g/l bis 1200 g/l, insbesondere 500 g/l bis 900 g/l oder 600 g/l bis 850 g/l. Zu den festen Darreichungsformen des Mittels zählen ferner Extrudate, Granulate, Tabletten oder Pouches. Alternativ kann das Mittel auch flüssig, gelförmig oder pastös sein, beispielsweise in Form eines nicht-wässrigen Flüssigwasch- oder -geschirrspülmittels oder einer nicht-wässrigen Paste oder in Form eines wässrigen Flüssigwasch- oder -geschirrspülmittels oder einer wasserhal-
tigen Paste. Weiterhin kann das Mittel als Einkomponentensystem vorliegen. Solche Mittel bestehen aus einer Phase. Alternativ kann ein Mittel auch aus mehreren Phasen bestehen. Ein solches Mittel ist demnach in mehrere Komponenten aufgeteilt. Embodiments of the present invention include all solid, powdered, liquid, gelatinous or pasty administration forms of agents described herein, which if appropriate can also consist of several phases and can be present in compressed or uncompressed form. The agent can be present as a free-flowing powder, in particular with a bulk density of 300 g / l to 1200 g / l, in particular 500 g / l to 900 g / l or 600 g / l to 850 g / l. The solid dosage forms of the composition also include extrudates, granules, tablets or pouches. Alternatively, the agent can also be liquid, gelatinous or pasty, for example in the form of a nonaqueous liquid washing or dishwashing detergent or a nonaqueous paste or in the form of an aqueous liquid washing or dishwashing detergent or a water-based dishwashing detergent. paste. Furthermore, the agent may be present as a one-component system. Such funds consist of one phase. Alternatively, an agent can also consist of several phases. Such an agent is therefore divided into several components.
Die hierin beschriebenen Wasch- oder Reinigungsmittel, die als pulverförmige Feststoffe, in nachverdichteter Teilchenform, als homogene Lösungen oder Suspensionen vorliegen können, können ferner zusätzlich alle bekannten und in derartigen Mitteln üblichen Inhaltsstoffe enthalten, wobei bevorzugt mindestens ein weiterer Inhaltsstoff in dem Mittel vorhanden ist. Die hierin beschriebenen Mittel können insbesondere Tenside, Builder (Gerüststoffe), Bleichmittel oder Bleichaktivatoren enthalten. Ferner können sie wassermischbare organische Lösungsmittel, Sequestrierungsmittel, Elektrolyte, pH-Regulatoren und/oder weitere Hilfsstoffe wie optische Aufheller, Vergrauungsinhibi- toren, Schaumregulatoren sowie Färb- und Duftstoffe sowie Kombinationen hiervon enthalten. The detergents or cleaners described herein, which may be in the form of powdered solids, in densified particulate form, as homogeneous solutions or suspensions, may further additionally contain all known ingredients customary in such compositions, preferably at least one further ingredient being present in the composition. In particular, the agents described herein may contain surfactants, builders, bleaches or bleach activators. In addition, they may contain water-miscible organic solvents, sequestering agents, electrolytes, pH regulators and / or further auxiliaries, such as optical brighteners, graying inhibitors, foam regulators, as well as dyes and fragrances, and combinations thereof.
Vorteilhafte Inhaltsstoffe hierin beschriebener Mittel sind offenbart in der internationalen Patentanmeldung WO2009/121725, dort beginnend auf Seite 5, vorletzter Absatz, und endend auf Seite 13 nach dem zweiten Absatz. Beispielhafte Formulierungen von Wasch- oder Reinigungsmitteln, die die hierin beschriebene Protease, Enzymstabilisator und Salz enthalten können, sind in den Patentschriften US6165966, Beispiel 1 , 2 und 3; WO20091 18375, Beispiel 1 und WO2013004636, Tabelle 1 und 3 offenbart. Auf diese Offenbarung wird ausdrücklich Bezug genommen und der dortige Offenbarungsgehalt in die vorliegende Patentanmeldung einbezogen. Advantageous ingredients of the compositions described herein are disclosed in International Patent Application WO2009 / 121725, beginning on page 5, penultimate paragraph, and ending on page 13, after the second paragraph. Exemplary formulations of detergents or cleaners which may contain the protease, enzyme stabilizer and salt described herein are described in US6165966, Example 1, 2 and 3; WO20091 18375, Example 1 and WO2013004636, Table 1 and 3 discloses. This disclosure is incorporated herein by reference and the disclosure is incorporated herein by reference.
Ein weiterer Erfindungsgegenstand ist ein Verfahren zur Reinigung von Textilien oder harten Oberflächen, das dadurch gekennzeichnet ist, dass in mindestens einem Verfahrensschritt ein hierin beschriebenes Mittel angewendet wird. A further subject of the invention is a method for the cleaning of textiles or hard surfaces, which is characterized in that in at least one method step a means described herein is used.
Hierunter fallen sowohl manuelle als auch maschinelle Verfahren, wobei maschinelle Verfahren bevorzugt sind. Verfahren zur Reinigung von Textilien zeichnen sich im allgemeinen dadurch aus, dass in mehreren Verfahrensschritten verschiedene reinigungsaktive Substanzen auf das Reinigungsgut aufgebracht und nach der Einwirkzeit abgewaschen werden, oder dass das Reinigungsgut in sonstiger Weise mit einem Waschmittel oder einer Lösung oder Verdünnung dieses Mittels behandelt wird. Entsprechendes gilt für Verfahren zur Reinigung von allen anderen Materialien als Textilien, insbesondere von harten Oberflächen. Alle denkbaren Wasch- oder Reinigungsverfahren können in wenigstens einem der Verfahrensschritte um die Anwendung eines hierin beschriebenen Wasch- oder Reinigungsmittels bereichert werden und stellen dann Ausführungsformen der vorliegenden Erfindung dar. These include both manual and mechanical processes, with mechanical processes being preferred. Methods for cleaning textiles are generally distinguished by the fact that various cleaning-active substances are applied to the items to be cleaned and washed off after the contact time, or that the items to be cleaned are otherwise treated with a detergent or a solution or dilution of this product. The same applies to processes for cleaning all other materials than textiles, especially hard surfaces. All conceivable washing or cleaning methods can be enriched in at least one of the method steps by the use of a washing or cleaning agent described herein and then represent embodiments of the present invention.
Ein weiterer Erfindungsgegenstand ist die Verwendung eines hierin beschriebenen Mittels zur Reinigung oder zum Waschen von Textilien oder zur Reinigung von harten Oberflächen.
Alle Sachverhalte, Gegenstände und Ausführungsformen, die für hierin beschriebene Mittel beschrieben sind, sind auch auf die vorstehend genannten Verfahren und Verwendungen anwendbar. Daher wird an dieser Stelle ausdrücklich auf die Offenbarung an entsprechender Stelle verwiesen mit dem Hinweis, dass diese Offenbarung auch für die vorstehenden beschriebenen Verfahren und Verwendungen gilt.
Another subject of the invention is the use of an agent described herein for cleaning or washing textiles or for cleaning hard surfaces. All aspects, objects, and embodiments described for means described herein are also applicable to the aforementioned methods and uses. Therefore, reference is made at this point expressly to the disclosure in the appropriate place with the statement that this disclosure also applies to the above described methods and uses.
Beispiele Examples
Beispiel 1 : Example 1 :
Verwendeter Peptid-Stabilisator: Used peptide stabilizer:
Als Peptid-Stabilisator/Peptid-Inhibitor (PI) wird das Peptid Methoxycarbonyl-Val-Ala-Leu-Aldehyd verwendet, das von der Firma Bachem (Bubendor, Schweiz) synthetisiert wurde. The peptide-stabilizer / peptide inhibitor (PI) used is the peptide methoxycarbonyl-Val-Ala-leu-aldehyde, which was synthesized by Bachem (Bubendor, Switzerland).
Enzym-Kinetik-Assay mit dem Substrat AAPF: Enzyme-kinetics assay with the substrate AAPF:
Die proteolytische Aktivität wurde über die Freisetzung des Chromophors para-Nitroanilin (pNA) aus dem Substrat suc-L-Ala-L-Ala-L-Pro-L-Phe-p-Nitroanilid (suc-AAPF-pNA) bestimmt. Die Protease spaltet das Substrat und setzt pNA frei. Die Freisetzung des pNA verursacht eine Zunahme der Extinktion bei 410 nm, deren zeitlicher Verlauf ein Maß für die enzymatische Aktivität ist (vgl. Del Mar et al., 1979). Die Messung erfolgt bei einer Temperatur von 25°C, bei pH 8,6 und einer Wellenlänge von 410 nm. Die Messzeit beträgt 5 min. bei einem Messintervall von 20s bis 60s. The proteolytic activity was determined by the release of the chromophore para-nitroaniline (pNA) from the substrate suc-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide (suc-AAPF-pNA). The protease cleaves the substrate and releases pNA. The release of pNA causes an increase in absorbance at 410 nm, the time course of which is a measure of enzymatic activity (see Del Mar et al., 1979). The measurement is carried out at a temperature of 25 ° C, at pH 8.6 and a wavelength of 410 nm. The measuring time is 5 min. at a measuring interval of 20s to 60s.
Ergebnisse zur Protease-Stabilisator-Leistunq: Results on protease stabilizer performance:
Die stabilisierende Wirkung des Peptid-Stabilisators/Peptid-Inhibitors wurde im Vergleich zu der Wirkung von Na-Borat bei verschiedenen Konzentrationen gemessen (durch inkubieren der Formulierung bei 30 ° C für die angegebene Anzahl von Tagen): The stabilizing effect of the peptide stabilizer / peptide inhibitor was measured in comparison to the effect of Na borate at various concentrations (by incubating the formulation at 30 ° C for the indicated number of days):
Inkubationszeit 7 14 28 42 Incubation period 7 14 28 42
(in Tagen) (in days)
% RA % RA % RA % RA % RA% RA% RA% RA
1 % Protease gem. 1% protease acc.
SEQ ID NO:1 mit: SEQ ID NO: 1 with:
1 % Borat 90 90 84 86 1% borate 90 90 84 86
0,1 mM PI 89 84 80 80 0.1 mM PI 89 84 80 80
0,5 mM PI 91 83 78 80 0.5 mM PI 91 83 78 80
1 % Protease gem. 1% protease acc.
SEQ ID NO:2 mit: SEQ ID NO: 2 with:
1 % Borat 95 1% borate 95
0,1 mM PI 91 0.1 mM PI 91
1 % Protease gem. 1% protease acc.
SEQ ID NO:3 mit: SEQ ID NO: 3 with:
1 % Borat 90 1% borate 90
0,1 mM PI 87 0.1 mM PI 87
0,5 mM PI 84
Wie oben zu erkennen ist, ist die Lagerstabilität der Proteasen durch den Wechsel von Borsäure auf den Peptid-Inhibitor (PI) herabgesetzt. 0.5 mM PI 84 As can be seen above, the storage stability of the proteases is reduced by the change of boric acid to the peptide inhibitor (PI).
Um die Wirkung des Modellsalzes (Na2S04) auf den Peptid-Inhibitor (Stabilisator) zu testen, wurden die jeweiligen Proteasen (SEQ ID Nos. 1-3) mit Borat oder mit dem Peptidinhibitor gelagert, wobei die Lagerung mit Peptidinhibitor zusätzlich unter Verwendung des Modellsalzes stattfand. In order to test the effect of the model salt (Na 2 SO 4) on the peptide inhibitor (stabilizer), the respective proteases (SEQ ID Nos. 1-3) were stored with borate or with the peptide inhibitor, wherein storage with peptide inhibitor was additionally carried out using the model salt took place.
Die relative Stabilität des Enzyms in beiden Ansätzen (1. mit Peptidinhibitor; 2. Mit Peptidinhibitor und Salz) wurde in Bezug auf die Stabilität mit Borat berechnet. The relative stability of the enzyme in both approaches (1. with peptide inhibitor, 2. with peptide inhibitor and salt) was calculated in terms of stability with borate.
Wie oben zu erkennen ist, bewirkt die Zugabe von Salz eine erhöhte Stabilität des Enzyms in der Gegenwart des Peptid-Inhibitor auf einen Wert, der sogar über dem beobachteten mit Stabilisierung durch Borat liegt. As can be seen above, the addition of salt causes increased stability of the enzyme in the presence of the peptide inhibitor to a level even greater than that observed with borate stabilization.
Beispiel 2: Example 2:
Beispielhafte Waschmittel-Formulierungen: Exemplary detergent formulations:
Die unten angegebenen Formulierungen können, falls nicht angegeben, mit einer Protease, einem Enzymstabilisator und einem Salz, wie oben beschrieben, ergänzt werden.
(A) Unless indicated, the formulations given below may be supplemented with a protease, an enzyme stabilizer and a salt as described above. (A)
(B) (B)
A B C D E F G H A B C D E F G H
C9-13-Alkylbenzolsulfonat, Na-Salz 9 10 6 7 5 15 15 9 C 9-13 -alkylbenzenesulfonate, Na salt 9 10 6 7 5 15 15 9
C12-18-Fettalkohol mit 7 EO 8 9 6 7 5 6 1 1 10C12-18 fatty alcohol with 7 EO 8 9 6 7 5 6 1 1 10
C12-18-Fettalkoholsulfat mit 2 EO - - 8 7 10 2 2 5C12-18 fatty alcohol sulphate with 2 EO - - 8 7 10 2 2 5
C12-18-Fettsäure, Na-Salz 4 3 3 3 4 2 4 7C12-18 fatty acid, Na salt 4 3 3 3 4 2 4 7
Zitronensäure 2 3 3 2 2 2 2 3Citric acid 2 3 3 2 2 2 2 3
Natriumhydroxid, 50% 3 3 2 3 3 3 3 4Sodium hydroxide, 50% 3 3 2 3 3 3 3 4
Enzyme (Amylase, Protease, Cel- + + + + + + + + lulase) Enzymes (amylase, protease, cel + + + + + + + + lulase)
Parfüm 1 0,5 0,5 1 1 1 1 1 Perfume 1 0.5 0.5 1 1 1 1 1
Propandiol - - - - - 5 5 -Propanediol - - - - - 5 5 -
Ethanol 1 ,5 1 ,5 1 ,5 1 ,5 1 ,5 1 ,5 1 ,5 5Ethanol 1, 5 1, 5 1, 5 1, 5 1, 5 1, 5 1, 5 5
PVA/Maleinsäure-Copolymer 0,1 - 0,1 - - - - -PVA / maleic acid copolymer 0.1 - 0.1 - - - - -
Optischer Aufheller - 0,1 - 0,1 0,2 0,2 0,2 0,2Optical brightener - 0.1 - 0.1 0.2 0.2 0.2 0.2
Trübungsmittel 0,2 - - - - - - -Opacifier 0.2 - - - - - - -
Phosphonsäure, Na-Salz 0,5 0,5 0,5 0,5 0,5 0,5 0,5 0,5Phosphonic acid, Na salt 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
Polymer 2 2 2 2 2 2 2 2Polymer 2 2 2 2 2 2 2 2
Wasser auf 100
Water at 100
Claims
1. Wasch- oder Reinigungsmittel, bevorzugt ein Flüssigwaschmittel, enthaltend 1. Detergent or cleaning agent, preferably containing a liquid detergent
(A) mindestens eine Protease; (A) at least one protease;
(B) mindestens einen Enzymstabilisator, wobei der mindestens eine Enzymstabilisator ausgewählt wird aus Verbindungen (B) at least one enzyme stabilizer, wherein the at least one enzyme stabilizer is selected from compounds
(I) der allgemeinen Strukturformel (I) (I) the general structural formula (I)
Z-A-NH-CH(R)-C(0)-X (I), wobei A ein Aminosäurerest ist; X Wasserstoff ist; Z ein N-Verkappungsrest ausgewählt aus Phosphoramidat [(R'0)2(0)P-], Sulfenamid [(SR')2-], Sulfonamid [(R'(0)2S-], Sulfonsäu- re [SOsH], Phosphinamid [(R')2(0)P-], Sulfamoyl Derivaten [R'0(0)2S-], Thioharnstoff [(R')2N(0)C-], Thiocarbamat [R'0(S)C-], Phosphonat [R'-P(0)OH], Amidophosphat ZA-NH-CH(R)-C(0)-X (I), where A is an amino acid residue; X is hydrogen; Z is an N-capping residue selected from phosphoramidate [(R'0) 2 (0)P-], sulfenamide [(SR') 2 -], sulfonamide [(R'(0) 2 S-], sulfonic acid [SOsH ], phosphinamide [(R')2(0)P-], sulfamoyl derivatives [R'0(0) 2 S-], thiourea [(R') 2 N(0)C-], thiocarbamate [R'0 (S)C-], phosphonate [R'-P(0)OH], amidophosphate
[R'0(OH)(0)P-], Carbamat (R'O(O)C-) und Harnstoff (R'NH(O)C-) ist, wobei jedes R' unabhängig ausgewählt wird aus geradkettigen oder verzweigten C1-C6 unsubstituierten Al- kyl-, Phenyl-, C7-C9 Alkylaryl- und Cycloalkyl-Resten, wobei der Cycloalkylring ein C4-C8 Cycloalkylring sein kann und ein oder mehrere Heteroatome enthalten kann, die ausgewählt werden aus O, N, und S; und R ausgewählt wird aus geradkettigen oder verzweigten C1-C6 unsubstituierten Alkyl-, Phenyl und C7-C9 Alkylarylresten; und Stereoisomeren, Tautomeren und Salzen davon; oder [R'0(OH)(0)P-], carbamate (R'O(O)C-) and urea (R'NH(O)C-), where each R' is independently selected from straight chain or branched C1-C6 unsubstituted alkyl, phenyl, C7-C9 alkylaryl and cycloalkyl radicals, where the cycloalkyl ring may be a C4-C8 cycloalkyl ring and may contain one or more heteroatoms selected from O, N, and S ; and R is selected from straight-chain or branched C1-C6 unsubstituted alkyl, phenyl and C7-C9 alkylaryl radicals; and stereoisomers, tautomers and salts thereof; or
(II) der allgemeinen Strukturformel (II)
wobei X Wasserstoff ist; B1 ein einzelner D- oder L-Aminosäurerest ist; Bo ein Aminosäurerest ist und Y aus einem oder mehreren, bevorzugt ein oder zwei, Aminosäureresten und optional aus einem N-Verkappungsrest besteht, wobei der N-Verkappungsrest wie unter (I) definiert ist; und (II) the general structural formula (II) where X is hydrogen; B1 is a single D or L amino acid residue; Bo is an amino acid residue and Y consists of one or more, preferably one or two, amino acid residues and optionally an N-capping residue, the N-capping residue being as defined under (I); and
(C) mindestens ein Salz der allgemeinen Strukturformel (III) (CE+)P(DF )q (III) entspricht, (C) at least one salt corresponds to the general structural formula (III) (C E+ ) P (D F )q (III),
wobei C ein Kation ausgewählt aus der Gruppe bestehend aus Al3+, Ca2+, Li+, Mg2+, Mn2+, Ni2+, K+, NR'V und Na+ ist, wobei jedes R" unabhängig voneinander für H oder eine lineare oder verzweigte, substituierte oder unsubstituierte Alkyl-, Aryl- oder Alkenylgruppe steht, die alle optional ein oder mehrere Heteroatom(e) enthalten können; E eine ganze Zahl von 1 bis 3 ist und der Valenz des Kations entspricht; p der Anzahl an Kationen im Salz entspricht; D ein Anion ausgewählt aus der Gruppe bestehend aus CH3COO", Br, CO32", Cl", C3H50(COO)33-, HCOO", HCO3-, HSO4-, C204 2_, S04 2_ und S03 2_ ist; F eine ganze Zahl von
1 bis 3 ist und der Valenz des Anions entspricht; q der Anzahl an Anionen im Salz entspricht; wobei die Nettoladung des Salzes 0 ist. where C is a cation selected from the group consisting of Al 3+ , Ca 2+ , Li + , Mg 2+ , Mn 2+ , Ni 2+ , K + , NR'V and Na + , each R" being independent of one another represents H or a linear or branched, substituted or unsubstituted alkyl, aryl or alkenyl group, all of which may optionally contain one or more heteroatoms; E is an integer from 1 to 3 and corresponds to the valence of the cation; p corresponds to the number of cations in the salt; D is an anion selected from the group consisting of CH3COO " , Br, CO3 2" , Cl " , C3H 5 0(COO)3 3 -, HCOO " , HCO3-, HSO4-, C 2 0 4 2_ , S0 4 2_ and S0 3 2_ ; F is an integer of is 1 to 3 and corresponds to the valence of the anion; q corresponds to the number of anions in the salt; where the net charge of the salt is 0.
2. Wasch- oder Reinigungsmittel nach Anspruch 1 , wobei 2. Detergent or cleaning agent according to claim 1, wherein
(A) das Wasch- oder Reinigungsmittel das Salz nach Strukturformel (III) in einer Konzentration von 50-2000 mM, bevorzugt in einer Konzentration von 200 mM, enthält; (A) the washing or cleaning agent contains the salt according to structural formula (III) in a concentration of 50-2000 mM, preferably in a concentration of 200 mM;
(B) das Wasch- oder Reinigungsmittel den Enzymstabilisator nach Strukturformel (I) und/oder (II) in einer Konzentration von 0,01 -50 mM, bevorzugt in einer Konzentration von 0,1-0,5 mM, enthält; und/oder (B) the washing or cleaning agent contains the enzyme stabilizer according to structural formula (I) and/or (II) in a concentration of 0.01-50 mM, preferably in a concentration of 0.1-0.5 mM; and or
(C) das Salz nach Strukturformel (III) Na2S04 ist. (C) the salt according to structural formula (III) is Na 2 S0 4 .
3. Wasch- oder Reinigungsmittel nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass3. Detergent or cleaning agent according to claim 1 or 2, characterized in that
(A) A ausgewählt ist aus Ala, Gly, Val, lle, Leu, Phe und Lys; (A) A is selected from Ala, Gly, Val, lle, Leu, Phe and Lys;
(B) R ausgewählt ist aus Methyl, iso-Propyl, sec-Butyl, iso-Butyl, -CeHs, -CH2-C6H5, und -CH2-CH2-C6H5; und/oder (B) R is selected from methyl, iso-propyl, sec-butyl, iso-butyl, -CeHs, -CH2-C6H5, and -CH2-CH2-C6H5; and or
(C) Z ausgewählt ist aus Methyl-, Ethyl- oder Benzylcarbamatgruppen [CH30-(0)C-; CH3CH20-(0)C-; oder C6H5CH20-(0)C-], Methyl-, Ethyl- oder Benzylharnstoffgruppen [CH3NH-(0)C-; CH3CH2NH-(0)C-; oder CeH5CH2NH-(0)C-], Methyl-, Ethyl- oder Benzylsul- fonamidgruppen [CH3S02-; CH3CH2S02-; oder C6H5CH2SO2-], und eine Methyl-, Ethyl oder Benzylamidophosphatgruppen [CH30(OH)(0)P-; CH3CH20(OH)(0)P-; oder (C) Z is selected from methyl, ethyl or benzyl carbamate groups [CH30-(0)C-; CH 3 CH 2 0-(0)C-; or C6H5CH 2 0-(0)C-], methyl, ethyl or benzylurea groups [CH 3 NH-(0)C-; CH 3 CH 2 NH-(0)C-; or CeH 5 CH 2 NH-(0)C-], methyl, ethyl or benzylsulfonamide groups [CH 3 S0 2 -; CH 3 CH 2 S0 2 -; or C6H5CH2SO2-], and a methyl, ethyl or benzylamidophosphate group [CH 3 0(OH)(0)P-; CH 3 CH 2 0(OH)(0)P-; or
CeH5CH20(OH)(0)P-]. CeH 5 CH 2 0(OH)(0)P-].
4. Wasch- oder Reinigungsmittel nach einem der Ansprüche 1-3, dadurch gekennzeichnet, dass 4. Detergent or cleaning agent according to one of claims 1-3, characterized in that
(A) Bo ein D- oder L-Aminosäurerest ist, ausgewählt aus Tyr, m-Tyrosin, 3,4- Dihydroxyphenylalanin, Phe, Val, Met, Nva, Leu, lle und Nie; (A) Bo is a D- or L-amino acid residue selected from Tyr, m-tyrosine, 3,4-dihydroxyphenylalanine, Phe, Val, Met, Nva, Leu, lle and Nie;
(B) B1 ein Aminosäurerest mit einer (optional substituierten) kleinen aliphatischen Seitengruppe, bevorzugt Ala, Cys, Gly, Pro, Ser, Thr, Val, Nva oder Nie ist. (B) B1 is an amino acid residue with an (optionally substituted) small aliphatic side group, preferably Ala, Cys, Gly, Pro, Ser, Thr, Val, Nva or Nie.
5. Wasch- oder Reinigungsmittel nach einem der Ansprüche 1-4, dadurch gekennzeichnet, dass Y B2, B3-B2, Z-B2, Z-B3-B2 ist, wobei B2 und B3 jeweils unabhängig voneinander ein Aminosäurerest sind und Z ein N-Verkappungsrest ist, wobei der N-Verkappungsrest wie in Anspruch 1 unter (I) definiert ist. 5. Detergent or cleaning agent according to one of claims 1-4, characterized in that YB 2 , B 3 -B 2 , ZB 2 , ZB 3 -B 2 , where B 2 and B 3 are each independently an amino acid residue and Z is an N capping residue, where the N capping residue is as defined in claim 1 under (I).
6. Wasch- oder Reinigungsmittel nach Anspruch 5, dadurch gekennzeichnet, dass 6. Detergent or cleaning agent according to claim 5, characterized in that
(A) B2 ausgewählt ist aus Val, Gly, Ala, Arg, Leu, Phe und Thr, und/oder (A) B 2 is selected from Val, Gly, Ala, Arg, Leu, Phe and Thr, and/or
(B) B3 ausgewählt ist aus Phe, Tyr, Trp, Phe-nylglycin, Leu, Val, Nva, Nie und lie.
(B) B 3 is selected from Phe, Tyr, Trp, Phenylglycine, Leu, Val, Nva, Nie and lie.
7. Wasch- oder Reinigungsmittel nach einem der Ansprüche 1-6, dadurch gekennzeichnet, dass der mindestens eine Enzymstabilisator ausgewählt wird aus Cbz-Arg-Ala-Tyr-H, Ac- Gly-Ala-Tyr-H, Cbz-Gly-Ala-Tyr-H, Cbz-Gly-Ala-Tyr-H, Cbz-Val-Ala-Tyr-H, Cbz-Gly-Ala- Phe-H, Cbz-Gly-Ala-Val-H, Cbz-Gly-Gly-Tyr-H, Cbz-Gly-Gly-Phe-H, Cbz-Arg-Val-Tyr-H, Cbz-Leu-Val-Tyr-H, Ac-Leu-Gly-Ala-Tyr-H, Ac-Phe-Gly-Ala-Tyr-H, Ac-Tyr-Gly-Ala-Tyr- H, Ac-Phe-Gly-Ala-Leu-H, Ac-Phe-Gly-Ala-Phe-H, Ac-Phe-Gly-Val-Tyr-H, Ac-Phe-Gly- Ala-Met-H, Ac-Trp-Leu-Val-Tyr-H, MeO-CO-Val-Ala-Leu-H, MeNCO-Val-Ala-Leu-H, MeO- CO-Phe-Gly-Ala-Leu-H, MeO-CO-Phe-Gly-Ala-Phe-H, MeS02-Phe-Gly-Ala-Leu-H, Me- S02-Val-Ala-Leu-H, PhCH20(OH)(0)P-Val-Ala-Leu-H, EtS02-Phe-Gly-Ala-Leu-H, PhCH2S02-Val-Ala-Leu-H, PhCH20(OH)(0)P-Leu-Ala-Leu-H, PhCH20(OH)(0)P-Phe-Ala- Leu-H, MeO(OH)(0)P-Leu-Gly-Ala-Leu-H, a-MAPI, ß-MAPI, Phe-urea-Arg-Val-Tyr-H, Phe-urea-Gly-Gly-Tyr-H, Phe-urea-Gly-Ala-Phe-H, Phe-urea-Gly-Ala-Tyr-H, Phe-urea-Gly- Ala-Leu-H, Phe-urea-Gly-Ala-Nva-H, Phe-urea-Gly-Ala-Nle-H, Tyr-urea-Arg-Val-Tyr-H, Tyr- urea-Gly-Ala-Tyr-H, Phe-Cys-Ser-Arg-Val-Phe-H, Phe-Cys-Ser-Arg-Val-Tyr-H, Phe-Cys- Ser-Gly-Ala-Tyr-H, Antipain, GE20372A, GE20372B, Chymostatin A, Chymostatin B und Chymostatin C. 7. Detergent or cleaning agent according to one of claims 1-6, characterized in that the at least one enzyme stabilizer is selected from Cbz-Arg-Ala-Tyr-H, Ac-Gly-Ala-Tyr-H, Cbz-Gly-Ala -Tyr-H, Cbz-Gly-Ala-Tyr-H, Cbz-Val-Ala-Tyr-H, Cbz-Gly-Ala-Phe-H, Cbz-Gly-Ala-Val-H, Cbz-Gly-Gly -Tyr-H, Cbz-Gly-Gly-Phe-H, Cbz-Arg-Val-Tyr-H, Cbz-Leu-Val-Tyr-H, Ac-Leu-Gly-Ala-Tyr-H, Ac-Phe -Gly-Ala-Tyr-H, Ac-Tyr-Gly-Ala-Tyr- H, Ac-Phe-Gly-Ala-Leu-H, Ac-Phe-Gly-Ala-Phe-H, Ac-Phe-Gly -Val-Tyr-H, Ac-Phe-Gly-Ala-Met-H, Ac-Trp-Leu-Val-Tyr-H, MeO-CO-Val-Ala-Leu-H, MeNCO-Val-Ala-Leu -H, MeO-CO-Phe-Gly-Ala-Leu-H, MeO-CO-Phe-Gly-Ala-Phe-H, MeS0 2 -Phe-Gly-Ala-Leu-H, Me- S0 2 -Val -Ala-Leu-H, PhCH 2 0(OH)(0)P-Val-Ala-Leu-H, EtS0 2 -Phe-Gly-Ala-Leu-H, PhCH 2 S0 2 -Val-Ala-Leu- H, PhCH 2 0(OH)(0)P-Leu-Ala-Leu-H, PhCH 2 0(OH)(0)P-Phe-Ala-Leu-H, MeO(OH)(0)P-Leu -Gly-Ala-Leu-H, a-MAPI, ß-MAPI, Phe-urea-Arg-Val-Tyr-H, Phe-urea-Gly-Gly-Tyr-H, Phe-urea-Gly-Ala-Phe -H, Phe-urea-Gly-Ala-Tyr-H, Phe-urea-Gly-Ala-Leu-H, Phe-urea-Gly-Ala-Nva-H, Phe-urea-Gly-Ala-Nle-H , Tyr-urea-Arg-Val-Tyr-H, Tyr-urea-Gly-Ala-Tyr-H, Phe-Cys-Ser-Arg-Val-Phe-H, Phe-Cys-Ser-Arg-Val-Tyr -H, Phe-Cys-Ser-Gly-Ala-Tyr-H, antipain, GE20372A, GE20372B, chymostatin A, chymostatin B and chymostatin C.
8. Wasch- oder Reinigungsmittel nach einem der Ansprüche 1-7, dadurch gekennzeichnet, dass die mindestens eine Protease in einer Menge von 0,05-5 Gew.-%, vorzugsweise 0,05-2 Gew.-%, und der mindestens eine Enzymstabilisator in einer Menge von 0,05-15 Gew.-%, vorzugsweise zu 0,05-5 Gew.-%, bezogen auf das Gesamtgewicht des Waschoder Reinigungsmittels in diesem enthalten sind. 8. Detergent or cleaning agent according to one of claims 1-7, characterized in that the at least one protease in an amount of 0.05-5% by weight, preferably 0.05-2% by weight, and the at least an enzyme stabilizer is contained in an amount of 0.05-15% by weight, preferably 0.05-5% by weight, based on the total weight of the washing or cleaning agent.
9. Verwendung eines Wasch- oder Reinigungsmittels nach einem der Ansprüche 1-8 zum Waschen von Textilien oder Reinigen von festen Oberflächen. 9. Use of a detergent or cleaning agent according to one of claims 1-8 for washing textiles or cleaning solid surfaces.
10. Verfahren zur Reinigung von Textilien oder harten Oberflächen, dadurch gekennzeichnet, dass in mindestens einem Verfahrensschritt ein Wasch- oder Reinigungsmittel nach einem der Ansprüche 1-8 angewendet wird. 10. A process for cleaning textiles or hard surfaces, characterized in that a detergent or cleaning agent according to one of claims 1-8 is used in at least one process step.
1 1. Verwendung eines Salzes zur Erhöhung der Wirkung eines Peptidstabilisators in einem Protease-haltigen Wasch- oder Reinigungsmittel, wobei das Salz der allgemeinen Strukturformel (III) 1 1. Use of a salt to increase the effect of a peptide stabilizer in a protease-containing detergent or cleaning agent, the salt having the general structural formula (III)
(CE+)P(DF )q (III) entspricht, (C E+ ) P (D F )q (III) corresponds,
wobei C ein Kation ausgewählt aus der Gruppe bestehend aus Al3+, Ca2+, Li+, Mg2+, Mn2+, Ni2+, K+, NRV und Na+ ist, wobei jedes R" unabhängig voneinander für H oder eine lineare oder verzweigte, substituierte oder unsubstituierte Alkyl-, Aryl- oder Alkenylgruppe steht, die alle optional ein oder mehrere Heteroatom(e) enthalten können; E eine ganze Zahl von 1 bis 3 ist und der Valenz des Kations entspricht; p der Anzahl an Kationen im Salz ent-
spricht; D ein Anion ausgewählt aus der Gruppe bestehend aus CH3COO", Br, CO32", Cl", C3H50(COO)33-, HCOO-, HCO3-, HSC ", C2O42-, S04 2_ und S03 2_ ist; F eine ganze Zahl von 1 bis 3 ist und der Valenz des Anions entspricht; q der Anzahl an Anionen im Salz entspricht; wobei die Nettoladung des Salzes 0 ist.
where C is a cation selected from the group consisting of Al 3+ , Ca 2+ , Li + , Mg 2+ , Mn 2+ , Ni 2+ , K + , NRV and Na + , where each R" independently represents H or a linear or branched, substituted or unsubstituted alkyl, aryl or alkenyl group, all of which may optionally contain one or more heteroatoms; E is an integer from 1 to 3 and corresponds to the valence of the cation; p the number of cations in the salt speaks; D an anion selected from the group consisting of CH3COO " , Br, CO3 2" , Cl " , C3H 5 0(COO)3 3 -, HCOO-, HCO3-, HSC " , C2O4 2 -, S0 4 2_ and S0 3 2_ is; F is an integer from 1 to 3 and corresponds to the valence of the anion; q corresponds to the number of anions in the salt; where the net charge of the salt is 0.
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EP3770237A1 (en) * | 2019-07-22 | 2021-01-27 | Henkel AG & Co. KGaA | Washing and cleaning agents with improved enzyme stability |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2021013684A1 (en) * | 2019-07-22 | 2021-01-28 | Henkel Ag & Co. Kgaa | Detergents and cleaning agents having improved enzyme stability |
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