CN1238002A - Liquid detergents containing proteolytic enzyme, peptide aldehyde and source of boric acid - Google Patents

Abstract

Aqueous liquid detergent compositions are described which comprise a proteolytic enzyme wherein the proteolytic activity is reversibly inhibited by a peptide aldehyde and a source of boric acid. In a particularly preferred embodiment, liquid detergent compositions are disclosed which contain a detersive surfactant, a proteolytic enzyme, a peptide aldehyde, boric acid, and diol ions. The combination of peptide aldehyde and boric acid act to provide improved stability of protease and other enzymes.

Description

The liquid washing agent that contains proteolytic ferment, peptide aldehyde and source of boric acid

Technical field

The present invention relates to contain the liquid detergent composition of enzyme.More particularly, the present invention relates to contain the liquid detergent composition of detergent surfactant, proteolytic ferment, peptide aldehyde and boric acid.The effect of the effect that promotes proteinase inhibitor is played in the combination of peptide aldehyde and boric acid.

Background of the present invention

The liquid hydration washing composition that contains proteolytic enzyme is known, especially in laundry and nursing field.Containing the problem that often runs in the liquid hydration washing composition of proteolytic enzyme in this class is to cause second kind of enzyme in the composition by proteolytic ferment, as the signs of degradation of lipase, amylase and cellulase or proteolytic enzyme itself.As a result, influence this stability in detergent composition of second kind of enzyme or proteolytic enzyme, and therefore make the detergent composition deleterious.

Problem has advised adopting various proteinase inhibitor or stablizer hereto.For example, the compound below many document suggestions are adopted promotes the stability of enzyme: the mixture of benzamidine hydrochloride, lower aliphatic alcohols or carboxylic acid, polyvalent alcohol and boron compound, fragrant boric acid ester and calcium, particularly calcium formiate.In recent years, find that some peptide aldehyde has the effect of stabilize proteins enzyme.

Obtained different successes although these compounds are used for liquid washing agent, they still have problems.For example, peptide aldehyde is quite expensive, and too complicated concerning formulator, in particular for liquid washing agent.Other inhibitor, for example calcium ion and boric acid are less expensive, but can not stabilized enzyme and peptide aldehyde.Therefore the purpose of this invention is to provide a kind of economy, effectively and be applicable to the proteinase inhibitor system of liquid detergent composition.

In order to reach this purpose, the present invention's suggestion adopts the composition of boric acid or its source and peptide aldehyde as reversible protease inhibitors in liquid detergent composition.Exist in the time of boric acid and peptide aldehyde proteolytic enzyme is had economical, improved stabilization.This new combination makes formulator increase handiness when the design stability system.The concentration that can adjust peptide aldehyde and boric acid produces rational and effective prescription, and reduces the problem of the product stability that is caused by the divalent ion that exists in liquid detergent substrate.

Particularly the present invention allows to adopt very small amount of peptide aldehyde in liquid detergent composition of the present invention.This is the key of the said less expensive concentrated liquid detergent composition of preparation the present invention.

Because the combination of boric acid and peptide aldehyde is the arrestin enzyme effectively, another advantage of the present invention is even also can joins in the liquid detergent composition that contains proteolytic enzyme now the highstrung enzyme of proteolytic degradation.

Background technology

Various proteinase inhibitor or stablizer have been advised using.For example the benzamidine hydrochloride is used in the US4566985 suggestion; Lower aliphatic alcohols or carboxylic acid are used in the EP376705 suggestion; The mixture of polyvalent alcohol and boron compound is used in the EP381262 suggestion; Fragrant boric acid ester is used in suggestion with EP91870072.5.Also can be referring to US5030378, on July 9th, 1991.Also can be referring to US4261868, US4404115, US4318818 and EP130756.

Use peptide derivant to come the arrestin enzyme to be disclosed in the treatment application.EP293881 discloses and has used the inhibitor of peptide boric acid as Trypsin enzyme serine protease.EP185390 and US4399065 disclose and have used some peptide aldehyde derivatives to be used to suppress coagulation of blood.J90029670 discloses common use photolytic activity α amino-aldehyde and has come inhibitory enzyme.Also can be referring to " Inhibition ofThrombin and Trypsin by Tripeptide Aldehydes ", Int.J.PeptideProtein Res., the 12nd volume (1978), pp.217-221; Gaal, Bacsy ﹠amp; Rappay and " Tripeptide Aldehyde Protease Inhibitors May Depress in VitroProlactin and Growth Hormone Release " Endocrinology, the 116th volume, No.4 (1985), pp.1426～1432; Rappay, Makara, Bajusz ﹠amp; Nagy.Some peptide aldehyde have been disclosed in EP-A-473502, are used to suppress and be the skin irritation of medium with proteolytic enzyme.

Can be especially referring to EP185390, WO94/04651 is disclosed on March 3rd, 1994, WO94/04652 is disclosed on March 3rd, 1994, EP583536, be disclosed on February 23rd, 1994, EP583535 discloses on February 3rd, 1994, EP583534 is disclosed on February 23rd, 1994, WO93/13125, be disclosed on July 8th, 1993, US4529525, US4537706, US4537707 and US5527487.

Summary of the present invention

The present invention is a liquid detergent composition, contains:

A) detergent surfactant of significant quantity;

B) active protein hydrolase;

C) contain the boron composition of source of boric acid and glycol; With

D) have the peptide aldehyde of following general formula:

Z-B-NH-CH(R)-C(O)H

Wherein B is the peptide chain that contains 1 to 5 amino acid moiety; Z is the end capped part of N, is selected from phosphoramidate [(R " O) ₂(O) P-], sulfinyl amine [(SR ") ₂-], sulphonamide [(R " (O) ₂S-], sulfonic acid [SO ₃H], phosphonic amide [(R ") ₂(O) P-], sulfonamide [R " O (O) ₂S-], thiocarbamide [(R ") ₂N (O) C-], thiocarbamate [R " O (S) C-], phosphonic acid ester [R "-P (O) OH], amidophosphoric acid base [R " O (OH) (O) P-], carbamate (R " O (O) C-) and urea [R " NH (O) C-], wherein R " be selected from the C of straight chain or collateralization respectively ₁-C ₆Unsubstituted alkyl, phenyl, C ₇-C ₉Alkylaryl and cycloalkyl moiety, wherein cycloalkyl ring can topped C ₄-C ₈, and containing one or several heteroatomss that are selected from O, N and S (preferred R " be selected from methyl, ethyl and benzyl), R is selected from the C of straight chain or collateralization ₁-C ₆Unsubstituted alkyl, phenyl and C ₇-C ₉The alkylaryl part.

Preferably, still randomly, detergent composition of the present invention also contains the calcium ion source of significant quantity.

Liquid detergent composition preferably of the present invention contains based on composition weight:

A) about 1 to about 95%, preferred about 8% to about 70% said detergent surfactant;

B) about 0.0001% to about 5%, preferred about 0.0003% to about 0.1% active protein hydrolase;

C) about 0.00001% to about 5%, and preferred about 0.0001% to about 1%, more preferably from about 0.0006% to about 0.5% above-mentioned peptide aldehyde;

D) boron composition, contain and have an appointment 0.25% to about 10%, preferred about 0.5% to about 5%, more preferably from about 0.75% to the boric acid of about 3% weight or can form the compound (is basic calculation with boric acid) of boric acid and account for composition about 1% to about 15% in said composition, preferred about 1.5% to about 10%, 2% polyvalent alcohol to about 7% weight more preferably from about is preferably with the glycol form; With

E) about 0.01% to about 1%, preferred about 0.05% to about 0.5% calcium ion.

Can be used for preferably subtilysin proteinoid enzyme of proteolytic ferment of the present invention, and can be selected from Alcalase , Subtilisin BPN ', protease A, proteolytic enzyme B and their mixture.

The boron composition contains boric acid or borate ion source, is selected from boron oxide compound, borax, other alkali metal borate, the boric acid of replacement; Polyvalent alcohol is glycol preferably, and is preferably selected from 1, the 2-propylene glycol.

If use, can be used for calcium ion source of the present invention and be preferably selected from calcium formiate, calcium chloride, lime acetate, calcium sulfate, calcium xylene sulfonate and their mixture.

Preferably, this liquid detergent composition further contains the enzyme below one or several of significant quantity: lipase, amylase, cellulase and their mixture.Preferred second kind of enzyme is lipase and is by carrying out clone gene by Humicola Lanuginosa, and prepare with Aspergillus Oryzae expressing gene.The usage quantity of lipase is that every gram about 10 arrives about 18000 lipase units, and preferred every gram is about Unit 60 to 6000.

In another preferred composition, second kind of enzyme is cellulase, and it is produced by HumicolaInsolens, and consumption is the about 0.0001% said cellulase to about 0.1% weight of whole composition.

The present composition can contain other detergent additives, includes, but are not limited to the material below one or several: profoamer, auxiliary agent, soil release polymer, polyacrylate polymers, dispersion agent, dye transfer inhibitor, pigment, spices, processing aid, whitening agent and their mixture.

All percentage ratios of the present invention and ratio all are weight, and all reference in this combination as a reference, unless other explanation is arranged.

Detailed description of the present invention

Definition-composition of the present invention contains the individual components of the present invention's qualification of " significant quantity " or " decontamination improvement amount "." significant quantity " or " decontamination improvement amount " is anyly can improve when the human consumer washs from matrix the amount of carrying out Fouling Cleaning or wiping out a blot on promptly dirty fabric or the dirty plate with measuring.Generally, this amount can change in wide region.

" work in coordination with " or the summation of the single effect that stabilizing effect that " more than adduction " is meant when in conjunction with calcium and peptide aldehyde enzyme is in the present invention obtained when only having a kind of component in detergent composition.

Liquid hydration detergent composition of the present invention contains four main components: (A) peptide aldehyde or its mixture, (B) proteolytic ferment or their mixture, (C) detergent surfactant and (D) calcium ion.Composition of the present invention preferably further contains (E) washing composition compatible second kind of enzyme or its mixture, and can further contain (F) other optional component.

Peptide aldehyde-detergent composition of the present invention contains the peptide aldehyde as first kind of main ingredient, and it has general formula:

Z-B-NH-CH(R)-C(O)H

Wherein B is the peptide chain that contains 1 to 5 amino acid moiety; Z is the end capped part of N, is selected from phosphoramidate [(R " O) ₂(O) P], sulfinyl amine [(SR ") ₂-], sulphonamide [(R " (O) ₂S-], sulfonic acid [SO ₃H], phosphoramide [(R ") ₂(O) P-], sulfonamide [R " O (O) ₂S-], thiocarbamide [(R ") ₂N (O) C-], thiocarbamate [R " O (S) C-], phosphonic acid ester [R "-P (O) OH], amidophosphoric acid ester [R " O (OH) (O) P-], carbamate (R " O (O) C) and urea [R " NH (O) C-], wherein each R " be selected from the C of straight chain or collateralization respectively ₁-C ₆Unsubstituted alkyl, phenyl, C ₇-C ₉Alkylaryl and cycloalkyl moiety, wherein cycloalkyl ring can topped C ₄-C ₈, and containing one or several heteroatomss that are selected from O, N and S (preferred R " be selected from methyl, ethyl and benzyl), R is selected from the C of straight chain or collateralization ₁-C ₆Unsubstituted alkyl, phenyl and C ₇-C ₉The alkylaryl part.

Preferred R partly be selected from methyl, sec.-propyl, sec-butyl, isobutyl-,-C ₆H ₅,-CH ₂-C ₆H ₅With-CH ₂CH ₂-C ₆H ₅, they can be produced by hydroxy-acid group being transformed into aldehyde group by amino acid Ala, Val, Ile, Leu, PGly (phenylglycocoll), Phe and HPhe (phenylalanine) respectively.Therefore, though these parts be not amino acid (and they be by or be not by the amino acid precursor synthetic) time, be used for illustrating of inhibitor of the present invention in order to simplify, the aldehyde of inhibitor partly is said to be by amino acid and produces [as " AlaH " expression chemical part " NHCH (CH by add " H " after with amino acid ₃) C (O) H "].

Preferred B peptide chain is selected from the peptide chain of the aminoacid sequence with following general formula:

Z-A ⁵-A ⁴-A ³-A ²-A ¹-NH-CH(R)-C(O)H

Make that when having amino acid they are following amino acid:

A ¹Be selected from Ala, Gly;

A ²Be selected from Val, Ala, Gly, Ile if exist;

A ³Be selected from Phe, Leu, Val, Ile if exist;

A ⁴If existing is any amino acid, but be preferably selected from Gly, Ala;

A ⁵If existing is any amino acid, but preferably Gly, Ala, Lys.

Aldehyde of the present invention can be prepared by corresponding amino acid, thereby said amino acid whose C-end is transformed into aldehyde group by hydroxy-acid group.This class aldehyde can be by known method preparation, for example as putting down in writing in US5015627, EP185930, EP583534 and DE3200812.

Without being limited by theory, can believe that peptide aldehyde of the present invention links to each other with proteolytic ferment in liquid detergent composition, thereby suppress said proteolytic ferment.By diluting in water, proteoclastic activity is recovered by the disassociation of proteolytic ferment/peptide aldehyde title complex.

The N-of the said proteinase inhibitor of the present invention is terminal to be protected with a N-end-blocking part blocking group that is selected from carbamate, urea, sulphonamide, phosphonic amide, thiocarbamide, sulfinyl amine, sulfonic acid, phosphoramide, thiocarbamate, amidophosphoric acid ester and phosphonic amide.But in highly preferred embodiment of the present invention, the N-end of said proteinase inhibitor is by methyl, ethyl or benzylamino manthanoate [CH ₃O-(O) C-; CH ₃CH ₂O-(O) C-or C ₆H ₅CH ₂O-(O) C-], methyl, ethyl or benzylurea [CH ₃NH-(O) C-; CH ₃CH ₂NH-(O) C-or C ₆H ₅CH ₂NH-(O) C-], methyl, ethyl or benzyl sulphonamide [CH ₃SO ₂-; CH ₃CH ₂SO ₂-or C ₆H ₅CH ₂SO ₂-] and methyl, ethyl or benzyl amidophosphoric acid ester [CH ₃O (OH) is P-(O); CH ₃CH ₂O (OH) is P-or C (O) ₆H ₅CH ₂O (OH) is P-(O)] group protects.

The synthetic of N-capping group can be found in the document below: Protective Groupsin Organic Chemistry, Greene, T., Wuts, P., John Wiley ﹠amp; Sons, New York, 1991,309-405 page or leaf; March, J, Advanced Organic Chemistry, Wiley Interscience, 1985,445,469 pages, Carey, F.Sundberg, R.AdvancedOrganic Chemistry, PartB, Plenum Press, New York, 1990,686-89 page or leaf; Atherton, E., Sheppard, R., Solid Phase Peptide Synthesis, Pierce Chemical, 1989,3-4 page or leaf; Grant, G., Synthetic Peptide, W.H.Freeman ﹠amp; Co., 1992,77～103 pages; Stewart, J., Young, J., Solid Phase Peptide Synthesis, second edition, IRL Press, 1984,3,5,11,14-18, the 28-29 page or leaf, Bodansky, M., Principles of Peptide Synthesis, Springer-Verlag, 1988,62,203,59-69 page or leaf, Bodansky, M., PeptideChemistry, Springer-Verlag, 1988,74-81 page or leaf, Bodansky, M.Bodansky, A., The Practice of Peptide Synthesis, Springer-Verlag, 1984, the 9-32 page or leaf.

The example that can be used for peptide aldehyde of the present invention is: CH ₃SO ₂Phe-Gly-Ala-Leu-H, CH ₃SO ₂Val-Ala-Leu-H, C ₆H ₅CH ₂O (OH) is P-Val-Ala-Leu-H, CH (O) ₃CH ₂SO ₂Phe-Gly-Ala-Leu-H, C ₆H ₅CH ₂SO ₂-Val-Ala-Leu-H, C ₆H ₅CH ₂O (OH) is P-Leu-Ala-Leu-H, C (O) ₆H ₅CH ₂O (OH) is P-Phe-Ala-Leu-H and CH (O) ₃O (OH) is P-Leu-Gly-Ala-Leu-H (O).

Method in synthetic a part of peptide aldehyde is disclosed among the synthetic embodiment below.

Synthetic embodiment 1

Tetrapeptide aldehyde Moc-Ala-Phe-Gly-Ala-LeuH's is synthetic

(a) Ala-Leu-OMe.HCl: toward being dissolved in 3.0 gram (14.83 mmole) Ala-Leu-OH among 50 milliliters of MeOH and being cooled to drip in 0 ℃ the solution 2.43 milliliters of (33.36 mmole) thionyl chloride.This solution is at room temperature stirred a night and evaporate to dryness, the product that quantitative recovery is required.

(b) Cbz-Gly-Ala-leucine methyl ester: restrain (1.98 mmole) Ala-Leu-OMe.HCl at CH toward 0.414 gram (1.98 mmole) Cbz-Gly-OH and 0.500 ₂Cl ₂In solution in add 0.607 milliliter of TEA, and then add 0.355 milliliter of DEPC.With one night of this solution stirring, evaporation, and residue is distributed between EtOAc and the 1NHCl.Use saturated NaHCO ₃With saturated NaCl continuous washing organic phase, dry (MgSO ₄) and the evaporation obtain 0.650 the gram pure products.

(c) Moc-Ala-Phe-OH: be dissolved among 4.23 milliliters of 1NNaOH and be cooled to drip in 0 ℃ the solution 0.419 gram (4.44 mmole) methyl-chloroformate toward 1.0 grams (4.23 mmole).Simultaneously, independently adding other 4.23 milliliters of 1NNaOH in the feed hopper, pH is remained between 9.0～9.5.After adding reactant was stirred 30 minutes at 0 ℃, at room temperature stirred 2 hours.At this moment solution is cooled to 0 ℃, and pH is adjusted to 9.5.Wash this basic solution with EtOAc (1X, 50 milliliters).Then water (0 ℃) is adjusted to pH=2.5 (2NHCl), and with EtOAc (3X, 50 milliliters) extract, dry (MgSO ₄), and evaporation is to obtain 1.07 gram straight products.

(d) Moc-Ala-Phe-Gly-Ala-Leu-OMe: restrain the Pd/C that adds 0.100 gram 10% in the solution of (1.22 mmole) Cbz-Gly-Ala-leucine methyl esters in 10 milliliters of MeOH toward 0.500.There was under the situation (under the pressure at balloon) hydrogenation in this solution 1 hour at 0.600 milliliter of 4.0MHCl/ diox, by diatomite filtration and evaporation.Residue is suspended in CH ₂Cl ₂In, add 0.342 milliliter of (2.45 mmole) TEA, then add 0.359 gram (1.22 mmole) Moc-Ala-Phe-OH and 0.219 milliliter of (1.34 mmole) DEPC.Stir after the night, evaporating solvent is distributed in residue among EtOAc and the 1NHCl, and uses saturated NaHCO continuously ₃Wash with NaCl.Drying, evaporation and column chromatography generate 0.450 gram straight product.

(e) Moc-Ala-Phe-Gly-Ala-leucine alcohol: by 0.182 gram (1.64 mmole) CaCl of dissolving in the mixture of 4 milliliters of ethanol and 2 milliliters of THF ₂Prepare a kind of solution.This mixture is cooled to-15 ℃, and adds 0.450 gram (0.820 mmole) Moc-Ala-Phe-Gly-Ala-Leu-OMe, then add 0.124 gram (3.28 mmole) NaBH ₄Reactant was stirred 2 hours, and with 10 milliliters of 1NHCl quenchings.Evaporating solvent distributes the remaining aqueous layer with EtOAc.Then use saturated NaHCO ₃With saturated NaCl washing organic phase.Dry (MgSO ₄), evaporation and chromatogram obtain 0.256 gram pure products.

(f) Moc-Ala-Phe-Gly-Ala-LeuH: by 0.623 gram (1.47 mmole) Dess-Martin periodinane is joined 1.8 liters of CH ₂Cl ₂In, then stir and be prepared into a kind of solution in 10 minutes.Then this solution is cooled to 0 ℃, once adds 0.256 gram (0.490 mmole) EtOC-Phe-Gly-Ala-leucine alcohol.Reaction continued 2 hours and impouring 2.55 gram (10.47 mmole) Na ₂S ₂O ₃At 30 milliliters of saturated NaHCO ₃In solution in.Stir after 10 minutes, extract this mixture with EtOAc (2X, 50 milliliters).With the extract drying (MgSO that merges ₄), evaporation, chromatography obtains 0.125 gram pure products on silicon-dioxide.

Synthetic embodiment 2

Synthetic aldehydic tripeptide EtOC-Phe-Gly-Ala-LeuH

(a) Ala-Leu-OMe.HCl: be dissolved among the 4.5LMeOH and be cooled to drip in the solution in 0 ℃ 178.6 milliliters of (4.95 moles) thionyl chloride toward 450 grams (2.20 moles).At room temperature with one night of this solution stirring, and be evaporated to drying, produce 543 gram (productive rate is 97.1%) required products.

(b) EtOC-Phe-Gly-OH: be dissolved among 2026 milliliters of 1NNaOH and be cooled to toward 450 gram (2.03 milliliters) Phe-Gly and drip methyl-chloroformate (3.1 milliliters, 40.0 mmoles) in 0 ℃ the solution.Simultaneously, in feed hopper independently, add 2026 milliliters of 1NNaOH in addition, pH is remained between 9.0～9.5.After adding, reactant was stirred 30 minutes at 0 ℃, at room temperature stirred 2 hours.At this moment, solution is cooled to 0 ℃, pH is adjusted to 9.5.With EtOAc (1X, 4L) washing.(2N, HCl) and with EtOAc (3X 8L) extracts, dry (MgSO water (0 ℃) to be adjusted to pH=2.5 again ₄), filter, and remove solvent, obtain 546 gram (productive rate 91.3%) pure products.

(c) EtOC-Phe-Gly-Ala-Leu-OMe: restrain (1.86 moles) Ala-Leu-OMe.HCl at 8 liters of CH toward 470 gram (1.86 moles) EtOC-Phe-Gly-OH and 546 ₂Cl ₂Solution in add 570 milliliters of (4.09 moles) TEA, then add 310.4 milliliters of (2.046 moles) DEPC.With solution stirring after one night,, and substitute with EtOAc (4 liters) with solution evaporation.Continuously with 2 liters of 2NHCl, saturated NaHCO ₃Wash this solution with saturated NaCl.Then with organic phase drying (MgSO ₄), filter and evaporation, obtain the required product of 916 grams (productive rate 93%).

(d) EtOC-Phe-Gly-Ala-leucine alcohol: toward 45.10 gram (0.406 mole) CaCl ₂Solution in add 1 liter of ethanol and 1 liter of THF100 gram (0.203 mole) EtOC-Phe-Gly-Ala-Leu-OMe, and mixture is cooled to-15 ℃.In this solution, add 30.7 gram (0.812 mmole) NaBH carefully ₄, then stirred 2 hours.To react then with 100 milliliters of 0.1NHCl quenchings.This solution is transferred among 4 liters of 1NHCl also with EtOAc (3X, 2.75 liters) extraction.With 4 liters of saturated NaHCO ₃Washing merges the EtOAc layer, dry (MgSO ₄) and evaporation.With ether (4 liters) development (twice), generate 69.2 gram (productive rate 73.4%) products.

(e) EtOC-Phe-Gly-Ala-LeuH: by 165.4 gram (0.39 mole) Dess-Martin perioninane are joined 1.8 liters of CH ₂Cl ₂In, then stir and prepared a kind of solution in 10 minutes.Then this solution is cooled to 0 ℃ and also once adds 60 gram (0.13 mole) EtOC-Phe-Gly-Ala-leucine alcohol.To react and continue 105 minutes and be poured into to restrain NaHCO by 6 premium on currency, 393 ₃With 431.7 gram (1.74 moles) Na ₂S ₂O ₃In the solution that constitutes.After stirring 10 minutes, be separated, finish and use CH ₂Cl ₂Extract (each 1.5 liters) other 2 times.Dry (MgSO ₄) extract that merges, evaporation, and (2X, 1L) ether development produce 51.7 gram (productive rate 86.2%) products.

Synthetic embodiment 3:

Synthetic dipeptides aldehyde Moc-Gly-Ala-LeuH

(a) Ala-Leu-OMe.HCl: toward being dissolved in 3.0 gram (14.83 mmole) Ala-Leu-OH among 50 milliliters of MeOH and being cooled to drip in 0 ℃ the solution 2.43 milliliters of (33.36 mmole) thionyl chloride.At room temperature stir one night of this solution and be evaporated to drying, generate the required product of quantitative yield.

(b) Cbz-Gly-Ala-leucine methyl ester: restrain (1.98 mmole) Ala-Leu-OMe.HCl at CH toward 0.414 gram (1.98 mmole) Cbz-Gly-OH and 0.500 ₂Cl ₂In solution in add 0.607 milliliter of TEA, then add 0.355 milliliter of DEPC immediately.With this one night of solution stirring and evaporation.Residue is distributed between EtOAc and the 1NHCl, uses saturated NaHCO ₃With saturated NaCl washing organic phase, dry (MgSO ₄) and evaporation, generate 650 milligrams of pure products.

(c) Moc-Gly-Ala-leucine methyl ester: be dissolved in adding 0.200 gram 10%Pd/C in 20 milliliters of solution among the MeOH toward 2.0 gram (4.90 mmole) Cbz-Gly-Ala-leucine methyl ester.After reactant fully being exitted and remove catalyzer by diatomite filtration, hydrogenation is 2 hours under the situation that has 2.45 milliliters of (9.81 mmole) 4.0MHCl/ dioxs.Evaporation MeOH generates 1.45 gram pure products, and it is suspended in 45 milliliters of CH ₂Cl ₂In and be cooled to 0 ℃.In this solution, add 1.45 milliliters of (3.25 mmole) TEA, then add 0.362 milliliter of methyl-chloroformate.Stir after the night evaporation CH ₂Cl ₂, residue is distributed between EtOAc and the 1NHCl.Separate organic phase and use NaHCO ₃With the NaCl washing, dry (MgSO ₄), evaporation, and, generate the required product of 0.820 gram with the chromatogram purification.

(d) Moc-Gly-Ala-leucine alcohol: toward 0.168 gram (1.51 mmole) CaCl ₂In the solution of 25 milliliters of ethanol and 15 milliliters of THF, add 0.250 gram Moc-Gly-Ala-leucine methyl esters.This solution is cooled to-15 ℃ also once adds 0.114 gram (3.02 mmole) NaBH ₄After reactant stirring 2 hours, with 20 milliliters of 1NHCl quenchings, on rotovape, concentrate, and extract with EtOAc (2X, 50 milliliters).Use saturated NaHCO ₃The extract that washing merges with NaCl, dry (MgSO ₄) and evaporation.On silicon-dioxide, purify, generate 0.167 gram pure products.

(e) Moc-Gly-Ala-LeuH: solution is by 0.418 (0.989 mmole) Dess-Martin periodinane is joined 5 milliliters of CH ₂Cl ₂In, then stir 10 minutes the preparation.Then, once add 0.100 gram (0.330 mmole) Moc-Gly-Ala-leucine alcohol, reactant was stirred 2 hours, and impouring contains 1.72 gram (6.93 mmole) Na for 25 milliliters ₂S ₂O ₃Saturated NaHCO ₃In the solution.After the restir 10 minutes, solution is extracted dry (MgSO with EtOAc (3X, 50 milliliters) ₄) and evaporation.Chromatogram on silicon-dioxide generates the required product of 0.016 gram.

Synthetic embodiment 4:

Synthetic N-(methyl sulphonyl)-Phe-Gly-Ala-LeuH

(a) N-Ms-Phe-Gly-OH: in feed hopper independently, be dissolved among 9 milliliters of 1NNaOH and be cooled to and add 0.766 milliliter of (9.9 mmole) methylsulfonyl chloride and 9 milliliters of 1NNaOH simultaneously in 0 ℃ the solution toward 2.0 gram (9.0 mmole) Phe-Gly-OH.After adding, reactant was stirred 15 minutes at 0 ℃, stirring at room 1 hour.At this moment, solution is cooled to 0 ℃, pH adjusts to 9.5, all EtOAc (1X, 50 milliliters) washing.Water (0 ℃) is adjusted to pH=2.5 (2NHCl), and extract, dry (MgSO with EtOAc (3X, 50 milliliters) ₄), filter and remove solvent, generate 2.0 gram pure products.

(b) N-Ms-Phe-Gly-Ala-leucine alcohol: solution is by 0.500 gram (1.67 mmole) N-Ms-Phe-Gly-OH is dissolved among 15 milliliters of THF, be cooled to-15 ℃ and add 0.366 milliliter of (3.33 mmole) NMM, then add 0.216 milliliter of (1.67 mmole) isobutyl chlorocarbonate preparation.With this solution stirring 5 minutes and with 0.374 gram (1.67 mmole) Ala-leucine alcohol.HCl joins in the mixture of 10 milliliters of THF and micro-DMF.Continue to stir 15 minutes at 0 ℃, continue to stir 2 hours in room temperature.With 5 milliliters of these solution of 1NHCl quenching, extract with EtOAc (3X, 50 milliliters), use saturated NaHCO ₃Extract with saturated NaCl washing merging.Then dry (MgSO ₄) organic phase that generates, to filter, evaporation and carry out chromatography on silicon-dioxide generates the required material of 0.260 gram.

(c) N-Ms-Phe-Gly-Ala-LeuH: solution is by past 5 milliliters of CH ₂Cl ₂Middle adding 0.337 restrains (0.798 mmole) Dess-Martin periodinane and stirs and prepared in 10 minutes.In this solution, once add 0.125 gram (0.266 mmole) N-Ms-Phe-Gly-Ala-leucine alcohol.Sustained reaction shows conversion fully until TLC, at this moment, 25 milliliters of solution impourings is contained 1.8 gram (5.586 mmole) Na ₂S ₂O ₃Saturated NaHCO ₃In.Stir after 10 minutes, extract this mixture with EtOAc (3X, 50 milliliters).Dry (MgSO ₄) extract that merges, evaporation, the silicon-dioxide chromatogram generates 0.048 gram product.

Synthetic embodiment 5:

Synthetic aldehyde proteinase inhibitor

Be dissolved in Moc-Leu-OH-L-leucine (5.0 gram, 38.2 mmoles) among 38 milliliters of 1NNaOH and be cooled to 0 ℃.Drip methyl-chloroformate (3.1 milliliters, 40.0 mmoles), simultaneously, independently adding 1NNaOH in the feed hopper, make pH remain on 9.0～9.5.Add and after pH is stabilized in 9.0-9.5, wash this solution with 200 milliliters of EtOAc, again with aqueous phase as acidified to pH=2.Extract this mixture with EtOAc (2X, 100 milliliters), dry (MgSO ₄), filter and remove solvent, generate 7.15 gram pure products.

Moc-Leu-leucine alcohol-toward 3.5 gram (18.52 mmole) Moc-Leu-OH then adds 2.4 milliliters of (18.52 mmole) isobutyl chlorocarbonates in 100 milliliters of THF and be cooled to add 2.04 milliliters of (18.52 mmole) N-methylmorpholines in-15 ℃ the solution immediately.After stirring 10 minutes, in 25 milliliters of THF, add 2.37 milliliters of (18.52 mmole) leucine alcohol, reactant was stirred 0.5 hour at-15 ℃, at room temperature stirred 1 hour.Then dilute this mixture and evaporate THF with 100 ml waters.Remaining water is distributed between EtOAc and the 1NHCl, uses NaHCO ₃The washing organic phase, dry (MgSO ₄) and evaporation, generate 5.33 gram pure products.

The Moc-Leu-LeuH-preparation contains 4.4 grams (10.41 mmole) and is suspended in 10 milliliters of CH ₂Cl ₂In Dess-Martin periodinane solution and stirred 10 minutes.Add 1.0 gram (3.47 mmole) Moc-Leu-leucines alcohol in this solution and this solution was at room temperature stirred 2 hours, then impouring contains 18 gram (72.87 mmole) Na for 100 milliliters ₂S ₂O ₃Saturated NaHCO ₃In.Extract dry (MgSO with this solution stirring 10 minutes and with EtOAc (2X, 125 milliliters) ₄) and evaporating solvent.Generate 0.550 gram pure products with the silicon-dioxide chromatography.

Synthetic embodiment 6:

Synthetic according to the following steps other peptide aldehyde.Buy some intermediate products by the provider place, this can find out in the step below.According to Martin, J.Org.Chem., 1983,48,4155 step is synthesized Dess-Martin periodinane.

I .Z-Gly-Ala-Leu-OMe-toward Z-Gly-Ala-OH (20.0 the gram, 0.071M) and Leu-OMe.HCl (12.9 the gram, 0.071M) in the solution in 250 milliliters of methylene dichloride in 10 minutes the dropping 21.9 milliliters of (0.157M) triethylamines (TEA).Add 11.9 milliliters of (0.078M) diethylcyanophosphonise (DECP) after current the adding.Mixture is stirred a night and removes solvent.Residue is dissolved in the ethyl acetate, with 1NHCl, saturated NaHCO ₃With the salt water washing.Use MgSO ₄Dry this solution filters and removes solvent.Reclaim the single product of 29.0 grams with TLC. ¹³C?NMR(CDCl ₃)15.93,18.60,21.77,22.69,24.72,40.80,44.20,48.70,50.87,52.13,65.28,66.84,127.92,128.00,128.41,136.36,156.76,,169.31,172.58,173.24。

(29.0 grams 0.071M) are dissolved in 300 milliliters of MeOH and 35 milliliters of 4.0MHCl are dissolved in the diox to II .Moc-Phe-Gly-Ala-Leu-OMe-with Z-Gly-Ala-Leu-OMe.In this solvent mixture, add 5.8 gram 10%Pd/C in batches.Suspension is fed H with the vent fan degassing and by balloon ₂Suspension is remained on H ₂Direct draught and stir a night.Suspension is filtered and uses the MeOH thorough washing by diatomite and sintered glass funnel.Remove solvent and develop residue with ether.Filtering suspension liquid, and under vacuum dry cake.Reclaim the non-white powder of 20.2 grams.(15.3 grams 0.068M) are dissolved in 500 milliliters of CH with thick product and Moc-Phe-OH ₂Cl ₂, and drip 29.9 milliliters of TEA (0.143M), drip 11.7 milliliters of (0.072M) DECP again.Mixture is stirred a night and removes solvent.Residue is dissolved among the EtOAc, with 1NHCl, saturated NaHCO ₃With the salt water washing.Dry (MgSO ₄) organic phase, filter, remove solvent, generate 21.3 gram products. ¹³C?NMR(CDCl ₃)16.66,16.83,20.01,22.46,23.41,25.40,40.11,41.72,43.75,49.39,51.37,52.87,56.42,65.92,77.39,77.55,77.81,78.24,127.42,128.96,129.19,130.09,137.41,157.62,169.00,172.63,173.24,174.00。

III .Moc-Phe-Gly-Ala-leucine alcohol-Moc-Phe-Gly-Ala-Leu-OMe (21.3 grams, 44.5 mmoles) is dissolved in the mixture of 400 milliliters of EtOH and 250 milliliters of THF.Solution is cooled to 0 ℃, and adds 9.88 gram (89.0 mmole) CaCl ₂Homogenizing suspension after 5 minutes, and in 5 minutes, add 6.73 gram (178.0 mmole) NaBH in batches ₄Solution was stirred 2 hours at 0 ℃, and with 1NHCl quenching reactant carefully.Under vacuum, remove EtOH and THF, extract the remainder water phase mixture with 500 milliliters of EtOAc.Use saturated NaHCO ₃, salt water washing organic phase, and use MgSO ₄Dry organic phase.Filter and remove solvent, generate the non-white crystalline material of 20.0 grams.Through silicon-dioxide chromatography (3.5%MeOH/CH ₂Cl ₂) generation 13.0 gram pure products.Rf=0.3(10％MeOH/CH ₂CL ₂), ¹³C?NMR(CDCl ₃)17.50,22.23,23.12,24.84,37.22,39.76,43.96,49.88,50.93,52.48,58.22,65.27,98.46,98.54,127.04,128.68,129.10,136.62,157.85,170.71,173.85,174.45。

IV .Moc-Phe-Gly-Ala-Leu-H-is suspended in 500 milliliters of CH with 29.9 gram (70.7 mmole) DESS-Martinperiodinane ₂Cl ₂In and stirred 10 minutes.Moc-Phe-Gly-Ala-leucine alcohol (10.6 grams, 23.5 mmoles) is dissolved in 100 milliliters of CH ₂Cl ₂In and join in the periodinane suspension with middling speed.Stir the mixture 1 hour and impouring contains 123 gram Na for 150 milliliters ₂S ₂O ₃NaHCO ₃In.Mixture was stirred 15 minutes and extract with EtOAc.Drying is also filtered organic phase, then removes solvent.Through silicon-dioxide chromatography (3.5%MeOH/CH ₂Cl ₂) generating the pure white solid of 5.1 grams, it is the mixture of methoxyl group hemiacetal and aldehyde. ¹³C?NMR(CDCl ₃,CD3OD)17.62,17.94,21.53,21.71,22.99,23.30,23.39,24.54,37.05,37.70,37.92,38.24,42.87,49.83,51.79,52.14,52.40,56.75,57.19,98.40,99.18,127.00,128.60,129.06,136.44,157.27,169.19,169.67,172.73,173.40,200.43。

V .Moc-Phe-OH-is dissolved in L-phenylalanine (5.0 grams, 30.2 mmoles) 30 milliliters of 1NNaOH and is cooled to 0 ℃.Drip methyl-chloroformate (2.53 milliliters, 31.8 mmoles), independently adding 30 milliliters of 1NNaOH in the feed hopper simultaneously.After adding, with 200 milliliters of EtOAc washing solns and acidifying water to pH=2.Extract mixture with EtOAc (2X, 100 milliliters), dry (MgSO ₄), filter and remove solvent, generate 6.0 gram products. ¹³CNMR(CDCl ₃)37.75,52.57,54.64,128.63,129.35,135.74,156.77,175.76。

VI .Mac-Phe-OH restrains (2.34 mmole) Phe-OBn.PTSA at Et toward 1.00 ₂At room temperature add 0.36 milliliter of (2.57 mmole) TEA in the solution of O.Then add 10 milliliters of MeOH, again 0.14 milliliter of (2.34 mmole) methyl isocyanate is added drop-wise to 4 milliliters of Et ₂Among the O.With in reaction mixture impouring 50 ml waters and be separated.Use MgSO ₄Solvent is filtered and removed to dry organic phase, generates 0.66 gram product (productive rate 96%). ¹³C?NMR(CDCl ₃) ₂7.05,38.47,53.45,54.64,65.90,127.43,127.85,128.48,129.28,130.27,135.23,136.22,158.17,173.08。In the solution of 25 milliliters of MeOH, add 0.120 gram Pd/C and make the suspension degassing toward crude product (2.11 mmole).At H ₂Direct draught is used balloon stirred suspension 1.5 hours.By diatomite filtration suspension, use the MeOH washing leaching cake.Remove solvent, generate 0.430 gram product. ¹³CNMR26.50,37.92,54.28,126.69,128.28,129.28,136.65,159.36,175.33。

VII .Mac-Phe-Gly-Ala-leucine alcohol-toward 0.200 gram Mac-Phe-OH (0.900 mmole) and 0.253 gram Gly-Ala-Leu-OMe.HCl (0.818 mmole, generate by the hydrogenation I according to the step of above-claimed cpd II) add 0.250 milliliter of TEA (1.80 mmole) in the solution in 15 milliliters of DMF, then 0.147 milliliter of DECP (0.900 mmole).Mixture is stirred a night and removes solvent.Be dissolved among the EtOAc residue and continuous 0.3NHCl, the saturated NaHCO of using ₃With the salt water washing.With the solution drying, filter and remove solvent, generate 0.300 gram product.Be dissolved in crude product (0.628 mmole) among 17 milliliters of EtOH and be cooled to 0 ℃.In this solution, once add 0.095 gram NaBH ₄After 45 minutes, the water quench solution is also extracted with EtOAc.Use MgSO ₄Solvent is filtered and removed to dry organic phase.At 4%MeOH/CH ₂Cl ₂On chromatography generate 0.200 gram pure products. ¹³C?NMR(CD ₃OD)16.84,21.05,22.60,24.51,25.66,37.41,39.73,42.67,49.65,56.63,64.33,126.63,128.32,128.96,137.12,160.01,170.45,173.60,175.03。

The past Dess-Martinperiodinane of VIII .Mac-Phe-Gly-Ala-Leu-H-(0.565 gram, 1.33 mmoles) is at 15 milliliters of CH ₂Cl ₂In suspension in add Mac-Phe-Gly-Ala-leucine alcohol (0.200 gram, 0.445 mmole) at CH ₂Cl ₂In suspended substance, and the suspension that generates stirred 0.5 hour.The mixture impouring is contained 2.32 gram Na ₂S ₂O ₃Saturated NaHCO ₃In, and with solution stirring 10 minutes, then extract with EtOAc.Use MgSO ₄Solvent is filtered and removed to dry organic phase.Residue is carried out the silicon-dioxide chromatography, generate 0.081 gram product. ¹³C NMR (10%CD ₃OD is at CDCl ₃In) 17.18,17.43,21.35,21.55,23.26,23.34,24.40,24.47,26.36,26.60,37.25,37.38,38.60,42.86,42.97,51.77,51.93,54.94,56.75,57.00,98.7,99.32,126.87,128.49,128.91,136.51,159.53,159.55,169.93,170.39,173.63,173.85,174.70。

Cbz=carboxylic benzene methoxy

The Gly=glycine

The Ala=L-Ala

The Leu=leucine

The Phe=phenylalanine

The OMe=methyl ester

The TEA=triethylamine

The DECP=diethylcyanophosphonise

The TLC=thin-layer chromatography

MeOH=methyl alcohol

The Pd/C=activated carbon-carried palladium

EtOH=ethanol

The THF=tetrahydrofuran (THF)

Mac=methylamino carbonyl

The Moc=methoxycarbonyl

The Etoc=ethoxy carbonyl

The Ms=methylsulfonyl

The another kind of main ingredient of proteolytic ferment-liquid detergent composition of the present invention is an active protein hydrolase.The mixture that also comprises proteolytic ferment.Proteolytic ferment can be animal, plant or microorganism (preferably) source.The proteolytic enzyme that is used for detergent composition of the present invention comprises (but being not limited to) trypsinase, subtilysin, Chymotrypsin and elastic type proteolytic enzyme.Being preferred for of the present invention is subtilysin proteinoid lytic enzyme.Particularly preferably be bacterial serine proteolytic ferment by Bacillus subtilis and/or Bacillus licheniformis preparation.The proteolytic enzyme generally content in this class I liquid I detergent composition will enough make every gram composition have 0.005 to 0.1Anson unit (AU) activity.

Suitable proteolytic ferment comprises Novo Industri A/S Alcalase  (preferably), Esperase , Savinase  (Copenhagen, Denmark), Gist-brocades ' Maxatase, Maxacal  and Maxapem15  (protein engineering Maxacal ) (Delft, Netherlands), with subtilysin BPN and BPN ' (preferably), they can industrially provide.Preferred proteolytic enzymes also can be the bacterial serine proteolytic enzyme of modification, for example by Genencor International, Inc. (SanFrancisco, California) produce, be documented in European patent 251446, on April 28th, 1987 (particularly 17,24 and 98 pages), and it is called as " proteolytic enzyme B ", and US5030378, Venegas, on July 9th, 1991, it is meant the bacterial serine proteolytic ferment (Genencor International) of modification, and it is called as " protease A " (identical with BPN ') in the present invention.Particularly, comprise the aminoacid sequence of protease A and its varient referring to the complete description on the 2nd and 3 hurdles of US5030378.Preferred proteolytic enzymes is selected from Alcalase  (NovoIndustri A/S), BPN ', protease A and proteolytic enzyme B (Genencor) and their mixture.Proteolytic enzyme B is the most preferred.

Another kind is preferably claimed the proteolytic enzyme of " proteolytic enzyme D " to be meant the carbonylic hydrolase varient with the undiscovered aminoacid sequence of nature, it is by being equal on said carbonylic hydrolase+position of 76 positions by the precursor carbonylic hydrolase, also preferred combination one or several be equal to be selected from according to the layout of bacillus amyloliquefaciens subtilysin sequence+99, + 101, + 103, + 104, + 107, + 123, + 27, + 105, + 109, + 126, + 128, + 135, + 156, + 166, + 195, + 197, + 204, + 206, + 210, + 216, + 217, + 218, + 222, + 260, + 265 and/or+274 amino acid residue position replaces a plurality of amino-acid residues to prepare with different amino acid, as Genencor International described in the April 20 nineteen ninety-five disclosed WO95/10615.

The effective protein proteins enzyme also be documented in following PCT open in: WO95/30010, November 9 nineteen ninety-five, The Procter; Gamble Company; WO95/30011, November 9 nineteen ninety-five, The Procter; Gamble Company and WO95/29979, November 9 nineteen ninety-five, The Procter; Among the Gamble Company.

Calcium-any water-soluble Ca salt can be used as calcium ion source, comprises calcium acetate, calcium formiate, calcium xylene sulfonate and calcium propionate.Divalent ion, for example zine ion and magnesium ion can replace all or part of calcium ion.Therefore, in liquid detergent composition of the present invention, calcium ion source can partly replace with another kind of divalent ion source.

Can be used for calcium of the present invention is that enzyme is acceptable.Therefore, claimed composition is substantially free of sequestering agent, for example can form the polyprotonic acid of the calcium composition that dissolves in composition.But, can adopt a spot of sequestering agent, as the mixture of polyprotonic acid or polyprotonic acid.The acceptable calcium of enzyme is defined as being effective to the amount of the calcium ion of enzyme component.Proceed from the reality, the acceptable calcium of enzyme is soluble calcium in not containing any storage combination of chelating agents thing, is equal to, or greater than 1.5 as the coordination equilibrium constant of sequestrant and calcium at 20 ℃.

Boric acid-composition of the present invention contains 0.25% to about 10%, and preferred about 0.5% to about 5%, and more preferably from about 0.75% to the boric acid of about 3% weight or can form the compound (based on boric acid calculating) of boric acid in composition.Preferred boric acid, although other compound, as boron oxide, borax and other alkali metal borate (as former-, partially-, sodium pyroborate, sodium pentaborate) also be suitable for.The boric acid that replaces (as phenyl-boron dihydroxide, butane boric acid with to bromophenyl boric acid) can be used for substituted boracic acid.

Composition of the present invention also can contain the polyvalent alcohol, particularly glycol of carbon, hydrogen and Sauerstoffatom.They preferably contain has an appointment 2 to about 6 hydroxyls.Example comprises propylene glycol (particularly 1,2-propylene glycol, it is preferred), ethylene glycol, glycerine, sorbyl alcohol, mannitol, glucose and their mixture.The content that polyvalent alcohol is general be composition about 1% to about 15%, preferred about 1.5% to about 10%, more preferably from about 2% to about 7% weight.

Detergent surfactant-significant quantity generally is about 1 to 95, and preferred about 8 to 70 weight % detergent surfactants also are another important components of the present invention.Detergent surfactant can be selected from negatively charged ion, nonionic, positively charged ion, both sexes, zwitterionics and their mixture.By selecting the kind and the amount of detergent surfactant, together with other auxiliary component disclosed by the invention, can prepare detergent composition of the present invention with the cleaning purposes that is used to do washing or other are different, particularly comprise dishwashing.According to particularly required end-use, can in wide region, select used special tensio-active agent.

Effect of the present invention is containing enzyme unfavorablely, for example is tangible especially in the composition of the component of some washing auxiliary detergent and tensio-active agent.They comprise (but being not limited to) anion surfactant, for example sulfated alkyl ether linear alkyl benzene sulfonate, alkyl-sulphate etc.Suitable tensio-active agent is described below.

The anion surfactant that anion surfactant-a class can adopt comprises alkyl sulfonate esters salt.Because they can be by reusable, nonoil feedstock production but are desirable.The preparation of alkyl sulfonate esters salt surfactant component can be carried out according to the currently known methods that is disclosed in the technical literature.For example, C ₈-C ₂₀The ol ester of carboxylic acid can adopt SO ₃Gas is according to " The Journal of the American Oil Chemists Society ", and 52 (1975), the method for pp.323-329 is carried out sulfonation.Proper raw material comprises the natural fat material that generates by as tallow, palm and coconut wet goods.

Preferred alkyl sulfonate esters salt surfactant, especially for the laundry purposes, contain alkyl sulfonate esters salt surfactant with following general structure:

R wherein ³Be C ₈-C ₂₀Alkyl, preferred alkyl, perhaps their combination, R ⁴Be C ₁-C ₆Alkyl, preferred alkyl, perhaps their combination, M is the solubility salt-forming cation.Suitable salt comprises metal-salt, as sodium, potassium and lithium salts and that replace or unsubstituted ammonium salt, as methyl-, dimethyl-, trimethylammonium-and quaternary ammonium cation, as tetramethyl-ammonium and the pyridine of dimethyl base, and by hydramine, as the positively charged ion of Monoethanolamine MEA BASF, diethanolamine and trolamine generation.Preferably R3 is C ₁₀-C ₁₆Alkyl, R ⁴Be methyl, ethyl or sec.-propyl.Particularly preferably be sulfonic acid methyl ester salt, wherein R ³Be C ₁₄-C ₁₆Alkyl.

Alkyl sulfate surfactant is the another kind of important anion surfactant of the present invention that can be used for.Except having good comprehensive cleaning capacity when being used in combination with polyhydroxy fatty acid amide (vide infra), temperature, wash concentration and the washing time that is included in various scopes provides the effect of good cleaning fat/oil, also can obtain the dissolving of alkyl-sulphate, and the improved preparation ability in liquid washing agent, refer to the water-soluble salt or the acid of following general formula: ROSO ₃M, wherein R C preferably ₁₀-C ₂₄Alkyl preferably has C ₁₀-C ₂₀The alkyl of moieties or hydroxyalkyl, more preferably C ₁₂-C ₁₈Alkyl or hydroxyalkyl, M is H or positively charged ion, as alkali metal cation (as sodium, potassium, lithium), replace or unsubstituted ammonium cation, as methyl, dimethyl-and trimethyl ammonium and quaternary ammonium cation, as tetramethyl-ammonium and lupetidine with by alkanolamine, as the positively charged ion of generations such as thanomin, diethanolamine, trolamine and their mixture, or the like.Usually, C _12-16The preferably lower wash temperature (as being lower than about 50 ℃) of alkyl chain, C ₁₆-C ₁₈The preferred higher wash temperature (as being higher than about 50 ℃) of alkyl chain.

Alkyl alkoxylated sulfate surfactant is another kind of effective anion surfactant.These tensio-active agents are that general formula is generally RO (A) _mSO ₃The water-soluble salt of M or acid, the R in the general formula is unsubstituted C ₁₀-C ₂₄Alkyl or contain C ₁₀-C ₂₄The hydroxyalkyl of moieties, preferred C ₁₂-C ₂₀Alkyl or hydroxyalkyl, more preferably C ₁₂-C ₁₈Alkyl or hydroxyalkyl, A are oxyethyl group or propoxy-unit, and m is greater than zero, generally between about 0.5 to 6, more preferably from about between 0.5 to about 3, M is H or positively charged ion, and they can be the ammonium cations of metallic cation (as sodium, potassium, lithium, calcium, magnesium etc.), ammonium or replacement for example.The propenoxylated vitriol of the vitriol of alkyl ethoxylated and alkyl can be considered in the present invention.The object lesson of the ammonium cation that replaces comprise methyl-, dimethyl-, trimethylammonium-ammonium and quaternary ammonium cation, as tetramethyl-ammonium, lupetidine with by the alkanol ammonium, as the positively charged ion of Monoethanolamine MEA BASF, diethanolamine and trolamine generation, and their mixture.Representational tensio-active agent is C ₁₂-C ₁₈Alkyl gathers b-oxide (1.0) vitriol, C ₁₂-C ₁₈Alkyl gathers b-oxide (2.25) vitriol, C ₁₂-C ₁₈Alkyl gathers b-oxide (3.0) vitriol and C ₁₂-C ₁₈Alkyl polyethoxylated (4.0) vitriol, wherein M is selected from sodium and potassium usually.

Other anion surfactant that other anion surfactant-can be used for washs purpose also can be included in herein the composition.They comprise soap, C ₉-C ₂₀Wire alkylbenzene sulfonate, C ₈-C ₂₂Primary-or secondary sulfonated alkane, C ₈-C ₂₄Olefin sulfonate; the sulfonated poly carboxylic acid (as being documented in the English Patent 1082179) of the pyrolysis product preparation by the sulfonation alkaline earth metal citrate; alkyl glycerol sulfonate; the fatty acyl group glycerol sulfonate; fatty oil base glycerol vitriol; alkylphenol ethylene oxide ether sulfate; paraffin sulfonate; alkylphosphonic; isethionate (isothionates) is as acyl isethinate; the N-acyl taurine salt; the fatty acid amide of methyl tauryl amine (tauride); aminosuccinic acid alkyl ester and sulfosuccinic acid alkyl ester; sulfosuccinic acid monoesters (particularly saturated and undersaturated C ₁₂-C ₁₈One ester), the diester of sulfo-succinic acid (particularly saturated and undersaturated C ₆-C ₁₄Diester), the vitriol of N-acyl group musculamine hydrochlorate, alkyl polysaccharide, for example vitriol of alkylpolyglycosides (the not Sulfated compound of nonionic is described below), the primary alkyl sulphates of collateralization, alkyl polyethoxye carboxylate salt, for example general formula is RO (CH ₂CH ₂O) _kCH ₂COO ^-M ⁺, wherein R is C ₈-C ₂₂Alkyl, k are from 0 to 10 integers, and M is the salt-forming cation of solubility, with the ethylenehydrinsulfonic acid esterification and with the salt of sodium hydroxide neutral lipid acid (ammonium salt that for example comprises sodium salt, sylvite, ammonium salt and replacement, as one, two and triethanolamine salt).Resinous acid and hydrogenant resinous acid also are suitable for, for example rosin, staybelite and be present in the Yatall MA or resinous acid prepared therefrom and hydrogenant resinous acid.Other example provides in Surface Active Agents and Detergents (I of Schwartz, Perry and Berch and II volume).The tensio-active agent of these types is disclosed in US3929678 usually, and on December 30th, 1975, the 23rd hurdle of Laughlin etc., 58 row are to the 29th hurdle 23 row (its at this in conjunction with as a reference).

Nonionic detergent surfactant-suitable nonionic detergent tensio-active agent is disclosed in US3929678, Laughlin etc., and the 13rd hurdle the 14th row on December 30th, 1975 is to the 16th hurdle the 6th row, and it is in this combination as a reference.The effective nonionogenic tenside of representational indefiniteness is as follows.

The condenses of the polyethylene oxide of alkylphenol, polyoxytrimethylene and polyoxybutylene.Usually, polyethylene oxide condensation compound is preferred.These compounds comprise and contain about 6 to the alkylphenol of the alkyl of the straight chain of about 12 carbon atoms or collateralization chain configuration and the condensation product of alkylene oxide.In a preferred embodiment, ethylene oxide exists to equal every mole of alkylphenol about 5 amounts to about 25 moles of ethylene oxide.Industrial available this class ionic surfactant pack is drawn together Igepal  CO-630, is sold by GAF Corporation; With Triton  X-45, X-114, X-100 and X-102, all by Rohm ﹠amp; Hass Company provides.These compounds generally are meant alkylphenol alkoxylates (as the alkylphenol b-oxide).

Fatty Alcohol(C12-C14 and C12-C18) and about 1 condensation product to about 25 moles oxyethane.The alkyl chain of Fatty Alcohol(C12-C14 and C12-C18) can be the uncle or the secondary alcohol of straight chain or collateralization, and contains usually and have an appointment 8 to about 22 carbon atoms.Particularly preferably be to have to contain about 10 and arrive the condensation product of about 18 moles oxyethane to the alcohol of the alkyl of about 20 carbon atoms and every mol of alcohol about 2.The example of industrial this class nonionogenic tenside that provides comprises Tergitol  15-S-9 (C ₁₁-C ₁₅The condensation product of linear secondary alcohol and 9 moles of ethylene oxide), Tergitol  24-L-6NMW (C ₁₂-C ₁₄The condensation product of the narrow molecular weight distribution of primary alconol and 6 moles of ethylene oxide), they all are to be provided by Union Carbide Corporation; Neodol  45-9 (C ₁₄-C ₁₅The condensation product of linear alcohol and 9 moles of ethylene oxide), Neodol  23-6.5 (C ₁₂-C ₁₃The condensation product of linear alcohol and 6.5 moles of ethylene oxide), Neodol  45-7 (C ₁₄-C ₁₅The condensation product of linear alcohol and 7 moles of ethylene oxide), Neodol  45-4 (C ₁₄-C ₁₅The condensation product of linear alcohol and 4 moles of ethylene oxide), provide by Shell Chemical Company and Kyro  EOB (C ₁₃-C ₁₅The condensation product of linear alcohol and 9 moles of ethylene oxide), by The Procter ﹠amp; Gamble Company provides.This class nonionogenic tenside typically refers to " alkyl ethoxylates ".

The oxyethane that condensation reaction by propylene oxide and propylene glycol generates and the condensation product of hydrophobic alkali.The preferred molecular weight of the hydrophobic part of these compounds is about 1500 to about 1800, and water insoluble.On this hydrophobic part, add that polyoxyethylene partly has the water miscible trend that improves whole molecule, and the fluid characteristics of product remains on about 50% the degree of polyoxyethylene content in the condensation product gross weight, and this is equivalent to carry out condensation with about 40 moles of ethylene oxide at the most.Some industrial Pluronic  tensio-active agents that provide are provided the example of this compounds, are provided by BASF.

The condensation product of oxyethane and the product that generates by the reaction of propylene oxide and ethylene diamine.The hydrophobic part of these products comprises the reaction product of ethylene diamine and excessive oxidation propylene, and molecular weight is about 2500 to about 3000 usually.Hydrophobic part and ethylene oxide condensation to condensation product contains 40% polyoxyethylene to about 80% weight of having an appointment, and molecular weight is about 5000 to about 11000.Some industrial Tetronic  compounds that provide are provided the example of this class nonionogenic tenside, are provided by BASF.

Semi-polar nonionic surfactants is the special nonionogenic tenside of a class, comprise water-soluble amine oxides, it contains some and contains about 10 and be selected to contain to the moieties of about 18 carbon atoms and 2 and have an appointment 1 to the alkyl of about 3 carbon atoms and the part of hydroxyalkyl; The water soluble oxidized phosphine contains some and contains about 10 and be selected to contain to the moieties of about 18 carbon atoms and 2 and have an appointment 1 to the alkyl of about 3 carbon atoms and the part of hydroxyalkyl; With water-soluble sulfoxide, contain some and contain about 10 and be selected to the moieties of about 18 carbon atoms and 2 and contain 1 alkyl and the hydroxyalkyl part of having an appointment to about 3 carbon atoms.

Semi-polarity nonionic detergent tensio-active agent comprises the amine oxide surfactant with following general formula: R wherein ³Be to contain to have an appointment 8 to alkyl, hydroxyalkyl or the alkyl phenyl of about 22 carbon atoms or their mixture; R ⁴Be to contain 2 alkylidene group or hydroxy alkylidene or their mixtures of having an appointment to about 3 carbon atoms; X is 0 to about 3; R ⁵Be to contain to have an appointment 1 to the alkyl or the hydroxyalkyl of about 3 carbon atoms or contain the polyethylene oxide group of 1 to about 3 the ethylene oxide group of having an appointment.R ⁵Group can interconnect, as forming a ring structure by Sauerstoffatom or nitrogen-atoms.

These amine oxide surfactants can be particularly including C ₁₀-C ₁₈Alkyl dimethyl amine oxide and C ₈-C ₁₂Alkoxyethyl dihydroxy ethyl amine oxide.

Alkyl polysaccharide, be disclosed in U84565647, Llenado, in 21 days January in 1986, it has and contains about 6 to about 30 carbon atoms, preferred about 10 hydrophobic groups to about 16 carbon atoms, and glycan, as the glycan glycosides, contain and have an appointment 1.3 to about 10, preferred about 1.3 to about 3, most preferably from about 1.3 hydrophilic radicals to about 2.7 sugar units.Can adopt any reducing sugar that contains 5 or 6 carbon atoms, as glucose, semi-lactosi, and the melampyrum base section can replace glucosyl part (randomly hydrophobic group is connected positions such as 2-, 3-, 4-, thereby generation glucose or the semi-lactosi different with glucoside or galactoside).In sugared key can be for example between 2-, 3-, 4-and/or the 6-position of position of additional sugar unit and previous sugar unit.

Randomly and be that the polyalkyleneimine chain that connects hydrophobic part and glycan part can be arranged with not too wishing.Preferred alkylene oxide is an oxyethane.Hydrophobic grouping generally comprises alkyl, saturated or undersaturated, collateralization or collateralization not, contain and have an appointment 8 to about 18, preferred about 10 to about 16 carbon atoms.Preferably alkyl is the saturated alkyl of straight chain.Alkyl can contain about at the most 3 hydroxyls and/or polyalkyleneimine chain and can contain approximately at the most 10, preferably is less than 5 alkylene oxide parts.Suitable alkyl polysaccharide be octyl group, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl and octadecyl, two-, three-, four-, five-and six glucosides, galactoside, lactoside, glucose, fructoside, fructose and/or semi-lactosi.Suitable mixture comprise coconut alkyl, two-, three-, four-and five glucosides and tallow alkyl four-, five-and six glucosides.

The general formula of preferred alkyl poly glucoside is:

R ²O (C _nH _2nO) _t(glucosyl) _x

R wherein ²Be selected from alkyl, alkyl phenyl, hydroxyalkyl, hydroxyalkyl phenyl and their mixture, wherein alkyl contains and has an appointment 10 to about 18, and preferred about 12 to about 14 carbon atoms; N is 2 or 3, preferred 2; T is 0 to about 10, preferred 0; X is about 1.3 to about 10, and preferred about 1.3 to about 3, most preferably from about 1.3 to about 2.7.This glucosyl is preferably generated by glucose.In order to prepare these compounds, at first generate alcohol or alkyl polyethoxye alcohol, the raw material reaction with glucose or glucose generates glucoside (being connected the 1-position) again.Following additional glucosyl unit and can be connected their the 1-position and glucosyl unit 2-, 3-, 4-and/or the 6-position of front, preferably mainly is the 2-position.

Fatty acid amide surfactant with following general formula:

R wherein ⁶Be to contain 7 the alkyl of having an appointment to the individual carbon atom in about 21 (preferred about 9 to about 17), and each R ⁷Be selected from hydrogen, C ₁-C ₄Alkyl, C ₁-C ₄Hydroxyalkyl and-(C ₂H ₄O) _xH, wherein x is about 1 to about 3.

Preferred amide is C ₈-C ₂₀Glutamine, a glycollic amide, diglycollic amide and isopropanol amide.

Cats product-cationic detersive tensio-active agent also can join in the composition of the present invention.Cats product comprises ammonium surfactant, as the alkyl dimethyl ammonium halide with have the tensio-active agent of following general formula:

[R ²(OR ³) _y][R ⁴(OR ³) _y] ₂R ⁵N ⁺X ^-

R wherein ²Be on alkyl chain, to contain 8 alkyl or the alkyl benzyls of having an appointment, R to about 18 carbon atoms ³Be selected from-CH ₂CH ₂-,-CH ₂CH (CH ₃)-,-CH ₂CH (CH ₂OH)-,-CH ₂CH ₂CH ₂-and their mixture; R ⁴Be selected from C ₁-C ₄Alkyl, C ₁-C ₄Hydroxyalkyl, benzyl, by connecting two R ⁴Group formation ring structure ,-CH ₂CHOHCHOHCOR ⁶CHOH-CH ₂OH, wherein R ⁶Be hexose or molecular weight less than about 1000 hexose polymkeric substance and the hydrogen when y is not 0; R ⁵With R ⁴Identical or alkyl chain, wherein R ²Add R ⁵The sum of carbon atom be not more than about 18; Y is 0 to about 10, and ading up to of y value 0 arrived approximately 15, and x is any compatible negatively charged ion.

Other can be used for cats product of the present invention and also is documented in US4228044, Cambre, and on October 14th, 1980, it is in this combination as a reference.

Can add amphoterics in other tensio-active agent-detergent composition of the present invention.These tensio-active agents generally are described as the aliphatic derivatives of secondary amine or tertiary amine, the perhaps aliphatic derivatives of heterocyclic secondary or tertiary amine, and wherein the fat base can be straight chain or side chain.An aliphatic substituting group contains at least about 8 carbon atoms, is generally 8 to about 18 carbon atoms, and at least one contains the anionic water-soluble group, as carboxylate radical, sulfonate radical, sulfate radical.Referring to US3929678, laughlin etc., the 19th hurdle on December 30th, 1975,18-35 is capable, exemplifies amphoterics.

In detergent composition of the present invention, also can add zwitterionics.These tensio-active agents generally are described as the derivative of derivative, heterocyclic secondary and tertiary amine of secondary amine and tertiary amine or quaternary ammonium, season phosphine or uncle's sulfonium compound derivative.Referring to US3929678, laughlin etc., the 19th hurdle 38 row on December 30th, 1975 exemplify zwitterionics to the 22nd hurdle 48 row.Both sexes and zwitterionics can be used in combination with one or several negatively charged ion and/or nonionogenic tenside usually.

Polyhydroxy fatty acid amide surfactant-liquid detergent composition of the present invention also can contain the heavy polyhydroxy fatty acid amide surfactant of enhancing enzyme." enhancing enzyme " is meant that the formulator of composition can select to join the amount of the polyhydroxy fatty acid amide in the composition, and it can improve the enzyme cleaning effect of detergent composition.Usually, for the general quantity of enzyme, the polyhydroxy fatty acid amide that adds about 1% weight can improve the usefulness of enzyme.

Detergent composition of the present invention will contain the polyhydroxy fatty acid amide surfactant of 1% weight of having an appointment, preferred about 3% to about 30% polyhydroxy fatty acid amide.The polyhydroxy fatty acid amide surfactant component contains the compound with following general structure: R wherein ¹Be H, C ₁-C ₄Alkyl, 2-hydroxyethyl, 2-hydroxypropyl or their mixture, preferred C ₁-C ₄Alkyl, more preferably C ₁Perhaps C ₂Alkyl, most preferably C ₁Alkyl (being methyl); And R ²Be C ₅-C ₃₁Alkyl, preferred straight chain C ₇-C ₁₉Alkyl or alkenyl, more preferably straight chain C ₉-C ₁₇Alkyl or alkenyl, most preferably straight chain C ₁₁-C ₁₅Alkyl or alkenyl or their mixture; Z is a polyhydroxy alkyl, and it contains and has at least 3 linear hydrocarbyl chains that directly are connected the hydroxyl on the chain, perhaps oxyalkylated derivative (preferred ethoxylation or propenoxylated).Z is preferably prepared in reductive amination process by reducing sugar; More preferably Z is sugar alcohol base section (glycityl).Suitable reducing sugar comprises glucose, fructose, maltose, lactose, semi-lactosi, seminose and wood sugar.Can adopt high dextrose maize treacle, high sinistrose maize treacle and high malt sugar maize treacle as raw material, the same with each sugar of listing above.These maize treacle can generate the mixture of the sugar component that is used for Z.Can think that this never means other proper raw material of eliminating.Z more preferably is selected from-CH ₂(CHOH) _nCH ₂OH ,-CH (CH ₂OH) (CHOH) _N-1CH ₂OH ,-CH ₂(CHOH) ₂-(CHOR ') (CHOH)-CH ₂OH and its oxyalkylated derivative, n is from 3 to 5 integer, comprises 3 and 5, R ' is hydrogen or ring-type or fatty monose.Sugar alcohol base most preferably, wherein n is 4, particularly-CH ₂-(CHOH) ₄-CH ₂OH.

R ' can be for example N-methyl, N-ethyl, N-propyl group, N-sec.-propyl, N-butyl, N-2-hydroxyethyl or N-2-hydroxypropyl.

R ²-CO-N＜can be is coconut monoethanolamide, stearylamide, oleylamide, laurylamide, myristic amide, decyl amide, palmitic amide, tallow acid amides etc. for example.

Z can be 1-deoxidation glucityl, 2-deoxidation fructityl, 1-deoxidation maltityl, 1-deoxidation lactityl, 1-deoxidation galactityl, 1-deoxidation mannityl, 1-deoxidation maltotriotityl or the like.

The method for preparing polyhydroxy fatty acid amide is known in the art.Usually, they can react in reductive amination process by alkylamine and reducing sugar and generate the corresponding N-alkyl polyhydroxy amine, make N-alkyl polyhydroxy amine and fatty aliphatic ester or triglyceride level form N-alkyl, N-polyhydroxy fatty acid amide product in condensation reaction/amination step reaction again.Be used to prepare the method for compositions that contains polyhydroxy fatty acid amide and be disclosed in for example GB809060, February 18 nineteen fifty-nine, Thomas Hedley; Co.Ltd., US2965576, December 20 nineteen sixty, E.R.Wilson and US2703798, Anthony M.Schwartz, March 8 nineteen fifty-five and US1985424, on December 25th, 1934, Piggott, they are all in this combination as a reference.

Second kind of enzyme-preferred composition of the present invention further contains the second kind of compatible enzyme of washing composition that improves performance." washing composition is compatible " is meant other component with liquid detergent composition, and be compatible as detergent surfactant and detergent builder.These second kind of enzyme is preferably selected from lipase, amylase, cellulase and their mixture.Term " second kind of enzyme " does not comprise top disclosed proteolytic ferment, and each composition that contains second kind of enzyme contains at least two kinds of enzymes like this, comprises at least a proteolytic ferment.The amount that is used in second kind of enzyme in the composition can change according to the type of enzyme.Usually the preferable amount of these second kind of enzyme is about 0.0001 to 0.3, more preferably 0.001 to 0.1 weight %.Can adopt mixture (as lipase) or two kinds or more of (as the cellulase and the lipase) of the enzyme of same kind.Can adopt the purification body or the non-purification body of enzyme.

Any fat hydrolase of liquid detergent composition that is applicable to all can be used for these compositions.Be applicable to that lipase of the present invention comprises bacterium or originated from fungus.

Suitable bacterium lipase comprises by Pseudomonas group, those that generate as Pseudomonasstutzeri ATCC19.154 microorganism, as be disclosed in the English Patent 1372034, its at this in conjunction with as a reference.Suitable lipase comprises those that can carry out positive immunological cross-reaction with the antibody of the lipase that is generated by microorganism Pseudomonasfluorescens IAM1057.This lipase and its method for purifying are documented in Japanese patent application 53-20487, are disclosed on February 24th, 1978.This lipase can be by Amano PharmaceuticalCo.Ltd., and Nagoya, Japan are meant that at this " Amano-P " provides with trade(brand)name Lipase P " Amano ".This quasi-lipase can adopt with Amano-P antibody and carry out positive immunological cross-reaction according to standard and the known immunodiffusion(ID) step of Ouchterlony (Acta.Med.Scan., 133,76-79 (1950)).These lipase and they are documented in US4707291 with the method that Amano-P carries out immunological cross-reaction, Thom etc., and in 17 days November in 1987, it is in this combination as a reference.Representational example is an Amano-P lipase, by the lipase of Pseudomonas fragi FERM P1339 (Amano-B provides with trade(brand)name) generation, by the lipase of Pseudomonas nitroreducens var.lipolyticum FERM P1338 (Amano-CES provides with trade(brand)name) generation, by Chromobacter viscosum, lipase as Chromobacter viscosum var.lipolyticum NRRLB3673 generation, industrial by Toyo Jozo Co.Tagata, Japan provides; With by US BiochemicalCorp., USA and Disoynth Co., Chromobacterviscosum lipase that The Netherlands provides and the lipase that provides by Pseudomonas gladioli.

Suitable fungal lipase comprises can be by those of Humicola lanuginosa and Thermomyceslanuginosus preparation.Most preferably be from the gene of Humicolalanuginosa and the lipase that obtains with Aspergillus oryzae expressing gene by the clone, (Novo Industri A/S) puts down in writing as european patent application 0258068, provided industrial with trade(brand)name Lipalse  by NovoNordisk A/S.

In these compositions, can adopt every gram lipase about 10 to 18000, preferred about 60 to 6000 lipase unit (LU/ gram).Lipase unit is the amount that per minute generates the lipase of the titratable lipid acid of 1 mmole under the stable situation of pH, wherein pH is 9.0, temperature is 30 ℃, matrix is the emulsion of the sweet oil and 3.3% Sudan Gum-arabic of 3.3% weight, has 13 mmoles/rise Ca in the Tutofusin tris buffered soln at 5 mmoles/rise ⁺⁺And 20 mmole/rise NaCl.

Any cellulase of liquid detergent composition that is applicable to all can be used in these compositions.Be applicable to that cellulase of the present invention comprises from those of bacterium and fungic origin.Preferably their best pH scope is 5 to 9.5.Can adopt the cellulase of about 0.0001 to 0.1 weight %.

Suitable cellulase is disclosed in US4435307, Barbesgaard etc., and on March 6th, 1984, in conjunction with as a reference, it discloses the fungal cellulase that is generated by Humicola insolens at this for it.Suitable cellulase also is disclosed in GB-A-2075028, among GB-A-2095275 and the DE-OS-2247832.

The example of the plain enzyme of this fibrid is by Humicola insolens (Humicola griseavar.thermoidea), the cellulase that generates of Humicola kind DSM1800 particularly, cellulase 212 that generates with the cellulase that generates by the fungi of Bacillus N or by the fungi that belongs to gene A eromonas and the cellulase that extracts by the liver pancreas of sea mollusk (Dolabella AuriculaSolander).

Anyly be applicable to that the amylase in the liquid detergent composition all can be used in these compositions.Amylase comprises, the amylase that generates by the special kind of B.licheniformis for example, and this is documented in the English Patent 1296839 (Novo) in more detail.Starch protolysate comprises for example Rapidase ^R/ Inernational Bio-Synthetics, Inc. and Termamyl ^RNovoIndustries.

Can adopt about 0.0001% to 0.55, the amylase of preferred 0.0005 to 0.1 weight %.

Optional components-detergent builder can randomly be included in the composition of the present invention.0 detergent builder to about 50% weight can be used for this.Can adopt inorganic assistant agent and organic additive.When containing auxiliary agent, composition contains the auxiliary agent at least about 1% usually, and can be inorganic assistant agent or organic additive.The liquid laundry preparation preferably contains has an appointment 3% to 30%, more preferably from about the detergent builder of 5 to 20% weight.

Inorganic assistant agent includes, but are not limited to basic metal, ammonium salt and the alkanol ammonium salts of polyphosphoric acid (tri-polyphosphate, pyrophosphate salt and vitreous state polymer metaphosphate typically), phosphonate, phytate, silicate, carbonate (comprising supercarbonate and sesquicarbonate), vitriol and silico-aluminate.Also can adopt the borate auxiliary agent and contain the auxiliary agent (being referred to as " borate auxiliary agent " herein) that can under washing composition storage or wash conditions, form boratory material.Adopt non-borate auxiliary agent in the composition preferably of the present invention,, particularly be lower than under about 40 ℃ wash conditions and use so that be lower than about 50 ℃.

The example of silicate auxiliary agent is an alkalimetal silicate, particularly SiO ₂: Na ₂The ratio of O those in 1.6: 1 to 3.2: 1 scope, and layered silicate for example are documented in US4664839, on May 12nd, 1987, the layered silicate among the H.P.Rieck, the document at this in conjunction with as a reference.But other silicate also is effectively, Magnesium Silicate q-agent for example, and it is used as crisp dose in granular preparation, as the stablizer of oxygen bleaching agent with as the component of froth suppressor system.

The example of carbonate auxiliary agent is alkaline-earth metal and alkali-metal carbonate, the mixture that comprises yellow soda ash and concentrated crystal soda and they and calcium carbonate superfine powder, this is disclosed in German patent application in 15,2321001,1973 on November, and it is disclosed in this combination as a reference.

The silico-aluminate auxiliary agent also is effective in the present invention.The silico-aluminate auxiliary agent is very important in the most normal commercially available heavy duty type granular detergent composition, and also is important adjuvant component in liquid detergent preparation.The silico-aluminate auxiliary agent comprises those with following chemical general formula:

M _z(zAlO ₂.ySiO ₂)

Wherein M is the ammonium of sodium, potassium, ammonium or replacement, and z is from about 0.5 to about 2, and y is 1; This material has the anhydrous silico-aluminate of every at least gram about 50 millinormal CaCO ₃The magnesium ion exchange capacity of hardness.Preferred aluminium-silicate is the zeolite builder with following general formula

Na _z[(AlO ₂) _z(SiO ₂) _y].xH ₂O

Wherein z and y are at least 6 integer, and the molar ratio of z and y is 1.0 in about 0.5 scope, and x is from about 15 to about 264 integer.

Effectively the silico-aluminate ion exchange material is industrial available.These silico-aluminates can be crystal or amorphous structure, and can be the silico-aluminate or the synthetic of natural generation.A kind of method that generates the silico-aluminate ion exchange material is disclosed in US3985669, Krummel etc., and in 12 days October in 1976, it is in this combination as a reference.Can be used for preferred composite crystals silico-aluminate ion exchange material of the present invention can zeolite A, zeolite P (B) and the name of X zeolite provide.In an especially preferred embodiment, the crystalline silica-aluminate ion exchange material has following general formula:

Na ₁₂[(AlO ₂) ₁₂(SiO ₂) ₁₂].xH ₂O

Wherein x is about 20 to about 30, especially about 27.This material is known as zeolite A.Preferably the particle diameter of silico-aluminate is about 0.1 to 10 micron an of diameter.

The object lesson of poly-phosphate is an alkali metal tripolyphosphates, trisodium phosphate, potassium and ammonium, trisodium phosphate and potassium and ammonium, former sodium phosphate and potassium, extent of polymerization about 6 in about 21 scopes Sodium polymetaphosphate and the salt of phytinic acid.

The example of phosphate builder is water-soluble ethane 1-hydroxyl-1, the 1-diphosphate, particularly sodium salt and sylvite, the water-soluble salt of Medronate, as trisodium salt and tripotassium salt, with the water-soluble salt of the Medronate that replaces, as the trisodium salt and the tripotassium salt of ethylidene, isopropylidene benzyl methylene radical and halogen methylene radical phosphoric acid.The phosphate builder of the above-mentioned type is disclosed in US3159581 and on December 1st, 3213030,1964 and October 19 nineteen sixty-five, Diehl; US3422021, on January 14th, 1969, Roy; With US3400148 and 3422137, September 3 nineteen sixty-eight and on January 14th, 1969, Quimby saidly is disclosed in this in conjunction with as a reference.

The organic detergent auxiliary agent that is preferred for the object of the invention comprises various polycarboxylic acid salt compounds.As of the present invention, " polycarboxylate " be meant have a plurality of, the compound of preferred at least 3 carboxylate groups.

The polycarboxylate auxiliary agent not only can join with the form of acid in the composition usually, can also add with the form of neutralized salt, and when using with salt form, basic metal is preferred as the salt of sodium, potassium and lithium or alkanol ammonium.

The polycarboxylate auxiliary agent that is comprised is various types of active substances.The polycarboxylate auxiliary agent of an important kind comprises the ether polycarboxylate.Many ether polycarboxylates are openly as detergent builder.Effectively ether polycarboxylate's example comprises oxygen two succinates, is disclosed in Berg.US3128287, on April 7th, 1964 and Lamberti etc., US3635830, on January 18th, 1972, they all this in conjunction with as a reference.

The concrete ether polycarboxylate that one class can be used as auxiliary agent effectively in the present invention also comprises those with following general formula:

CH(A)(COOX)-CH(COOX)-O-CH(COOX)-CH(COOX)(B)

Wherein A is H or OH; B be H or-O-CH (COOX)-CH ₂(COOX); X is H or salt-forming cation.For example, if in above-mentioned general formula, A and B are H, and this compound is oxygen two Succinic Acid and its water-soluble salt so.If A is OH, B is H, and this compound is tartrate one Succinic Acid (TMS) and its water-soluble salt so.If A is H, B is-O-CH (COOX)-CH ₂(COOX), this compound is tartrate two Succinic Acid (TDS) and its soluble salt so.The mixture of these auxiliary agents is particularly preferred in the present invention.Particularly preferably be TMS and TDS with the weight ratio of TMS and TDS be about 97: 2 to 20: 80 mixture.These auxiliary agents are disclosed in US4663071, Bush etc., on May 5th, 1987.

Suitable ether polycarboxylate also comprises ring compound, particularly alicyclic compound, for example is documented in US3923679,3835163,4158635,4120874 and 4102903, and they are incorporated herein by reference all.

Other effective washing auxiliary detergent comprises the ether hydroxy-polycarboxylate with following structure:

HO-[C(R)(COOM)-C(R)(COOM)-O] _n-H

Wherein M is hydrogen or positively charged ion, and wherein the salt of Sheng Chenging is water miscible, the ammonium cation of preferred as alkali, ammonium or replacement, n is about 2 to about 15 (preferred n about 2 is to about 10, and more preferably n is about 2 to about 4 mean number), and each R is identical or different, and be selected from hydrogen, C _1-4Alkyl or C _1-4The alkyl that replaces (preferred R is a hydrogen).

Also have other ether polycarboxylate's auxiliary agent comprise maleic anhydride and ethylidene or vinyl methyl ether, 1,3,5-trihydroxybenzene-2,4, the multipolymer of 6-trisulfonic acid and carboxyl methyl oxygen Succinic Acid.

Organic polycarboxylate auxiliary agent also comprises the ammonium salt of basic metal, ammonium and the replacement of various poly-acetate.Example is the ammonium salt of sodium, potassium, lithium, ammonium and the replacement of ethylene diaminetetraacetic acid and nitrilotriacetic acid(NTA).

Also comprise polycarboxylate, as mellitic acid, Succinic Acid, oxygen two Succinic Acid, polymaleic acid, benzene 1,3,5-three acid and carboxyl methyl oxygen Succinic Acid and their soluble salt.

The Citrate trianion auxiliary agent is to the polycarboxylate auxiliary agent of heavy duty liquid detergent preparation particularly important as citric acid and its soluble salt (particularly sodium salt), also can be used in the particulate composition.

Other carboxylate salt auxiliary agent comprises the carbohydrate of carboxylate saltization, is disclosed in US3723322, Diehl, and on March 28th, 1973, it is incorporated herein by reference.

What also be applicable to detergent composition of the present invention is 3,3-dicarboxyl-4-oxa--1, and 6-adipate and relevant compound, they are disclosed in US4566984, Bush, on January 28th, 1986, it is incorporated herein by reference.Effectively the Succinic Acid auxiliary agent comprises C ₅-C ₂₀Dialkyl succinylsuccinate and its salt.The particularly preferred compound of this class is the dodecenyl succinic Succinic Acid.Dialkyl succinylsuccinate has general formula: R-CH (COOH) CH usually ₂(COOH), i.e. the derivative of Succinic Acid, wherein R is a hydrocarbon, as C ₁₀-C ₂₀Alkyl or alkenyl, preferred C ₁₂-C ₁₆Perhaps wherein R can be replaced by hydroxyl, sulfo group, sulfoxide or sulfone substituting group, and they all are documented in the above-mentioned patent.

The succinate auxiliary agent preferably uses with the form of their water-soluble salts, comprises sodium, potassium, ammonium and alkanol ammonium salts.

The concrete example of succinate auxiliary agent comprises: lauryl succinate, myristyl succinate, palmityl succinate, 2-dodecenyl succinic succinate (preferably), 2-15 carbene base succinates etc.The lauryl succinate is preferred auxiliary agent and is disclosed in european patent application 86200690.5/0200263, is disclosed on November 5th, 1986.

Effectively the example of auxiliary agent also comprises the sodium salt and the sylvite of the multipolymer of carboxyl methyl oxygen propanedioic acid, carboxyl methyl oxygen Succinic Acid, suitable-the hexanaphthene hexacarboxylic acid, suitable-the pentamethylene tetracarboxylic acid, water miscible polyacrylic acid (molecular weight also can be used as dispersion agent greater than about 2000 polyacrylic acid) and maleic anhydride and vinyl methyl ether or ethene.

Other suitable polycarboxylate is poly-acetal carboxylate salt, and it is disclosed in US4144226, Crutchfield etc., and on March 13rd, 1979, it is incorporated herein by reference.These polyacetal carboxylations can prepare by the ester of hydroxyl oxalic acid and initiators for polymerization are mixed under polymeric reaction condition.The poly-acetal carboxylate salt that then will generate is connected on the chemically stable end group stable poly-acetal carboxylicesters and makes quick depolymerization reaction does not take place in basic solution, is transformed into corresponding salt and joins in the tensio-active agent.

The polycarboxylate auxiliary agent also is disclosed in US3308067, Diehl, and on March 7th, 1967, it is incorporated herein by reference.This class material comprises aliphatic carboxylic acid, as the homogeneous of toxilic acid, itaconicacid and methylene radical propanedioic acid and the water-soluble salt of multipolymer.

Also can adopt other organic additive as known in the art.For example, can adopt monocarboxylic acid and its soluble salt that has long chain hydrocarbon groups.They comprise the material that is commonly referred to " soap ".The general C that adopts ₁₀-C ₂₀Chain length.Alkyl can be saturated or undersaturated.

Other optional component comprises stain remover, sequestrant, scale removal/anti-deposition agent, polymeric dispersion agent, SYNTHETIC OPTICAL WHITNER, whitening agent, suds suppressor, solvent and refiner again.

Detergent composition of the present invention can be mixed with various compositions, for example detergent for washing clothes and hard surface cleaner or dishwashing composition.

Composition of the present invention further describes by the following examples.The embodiment I

Following composition is by preparing with the listed component of listed mixed.In this embodiment, adopt peptide aldehyde below one or several:

Peptide aldehyde 1:CH ₃O-(O) C-Phe-Gly-Ala-LeuH

Peptide aldehyde 2:CH ₃N-(O) C-Phe-Gly-Ala-LeuH

Peptide aldehyde 3:CH ₃O-(O) C-Phe-Gly-Ala-PheH

Peptide aldehyde 4:CH ₃N-(O) C-Phe-Gly-Ala-PheH

Peptide aldehyde 5:CH ₃SO ₂Phe-Gly-Ala-Leu-H

Peptide aldehyde 6:CH ₃SO ₂Vai-Ala-Leu-H

Peptide aldehyde 7:C ₆H ₅CH ₂O (OH) is P-Val-Ala-Leu-H (O)

Peptide aldehyde 8:CH ₃CH ₂SO ₂-Phe-Gly-Ala-Leu-H

Peptide aldehyde 9:C ₆H ₅CH ₂SO ₂-Val-Ala-Leu-H

Peptide aldehyde 10:C ₆H ₅CH ₂O (OH) is P-Leu-Ala-Leu-H (O)

Peptide aldehyde 11:C ₆H ₅CH ₂O (OH) is P-Phe-Ala-Leu-H (O)

Peptide aldehyde 12:CH ₃O (OH) is P-Leu-Gly-Ala-Leu-H (O)

Composition	????A	????B	????C	????D	???E	???F
							LINER ALKYL BENZENE SULPHONIC ACID SOFT 96	????8.5	???15	???6.5	???10	??12.5	???4
???C 12015Sodium alkyl sulfate	????1	????2	???1	????2	??0	???0
							????C 14015The vitriol of the ethoxylation that alkyl is 2.5 times	????10	????5	???10.5	????0	??11	???9
??????C 12Glucamide	????0	????0	???9	????0	??0	???5

The C of 7 times of ethoxylations 12015Alcohol	????3	????10	????4	????7	???2.5	????0
							Lipid acid	????2	????5	????5	????4	????2	????2
Citric acid	????6	????7	????4	????6	????4	????5
							?C 12014The Succinic Acid that alkenyl replaces	????0	????6	????0	????5	????0	????6
Sodium hydroxide	????2	????6	????2	????4	????1	????1.5
							Ethanol	????2	????1.5	????2	????4	????2	????1.5
Monoethanolamine MEA BASF	????6	????5	????4	????0	????0	????0
							1,20 propylene glycol	????12	????10	????5	????5	????4	????6
Amylase (143KNU/ gram)	????0	????0	???0.1	????0	????0	????0.2
							Lipolase  (100KL U/ restrains industry solution)	????0.5	????0.2	???0.5	????0.5	????0.4	????0
Proteolytic enzyme B (34 grams per liter industry solution)	????0.9	????0	???0.5	????0	????1.2	????0
							Savinase  (industry solution)	????0	????0.3	???0	????0.4	????0.2	????0.3
????Carezyme	????0.5	????1	???0.8	????0	????0.2	????0.8
							Peptide aldehyde 1012	????0.009	????0.005	???0.001	????0.0005	????0.0013	????0.1
Boric acid	????0.25	????0.5	???0.75	????5	????2	????8
							Calcium ion (CaCl 2)	????0	????0	????0	????0	???0.01	????0
Water and micro substance	Equilibrate to 100%

Claims (10)

1. liquid detergent composition, contain:

A) account for the detergent surfactant of 1% to 95% weight of composition;

B) active protein hydrolase;

C) the boron composition of boracic acid source and polyvalent alcohol; With

D) have the peptide aldehyde of following general formula:

Z-B-NH-CH (R)-C (O) H wherein B is the peptide chain that contains 1 to 5 amino acid moiety; Z is the end capped part of N-, is selected from phosphoramidate [(R " O) ₂(O) P-], sulfinyl amine [(SR ") ₂-], sulphonamide [(R " (O) ₂S-], sulfonic acid [SO ₃H], phosphonic amide [(R ") ₂(O) P-], sulfonamide [R " O (O) ₂S-], thiocarbamide [(R ") ₂N (O) C-], thiocarbamate [R " O (S) C-], phosphonic acid ester [R "-P (O) OH], amidophosphoric acid ester [R " O (OH) (O) P-], carbamate (R " O (O) C-) and urea [R " NH (O) C-], wherein each R " be selected from the C of straight chain or collateralization respectively ₁-C ₆Unsubstituted alkyl, phenyl, C ₇-C ₉Alkylaryl and cycloalkyl moiety, wherein cycloalkyl ring can be C ₄-C ₈, and contain the heteroatoms that one or several are selected from O, N and S; And R is selected from the C of straight chain or collateralization ₁-C ₆Unsubstituted alkyl, phenyl and C ₇-C ₉The alkylaryl part.

2. the liquid detergent composition of claim 1, wherein R partly be selected from methyl, sec.-propyl, sec-butyl, isobutyl-,-C ₆H ₅,-CH ₂-C ₆H ₅With-CH ₂CH ₂-C ₆H ₅

3. the liquid detergent composition of claim 2, wherein said B peptide chain is selected from the peptide chain of the aminoacid sequence with following general formula:

Z-A ⁵-A ⁴-A ³-A ²-A ¹-NH-CH(R)-C(O)H

Make that when having amino acid they are following amino acid:

A ¹Be selected from Ala, Gly;

A ²Be selected from Val, Ala, Gly, Ile if exist;

A ³Be selected from Phe, Leu, Val, Ile if exist;

A ⁴If existing is any amino acid;

A ⁵If existing is any amino acid.

4. the liquid detergent composition of claim 3, wherein N-is terminal protects with a N-end-blocking part blocking group that is selected from carbamate, urea, sulphonamide, phosphonic amide, thiocarbamide, sulfinyl amine, sulfonic acid, phosphoramide, thiocarbamate, amidophosphoric acid ester and phosphonic amide.

5. the liquid detergent composition of claim 4, wherein the N-end of said proteinase inhibitor is by methyl, ethyl or benzylamino manthanoate [CH ₃O-(O) C-; CH ₃CH ₂O-(O) C-or C ₆H ₅CH ₂O-(O) C-], methyl, ethyl or benzylurea [CH ₃NH-(O) C-; CH ₃CH ₂NH-(O) C-or C ₆H ₅CH ₂NH-(O) C-], methyl, ethyl or benzyl sulphonamide [CH ₃SO ₂-; CH ₃CH ₂SO ₂-or C ₆H ₅CH ₂SO ₂-] and methyl, ethyl or benzyl amidophosphoric acid ester [CH ₃O (OH) is P-(O); CH ₃CH ₂O (OH) is P-or C (O) ₆H ₅CH ₂O (OH) is P-(O)] radical protection.

6. the liquid detergent composition of claim 1, wherein said peptide aldehyde is selected from: CH ₃SO ₂Phe-Gly-Ala-Leu-H, CH ₃SO ₂Val-Ala-Leu-H, C ₆H ₅CH ₂O (OH) is P-Val-Ala-Leu-H, CH (O) ₃CH ₂SO ₂Phe-Gly-Ala-Leu-H, C ₆H ₅CH ₂SO ₂-Val-Ala-Leu-H, C ₆H ₅CH ₂O (OH) is P-Leu-Ala-Leu-H, C (O) ₆H ₅CH ₂O (OH) is P-Phe-Ala-Leu-H and CH (O) ₃O (OH) is P-Leu-Gly-Ala-Leu-H (O).

7. the liquid detergent composition of claim 1, wherein the boron composition contains boric acid or is selected from the boric acid of boron oxide compound, borax, other alkali metal borate, replacement and the source of boric acid of their mixture; And polyvalent alcohol is a glycol.

8. the liquid detergent composition of claim 1 further contains the calcium ion source of significant quantity.

9. the liquid detergent composition of claim 8 contains:

A) 8% to 70% said detergent surfactant;

B) 0.001% to 5% active protein hydrolase;

C) described boron composition contains the boric acid of 0.25% to 10% weight or can produce the compound of boric acid and account for the polyvalent alcohol of said composition weight 1% to 15% in said composition;

D) 0.00001% to 5% said peptide aldehyde; With

E) 0.01% to 1% calcium ion.

10. the liquid detergent composition of claim 1 further contains one or more following enzymes of significant quantity: lipase, amylase, cellulase and their mixture.