CA2265879A1 - Liquid detergents containing proteolytic enzyme and protease inhibitors - Google Patents

Abstract

Aqueous liquid detergent compositions are described which comprise a proteolytic enzyme wherein the proteolytic activity is reversibly inhibited by a protease inhibitor selected from the group consisting of aldehydes and trifluoromethyl ketones.

Description

CA 02265879 l999-03- 11W0 98/ 13458 PCT/US97/166211LIQUID DETERGENTS CONTAINING PROTEOLYTICENZYME AND PROTEASE INHIBITORS51 O1520253035TECHNICAL FIELDThis invention relates to liquid detergent compositions containing enzymes.More specifically, this invention pertains to liquid detergent compositionscontaining a detersive surfactant, a proteolytic enzyme, and a protease inhibitorselected from the group consisting of aldehydes and trifluromethyl ketones.BACKGROUND OF THE INVENTIONProtease-containing liquid aqueous detergents are well-known, especially inthe context of laundry washing. A commonly encountered problem in suchprotease-containing liquid aqueous detergents is the degradation phenomenon by theproteolytic enzyme of second enzymes in the composition, such as amylase, lipase,and cellulase, or on the protease itself. As a result, the stability of the secondenzyme or the protease itself in the detergent composition is affected and thedetergent composition consequently performs less well.In response to this problem, it has been proposed to use various proteaseinhibitors or stabilizers. For instance, various references have proposed the use ofthe following compounds to aid in the stabilization of enzymes: benzamidinehydrochloride, lower aliphatic alcohols or carboxylic acids, mixtures of a polyol anda boron compound, aromatic borate esters, and calcium, particularly calciumformate. Recently, it was discovered that certain peptide aldehydes andtrifluromethyl ketones act to stabilize protease enzyme.Although these compounds have been used to varying success in liquiddetergents, they are not free of problems. For example certain peptide aldehydes canbe rather expensive and create complexities for the formulators, especially for liquiddetergents. Other inhibitors such as calcium. and boric acids are less expensive butdo not stabilize enzymes as well as peptide aldehydes. It is thus an object of thepresent invention to provide a protease inhibitor which is economical, effective andsuitable for use in a liquid detergent composition.W0 98/13458101520253035CA 02265879 l999-03- llPCT/US97/16621BACKGROUND ARTIt has been proposed to use various protease inhibitors or stabilizers. Forinstance, US 4,566,985 proposes to use benzamidine hydrochloride; EP 376 705proposes to use lower aliphatic alcohols or carboxylic acids; EP 381 262 proposes touse a mixture of a polyol and a boron compound; and EP9l 870072.5 proposes to usearomatic borate esters. See also U.S. Pat. No. 5,030,378 issued July 9, 1991. Alsosee US4,26l,868; US4,404,1 15; US4,3l8,8l8; and EP130,756.The use of peptide derivatives for the inhibition of proteins appears to havebeen disclosed in therapeutic applications. EP 293 881 discloses the use of peptideboronic acids as inhibitors of trypsin-like serine proteases. EP 185 390 and US4,399,065 disclose the use of certain peptide aldehydes derivatives for the inhibitionof blood coagulation. J 90029670 discloses the use of optically active alpha aminoaldehydes for the inhibition of enzymes in general. See also "Inhibition ofThrombin and Trypsin by Tripeptide Aldehydes", Int. J. Peptide Protein Res., Vol12 (1978), pp. 217-221; Gaal, Bacsy & Rappay, and "Tripeptide Aldehyde Protease-Inhibitors May Depress in Vitro Prolactin and Growth Hormone Release"Endocrinology, Vol. 116, No. 4 (1985), pp. 1426-1432; Rappay, Makara, Bajusz &Nagy. Certain peptide aldehydes have also been disclosed in EP—A-473 502 forinhibiting protease-mediated skin irritation.In particular see EP185,390, WO94/04651, published 3 March 1994,W094/04652, published 3 March 1994, EP 583,536, published February 23, 1994,EP 583,535, published February 3, 1994, EP 583,534, published February 23, 1994,WO 93/13125, published July 8, 1993, US4,529,525, US4,537,706, US4,537,707,and US5,527,487.SUMMARY OF THE INVENTIONThe invention herein is a liquid detergent composition comprising:a) an effective amount of a detersive surfactant;b) an active proteolytic enzyme; and ic) a protease inhibitor having the formula:Z-A-NH-CH(R)-C(O)-Xwherein A is an amino acid moiety; X is hydrogen or CF3; Z is an N-cappingmoiety selected from the group consisting of carbamates, ureas, sulfonamides,phosphonamides,thioureas, sulfenamides, sulfonic acids, phosphinamides,thiocarbamates, arnidophosphates, sulfamoyl derivatives, and phosphonamides; andR is selected from the group consisting of straight or branched C1 - C5 unsubstitutedW0 98l13458101520253035CA 02265879 l999-03- llPCT/US97/16621alkyl, phenyl, and C7 - C9 alkylaryl moieties. Preferred compositions furthercomprise a source of calcium ion or boric acid.Preferably, the liquid detergent compositions herein comprise, by weight ofcomposition:a) from about 1 to about 95%, preferably from about 8% to about 70%, of saiddetersive surfactant;b) from about 0.0001% to about 5%, preferably from about 0.0003% to about0.1%, of an active proteolytic enzyme;c) from about 0.00001% to about 5%, preferably from about 0.0001% to about1%, more preferably from about 0.0006% to about 0.5%, of the described proteaseinhibitor;d) optionally, from about 0.01% to about 1%, preferably from about 0.05% toabout 0.5%, of calcium ion; ande) optionally, from about 0.25% to about 10%, preferably from about 0.5% toabout 5%, of boric acid or a compound capable of forming boric acid, preferablywith a diol.The proteolytic enzyme useful herein is preferably a subtilisin-type proteaseand may be selected from the group consisting of Alcalase®, Subtilisin BPN',Protease A, Protease B, and mixtures thereof.The source of calcium ion for use herein is preferably selected from calciumformate, calcium xylene sulfonate, calcium chloride, calcium acetate, calciumsulfate. and mixtures thereof.The dishcare compositions herein may contain further detersive adjuncts,including but not limited to, one or more of the following: suds boosters, chelants,polyacrylate polymers, dispersing agents, dyes, perfumes, processing aids, andmixtures thereof. Moreover for dishcare compositions, the liquid detergentcompositions may further comprise an effective amount of amylase enzyme.Additionally, the dishcare compositions may optionally comprise an effectiveamount of a source of boric acid and a diol. Typically dishcare compositions willoptionally, but preferably, comprise from about 0.25% to about 10%, preferablyfrom about 0.5% to about 5%, more preferably from about 0.75% to about 3%, byweight of boric acid or a compound capable of forming boric acid and a diol, e.g.1 ,2-propaneidiol.In a preferred embodiment for heavy duty detergent compositions useful inlaundry care, the liquid detergent composition further comprises an effective amountone or more of the following enzymes: lipase, amylase, cellulase, and mixturesthereof. Preferably for laundry compositions, the second enzyme is lipase and isW0 98/ 13458101520253035CA 02265879 l999-03- llPCT/US97/ 1662 1obtained by cloning the gene from Humicola Lanuginosa and expressing the gene inAspergillus Ogzae. Lipase is utilized in an amount of from about 10 to about18000 lipase units per gram, preferably from about from about 60 to about 6000units per gram.In another preferred composition useful for laundry care, the second enzyme isa cellulase derived from Humicola Insolens and is utilized in an amount of fromabout 0.0001% to about 0.1% by weight of the total composition of said cellulase.The compositions herein may contain further detersive adjuncts, including butnot limited to, one or more of the following: suds boosters, builders, soil releasepolymers, polyacrylate polymers, dispersing agents, dye transfer inhibitors, dyes,perfumes, processing aids, brighteners, and mixtures thereof. Additionally, forlaundrycare compositions, the detersive surfactant is typically present in an amountof from about 10% to about 70%, by weight of total composition. Moreover, thelaundry compositions may optionally comprise an effective amount of a source ofboric acid and a diol. Typically laundry compositions will optionally, butpreferably, comprise from about 0.25% to about 10%, preferably from about 0.5% toabout 5%, more preferably from about 0.75% to about 3%, by weight of boric acidor a compound capable of forming boric acid and a diol, e.g. 1,2-propaneidiol.All percentages and proportions herein are by weight, and all references citedare hereby incorporated by reference, unless otherwise specifically indicated.DETAILED DESCRIPTION OF THE INVENTIONDefinitions - The present detergent compositions comprise an "effectiveamount" or a "stain removal-improving amount" of individual components definedherein. An "effective amount" or "stain removal-improving amount" is any amountcapable of measurably improving soil cleaning or stain removal from a substrate,i.e., soiled fabric or soiled dishware, when it is washed by the consumer. In general,this amount may vary quite widely.The liquid aqueous detergent compositions according to the present inventioncomprise three essential ingredients: (A) a protease inhibitor selected from the groupconsisting of aldehydes and trifluromethyl ketones, or a mixture thereof, asdescribed herein, (B) a proteolytic enzyme or a mixture thereof, and (C) a detersivesurfactant. The compositions according to the present invention preferably furthercomprise (D) a source of calcium ions, (E) a detergent-compatible second enzyme ora mixture thereof, (F) boric acid and a diol, and may further comprise (G) otheroptional ingredients.Protease Inhibitors - The detergent compositions according to the presentinvention comprise, as a first essential ingredient, a protease inhibitor selected fromWO 98/13458101520253035CA 02265879 l999-03- llPCT/US97/16621the group consisting of aldehydes and trifluromethyl ketones, or mixtures thereof,having the formula:Z-A-NH-CH(R)-C(O)-Xwherein A is an amino acid moiety (preferred A moieties are selected from thegroup consisting of Ala, Gly, Val, Ile, Leu, Phe, Lys); X is hydrogen or CF3; Z is anN-capping moiety selected from the group consisting of phosphoramidate[(R'O)2(O)P-], sulfenamide [(SR')2-], sulfonamide [(R'(O)2S-], sulfonic acid[SO3H], phosphinarnide [(R')2(O)P-], sulfamoyl derivative [R'O(O)2S-], thiourea[(R')2N(O)C-], thiocarbamate [R'O(S)C-], phosphonate [R'-P(O)OH],amidophosphate [R'O(OH)(O)P-], carbamate: (R'O(O)C-), and urea (R'NH(O)C-),wherein each R‘ is independently selected from the group consisting of straight orbranched C1-C6 unsubstituted alkyl, phenyl, C7-C9 alkylaryl, and cycloalkylmoieties, wherein the cycloalkyl ring may span C4-C3 and may contain one or moreheteroatoms selected from the group consisting of O,N,and S; and R is selected fromthe group consisting of straight or branched (31 - C6 unsubstituted alkyl, phenyl, andC7 - C9 alkylaryl moieties.Preferred R moieties are selected from the group consisting of methyl, iso-propyl, sec-butyl, iso-butyl, -C6H5, -CH2-C5H5, and -CH2Cl-I2-C6H5, whichrespectively may be derived from the amino acids Ala, Val, Ile, Leu, PGly(phenylglycine), Phe, and HPhe (homophenylalanine) by converting the carboxylicacid group to an aldehyde or trifluromethyl ketone group. While such moieties aretherefore not amino acids (and they may or may not have been synthesized from anamino acid precursor), for purposes of simplification of the exemplification ofinhibitors useful here, the aldehyde portion of the inhibitors are indicated as derivedfrom amino acids by the addition of "H" after the analogous amino acid [e.g., "-A1aH" represents the chemical moiety "-NI-ICH(CH3)C(O)H"]. Trifluromethylketones are similarly represented by the addition of "CF3" after the analogous aminoacid (e.g., "-AlaCF3" represents the chemical moiety "-NI-ICH(CH3)C(O)CF3"].The present invention aldehydes may be prepared from the correspondingamino acid whereby the C-terminal end of said amino acid is converted from acarboxylic group to an aldehyde group. Such aldehydes may be prepared by knownprocesses, for instance as described in US 5015627, EP 185 930, EP 583,534, andDE 32 00 812.The present invention trifluromethyl ketones may be prepared from thecorresponding amino acid whereby the C-terminal end of said amino acid isW0 98/ 13458101520253035CA 02265879 l999-03- llPCT/US97/ 16621converted from a carboxylic group to the trifluromethyl ketone group. Suchtrifluromethyl ketones may be prepared by known processes, for instance asdescribed in EP 583,535.While not wanting to be bound by theory it is believed that the proteaseinhibitors according to the present invention bind to the proteolytic enzyme in theliquid detergent composition, thereby inhibiting said proteolytic enzyme. Upondilution in water, the proteolytic activity is restored by dissociation of the proteolyticenzyme/protease inhibitor complex.The N-terrninal end of said protease inhibitors according to the presentinvention is protected by one of the N-capping moiety protecting groups selectedfrom the group consisting of carbamates, ureas, sulfonamides,phosphonamides,thioureas, sulfenamides, sulfonic acids, phosphinamides,thiocarbamates, amidophosphates, and phosphonamides. However, in a highlypreferred embodiment of the present invention, the N-terrninal end of said proteaseinhibitor is protected by a methyl, ethyl or benzyl carbamate [CH3O-(O)C-;CI-I3CH2O—(O)C-; or C5H5CH2O-(O)C-], methyl, ethyl or benzyl urea [CH3NH-(O)C—; CH3CH2NH-(O)C-; or C6H5Cl-I2NH-(O)C-], methyl, ethyl or benzylsulfonamide [CH3 S02-; CH3CH2SO2-; or C6H5CI-I2SO2—], and methyl, ethyl orbenzyl amidophosphate [CH3O(OH)(O)P-; CH3CH2O(OH)(O)P-; orC6H5CH2O(OH)(O)P-] groups.Synthesis of N-capping groups can be found in the following references:Protective Groups in Organic Chemistg, Greene, T., Wuts, P., John Wiley & Sons,New York, 1991, pp 309-405; March, 1, Advanced Organic Chemistgg, WileyInterscience, 1985, pp. 445, 469, Carey, F. Sundberg, R., Advanced OrganicChemistg, 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. 3,5,11,14-18,28-29. Bodansky, M., Principles of Peptide Synthesis, Springer-Verlag, 1988, pp.62, 203, 59-69; Bodansky, M., Peptide Chemistgg, Springer-Verlag, 1988, pp. 74-81, Bodansky, M., Bodansky, A., The Practice of Peptide Synthesis, Springer-Verlag, 1984, pp. 9-32.Examples of protease inhibitors for use herein are: CH3O-(O)C-Ala-LeuH;CH3CH2O-(O)C-Ala-LeuH; C5H5CH2O-(O)C-Ala-LeuH; CH3O-(O)C-Ala-LeuCF3; CH3CH2O-(O)C-Ala-LeuCF3; C6H5CH2O-(O)C-Ala-LeuCF3; CH3O-(O)C-Ala-IleH; CH3CH2O-(O)C-Ala-IleH; C6H5CH2O-(O)C-Ala-IleH; CH3O-(O)C—Ala-IleCF3; CH3CH2O-(O)C-Ala—IleCF3; C6H5CH2O-(O)C-Ala-IleCF3;W0 98/ 13458101520253035CA 02265879 l999-03- llPCT/US97/16621CH3O—(O)C-Gly-LeuH; CH3 CH2O-(O)C-Gly-LeuH; C6H5CH2O-(O)C-Gly-LeuH;CH3O-(O)C-Gly-LeuCF 3 ; CH 3 CHZO-(O)C -Gly-LeuCF 3 ; C6H 5CH2O-(O)C-G1y-LeuCF3; CH3O-(O)C-Gly-IleH; CH3CH2O--(O)C-Gly-IleH; C5H 5CH2O—(O)C-Gly-IleH; CH3O-(O)C-Gly-IleCF3; CH3 CHZO-(O)C-Gly-IleCF 3; C51-I 5 CH2O-(O)C-Gly-IleCF 3; CH3NH-(O)C-Ala-LeuH; CH3CH2NH-(O)C—Ala~LeuH;C6H5CH2NH-(O)C-Ala—LeuH; CH3NH-(O)~C-Ala-LeuCF3; CH3CH2NH-(O)C-Ala-LeuCF 3; C6H 5CH2NH-(O)C-Ala-LeuCF 3 ; CH3NH-(O)C-Ala-IleH;CH3CH2NH-(O)C-Ala-IleH; C6H5CH2NH-(O)C-Ala-IleH; CH3NH-(O)C-Ala-IleCF3; CH3 CH2NH-(O)C~Ala-IleCF3; C6!-I5CHQNH-(O)C-Ala-IleCF 3; CH3NH-(O)C-Gly-LeuH; CH3CH2NH-(O)C-Gly—LeuH; C6H5CH2NH-(O)C-Gly-LeuH;CH3NH-(O)C-Gly-LeuCF3; CH3CH2NH-(O)C-Gly-LeuCF3; C5H5CH2NH-(O)C-Gly-LeuCF 3; CH3NH-(O)C-Gly-IleH; CH3 CHQNH-(O)C-Gly-IleH; C5H 5 CH2NH-(O)C-Gly-IleH; CH3NH-(O)C-Gly-I1eCF3; CH3CH2NH-(O)C-Gly-IleCF3;C5H5CH2NH-(O)C-Gly-IleCF3; CH3 S02-Ala-LeuH; CH3CH2SO2-Ala-LeuH;C6H5CH2SO2-Ala-LeuH; CH3SO2-Ala-LeuCF3; CH3CH2SO2-Ala-LeuCF3;C6H5CH2SO2-Ala-LeuCF3; CH3SO2—Ala-IleH; CH3CI-I2 S02-Ala-IleH;C5H5CH2SO2-Ala-IleH; CH3 S02-Ala-IleC3F3; CH3CH2SO2-Ala-IleCF3;C6H 5 CH2 S02-Ala-IleCF 3 ; CH3 S02-Gly-LeuH; CH3CH2SO2—Gly-LeuH;C61-I5CH2SO2-Gly-LeuH; CH3 S02-Gly-LeuCF3; CH3CH2 S02-Gly-LeuCF 3;C6H 5CH2 S02-Gly-LeuCF 3; CH3 SO2-Gly-IleH; CH3CH2SO2-Gly-IleH;C6H5CH2SO2-Gly-IleH; CH3 SO2—Gly-IleC F3; CH3CH2SO2-Gly-IleCF3;C6H5CH2SO2-Gly-IleCF3; CH3O(OH)(O)P—Ala-LeuH; CH3CH2O(OH)(O)P-Ala-LeuH; C6H5CH2O(OH)(O)P-Ala-LeuH; CH3O(OH)(O)P-Ala-LeuCF3;CH3CH2O(OH)(O)P-Ala-LeuCF3; C5H5CH2O(OH)(O)P-Ala-LeuCF3;CH3O(OH)(O)P-Ala-I1eH; CH3CH2O(OH)(O)P-Ala-IleH; C6H5CH2O(OH)(O)P—Ala-IleH; CH3O(OH)(O)P-Ala-IleCF3; CH3CH2O(OH)(O)P-Ala-IleCF3;C6H5CH2O(OH)(O)P-Ala-IleCF3; CH3O(OH)(O)P-Gly-LeuH;CH3CH2O(OH)(O)P-Gly-LeuH; C6H5CH2O(OH)(O)P-Gly-LeuH;CH3O(OH)(O)P-Gly-LeuCF3; CH3CH2O(OH)(O)P-Gly-LeuCF3;C6H5CH2O(OH)(O)P-Gly-LeuCF3; CH3O(OH)(O)P-Gly-IleH;CH3CH2O(OH)(O)P-Gly-IleH; C5H5CH2O(OH)(O)P-Gly-IleH; CH3O(OH)(O)P-Gly-I1eCF3; CH3CH2O(OH)(O)P-Gly-IICCF3§ and C6H5CH2O(OH)(O)P-Gly-IleCF 3.In the Synthesis Examples hereinafter, methods are disclosed to synthesizecertain of these protease inhibitors.WO 98/13458101520253035CA 02265879 l999-03- llPCT/US97/16621Synthesis Example 1:Synthesis of an aldehyde Drotease inhibitorMoe-Leu-OH-L-Leucine (5.0 g, 38.2 mmol) is dissolved in 38 ml 1N NaOH andcooled to 0°C. Methyl chloroformate (3.1 ml, 40.0 mmol) is added dropwise whilein a separate addition funnel 1N NaOH is added as to maintain pH at 9.0-9.5. Afteraddition is complete and the pH stabilized at 9.0-9.5 the solution is washed with 200ml EtOAc, the aqueous phase is then acidified to pH = 2. This mixture is extractedwith EtOAc (2X 100 ml), dried (MgSO4), filtered, and the solvent removed toafford 7.15 g pure product.Moc-Leu-Leucinol- To a solution of 3.5 g (18.52 mmol) Moc-Leu—OH in 100 mlTHF, cooled to -15°C, 2.04 ml (18.52 mmol) of N-methyl morpholine is addedfollowed immediatedly by 2.4 ml (18.52 mmol) isobutyl chloroforrnate. Afterstirring for 10 minutes 2.37 ml (18.52 mmol) of leucinol in 25 ml of THF is addedand the reaction stirred 0.5 h at -15°C and 1 h at room temperature. The mixture isthen diluted with 100 ml of H20 and the THF evaporated. The remaining aqueousphase is partitioned between EtOAc and 1N HC1, the organic phase washed withNaHCO3, dried (MgSO4) and evaporated to afford 5.33 g pure product.Moe-Leu-LeuH-A solution containing 4.4 g (10.41 mmol) Dess-Martin periodinanesuspended in 100 ml CH2Cl2 is prepared and stirred for 10 minutes. To this solution1.0 g (3.47 mmo1)Moc-Leu-Leucinol is added and the solution stirred 2 h at roomtemperature followed by pouring into 100 ml of saturated NaHCO3 containing 18 g(72.87 mmo1)Na2S2O3. This solution is stirred 10 minutes and then extracted withEtOAc (2X, 125ml), dried (MgSO4) and the solvent evaporated. Chromatographyon silica affords 0.550 g of pure product.Synthesis Example 2:Synthesis of a trifluoromethylketone protease inhibitorN-trityl-leucine methyl ester- To a solution of 2.50 g (13.8 mmol) of Leu-OMe.HClin 100 ml CH2Cl2 is added 3.86 ml TEA (27.5 mmol) dropwise. After the additionis complete 3.76 g (13.5 mmol) of triphenylmethyl chloride in 15 ml CH2C12 isadded dropwise. The mixture is stirred for 4 H. The solution is diluted with 5%EtOAc/petroleum ether and washed with water. The organic phase is dried (MgSO4)W0 98/13458101520253035CA 02265879 l999-03- llPCT/US97/16621filtered and the solvent removed. The residue is chromatographed on silica to give4.8 g of pure product (90% yield).N-trityl-leucinal-To a cold (O°) solution of 4.70 g (12.2 mmol) of N-trityl—leucinemethyl ester in 100ml THF is added 28.1 ml of a 1.5M solution ofdiisobutylaluminum hydride (42.2 mol) in THF dropwise. The solution is stirred for6 h at this temperature and the reaction quenched with saturated Na-K tartrate,extracted with EtOAc, dried (MgSO4), filtered and the solvent removed. Recovered4.13 g of the desired material that is used without purification. To a solution fo 1.29g (14.9 mmol) of oxalyl chloride in 20 ml CH2Cl2 at -78°C is added 2.26 ml DMSO(29.8 mmol) in 5 ml CH2Cl2 dropwise. After the addition is complete, 4.13 g (11.5mmol) of crude N-trityl-leucinol in 10 ml CHZCI2 is added. The solution is warmedto 0°C and poured into a mixture of water and ether. The phases are separated andthe ether phase dried (MgSO4) and evaporated to afford 1.37 g of the desiredcompound.5-Methyl-3-tritylamino-1,1,1-trifluoro-2-hexanol- To a solution of 1.37 g (3.83mmol) of N-trityl-leucinal and 0.653 ml (4.59 mmol) of CF3TMS in THF is added0.121 g (0.383 mmol) of tetrabutylammonium fluoride trihydrate in one portion. Thesolution is stirred for 3 h at room temperature and the solvent removed. The residueis dissolved in EtOAc, washed with water, dried (MgSO4), and the solvent removedto afford 1.20 g of the product that is chromatographed on silica (recover 0.760 gpure product).Moc-Ala-OH-Alanine (5.0 g, 56.2 mmol) is dissolved in 56 ml IN NaOH andcooled to 0°C. Methyl chloroformate (5.57 ml, 58.9 mmol) is added dropwise whilein a separate addition funnel 1N NaOH is added as to maintain pH at 9.0-9.5. Afteraddition is complete and the pH stabilized at 9.0-9.5 the solution is washed with 200ml EtOAc, the aqueous phase is then acidified to pH = 2. This mixture is extractedwith EtOAc (2X 100 ml), dried (MgSO4), filtered, and the solvent removed toafford 7.15 g pure product.3-(N-(Moc-Ala))-5-methyl-1,1,1-trifluoro-2-hexanol- To a solution of 1.21 g (2.83mmol) of 5-methyl-3-tritylamino-1,1,1-trifluoro-2-hexanol in 10 ml dioxane isadded 5 ml of 4.0 M HCl in dioxane. The solution is stirred for 2 h at roomtemperature and the solvent removed. The residue is triturated with ether and thesolid material filtered. The resulting HC1 salt (0.627 g, 2.83 mmol) is suspended inWO 98113458101520253035CA 02265879 l999-03- llPCT/US97/166211 010 ml CH2Cl2 and Moc-Ala-OH added (0.416 g, 2.83 mmol). To this mixture isadded 0.870 ml (6.23 mmol) TEA followed immediately by the addition of 0.473 ml(3.12 mmol) of DEPC. The mixture is stirred overnight and the solvent removed.The residue is dissolved in EtOAc and washed with 1N HCI, saturated NaHCO3,and brine. The solution of product is dried (MgSO4), filtered and the solventremoved to give 0.650 g product.Moc-Ala—LeuCF3— To a slurry of 2.63 g (6.21 mmol) of Dess-Martin periodinane in15 ml CH2Cl2 is added 0.650 g (2.07 mmol) of 3-(Moe-Ala)-5-methyl-1,1,l-trifluoro-2-hexanol in 5 ml CH2Cl2 and the slurry stirred for 3 h. To this mixture isadded 10.88 g (43.47 mmol) of Na2S2O3 in 50 ml saturated NaHCO3 and theresulting solution stirred for 10 min. The solution is extracted with EtOAc and theorganic phase dried (MgSO4), filtered and the solvent removed. The residue ischromatographed on silica to afford 0.425 g of pure product.Z = carbobenzyloxyGly = glycineAla = alanineLeu = leucinePhe = phenylalanineOMe = methyl esterTEA = triethylamineDECP = diethylcyanophosphonateTLC = thin layer chromatographyMeOH = methanolPd/C = palladium on activated carbonEtOH = ethanolTHF = tetrahydrofuranMac = methylaminocarbonylMoc = methoxycarbonylProteolytic Enzyme — Another essential ingredient in the present liquiddetergent compositions is active proteolytic enzyme. Mixtures of proteolyticenzyme are also included. The proteolytic enzyme can be of animal, vegetable ormicroorganism (preferred) origin. The proteases for use in the detergentcompositions herein include (but are not limited to) trypsin, subtilisin, chymotrypsinand elastase—type proteases. Preferred for use herein are subtilisin-type proteolyticenzymes. Particularly preferred is bacterial serine proteolytic enzyme obtained fromW0 98/13458101520253035CA 02265879 l999-03- ll1 1 PCTIUS97/16621Bacillus subtilis and/or Bacillus licheniformis. Protease enzymes are usually present in such liquid detergent compositions at levels sufficient to provide from 0.005 to0.1 Anson units (AU) of activity per gram of composition.Suitable proteolytic enzymes include Novo Industri A/S Alca1ase® (preferred),Esperase® , Savinase® (Copenhagen, Demnark), Gist-brocades' Maxatase®,Maxacal® and Maxapem l5® (protein engineered Maxacal®) (Delft, Netherlands),and subtilisin BPN and BPN'(preferred), which are commercially available.Preferred proteolytic enzymes are also modifiied bacterial serine proteases, such asthose made by Genencor International, Inc.(San Francisco, California) which aredescribed in European Patent 251,446, filed April 28, 1987 (particularly pages 17,24 and 98), and which is called herein "Protease B", and U.S. Patent 5,030,378,Venegas, issued July 9, 1991, which refers to a modified bacterial serine proteolyticenzyme (Genencor Intemational) which is called "Protease A" herein (same asBPN'). In particular see columns 2 and 3 of U .S. Patent 5,030,378 for a completedescription, including amino sequence, of Protease A and its variants. Preferredproteolytic enzymes, then, are selected from the group consisting of Alcalase ®(Novo Industri A/S), BPN', Protease A and Protease B (Genencor), and mixturesthereof. Protease B is most preferred.Another preferred protease, referred to as "Protease D" is a carbonylhydrolase variant having an amino acid sequence not found in nature, which isderived from a precursor carbonyl hydrolase by substituting a different amino acidfor a plurality of amino acid residues at a position in said carbonyl hydrolaseequivalent to position +76, preferably also in combination with one or more aminoacid residue positions equivalent to those selected from the group consisting of +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 +274according to the numbering of Bacillus amylaliquefaciens subtilisin, as described inW0 95/ 10615 published April 20, 1995 by Genencor International.Useful proteases are also described in PCT publications: WO 95/30010published Novenber 9, 1995 by The Procter & Gamble Company; W0 95/30011published Novenber 9, 1995 by The Procter & Gamble Company; WO 95/29979published Novenber 9, 1995 by The Procter & Gamble Company.Detersive Surfactant - An effective amount, typically from about 1 to 95,preferably about 8 to 70, weight %, of detersive surfactant is yet another essentialingredient in the present invention. The detersive surfactant can be selected fromthe group consisting of anionics, nonionics, cationics, arnpholytics, zwitterionics,and mixtures thereof. By selecting the type and amount of detersive surfactant,W0 98/13458101520253035CA 02265879 l999-03- ll12 PCT/US97/16621along with other adjunct ingredients disclosed herein, the present detergentcompositions can be formulated to be used in the context of laundry cleaning or inother different cleaning applications, particularly including dishwashing. Theparticular surfactants used can therefore vary widely depending upon the particularend-use envisioned.The benefits of the present invention are especially pronounced incompositions containing ingredients that are harsh to enzymes such as certaindetergency builders and surfactants. These include (but are not limited to) anionicsurfactants such as alkyl ether sulfate linear alkyl benzene sulfonate, alkyl sulfate,etc. Suitable surfactants are described below.Anionic Surfactants - One type of anionic surfactant which can be utilizedencompasses alkyl ester sulfonates. These are desirable because they can be madewith renewable, non—petroleum resources. Preparation of the alkyl ester sulfonatesurfactant component can be effected according to known methods disclosed in thetechnical literature. For instance, linear esters of Cg-C20 carboxylic acids can besulfonated with gaseous S03 according to "The Journal of the American OilChemists Society," 52 (1975), pp. 323-329. Suitable starting materials wouldinclude natural fatty substances as derived from tallow, palm, and coconut oils, etc.The preferred alkyl ester sulfonate surfactant, especially for laundryapplications, comprises alkyl ester sulfonate surfactants of the structural formula:R3—cH(so3M)-c(o)—oR4wherein R3 is a Cg-C20 hydrocarbyl, preferably an alkyl, or combination thereof,R4 is a C1-C6 hydrocarbyl, preferably an alkyl, or combination thereof, and M is asoluble salt-forrning cation. Suitable salts include metal salts such as sodium,potassium, and lithium salts, and substituted or unsubstituted armnonium salts, suchas methyl-, dimethyl, -trimethyl, and quaternary ammonium cations, e. g.tetramethyl-arnmonium and dimethyl piperdinium, and cations derived fromalkanolamines, e.g. monoethanol-amine, diethanolamine, and triethanolamine.Preferably, R3 is C10-C15 alkyl, and R4 is methyl, ethyl or isopropyl. Especiallypreferred are the methyl ester sulfonates wherein R3 is C14-C16 alkyl.Alkyl sulfate surfactants are another type of anionic surfactant of importancefor use herein. In addition to providing excellent overall cleaning ability when usedin combination with polyhydroxy fatty acid amides (see below), including goodgrease/oil cleaning over a wide range of temperatures, wash concentrations, andwash times, dissolution of alkyl sulfates can be obtained, as well as improvedformulability in liquid detergent formulations are water soluble salts or acids of theformula ROSO3M wherein R preferably is a C10-C24 hydrocarbyl, preferably anW0 98/134158101520253035CA 02265879 l999-03- ll1 3 PCT/US97/16621alkyl or hydroxyalkyl having a C10-C20 alkyl component, more preferably a C12-C13 alkyl or hydroxyalkyl, and M is H or a cation, e.g., an alkali metal cation (e.g.,sodium, potassium, lithium), substituted or unsubstituted ammonium cations such asmethyl-, dimethyl-, and trimethyl ammonium and quaternary ammonium cations,e.g., tetramethyl-ammonium and dimethyl piperdinium, and cations derived fromalkanolamines such as ethanolamine, diethanolamine, triethanolamine, and mixturesthereof, and the like. Typically, alkyl chains of C12_16 are preferred for lower washtemperatures (e.g., below about 50°C) and C16-13 alkyl chains are preferred forhigher wash temperatures (e.g., above about 50°C).Alkyl alkoxylated sulfate surfactants are another category of useful anionicsurfactant. These surfactants are water soluble salts or acids typically of the formulaRO(A)mSO3M wherein R is an unsubstituted C10-C24 alkyl or hydroxyalkyl grouphaving a C10-C24 alkyl component, preferably a C12-C20 alkyl or hydroxyalkyl,more preferably C12-C13 alkyl or hydroxyalkyl, A is an ethoxy or propoxy unit, mis greater than zero, typically between about 0.5 and about 6, more preferablybetween about 0.5 and about 3, and M is H or a cation which can be, for example, ametal cation (e.g., sodium, potassium, lithium, calcium, magnesium, etc.),ammonium or substituted-ammonium cation. Alkyl ethoxylated sulfates as well asalkyl propoxylated sulfates are contemplated herein. Specific examples ofsubstituted ammonium cations include methyl-, dimethyl-, trimethyl-ammonium andquaternary ammonium cations, such as tetramethyl-ammonium, dimethylpiperidinium and cations derived from alkanolamines, e.g. monoethanolamine,diethanolamine, and triethanolamine, and mixtures thereof. Exemplary surfactantsare C12-C13 alkyl polyethoxylate (1.0) sulfat;e, C12-C13 alkyl polyethoxylate (2.25)sulfate, C12-C13 alkyl polyethoxylate (3.0) sulfate, and C12-C13 alkylpolyethoxylate (4.0) sulfate wherein M is conveniently selected from sodium andpotassium.Other Anionic Surfactants - Other anionic surfactants useful for detersivepurposes can also be included in the compositions hereof. These can include salts(including, for example, sodium, potassium, ammonium, and substituted ammoniumsalts such as mono-, di- and triethanolamine salts) of soap, C9-C20 linearalkylbenzenesulphonates, C3-C22 primary or secondary alkanesulphonates, C3—C24olefinsulphonates, sulphonated polycarboxylic acids prepared by sulphonation of thepyrolyzed product of alkaline earth metal citrates, e.g., as described in British patentspecification No. 1,082,179, alkyl glycerol sulfonates, fatty acyl glycerol sulfonates,fatty oleyl glycerol sulfates, alkyl phenol ethylene oxide ether sulfates, paraffinsulfonates, alkyl phosphates, isothionates such as the acyl isothionates, N-acylW0 98/13458101520253035CA 02265879 l999-03- ll1 4 PCT/U S97/ 1662 ltaurates, fatty acid amides of methyl tauride, alkyl succinamates and sulfosuccinates,monoesters of sulfosuccinate (especially saturated and unsaturated C 12-C13monoesters) diesters of sulfosuccinate (especially saturated and unsaturated C5-C14diesters), N-acyl sarcosinates, sulfates of alkylpolysaccharides such as the sulfates ofalkylpolyglucoside (the nonionic nonsulfated compounds being described below),branched primary alkyl sulfates, alkyl polyethoxy carboxylates such as those of theformula RO(CH2CH2O)kCH2COO-M+ wherein R is a Cg-C22 alkyl, k is aninteger from 0 to 10, and M is a soluble salt—forming cation, and fatty acidsesterified with isethionic acid and neutralized with sodium hydroxide. Resin acidsand hydrogenated resin acids are also suitable, such as rosin, hydrogenated rosin,and resin acids and hydrogenated resin acids present in or derived from tall oil.Further examples are given in "Surface Active Agents and Detergents" (Vol. I and IIby Schwartz, Perry and Berch). A variety of such surfactants are also generallydisclosed in U.S. Patent 3,929,678, issued December 30, 1975 to Laughlin, et al. atColumn 23, line 58 through Column 29, line 23 (herein incorporated by reference).Nonionic Detergent Surfactants - Suitable nonionic detergent surfactants aregenerally disclosed in U.S. Patent 3,929,678, Laughlin et al., issued December 30,1975, at column 13, line 14 through column 16, line 6, incorporated herein byreference. Exemplary, non-limiting classes of useful nonionic surfactants are listedbelow.The polyethylene, polypropylene, and polybutylene oxide condensates of alkylphenols. In general, the polyethylene oxide condensates are preferred. Thesecompounds include the condensation products of alkyl phenols having an alkylgroup containing from about 6 to about 12 carbon atoms in either a straight chain orbranched chain configuration with the alkylene oxide. In a preferred embodiment,the ethylene oxide is present in an amount equal to from about 5 to about 25 molesof ethylene oxide per mole of alkyl phenol. Commercially available nonionicsurfactants of this type include I gepal® CO-630, marketed by the GAF Corporation;and Triton® X-45, X-114, X-100, and X-102, all marketed by the Rohm & HaasCompany. These compounds are commonly referred to as alkyl phenol alkoxylates,(e.g., alkyl phenol ethoxylates).The condensation products of aliphatic alcohols with from about 1 to about 25moles of ethylene oxide. The alkyl chain of the aliphatic alcohol can either bestraight or branched, primary or secondary, and generally contains from about 8 toabout 22 carbon atoms. Particularly preferred are the condensation products ofalcohols having an alkyl group containing from about 10 to about 20 carbon atomswith from about 2 to about 18 moles of ethylene oxide per mole of alcohol.WO 98/13458101520253035CA 02265879 l999-03- llPCT/US97/16621l 5Examples of commercially available nonionic surfactants of this type includeTergitol® l5-S-9 (the condensation product of C 1 ]-C15 linear secondary alcoholwith 9 moles ethylene oxide), Tergitol® 24—L-6 NMW (the condensation product ofC 12-C14 primary alcohol with 6 moles ethylene oxide with a narrow molecularweight distribution), both marketed by Union Carbide Corporation; Neodol® 45-9(the condensation product of C14-C15 linear alcohol with 9 moles of ethyleneoxide), Neodol® 23-65 (the condensation product ofC12-C13 linear alcohol with6.5 moles of ethylene oxide), Neodol® 45-7 (the condensation product of C14-C 1 5linear alcohol with 7 moles of ethylene oxide), Neodol® 45-4 (the condensationproduct of C14-C1 5 linear alcohol with 4 moles of ethylene oxide), marketed byShell Chemical Company, and Kyro® EOB (the condensation product of C13-C1 5alcohol with 9 moles ethylene oxide), marketed by The Procter & GambleCompany. This category of nonionic surfactant is referred to generally as "alkylethoxylates."The condensation products of ethylene oxide with a hydrophobic base formed‘by the condensation of propylene oxide with propylene glycol. The hydrophobicportion of these compounds preferably has a molecular weight of from about 1500to about 1800 and exhibits water insolubility. The addition of polyoxyethylenemoieties to this hydrophobic portion tends to increase the water solubility of themolecule as a whole, and the liquid character of the product is retained up to thepoint where the polyoxyethylene content is about 50% of the total weight of thecondensation product, which corresponds to condensation with up to about 40 molesof ethylene oxide. Examples of compounds of this type include certain of thecommercially-available Pluronic® surfactants, marketed by BASF.The condensation products of ethylene oxide with the product resulting fromthe reaction of propylene oxide and ethylenediamine. The hydrophobic moiety ofthese products consists of the reaction product of ethylenediamine and excesspropylene oxide, and generally has a molecular weight of from about 2500 to about3000. This hydrophobic moiety is condensed with ethylene oxide to the extent thatthe condensation product contains from about 40% to about 80% by weight ofpolyoxyethylene and has a molecular weight of from about 5,000 to about 11,000.Examples of this type of nonionic surfactant include certain of the commerciallyavailable Tetronic® compounds, marketed by BASF.Semi-polar nonionic surfactants are a special category of nonionic surfactantswhich include water-soluble amine oxides containing one alkyl moiety of fromabout 10 to about 18 carbon atoms and 2 moieties selected from the group consistingof alkyl groups and hydroxyalkyl groups containing from about 1 to about 3 carbonW0 98/13458101520253035CA 02265879 l999-03- llPCT/US97/ 166211 6atoms; water-soluble phosphine oxides containing one alkyl moiety of from about10 to about 18 carbon atoms and 2 moieties selected from the group consisting ofalkyl groups and hydroxyalkyl groups containing from about 1 to about 3 carbonatoms; and water-soluble sulfoxides containing one alkyl moiety of from about 10 toabout 18 carbon atoms and a moiety selected from the group consisting of alkyl andhydroxyalkyl moieties of from about 1 to about 3 carbon atoms.Semi-polar nonionic detergent surfactants include the amine oxide surfactantshaving the formulaR3(0R4)XN(O)(R5)2wherein R3 is an alkyl, hydroxyalkyl, or alkyl phenyl group or mixtures thereofcontaining from about 8 to about 22 carbon atoms; R4 is an alkylene orhydroxyalkylene group containing from about 2 to about 3 carbon atoms or mixturesthereof; x is from 0 to about 3; and each R5 is an alkyl or hydroxyalkyl groupcontaining from about 1 to about 3 carbon atoms or a polyethylene oxide groupcontaining from about 1 to about 3 ethylene oxide groups. The R5 groups can beattached to each other, e.g., through an oxygen or nitrogen atom, to form a ringstructure.These amine oxide surfactants in particular include C10-C13 alkyl dimethylamine oxides and Cg-C12 alkoxy ethyl dihydroxy ethyl amine oxides.Alkylpolysaccharides disclosed in U.S. Patent 4,565,647, Llenado, issuedJanuary 21, 1986, having a hydrophobic group containing from about 6 to about 30carbon atoms, preferably from about 10 to about 16 carbon atoms and apolysaccharide, e.g., a polyglycoside, hydrophilic group containing from about 1.3to about 10, preferably from about 1.3 to about 3, most preferably from about 1.3 toabout 2.7 saccharide units. Any reducing saccharide containing 5 or 6 carbon atomscan be used, e.g., glucose, galactose and galactosyl moieties can be substituted forthe glucosyl moieties. (Optionally the hydrophobic group is attached at the 2-, 3-, 4-,etc. positions thus giving a glucose or galactose as opposed to a glucoside orgalactoside.) The intersaccharide bonds can be, e.g., between the one position of theadditional saccharide units and the 2-, 3-, 4-, and/or 6- positions on the precedingsaccharide units.Optionally, and less desirably, there can be a polyalkylene-oxide chain joiningthe hydrophobic moiety and the polysaccharide moiety. The preferredalkyleneoxide is ethylene oxide. Typical hydrophobic groups include alkyl groups,either saturated or unsaturated, branched or unbranched containing from about 8 toabout 18, preferably from about 10 to about 16, carbon atoms. Preferably, the alkylgroup is a straight chain saturated alkyl group. The alkyl group can contain up toW0 98/123458101520253035CA 02265879 l999-03- ll1 7 PCTIU S97/ 16621about 3 hydroxy groups and/or the polyalkyleneoxide chain can contain up to about10, preferably less than 5, alkyleneoxide moieties. Suitable alkyl polysaccharidesare octyl, nonyl, decyl, undecyldodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl,heptadecyl, and octadecyl, di-, tri-, tetra-, penta-, and hexaglucosides, galactosides,lactosides, glucoses, fructosides, fructoses and/or galactoses. Suitable mixturesinclude coconut alkyl, di-, tri-, tetra-, and pentaglucosides and tallow alkyl tetra-,penta-, and hexa-glucosides.The preferred alkylpolyglycosides have the formulaR2O(CnH2nO)t(81YC05Y1)xwherein R2 is selected from the group consisting of alkyl, alkyl-phenyl,hydroxyalkyl, hydroxyalkylphenyl, and mixtures thereof in which the alkyl groupscontain from about 10 to about 18, preferably from about 12 to about 14, carbonatoms; n is 2 or 3, preferably 2; t is from 0 to about 10, preferably 0; and x is fromabout 1.3 to about 10, preferably from about 1.3 to about 3, most preferably fromabout 1.3 to about 2.7. The glycosyl is preferably derived from glucose. To preparethese compounds, the alcohol or alkylpolyethoxy alcohol is formed first and thenreacted with glucose, or a source of glucose, to form the glucoside (attachment at the1-position). The additional glycosyl units can then be attached between their 1-position and the preceding glycosyl units 2-, 3-, 4- and/or 6-position, preferablypredominantly the 2-position.Fatty acid amide surfactants having the formula:R5—C(O)~N(R7)2wherein R6 is an alkyl group containing from about 7 to about 21 (preferably fromabout 9 to about 17) carbon atoms and each R7 is selected from the group consistingof hydrogen, C1-C4 alkyl, C1-C4 hydroxyalkyl, and -(C2H4O)xH where x variesfrom about 1 to about 3.Preferred amides are C3-C20 ammonia amides, monoethanolamides,diethanolamides, and isopropanolamidesfCationic Surfactants - Cationic detersive surfactants can also be included indetergent compositions of the present invention. Cationic surfactants include theammonium surfactants such as alkyldimethylarnrnonium halogenides, and thosesurfactants having the formula:[R2(OR3)y][R4(OR3)y]2R5N+X'wherein R2 is an alkyl or alkyl benzyl group having from about 8 to about 18 carbonatoms in the alkyl chain, each R3 is selected from the group consisting of -CH2CH2-, -CH2CI-l(CH3)-, -CH2CH(CH2OH)-, -CH2CH2CH2-, and mixturesthereof; each R4 is selected from the group consisting of C 1-C4 alkyl, C1-C4WO 98113458101520253035CA 02265879 l999-03- ll1 8 PCT/US97/16621hydroxyalkyl, benzyl, ring structures formed by joining the two R4 groups, -CI-I2CHOHCHOHCOR6CHOH-CHQOH wherein R6 is any hexose or hexosepolymer having a molecular weight less than about 1000, and hydrogen when y isnot 0; R5 is the same as R4 or is an alkyl chain wherein the total number of carbonatoms of R2 plus R5 is not more than about 18; each y is from 0 to about 10 and thesum of the y values is from 0 to about 15; and X is any compatible anion.Other cationic surfactants useful herein are also described in U.S. Patent4,228,044, Cambre, issued October 14, 1980, incorporated herein by reference.Other Surfactants - Ampholytic surfactants can be incorporated into thedetergent compositions hereof. These surfactants can be broadly described asaliphatic derivatives of secondary or tertiary amines, or aliphatic derivatives ofheterocyclic secondary and tertiary amines in which the aliphatic radical can bestraight chain or branched. One of the aliphatic substituents contains at least about 8carbon atoms, typically from about 8 to about 18 carbon atoms, and at least onecontains an anionic water-solubilizing group, e.g., carboxy, sulfonate, sulfate. SeeU.S. Patent No. 3,929,678 to Laughlin et al., issued December 30, 1975 at column19, lines 18-35 for examples of ampholytic surfactants.Zwitterionic surfactants can also be incorporated into the detergentcompositions hereof. These surfactants can be broadly described as derivatives ofsecondary and tertiary amines, derivatives of heterocyclic secondary and tertiaryamines, or derivatives of quatemary ammonium, quaternary phosphonium or tertiarysulfonium compounds. See U.S. Patent No. 3,929,678 to Laughlin et al., issuedDecember 30, 1975 at column 19, line 38 through column 22, line 48 for examplesof zwitterionic surfactants. Ampholytic and zwitterionic surfactants are generallyused in combination with one or more anionic and/or nonionic surfactants.Polvhvdroxv Fatty Acid Amide Surfactant - The liquid detergent compositionshereof may also contain an enzyme-enhancing amount of polyhydroxy fatty acidamide surfactant. By "enzyme-enhancing" is meant that the formulator of thecomposition can select an amount of polyhydroxy fatty acid amide to beincorporated into the compositions that will improve enzyme cleaning performanceof the detergent composition. In general, for conventional levels of enzyme, theincorporation of about 1%, by weight, polyhydroxy fatty acid amide will enhanceenzyme performance.The detergent compositions herein will typically comprise about 1% weightbasis, polyhydroxy fatty acid amide surfactant, preferably from about 3% to about30%, of the polyhydroxy fatty acid amide. The polyhydroxy fatty acid amidesurfactant component comprises compounds of the structural formula:WO 98113458101520253035CA 02265879 l999-03- ll1 9 PCT/U S97/ 16621R2 — c<o) - N(R1) - zwherein: R1 is l-I, C1-C4 hydrocarbyl, 2-hydroxy ethyl, 2—hydroxy propyl, or amixture thereof, preferably C1-C4 alkyl, more preferably C1 or C2 alkyl, mostpreferably C1 alkyl (i.e., methyl); and R2 is a C5-C31 hydrocarbyl, preferablystraight chain C7-C19 alkyl or alkenyl, more preferably straight chain C9-C17 alkylor alkenyl, most preferably straight chain C11-C15 alkyl or alkenyl, or mixturesthereof; and Z is a polyhydroxyhydrocarbyl having a linear hydrocarbyl chain withat least 3 hydroxyls directly connected to the chain, or an alkoxylated derivative(preferably ethoxylated or propoxylated) thereof. Z preferably will be derived froma reducing sugar in a reductive amination reaction; more preferably Z will be aglycityl. Suitable reducing sugars include glucose, fructose, maltose, lactose,galactose, mannose, and xylose. As raw materials, high dextrose corn syrup, highfructose corn syrup, and high maltose corn syrup can be utilized as well as theindividual sugars listed above. These corn syrups may yield a mix of sugarcomponents for Z. It should be understood that it is by no means intended toexclude other suitable raw materials. Z preferably will be selected from the groupconsisting of -CH2-(CHOH)n-CH2OH, -CH(CH2OH)-(CHOI-I)n-1-CHZOH, -CI-l2-(CHOH)2(CHOR')(CHOH)-CHZOH, and alkoxylated derivatives thereof, where n isan integer from 3 to 5, inclusive, and R‘ is H or a cyclic or aliphatic monosaccharide.Most preferred are glycityls wherein n is 4, particularly -CH2-(CHOH)4-CHZOH.R’ can be, for example, N-methyl, N-ethyl, N-propyl, N-isopropyl, N-butyl, N-2-hydroxy ethyl, or N-2-hydroxy propyl.R2-CO-N< can be, for example, cocamide, stearamide, oleamide, lauramide,myristamide, capricarnide, palmitamide, tallowamide, etc.Z can be 1-deoxyglucityl, 2-deoxyfructityl, 1-deoxymaltityl, 1-deoxylactityl,1-deoxygalactityl, 1-deoxymarmityl, 1-deoxymaltotriotityl, etc.Methods for making polyhydroxy fatty acid amides are known in the art. Ingeneral, they can be made by reacting an alkyl amine with a reducing sugar in areductive amination reaction to form a corresponding N-alkyl polyhydroxyarnine,and then reacting the N-alkyl polyhydroxyamine with a fatty aliphatic ester ortriglyceride in a condensation/arnidation step to form the N-alkyl, N-polyhydroxyfatty acid amide product. Processes for making compositions containingpolyhydroxy fatty acid amides are disclosed, for example, in G.B. PatentSpecification 809,060, published February 18, 1959, by Thomas Hedley & Co., Ltd.,U.S. Patent 2,965,576, issued December 20, 1960 to E. R. Wilson, and U.S. Patent2,703,798, Anthony M. Schwartz, issued March 8, 1955, and U.S. Patent 1,985,424,W0 98/ 13458101520253035CA 02265879 l999-03- llPCT/US97/1662120issued December 25 , 1934 to Piggott, each of which is incorporated herein byreference.Second Enzyme - Preferred compositions herein fiirther comprise aperforrnance-enhancing amount of a detergent-compatible second enzyme. By"detergent-compatible" is meant compatibility with the other ingredients of a liquiddetergent composition, such as detersive surfactant and detergency builder. Thesesecond enzymes are preferably selected from the group consisting of lipase,amylase, cellulase, and mixtures thereof. The term "second enzyme" excludes theproteolytic enzymes discussed above, so each composition which has a secondenzyme contains at least two kinds of enzyme, including at least one proteolyticenzyme. The amount of second enzyme used in the composition varies according tothe type of enzyme. In general, from about 0.0001 to 0.3, more preferably 0.001 to0.1, weight % of these second enzymes are preferably used. Mixtures of the sameclass of enzymes (e. g. lipase) or two or more classes (e.g. cellulase and lipase) maybe used. Purified or non-purified forms of the enzyme may be used.Any lipolytic enzyme suitable for use in a liquid detergent composition can beused in these compositions. Suitable lipase enzymes for use herein include those ofbacterial and fungal origin.Suitable bacterial lipases include those produced by microorganisms of thePseudomonas groups, such as Pseudomonas s_’tt1_t_ze_ri ATCC 19.154, as disclosed inBritish Patent 1,372,034, incorporated herein by reference. Suitable lipases includethose which show a positive immunological cross-reaction with the antibody of thelipase produced by the microorganism Pseudomonas fluorescens IAM 1057. Thislipase and a method for its purification have been described in Japanese PatentApplication 53-20487, laid open on February 24, 1978. This lipase is available fromAmano Pharmaceutical Co. Ltd., Nagoya, Japan, under the trade name Lipase P"Amano," hereinafter referred to as "Amano-P." Such lipases should show apositive immunological cross-reaction with the Amano-P antibody, using thestandard and well—known immunodiffusion procedure according to Ouchterlony(Acta. Med. Scan., 133, pages 76-79 (1950)). These lipases, and a method for theirimmunological cross-reaction with Amano-P, are also described in U.S. Patent4,707,291, Thom et al., issued November 17, 1987, incorporated herein byreference. Typical examples thereof are the Amano-P lipase, the lipase exPseudomonas frag; FERM P 1339 (available under the trade name Amano-B), lipaseex Pseudomonas nitroreducens var. lipolvticum FERM P 1338 (available under thetrade name Amano-CES), lipases ex Chromobacter viscosum, e.g. Chromobacterviscosum var. lipolylicum NRRLB 3673, commercially available from Toyo JozoW0 98Il3458101520253035CA 02265879 l999-03- ll2 1 PCT/US97/ 16621Co., Tagata, Japan; and further Chromobacter viscosum lipases from U.S.Biochemical Corp., U.S.A. and Disoynth C0,, The Netherlands, and lipases exPseudomonas gladioli.Suitable fungal lipases include those producible by Humicola lanuginosa andThermomyces lanuginosus. Most preferred is lipase obtained by cloning the genefrom Humicola lanuginosa and expressing the gene in Aspergillus gmgg asdescribed in European Patent Application 0 2158 068 (Novo Industri A/S),commercially available from Novo Nordisk A/S under the trade name Lipolase®.From about 10 to 18,000, preferably about 60 to 6,000, lipase units per gram(LU/g) of lipase can be used in these compositions. A lipase unit is that amount oflipase which produces 1 mmol of titratable fatty acid per minute in a pH stat, wherepH is 9.0, temperature is 30°C, substrate is an emulsion of 3.3wt % of olive oil and3.3% gum arabic, in the presence of 13 mmol/l Ca++ and 20 mmol/l NaCl in 5mmol/l Tris-buffer.Any cellulase suitable for use in a liquid detergent composition can be used in-these compositions. Suitable cellulase enzymes for use herein include those frombacterial and fungal origins. Preferably, they will have a pH optimum of between 5and 9.5. From about 0.0001 to 0.1 weight % cellulase can be used.Suitable cellulases are disclosed in U.S. Patent 4,435,307, Barbesgaard et al.,issued March 6, 1984, incorporated herein by reference, which discloses fungalcellulase produced from Humicola insolens. Suitable cellulases are also disclosed inGB-A-2.075.028, GB-A-2.095.275 and DE-OS-2.247.832.Examples of such cellulases are cellulases produced by a strain of Humicolainsolens (Humicola grisea var. thermoidea), particularly the Humicola strain DSM1800, and cellulases produced by a fungus of Bacillus N or a cellulase 212-producing ftmgus belonging to the genus Agromonas, and cellulase extracted fromthe hepatopancreas of a marine mollusc (Dolabella Auricula Solander).Any amylase suitable for use in a liduid detergent composition can be used inthese compositions. Amylases include, for example, amylases obtained from aspecial strain of B.licheniformis, described in more detail in British PatentSpecification No. 1,296,839 (Novo). Amylolytic proteins include, for example,RapidaseR, International Bio-Synthetics, Inc. and TerrnamylR Novo Industries.From about 0.0001% to 0.55, preferably 0.0005 to 0.1, wt. % amylase can beused.Calcium - The compositions herein may optionally comprise a calcium ionsource. Any water-soluble calcium salt can be used as a source of calcium ions,including calcium acetate, calcium formate, calcium xylene sulfonate, and calciumW0 98/ 13458101520253035CA 02265879 l999-03- llPCT/US97/1662122propionate. Divalent ions, such as zinc and magnesium ions, can replace thecalcium ion completely or in part. Thus in the liquid detergent compositions herein,the source of calcium ions can be partially substituted with a source of anotherdivalent ion.The calcium useful herein is enzyme-accessible. Therefore, the preferredcompositions are substantially free of sequestrants, for example, polyacids capableof forming calcium complexes which are soluble in the composition. However,minor amounts of sequestrants such as polyacids or mixtures of polyacids can beused. The enzyme-accessible calcium is defined as the amount of calcium-ionseffectively available to the enzyme component. From a practical standpoint theenzyme-accessible calcium is therefore the soluble calcium in the composition in theabsence of any storage sequestrants, e.g., having an equilibrium constant ofcomplexation with calcium equal to or greater than 1.5 at 20°C.Boric Acid - The compositions herein also optionally contain from about0.25% to about 10%, preferably from about 0.5% to about 5%, more preferably fromabout 0.75% to about 3%, by weight of boric acid or a compound capable offorming boric acid in the composition (calculated on the basis of the boric acid).Boric acid is preferred, although other compounds such as boric oxide, borax andother alkali metal borates (e.g., sodium ortho—, meta-, pyroborate, an sodiumpentaborate) are suitable. Substituted boric acids (e.g., phenylboronic acid, butaneboronic acid, and p-bromo phenylboronic acid) can also be used in place of boricacid.The compositions of the present invention can also contain polyols, especiallydiols, containing only carbon, hydrogen and oxygen atoms. They preferably containfrom about 2 to about 6 hydroxy groups. Examples include propylene glycol(especially 1,2 propanediol, which is preferred), ethylene glycol, glycerol, sorbitol,mannitol, glucose, and mixtures thereof. The polyol generally represents from about1% to about 15%, preferably from about 1.5% to about 10%, more preferably fromabout 2% to about 7%, by weight of the composition.Optional Ingredients - Detergent builders can optionally be included in thecompositions herein, especially for laundry compositions. Inorganic as well asorganic builders can be used. When present, the compositions will typicallycomprise at least about 1% builder and can be either an inorganic or organic builder.Liquid laundry formulations preferably comprise from about 3% to 30%, morepreferably about 5 to 20%, by weight, of detergent builder.Inorganic detergent builders include, but are not limited to, the alkali metal,ammonium and alkanolamrnonium salts of polyphosphates (exemplified by theW0 98/ 13458101520253035CA 02265879 l999-03- llPCT/US97/1662123tripolyphosphates, pyrophosphates, and glassy polymeric meta-phosphates),phosphonates, phytic acid, silicates, carbonates (including bicarbonates andsesquicarbonates), sulphates, and aluminosilicates. Borate builders, as well asbuilders containing borate-forming materials that can produce borate under detergentstorage or wash conditions (hereinafter, collectively "borate builders"), can also beused. Preferably, non-borate builders are used in the compositions of the inventionintended for use at wash conditions less than about 50°C, especially less than about40°C.Examples of silicate builders are the alkali metal silicates, particularly thosehaving a SiO2:Na2O ratio in the range 1.6:] to 3.2:] and layered silicates, such asthe layered sodium silicates described in U.S. Patent 4,664,839, issued May 12,1987 to H. P. Rieck, incorporated herein by reference. However, other silicates mayalso be useful such as for example magnesium silicate, which can serve as acrispening agent in granular formulations, as a stabilizing agent for oxygen bleaches,and as a component of suds control systems.Examples of carbonate builders are the alkaline earth and alkali metalcarbonates, including sodium carbonate and sesquicarbonate and mixtures thereofwith ultra-fine calcium carbonate as disclosed in German Patent Application No.2,321,001 published on November 15, 1973, the disclosure of which is incorporatedherein by reference.Aluminosilicate builders are useful in the present invention. Aluminosilicatebuilders are of great importance in most currently marketed heavy duty granulardetergent compositions, and can also be a significant builder ingredient in liquiddetergent formulations. Aluminosilicate builders include those having the empiricalformula:Mz(2.AlO2.ySiO2)wherein M is sodium, potassium, ammonium or substituted ammonium, z is fromabout 0.5 to about 2; and y is 1; this material having a magnesium ion exchangecapacity of at least about 50 milligram equivalents of CaCO3 hardness per gram ofanhydrous aluminosilicate. Preferred aluminb-silicates are zeolite builders whichhave the formula:Naz[(AlO2)z (SiO2)y].xH2Owherein z and y are integers of at least 6, the molar ratio of z to y is in the rangefrom 1.0 to about 0.5, and x is an integer from about 15 to about 264.Useful aluminosilicate ion exchange materials are commercially available.These aluminosilicates can be crystalline or amorphous in structure and can benaturally-occurring aluminosilicates or synthetically derived. A method forW0 98/13458101520253035CA 02265879 l999-03- llPCT/US97/1662124producing aluminosilicate ion exchange materials is disclosed in U.S. Patent3,985,669, Krummel, et al., issued October 12, 1976, incorporated herein byreference. Preferred synthetic crystalline aluminosilicate ion exchange materialsuseful herein are available under the designations Zeolite A, Zeolite P (B), andZeolite X. In an especially preferred embodiment, the crystalline aluminosilicateion exchange material has the formula:Nat2[(A102)12(Si02)121'xH20wherein x is from about 20 to about 30, especially about 27. This material is knownas Zeolite A. Preferably, the aluminosilicate has a particle size of about 0.1-10microns in diameter.Specific examples of polyphosphates are the alkali metal tripolyphosphates,sodium, potassium and ammonium pyrophosphate, sodium and potassium andammonium pyrophosphate, sodium and potassium orthophosphate, sodiumpolymeta phosphate in which the degree of polymerization ranges from about 6 toabout 21, and salts of phytic acid.Examples of phosphonate builder salts are the water-soluble salts of ethane 1-hydroxy—1, 1-diphosphonate particularly the sodium and potassium salts, the water-soluble salts of methylene diphosphonic acid e.g. the trisodium and tripotassiumsalts and the water-soluble salts of substituted methylene diphosphonic acids, suchas the trisodium and tripotassium ethylidene, isopyropylidene benzylmethylideneand halo methylidene phosphonates. Phosphonate builder salts of theaforementioned types are disclosed in U.S. Patent Nos. 3,159,581 and 3,213,030issued December 1, 1964 and October 19, 1965, to Diehl; U.S. Patent No.3,422,021 issued January 14, 1969, to Roy; and U.S. Patent Nos. 3,400,148 and3,422,137 issued September 3, 1968, and January 14, 1969 to Quimby, saiddisclosures being incorporated herein by reference.Organic detergent builders preferred for the purposes of the present inventioninclude a wide variety of polycarboxylateicompounds. As used herein,"polycarboxylate" refers to compounds having a plurality of carboxylate groups,preferably at least 3 carboxylates.Polycarboxylate builder can generally be added to the composition in acidform, but can also be added in the form of a neutralized salt. When utilized in saltform, alkali metals, such as sodium, potassium, and lithium, or alkanolammoniumsalts are preferred.Included among the polycarboxylate builders are a variety of categories ofuseful materials. One important category of polycarboxylate builders encompassesthe ether polycarboxylates. A number of ether polycarboxylates have been disclosedW0 98/13458101520253035CA 02265879 l999-03- llPCT/US97ll662125for use as detergent builders. Examples of useful ether polycarboxylates includeoxydisuccinate, as disclosed in Berg, U.S. Patent 3,128,287, issued April 7, 1964,and Lamberti et al., U.S. Patent 3,635,830, issued January 18, 1972, both of whichare incorporated herein by reference.A specific type of ether polycarboxylates useful as builders in the presentinvention also include those having the general formula:CH(A)(COOX)-CH(COOX)-O--CI-I(COOX)-CH(COOX)(B)wherein A is H or OH; B is H or -O-CH(COOX)-CH2(COOX); and X is H or a salt-forming cation. For example, if in the above general formula A and B are both H,then the compound is oxydissuccinic acid and its water-soluble salts. If A is OH andB is H, then the compound is tartrate monosuccinic acid (TMS) and its water-solublesalts. If A is H and B is -O-CH(COOX)-CI~I[2(COOX), then the compound is tartratedisuccinic acid (TDS) and its water-soluble salts. Mixtures of these builders areespecially preferred for use herein. Particularly preferred are mixtures of TMS andTDS in a weight ratio of TMS to TDS of from about 9723 to about 20:80. Thesebuilders are disclosed in U.S. Patent 4,663,071, issued to Bush et al., on May 5,1987.Suitable ether polycarboxylates also include cyclic compounds, particularlyalicyclic compounds, such as those described in U.S. Patents 3,923,679; 3,835,163;4,158,635; 4,120,874 and 4,102,903, all of which are incorporated herein byreference.Other useful detergency builders include the ether hydroxypolycarboxylatesrepresented by the structure:HO-[C(R)(COOM)-C(R)(COOM)-0],,-Hwherein M is hydrogen or a cation wherein the resultant salt is water-soluble,preferably an alkali metal, ammonium or substituted armnonium cation, n is fromabout 2 to about 15 (preferably n is from about 2 to about 10, more preferably naverages from about 2 to about 4) and each R is the same or different and selectedfrom hydrogen, C1_4 alkyl or C1_4 substituted alkyl (preferably R is hydrogen).Still other ether polycarboxylates include copolymers of maleic anhydride withethylene or vinyl methyl ether, 1, 3, 5-trihydroxy benzene-2, 4, 6-trisulphonic acid,and carboxymethyloxysuccinic acid.Organic polycarboxylate builders also include the various alkali metal,ammonium and substituted ammonium salts of polyacetic acids. Examples includethe sodium, potassium, lithium, ammonium and substituted ammonium salts ofethylenediamine tetraacetic acid, and nitrilotriacetic acid.W0 98/ 13458101520253035CA 02265879 l999-03- 11PCT /US97/1662126Also included are polycarboxylates such as mellitic acid, succinic acid,oxydisuccinic acid, polymaleic acid, benzene 1,3,5-tricarboxylic acid, andcarboxymethyloxysuccinic acid, and soluble salts thereof.Citrate builders, e.g., citric acid and soluble salts thereof (particularly sodiumsalt), are polycarboxylate builders of particular importance for heavy duty liquiddetergent formulations, but can also be used in granular compositions.Other carboxylate builders include the carboxylated carbohydrates disclosed inU.S. Patent 3,723,322, Diehl, issued March 28, 1973, incorporated herein byreference.Also suitable in the detergent compositions of the present invention are the3,3-dicarboxy-4-oxa-1,6-hexanedioates and the related compounds disclosed in U.S.Patent 4,566,984, Bush, issued January 28, 1986, incorporated herein by reference.Useful succinic acid builders include the C5-C20 alkyl succinic acids and saltsthereof. A particularly preferred compound of this type is dodecenylsuccinic acid.Alkyl succinic acids typically are of the general formulaR-CH(COOH)CH2(COOH) i.e., derivatives of succinic acid, wherein R ishydrocarbon, e.g., C10-C20 alkyl or alkenyl, preferably C12—C16 or wherein R maybe substituted with hydroxyl, sulfo, sulfoxy or sulfone substituents, all as describedin the above-mentioned patents.The succinate builders are preferably used in the form of their water-solublesalts, including the sodium, potassium, ammonium and alkanolammonium salts.Specific examples of succinate builders include: laurylsuccinate,myristylsuccinate, palmitylsuccinate, 2-dodecenylsuccinate (preferred), 2-pentadecenylsuccinate, and the like. Laurylsuccinates are the preferred builders ofthis group, and are described in European Patent Application 86200690.5/0,200,263,published November 5, 1986.Examples of useful builders also include sodium and potassiumcarboxymethyloxymalonate, carboxymethyloxysuccinate, cis-cyclo-hexane-hexacarboxylate, cis-cyclopentane-tetracarboxylate, water-soluble polyacrylates(these polyacrylates having molecular weights to above about 2,000 can also beeffectively utilized as dispersants), and the copolymers of maleic anhydride withvinyl methyl ether or ethylene.Other suitable polycarboxylates are the polyacetal carboxylates disclosed inU.S. Patent 4,144,226, Crutchfield et al., issued March 13, 1979, incorporated hereinby reference. These polyacetal carboxylates can be prepared by bringing together,under polymerization conditions, an ester of glyoxylic acid and a polymerizationinitiator. The resulting polyacetal carboxylate ester is then attached to chemicallyWO 98/1345810152025CA 02265879 l999-03- llPCT/U S97/ 1662127stable end groups to stabilize the polyacetal carboxylate against rapiddepolymerization in alkaline solution, converted to the corresponding salt. andadded to a surfactant.Polycarboxylate builders are also disclosed in U.S. Patent 3,308,067, Diehl,issued March 7, 1967, incorporated herein by reference. Such materials include thewater-soluble salts of homo- and copolymers of aliphatic carboxylic acids such asmaleic acid, itaconic acid and methylenemalonic acid.Other organic builders known in the art can also be used. For example,monocarboxylic acids, and soluble salts thereof, having long chain hydrocarbyls canbe utilized. These would include materials generally referred to as "soaps." Chainlengths of C10-C20 are typically utilized. The hydrocarbyls can be saturated orunsaturated.Other optional ingredients include soil release agents, chelating agents, claysoil removal/anti redeposition agents, polymeric dispersing agents, bleaches,brighteners, suds suppresors, solvents and aesthetic agents.The detergent composition herein can be formulated as a variety ofcompositions, for instance as laundry detergents as well as hard surface cleaners ordishwashing compositions.The compositions according to the present invention are further illustrated bythe following examples.EXAMPLE IThe following compositions are made by combining the listed ingredients inthe listed proportions.Compositions A _ _C_ D_ _E ELinear alkyl benzene 8.5 15 6.5 10 12.5 4sulfonic acid ISodium C 12.1 5 l 2 l 2 -- --alkyl sulfateC14_15 alkyl 2.5 times 10 5 10.5 -- ll 9ethoxylated sulfateC12 glucose amide -- -- 9 -- -- 5C1245 alcohol 7 times 3 10 4 7 2.5 --ethoxylatedFatty acid 2 5 5 4 2 2Citric acid 6 7 4 6 4 5CA 02265879 l999-03- 11W0 98/13458 PCTIUS97/1662128C1_7__14 alkenyl -- 6 —— 5 -— 6substituted, succinic acidSodium hydroxide 2 6 2 4 1 1 5Ethanol 2 1.5 2 4 2 1.5Monoethanolamine 6 5 4 —- -- --1,2-Propanediol 12 10 5 5 4 6Amylase (143 KNU/g) -- -— 0.1 -- -- 0.2Lipolase® (IOOKLU/g 0.5 0.2 0.5 0.5 0.4 -—commercial solution) ‘Protease B (34 g/L 0.9 -- 0.5 -- 1.2 --commerical solution)Savinase® -— 0.3 —— 0.4 0.2 0.3(commercial solution)Carezyme® 0.5 1 0.8 -— 0.2 0.8Aldehyde Inhibitorl 0.009 0.005 0.001 0.0005 0.0003 0.01Calcium Ions 0.01 0.5 0.1 0.05 0.9 0.25Water and minors Balance to 100%1) The aldehyde protease inhibitor according to Synthesis Example 1.EXAMPLE IIThe following formula is prepared.Component fltjfi/3)Alkyl, 1.4 ethoxylated, sulfate 30Amine oxide 6Polyhydroxy fatty acid amide 4Nonionic surfactant (Cl IE9) 5Mg ion from MgCl2 ' 1Ca ion from CaCl2 0.2Aldehyde Inhibitor* 0.0025Sodium xylene sulfonate 4Solvent 6Water to 100%pH to 85 *Aldehyde of Synthesis Example 1.EXAMPLE IIIWO 98/134585CA 02265879 l999-03- llPCT/US97/1662129The following compositions are made by combining the listed ingredients inthe listed proportions.mgLt’Li6_nt_S A_(_V1t_1Z<t) _|:(_W;%) _£_C W1 _l% D_(wt %lLAS 0 0 0 12AExS1 22.1 24.7 33.5 3Polyhydroxy fatty 4.6 1.2 4.2 0acid amideAmine Oxide 4.6 1.2 4.8Betaine 0 1.2Nonionic 6.7 4.1 0SurfactantMg(OH)2 0.5 0.5 0.7 0Ca ion from CaCl2 0.1 0.3 0.4 0.]Calcium xylene 4.5 0 4 0sulfonatePolyethylene 3 0 0 0glycolPolypropylene 1 .5 0 0 0glycol 2000Balance, water to 100% to ll00% to 100% to 100%Protease A or 0.001-0.01 0.001-0.0] 0.005-0.01 0.0003-0.01Protease BAldehyde 0.00025- 0.00025- 0.00025- 0.00125-Inhibitorz 0.0025 0.0025 0.0025 0.00251 x= the degree of ethoxylation. The average degree of ethoxylation for thecompositions are: A=2.2, B=0.6, C=1.4, D=2.2.2 The aldehyde of Synthesis Example 1 is used herein.

Claims (9)

WHAT IS CLAIMED IS:

1. A liquid detergent composition comprising:
a) from 1% to 95%, by weight of composition, of a detersive surfactant;
b) an active proteolytic enzyme; and c) a protease inhibitor having the formula:

Z-A-NH-CH(R)-C(O)-X

wherein A is an amino acid moiety; X is hydrogen or CF3; Z is an N-capping moiety selected from the group consisting of carbamates, ureas, sulfonamides, phosphonamides,thioureas, sulfenamides, sulfonic acids, phosphinamides, thiocarbamates, amidophosphates, sulfamoyl derivatives, and phosphonamides; and R is selected from the group consisting of straight or branched C1 - C6 unsubstituted alkyl, phenyl, and C7 - C9 alkylaryl moieties.

2. A liquid detergent composition according to Claim 1 wherein the R is selectedfrom the group consisting of methyl, iso-propyl, sec-butyl, iso-butyl, -C6H5, -CH2-C6H5, and -CH2CH2-C6H5

3. A liquid detergent composition according to either of Claims 1 or 2 comprising:
a) from 8 to 70% of said detersive surfactant;
b) from 0.0001% to 5% of an active proteolytic enzyme;
c) from 0.00001% to 5% of a protease inhibitor.

4. A liquid detergent composition according to any of Claims 1-3 further comprising a source of calcium ions.

5. A liquid detergent composition according to any of Claims 1-4 wherein the N-capping Z moiety is selected from the group consisting of (R'O)2(O)P-, (SR')2- ,R'(O)2S-, SO3H, (R')2(O)P-, R'O(O)2S-, (R')2N(O)C-, R'O(S)C-, R'-P(O)OH, R'O(OH)(O)P-, R'O(O)C-, and R'NH(O)C-, wherein each R' is independently selected from the group consisting of straight or branched C1-C6 unsubstituted alkyl, phenyl, C7-C9 alkylaryl, and cycloalkyl moieties, wherein the cycloalkyl ring may span C4-C8 and may contain one or more heteroatoms selected from the group consisting of O,N,and S.

6. A liquid detergent composition according to any of Claims 1-5 wherein said proteolytic enzyme is a subtilisin-type protease.

7. A liquid detergent composition according to any of Claims 1-6 wherein said composition is a light duty detergent composition suitable for dishcare comprising amylase enzyme.

8. A liquid detergent composition according to any of Claims 1-6 wherein said composition is a heavy duty detergent composition suitable for laundrycare further comprising an effective amount one or more of the following second enzymes: lipase, amylase, cellulase, and mixtures thereof.

9. A liquid laundry detergent composition according to any of Claims 1-8 furthercomprising from 0.25% to 10% by weight of boric acid or a compound capable of forming boric acid and a polyol.