CA2232878C - Liquid detergents with ortho-substituted phenylboronic acids for inhibition of proteolytic enzymes - Google Patents
Liquid detergents with ortho-substituted phenylboronic acids for inhibition of proteolytic enzymes Download PDFInfo
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Abstract
The present invention is directed to phenylboronic acid compounds suitable for use in the preparation of liquid laundry detergents containing a protease and at least one additional enzyme wherein the additional enzyme is protected from degradation by the protease during storage by the presence of certain ortho substituted phenylboronic acids.
Description
CA 02232878 1998-0~-12 LIQUID DETERGENTS WITH ORTHO-SUBSTITUTED
PHENYLBORONIC ACIDS FOR INHIBITION OF PROTEOLYTIC ENZYMES
This application has been divided out of Canadian Patent Application Serial No.
PHENYLBORONIC ACIDS FOR INHIBITION OF PROTEOLYTIC ENZYMES
This application has been divided out of Canadian Patent Application Serial No.
2,173,107 filed October 28, 1994, entered Canadian national phase on March 29, 1996.
FIELD OF THE INVENTION
The invention pertains to novel phenylboronic acid compounds suitable for use in the preparation of liquid laundry detergents containing a protease enzyme and at least one additional enzyme. The additional enzyme is protected from degradation by the protease during storage of the detergent by the presence of certain phenylboronic acids.
BACKGROUND OF THE INVENTION
Protease-containing liquid detergent compositions are well known. A
commonly encountered problem, particularly with heavy duty liquid laundry detergents, is the degradation by proteolytic enzyme of second (non-protease) enzymes in thecomposition, such as lipase, amylase and cellulase or combinations thereof. The 15 performance of the second enzyme upon storage, and its stability in product are thus impaired by proteolytic enzyme.
Boronic acids are known to reversibly inhibit proteolytic enzyme activity. This inhibition is reversible upon dilution, as occurs when a laundry detergent containing the enzyme is dissolved in the preparation of laundry wash water.
The inhibition constant (Ki) is ordinarily used as a measure of capacity to inhibit enzyme activity, with a low Ki indicating a more potent inhibitor. However, it has been found that not all boronic acids are sufficiently effective inhibitors of proteolytic enzyme in liquid detergents, particularly heavy duty liquid laundry detergents, regardless of their Ki values. This is believed to be due to a base catalyzed 25 decomposition of the boronic acid caused by the alkaline medium of a heavy duty liquid, with the extent and rate of the decomposition being dependent on the structure of the boronic acid molecule.
A discussion of the inhibition of one proteolytic enzyme, subtilisin, is provided in Philipp, M. and Bender, M.L., "Kinetics of Subtilisin and Thiosubtilisin", Molecular 30 & Cellular Biochemistry, vol. 51, pp. 5-32 (1983). Inhibition constants for boronic acids are provided therein, and boronic acids are cited as subtilisin inhibitors. Low Ki values are said to indicate more effective inhibitors.
One class of boronic acid, peptide alkylboronic acid, is discussed as an inhibitor of trypsin-like serine proteases such as thrombin, plasma kallikrein and 35 plasmin, especially in pharamaceuticals, in European Patent Application 0 293 881, Kettner et al., published December 7, 1988.
CA 02232878 1998-0~-12 European Patent No. 4~6,073, published November 14, 1990 discloses liquid detergent compositions containing certain bacterial serine proteases and lipases.
U.S. Patent No. 4,90~,150, Hessel et al, issued March 13, 1990 describes liquid S detergent compositions containing lipolytic enzymes wherein the stability of the lipolytic enzyme is said to be improved by incl-~sion of particular nonionic ethylene glycol containing copolymers.
U.S. Patent No. 4,566,9~, Bruno et a], issued January 2S, 1986 describes liquid cleaning compositions containing a mixture of enzymes incl~lding a protease and second 10 enzymes. The composition also contains an effective amount of benzamidine hydrohalide to inhibit the digestive effect of protease on the second enzymes. The inhibition effect is reversed upon dilution.
In European Application 0 376 705, Cardinali et al, published July 4, 1990, liquid detergent compositions containing a mixture of lipolytic enzymes and proteolytic 15 enzymes have been described. The storage stability of the lipolytic enzyme is said to be enhanced by the inclusion of a lo~ver aliphatic alcohol and a salt of a lower carboxylic acid and a surfactant system which is predominantly nonionic.
In ~uropean Patent Application 0 3S1 262, Aronson et al, published August S, 1990, mixtures of proteolytic and lipolytic enzymes in a liquid medium have been20 disclosed. Tlle stability of lipolytic enzylne is said to be improYed by the addition of a stabilizing system comprising boron compoul1d and a polyol ~Yhich are capable ofreactin;,, ~hereby the polyol has a first bindhlg constant ~ith the boron compound of at least 500 l/mole and a second binding constant of at least 1000 I'/mole2.
PCT ~pplication WO 92/19707, published October 30, 1992 discloses meta 25 substituted boronic acids as reversible plotease inhibitors in liquid laundry detergents.
Tl~ey are indicated as being supel ior to the para substituted isomers for this purpose.
Tlle stabilit~ of se~eral substit~lted phenylbolollic acids is discussecl by K~ ila et a]. in Call2diall Jonrl1al of Chemistry at 30SI-3090 (]963).
-2a-SUMMARY OF THE INVENTION
The present invention is directed to phenylboronic acid compounds of the formulas:
B (OH)2 Y~X
Y
o here X is selected from the group consisting of-NHR, -OCR~
o -~rHCR, or -NHS02R, wherein R is Cl-C3 al~yl and ~,herein each Y is selected 5from the group consisting of H~ C I -C4 all~l and halogen~ and b.
B(0H)2 Y ~Q(A)n~
~;herein Q is -O- or -N~ A is an arnino acid moiety or 2 pep.ide moiety comprised of 2 combination of arr ino acid moie;ies, the amino acid being selected from the group consis~ing of A~a, ~r~ sn, Asp, Cys, Gln, Glu~ Gly, His, lle, Leu, Lys~ ei, P'ne, Prc .
Ser, Thr, Trp, Tyr and ~'al, the 2mino acid or peptide moie;~ being lin.~;ed to Q as ar, 10 es~e, or amide through the czrbo~ylic acid 2~ the C terminus, P is selected from the ~roup consisting of hydro,gen, and arnine protecting groups, n is 1-5 Y is selected fron~
the group consisting of hydrogen, C I -C4 al!;yl and halogen These novel compounds are suitable for use in the preparations of alkaline laundry detergent compositions comprising:
15a. from about O.OOI to 10 weight % of certain phenylboronic acids having structures described hereinafter;
b. from about O.OOOI to 1.0 weight ~,'0 of proteolytic enzyme;
c. a performance-enhancing amount of at least one detergent-compatible second enzyme; and CA 02232878 1998-0';,-12 ~YO gS/12655 Pc~ s9~112407 . from about 1 to 80 weight % of detersive surf2c;ant.
e. a lic~uid medium f. sufficient alkaline material to provide said composition with a pH of greater than 7 ~~hen measured as a 10% aqueous solution.
s DESCRIPTION OF T~ IN~ 'T10~
The instant liquid detergent compositions contain five essential ingredients: (a) celtain phenyl boronic acids, (b) proteolytic en~me, (c) detergent-compatible second enzyme, (d) detersive sutfactant, (e) a liquid medium, and (f) sufficient alkaline material 0 to provide the composition with a pH of greater than 7 wh~n measured as a 10~/O
solution in water. All percentages and proportions herein are "by weight" un~essspecified otherwise.
(a) o-Substituted Phenylboronic Acids The boronic acids comptising component (a) of the composition of the presen~
15 invention are ottho-substituted phenylboronic acids which have the following forrnulas:
(1) ' B (OH)2 Y~X
where ~ is -NO?, -NH2, -N~, -OH, -O~, -OCR, -N~I~R or -NHS02:~, wherein ~ is Cl-C4 (preferably Cl-C2) aL~I or aryl"and wherein ea~h ~ is H, Cl-C4 20 (preferably Cl-C2) aL~l or halogen (e.~,., chloro- or bromo).
(2) B (OH)2 Y [~Q(a)n~
wherein Q is -O- or -NH, A is an amino acid moiety or a pe?iide moiety comprised ~5 of a combination of amino acid tnoieties, tlle alnino acid, ~ng sele~ted fromal~Line (~la), arginine (Arg), asparagine (Asn), aspar~ic 2Ci~ (Asp), cysteine (C~s), glutarnine (Gln), glutamic acid (Glu), glycine (Gly), histidine (~-~is), isoleucine (lle), leucine (I leu), Iysine (Lys), methionine (Met), phenyalanine (Phe), proLine (Pro), ~ serine (Ser), threon~ne (Thr), tryptopl~an (Trp), tyrosine (T~;r) and valirle (~al), the 30 said amino acid or: peptide moiety being Lin~ied to Q as an es~er or amide through the W O95112655 PCT~S94/12407 carboxylic acid of said amino acid or peptide at the C terrninus, P is hydrogen or an amine protecting group, n is l-5, and ~ach Y is H, Cl-C4 alkyl or halogen.
Preferred amino acids are alanine, leucine, valine, isoleucine proline, phenylalanine, tryptophan glycine, arginine, and methionine Amine protecting groups are groups s which are attached to the amine end of an amino acid or peptide to block reaction by the amine when the carboxylic acid group is being reacted with another material.Typical amine protecting groups are methoxycarbonylJ benzyloxycarbonyl and tertiarybutoxycarbonyl .
Y is preferably H in both Type l) and Type ~ compounds The preferred o compounds are those of Type (l) wherein X is -NH~CH3, and the compounds of Type 2 wherein Q is -NH. I .
The compounds of Type (l) wherein X is -NHR, -NHlR,- . ~
NHS02~ and -O~?R wherein R is aryl, or Cl to C3 aL~cyl, and the compounds of Type 2 are novel and are the subject matter of the present invention.
lS - It is believed that boronic acids inhibit proteolytic enzyme activity by forming a reversible covalent bond to the serine hydroxyl group in the active site of the proteolytic enzyme. Upon dilution, under typical wash conditions, protease activity is regained once this bond is broken and the boronic acid diffuses away from the proteolytic enzyme.
Aside from the ability to bond with protease, the efficacy of a protease inhibitor is also deterrnined by the ir~herent chemical stability of the inhibitor in the medium in whicll it is use~d.
The ortho substituted phenylboronic acids are superior to the compa~ble meta and ~ substituted compounds. This is believed ~5 to ~e due to (l) their better chemic~l stability in a concentrated allcaline detergent medium, and/or (2) their higher binding affil ity to the protease.
Examples of boronic acids are: o-hydroxyphenylboronic acid, o-nitrophenylboronic acid, o-aminopllenylboronic acid, o-N-acetylaminophenyl~oronic acid, ~oc-~iie-Gly-~la-o- aminophenylhoronic acid, o-I~T-sulfonamidophenyl~oronic acid, 2-amino-4-chlorophenylb~ronic acid, 2-nitro-3-ethylphenylboronic acid, Z-Gly-Ala-o- arninophenylboronic acid. In the above-recited peptide derivatives, the tenn "Moc" means methoxycar~onyl and the te~n Zmeans ~nzyloxycar~onyl, both of which are amine protecting gTOUpS The peptide deriYati~es without the amine protecting groups a;re also useful.
The ortho substituted ~oronic acids can conver~iently be made, starting with the process described by Seaman et al., J. Am. Chem. S~c., ~'ol. 53, p. 71 l (Feb.
CA 02232878 1998-0~-12 - ]931). The process involves preparation of o-nitro phenylboronic acid by reaction of fuming nitric acid with pllenylboronic acid in the presence of acetic anllydride. The product is a mixture of approximately 95% ortho and 5% E~ nitro phenylboronic acid.
The ortho and ~ isomers can be separated by crystallization. The o-nitro compound 5 can be converted to other derivatives by known reaction means. For example, the corresponding amino derivative can be prepared by catalytic hydrogenation of thenitro compound.
The hydroxyl derivative can be prepared by diazotization of the o-amino derivative, followed by hydrolysis. The ether and ester derivatives can be prepared by 10 kno-vn reactions from the hydroxyl derivative, e.g., reaction with an alkyl chloride to fonn the ether and ~Vit]1 a carboxylic acid to forrn the ester.
The amido derivative can be prepared by reacting the o-amino derivative with acetic anhydride.
The peptide derivative can be prepared by reacting the o-amino derivative ~vith 15 ethylenegl~col to produce-tlle cyclic boronic ester, reacting the o-amino group with the desired peptide and then hydrolyzing the boronic ester back to the acid form.
The sulfonamido derivative can be prepared by reacting the o-amino derivative witl1 an alkyl sulfonyl chloride.
In the above liquid detergent compositions, from about 0.001 to 10%, preferabl~
about 0.02 to 5%, most preferably 0.05 to 2% of the ortho substituted phenylboronic acid is ~Ised.
(b) Proteol~tic Enzvme A second essential ingredient in the above liquid detergent compositions is fromabout 0.000] to 1.0%, preferably about 0.0005 to 0.5%, most preferably abo~lt 0.002 to 25 0.1%, of proteolytic en~yme. Mi~;t-lres of proteolytic enzylnes are also includecl ~Yit]-in tl~e terml proteolytic enzyme 11Creil1 The proteolytic cnz~tl1e can be of animal, vegetable or microorgal1islll (preferred) origim More prefened is serine proteol~tic enzymc of bacteri~l origin. Purifiecl or nollp~llifiecl fonns of tlle enz~me ma) be ~Ised. Proteolytic enz~lne, prod~lcecl by chelnically or geneticall~ modified mutal1ts are incl~lclecl by 30 c3efinition, as are close strllct~n-al enzyn1c ~ariants. Partic~llarly prefelred is bactcrial serine pro,eol~tic enz~ne obtained from Bacilllls subtilis and/or Bacillus licl~enifoln1is.
Suitable proteolytic enzymes inclllde Alcalase~), Esperase~), Savinase~), all available from NOVO Nordisk N/A; Maxatase~, Ma~;acal~), and Ma~;apem lSi~ (protei engineered Ma~;acal~), all ,available from Gist Brocades, and sllbtilisin - BPN and BPN', available from Sigma Chemical Company. Preferred proteolytic enzymes are also modified bacterial serine proteases, such as those described in European Patent Application 251,446, Wells et al., published January 7, 1988, and wl1ich is called herein "Protease B", and in U.S. Patent No. 5,030,37S, Venegas, issued July 9, 1991, ~vhich refers to a modified bacterial serine proteolytic enzyme which is called "Protease A" herein. Preferred proteolytic enzymes are selected from the group consisting of Savinase~), Maxacal~), BPN', Protease A and Protease B, and mixtures thereof. Another preferred protease is tl1at described in the patent application CA 2,173,105 of A. Baeck, C. K. Ghosh, P. P. Greycar, ~. R. Bott and L. J. Wilson entitled "Protease Containing Cleaning Compositions," published April 20, 1995.
(c) Second Enzyme Tlle third essential ingredient in the above liquid compositions is a performance-enhancing amount of a detergent-compatible second enzy,rne. By "performance-enhancing" is meant improving the enzyme-based cleaning perforrnance of the composition beyond that achieved by use of the protease. By "detergent-compatib]e" is - meant compatibility ~vith the other ingredients of a liquid detergent composition, such as detersive surfactant, detergency builder, and alkaline pH. These second en~ymes are preferably selected from the group consisting of lipase, amylase, ce]lulase, and mixtures thereof. The terrn "second enzyme" excludes the proteo]ytic enzymes discussed abo~e~ so each composition herein contains at least h~o kinds of enz~me, including at least one proteolytic enzyme and at least one additional enzyme ~hich is nol a protease.
The amount of second enzyme used in the composition varies according to the type of enz~me and the use intended. In general, from about 0.000~ to 1.0%, morepreferably 0.001 to 0.5% on an active basis of these second enzymes are preferably used.
~ tures of enzyl11es from the same class (e.g. Iipase) or t~o Ol nlore classes (e.g. celllllase alld lipase) nlay be usec~ PLII jfiCCd or non-pllrified fcrnls of the enzylnc may be used.
Lipase and cell~llases are partic~llar]y preferrcd as second enz)~mcs herein.
Any lipase suitab]e for ~ISC in a liquid detergent ColllpC)sitio;1 can bc ~lsed llereill.
Suitable lipases for use hereil1 inc]ucle those of bactelial and fnnoal origin. Lipases from cl~enlically or genetically n1odifie(1 mutallts are included.
CA 02232878 1998-0~-12 - Suitable bacterial lipases include tllose produced by Pseudomonas, such as Pseudomonas stutzeri ATCC 19.154, as disclosed in British Patent 1,372,034. Suitable lipases include those which show a positive immunological cross-reaction with the antibody of the lipase produced by the microorganism Pseudomonas fluorescens IAM5 1057. This lipase and a method for its purification have been described in Japanese Patent Application 53-20487, laid open on February 24, 1978. This lipase is available under the trade name Lipase P "Amano," hereinafter referred to as ''Amano-P"
from Toyo Jozo Co., Togata Japan. Such lipases should sho~Y a positive immunological cross reaction with the Amano-P antibody, ~lsing tlle standard and ~vell-known 10 immunodiffusion procedure according to O~lcllterlony (Acta. Med. Scan., 133, pages-76-79 (1950)). These lipases, and a method for their immunological cross-reaction with Amano-P, are also described in U.S. Patent No. 4,707,29], Thom et al., issued November 17, 1987. Typical examples thereof are the Amano-P lipase, the lipase ex Pseudomonas fra i FERM P 1339 (available under the trade name Amano-B), lipase ex Psuedomonas 15 nitroredllcens var. Iipolytic~lm FERM P 1338 (available under the trade name Amano-CES), lipases ex Chromobacter ~iscosum, e.g. Chromobacter viscosum var.
lipolYticum NRRlB 3673, and fi~rther Chromobacter viscosum lipases, and lipases ex Pseudomonas ~ladioli. Other lipases of interest are Amano AKG and Bacillis Sp lipase (e.g., SolYay enzymes).
Other lipases ~Yhich are of interest ~here they are detergent-compatib]e are those described in U.S. Patent No. 5,223,169, El-Sayed et a]., issued June 29, 1993, EP A O 385 401, publislled September 5, 1990, IJ.S. Patent l\'o. 5,153,135, Farin et al., issued October G, 1992, and U.S. Patent No. 5,07~,S9~, Jars, issued Januar~ 7, 199~.
Suitable fungal lipases include those prod~lcible by Humicola lanu~Jinosa and Thermom~ces lan~l~inosus. Most preferred is lipase obtained by cloning the gene from I~umicola lanu~ osa alld e~;pressing thc genc in Asl)ereillus or~:ae as described in Eulopeall Patent Application 0 25~ n6~, comlnerciall~ available luldel the trade nal11e Lipolase~.
Froln about 2 to 20,000, preferably abollt 10 to 6,000, lipase nnits of lipase per gran1 (LU/g) of plodllct are typically use(l in tllese colnpositiol~s. A lipase ~nlit is that amoul1t of lipase ~YIlicll prod~lces ] n1mo] of titratable butyric acid per n1il1-lte in a pH
stat, ~vhere pH is 7.0, temperat~ne is 30~C, and sllbstrate is an emulsioll of trib~ltyrin and gLlm arabic, in the presence of Ca2+ and NaCI in phosphate buffer.
Any cellulase suitable for ~Ise in a liq~id detergent composition can be ~lsed in these compositions. Suitable cellulase enzymes for use herein include those of bacterial and ~Ingal origins. Preferably, they ~Yill have a pH optimum of bet~veen 5 and 9.~. From about 0.0001 to 1.0, preferably 0.001 to 0.5% on an actiYe enzyme basis of cellulase can be used.
S Suitable cellulases are disclosed in l~.S. Patent No. 4,435,307, Barbesgaard et al., issued March 6, 1984, which discloses fungal cellulase produced from Humicola insolens.
Suitable cellulases are also disclosed in GB-A-2,095,275 and U.S. Patent No. 3,844,890, Horikoshi et al., issued October 29, 1974.
Examples of such cellulases are cellulases produced by a strain of Humicola 10 insolens (Humicola ~risea var. thermoidea), particularly the Humicola strain DSM 1S00, and cellulases produced by a fungus of Bacillus N or a cellulase 212-producing fungus belonging to the ~enus Aeromonas, and cellulase e~;tracted from the hepatopancreas of a marine mollusc (Dolabella Auricula Solander).
Any amylase suitable for use in a liquid detergent composition can be used in 15 tllese compositions. Amylases include, for example, a-amylases obtained from a special strain of B.licheniforrns, described in more detail in British Patent Specification No.
1,296,839. Amylolytic proteins include, for example, Rapidasen', and TermamylT~'aYailable from NOVO l~ordisk and Ma~;amyl, available from Gist Brocades.
From about 0.0001 to 1.0%, preferably 0.0005 to 0.5% on an active enzyme 20 basis of amylase will typically be used.
(d) Detersive S~lrfactant From about 1% to ~0%, preferably about 3% to 50%, most preferably about 10%
to 30%, of sulfactant is an essential in,o,redient in detergent compositions.
The surfactant can be selected from the group consisting of anionics, 25 nonionics, cationics, ampllolytics, z~vitterio]lics, and mi~;tures thereof. Aniollic and nonionic surfactallts are preferl-ed.
Al~y] su]fate surfactants, eitl~er primary Ol secoo~lary, ale a t~pe of anionic smfactant of importance for use hereill. All~yl sulfates Jlave the cen~ral fonnula ROSO3M ~vherein R preferably is a C,0-C2, hyclrocarbyl, preferabl~! a al~yl straight or 30 brancl~ed chaill or hydro~;yalliyl ha~ inc, a C~0-C~o al~yl componeni, more preferably a C,,-C,s al~yl or hydlo~;yalLiyl, and M is H or a cation, e.g., an al~ali metal cation (e.g., sodhlm potassium, lithiulll), substitllted or unsubstitllted ammoniulll cations sucl~ as metllyl-, dimethyl-, and trillletllyl ammonium and quaternar~ ammonium cations, e.~,., tetrametllyl-ammolliulll and dimethyl piperdinium, and cations deri~ed from 35 alkalloJamilles sucll as ethallolamille, diethanolanlille, triethano]alllille, and mi~tures thereof, and the lil~e. l'ypically, all~y] cllains of Cl,-CI6 ale preferred for lo~ver wasl WOgS/12655 PCTrUS94/12407 tempera.~tures (e.g.~ belo-v about 50'aC) and C 16-18 al'~yl chains are preferred for hioher wash temperatures (e.g.~ about 50~C).
Al'~;yl alkoxylated sulfate surfactants are another cate~Cry of useful anionic surfactant. These surfactants are water soluble salts or acids typically of the for s formula RO(A)mS03M wherein R is an unsubstituted Clo-C~4 alkvl or hydroxyalkvl group having a C I o-C24 alkyl component~ preferably a C 1 2-C20 alkyl or hydroxyal};yl~
more preferably C 1 2-C 18 alkyl or hydroxyalkyl~ A is an ethoxy or propoxy unit~ m is greater than zero~ typically between about 0.5 and about 6~ more preferably between about 0.5 and about 3~ and M is H or a cation ~hich can be, for example~ a metalcation (e.g.~ sodium~ potassium, lithium, calcium~ magnesium~ etc.)~ ammonium orsubstituted-ammor. ium cation. PJ~yl ethoxylated sulfates as well as alkyl propoxylated sulfates are contemplated herein. Specific examples of substituted arrlrnonium cations include methyl-, dimethyl-~ trimethyl-arnrnonium and quaternary ammonium cations~
such as tetramethyl-ammonium~ dimethyl piperdinium and cations derived frorn s alkanolamines~ e.g.~ monoethanolamine~ diethanolarnine~ and triethanolamine, and rnixtures thereof. Exempiary surfactants are C12CI~ alkyl poiyetho.~late (1.0) sulfate, Cl~-CIs alkyl polyethoxylate (2.25) sulfate, C12-Cl~ a~l;yl polyethoxylate (3.0)sulfate, and C~ 2-C1 8 alkvl polyethoxylate (a,.O) sulfate wherein M is conveniently selected ~rom sodium and potassium.
Other anior ic surfactants useful for detersive purposes czn also be included inthe compositions hereof. These can include salts (including~ for e~;ample, sodium potassium~ ammonium, and substituted ammonium salts such ?. rr,ono-~ di- and triethanolamine salts) of soap, Cg-C20 linear alkylbenzenesulphonates~ C~-C22 primar~
or secondary alkanesulphonates~ Cg-C24 olefinsulphonates, sulphonated polycarboxylic 2s acids, alkyl glycerol sulfonates, fatty acyl glycerol sulfonates, fztty oleyl glycerol sulfates, alkyl phenol ethylene oxide ether sulfates, paraffin sulfonates, alkylphosphates, isothionates such as the acyl isothionates~ ~-acyl tzurates~ fatty acid arnides of methyl tauride, alkyl succinamates and sul~osuccin2.~ s~ monoesters of sulfosuccinate (especially saturated and unsaturated C12-C~ monoesters) diesters of sulfosuccinate (especially saturated and unsaturated C6-C14 àies~ers)~ N-acyl sarcosinates, sulfates of alkylpolysaccharides such ~s the sulfa es of alk~lpolyglucoside~
branched primary alkyl sulfates, all~l polyethoxy carboxylates sarh as those of the formula RO(CH2CH2O)kCH2COO-I~ wherein R is 2 CS-C2~ z~ k is arl integer from 0 to 10, and M is a soluble salt-forrning cation, znd fatty zci~j esterified with 3~i esethionic acid and neutrali~ed ~ ~ith sodium hydro~;ide. Further exarnples are gi~en in Surface Active A~ents and Deter~ents (Vo~. I and Il by Sch~ znz~ Perry and Berch).
Nonionic surfactants such as block alkylene oxide condensate of C6 to C 1 ~
alkyl phenols, alkylene oxide condensates of C8-C22 alkanols and ethylene oxide/propylene oxide block polymers (PluronicT~'-BASF Corp.), as well as semi polar nonionics (e.g., amine oxides and phosphine oxides) can be used in the present compositions. An extensive disclosure of these types of surfactants is found in U.S.
PatentNo. 3,929,678, Laughlin et al., issued December 30, 1975.
Amphol~ic and zwitterionic surfactants s~lch as described in U.S. Patent No.
3,929,678, supra can also be used in the compositions of the invention.
Cationic surfactants suitable for use in the compositions herein are described in U.S. Patent No. 4,228,044 Carnbre, issued October 14, 1980.
Alkylpolysaccharides such as disclosed in U.S. PatentNo. 4,S65,647 Llenado can be used as surfactants in the compositions.
Polyhydroxy fatty acid amides can be used as surfactants herein.
These materials have the fo;rrnula:
O R, lS 11 1 wherein: R~ is H, Cl-C4 hydrocarbyl, 2-hydroxy ethyl, 2-hydroxy propyl, or a mixture thereof, preferably C,-C4 alkyl, more preferably C, or C2 alkyl, most preferably C, alkyl (i.e., methyl); and R2 is a C5-C3, hydrocarbyl, preferably straight chain C7-C,~ alkyl or 20 alken~l, more preferably straight chain C9-C,7 a]liyl or all;eny], most preferably straight Cllain C"-C,5 alkyl or alkenyl, or mixtures thereof; and Z is a polyhydroxyhydrocarbyl having a ]inear hydrocarbyl chain with at least 3 hydroxyls directly connected to the cllain or an alkoxylatecl derivative (preferably ethoxy]ated or propo:;y]ated) thereof. Z
preferably ~ill be deri~ed from a reducillg sugar in a red~lcti~e 2mination reaction; more 25 preferab]y Z ~vill be a glycityl. Suitable red~lcing s~lgars include gl~cose, fi-uctose, Jnaltose, lactose, galactose, mallllose, ancl xy]osc. As ra~ materials, high dextlose corn syrllp, high fi-Llctose corn syrup, and high maltose COIIl syr-lp can be lltilized as ~vell as the in~liYid~lal sugars listed above. T]lese COIIl SylllpS Inay yie]d 2 mi:~ of s~gar componentS for Z. ]t Sl~O~llcl be ~Inclel-stood that it is by no means in~ended to exc]LIdc 30 othel suitable ra~v matelials. Z prefel-ably ~vill be selected fiom the ~ro~lp consisting of --CH2--(CHOH)n--CH20H,--CH(CH~OH~(CHOH)n.,~CH20H, --CH2--(CHOH)2(CHOR')(CHOH~CH2OH, and allioxylated deri~ atiYes thel-eof, wllere n is an integer fiom 3 to 5, inc]~lsi~e, and R' is H or a cyclic CA 02232878 1998-0~-12 WO95/12655 PCTrUS9~/12407 or alipha~tic monosaccharide. Most preferred zre glycityls ~vherein n is 4~ particularly -CH2-(CHOH)4-CH20H .
In Formula (I), Rl can be~ for example~ methyl~ ethyl~ propyl~ isopropYI~ butyl,2-hydroxy ethyl~ or 2-hydroxy propyl.
s R2CO-N< can be~ for example, cocamide, stearamide~ oleamide, lauramide, myristamide. capricarnide, palrnitamide, tallowarr~ide, etc.
Z can be l-deoxyglucityl, 2-deoxyfiuctityl~ I-deoxymaltityl~ I-deoxylactityl, 1-deoxygalactityl, I-deoxymannityl, I-deoxymaltotriotityl, etc.
A particularly desirable surfactant of this type for use in the compositions herein o is all~yl-N-methyl glucomide, a compound ofthe above formula wherein R2 is all;yl (preferably Cl l-C13), R, is methyl and Z is l-deoxyglucityl.
(e) Liquid Medium The liquid medium of the compositions herein is typically water, but may be a an organic solvent ~vhich is miscible with water or a combination of one or more of such organic solvents and water. Examples of suitable water rniscible organic solvents are ethanol, propanol, isopropanol, ethylene glycol, propylene glycol and glycerine.
The liquid medium comprises at least 10%, typically from about 10% to 70%, preferably 20% to 60% and most preferably about 40% to 50% ofthe composition.
(f) Alkaline Material The compositions herein are forrnulated to have an alkaline pH, i.e., a pH
greater than 7 when measured as a 10% solution in water. Typical]y the pH ~ill be between about 7.5 and I 1, preferably from about 7.5 to ~.5. The desired pH can be achieved by use of buffers (e.g., sodium bicarbonate, disodium hydrogen phosphate) alkalis (e.g., sodium hydro~ide)~ alkaline detergency builders (such as described beio~v)~
andlor organic bases such as monoethanolamine as is well kno~ n to those skilled in the art (g) Optional In~redients The compositions herein can contain ~arious optional ingredients. A
preferred optional ingredient is a detergency builder. These materials are used at le~els of from 1% to about 50%~ preferably about 3% to 30%, more preferably about 5% to 20% in the composition herein. Inorganic as ~ell 2S organic builders can be used.
Inorganic detergency builders include, but are not limited to~ the alkali metal, ammonium and all;anolammonium salts of polyphosphatés (exemplified by CA 02232878 1998-0~-12 the tripolyphosphates, pyrophospllates, and glassy polymeric meta-phosphates), phosphonates, phytic acid, silicates, carbonates (including bicarbonates and sesquicarbonates), sulphates, and aluminosilicates Borate builders, as well as builders containing borate-forrning materials that can produce borate under detergent 5 storage or wash conditions (hereinafter, collectively "borate builders"), can also be used. Preferably, non-borate builders are used in the compositions of the invention intended for use at wash conditions less than about 50~C, especially less than ~bout 40~C.
Examples of silicate builders are the alliali metal silicates, particularly those having a SiO2:Na20 ratio in the range 1.6:1 to 3.2:1 and layered silicates, such as the layered sodium silicates described in U.S. Patent ~o. 4,664,839, issued May 12, 19~7 to H. P. Riecli. However, other silicates may also be useful such as for example magnesium silicate, ~vhich can serve as a stabilizing agent for o~y,en bleaches, and as a component of suds control systems.
E~amples of carbonate builders are the all~aline earth and al~;ali metal carbonates, 15 including sodium carbonate and sesquicarbonate and mixtures thereof.
Aluminosilicate builders are also useful in the detergent compositions descrlbed herein.
Aluminosilicate builders are of great importance in most currentl~ mar}~eted heavy duty granular detergent compositions, and can also be a significant builder ingredient in liquid detergent formulations. Aluminosilicate builders include those ha~ ing the empirical 20 formula:
Mz(zAl02 YSio2) ~vherein M is sodium, potassium, ammoniunl or substituted ammoni~lm, z is from about 0.5 to about 2; and y is 1; this material having a magnesium ion e~;change capacity of at least about 50 milligram equiva]ents of CaC03 llardness per gram o, anllydrous 25 alulllinosilicate. Preferred alumillosilicates are zeolite buildels ~hi~h ha~e the formu]a:
Naz[(Al02)z (SiO~)y] ~;H~O
~vhereill z ancl y are integers of at least 6, tlle n~olar ratio of z to ! i~ in tlle range from 1.0 to about 0.5, and ~; is an integer from about 15 to about 26 .
Specific e~;alllples of polypllospllates are the alliali Ineta!
30 tripolyl)llospllates~ socliulll, potassiulll allcl am~llo~ pyJophosp'l2.. sodiulll alld potassium ancl amlllollium pyl-opllospllate, sodi~lm ancl potassi-ull orhophosphate, sodiu polymeta phospllate in ~vhicll the degree of polynielizatioll range, fr~m abo~lt 6 to about 21, and salts of phytic acicl.
Preferred organic detergent builders for the detergent compositions described herein include a wide variety of polycarboxylate compounds. As used herein, "polycarboxylate'' refers to compounds having a plurality of carboxylategroups, preferably at least 3 carboxylates.
Polycarboxylate builder can generally be added to the composition in acid form, but can a]so be added in t]le forrn of a neutralized salt. When utilized in salt forrn, alkali metals, such as sodium, potassium, and litllium, c,r alkanolammonium salts are preferred.
Included among the polycarboxylate builders are a variety of categories of useful materials. One important category of polycarboxylate builders encompasses the etller 10 polycarboxylates. A number of ether polycarboxylates have been disclosed for use as detergent builders. Examples of useful ether polycarbo~;y]ates include oxydisuccinate, as disclosed in Berg, U.S. Patent No. 3,128,2~7, issued April 7, 1964, and Lamberti et al., U.S. Patent~lo. 3,635,830, iss~led January IS, 1972.
A specific type of ether polycarbo~;ylates usefu] as builders in tlle present 15 invention also include tl)ose llaving the general forn~u]a:
CH(A)(COO~CH(COOX)~CH(COOX}CH(COO~f)(B) ~vherein A is H or O~I; B is H or--O CH(COOX~CH2(COO~); and X is H or a salt-forming cation. For e~ample, if in the aboYe general forrnula A and B are both H, then the compo~lnd is o~;ydissuccinic acid and its ~vater-so]uble salts. If A is OH and B is H, 20 tllen the compound is tartrate mollosuccillic acid (TMS) and its ~ ater-soluble salts. If A
is H and B is--O--CH(COOX~CH2(COO~), then the compound is tartrate disuccil1ic acid (TDS) and its ~vater-soluble salts. Mixtures of these b~lilders are especial]y prefened for use ]~erein. Particl~lally preferred are mi~t-lres of TMS and TDS in a ~veight ratio of TMS to TDS of fiom about 97:3 to about 20:~0. These bllilders are disclosed in U.S.
25 I'atent No. 4,663,071, issnecl to Bllsh et al., on Ma~ 5, 19S7.
~iuitable ethel polycalbo~;~dates also inclllcle cyclic compo~nù" paltic~llarly alic!'clic con~poullds, sucll as those described in U.~. Patent Nos. 3 ~)23,679; 3,~35,]63;
FIELD OF THE INVENTION
The invention pertains to novel phenylboronic acid compounds suitable for use in the preparation of liquid laundry detergents containing a protease enzyme and at least one additional enzyme. The additional enzyme is protected from degradation by the protease during storage of the detergent by the presence of certain phenylboronic acids.
BACKGROUND OF THE INVENTION
Protease-containing liquid detergent compositions are well known. A
commonly encountered problem, particularly with heavy duty liquid laundry detergents, is the degradation by proteolytic enzyme of second (non-protease) enzymes in thecomposition, such as lipase, amylase and cellulase or combinations thereof. The 15 performance of the second enzyme upon storage, and its stability in product are thus impaired by proteolytic enzyme.
Boronic acids are known to reversibly inhibit proteolytic enzyme activity. This inhibition is reversible upon dilution, as occurs when a laundry detergent containing the enzyme is dissolved in the preparation of laundry wash water.
The inhibition constant (Ki) is ordinarily used as a measure of capacity to inhibit enzyme activity, with a low Ki indicating a more potent inhibitor. However, it has been found that not all boronic acids are sufficiently effective inhibitors of proteolytic enzyme in liquid detergents, particularly heavy duty liquid laundry detergents, regardless of their Ki values. This is believed to be due to a base catalyzed 25 decomposition of the boronic acid caused by the alkaline medium of a heavy duty liquid, with the extent and rate of the decomposition being dependent on the structure of the boronic acid molecule.
A discussion of the inhibition of one proteolytic enzyme, subtilisin, is provided in Philipp, M. and Bender, M.L., "Kinetics of Subtilisin and Thiosubtilisin", Molecular 30 & Cellular Biochemistry, vol. 51, pp. 5-32 (1983). Inhibition constants for boronic acids are provided therein, and boronic acids are cited as subtilisin inhibitors. Low Ki values are said to indicate more effective inhibitors.
One class of boronic acid, peptide alkylboronic acid, is discussed as an inhibitor of trypsin-like serine proteases such as thrombin, plasma kallikrein and 35 plasmin, especially in pharamaceuticals, in European Patent Application 0 293 881, Kettner et al., published December 7, 1988.
CA 02232878 1998-0~-12 European Patent No. 4~6,073, published November 14, 1990 discloses liquid detergent compositions containing certain bacterial serine proteases and lipases.
U.S. Patent No. 4,90~,150, Hessel et al, issued March 13, 1990 describes liquid S detergent compositions containing lipolytic enzymes wherein the stability of the lipolytic enzyme is said to be improved by incl-~sion of particular nonionic ethylene glycol containing copolymers.
U.S. Patent No. 4,566,9~, Bruno et a], issued January 2S, 1986 describes liquid cleaning compositions containing a mixture of enzymes incl~lding a protease and second 10 enzymes. The composition also contains an effective amount of benzamidine hydrohalide to inhibit the digestive effect of protease on the second enzymes. The inhibition effect is reversed upon dilution.
In European Application 0 376 705, Cardinali et al, published July 4, 1990, liquid detergent compositions containing a mixture of lipolytic enzymes and proteolytic 15 enzymes have been described. The storage stability of the lipolytic enzyme is said to be enhanced by the inclusion of a lo~ver aliphatic alcohol and a salt of a lower carboxylic acid and a surfactant system which is predominantly nonionic.
In ~uropean Patent Application 0 3S1 262, Aronson et al, published August S, 1990, mixtures of proteolytic and lipolytic enzymes in a liquid medium have been20 disclosed. Tlle stability of lipolytic enzylne is said to be improYed by the addition of a stabilizing system comprising boron compoul1d and a polyol ~Yhich are capable ofreactin;,, ~hereby the polyol has a first bindhlg constant ~ith the boron compound of at least 500 l/mole and a second binding constant of at least 1000 I'/mole2.
PCT ~pplication WO 92/19707, published October 30, 1992 discloses meta 25 substituted boronic acids as reversible plotease inhibitors in liquid laundry detergents.
Tl~ey are indicated as being supel ior to the para substituted isomers for this purpose.
Tlle stabilit~ of se~eral substit~lted phenylbolollic acids is discussecl by K~ ila et a]. in Call2diall Jonrl1al of Chemistry at 30SI-3090 (]963).
-2a-SUMMARY OF THE INVENTION
The present invention is directed to phenylboronic acid compounds of the formulas:
B (OH)2 Y~X
Y
o here X is selected from the group consisting of-NHR, -OCR~
o -~rHCR, or -NHS02R, wherein R is Cl-C3 al~yl and ~,herein each Y is selected 5from the group consisting of H~ C I -C4 all~l and halogen~ and b.
B(0H)2 Y ~Q(A)n~
~;herein Q is -O- or -N~ A is an arnino acid moiety or 2 pep.ide moiety comprised of 2 combination of arr ino acid moie;ies, the amino acid being selected from the group consis~ing of A~a, ~r~ sn, Asp, Cys, Gln, Glu~ Gly, His, lle, Leu, Lys~ ei, P'ne, Prc .
Ser, Thr, Trp, Tyr and ~'al, the 2mino acid or peptide moie;~ being lin.~;ed to Q as ar, 10 es~e, or amide through the czrbo~ylic acid 2~ the C terminus, P is selected from the ~roup consisting of hydro,gen, and arnine protecting groups, n is 1-5 Y is selected fron~
the group consisting of hydrogen, C I -C4 al!;yl and halogen These novel compounds are suitable for use in the preparations of alkaline laundry detergent compositions comprising:
15a. from about O.OOI to 10 weight % of certain phenylboronic acids having structures described hereinafter;
b. from about O.OOOI to 1.0 weight ~,'0 of proteolytic enzyme;
c. a performance-enhancing amount of at least one detergent-compatible second enzyme; and CA 02232878 1998-0';,-12 ~YO gS/12655 Pc~ s9~112407 . from about 1 to 80 weight % of detersive surf2c;ant.
e. a lic~uid medium f. sufficient alkaline material to provide said composition with a pH of greater than 7 ~~hen measured as a 10% aqueous solution.
s DESCRIPTION OF T~ IN~ 'T10~
The instant liquid detergent compositions contain five essential ingredients: (a) celtain phenyl boronic acids, (b) proteolytic en~me, (c) detergent-compatible second enzyme, (d) detersive sutfactant, (e) a liquid medium, and (f) sufficient alkaline material 0 to provide the composition with a pH of greater than 7 wh~n measured as a 10~/O
solution in water. All percentages and proportions herein are "by weight" un~essspecified otherwise.
(a) o-Substituted Phenylboronic Acids The boronic acids comptising component (a) of the composition of the presen~
15 invention are ottho-substituted phenylboronic acids which have the following forrnulas:
(1) ' B (OH)2 Y~X
where ~ is -NO?, -NH2, -N~, -OH, -O~, -OCR, -N~I~R or -NHS02:~, wherein ~ is Cl-C4 (preferably Cl-C2) aL~I or aryl"and wherein ea~h ~ is H, Cl-C4 20 (preferably Cl-C2) aL~l or halogen (e.~,., chloro- or bromo).
(2) B (OH)2 Y [~Q(a)n~
wherein Q is -O- or -NH, A is an amino acid moiety or a pe?iide moiety comprised ~5 of a combination of amino acid tnoieties, tlle alnino acid, ~ng sele~ted fromal~Line (~la), arginine (Arg), asparagine (Asn), aspar~ic 2Ci~ (Asp), cysteine (C~s), glutarnine (Gln), glutamic acid (Glu), glycine (Gly), histidine (~-~is), isoleucine (lle), leucine (I leu), Iysine (Lys), methionine (Met), phenyalanine (Phe), proLine (Pro), ~ serine (Ser), threon~ne (Thr), tryptopl~an (Trp), tyrosine (T~;r) and valirle (~al), the 30 said amino acid or: peptide moiety being Lin~ied to Q as an es~er or amide through the W O95112655 PCT~S94/12407 carboxylic acid of said amino acid or peptide at the C terrninus, P is hydrogen or an amine protecting group, n is l-5, and ~ach Y is H, Cl-C4 alkyl or halogen.
Preferred amino acids are alanine, leucine, valine, isoleucine proline, phenylalanine, tryptophan glycine, arginine, and methionine Amine protecting groups are groups s which are attached to the amine end of an amino acid or peptide to block reaction by the amine when the carboxylic acid group is being reacted with another material.Typical amine protecting groups are methoxycarbonylJ benzyloxycarbonyl and tertiarybutoxycarbonyl .
Y is preferably H in both Type l) and Type ~ compounds The preferred o compounds are those of Type (l) wherein X is -NH~CH3, and the compounds of Type 2 wherein Q is -NH. I .
The compounds of Type (l) wherein X is -NHR, -NHlR,- . ~
NHS02~ and -O~?R wherein R is aryl, or Cl to C3 aL~cyl, and the compounds of Type 2 are novel and are the subject matter of the present invention.
lS - It is believed that boronic acids inhibit proteolytic enzyme activity by forming a reversible covalent bond to the serine hydroxyl group in the active site of the proteolytic enzyme. Upon dilution, under typical wash conditions, protease activity is regained once this bond is broken and the boronic acid diffuses away from the proteolytic enzyme.
Aside from the ability to bond with protease, the efficacy of a protease inhibitor is also deterrnined by the ir~herent chemical stability of the inhibitor in the medium in whicll it is use~d.
The ortho substituted phenylboronic acids are superior to the compa~ble meta and ~ substituted compounds. This is believed ~5 to ~e due to (l) their better chemic~l stability in a concentrated allcaline detergent medium, and/or (2) their higher binding affil ity to the protease.
Examples of boronic acids are: o-hydroxyphenylboronic acid, o-nitrophenylboronic acid, o-aminopllenylboronic acid, o-N-acetylaminophenyl~oronic acid, ~oc-~iie-Gly-~la-o- aminophenylhoronic acid, o-I~T-sulfonamidophenyl~oronic acid, 2-amino-4-chlorophenylb~ronic acid, 2-nitro-3-ethylphenylboronic acid, Z-Gly-Ala-o- arninophenylboronic acid. In the above-recited peptide derivatives, the tenn "Moc" means methoxycar~onyl and the te~n Zmeans ~nzyloxycar~onyl, both of which are amine protecting gTOUpS The peptide deriYati~es without the amine protecting groups a;re also useful.
The ortho substituted ~oronic acids can conver~iently be made, starting with the process described by Seaman et al., J. Am. Chem. S~c., ~'ol. 53, p. 71 l (Feb.
CA 02232878 1998-0~-12 - ]931). The process involves preparation of o-nitro phenylboronic acid by reaction of fuming nitric acid with pllenylboronic acid in the presence of acetic anllydride. The product is a mixture of approximately 95% ortho and 5% E~ nitro phenylboronic acid.
The ortho and ~ isomers can be separated by crystallization. The o-nitro compound 5 can be converted to other derivatives by known reaction means. For example, the corresponding amino derivative can be prepared by catalytic hydrogenation of thenitro compound.
The hydroxyl derivative can be prepared by diazotization of the o-amino derivative, followed by hydrolysis. The ether and ester derivatives can be prepared by 10 kno-vn reactions from the hydroxyl derivative, e.g., reaction with an alkyl chloride to fonn the ether and ~Vit]1 a carboxylic acid to forrn the ester.
The amido derivative can be prepared by reacting the o-amino derivative with acetic anhydride.
The peptide derivative can be prepared by reacting the o-amino derivative ~vith 15 ethylenegl~col to produce-tlle cyclic boronic ester, reacting the o-amino group with the desired peptide and then hydrolyzing the boronic ester back to the acid form.
The sulfonamido derivative can be prepared by reacting the o-amino derivative witl1 an alkyl sulfonyl chloride.
In the above liquid detergent compositions, from about 0.001 to 10%, preferabl~
about 0.02 to 5%, most preferably 0.05 to 2% of the ortho substituted phenylboronic acid is ~Ised.
(b) Proteol~tic Enzvme A second essential ingredient in the above liquid detergent compositions is fromabout 0.000] to 1.0%, preferably about 0.0005 to 0.5%, most preferably abo~lt 0.002 to 25 0.1%, of proteolytic en~yme. Mi~;t-lres of proteolytic enzylnes are also includecl ~Yit]-in tl~e terml proteolytic enzyme 11Creil1 The proteolytic cnz~tl1e can be of animal, vegetable or microorgal1islll (preferred) origim More prefened is serine proteol~tic enzymc of bacteri~l origin. Purifiecl or nollp~llifiecl fonns of tlle enz~me ma) be ~Ised. Proteolytic enz~lne, prod~lcecl by chelnically or geneticall~ modified mutal1ts are incl~lclecl by 30 c3efinition, as are close strllct~n-al enzyn1c ~ariants. Partic~llarly prefelred is bactcrial serine pro,eol~tic enz~ne obtained from Bacilllls subtilis and/or Bacillus licl~enifoln1is.
Suitable proteolytic enzymes inclllde Alcalase~), Esperase~), Savinase~), all available from NOVO Nordisk N/A; Maxatase~, Ma~;acal~), and Ma~;apem lSi~ (protei engineered Ma~;acal~), all ,available from Gist Brocades, and sllbtilisin - BPN and BPN', available from Sigma Chemical Company. Preferred proteolytic enzymes are also modified bacterial serine proteases, such as those described in European Patent Application 251,446, Wells et al., published January 7, 1988, and wl1ich is called herein "Protease B", and in U.S. Patent No. 5,030,37S, Venegas, issued July 9, 1991, ~vhich refers to a modified bacterial serine proteolytic enzyme which is called "Protease A" herein. Preferred proteolytic enzymes are selected from the group consisting of Savinase~), Maxacal~), BPN', Protease A and Protease B, and mixtures thereof. Another preferred protease is tl1at described in the patent application CA 2,173,105 of A. Baeck, C. K. Ghosh, P. P. Greycar, ~. R. Bott and L. J. Wilson entitled "Protease Containing Cleaning Compositions," published April 20, 1995.
(c) Second Enzyme Tlle third essential ingredient in the above liquid compositions is a performance-enhancing amount of a detergent-compatible second enzy,rne. By "performance-enhancing" is meant improving the enzyme-based cleaning perforrnance of the composition beyond that achieved by use of the protease. By "detergent-compatib]e" is - meant compatibility ~vith the other ingredients of a liquid detergent composition, such as detersive surfactant, detergency builder, and alkaline pH. These second en~ymes are preferably selected from the group consisting of lipase, amylase, ce]lulase, and mixtures thereof. The terrn "second enzyme" excludes the proteo]ytic enzymes discussed abo~e~ so each composition herein contains at least h~o kinds of enz~me, including at least one proteolytic enzyme and at least one additional enzyme ~hich is nol a protease.
The amount of second enzyme used in the composition varies according to the type of enz~me and the use intended. In general, from about 0.000~ to 1.0%, morepreferably 0.001 to 0.5% on an active basis of these second enzymes are preferably used.
~ tures of enzyl11es from the same class (e.g. Iipase) or t~o Ol nlore classes (e.g. celllllase alld lipase) nlay be usec~ PLII jfiCCd or non-pllrified fcrnls of the enzylnc may be used.
Lipase and cell~llases are partic~llar]y preferrcd as second enz)~mcs herein.
Any lipase suitab]e for ~ISC in a liquid detergent ColllpC)sitio;1 can bc ~lsed llereill.
Suitable lipases for use hereil1 inc]ucle those of bactelial and fnnoal origin. Lipases from cl~enlically or genetically n1odifie(1 mutallts are included.
CA 02232878 1998-0~-12 - Suitable bacterial lipases include tllose produced by Pseudomonas, such as Pseudomonas stutzeri ATCC 19.154, as disclosed in British Patent 1,372,034. Suitable lipases include those which show a positive immunological cross-reaction with the antibody of the lipase produced by the microorganism Pseudomonas fluorescens IAM5 1057. This lipase and a method for its purification have been described in Japanese Patent Application 53-20487, laid open on February 24, 1978. This lipase is available under the trade name Lipase P "Amano," hereinafter referred to as ''Amano-P"
from Toyo Jozo Co., Togata Japan. Such lipases should sho~Y a positive immunological cross reaction with the Amano-P antibody, ~lsing tlle standard and ~vell-known 10 immunodiffusion procedure according to O~lcllterlony (Acta. Med. Scan., 133, pages-76-79 (1950)). These lipases, and a method for their immunological cross-reaction with Amano-P, are also described in U.S. Patent No. 4,707,29], Thom et al., issued November 17, 1987. Typical examples thereof are the Amano-P lipase, the lipase ex Pseudomonas fra i FERM P 1339 (available under the trade name Amano-B), lipase ex Psuedomonas 15 nitroredllcens var. Iipolytic~lm FERM P 1338 (available under the trade name Amano-CES), lipases ex Chromobacter ~iscosum, e.g. Chromobacter viscosum var.
lipolYticum NRRlB 3673, and fi~rther Chromobacter viscosum lipases, and lipases ex Pseudomonas ~ladioli. Other lipases of interest are Amano AKG and Bacillis Sp lipase (e.g., SolYay enzymes).
Other lipases ~Yhich are of interest ~here they are detergent-compatib]e are those described in U.S. Patent No. 5,223,169, El-Sayed et a]., issued June 29, 1993, EP A O 385 401, publislled September 5, 1990, IJ.S. Patent l\'o. 5,153,135, Farin et al., issued October G, 1992, and U.S. Patent No. 5,07~,S9~, Jars, issued Januar~ 7, 199~.
Suitable fungal lipases include those prod~lcible by Humicola lanu~Jinosa and Thermom~ces lan~l~inosus. Most preferred is lipase obtained by cloning the gene from I~umicola lanu~ osa alld e~;pressing thc genc in Asl)ereillus or~:ae as described in Eulopeall Patent Application 0 25~ n6~, comlnerciall~ available luldel the trade nal11e Lipolase~.
Froln about 2 to 20,000, preferably abollt 10 to 6,000, lipase nnits of lipase per gran1 (LU/g) of plodllct are typically use(l in tllese colnpositiol~s. A lipase ~nlit is that amoul1t of lipase ~YIlicll prod~lces ] n1mo] of titratable butyric acid per n1il1-lte in a pH
stat, ~vhere pH is 7.0, temperat~ne is 30~C, and sllbstrate is an emulsioll of trib~ltyrin and gLlm arabic, in the presence of Ca2+ and NaCI in phosphate buffer.
Any cellulase suitable for ~Ise in a liq~id detergent composition can be ~lsed in these compositions. Suitable cellulase enzymes for use herein include those of bacterial and ~Ingal origins. Preferably, they ~Yill have a pH optimum of bet~veen 5 and 9.~. From about 0.0001 to 1.0, preferably 0.001 to 0.5% on an actiYe enzyme basis of cellulase can be used.
S Suitable cellulases are disclosed in l~.S. Patent No. 4,435,307, Barbesgaard et al., issued March 6, 1984, which discloses fungal cellulase produced from Humicola insolens.
Suitable cellulases are also disclosed in GB-A-2,095,275 and U.S. Patent No. 3,844,890, Horikoshi et al., issued October 29, 1974.
Examples of such cellulases are cellulases produced by a strain of Humicola 10 insolens (Humicola ~risea var. thermoidea), particularly the Humicola strain DSM 1S00, and cellulases produced by a fungus of Bacillus N or a cellulase 212-producing fungus belonging to the ~enus Aeromonas, and cellulase e~;tracted from the hepatopancreas of a marine mollusc (Dolabella Auricula Solander).
Any amylase suitable for use in a liquid detergent composition can be used in 15 tllese compositions. Amylases include, for example, a-amylases obtained from a special strain of B.licheniforrns, described in more detail in British Patent Specification No.
1,296,839. Amylolytic proteins include, for example, Rapidasen', and TermamylT~'aYailable from NOVO l~ordisk and Ma~;amyl, available from Gist Brocades.
From about 0.0001 to 1.0%, preferably 0.0005 to 0.5% on an active enzyme 20 basis of amylase will typically be used.
(d) Detersive S~lrfactant From about 1% to ~0%, preferably about 3% to 50%, most preferably about 10%
to 30%, of sulfactant is an essential in,o,redient in detergent compositions.
The surfactant can be selected from the group consisting of anionics, 25 nonionics, cationics, ampllolytics, z~vitterio]lics, and mi~;tures thereof. Aniollic and nonionic surfactallts are preferl-ed.
Al~y] su]fate surfactants, eitl~er primary Ol secoo~lary, ale a t~pe of anionic smfactant of importance for use hereill. All~yl sulfates Jlave the cen~ral fonnula ROSO3M ~vherein R preferably is a C,0-C2, hyclrocarbyl, preferabl~! a al~yl straight or 30 brancl~ed chaill or hydro~;yalliyl ha~ inc, a C~0-C~o al~yl componeni, more preferably a C,,-C,s al~yl or hydlo~;yalLiyl, and M is H or a cation, e.g., an al~ali metal cation (e.g., sodhlm potassium, lithiulll), substitllted or unsubstitllted ammoniulll cations sucl~ as metllyl-, dimethyl-, and trillletllyl ammonium and quaternar~ ammonium cations, e.~,., tetrametllyl-ammolliulll and dimethyl piperdinium, and cations deri~ed from 35 alkalloJamilles sucll as ethallolamille, diethanolanlille, triethano]alllille, and mi~tures thereof, and the lil~e. l'ypically, all~y] cllains of Cl,-CI6 ale preferred for lo~ver wasl WOgS/12655 PCTrUS94/12407 tempera.~tures (e.g.~ belo-v about 50'aC) and C 16-18 al'~yl chains are preferred for hioher wash temperatures (e.g.~ about 50~C).
Al'~;yl alkoxylated sulfate surfactants are another cate~Cry of useful anionic surfactant. These surfactants are water soluble salts or acids typically of the for s formula RO(A)mS03M wherein R is an unsubstituted Clo-C~4 alkvl or hydroxyalkvl group having a C I o-C24 alkyl component~ preferably a C 1 2-C20 alkyl or hydroxyal};yl~
more preferably C 1 2-C 18 alkyl or hydroxyalkyl~ A is an ethoxy or propoxy unit~ m is greater than zero~ typically between about 0.5 and about 6~ more preferably between about 0.5 and about 3~ and M is H or a cation ~hich can be, for example~ a metalcation (e.g.~ sodium~ potassium, lithium, calcium~ magnesium~ etc.)~ ammonium orsubstituted-ammor. ium cation. PJ~yl ethoxylated sulfates as well as alkyl propoxylated sulfates are contemplated herein. Specific examples of substituted arrlrnonium cations include methyl-, dimethyl-~ trimethyl-arnrnonium and quaternary ammonium cations~
such as tetramethyl-ammonium~ dimethyl piperdinium and cations derived frorn s alkanolamines~ e.g.~ monoethanolamine~ diethanolarnine~ and triethanolamine, and rnixtures thereof. Exempiary surfactants are C12CI~ alkyl poiyetho.~late (1.0) sulfate, Cl~-CIs alkyl polyethoxylate (2.25) sulfate, C12-Cl~ a~l;yl polyethoxylate (3.0)sulfate, and C~ 2-C1 8 alkvl polyethoxylate (a,.O) sulfate wherein M is conveniently selected ~rom sodium and potassium.
Other anior ic surfactants useful for detersive purposes czn also be included inthe compositions hereof. These can include salts (including~ for e~;ample, sodium potassium~ ammonium, and substituted ammonium salts such ?. rr,ono-~ di- and triethanolamine salts) of soap, Cg-C20 linear alkylbenzenesulphonates~ C~-C22 primar~
or secondary alkanesulphonates~ Cg-C24 olefinsulphonates, sulphonated polycarboxylic 2s acids, alkyl glycerol sulfonates, fatty acyl glycerol sulfonates, fztty oleyl glycerol sulfates, alkyl phenol ethylene oxide ether sulfates, paraffin sulfonates, alkylphosphates, isothionates such as the acyl isothionates~ ~-acyl tzurates~ fatty acid arnides of methyl tauride, alkyl succinamates and sul~osuccin2.~ s~ monoesters of sulfosuccinate (especially saturated and unsaturated C12-C~ monoesters) diesters of sulfosuccinate (especially saturated and unsaturated C6-C14 àies~ers)~ N-acyl sarcosinates, sulfates of alkylpolysaccharides such ~s the sulfa es of alk~lpolyglucoside~
branched primary alkyl sulfates, all~l polyethoxy carboxylates sarh as those of the formula RO(CH2CH2O)kCH2COO-I~ wherein R is 2 CS-C2~ z~ k is arl integer from 0 to 10, and M is a soluble salt-forrning cation, znd fatty zci~j esterified with 3~i esethionic acid and neutrali~ed ~ ~ith sodium hydro~;ide. Further exarnples are gi~en in Surface Active A~ents and Deter~ents (Vo~. I and Il by Sch~ znz~ Perry and Berch).
Nonionic surfactants such as block alkylene oxide condensate of C6 to C 1 ~
alkyl phenols, alkylene oxide condensates of C8-C22 alkanols and ethylene oxide/propylene oxide block polymers (PluronicT~'-BASF Corp.), as well as semi polar nonionics (e.g., amine oxides and phosphine oxides) can be used in the present compositions. An extensive disclosure of these types of surfactants is found in U.S.
PatentNo. 3,929,678, Laughlin et al., issued December 30, 1975.
Amphol~ic and zwitterionic surfactants s~lch as described in U.S. Patent No.
3,929,678, supra can also be used in the compositions of the invention.
Cationic surfactants suitable for use in the compositions herein are described in U.S. Patent No. 4,228,044 Carnbre, issued October 14, 1980.
Alkylpolysaccharides such as disclosed in U.S. PatentNo. 4,S65,647 Llenado can be used as surfactants in the compositions.
Polyhydroxy fatty acid amides can be used as surfactants herein.
These materials have the fo;rrnula:
O R, lS 11 1 wherein: R~ is H, Cl-C4 hydrocarbyl, 2-hydroxy ethyl, 2-hydroxy propyl, or a mixture thereof, preferably C,-C4 alkyl, more preferably C, or C2 alkyl, most preferably C, alkyl (i.e., methyl); and R2 is a C5-C3, hydrocarbyl, preferably straight chain C7-C,~ alkyl or 20 alken~l, more preferably straight chain C9-C,7 a]liyl or all;eny], most preferably straight Cllain C"-C,5 alkyl or alkenyl, or mixtures thereof; and Z is a polyhydroxyhydrocarbyl having a ]inear hydrocarbyl chain with at least 3 hydroxyls directly connected to the cllain or an alkoxylatecl derivative (preferably ethoxy]ated or propo:;y]ated) thereof. Z
preferably ~ill be deri~ed from a reducillg sugar in a red~lcti~e 2mination reaction; more 25 preferab]y Z ~vill be a glycityl. Suitable red~lcing s~lgars include gl~cose, fi-uctose, Jnaltose, lactose, galactose, mallllose, ancl xy]osc. As ra~ materials, high dextlose corn syrllp, high fi-Llctose corn syrup, and high maltose COIIl syr-lp can be lltilized as ~vell as the in~liYid~lal sugars listed above. T]lese COIIl SylllpS Inay yie]d 2 mi:~ of s~gar componentS for Z. ]t Sl~O~llcl be ~Inclel-stood that it is by no means in~ended to exc]LIdc 30 othel suitable ra~v matelials. Z prefel-ably ~vill be selected fiom the ~ro~lp consisting of --CH2--(CHOH)n--CH20H,--CH(CH~OH~(CHOH)n.,~CH20H, --CH2--(CHOH)2(CHOR')(CHOH~CH2OH, and allioxylated deri~ atiYes thel-eof, wllere n is an integer fiom 3 to 5, inc]~lsi~e, and R' is H or a cyclic CA 02232878 1998-0~-12 WO95/12655 PCTrUS9~/12407 or alipha~tic monosaccharide. Most preferred zre glycityls ~vherein n is 4~ particularly -CH2-(CHOH)4-CH20H .
In Formula (I), Rl can be~ for example~ methyl~ ethyl~ propyl~ isopropYI~ butyl,2-hydroxy ethyl~ or 2-hydroxy propyl.
s R2CO-N< can be~ for example, cocamide, stearamide~ oleamide, lauramide, myristamide. capricarnide, palrnitamide, tallowarr~ide, etc.
Z can be l-deoxyglucityl, 2-deoxyfiuctityl~ I-deoxymaltityl~ I-deoxylactityl, 1-deoxygalactityl, I-deoxymannityl, I-deoxymaltotriotityl, etc.
A particularly desirable surfactant of this type for use in the compositions herein o is all~yl-N-methyl glucomide, a compound ofthe above formula wherein R2 is all;yl (preferably Cl l-C13), R, is methyl and Z is l-deoxyglucityl.
(e) Liquid Medium The liquid medium of the compositions herein is typically water, but may be a an organic solvent ~vhich is miscible with water or a combination of one or more of such organic solvents and water. Examples of suitable water rniscible organic solvents are ethanol, propanol, isopropanol, ethylene glycol, propylene glycol and glycerine.
The liquid medium comprises at least 10%, typically from about 10% to 70%, preferably 20% to 60% and most preferably about 40% to 50% ofthe composition.
(f) Alkaline Material The compositions herein are forrnulated to have an alkaline pH, i.e., a pH
greater than 7 when measured as a 10% solution in water. Typical]y the pH ~ill be between about 7.5 and I 1, preferably from about 7.5 to ~.5. The desired pH can be achieved by use of buffers (e.g., sodium bicarbonate, disodium hydrogen phosphate) alkalis (e.g., sodium hydro~ide)~ alkaline detergency builders (such as described beio~v)~
andlor organic bases such as monoethanolamine as is well kno~ n to those skilled in the art (g) Optional In~redients The compositions herein can contain ~arious optional ingredients. A
preferred optional ingredient is a detergency builder. These materials are used at le~els of from 1% to about 50%~ preferably about 3% to 30%, more preferably about 5% to 20% in the composition herein. Inorganic as ~ell 2S organic builders can be used.
Inorganic detergency builders include, but are not limited to~ the alkali metal, ammonium and all;anolammonium salts of polyphosphatés (exemplified by CA 02232878 1998-0~-12 the tripolyphosphates, pyrophospllates, and glassy polymeric meta-phosphates), phosphonates, phytic acid, silicates, carbonates (including bicarbonates and sesquicarbonates), sulphates, and aluminosilicates Borate builders, as well as builders containing borate-forrning materials that can produce borate under detergent 5 storage or wash conditions (hereinafter, collectively "borate builders"), can also be used. Preferably, non-borate builders are used in the compositions of the invention intended for use at wash conditions less than about 50~C, especially less than ~bout 40~C.
Examples of silicate builders are the alliali metal silicates, particularly those having a SiO2:Na20 ratio in the range 1.6:1 to 3.2:1 and layered silicates, such as the layered sodium silicates described in U.S. Patent ~o. 4,664,839, issued May 12, 19~7 to H. P. Riecli. However, other silicates may also be useful such as for example magnesium silicate, ~vhich can serve as a stabilizing agent for o~y,en bleaches, and as a component of suds control systems.
E~amples of carbonate builders are the all~aline earth and al~;ali metal carbonates, 15 including sodium carbonate and sesquicarbonate and mixtures thereof.
Aluminosilicate builders are also useful in the detergent compositions descrlbed herein.
Aluminosilicate builders are of great importance in most currentl~ mar}~eted heavy duty granular detergent compositions, and can also be a significant builder ingredient in liquid detergent formulations. Aluminosilicate builders include those ha~ ing the empirical 20 formula:
Mz(zAl02 YSio2) ~vherein M is sodium, potassium, ammoniunl or substituted ammoni~lm, z is from about 0.5 to about 2; and y is 1; this material having a magnesium ion e~;change capacity of at least about 50 milligram equiva]ents of CaC03 llardness per gram o, anllydrous 25 alulllinosilicate. Preferred alumillosilicates are zeolite buildels ~hi~h ha~e the formu]a:
Naz[(Al02)z (SiO~)y] ~;H~O
~vhereill z ancl y are integers of at least 6, tlle n~olar ratio of z to ! i~ in tlle range from 1.0 to about 0.5, and ~; is an integer from about 15 to about 26 .
Specific e~;alllples of polypllospllates are the alliali Ineta!
30 tripolyl)llospllates~ socliulll, potassiulll allcl am~llo~ pyJophosp'l2.. sodiulll alld potassium ancl amlllollium pyl-opllospllate, sodi~lm ancl potassi-ull orhophosphate, sodiu polymeta phospllate in ~vhicll the degree of polynielizatioll range, fr~m abo~lt 6 to about 21, and salts of phytic acicl.
Preferred organic detergent builders for the detergent compositions described herein include a wide variety of polycarboxylate compounds. As used herein, "polycarboxylate'' refers to compounds having a plurality of carboxylategroups, preferably at least 3 carboxylates.
Polycarboxylate builder can generally be added to the composition in acid form, but can a]so be added in t]le forrn of a neutralized salt. When utilized in salt forrn, alkali metals, such as sodium, potassium, and litllium, c,r alkanolammonium salts are preferred.
Included among the polycarboxylate builders are a variety of categories of useful materials. One important category of polycarboxylate builders encompasses the etller 10 polycarboxylates. A number of ether polycarboxylates have been disclosed for use as detergent builders. Examples of useful ether polycarbo~;y]ates include oxydisuccinate, as disclosed in Berg, U.S. Patent No. 3,128,2~7, issued April 7, 1964, and Lamberti et al., U.S. Patent~lo. 3,635,830, iss~led January IS, 1972.
A specific type of ether polycarbo~;ylates usefu] as builders in tlle present 15 invention also include tl)ose llaving the general forn~u]a:
CH(A)(COO~CH(COOX)~CH(COOX}CH(COO~f)(B) ~vherein A is H or O~I; B is H or--O CH(COOX~CH2(COO~); and X is H or a salt-forming cation. For e~ample, if in the aboYe general forrnula A and B are both H, then the compo~lnd is o~;ydissuccinic acid and its ~vater-so]uble salts. If A is OH and B is H, 20 tllen the compound is tartrate mollosuccillic acid (TMS) and its ~ ater-soluble salts. If A
is H and B is--O--CH(COOX~CH2(COO~), then the compound is tartrate disuccil1ic acid (TDS) and its ~vater-soluble salts. Mixtures of these b~lilders are especial]y prefened for use ]~erein. Particl~lally preferred are mi~t-lres of TMS and TDS in a ~veight ratio of TMS to TDS of fiom about 97:3 to about 20:~0. These bllilders are disclosed in U.S.
25 I'atent No. 4,663,071, issnecl to Bllsh et al., on Ma~ 5, 19S7.
~iuitable ethel polycalbo~;~dates also inclllcle cyclic compo~nù" paltic~llarly alic!'clic con~poullds, sucll as those described in U.~. Patent Nos. 3 ~)23,679; 3,~35,]63;
4,15S,635; 4,120,~74 and 4,102,903.
Otller usefnJ detergellcy buildels inclllcle tlle ether h~lro.~;~p~lycal-bo?;~Jates 30 represelltcd by the strLlctlllc:
I-IO~C(l~)(COOI\1~C(R)(COO;~}O],--H
~vherein M is ~1ydrogen or a cation ~vherein the resultant s~lt is ~ater-soluble, preferabl~ -an all~ali metal, ammol1illln or substituted anlmolli-ln1 cation, n is frc)m CA 02232878 1998-0~-12 about 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 selected from hydrogen~ C,-C4 alkyl or C,-C4 substituted alkyl (preferably R is hydrogen).
Still other ether polycarboxylates include copolymers of maleic anhydride ~vith ethylene or vinyl methyl ether, 1,3,5-trihydroxy benzene-2,4,6-trisulphonic acid, and carboxymethyloxysuceinic acid.
Organic polycarboxylate builders also include tlle various alkali metal, ammonium and substituted ammonium salts of polyacetic acids. Examples include the sodium, potassium, lithium, ammonium and substituted ammonium salts of 10 ethylenediamine tetraacetic acid, and nitrilotriacetic acid.
Also included are polycarboxylates such as mellitic acid, succinic acid, oxydisuccinic acid, polymaleic acid, benzene 1,3,5-tricarboxylic acid, and carboxymethyloxysuccinic acid, and soluble salts tllereof.
Citrate builders, e.g., citric acid and sol~lble salts thereof 15 (particular]y sodium salt), are suitable polycarboxylate builders for the compositions herein.
Other carboxylate builders include the carboxylated carbohydrates disclosed in U.S. Patent No. 3,723,322, Diehl, issued March 2~, 1973.
Also suitable in the detergent compositions are the 3,3-20 dicarbo?;y-4-oxa-1,6-hexanedioates and the related compounds disclosed in U.S. Patent No. 4,566,984, Bush, issued January 2S, 19~6.
Usef ll succinic acid builders include tlle C5-C20 all;yl succinic acids and salts thereof. A particularly preferred compound of this type is dodecen~l-succinic acid.
Alk~l succinic acids t~pically are of the general formula R~H(COOH)CH,(COOH) i.e., 25 deri~ati~es of SUCCilliC acid, ~ ereill R is llydrocalboll, e.g., C,0-C,. all;yl or a~kenyl, preferably C"-C!6 Ol ~-llereill R may bc sul)stituted ~it]l llyclro~;~l sulfo, sulfoxy or sulfone substituellts, all as describecl in the above-mention~cl pate ns.
The succinate builclels are preferably ~lsed in the form of th- ir ~ ~ater-so]-lble salts, including the sodium, potassiulll, amrllolliurl} and alkanolammoniu~l salts.
Specific e~;amp]eS of succillate luilders include: laur~ls-lcein2tc, myrist~lsuccil1ate, palmitylsuccil1ate, 2-clodecenylsuccinate (preferred), '~'-pentadecenylsuccinate, and the likc. Laulylsuccinates are the preferred builders of this group, and are described in European Patent 200,263 CA 02232878 1998-0~-12 published November 5, 1986.
Another type of usef ll builder consists of ethylenediamine disuccinic acid and the alkali metal and ammonium salts thereof. See U.S. Patent No. 4,704,233, Hartman et al.
Examples of useful builders also include sodiurn and potassium 5 carboxymethylo~cymalollate, carboxymethyloxysuccinate, ciscyclohexanehexacarboxylate, ciscyclopentanetetracarboxylate, and the copolymers of maleic anhydride with vinyl methyl ether or ethylene.
Other suitable polycarboxylates are the polyacetal carbo~;ylates disclosed in U.S.
Patent No. 4,144,226, Crutchfield et al., issued March 13, 1979. These polyacetal 10 carboxylates can be prepared by bringing togetller, under polymerization conditions, an ester of glyoxylic acid and a polymerization initiator. The resulting polyacetalcarboxylate ester is tllen attached to chemically stable end groups to stabilize the polyacetal carboxylate against rapid depolymerization in al~aline solution, and converted to the corresponding salt.
Polycarboxylate b~ilders are also disclosed in U.S. Patent No. 3,308,067, Diehl,issued March 7, 1967. Such materials include the water-soluble salts of homo- and copolymers of aliphatic carboxylic acids such as maleic acid, itaconic acid, mesaconic acid, fumaric acid, aconitic acid, citraconic acid and methylenemalonic acid.
A particularly desirable b~lilder system for use herein is one comprising a mi~;ture 20 of a C,0-C,s monocarbo~;ylic acid and citric acid or a salt thereof. ~hen using this system, tlle composition ~ill preferably contain from abo~lt 1% to about 18% of the monocarboxylic acid and from abo~lt 0.2% to 10% of the citric acid or citrate salt.
Other optional ingredients for the compositions herein include soil release polymers, optical brightenels, hydrotropes, bleaches, bleach ac;i~a;ors, s~lds control 25 agents, antibacterial agellts, ancl additional en~yllle stabilizers, e.~., etho~;ylated tetraeth)~lene pentalllinc.
The composition will be illustrated by the following examples, which are not to be construed in an}~ way as limitatiolls on the in~ention.
~YO95/12655 PCT~VS94J12407 .~ EXAMPLE I
Preparation of o-aminophenvlboronic Acid To a three necked round bottom flask equipped with an addition funnel d s (and argon in~et), thermometer and septum is added phenylboronic acid (40.13 g~
0.33 moles). Acetic anhydride (400 rn~) is charged through the septum via syringe. Using a stir bar the mixture is then stirred under argon until the temperature reaches 0~C with externa~ cooling lice bath). Fuming nitric acid (25.01 g, 0.397 moles) is added slowly over the course of thirty minutes. The o reaction is then allowed to stir an additional two hours at O~C~ before removing the ice bath and allowing the reaction to warm to room temperature. The reaction is poured into ice water ( I L) at which point it appears cloudy, Afterstirring overnight, however, it becomes homogeneous. The solution is paced on a rotary evaporator at 40~C under a 5 rnm vacuum. When the volume is reduced by about 50%~ enough water is added to bring the volume back to 100%. This process is repeated twice more, before bringing the volume to about 300 rnl on the rotary evaporator when a precipitate is noticed. Twenty hours are allowed for complete crystallization, and the solids (p-nitrobenzeneboror~ic acid~ 3.66 g) ~ are removed by filtration. Enough water is then added to the fil;rate to bring the total volume to 800 rn~. The volume is reduced once more under reduced pressure to about 150 rn~ when a precipitate begins to form. The solids (o-nitrophenylboronic acid, 48.04 g) are collected by filtration and dried in a vacuum oven To a pressure vessel is added o-nitrophenylboronic acid (31.64 g), 10%
palladium on carbon (6.3 ~) and ethanol (100 m~. The vessel is shook at room temperature under S0 psi hydrogen on a PARR shaker. After four hours the catalyst is removed by filtration, and the filtrate taken to dryness under reduced pressure. The solids (o-aminophenylboronic acid, 24.4 g) are dried under vacuum for 18 hours.
WO95112655 PCTrUS94/124n7 Preparation of o-N-Acetvlaminophenvlboronic Acid '~
sTo a solution of o-aminophenylboronic acid (6.73 g~ 4~.1 mmoles) in dioxane ( 100 ml) is added acetic anhydride (25.1 g 246 mmoles). The reaction isheated at 100~C for 17 hours. After cooling~ the reaction volatiles are removed under reduced pressure to leave a thick yellow gel, which a~er chromatography affords o-N-acetylaminophenylboronic acid (7.33 g).
~YO95/126~5 PCT/US9~112~n7 EXAMPL~ 3 Preparation of Z-Glv-Ala-o- Aminophenvlboronic Acid To a solution of o-aminophenylboronic acid (13.7 g~ 100 rrunoles) in dich!oromethane (200 ml) is added ethylene glycol (6.30 g, 10~ rnmoles). The - solution is shaken for 20 rninutes~ and then stirred over solid sodium sulfate, s Removal of the volatiles affords ethylene o-aminophenylboronate. ' To a flame dried three neck round bottam flask equipped with septum, stopper and gas inlet,is added ethylene o-aminophenylboronate (0.36 g~ 2.20 mmoles) in dry dimethylfor,mamide ( 10 ml). To this solution is added Z-GI~-Ala (0.62 g, 2.21 mrnoles), triethylamine (0.62 ml, 4.45 mrnoles~, and finally diethyl 2.0 cyanophosphonate ~0.37 ml, 2.44 mmoles). AflLer stirring the reaction at room temperature for 17 hours~ the DMF is removed under reduced pressure. The remaining residue is dissolved in ethy~ acetate~ and washed sequentially ~ith 10%
H~l~ saturated sodium bicarbonate~ and brine. A~er drying the organic phase over magnesium sulfate~ the salts are removed by filtration and hltrate 2:5 concentrated in vacuum to leave (0.63 g) of 7-Gly-Ala-o- arninophenylboronic acid. This compound can be used ''as is" in the present invention, or the benzylo~cycarbonyl (Z) group can be removed by hydrogenol~ sis ~see first step o~
Example 4).
~VO95/12655 PCTrUS94/12~07 Preparation of Moc-Phe-Glv-Ala-o- Aminophenv1boronic Acid ~o To a pressure vessel is added Z-Gly-Ala-o- aminophenylboronic acid, the - compound of Example 3 (0.60 g, 1.5 rnmoles), ethanol (20 rnl), and 10%palladium on carbon (0.12 g). The vessel is shoo~ under ~0 psi hydrogen on a PARR apparatus for three hours at room temperature. The catalyst is removed by filtration and the solvent removed under reduced pressure to leave a paste, which was further dried in a vacuum oven to yield H-Gly-Ala-o-aminophenylboronic acid (0.38 g). H-Gly-Ala-o- aminophenylboronic acid (0.354 g~ 1.33 mmoles) is then stirred vigorously for thirty rrLinutes in dichloromethane (20 ml) containing ethylene ~Iycol (0.25 ml) and magnesium sulfate (2 g). The solution is filtered and the vo!atiles removed under reduced pressure. The residue is dissolved in dichloromethane and ~ ashed Witll cold ~ water After drying theJorganic phase over ma~nesium sulfate, the solvent is removed under reduced pressure to leave ethylene H-Gly-A!a-o-arninophenylboronate, which is added (.302 g, 1.04 rr~rnoles) to a flame dried three necked flask equipped with a stopper, septum, and gas inlet. While stirring under an argon atmosphere at room temperature, first ?-IOC-Phe (0.232 g~ 1.03 mmoles) dissolved in DM~ (3 ml), and then triethy]amine (0.29 ml, 2.0~ mmoles) is added via a syringe. Lastly diethyl cyanophosphonate (0. ] 7 rnl~ 1.12 mmoles) dissolved in DMF (7 ml) is added. A~[cr the reaction is stirred eighteen hours at room temperature, the DMF is removed under reduced pressure. After drying the or~ganic phase ~vith magnesium sulfate, the solids are remo~ed by filtration arld the filtrate concentrated under vacuum to leave Moc-Phe-Gly-A!a-o-aminophenylboronic acid (0.30 g). This material can be used 'las is" in the present invention, or the metho~carbonyl group (Moc) can be removed by hydro!ysis.
WO95112655 PCTfiUS9~112~07 EXAM:PLE ~
A liquid laundry detergent is prepared by mixing the following ingredients:
WT %
C14-15 alkyl (ethoxy 2.25) sulfonic acid18.0 C 12-13 alkyl ethoxylate (9) 2.0 C 1 2-N-methylglucamide 5 0 ~ Citricacid 4 0 Ethanol 3 . 5 Monoethanolamine 2.0 1~ Propanediol 7.0 Sodium Formate 0.6 Boric acid 2.0 Tetraethy]ene pentamine ethoxylate (16)1.18 Protease B (3 4 g/l) ] . 16 Lipolase ( I 00K LU/g)* 0 10 Carezyme (5000 CevL~g)~ 0.~0 Soil release Polyrner 0.1~
Silicone Suds suppresser 0.10 Brightener 0 10 o-Acetylaminophenylboronic acid 0.30 ~'ater, NaOH* ~ * and minors Balance to I OOQ/o A lipase from NOVO Nordisk NIA.
~* A cellulase from NOVO Nordisk NIA.
0 *** Sufficient NraOH is used to neutralize the acidic materials used inpreparing the composition and to produce a pH of about 8 when the finished composition is dissolved in ~~ater at a concentration of 10%.
The composition is prepared according to the follo~ ing procedure t~ The alkyl polyethoxylate sulfonic acid is first mixed thorough~y with CA 02232878 1998-0~-12 W O95112655 PCrrus9~ll2~o7 monoeth~anolamine, NaOH and alkyl polyetho~ylate. Then, boric acid and citric acid are added slowly while the solution is being stirred rapidly to reach a pH
around 8Ø The N-methyl glucamide, brightener, ethoxylated tetraethy]ene pentamine and soil release polymer are added. NaOH is used to finally adjust thes pH to ~.0 at 10% concentration in water.
After the temperature is lowered, sodium formate~ o-acetylaminophenylboronic acid, enzymes~ and suds suppresser are added. Water ~ is added finally to achieve the final target composition Ethanol and propylene glycol are present in the alkylpolyethoxylate 0 sulfonic acid and N-methyl glucamide surfactants which are used in the composition.
Comparable compositions are prepared by substituting Moc-Phe-Gly-Ala-o- arninophenylboronic acid, o-aminophenylboronic acid, o-nitro-phenylboronic acid or Z-Gly-Ala-o- aminophenylboronic acid for o-5 acetylaminophenylboronic acid.
WO95112655 PCTrUS9~112~7 E~ PLE 6 A liquid laundry detergent is prepared by mixing the following ingredients, and using a preparation procedure substantially the same as in Example 5.
WT %
C14-15 alkyl (ethoxy ~ 5) sulfonic acid13.80 C12-13 alkyl ethoxylate (9) 2.22 C12.3 Linear alkyl benzene sulfonic acid 9.86 Citric acid 7.10 Ethanol 1.93 Monoethanolarnine 0.7 1 1~2 Propanediol 7.89 Sodium cumene sulfonate 1.80 Sodium Formate 0.08 Sodium Hydroxide 6.70 Tetraethylene pentamine ethoxylate ( 16) 1.18 Protease B (34 gll) 1.16 Lipolase ( I OOK LU/g) * 0. 90 Soil release Polymer 0.29 Silicone Suds suppressor 0.01 Brightener 0. 10 o-Acet~lanLinophenylboronic acid 0.1 O
Water and minors 13alance to 100%
I1) A lipase from NOVO Nordisl; ~I/A
The comyosition has a pH ( 10% solution) in ~-ater of about 8.1.
Otller usefnJ detergellcy buildels inclllcle tlle ether h~lro.~;~p~lycal-bo?;~Jates 30 represelltcd by the strLlctlllc:
I-IO~C(l~)(COOI\1~C(R)(COO;~}O],--H
~vherein M is ~1ydrogen or a cation ~vherein the resultant s~lt is ~ater-soluble, preferabl~ -an all~ali metal, ammol1illln or substituted anlmolli-ln1 cation, n is frc)m CA 02232878 1998-0~-12 about 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 selected from hydrogen~ C,-C4 alkyl or C,-C4 substituted alkyl (preferably R is hydrogen).
Still other ether polycarboxylates include copolymers of maleic anhydride ~vith ethylene or vinyl methyl ether, 1,3,5-trihydroxy benzene-2,4,6-trisulphonic acid, and carboxymethyloxysuceinic acid.
Organic polycarboxylate builders also include tlle various alkali metal, ammonium and substituted ammonium salts of polyacetic acids. Examples include the sodium, potassium, lithium, ammonium and substituted ammonium salts of 10 ethylenediamine tetraacetic acid, and nitrilotriacetic acid.
Also included are polycarboxylates such as mellitic acid, succinic acid, oxydisuccinic acid, polymaleic acid, benzene 1,3,5-tricarboxylic acid, and carboxymethyloxysuccinic acid, and soluble salts tllereof.
Citrate builders, e.g., citric acid and sol~lble salts thereof 15 (particular]y sodium salt), are suitable polycarboxylate builders for the compositions herein.
Other carboxylate builders include the carboxylated carbohydrates disclosed in U.S. Patent No. 3,723,322, Diehl, issued March 2~, 1973.
Also suitable in the detergent compositions are the 3,3-20 dicarbo?;y-4-oxa-1,6-hexanedioates and the related compounds disclosed in U.S. Patent No. 4,566,984, Bush, issued January 2S, 19~6.
Usef ll succinic acid builders include tlle C5-C20 all;yl succinic acids and salts thereof. A particularly preferred compound of this type is dodecen~l-succinic acid.
Alk~l succinic acids t~pically are of the general formula R~H(COOH)CH,(COOH) i.e., 25 deri~ati~es of SUCCilliC acid, ~ ereill R is llydrocalboll, e.g., C,0-C,. all;yl or a~kenyl, preferably C"-C!6 Ol ~-llereill R may bc sul)stituted ~it]l llyclro~;~l sulfo, sulfoxy or sulfone substituellts, all as describecl in the above-mention~cl pate ns.
The succinate builclels are preferably ~lsed in the form of th- ir ~ ~ater-so]-lble salts, including the sodium, potassiulll, amrllolliurl} and alkanolammoniu~l salts.
Specific e~;amp]eS of succillate luilders include: laur~ls-lcein2tc, myrist~lsuccil1ate, palmitylsuccil1ate, 2-clodecenylsuccinate (preferred), '~'-pentadecenylsuccinate, and the likc. Laulylsuccinates are the preferred builders of this group, and are described in European Patent 200,263 CA 02232878 1998-0~-12 published November 5, 1986.
Another type of usef ll builder consists of ethylenediamine disuccinic acid and the alkali metal and ammonium salts thereof. See U.S. Patent No. 4,704,233, Hartman et al.
Examples of useful builders also include sodiurn and potassium 5 carboxymethylo~cymalollate, carboxymethyloxysuccinate, ciscyclohexanehexacarboxylate, ciscyclopentanetetracarboxylate, and the copolymers of maleic anhydride with vinyl methyl ether or ethylene.
Other suitable polycarboxylates are the polyacetal carbo~;ylates disclosed in U.S.
Patent No. 4,144,226, Crutchfield et al., issued March 13, 1979. These polyacetal 10 carboxylates can be prepared by bringing togetller, under polymerization conditions, an ester of glyoxylic acid and a polymerization initiator. The resulting polyacetalcarboxylate ester is tllen attached to chemically stable end groups to stabilize the polyacetal carboxylate against rapid depolymerization in al~aline solution, and converted to the corresponding salt.
Polycarboxylate b~ilders are also disclosed in U.S. Patent No. 3,308,067, Diehl,issued March 7, 1967. Such materials include the water-soluble salts of homo- and copolymers of aliphatic carboxylic acids such as maleic acid, itaconic acid, mesaconic acid, fumaric acid, aconitic acid, citraconic acid and methylenemalonic acid.
A particularly desirable b~lilder system for use herein is one comprising a mi~;ture 20 of a C,0-C,s monocarbo~;ylic acid and citric acid or a salt thereof. ~hen using this system, tlle composition ~ill preferably contain from abo~lt 1% to about 18% of the monocarboxylic acid and from abo~lt 0.2% to 10% of the citric acid or citrate salt.
Other optional ingredients for the compositions herein include soil release polymers, optical brightenels, hydrotropes, bleaches, bleach ac;i~a;ors, s~lds control 25 agents, antibacterial agellts, ancl additional en~yllle stabilizers, e.~., etho~;ylated tetraeth)~lene pentalllinc.
The composition will be illustrated by the following examples, which are not to be construed in an}~ way as limitatiolls on the in~ention.
~YO95/12655 PCT~VS94J12407 .~ EXAMPLE I
Preparation of o-aminophenvlboronic Acid To a three necked round bottom flask equipped with an addition funnel d s (and argon in~et), thermometer and septum is added phenylboronic acid (40.13 g~
0.33 moles). Acetic anhydride (400 rn~) is charged through the septum via syringe. Using a stir bar the mixture is then stirred under argon until the temperature reaches 0~C with externa~ cooling lice bath). Fuming nitric acid (25.01 g, 0.397 moles) is added slowly over the course of thirty minutes. The o reaction is then allowed to stir an additional two hours at O~C~ before removing the ice bath and allowing the reaction to warm to room temperature. The reaction is poured into ice water ( I L) at which point it appears cloudy, Afterstirring overnight, however, it becomes homogeneous. The solution is paced on a rotary evaporator at 40~C under a 5 rnm vacuum. When the volume is reduced by about 50%~ enough water is added to bring the volume back to 100%. This process is repeated twice more, before bringing the volume to about 300 rnl on the rotary evaporator when a precipitate is noticed. Twenty hours are allowed for complete crystallization, and the solids (p-nitrobenzeneboror~ic acid~ 3.66 g) ~ are removed by filtration. Enough water is then added to the fil;rate to bring the total volume to 800 rn~. The volume is reduced once more under reduced pressure to about 150 rn~ when a precipitate begins to form. The solids (o-nitrophenylboronic acid, 48.04 g) are collected by filtration and dried in a vacuum oven To a pressure vessel is added o-nitrophenylboronic acid (31.64 g), 10%
palladium on carbon (6.3 ~) and ethanol (100 m~. The vessel is shook at room temperature under S0 psi hydrogen on a PARR shaker. After four hours the catalyst is removed by filtration, and the filtrate taken to dryness under reduced pressure. The solids (o-aminophenylboronic acid, 24.4 g) are dried under vacuum for 18 hours.
WO95112655 PCTrUS94/124n7 Preparation of o-N-Acetvlaminophenvlboronic Acid '~
sTo a solution of o-aminophenylboronic acid (6.73 g~ 4~.1 mmoles) in dioxane ( 100 ml) is added acetic anhydride (25.1 g 246 mmoles). The reaction isheated at 100~C for 17 hours. After cooling~ the reaction volatiles are removed under reduced pressure to leave a thick yellow gel, which a~er chromatography affords o-N-acetylaminophenylboronic acid (7.33 g).
~YO95/126~5 PCT/US9~112~n7 EXAMPL~ 3 Preparation of Z-Glv-Ala-o- Aminophenvlboronic Acid To a solution of o-aminophenylboronic acid (13.7 g~ 100 rrunoles) in dich!oromethane (200 ml) is added ethylene glycol (6.30 g, 10~ rnmoles). The - solution is shaken for 20 rninutes~ and then stirred over solid sodium sulfate, s Removal of the volatiles affords ethylene o-aminophenylboronate. ' To a flame dried three neck round bottam flask equipped with septum, stopper and gas inlet,is added ethylene o-aminophenylboronate (0.36 g~ 2.20 mmoles) in dry dimethylfor,mamide ( 10 ml). To this solution is added Z-GI~-Ala (0.62 g, 2.21 mrnoles), triethylamine (0.62 ml, 4.45 mrnoles~, and finally diethyl 2.0 cyanophosphonate ~0.37 ml, 2.44 mmoles). AflLer stirring the reaction at room temperature for 17 hours~ the DMF is removed under reduced pressure. The remaining residue is dissolved in ethy~ acetate~ and washed sequentially ~ith 10%
H~l~ saturated sodium bicarbonate~ and brine. A~er drying the organic phase over magnesium sulfate~ the salts are removed by filtration and hltrate 2:5 concentrated in vacuum to leave (0.63 g) of 7-Gly-Ala-o- arninophenylboronic acid. This compound can be used ''as is" in the present invention, or the benzylo~cycarbonyl (Z) group can be removed by hydrogenol~ sis ~see first step o~
Example 4).
~VO95/12655 PCTrUS94/12~07 Preparation of Moc-Phe-Glv-Ala-o- Aminophenv1boronic Acid ~o To a pressure vessel is added Z-Gly-Ala-o- aminophenylboronic acid, the - compound of Example 3 (0.60 g, 1.5 rnmoles), ethanol (20 rnl), and 10%palladium on carbon (0.12 g). The vessel is shoo~ under ~0 psi hydrogen on a PARR apparatus for three hours at room temperature. The catalyst is removed by filtration and the solvent removed under reduced pressure to leave a paste, which was further dried in a vacuum oven to yield H-Gly-Ala-o-aminophenylboronic acid (0.38 g). H-Gly-Ala-o- aminophenylboronic acid (0.354 g~ 1.33 mmoles) is then stirred vigorously for thirty rrLinutes in dichloromethane (20 ml) containing ethylene ~Iycol (0.25 ml) and magnesium sulfate (2 g). The solution is filtered and the vo!atiles removed under reduced pressure. The residue is dissolved in dichloromethane and ~ ashed Witll cold ~ water After drying theJorganic phase over ma~nesium sulfate, the solvent is removed under reduced pressure to leave ethylene H-Gly-A!a-o-arninophenylboronate, which is added (.302 g, 1.04 rr~rnoles) to a flame dried three necked flask equipped with a stopper, septum, and gas inlet. While stirring under an argon atmosphere at room temperature, first ?-IOC-Phe (0.232 g~ 1.03 mmoles) dissolved in DM~ (3 ml), and then triethy]amine (0.29 ml, 2.0~ mmoles) is added via a syringe. Lastly diethyl cyanophosphonate (0. ] 7 rnl~ 1.12 mmoles) dissolved in DMF (7 ml) is added. A~[cr the reaction is stirred eighteen hours at room temperature, the DMF is removed under reduced pressure. After drying the or~ganic phase ~vith magnesium sulfate, the solids are remo~ed by filtration arld the filtrate concentrated under vacuum to leave Moc-Phe-Gly-A!a-o-aminophenylboronic acid (0.30 g). This material can be used 'las is" in the present invention, or the metho~carbonyl group (Moc) can be removed by hydro!ysis.
WO95112655 PCTfiUS9~112~07 EXAM:PLE ~
A liquid laundry detergent is prepared by mixing the following ingredients:
WT %
C14-15 alkyl (ethoxy 2.25) sulfonic acid18.0 C 12-13 alkyl ethoxylate (9) 2.0 C 1 2-N-methylglucamide 5 0 ~ Citricacid 4 0 Ethanol 3 . 5 Monoethanolamine 2.0 1~ Propanediol 7.0 Sodium Formate 0.6 Boric acid 2.0 Tetraethy]ene pentamine ethoxylate (16)1.18 Protease B (3 4 g/l) ] . 16 Lipolase ( I 00K LU/g)* 0 10 Carezyme (5000 CevL~g)~ 0.~0 Soil release Polyrner 0.1~
Silicone Suds suppresser 0.10 Brightener 0 10 o-Acetylaminophenylboronic acid 0.30 ~'ater, NaOH* ~ * and minors Balance to I OOQ/o A lipase from NOVO Nordisk NIA.
~* A cellulase from NOVO Nordisk NIA.
0 *** Sufficient NraOH is used to neutralize the acidic materials used inpreparing the composition and to produce a pH of about 8 when the finished composition is dissolved in ~~ater at a concentration of 10%.
The composition is prepared according to the follo~ ing procedure t~ The alkyl polyethoxylate sulfonic acid is first mixed thorough~y with CA 02232878 1998-0~-12 W O95112655 PCrrus9~ll2~o7 monoeth~anolamine, NaOH and alkyl polyetho~ylate. Then, boric acid and citric acid are added slowly while the solution is being stirred rapidly to reach a pH
around 8Ø The N-methyl glucamide, brightener, ethoxylated tetraethy]ene pentamine and soil release polymer are added. NaOH is used to finally adjust thes pH to ~.0 at 10% concentration in water.
After the temperature is lowered, sodium formate~ o-acetylaminophenylboronic acid, enzymes~ and suds suppresser are added. Water ~ is added finally to achieve the final target composition Ethanol and propylene glycol are present in the alkylpolyethoxylate 0 sulfonic acid and N-methyl glucamide surfactants which are used in the composition.
Comparable compositions are prepared by substituting Moc-Phe-Gly-Ala-o- arninophenylboronic acid, o-aminophenylboronic acid, o-nitro-phenylboronic acid or Z-Gly-Ala-o- aminophenylboronic acid for o-5 acetylaminophenylboronic acid.
WO95112655 PCTrUS9~112~7 E~ PLE 6 A liquid laundry detergent is prepared by mixing the following ingredients, and using a preparation procedure substantially the same as in Example 5.
WT %
C14-15 alkyl (ethoxy ~ 5) sulfonic acid13.80 C12-13 alkyl ethoxylate (9) 2.22 C12.3 Linear alkyl benzene sulfonic acid 9.86 Citric acid 7.10 Ethanol 1.93 Monoethanolarnine 0.7 1 1~2 Propanediol 7.89 Sodium cumene sulfonate 1.80 Sodium Formate 0.08 Sodium Hydroxide 6.70 Tetraethylene pentamine ethoxylate ( 16) 1.18 Protease B (34 gll) 1.16 Lipolase ( I OOK LU/g) * 0. 90 Soil release Polymer 0.29 Silicone Suds suppressor 0.01 Brightener 0. 10 o-Acet~lanLinophenylboronic acid 0.1 O
Water and minors 13alance to 100%
I1) A lipase from NOVO Nordisl; ~I/A
The comyosition has a pH ( 10% solution) in ~-ater of about 8.1.
Claims (7)
1. Phenylboronic acid compounds of the formulas:
where X is selected from the group consisting of -NHR, or -NHSO2R, wherein R is C1-C3 alkyl and wherein each Y is selected from the group consisting of H, C1-C4 alkyl and halogen, and wherein Q is -O- or -NH, A is an amino acid moiety or a peptide moiety comprised of a combination of amino acid moieties, the amino acid being selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr and Val, the amino acid or peptide moiety being linked to Q
as an ester or amide through the carboxylic acid at the C terminus, P is selected from the group consisting of hydrogen, and amine protecting groups, n is 1-5 and Y is selected from the group consisting of hydrogen, C1-C4 alkyl and halogen.
where X is selected from the group consisting of -NHR, or -NHSO2R, wherein R is C1-C3 alkyl and wherein each Y is selected from the group consisting of H, C1-C4 alkyl and halogen, and wherein Q is -O- or -NH, A is an amino acid moiety or a peptide moiety comprised of a combination of amino acid moieties, the amino acid being selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr and Val, the amino acid or peptide moiety being linked to Q
as an ester or amide through the carboxylic acid at the C terminus, P is selected from the group consisting of hydrogen, and amine protecting groups, n is 1-5 and Y is selected from the group consisting of hydrogen, C1-C4 alkyl and halogen.
2. The compounds of Claim 1, wherein each Y is hydrogen.
3. A compound of Claim 2, wherein in formula a, X is
4. A compound of Claim 1, wherein in formula b, Q is -NH and P is selected from the group consisting of hydrogen, methoxycarbonyl, benzyloxycarbonyl and tertiarybutoxycarbonyl.
5. A compound of Claim 4, wherein A is selected from the group consisting of Ala, Leu, Val, Ile, Pro, Phe, Trp, Gly, Arg and Met and mixtures thereof.
6. A compound of Claim 4, wherein A is selected from the group consisting of Ala, Gly, Phe and mixtures thereof.
7. A compound of Claim 2, wherein in formula a, X is
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US149,171 | 1993-11-05 | ||
| US08/149,171 US5431842A (en) | 1993-11-05 | 1993-11-05 | Liquid detergents with ortho-substituted phenylboronic acids for inhibition of proteolytic enzyme |
| CA002173107A CA2173107A1 (en) | 1993-11-05 | 1994-10-28 | Liquid detergents with ortho-substituted phenylboronic acids for inhibition of proteolytic enzyme |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002173107A Division CA2173107A1 (en) | 1993-11-05 | 1994-10-28 | Liquid detergents with ortho-substituted phenylboronic acids for inhibition of proteolytic enzyme |
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| Publication Number | Publication Date |
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| CA2232878A1 CA2232878A1 (en) | 1995-05-11 |
| CA2232878C true CA2232878C (en) | 2001-02-20 |
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| CA002232878A Expired - Fee Related CA2232878C (en) | 1993-11-05 | 1994-10-28 | Liquid detergents with ortho-substituted phenylboronic acids for inhibition of proteolytic enzymes |
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| Country | Link |
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| CA2232878A1 (en) | 1995-05-11 |
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