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Publication numberUS3775331 A
Publication typeGrant
Publication dateNov 27, 1973
Filing dateDec 15, 1971
Priority dateDec 22, 1970
Also published asDE2162353A1
Publication numberUS 3775331 A, US 3775331A, US-A-3775331, US3775331 A, US3775331A
InventorsG Borrello
Original AssigneeColgate Palmolive Co
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Manufacture of enzyme spheres
US 3775331 A
Abstract  available in
Previous page
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Claims  available in
Description  (OCR text may contain errors)

Nov. 27, 1973 i G. BORRELLO 3,775,331

MANUFACTURE OF ENZYME SPHERES Filed Dec. 15, 1971 5 Sheets-Sheet 5. BORRELLO 3,775,331

Nov. 27, 1973 MANUFACTURE OF ENZYME SPHERES 5 Sheets-Sheet Filed Dec. i5, 197i Nov. 27, 1 973 r I G. BORRELLO 3,775,331

MANUFACTURE OF ENZYME SPHERES Filed Dec. 15, 1971 3 Sheets-Sheet 3 United States Patent Oflice 3,775,331 Patented Nov. 27, 1973 3,775,331 MANUFACTURE OF ENZYME SPHERES Giuseppe Borrello, Anzio, Italy, assignor to Colgate- Palmolive Company, New York, N.Y.

Filed Dec. 15, 1971, Ser. No. 208,234 Claims priority, application Italy, Dec. 22, 1970, 55,581/ 70 Int. Cl. Clld 7/42 US. Cl. 252-89 10 Claims ABSTRACT OF THE DISCLOSURE A process for the manufacture of enzymatic compositions in spherical form, having increased stability upon storage and on exposure to oxidizing agents, which comprises mixing a normally solid enzyme with a normally solid synthetic organic surface active agent at a temperature at which the enzyme is stable and for a period long enough to form a homogeneous mixture thereof, compressing the mixture under pressure and mechanically working it to make it plastic, forcing the Worked mixture through small openings to produce filaments thereof having a diameter approximately that of the desired spheres, rolling a bed of filaments of such lengths in frictional contact with surfaces to rub off portions thereof, continuing said rolling until the filaments are reduced to a length about that of the diameter thereof and are rounded into spherical shape, and removing such rounded particles from an upper portion of the bed; and the enzymatic compositions produced thereby.

This invention relates to enzymatic compositions in spherical form. More particularly, it relates to a method of making such compositions and blends thereof with other detergent constituents, to make effective enzymatic clean ing compositions.

Various enzymes have been added to detergent compositions to improve their cleaning and stain-removing properties. Such enzymes are normally in powdered form and when blended into the other ingredients of the detergent they may form dusts when being used and such dusts, especially those of proteolytic enzymes, can be irritating to human respiratory organs. To minimize dust, efforts have been made to convert the enzyme powder to larger size particles, but such efforts have been only partially successful. This is largely because of the instabilities of many enzymes to high temperature processing, processes conducted in the presence of aqueous solutions or slurries of highly alkaline detergent builders, and in the presence of oxidants, such as per-compounds, often desirably employed in detergent formulations. As the spray drying process for making detergent compositions involves high temperatures and aqueous processing with adverse effects on enzymatic activity, there is a need for a commercial method for producing enzymatic detergent compositions in which the enzyme constituent will be at full strength and will not dust or sift during storage or use.

In accordance with the present invention, a process for the manufacture of enzymatic compositions in spherical form, having increased stability upon storage and on exposure to oxidizing agents, comprises the mixing of a normally solid enzyme with a normally solid synthetic organic surface active agent at a temperature at which the enzyme is stable and for a period long enough to make a homogeneous mixture under a sufficiently high pressure and mechanically working it to make it plastic, forcing the plastic, worked mixture through small openings to produce spaghetti-like filaments thereof having a diameter approximately that of the desired spheres, breaking the filaments so that they will have lengths less than twice the diameter thereof, rolling a bed of filaments of such lengths in frictional contact with surfaces to rub off portions thereof, continuing said rolling until the filaments are reduced to a length about that of the diameter thereof and are rounded into spherical shape, and removing such rounded particles from an upper portion of the bed.

In preferred embodiments of the invention the surface active agent employed will be an anionic or nonionic detergent, such as magnesium lauryl sulfate or higher alkyl polyethoxy ethanol, the enzyme will be a proteolytic enzyme, the rolling action will be caused by rotating a friction disc under a bed of filaments of enzyme composition and the product will be blended with a spray dried, perborate-containing built synthetic detergent composition to increase its stain and soil-removing action.

Various objects, detail, construction, operations, uses and advantages of the present invention, in its various aspects will be apparent from the following description, taken in conjunction with the accompanying drawing of embodiments of means for practicing the process of the invention, in which drawing:

FIG. 1 is a schematic flow diagram illustrating preparation of the enzyme spheres;

FIG. 2 is a simplified vertical sectional view of apparatus for converting filaments or rods of enzyme compositions to spherical form;

FIG. 3 is a fragmentary perspective view of the corrugated dish or frictional supporting member of the apparatus of FIG. 2; and

FIG. 4 is a partially disassembled view of an extruder which may be employed to make the filaments that are subsequently converted to spherules.

In FIG. 1 is illustrated a weigh hopper 11 having indicator means 13 for showing the weights of materials charged. The bottom of the hopper 15 is capable of being opened when it is desired to drop the charge into mixer 17. The mixer may be a soap amalgamator having a horizontally rotating mixing blade 19 or may be any other suitable blending apparatus capable of producing a homogeneous powder or other solids dispersion of the components of the composition to be made into enzyme spheres. After suflicient mixing the amalgamator is usually tipped and the discharged material is conveyed by a belt, not shown, to apparatus for working the composition, wherein it is normally made into a plastic film, mass, extrudate or chip and loses its powder form. Illustrated is a three roll mill but various other more complicated mills and equivalent working and extruding apparatuses may be emplolyed instead. Mill 21 squeezes the composition between the rolls thereof and transfers it to the faster moving of the contacting rolls, from the third of which 23, it is removed by a cutting knife 25. The. worked composition, in chip, ribbon or other suitable form is fed to an extruder 27 which compresses it and forces it out through a screen 29 having a plurality of fine openings 31 so that the enzyme composition is discharged as filaments, rods or spaghetti-like material. The diameter of the filaments is regulated by choosing a screen 29 with the proper hole size and such diameter regulates the size of the spherules to be produced subsequently.

To prevent the filaments from adhering and forming larger rods or aggregates when they are discharged from extruder or plodder 27, they may be cooled or moisture or other solvent or plasticizer therein may be removed by evaporation. Numeral 33 represents such means for deplasticizing the filaments. The composition, in filamentary form, may then be broken into smaller pieces, each of which is generally less than twice the filamentary diameter or the filaments may be charged directly to a machine for converting them to spherical form, which also breaks them down before spherulizing them. In some instances, cooling and/or evaporation may be dispensed with and in other cases the ordinary cooling and evaporation occurring during the feeding of the spaghetti to a spheronizing machine may be sufiicient to produce enough surface hardness or dryness to prevent objectionable adhesion.

In the sphere-making machine 35 a whirling corrugated plate or dish rolls the short rod-like particles in a helical path around the inner cylindrical wall of the machine or an inner wall of the dish, so that the particles are rubbed at the ends thereof, until the particle length is reduced to near the diameter, at which time subsequent abrasion rounds the particle to spherical form. As illustrated, particles 37 on rotating dish 39 are driven outwardly and are removed through exit 41. They are subsequently charged to another such machine 43 and from there are delivered to machine 45. The plural spheronizing actions allow continuous production of the enzyme spheres because the subsequent machine treatments help remove any oversize and undersize particles which' might have accompanied the discharge from machine 35. The final spherical product, removed at exit 47, is of the desired size and the particle size distribution is very limited, due primarily to the fact that the spaghett diameter is controlled and the final spheres are of approximately that diameter.

In FIG. 2 a more detailed view of a spheronizing machine and its operation is given. Spaghetti, rods, or filaments of enzyme composition are charged through hopper 49 into machine 51 and fall onto corrugated, plate 53 having a supporting surface 63. The dish is rotated in a horizontal plane by the action of shaft 55 which is keyed to V-belt pulley 57, driven by a prime mover, not shown. After charging of the enzyme filaments, they are allowed to pursue helical, rolling paths inside machine 51 in contact with wall 59 thereof. The upper surface 63 of plate 53 is provided as corrugated, the corrugations being effected by generally uniformly, spaced, squareshape depressed areas 64 bridged by a grid-like network 66. The bridging elements or ribs 68 of the grid network being elevated and, therefore, raised projections relative to areas 64 act to drive the particles and keep them in continuous motion. Fan 65 blows undersized particles 67, which pass through the clearance 71 between the dish and the machine wall. Fan 65 promotes the flow of air through the bed of enzyme beads, aiding in evaporating moisture therefrom and in cooling the beads, and also promotes removal of the fines from the bead bed 73. Such fines are removed through outlet 75, by any suitable means, including vibrating action, vacuum, pressure and gravity.

After sufficient rolling to reduce the filaments or rods to spherical form, the spheres may be removed through chute 79 by opening gate 77. Such spheres will be free of fines, the fines being in the lower portion of the bed or having previously been removed. Also, usually the portions of the spheres that previously were out ends have been polished and covered with the binder or surface active material which is the other component of the enzyme composition, in addition to the enzyme, itself.

In batch processes, the spheres removed may be utilized immediately or may be employed to add enzymes to other products, e.g., laundry detergents. In continuous processes, the withdrawn spheres may subsequently be rolled and rounded even more by using them as feeds to additional spherulizing machines of the type described, in which subsequent operations any fines will be removed and oversiged particles will be reduced and rounded.

In FIG. 3 is shown an enlarged perspective detail the character of the surface 63 of the plate 53. Other designs may be employed so long as they are effective in carrying the filaments and beads over the surface thereof and in promoting a rolling action without objectionably great impact effects which might fracture the beads. Also, instead of utilizing the rotating dish-shaped support for the bed of beads and filaments, the moving plate portion may be a fiat disc with driving projections on it, which disc is surrounded by a dish-shaped stationary enclosure. Such a structure improves the degree of abrasion on particle contacts because there is a greater relative motion when the particles strike a stationary member rather than one moving at approximately the same speed. Of course, with or without a moving or stationary dish, abrading action will occur when the breads strike the wall 59 of machine 51.

In FIG. 4 is shown a meshing twin screw extruder for producing the rods or filaments to be charged to the spheronizing machine. Extruder 81 includes a hopper 83, barrel 85 and in the barrel, a twin screw extruder 87 for compressing, compacting, plasticizing and forcing the charged composition into discharge section 89, from whence additional meshing twin screws 91 and 93 force the enzyme composition through perforations 95 in screens 97 and 99, producing rods or filaments having a cross-sectional shape like that of the perforations. A very useful feature of the extruder is the provision of means for cooling the composition being extruded, which means are shown as internal cooling passages 101 and 103, through which cooling water or other fluid may be allowed to flow into the screw interiors by opening of valves 105 and 107. In operation, screens 97 and 99 will be tightly clamped or bolted in place on extruder 81 about twin screws 91 and 93 so that the only outlets from the extruder are the perforations 95 in the screens. Instead of utilizing perforated screens of the type shown, wire meshes may be employed or one of the screens may be blanked off, so as to have spaghetti discharged only from the bottom of the extruder, from which it may be dried, cooled or immediately dropped into a spheronizing machine.

The enzymes employed may be any suitable enzymatic compounds capable of chemically attacking and helping to remove various soils and stains. Although hydrolytic, lipolytic, oxidizing, reducing and glycolytic enzymes, such as catalase, lipase, maltase, amylase and phosphatase are useful enzymes, in the present compositions proteolytic enzymes will be used most often. Such enzymes are active on proteinaceous materials and catalyze the digestion or degradation of such materials, which are often present in the form of a stain on a fabric. Such enzymes are useful over a range of pHs from 4 to 12, preferably from 8 to 11, and often individual enzymes have particular narrow pH ranges over which they exhibit greatest activities. Among the suitable proteolytic enzymes there may be mentioned pepsin, trypsin, chymotrypsin, papain, bromelain, collagenase, keratinase, amino peptidase, elastase, subtilisin and aspergillopepidases A and B. The preferred enzymes are subtilisin enzymes manufactured and cultivated from special strains of spore-forming bacteria, particularly Bacillus subtilis. Among the proteolytic enzymes derived from spore forming bacilli, such as Bacillus subtilis, are those commerically marketed as Alcalase SP 72 and SP 74, which may be de-dusted, and/or of sulfate and chloride types (the diluent being sulfate or chloride). Such materials usually have Anson ratings of 1.5 or 4 AU per gram. Similar enzymes, marked under the name Protease, are Proteases AP, ATP 40, ATP 120, L-252, L-423, AP 10 and MP 10X. Under the name Maxatase are sold such enzymes having activities of 300,000 and 500,000 D.U. (K.G.).

Proteolytic and other enzymes are generally available in powdered form and most often the powders are extremely fine, having particle sizes such that all or substantially all of the enzyme passes through a 60 mesh US. Standard Sieve Series sieve, with a major proportion, usually over 70% thereof, passing through a 100 mesh sieve. The particle sizes are usually between 0.01 mm. and 0.15 and may average about 0.1 mm. The enzyme particles also usually include a carrier material, e.g., an inorganic salt, with the organic content generally being only a minor proportion of the powder, by weight. Thus, the organic enzyme may be diluted with various salts, such as calcium sulfate, sodium chloride, sodium sulfate and other suitable inert materials. Normally, the proportion of organic enzyme present may be from 5 to 20%, but greater or lesser proportions may also be utilized. Preferred carriers are sodium chloride and sodium sulfate. The function of the carrier is to maintain the organic material in a flowable form and to prevent it from lumping or adhering to container walls, etc. Another function of the substrate material is to convert the active enzyme to a more dilute product so that it may be conveniently added to other preparations in which enzymatic action is desired. Thus, the enzymatic activity of the proteolytic enzymes will normally be from 0.5 to 5 AU per gram, usually from 1.5 to 4 AU per gram.

The synthetic organic surface active agent employed, which is useful as a carrier, binder and stabilizer or protector for the enzyme, may be any suitable such material, including anionic, nonionic and amphoteric surface active agents and in some cases cationics, also. Although wetting agents which do not possess detergent characteristics may be used, normally the surface active material will be a detergent, of either the anionic or nonionic type.

Of the anionic detergents it is preferred to utilize those which are sulfate or sulfonated and include a hydrocarbyl of from 8 to 22, preferably 10 to 18 carbon atoms. The sulfuric and sulfonic group of such detergents may be jointed directly or indirectly to a hydrophobic organic group which comprises the hydrocarbyl, preferably higher alkyl. The higher alkyl substituent may be either straightchained or branched but in most cases a straight-chained, biodegradable radical will be preferred. The straightchained alkyl groups include n-decyl, n-dodecyl, n-tetradecyl and n-hex adecyl, which were formerly derived from petroleum hydrocarbons. Instead of such alkyl sulfates, there may be used alkyl sulfonates; alkyl aryl sulfonates; alkyl polyoxy-lower alkylene sulfates; monoglyceride sulfates; sulfated higher alkyl phenyloxyethylene lower alkanols; sulfated middle alkyl phenyl polyoxyethylene ethanols; sulfated polyoxyethylene ethanols; sulfated polylower oxyalkylene lower alkanols; olefin sulfonates; and other suitable anionic detergents and surface active agents. In such compounds, the alkyl groups will be of 8 to 22 carbon atoms, preferably from 10 to 16 or 18 carbon atoms, the aryls will be benzene or lower alkyl substituted benzene (lower alkyl will be of 1 to 4 carbon atoms), the lower alkoxy groups will be of 1 to 4 carbon atoms and the polyalkoxies will contain from 3 to 50 alkoxy groups. Although straight-chain radicals are preferred for biodegradability, branched-chain compounds may also be employed. The various water-soluble anionic detergents and surface active agents will generally be in the forms of their water soluble salts, with the salt forming ions preferably being metals, ammonium, lower alkanolamine or lower alkyl amine. Preferred metal ions are magnesium, sodium, potassium and calcium. Of these, particularly desirable results have been obtained utilizing the. magnesium salts, especially magnesium lauryl sulfate or equivalent detergents obtained from vegetable or animal sources, e.g., magnesium coconut oil alcohol sulfate. Exemplary of other anionic detergents that may be employed are magnesium myristyl sulfate; sodium cetyl sulfate; potassium stearyl sulfate; sodium n-dodecyl benzene sulfonate; potassium n-hexadecyl benzene sulfonate; sodium n-dodecyl toluene sulfonate; sodium propylene tetramer benzene sulfonate; sodium lauryl sulfonate; ammonium coconut oil fatty acids monoglyceride sulfates, triethanolamine n-decyl sulfonates; sodium n-lauroyl sarcosines; sodium oleyl isethionate; potassium lauroyl nmethyl tauride; magnesium dodecyl glycerol ether sulfonate; sodium lauryl tri (oxyethylene) sulfate; nonyl phenol hexa (oxyethylene) sulfate; and lauryl deca (oxyethylene) ethanol sulfate, sodium salts.

The non-detergeut synthetic organic surface active agents that may be used are preferably lower alkyl substituted benzene sulfonates, such as toluene sulfonates, xylene sulfonates and cumene sulfonates, but may also a'iiassi 6 include naphthalene sulfonates and related compounds. in such' cases, the lower alkyl group will be from 1 to 4 carbon atoms and from 1 to 3 of these may be present on the aromatic nucleus. The salt forming ions will be the same as previously described with respect to the detergents.

Nonionic surface active agents include those surface active or detergent compounds which contain an organic hydrophobic group and a hydrophilic group. The hydrophilic group usually includes a solubilizing radical such as carboxylate, hydroxyl, amido or amino attached to an ethylene oxide or polyethylene oxide or a hydration product thereof, such as polyethylene glycol. Exemplary of such compounds are the polyethoxylated higher alkanols, polyethoxylated carboxylic acid esters, and condensation products of propylene glycol, propylene oxide and ethylene oxide, known as Pluronics. The molecular weights of such compounds may range from about 100 to as much as 10,000, where a sufficiently high proportion of ethylene oxide is present. Specific examples of such compounds which may be useful in the practice of the present invention include Alfol (mixture of C and C fatty alcohols condensed with 50 moles of ethylene oxide); Pluronic F68; reaction product of isooctylphenol with from 6 to moles of ethylene oxide; condensation products of 6 to 10 carbon alkyl thiophenols with 10 to 15 moles of ethylene oxide; and polyethylene oxide condensation products with lauryl alcohol, cetyl alcohol or stearyl alcohol. Only a limited number of the anionic and the nonionic agents useful in the practice of this invention are listed here. Other such compounds may be found in the text, Synthetic Detergents by Schwartz, Perry and Berch, published in 1958 by Interscience Publishers, New York, at pp. 25-143.

With the enzyme and surface active binder for it, there may often desirably be present other materials which are useful in making good enzyme spheres and at the same time perform desirable functions in the detergent compositions in which such spheres may be incorporated. Thus, various carrier materials such as the sodium, potassium and magnesium sulfates, chlorides, carbonates, bicarbonates, sesquicarbonates, or borates may be included, some of which help to form a hard bead by hydration reactions. Other carriers perform both hardening and building activities. Included among these are the sodium, potassium and magnesium tripolyphosphates, pyrophosphates, orthophosphates and tetraborates. Such inorganic salts may furnish the nuclei for the enzymes and surface active agents in the manufacture of the present enzyme spheres and, with the surface active agents, may aid in solubilizing the enzyme in the wash water in which it is ultimately employed.

With the enzyme, surface active agent and inorganic salt it will usually be desirable or necessary to employ a solvent so as to plasticize the rest of the ingredients satisfactorily. The preferred solvent is water, usually deionized, although it may accompany some of the other starting materials. Water has the advantage of being cheap and is comparatively easily removed, when desired. Also, of course, it is an excellent solvent for the present materials.

In addition to the main constituents previously mentioned, various adjuvants may be present to give the product desired end use or processing characteristics. Thus, additional binder materials such as the water-soluble gums, either natural or synthetic, may be present. These include sodium carboxymethyl cellulose; hydroxypropyl methyl cellulose; methyl cellulose; polyvinyl alcohol; polyvinylpyrrolidone; starches; gum acacia, agar agar; alginates; and guar gum. Various sequestrants may be present, including nitrilotriacctic acid salts; ethylene diamine tetraacetic acid salts; gluconates; citrates; and organophosphates. These will usually be alkali metal or alkaline earth metal salts. Bactericides, such as tribromosalicylanilides, trichlorocarbanilide, hexachlorophene and para-chloro-meta-xylenol may be present. Optical bleaches can be employed, such as triazinyl diamino-stilbene disulfonate, naphthotriazolyl stilbene sulfonate and bis-benzoxazolyl derivatives. Titanium dioxide, magnesium carbonate or zinc carbonate may be used as whitening pigments. Of course, various coloring agents may be em ployed, including methylene blue, phthalocyanine green, toluidine lake yellow, lutetia solid yellow and brilliant blue. Various other dyes, preferably RD. and C. colors, may be employed. Among other adjuvants may be mentioned perfumes, buffering agents, pH adjusting agents, foam improvers, e.g., lauric myristic diethanolamide, fungicides, preservatives, stabilizers, antioxidants, ultraviolet absorbers, fabric softeners and antistatic agents.

The proportions of normally solid synthetic organic surface active agent and enzyme in the enzyme bead will normally be so regulated that the surface active material will comprise from 1 to 50 times the content of the organic enzyme. Such proportions ignore the inorganic salt carrier or diluent usually present with the enzyme. Preferably, the surface active material is from to 30 times the weight of the active enzyme. In many compositions, the surface active agent and the enzyme, plus its carrier, if such is present, constitute the entire detergent bead but in preferred products there is also present additional inorganic salt, preferably sodium sulfate, anhydrous. Often, the sodium sulfate will be a major or substantial constituent of such products. These three member product composition beads will normally comprise from 5 to 70% surface active agent, preferably magnesium lauryl sulfate; to 80% of inorganic salt, preferably anhydrous sodium sulfate or sodium sulfate mixed with sodium chloride; and from 1 to 20% of enzyme, preferably of the proteolytic type. Preferred proportions are from 10 to 50% surfactant; 20 to 60% inorganic salt; and 2 to 10% enzyme.

Normally the composition figures given above, which are on an anhydrous basis, have to be diminished proportionately to allow for the presence of moisture and/or adjuvants in the beads. It is normally preferred not to include any adjuvants other than the surface active agent and the inorganic salt because they might have a deleterious effect on the enzyme. Nevertheless, in those instances where they may be usefully added, the proportions thereof will usually be held to less than 20% of the bead, preferably less than 10% thereof and proportions of individual adjuvants will generally be less than 5%, preferably less than 2%, all figures being on an as is basis. The percentage of moisture, also on such basis, is generally from 1 or 2 to preferably from 3 to 10%. Because moisture may be removed during the spherulizing process and is also sometimes added during that process to regulate plasticity of the filaments and beads, the proportions of moisture in the charge to the sphere-making machine and added or subtracted during operation of that machine will be modified accordingly. Thus, for example, if the materials charged are fairly low in moisture, containing, for example, 1 to 5% thereof, more may be added during the spherulizing process and then, also during this process, some of this moisture may be evaporated off. If the product is not satisfactorily dry, additional moisture may be removed by evaporation or hydration on cooling, after the spheres are produced and are withdrawn from the spherulizing apparatus.

Particle sizes of the spheres made may be controlled by the use of particular extruder screens. Generally, for normal commercial use of the enzyme beads either as pre-soak enzyme preparations or as additives for laundry detergents, usually of the spray dried type, the particle sizes will be such that the average diameters fall within the range of 0.254 mm. to 2.54 mm., preferably from 0.51 mm. to 2.0 mm. It is preferred that substantially all of the enzyme spheres have diameters within the range of 0.254 mm. to 2.54 mm., most preferably .51 mm. to 2.03 mm. in the most preferred products. Such sizes and size distributions give quick solubilities, easy flow-abilities, are non-dusting and do not sift out from the average spray dried detergent compositions.

In making the enzyme beads of this invention the procedure outlined in FIG. 1 is generally followed. Initially, the weights of the various enzyme bead constituents are added to a mixer or amalgamator, usually in the dry or semi-dry state. If it is desirable to add water or other solvent or plasticizing chemical to the mixer this is done but usually the quantity added will be very minor. The reason that water may be added at this stage is to blend it in with the other ingredients so that a plastic chip may be obtained off the mill or kneader and the plodding or extrusion operations can proceed satisfactorily. The weighing and mixing are effected at temperatures at which the enzyme is stable in the presence of the other ingredients. Such temperature will preferably be about room temperature but may range from 10 to S0 to 60 C. The mixing time will usually be from 1 to 30 minutes and preferably, the shorter the time, the better, so long as a. homogeneous mixture is obtained. Of course, the products mixed should all be in fairly fine granular or powder form to promote best mixing and substantially all of the ingredients will pass through a 10 mesh sieve. The enzyme will usually be more finely divided than the other ingreclients and a major proportion thereof will pass through a mesh sieve, with substantially all of the enzyme passing a 60 mesh sieve.

After thorough mixing, the particulate mixed material is charged to a plasticizing device, such as a kneader or a mill. Preferably, a mill is used and normally it will have from five to seven rolls, rather than the three rolls illustrated for simplicity. The milling or kneading operation also helps to distribute the enzyme throughout the surface active agent and facilitates coating of the enzyme with a film of the more plastic, waxier surface active material. In the milling operation, ribbons may be produced which are of thicknesses from 0.076 mm. to 0.51 mm., generally from 0.127 mm. to 0.38 mm. Of course, the thinner the chip the better the mixing and the greater the working of the composition by the mill.

Ribbons or chips from the mill or discharge from the kneader will next be fed to a plodder or other suitable extruder, such as that illustrated in FIG. 4. The plodder or extruder also mechanically works the composition to promote even mixing of the enzyme composition constituents, but its main function is to discharge the enzyme composition in desired filamentary or rod form. To effect this, high pressures are obtained, on the order of from 100 to 500 pounds per square inch, by means of a suitable feeding device, such as complementing twin screws or a worm and barrel. Then the charged material is forced through perforations in a plodder end plate or screen or in an extruder screen to form the desired filaments. While the perforations may be of different sizes and shapes, normally they will all be circular and the same size so as to promote uniformity of the product. Preferably, the holes in the screen are circular and the diameter thereof is in the range of from 0.254 mm. to 2.54 mm., preferably about 0.51 mm. to 2.03 mm. and most preferably around 1.27 mm.

The working of the enzyme composition in the milling or kneading and extruding or plodding operations generate some heat and causes evaporation of some moisture. Moisture loss may be diminished by utilizing cooling on the mill rolls and in the extruder, in which cooling water of a temperature of 20 to 40 C. may circulate through the rolls or inside the extruder screws. If desired, moisture may be added to make the mix more plastic in the extruder so as to promotePthe discharge of continuous filaments of enzyme composition. Suitable double screw extruders are well known.

The whirling disc spherulizing machine may be charged directly with the filaments produced by the extruder or these filaments may first be treated to make them more readily breakable into small sections, from which the desired spheres are rolled. If the extruded filaments are not plastic enough, this may be corrected by heating them or moistening them slightly before charging to the spherulizer. If they are too tacky, so that they tend to adhere together and not maintain their separate identities, plasticity may be diminished by cooling or by evaporation of moisture before charging to the spherulizing machine. Heating and cooling may be effected by air blasts or, in case of heating, by radiation. Moisture addition and subtraction may be effected by spraying small droplets of moisture onto the filaments as they are discharged from the extruder or by heating them.

The machine in which the main operations of the present invention are conducted, the sphere rolling machine, comprises a horizontally rotating frictional plate whose function it is to impart a whirling motion to filaments or rods or broken products of such filaments, and spheres. The movement in the machine will break down longer filaments into particles which are less than twice the filamentary diameter, or such breaking may be effected earlier. The rounding of such particles takes place by contact with the whirling plate, the sides of the dish, the internal machine wall and with other particles. Usually, when the motions of the particles are helical, they are rolling in contact with various surfaces and are being abraded to spherical form. The obtaining of such a helical motion depends on a number of variables, including: the speed of the disc; the types and number of projections on the disc; the size of the machine; the filamentary diameter; the total volume of beads and particles; the plasticity of the compositions; the friability of the composition; and the densities of the particles. Although all these variables are of importance, it appears that the major factors are projections, disc speed, product density and plasticity. Of these, the disc characteristics and the plasticity can often be easily controlled during a rolling operation so as to obtain best results. For example, by use of a variable speed drive, the number of revolutions made by the disc may be changed from as few as 100 to 2,000 or 5,000 per minute, although the speed will normally be from 300 to 1,500 r.p.m. By changing the type of corrugation, rib or projection on the whirling plate or by changing the size thereof, more or less impetus may be given to the particles. By adjustments in the composition, its moisture content or the temperature, plasticity may be varied. Thus, by experimentation during use the best rolling action may be obtained for most efficient production of the enzyme spheres. Similarly, the spherulizing time may be determined empirically so as to avoid unnecessary time on the machine and undesired size reduction after the wanted spherical product is made.

In preferred machines the areas 64 will be comparatively small, usually being from 1 mm. to mm. and preferably from 2 mm. to 4 mm.'on a side. Also, they will be radially positioned for most efficient operation. The plasticity of the filaments or rods will be such that these materials resemble a comparatively soft soap, just firm enough to maintain their shape but not so plastic as to adhere to other particles to form larger aggregates. The desired plasticity may be obtained by additions of moisture or by evaporations of water from the moving bed. Thus, the drawing of air through the bed by a rotating fan or by natural circulation will cause some evaporation and this may be compensated for by addition of a fine stream of water to the bed. A dye may be added to this water to color the particles at a suitable stage in their processing, if that is desired. Also, either batch or continuous operations may be effected. In batch operations complete spherulization may take place in as little as ten seconds but sometimes as long as five minutes will be required. Generally, however, processing times less than one minute are practicable. Because the spherulizing machine operates at about room temperature, generally being at from 10 to 60 C., preferably from 20 to 40 C., there is little decomposition of enzyme during processing. Furthermore, because the enzyme beads can be incorporated in much larger proportions of detergent product, through-puts of the final enzymatic detergent products may be very large. Also, the product made, if it contains too much moisture, may be dried after removal from the spherulizing machine, but this is not usually necessary.

The spherulizer employed is preferably that identified as a Marumerizer, sold by Elanco Products Company of Italy. Various suitable models are available with charge capacities ranging from 2 to 150 lbs. Such machines usually include stainless steel plates, dishes and internal walls and satisfactorily and reproducibly make enzyme spheres of the desired sizes. Such spheres, although they may tend to be somewhat heavier than may spray dried detergent products, can be made with a bulk density of from 0.3 to 1 g./ml., preferably from 0.3 to 0.6 g./ml. The beads produced are suprisingly uniform in size generally varying only i5% in diameter. However, if desired, sieving or other classifying operation may be undertaken after removal of the product from the spherulizer.

After manufacture of the enzyme spheres, they may be packaged for direct use in enzymatic pre-soak compositions, intended to remove or loosen stains from articles of laundry before washing thereof, or they may be compounded with other materials, such as builders, organic detergents and fillers. If it is desired to make enzymatic synthetic detergents, the beads will be mixed with detergent formulations, preferably spray dried beads thereof. Pre-soak compositions may contain a buffering agent or a pH-adjusting material to regulate the pH of a water solution of the pre-soak to that at which the enzyme is most effective, e.g., 7.5-8.5 or 9-10. Whether being employed in a pre-soak, a light duty or a built detergent composition, the enzyme will usually be present in sufiicient quantity so that in the case of a proteolytic enzyme, for example, an enzymatic activity of from 0.2 to 10, preferably from 0.5 to 5 Anson units per g. will be obtained.

In the art of removing stains from laundry, whether those stains be from fruit dyes, gravies, chocolate, coffee, tea, grass, inks, other proteinaceous materials, synthetic dyes or other common staining items or chemicals, the proteolytic enzymes appear to be the most effective, even when the stain is not primarily a protein stain. Although the enzyme spheres are good stain-removers, there is often also the need for a bleaching agent to be employed so that color may also be removed by oxidation, reduction or other such chemical mechanism. Since the preferred bleaching agents containing chlorine are usually not employed with enzymes because of chemical interactions which defeat the enzymatic action, other oxidizing agents which release oxygen are usually included in enzymatic preparations. Suitable per-compounds include the alkali metal salts of persulfuric acid and percarbonic acid, hydrogen peroxide, the perborates, especially sodium perborate, and the sodium, potassium and other metal salts of the per-acids. Although the perborates, particularly sodium perborate, are preferred for use, it has been found that when enzymatic compositions containing such compounds are stored for from one to six months, enzymatic action is significantly diminished. For example, the quantity of available enzyme in the product may be decreased from 30 to 100%. This serious deficiency which has helped to prevent the successful wide scale marketing of per-compounds in enzymatic detergents and pre-soak compositions, has been minimized when detergent compositions containing both perborate and enzymes are prepared using globular or spherical enzyme compositions.

In the preferred heavy duty detergent compositions, the synthetic organic detergent, which may be any of those commercially used or previously described in this specification, usually constitutes from to 35%; inorganic salt builders, e.g., pentasodium tripolyphosphate or substitutes therefor, such as trisodium nitrilotriacetate, are from 20 to 80%; inorganic filler salts, such as sodium sulfate, are from 0 to 40%; adjuvants are from 1 to 25%; and per-compounds, e.g., sodium perborate, are from 1 to 20%, preferably from 2 to with the perborate or other per-compound normally being post-added when the detergent composition is produced by spray drying. Enzyme spheres may be added also to non-spray dried detergent compositions preferably containing percompounds. The percentage of enzyme beads added to the detergent particles in the making of an enzymatic per-compound detergent, will usually be from 0.5 to preferably from 1 to 10% thereof. Furthermore, the ingredients of the present compositions will generally be chosen so as to assure that a 1% solution of the final preparation in water has a pH in the range of from 6.5 to 9.5 or 10, preferably from 7.5 to 9, so that enzyme stability during storage may be greatest.

Why the perborate detergent composition containing the present enzyme spheres should be so stable, with respect to enzymatic activity, despite long periods of storage at room temperature and at elevated temperatures, even under high humidity conditions, has not yet been definitely established. The insulating effect of the surface active agent or binder with which the enzyme preparation is formulated before rolling into spheres may help to prevent reaction with per-compounds in a detergent composition. Also the very low surface:volume ratio of the spheres may contribute to stability, as the more plastic binder or surface active agent may be brought to the surface of the particle during rolling, thereby minimizing contact of the enzyme with the perborate. The sphere is also less likely to fracture than is a rod or filament, thus preventing the exposure of new surfaces to the per-compound. Finally, the synthetic detergent may act as a stabilizer. Whatever the reason, it is an established fact that heavy duty perborated detergents to which the present enzyme beads have been added are much more stable on storage than are granular or powdered products of similar compositions or spray dried or spray cooled detergent beads containing both perborate and enzyme. In fact, in many instances in the present heavy duty detergents, with or without perborate present, the beads act to stabilize the enzyme. Thus, such compositions may contain a greater enzymatic activity after storage than does pure enzyme or enzyme plus filler salt treated under the same conditions but without contacting perborate or other detergent composition constituents.

The following examples illustrate specific embodiments of the invention. Unless otherwise mentioned, all parts given are by weight and all temperatures are in degrees C.

EXAMPLE 1 Kilograms Magnesium lauryl sulfate (Empicol MLV from Marchon) 9.12 Sodium sulfate, anhydrous, fine powder 4.88 Proteolytic enzyme, Alcalase" (Novo Industries,

1.5 AU/g., sulfate type) 5.00 Water, deionized 1.00

The magnesium lauryl sulfate, which includes 78.6% of active ingredient, 5.9% of magnesium sulfate, 2.3% of lauryl alcohol and about 13% of water, the sodium sulfate, and Alcalase, which includes about 11% of organic material, 70% sodium chloride and the balance sodium sulfate, are blended together and the water is added to the mixture in an amalgamator of the type such as is normally employed in the manufacture of soap. The materials all pass through a 60 mesh sieve and the Alcalase particle size is between 0.01 and 0.15 mm. in diameter. After mixing at room temperature (25 C.) for about three minutes, the mix is passed through a three roll mill, with the temperature of the mill maintained by cooling water passing through the rolls so that the chip of enzyme preparation resulting is at a temperature of 30 to 40 C. The chip taken off the mill at a conven tional knife is about 0.203 mm. thick. Next, the chips are fed to a soap type plodder, having a single worm in a barrel which develops a pressure of about 300 lbs. per square inch and forces the plasticized composition through a perforated plate covered with a wire net having 0.5 mm. openings in it. The filaments or rods discharged from the plodder break into smaller pieces, generally of a length of 1 to 10 millimeters. These are cooled and partially dried so that they are non-adhering to each other at room temperature. The cooling is from a temperature of about 30 C. to 25 C. and the drying decreases the moisture content to about 9%, from 11%. In addition, some of the sodium sulfate becomes hydrated, further diminishing the tendency of the product to adhere or cohere with other filaments.

The rods or filaments obtained from the plodder are next spheronized by being charged to a Marumerizer, Model Q-400, at about 25 C., and the speed of the corrugated supporting plate of the machine is raised to 800 r.p.m. Within four minutes the rods are broken to lengths less than twice the filamentary diameter and rolled to spherical shape. The rolling follows a helical path in contact with the machine walls, supporting dish, projections and other particles. During the processing in the Marumerizer, a fan on the same shaft as the revolving corrugated plate circulates air through the bed of particles, helping to maintain them separate and aiding in removing fines so that these do not mix in with the 0.5 mm. spheres produced and withdrawn near the top of the bed, as illustrated in FIG. 2.

The beads produced are substantially all spherical in shape and have particle sizes within a range of about 0.5 mm. average diameter, preferably :10 or -5%. Their bulk density is about 0.6 g./ml. They are free-flowing, form-maintaining, attractively regular in appearance and may be packed or shipped to storage, without preliminary drying or cooling, although such steps may some times be employed. The final moisture content of the product is in the range of 512%, preferebaly 8-1l%, by weight. When checked for enzymatic activity, it is confirmed that none of this is lost during the processing.

Twenty-eight parts of the spheres produced were added to 972 parts of a commercial, low sudsing, perborated heavy duty synthetic organic detergent so as to produce a product having an enzymatic action of about 0.01 Au/ g. The perborated detergent is a spray dried product to which perborate has been post-added having beads of a size that pass through a 60 mesh sieve, most of which are about 0.5 mm. in diameter. The detergent includes 1.5 parts of sodium perborate, 3 parts sodium tripolyphosphate, 1 part of sodium coco-tallow soap, 0.5 part ethoxylated polyalkylene glycol (Tergitol XD), 0.8 part of sodium silicate, 0.8 part of Na SO and 0.5 part water. It is noted that after mixing in of the detergent spheres, they are well distributed in the synthetic detergent composiion and do not settle out therefrom. Bulk densities of the products are approximately the same and the bead sizes are the same, leading to that desired result. On storage for periods of time up to six months, loss in enzymatie activity is less for the mixture than for the Alcalase alone. After four weeks at an elevated temperature, 43 C., packed in cartons containing no moisture barriers, the enzyme powder alone loses about 19% of its activity, while the enzyme spheres of the mentioned built detergent lose about 16%. When the enzyme powder alone is added to the built detergent, within about one week at 43 C. it loses almost 100% of its enzymatic activity. The enzymatic perborate-containing built detergent of the invention is an excellent washing agent and enzymatically removes stains from the laundry. It is also useful as a pre-soak composition, if desired.

Substantially following the procedure of Example 1, various raw materials are blended together in a soap type amalgamator, milled on a three roll mill and extruded through a plodder perforated plate having openings of a diameter of 7 mm. (a minor change in procedure is to save one kilogram of sodium sulfate for later use in the spheronizing machine). The green cylindrical rods, of 7 mm. in diameter and 1 centimeter length, are then extruded through an Elanco extruder, such as that illustrated in FIG. 4, which is equipped with two perforated plates having openings of 1 millimeter diameter. The processing conditions are otherwise the same as those employed in Example 1 and the temperature in the extruder, which is at a pressure of about 200 lbs. per square inch, is about 35 C. The extrudate, in the form of cylindrical strands of 1 millimeter diameter, is aged for three minutes at room temperature, during which time it cools to 30 C. and loses about 0.5% moisture. It is then charged into a Marumerizer spheronizing machine, the plate is spun at 400 to 800 r.p.m. for about five minutes, at the end of which time the finely powdered sodium sulfate is added, and the product is discharged and sieved on a US. No. 12 sieve to separate out the few coarse particles formed (about 1%). The operating temperature in the spheronizer ranges from 29 to 36 C. and the final product has a moisture content of about 11.1%. The product is almost perfectly spheroidal and of a pleasant green hue. It is practically free from fines and in fact, no fine fragments are recovered from the dish of the Marumerizer apparatus.

The beads produced are blended with the perborated detergent product, as described in Example 1, and checks on enzymatic activity are made after storage. It is found that the loss of enzyme activity after four weeks at 43 C. is only 6.6%, whereas greater losses are encountered for the Alcalase alone, under such conditions.

EXAMPLE 3 Kilograms Oxylated alkanol (C -C alcohol, 50 moles ethyl- All of the materials except the titanium dioxide are processed in a manner like that of Example 2. The titanium dioxide is added in the spheronizing machine. Actual moisture found is 1.2%, in the final product. Enzymatic stability after four weeks at 43 C. is not as good as stabilities noted in Examples 1 and 2 but is much better than with compositions comprising perborated detergent and enzyme, without the enzyme having been treated aocording to the present invention. Thus, the 31% loss in enzymatic activity observed in the above test corresponds to the loss noted when enzyme is added to heavy duty detergents containing no perborate. The product obtained is one which has 99%. thereof passing through a No. 20 sieve and remaining on a No. 60 sieve. It is an excellent cleaning agent and may be used as a pre-soak for removing stains from laundry.

In other experiments, when different surface active agents, either of the anionic ornonionic types, as previously described, are substituted in whole or in part for the surface active agents of the above working examples, similar improved enzyme spheres are obtained. This is also the case when different extruders or spheronizers are used or the processes are modified so as to add moisture at any suitable point therein, e.g., in the spheronizing, 'vary the dish speeds of the spheronizer, modify the formulas to omit inorganic filler salt or include other builder salts, or recycle some of the fines removed from the spheronizing machine back to the amalgamator. For example, when from 0.5 to 5% of moisture is added in the spheronizing machine, it aids the surface active agent in coating the enzyme, forming a film of surface active agent on the outside of the spherical product. The coating and rolling action are also modified when dish speeds are changed so that the particles move at rates of from 50 to 150 lineal feet per second. If the ED. & C. dye solutions are added in the spheronizer, less dye can be employed to obtain the same degree of coloration and, at the same time, plasticity of the spheres can be desirably affected. When nitrilotriacetates are substituted for builders or fillers in the enzymatic preparations to be spheronized, good products are also obtainable. Similarly, when hydrotropic salts are used instead of detergent salts, in whole or in part, the desired spheres result.

The invention has been described with respect to vari ous examples and illustrations thereof but it is evident that it is not to be limited to them, because it will be apparent to one of skill in the art that substitutes and equivalents may be employed without departing from the spirit of the invention or the scope of the claims.

What is claimed is:

1. A process for the manufacture of enzymatic compositions in spherical form, having increased stability upon storage and on exposure to oxidizing agents, which comprises mixing 1 part by weight of a normally solid enzyme with from 1 to 50 parts by weight of a normally solid synthetic organic surface active agent selected from the group consisting of anionic, nonionic, amphoteric, and cationic surface active agents at a temperature in the range of 10 C. to 60 C. which the enzyme is stable and for a period of from 1 to 30 minutes and sufiicient to make a homogeneous, plasticizable mixture of enzyme and surface active agent; compressing and mechanically working the plastic mixture at a temperature in the range of 10 C. to 60 C. to make it plastic and to force the plastic, mechanically worked mixture through small openings at pressures from to 500 p.s.i.g. to produce spaghetti-like filaments thereof having a diameter in the range of from .254 mm. to 2.54 mm. which is approximately equal to that of the desired spheres; rolling a bed of filament at a temperature of from 10 C. to 60 C. in contact with frictional surfaces rotating at a speed from 100 to 5000 r.p.m. to break said filaments and to rub off portions thereof; continuing said rolling for from 10 seconds to up to five minutes until the filaments are reduced to a length about that of the diameter thereof and are rounded into spherical shape; and removing such rounded particles from an upper portion of the bed.

2. A process according to claim 1 wherein said enzyme spheres are useful for blending with detergent compositions without separating from them, said enzyme is in the form of a powder and is mixed with an anionic or nonionic synthetic organic surface active agent, said mixture of enzyme and surface active agent further includes 0.5% to 20% by weight of water, and said compressing and mechanical working are effected by milling and extruding.

3. A process according to claim 2 wherein said enzyme spheres have average diameters within the range of 0.51 mm. to 2.03 mm., said enzyme is a proteolytic enzyme in the form of a fine powder, substantially all of which passes through a 60-mesh US. Standard Sieve Series sieve, and said rolling is effected in a machine by rotating disc having means thereon projecting away from the disc surface to impart a circular motion to the filaments in a bed in contact with such disc and to cause a rolling motion of such filaments and spheres produced in contact with such disc, outer machine walls and with each other to round out the particles.

4. A process according to claim 3 wherein said enzyme spheres consist essentially of 1% to 20% by weight of protease, to 70% by weight of a detergent selected from the group consisting of C -C alkyl sulfates and condensation products of C -C fatty alcohols with 3 to 50 moles of ethylene oxide, to 80% by weight of water-soluble detergent builder salt selected from the group consisting of inorganic sodium and potassium sulfates, chlorides, carbonates, bicarbonates, borates and phosphates and trisodium nitrilotriacetate, and 1% to by weight of water, with a portion of the water present being added to and evaporated from the filaments during said rolling operation.

5. A process according to claim 4 wherein said enzyme is a subtilisin enzyme preparation consisting essentially of 5% to by weight of organic enzyme material, sodium chloride and sodium sulfate, a major proportion of said preparation passes through a 100 mesh sieve, said preparation has an activity of about 0.5 to 5 Anson units per gram, said alkyl sulfate is magnesium lauryl sulfate, the moisture removed during rolling is from 1% to 10% by weight and the final moisture content of the spherules is from 2% to 15 by weight.

6. A process according to claim 4 which includes the added step of blending 0.5% to 20% by weight of said enzyme spheres with a particulate heavy duty synthetic detergent composition which consists essentially of 5% to 35% by weight of an anionic or nonionic synthetic organic detergent and the balance a water-soluble, detergent builder salt selected from the group consisting of inorganic sodium and potassium sulfates, chlorides, carbonates, bicarbonates, borates and phosphates and trisodium nitrilotriacetate in the form of spray dried beads, the proportion of enzyme composition spheres in the product is from 1% to 10% and said enzyme spheres and said heavy duty synthetic detergent compositions are of about the same sizes and densities, so that the product made includes evenly distributed enzyme composition spherules which are non-settling from the detergent heads.

7. A process according to claim 6 wherein the said synthetic detergent composition contains from 1% to 20% by weight of alkali metal perborate.

8. A process according to claim 1 wherein said spaghetti-like filaments are cooled and/or moisture is evaporated from them to decrease the plasticity thereof and to promote ready breaking before rolling to spherical shape.

9. A process according to claim 2 wherein said extruded filaments are broken into pieces having a length generally less than twice the filament diameter prior to said rolling.

10. An enzymatic composition made by the process of claim 1.

References Cited UNITED STATES PATENTS 3,650,967 3/1972 Johnson -63 FOREIGN PATENTS 1,204,123 9/1970 Great Britain 252Dig. 12

WILLIAM E. SCHULZ, Primary Examiner U.S. Cl. X.R.

195-68; 252Dig. 12

Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4009076 *Nov 2, 1973Feb 22, 1977Lever Brothers CompanyEnzyme granules
US4016040 *Nov 1, 1974Apr 5, 1977Colgate-Palmolive CompanyPreparation of enzyme-containing beads
US4016041 *Jan 22, 1976Apr 5, 1977Lever Brothers CompanyProcess of making granular enzymes of reduced stickiness
US4087368 *Jul 1, 1975May 2, 1978Colgate-Palmolive CompanyWater-soluble enzyme granules
US4090973 *Jun 24, 1976May 23, 1978The Procter & Gamble CompanyMethod for making stable detergent compositions
US4106991 *Jun 28, 1977Aug 15, 1978Novo Industri A/SEnzyme granulate composition and process for forming enzyme granulates
US4115292 *Apr 20, 1977Sep 19, 1978The Procter & Gamble CompanyEnzyme-containing detergent articles
US4176079 *Apr 20, 1977Nov 27, 1979The Procter & Gamble CompanyWater-soluble enzyme-containing article
US4242219 *Jun 26, 1978Dec 30, 1980Gist-Brocades N.V.Novel enzyme particles and their preparation
US4503146 *Apr 5, 1983Mar 5, 1985Technicon Instruments CorporationMethod for eliminating turbidity in a biological fluid and reagent therefor
US4801544 *Dec 8, 1986Jan 31, 1989The Clorox CompanyMethod of improving the storage life of liquid compositions containing enzymes
US4816411 *Aug 26, 1986Mar 28, 1989Technicon Instruments CorporationMethod for eliminating turbidity in a biological fluid and reagent therefor
US4876198 *Aug 19, 1988Oct 24, 1989Novo Industri A/SMethod for production of an enzyme granulate
US4940665 *Dec 26, 1986Jul 10, 1990Showa Denko K. K.Method for granulation of enzyme
US5443764 *Oct 11, 1994Aug 22, 1995Ici Australia Operations Propietary LimitedWater-dispersible granules
US6136772 *May 14, 1997Oct 24, 2000Novo Nordisk A/SEnzyme-containing granules and process for the production thereof
US8308469 *Sep 17, 2008Nov 13, 2012Fuji Paudal Conmpany LimitedCleaning device and fine-particle processing device therewith
EP0202409A2 *Mar 13, 1986Nov 26, 1986Miles Inc.A process for the production of viable and stable dry microorganisms for food and agricultural purposes
WO2002053652A1 *Dec 29, 2000Jul 11, 2002Roha Dyechem LtdManufacturing process of spheroidal food dyes
WO2002102959A1 *Jun 8, 2002Dec 27, 2002Henkel KgaaStorage-stable washing and/or cleaning agent having a low zeolite content
U.S. Classification510/305, 510/374, 510/306, 510/451, 435/187, 435/188, 510/320, 510/530, 510/438, 510/392
International ClassificationA24C1/00, C11D17/06, C11D3/38, C11D3/386, B01J2/10, B01J2/20, A24C1/30
Cooperative ClassificationB01J2/10, B01J2/20, C11D3/38672, C11D17/065
European ClassificationB01J2/10, C11D3/386M, B01J2/20, C11D17/06H