The present invention relates to enzyme-containing granules comprising (a) an enzyme and (b) a core which intrinsically is capable of absorbing at least 5% w/w (based on the weight of the core) of water and to processes for the production of such granules comprises (a) contacting absorbent cores, capable of absorbing at least 5% w/w (based on the weight of the core) of water, with a liquid medium, such as an aqueous medium, containing an enzyme in dissolved and/or dispersed form, the amount of the liquid medium employed being such that substantially no attendant agglomeration of the resulting product occurs; and (b) at least partially removing volatile components of the liquid medium from the resulting product.

The present invention relates to an enzyme-containing granulate (made up of enzyme-containing granules or particles) with extremely low tendency to dust formation, to a process for producing such a granulate, and to the use of said granulate for a number of industrial applications.
The industrial use of enzymes, notably enzymes of microbial origin, has become increasingly common. Enzymes are used in numerous industries, including, for example, the starch-processing industry and the detergent industry. It is well known that the use of enzymes, particularly proteolytic enzymes, in the detergent industry has given rise to industrial hygiene concerns for detergent factory workers, particularly due to the health risks (including the risk of allergy development) associated with any formation of enzyme-containing dust which may occur.
Since the introduction of enzymes into the detergent industry, a lot of effort has been devoted to improving the granulation and coating of enzymes so as to reduce enzyme dust formation.
One type of process for producing an enzyme-containing granule comprises coating the surface of a core with an enzyme followed by an outer layer coating. U.S. Pat. No. 5,324,649 describes coating of the surface of a non-pareil core with an enzyme followed by an outer layer coating. U.S. Pat. No. 4,689,297 and EP 0 532 777 describe a process which comprises applying an enzyme on the surface of a salt crystal based core or a non-pareil core, by spraying the enzyme onto the core in a fluid-bed followed by an outer layer coating.
Yet another type of process essentially comprises: (i) mixing an enzyme with suitable granulation components (preferably as dry matter), such as filler, binder, fibrous material and a granulation agent (e.g. water) in a granulator (e.g. a mixer), and (ii) processing the mixture in a granulating apparatus until the granule has the desired particle distribution and degree of roundness (sphericity).
Numerous references describe processes for making enzyme-containing granules by such a process. Such references include U.S. Pat. No. 4,242,219, U.S. Pat. No. 4,740,469, WO 94/04665, U.S. Pat. No. 4,940,665, EP 564476, EP 168526, U.S. Pat. No. 4,661,452, U.S. Pat. No. 4,876,198, WO 94/16064 and U.S. Pat. No. 4,106,991.
Further, U.S. Pat. No. 5,494,600 and U.S. Pat. No. 5,318,903 describe a process comprising absorption of an enzyme into a porous hydrophobic core (e.g. a porous hydrophobic silica core) followed by coating.
Although granulation techniques have improved, in order to take account of increasing environmental concerns and heightened awareness in the field of industrial hygiene, there remains a continuing need for enzyme-containing, granular compositions exhibiting even lower dust formation than presently available products.
An object of the present invention is to provide such enzyme-containing granular compositions, and improved processes for producing such compositions.
It has surprisingly been found that extremely low tendency to dust formation by enzyme-containing granules is achievable when the granules are based on suitably selected cores (particles), more specifically cores fulfilling, in particular, certain requirements with respect to liquid-absorption properties.
A first aspect of the present invention thus relates to an enzyme-containing granule comprising:
(a) an enzyme, and
(b) a core which intrinsically is capable of absorbing at least 5% by weight (w/w) of water (relative to the weight of the core).
In keeping with this first aspect of the invention, a further aspect of the invention relates to a process for producing enzyme-containing granules from absorbent cores, the process comprising:
(a) contacting absorbent cores, capable of absorbing at least 5% w/w (based on the weight of the core) of water, with a liquid medium containing an enzyme in dissolved and/or dispersed form, the amount of the liquid medium employed being such that substantially no attendant agglomeration of the resulting product occurs; and
(b) at least partially removing volatile components of the liquid medium from the resulting product.
Cores
Cores forming the basis of enzyme-containing granules of the invention (and in the context of processes according to the invention for the preparation of such granules) are cores which, in the absence of a hydrophobicity-reducing substance or surface-tension-reducing substance (such as a surfactant) and of constituents of the enzyme-containing granules (notably the enzyme or enzymes in question) other than those of the core itself, have an intrinsic (i.e. inherent, innate or xe2x80x9cnativexe2x80x9d) ability to absorb at least 5% w/w of water when brought into contact with water (i.e. essentially pure, liquid water).
Cores of relevance in the context of the invention are preferably capable of absorbing at least 10% w/w (based on core weight) of water, more preferably at least 15% w/w and still more preferably at least 20% w/w. Particularly preferable cores are cores capable of absorbing at least 30% w/w of water, such as cores capable of absorbing at least 33% w/w. Certain preferred types of cores have an even greater water-absorption capacity (e.g. about 40% w/w or more of water).
The ability of a particular type of core to absorb water may suitably be determined, for example, by spraying a measured amount of water onto a measured amount of cores with mixing in a mixer [e.g. as described in Example 1 herein (vide infra)] and observing the appearance and behaviour of the cores in the course of spraying; ambient conditions (ambient temperature, pressure etc.) are generally suitable. In general, as long as the amount of cores in question is able to absorb water there is essentially no agglomeration of the wetted cores (i.e. agglomeration to form lumps or the like) and it is possible to remove the resulting individual particles and dry them without significantly changing the overall particle size distribution.
In the context of the invention, a quoted weight percentage of water which a given type of core is capable of absorbing is thus a xe2x80x9cmacroscopicxe2x80x9d, overall value determined using a relatively large amount (and thereby a large number) of cores (particles) of the given type, such as a multi-kilogram quantity (e.g. an amount of about 5, 10, 15 or more kilograms of the given type of core).
If appropriate, smaller quantities of cores may, however, be employed for the determination of water-absorption capacity, provided (i) the number of individual core particles in the sample employed is sufficiently high to be adequately representative of the bulk cores, and (ii) the sample employed is sufficiently large to permit satisfactorily gradual addition of water (preferably by spraying), with adequate mixing, while observing the appearance/behaviour of the cores with respect to surface wetness and tendency to agglomerate.
With a poorly absorbing or non-absorbing core material, agglomeration of the granules will normally occur upon introduction of only a small amount of water, and consequently it will generally not be possible to maintain the initial overall particle size distribution.
An example of a poorly absorbing core material is a conventional sugar/starch-based particle of the so-called nonpareil type. In working examples herein (vide infra) it is shown, inter alia, that a typical nonpareil core product is able to absorb less than 4% of water by weight (relative to the core).
Preferred embodiments of enzyme-containing granules of the invention are granules wherein at least part of the total amount of enzyme present in the granule is absorbed within the core; such granules will often be granules wherein at least part of the total amount of enzyme present in the granule has been absorbed into the core via contact of the outer surface of the core with a liquid medium containing the enzyme in question.
Such embodiments appear [cf. the working examples herein (vide infra)] to be advantageous in relation to achieving improvement in a number of characteristics or properties of enzyme-containing granules of the invention relative to enzyme-containing granules of known types; these characteristics or properties include:
tendency of the granules to form dust (particularly enzyme-containing dust);
enzymatic activity yield of the granules (i.e. degree of retention, in a batch of product granules, of the total original enzymatic activity of the enzyme preparation used to prepare the batch);
degree of retention of enzymatic activity during storage of the granules under various conditions; and
degree of retention of enzymatic activity following aggressive treatments such as exposure to high temperatures and/or high humidity.
Moreover, without being bound to any theory it is believed [as also mentioned below (see Example 11 herein)] that the presence, within the core, of absorbed enzyme enhances the adherence of enzyme deposited on the outer surface of an absorbent core of the type of relevance in the context of the invention, leading to corresponding reduction in the tendency to dust formation by such a product.
In relation to embodiments of enzyme-containing granules of the invention wherein a part of the total enzyme content is absorbed within the core, valuable embodiments include those wherein at least 10% w/w, such as at least 25% w/w, e.g. at least 40% w/w of the total enzyme content (calculated as active enzyme protein) is present as enzyme absorbed within the core.
Particularly valuable embodiments include those wherein at least 90% w/w of the total enzyme content of the granule is present as enzyme absorbed within the core, and it is possible (employing, e.g., a process according to the invention) to obtain enzyme-containing granules of the invention in which essentially all (i.e. essentially 100% w/w) of the enzyme content of the granule is present as enzyme absorbed within the core.
In may be mentioned this connection that for a given distribution of the enzyme content of granules of the invention between (i) core-absorbed enzyme and (ii) enzyme present on the surface of the core or in/on one or more coating layers, the absolute amount of enzyme protein which is present as enzyme absorbed within the core will, of course, depend on the total amount of enzyme present in the granule.
Cores forming the basis of enzyme-containing granules of the invention, and cores employed in the process according to the invention, are preferably shaped so that the ratio between the largest and the smallest diameter thereof is less than 3; granules of the inventionxe2x80x94whether uncoated or coated (vide infra)xe2x80x94are likewise preferably shaped so that the ratio between the largest and the smallest diameter thereof is less than 3. For both cores and enzyme-containing granules, the latter ratio is preferably less than 2, more preferably xe2x89xa61.5 (i.e. between 1 and 1.5), and it is particularly preferred that the ratio in question is at most 1.2.
In should be noted that in the context of the present invention, values of the above-mentioned ratio between the largest and the smallest diameters of cores or granules as recited herein are normally determined as the mean value of the ratio in question for a representative number of particles taken at random from a sample of the cores or granules in question. For the majority of preferred types/shapes of cores or granules in the context of the invention, measurement of the ratio in question (e.g. by microscopy) for each of 20 or more particles taken at random from a sample of cores or granules, respectively, provides a reliable basis for calculating a satisfactorily reproducible mean value.
For most purposes, cores forming the basis of enzyme-containing granules of the invention, cores employed in the process according to the invention, as well as enzyme-containing granules of the invention perse, are substantially spherical, i.e. such that the ratio in question is about 1 (in that for a strictly spherical particle, the ratio in question is of course 1.0).
The ratio between the largest and the smallest diameter of a core or a granule may in general be taken as the ratio between the largest and the smallest dimension (linear dimension) of the core or the granule, respectively, in a direction passing substantially through the center of the particle.
With regard to the term xe2x80x9ccenter of the particlexe2x80x9d it will be apparent that particles (cores or granules) which are substantially axially symmetric, such as substantially spherical or ellipsoidal particles, will have a geometrically rather well-defined center. In such cases the term xe2x80x9ccenter of the particlexe2x80x9d may be interpreted in a geometric manner.
Particles of more irregular shape will, however, in general not have a geometrically definable center, and in such cases the xe2x80x9ccenter of the particlexe2x80x9d may [in that irregularly shaped particles (cores, granules) arexe2x80x94for most purposesxe2x80x94generally not preferred types in the context of the invention] be understood to be the center of gravity of the particle in question.
It is further preferred that cores forming the basis of enzyme-containing granules of the invention, cores employed in the process according to the invention, as well as enzyme-containing granules of the invention per se [whether the granules are uncoated or coated (vide infra)] have a substantially smooth surface, i.e. a surface which is essentially free of protuberances, spikes, secondary particles, irregularities, cavities, craters, indentations, pits and the like.
The degree of xe2x80x9csmoothnessxe2x80x9d of cores or granules in the context of the invention will, in general, be based on an overall assessment of the surface characteristics of a representative sample of bulk cores or granules, respectively. Particularly in the context of particles (cores or granules) which are substantially spherical, the term xe2x80x9csmoothxe2x80x9d may further be taken to indicate that the mean value, for a representative number (e.g. xe2x89xa720 particles), of the ratio between the largest and the smallest linear dimension of the particles, in a direction passing through the center of the particle, and measured on any given partial segment of the outer surface of the particle, is less than 1.15, preferably less than 1.10, and more preferably less than 1.05.
Preferred types of cores in the context of the invention include cores comprising starch and/or modified starch, notably cores containing a total of at least 25% w/w (based on total core weight), such as at least 50% w/w, of starch and/or modified starch.
Enzyme-containing granules based on cores comprising a total of at least 75% w/w of starch and/or modified starch, e.g. a total of at least 80% w/w, such as a total of at least 85% w/w (based on total core weight) of starch and/or modified starch, appear, in general, to possess particularly advantageous properties (e.g. properties such as low tendency to dust formation, heightened retention of enzyme activity, etc, as discussed earlier, above).
Highly preferred cores of this type are cores containing a total of at least 90% w/w, particularly at least 95% w/w (based on total core weight), of starch and/or modified starch, especially cores consisting essentially exclusively of (i.e. containing a total of essentially 100% w/w of) starch and/or modified starch.
It will be apparent that the above-mentioned total weight percentages (% w/w) of starch and/or modified starch are expressed as percentages of the weight of the core(s) per se, [i.e. the cores in their xe2x80x9cnativexe2x80x9d or innate state, not including the enzyme and/or any other components which enter or adhere to the core(s) in the course of preparation of enzyme-containing granules in accordance with the invention].
Starches (naturally occurring starches) from a wide variety of plant sources appear to be suitable in the context of the invention (either as starches perse, or as the starting point for modified starches), and relevant starches include starch from: cassava [notably from bitter cassava (Manihot esculenta) or sweet cassava (Manihot dulcis)]; sago-palm (Metroxylon spp., such as M. sagu); potato (Solanum tuberosum); rice (Oryza spp.); corn (maize, Zea mays); wheat (Triticum spp.); barley (Hordeum spp., such as H. vulgare) sweet potato (Ipomoea batatas); sorghum (Sorghum spp.); and yam (Dioscorea spp.).
Other types of starch of potential value in the context of the invention include starch from: rye (Secal cereale); oat (Avena spp., such as A. sativa); millet (e.g. from species of Digitaria, Panicum, Paspalum, Pennisetum or Setaria); buckwheat (Fagopyrum spp., such as F. esculentum); waxy maize; other cereals; arrowroot (e.g. Maranta arundinacea); taro (Colocasia spp., such as C. antiquorum or C. esculenta); tannia (Xanthosoma sagittifolium); Amaranthus spp.; and Chenopodium spp.
Cassava starch is among preferred starches in the context of the invention; in this connection it may be mentioned that cassava and cassava starch are known under various synonyms, including tapioca, manioc, mandioca and manihot.
As is well known, starches consist, in general, essentially of macromolecular polymers composed of xcex1-D-glucopyranose units. Linear or substantially linear polymeric forms in which these units are linked by xcex1-D-(1xe2x86x924) linkages are known as xe2x80x9camylosexe2x80x9d. Branched polymeric forms containing xcex1-D-glucopyranose units linked by both xcex1-D-(1xe2x86x924) and xcex1-D-(1xe2x86x926) linkages are known as xe2x80x9camylopectinxe2x80x9d, the xcex1-D-(1xe2x86x926) linkages accounting typically for about 5-6% of the glycosidic linkages therein.
In this connection, starches from different vegetable sources contain different proportions of amylose and amylopection. Thus, for example, starch from potatoes typically contains ca. 20% w/w of amylose and ca. 80% w/w of amylopectin, whereas so-called xe2x80x9cwaxy maize starchxe2x80x9d generally contains xe2x89xa62% w/w of amylose and  greater than 98% w/w of amylopectin.
In relation hereto it may be mentioned that a considerable amount of effort has been expended with a view to obtaining strains (e.g. genetically manipulated strains) of starch-producing plants which can produce starches having an altered amylose/amylopectin balance (ratio) relative to that of starch produced by the plant as it occurs in nature.
Starches having widely differing proportions of amylose and amylopectin, respectively, are believed to be of value in the context of the present invention. Thus, high-amylose starches, high-amylopectin starches, and starches having intermediate amylose/amylopectin ratiosxe2x80x94including starches from genetically modified plant sourcesxe2x80x94are all of relevance in the context of the invention, either as starches per se or as sources of modified starches.
As employed in the context of the present invention, the term xe2x80x9cmodified starchxe2x80x9d denotes a starch (native starch) which has undergone some kind of at least partial chemical modification, enzymatic modification, and/or physical or physicochemical modification, and whichxe2x80x94in generalxe2x80x94exhibits altered properties relative to the xe2x80x9cparentxe2x80x9d starch.
Relevant chemical modifications include, but are not limited to: esterification of hydroxy groups (achieved, e.g., via acetyl-ation); etherification of hydroxy groups; oxidation (achieved, e.g., via reaction with chlorine or hypochlorite); and cross-linking (achieved, e.g., by reaction with formaldehyde or epichlorohydrin).
Etherified starches (e.g. carboxymethyl-starches or hydroxyalkyl-starches) and/or esterified starches can serve, inter alia, as binders (vide infra) in cores of relevance in the context of the invention.
Relevant enzymatic modifications include, for example, treatment with a starch-degrading or starch-modifying enzyme, e.g. an amylase, such as an xcex1-amylase or glucoamylase. In this connection, a particularly interesting possibility is modification of the absorption properties (and possibly other properties) of existing starch-containing cores, including cores consisting predominantly or essentially exclusively of starch and/or partly gelatinized starch (vide infra), by controlled treatment thereof with a starch-degrading enzyme so as to modify (normally increase), the porosity/absorption capacity of cores [for example via the creation of new pores, and/orvia increase in the size and/or number and/or extent (xe2x80x9cdepthxe2x80x9d) of existing pores therein].
Relevant physical or physicochemical modifications include, in particular, so-called gelatinization. The term xe2x80x9cgelatinizedxe2x80x9d, in the context of starch, is used herein in accordance with usage in the art (see, e.g., A. Xu and P. A. Seib, Cereal Chem. 70 (1993), pp. 463-70).
When a core comprising a porous aggregate of starch grains is partly gelatinized (e.g. by heating under water vapour pressure), it is believed that the starch grains situated at or near the outer surface of the core undergo a process wherein the amylose and/or amylopectin in the grains in question forms an internal network/structure which results in greater elasticity and physical strength of the outer part of the core.
The degree of gelatinization may suitably be determined using differential scanning calorimetry (DSC) as described by A. Xu and P. A. Seib (loc cit.) (see Example 21 herein for further details).
In a further aspect of the invention, very useful cores of the type (discussed above) comprising starch and/or modified starch are cores which comprise partly gelatinized starch; preferred cores of this type include cores consisting essentially exclusively of partly gelatinized starch.
In such cores it is generally desirable that the degree of gelatinization (vide infra) of the starch is greater than 0.5%, such as at least 2%, and at most 95%. For many types of starch, a preferred range of degree of gelatinization in this connection is from 10% to 60% gelatinization.
Starch-containing cores with very low degrees of starch gelatinization appear to have lower physical strength than corresponding cores with high degrees of starch gelatinization. On the other hand, the water-absorption ability of starch-containing cores with high degrees of starch gelatinization appears to be lower than for cores with lower degrees of starch gelatinization.
Particularlyxe2x80x94but not exclusivelyxe2x80x94in the case of cores consisting predominantly, or essentially solely, of partly gelatinized starch, degrees of starch gelatinization in the range of 30-60%, such as in the range of 30-50%, appear to be associated, inter alla, with a combination of very satisfactory absorption capacity, a high degree of sphericity and surface smoothness, and satisfactorily high physical strength (resistance to crushing). As is apparent from the working examples herein (vide infra), starch-based cores of this type can be supplied by existing suppliers, and have been found to exhibit a very desirable combination of properties in the context of numerous aspects within the scope of the present invention.
In connection with the use, in particular, of starches as core materials in the context of the invention, it is contemplated that as an alternative to substantially homogeneous, starch-based core particles it will be possible to employ core particles which comprise a layer of absorbent starch (e.g. cassava starch or rice starch) deposited on an inner carrier material (e.g. an insoluble silicate, carbonate or the like) which may or may not itself possess the water-absorption properties which are otherwise characteristic of cores in the context of the invention.
In this connection, further types of absorbent cores which appear to be suitable in the context of the invention include cores comprising a non-hydrophobic silicate or siliceous material as an absorbent material. Examples of such materials which may be prepared in, or are available in, granular form are bentonite, fuller""s earth (both of which consist predominantly of the smectite mineral montmorillonite), diatomaceous earths (infusorial earths, e.g. kieselguhr, tripolite, tripoli or diatomite) and other smectite minerals (such as beidellite, nontronite, saponite, sauconite or hectorite).
Cores forming the basis of enzyme-containing granules according to the invention, or employed in the process of the invention, mayxe2x80x94where appropriate and relevantxe2x80x94comprise one or more materials (additives or adjuvants) such as binders, fillers, plasticizers, fibrous materials and/or so-called xe2x80x9csuperabsorbentsxe2x80x9d.
Binders: When incorporated in cores in the context of the invention, binder(s) will suitably be present in amounts constituting up to about 20% of the total weight of the core. Appropriate binders will generally be binders which are conventionally used in the field of granulation and which have a high melting point, or do not melt, and are of a non-waxy nature. Such binders may be low or high molecular weight binders, including water-soluble binders and water-based emulsion binders. Included in this connection are carbohydrate-type binders ranging from substances of the monosaccharide type to substances of the polysaccharide type, as well as derivatives thereof. Oligosaccharide-type binders, e.g. certain dextrins, are often well suited.
Examples of binders of the polysaccharide derivative type include starch derivatives (some types of which have already been mentioned above in connection with modified starches), such as starch esters (e.g. starch acetate), starch ethers (such as carboxymethyl-starch or hydroxyalkyl-starches, e.g. hydroxymethyl-, hydroxyethyl- or hydroxypropyl-starch) and cellulose derivatives, such as methylhydroxypropyl-cellulose, hydroxypropyl-cellulose, methyl-cellulose, carboxymethyl-cellulose (CMC) as well as CMC sodium salt.
Further examples of relevant binders include polyacrylates, polymethacrylates, acrylic acid/maleic acid copolymers and vinyl-group-containing compounds, such as polyvinyl alcohol, hydrolysed polyvinyl acetate and polyvinylpyrrolidone.
Fillers: Fillers appropriate for incorporation in cores in the context of the present invention include inert materials used to add bulk and reduce cost, or used for the purpose of adjusting the intended enzyme activity in the finished granulate. Examples of such fillers include, but are not limited to, water-soluble substances such as urea, various salts (such as sodium chloride, ammonium sulphate or sodium sulphate) and sugars, and water-dispersible agents such as clays, talc, silicates or starches.
Plasticizers: In certain types of cores of relevance in the context of the invention, plasticizer(s) may suitably be present in amounts constituting up to about 10% of the total weight of the core. Plasticizers serve generally to reduce brittleness and/or enhance deformability, and will typically be low molecular weight organic compounds of low volatility [such as polyols (e.g. glycols such as ethylene glycol), urea and phthalate esters (such as dibutyl or dimethyl phthalate)]. Water may in some cases serve as a plasticizer.
Fibrous materials: When incorporated in cores in the context of the invention, fibrous material(s) will suitably be present in amounts constituting up to about 30% of the total weight of the core, preferably between 5 and 15%. Suitable fibrous materials include materials which have high tensile strength and are in the form of fine filaments having a diameter of 1-50 xcexcm and a length equal to at least four diameters. Typical fibrous materials include, but are not limited to: cellulose fibres, glass fibres, metal fibres, rubber fibres, azion fibres (manufactured from naturally occurring proteins from corn, peanuts and milk) and synthetic polymer fibres (such as fibres of Rayon(trademark), Nylon(trademark), polyester, polyolefin, Saran(trademark), Spandex(trademark) and vinal(trademark). Cellulose fibres are very suitable fibres in this connection, and will often suitably have an average fibre length in the range of 150-300 xcexcm and a diameter in the range of about 20-40 xcexcm.
Superabsorbents: Certain types ofxe2x80x94in particularxe2x80x94macro-molecular substances possess the ability to absorb many times their own weight of water or certain aqueous media. Substances of this type [which include various types of synthetic polymers as well as substances derived from polymers of natural origin, and which have found applications, for example, as body fluid absorbents (e.g. in wound dressings, diapers, sanitary towels and the like)] are sometimes referred to as xe2x80x9csuperabsorbentsxe2x80x9d, and such substances may be present as a component of cores which form the basis for enzyme-containing granules of the invention.
One group of interesting superabsorbent materials, described in WO 96/03440, comprises readily biodegradable substances derivedxe2x80x94via an enzymatic processxe2x80x94from certain naturally occurring phenolic polysaccharides, such as phenolic pectins, and such substances are well suited as water-absorbent components in cores of relevance in the context of the invention.
At this point it is appropriate to mention another class of absorbent cores which are well suited as the basis for enzyme-containing granules of the invention, namely xe2x80x9cplaceboxe2x80x9d (enzyme-free) cores prepared in accordance with the general methodology of U.S. Pat. No. 4,106,991 but without the inclusion of an enzyme. U.S. Pat. No. 4,106,991 describes the production of so-called xe2x80x9cT-granulatesxe2x80x9d comprisingxe2x80x94in addition to enzymexe2x80x942-40% w/w of fibrous cellulose, together with binder (e.g. one of those mentioned above in the context of binders for cores or relevance in the context of the invention), filler (typically a salt such as sodium sulphate or sodium chloride, optionally together with a minor proportion of a whitener such as titanium dioxide or kaolin) and a liquid-phase granulating agent (water and/or a waxy substance such as a polyglycol, fatty alcohol, ethoxylated fatty alcohol or the like). By preparing granulates in accordance with U.S. Pat. No. 4,106,991 (which employs drum granulation of a mixture of enzyme, fibrous cellulose, binder, filler, and liquid-phase granulating agent), but without incorporation of enzyme, absorbent cores which are well suited as cores in the context of the present invention may be prepared. Cores of this type, which may appropriately be termed xe2x80x9cplacebo Txe2x80x9d cores, may also be prepared using xe2x80x9cfillerxe2x80x9d materials other than salts (such as powdered starch, e.g. powdered rice starch).
As already indicated to some extent above, it is preferable that core particles forming the basis of enzyme-containing granules of the invention have relatively high physical strength. In the context of the invention the strength of a substantially spherical core particle may suitably be determined as the ratio between the force required to initiate crushing of the particle under the test conditions as specified below (vide infra), and the square of the core diameter (i.e. regarding the particle as being substantially spherical).
It is preferable that the mean value of this ratio, determined for a representative number of cores (suitably xe2x89xa720 cores) taken at random from a bulk quantity of cores, is greater than 400 g/mm2, more preferably greater than 600 g/mm2, such as greater than 800 g/mm2. It is especially desirable that the ratio in question is greater than 1000 g/mm2, more preferably greater than 1200 g/mm2, in particular greater than 1400 g/mm2, and most preferably greater than 1600 g/mm2.
The principle of a crushing test suitable for measuring the strength of a core particle (or a finished enzyme-containing granule) in the context of the present invention is illustrated in FIG. 1 herein (vide infra). The test is performed as follows:
1) A particle of core material is placed between an aluminium plate and a Plexiglas(trademark) [transparent poly(methyl methacrylate)-type polymer] plate (each plate measuring 218 mmxc3x9740 mm, thickness 3.2 mm) as shown in FIG. 1; the Plexiglas(trademark) plate is strengthened by two aluminium U-profiles attached to the edges of the plate [as indicated in the xe2x80x9cfront viewxe2x80x9d (end view) at the bottom of FIG. 1] and extending along the full length of the plate;
2) increasing loads (circular/cylindrical weights) are placed successively on the end of the Plexiglas(trademark) plate, closest to the core, as shown in FIG. 1, such that the center of mass of the weight is positioned in the middle of the width of the plate, and 20 mm from the end thereof; at the same time, the particle is observed through the transparent plate by means of a microscope;
3) the loading (in grams) at which crushing of the particle begins (as assessed visually) is measured, and is divided by the square of the diameter of the core particle (in mm2) to obtain the strength of the core particle.
Alternatively, the physical strength of particles of core material (or of granules according to the invention) can be measured according to either the Heubach method or the Novo Nordisk attrition method, both of which give a measure of the dust-formation tendency of particles; protocols for the latter two methods (EAL-SM-0289.01/01 and AF 225/2-GB, respectively) are obtainable on request from Novo Nordisk A/S, Bagsvaerd, Denmark. In both of the latter methods a bed of particles is subjected to the action of rolling steel balls, with simultaneous suction of air through the bed to collect dust and fragments created during the process.
For numerous applications of enzyme-containing granules of the invention, the mean particle size of the granules (and in many cases, correspondingly, of the core particles therein) will suitably be in the range from 50 to 4000 xcexcm, such as 200-2000 xcexcm (e.g. in the range of 200-1000 xcexcm). The optimal mean core particle size will generally depend on the intended use of the final enzyme-containing granulate.
Embodiments of enzyme-containing granulates of the invention are well suited for use, for example, in detergents, in animal feed compositions, in baking and in the treatment of textiles. By way of example, for detergent applications the preferred mean granule particle size (and, in many cases, the corresponding mean core particle size) will often be in the range of 250-2000 xcexcm (such as 300-2000 xcexcm), whereas for baking applications the preferred mean core particle size will often be in the range of 50-200 xcexcm. Granules (and, correspondingly, often cores) of a size greater than 4000 xcexcm, such as particles of size of the order of 10000 xcexcm, may be appropriate for certain applications (e.g. in the treatment of textiles).
The overall particle size distribution is preferably relatively narrow, e.g. such that for at least 90%, more preferably 95%, of the particles in a given sample the ratio between the largest and the smallest particle size is less than 4:1, preferably less than 3:1, more preferably less than 2:1, and most preferably less than 1.5:1.
Granular core particles suitable as the basis for enzyme-containing granules in accordance with the present invention may be prepared, e.g., by conventional granulation methods such as tumbling, rolling, pelletization, extrudation/-spheroidization, and/or mechanical agitation of the starting material, e.g. starting material comprising starch or a silicate/siliceous material. Examples of suitable absorbent cores (xe2x80x9cplacebo Txe2x80x9d cores) which may be prepared by drum granulation (in the manner disclosed in U.S. Pat. No. 4,106,991) are described above (see also Examples 8 and 13 herein).
Coating layers
The granules of the present invention may comprise one, two or more coating layers. Such coating layers may, for example, be one or more intermediate coating layers, or one or more outside coating layers, or a combination thereof.
Coating layers may perform any of a number of functions in a granule composition, depending on the intended use of the enzyme granule. Thus, for example, a coating may achieve one or more of the following effects:
(i) further reduction of the dust-formation tendency of an uncoated granule according to the invention;
(ii) protection of enzyme(s) in the granule against oxidation by bleaching substances/systems (e.g. perborates, percarbonates, organic peracids and the like);
(iii) dissolution at a desired rate upon introduction of the granule into a liquid medium (such as an aqueous medium);
(iv) provision of a barrier against ambient moisture in order to enhance the storage stability of the enzyme and reduce the possibility of microbial growth within the granule.
In appropriate embodiments of granules according to the present invention, the coating layer may be composed as described in U.S. Pat. No. 4,106,991 [e.g. with a waxy material such as polyethylene glycol (PEG), optionally followed by powdering with a whitener such as titanium dioxide].
A given coating layer may contribute from 0.5% to as much as 50% by weight of the finished granule.
Coating layers in/on granules of the present invention may further comprise one or more of the following: anti-oxidants, chlorine scavengers, plasticizers, pigments, lubricants (such as surfactants or antistatic agents) and additional enzymes.
Plasticizers useful in coating layers in the context of the present invention include, for example: polyols such as sugars, sugar alcohols, or polyethylene glycols (PEGs) having a molecular weight less than 1000; urea, phthalate esters such as dibutyl or dimethyl phthalate; and water.
Suitable pigments include, but are not limited to, finely divided whiteners, such as titanium dioxide or kaolin, coloured pigments, water soluble colorants, as well as combinations of one or more pigments and water soluble colorants.
As used in the present context, the term xe2x80x9clubricantxe2x80x9d refers to any agent which reduces surface friction, lubricates the surface of the granule, decreases tendency to build-up of static electricity, and/or reduces friability of the granules. Lubricants can also play a related role in improving the coating process, by reducing the tackiness of binders in the coating. Thus, lubricants can serve as anti-agglomeration agents and wetting agents.
Examples of suitable lubricants are polyethylene glycols (PEGs) and ethoxylated fatty alcohols.
As already mentioned, the present invention also relates to a process for producing enzyme-containing granules from absorbent cores, the process comprising:
(a) contacting absorbent cores, capable of absorbing at least 5% w/w (based on the weight of the core) of water, with a liquid medium containing an enzyme in dissolved and/or dispersed form, the amount of the liquid medium employed being such that substantially no attendant agglomeration of the resulting product occurs; and
(b) at least partially removing volatile components of the liquid medium from the resulting product.
Preferred characteristics of cores suitable for use in the process of the invention are those already discussed above in connection with enzyme-containing granules of the invention.
In the process of the invention, the contacting of the absorbent cores with a liquid medium (such as an aqueous medium) comprising dissolved and/or dispersed enzyme is suitably carried out, for example, by spraying the cores with the solution/dispersion under mixing conditions, or by applying (e.g. by spraying) the enzyme solution/dispersion to cores which are fluidized (e.g. in a fluid-bed apparatus), or by a combination of both techniques.
Contacting of cores with enzyme via a mixing technique is generally well suited in the context of the invention, since it facilitatesxe2x80x94when appropriatexe2x80x94addition, in step (a) of the process of the invention, of the enzyme-containing solution or dispersion to the cores in an amount, and for a period of time, which is sufficient to wholly (or partly) exploit the absorption capacity of the cores, but which does not leave any significant amount of free liquid phase (i.e. enzyme-containing solution or dispersion) on or between the resulting individual particles, i.e. such that there is insufficient free (unabsorbed) liquid phase to cause agglomeration of the particles to occur. If surplus (unabsorbed) liquid phase is present there is a risk of agglomeration occurring, with attendant unwanted formation of lumps in the bulk granulate.
Conventional mixing equipment can satisfactorily be used to mix the cores with the enzyme-containing liquid medium. The mixing equipment can be a batch mixer or a continuous mixer, such as a convective mixer [see, e.g., Hamby et al., Mixing in the Process Industries, pp. 39-53 (ISBN 0-408-11574-2)]. Non-convective mixing equipment, e.g. rotating drum mixers or so-called pan-granulators, may also be employed.
As already indicated, conditions whereby the cores are fluidized (such as in a fluid-bed apparatus or other form of fluidizing equipment, such as a Huttlin-type fluidizer) may also be employed when contacting the cores and the enzyme-containing liquid medium. For a description of suitable fluid-bed equipment, see, e.g., Hamby et al., Mixing in the Process Industries, pp. 54-77 (ISBN 0-408-11574-2).
In general, it is advantageous that the enzyme-containing liquid medium employed in the process of the invention contains dissolved enzyme. This will normally be the case when working with aqueous media. It is further desirable that the process is carried out under conditions such that absorption of the liquid phase (which will often contain dissolved enzyme) of the liquid medium by the cores takes place to some extent in step (a) of the process, often preferably to an extent such that essentially complete absorption of the liquid phase by the cores takes place before taking any measures to remove volatile components of the liquid medium from the resulting product.
In this connection, the process of the invention may thus be performed, for example, under conditions whereby essentially no removal, or at least very little removal, of volatile components takes place during the contacting phase. When using a mixer set-up in the contacting step, this may generally be achieved by simply ensuring that temperature in the mixer is not too high (e.g. such that the temperature is ambient temperature or below); when using fluidized conditions in the contacting step, this condition may generally be met by employing fluidizing air of sufficiently low temperature (e.g. a temperature below 30xc2x0 C., such as ambient temperature or below).
Volatile components may subsequently be removed, for example, in a mixer, under mixing conditions (e.g. by applying heat and/or reduced pressure) or under fluidized conditions, e.g. in a fluid-bed apparatus (for example by the application of suitably hot fluidizing air). The temperatures employed should, of course, be such that no significant loss of enzyme activity of the product granules occurs.
Alternatively, some degree of evaporation of volatile components may be allowed to take place simultaneously with the performance of the contacting step. Thus, for example, when employing a mixer set-up in the contacting step, the mixer may be heated to a moderately elevated temperature in order to cause some evaporation of volatiles during the contacting stage; when employing fluidized conditions in the contacting step, the fluidizing air itself may be heated to a moderately elevated temperature. As before, the temperatures employed should, of course, be such that no significant loss of enzyme activity of the product granules occurs.
When drying product granules, they may suitably be retained in the process apparatus for a period of time sufficient to reduce the moisture content (in the case of products prepared using an aqueous, enzyme-containing medium) to a level below 10% w/w free moisture, preferably below 5% w/w free moisture.
As already discussed (vide supra), cores employed in the context of the invention are intrinsically able to absorb suitable amounts of water (and thereby of aqueous media), and consequently there is no need to include a surfactant in the enzyme-containing liquid medium in order for the cores to be able to absorb a sufficient amount of a hydrophilic polypeptide such as an enzyme.
This is particularly advantageous with respect to the production of enzyme-containing granulates for use in industries such as the baking industry or the animal feed industry, where the presence of surfactant in the granules is generally undesirable.
Nevertheless, in certain situations, such as when a product of higher enzymatic activity than usual is required (e.g. for use in the detergent industry), it may be advantageous, at least for certain types of absorbent core, to include an appropriate amount of surfactant in the enzyme-containing liquid medium for the purpose of enhancing and/or accelerating absorption of enzyme by the core. Surfactants suitable for this purpose include numerous types of cationic, anionic, non-ionic or zwitterionic surfactants, and suitable examples hereof are mentioned below, in connection with the discussion of detergent compositions (vide infra).
In order to promote formation of a dense, compact (smooth/regular) granule surface after contacting the cores with the enzyme-containing liquid phase, the presence in the mixer of a rapidly rotating granulating device (xe2x80x9cchoppersxe2x80x9d) is preferable. Reference may be made to U.S. Pat. No. 4,106,991 for further details.
Another way in which to promote the formation of a dense, compact (smooth/regular) surface after contacting the cores with the liquid medium is to treat the moist granulate in a Marumerizer(trademark). Reference may be made to U.S. Pat. No. 4,106,991 for further details.
When an aqueous, enzyme-containing solution/dispersion is employed in accordance with the invention, the solution (i.e. the liquid phase of the aqueous medium) will normally preferably have a dry matter content of from 2% w/w to 50% w/w [dry matter consisting of enzyme protein(s), possibly together with other organic and inorganic materials]. When dispersed enzyme is present, the solution/dispersion will suitably have a dry matter content of from 10% w/w to 70% w/w [including dry matter originating from both dissolved and dispersed (undissolved) material].
The term xe2x80x9cdispersionxe2x80x9d as used in this connection designates a system containing solid particles, at least some of which comprise or consist of enzyme, of a size from the colloidal size range and upwards, and which are suspended, slurried or otherwise distributed in a liquid phase (such as an aqueous phase). The term xe2x80x9cdispersionxe2x80x9d in the context of the invention thus embraces, inter alla, suspensions and slurries.
In a preferred aspect of the process of the invention, dispersed enzyme present in the liquid medium employed in step (a) comprises enzyme in crystalline form.
In the process of the invention it is preferable that the enzyme-containing liquid medium (solution or solution/-dispersion) is added to the particulate cores in a weight ratio (liquid medium:cores) of at least 0.05:1, more preferably at least 0.1:1, such as at least 0.15:1, for example at least 0.2:1, and often at least 0.5:1. The ratio employed will, in general, depend on the absorption capacity of the cores, and on the required strength of the final enzyme-containing granules.
One, two or more coating layers may be applied to the dried or partly dried, enzyme-containing granules by conventional methods, such as by pan-coating, mixer-coating, and/or fluid-bed coating. Suitable coatings/coating components include those already discussed above in connection with enzyme-containing granules of the invention.
Enzymes
Any enzyme or combination of different enzymes may be employed in the context of the present invention. Accordingly, when reference is made to xe2x80x9can enzymexe2x80x9d this will in general be understood include combinations of one or more enzymes.
The enzyme classification employed in the present specification with claims is in accordance with Recommendations (1992) of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology, Academic Press, Inc., 1992.
It is to be understood that enzyme variants (produced, for example, by recombinant techniques) are included within the meaning of the term xe2x80x9cenzymexe2x80x9d. Examples of such enzyme variants are disclosed, e.g., in EP 251,446 (Genencor), WO 91/00345 (Novo Nordisk A/S), EP 525,610 (Solvay) and WO 94/02618 (Gist-Brocades NV).
Types of enzymes which may appropriately be incorporated in granules of the invention include:
hydrolases [EC 3; such as lipases (EC 188.8.131.52) and other carboxylic ester hydrolases (EC 3.1.1); phytases, e.g. 3-phytases (EC 188.8.131.52) and 6-phytases (EC 188.8.131.52); xcex1-amylases (EC 126.96.36.199) and other glycosidases (EC 3.2, which fall within a group denoted herein as xe2x80x9ccarbohydrasesxe2x80x9d); peptidases (EC 3.4, also known as proteases); and other carbonyl hydrolases];
oxidoreductases [EC 1; such as peroxidases (EC 1.11.1), laccases (EC 184.108.40.206) and glucose oxidases (EC 188.8.131.52)];
transferases (EC 2); isomerases (EC 5); and ligases (EC 6).
Examples of commercially available proteases (peptidases) include Esperase(trademark), Alcalase(trademark), Neutrase(trademark), Durazym(trademark), Savinase(trademark), Pyrase(trademark), Pancreatic Trypsin NOVO (PTN), Bio-Feed(trademark) Pro and Clear-Lens(trademark) Pro (all available from Novo Nordisk A/S, Bagsvaerd, Denmark).
Other commercially available proteases include Maxatase(trademark), Maxacal(trademark), Maxapem(trademark), Opticlean(trademark) and Purafect(trademark) (available from Genencor International Inc. or Gist-Brocades).
Examples of commercially available lipases include Lipolase(trademark), Lipolase(trademark) Ultra, Lipozyme(trademark), Palatase(trademark), Novozym(trademark) 435 and Lecitase(trademark) (all available from Novo Nordisk A/S).
Other commercially available lipases include Lumafast(trademark) (Pseudomonas mendocina lipase from Genencor International Inc.); Lipomax(trademark) (Ps. pseudoalcaligenes lipase from Gist-Brocades/Genencor Int. Inc.; and Bacillus sp. lipase from Solvay enzymes. Further lipases are available from other suppliers.
In the present context, the term xe2x80x9ccarbohydrasexe2x80x9d is used to denote not only enzymes capable of breaking down carbohydrate chains (e.g. starches) of especially five- and six-membered ring structures (i.e. glycosidases, EC 3.2), but also enzymes capable of isomerizing carbohydrates, e.g. six-membered ring structures such as D-glucose to five-membered ring structures such as D-fructose.
Carbohydrases of relevance include the following (EC numbers in parentheses): xcex1-amylases (184.108.40.206), xcex2-amylases (188.8.131.52), glucan 1,4-xcex1-glucosidases (188.8.131.52), cellulases (126.96.36.199), endo-1,3(4)-xcex2-glucanases (22.214.171.124), endo-1,4-xcex2-xylanases (18.104.22.168), dextranases (184.108.40.206), chitinases (184.108.40.206), polygalacturonases (188.8.131.52), lysozymes (126.96.36.199), xcex2-glucosidases (22.214.171.124), xcex1-galactosidases (22.214.171.124), xcex2-galactosidases (18.104.22.168), amylo-1,6-glucosidases (126.96.36.199), xylan 1,4-xcex2-xylosidases (126.96.36.199), glucan endo-1,3-xcex2-D-glucosidases (22.214.171.124), xcex1-dextrin endo-1,6-xcex1-glucosidases (126.96.36.199), sucrose a-glucosidases (22.214.171.124), glucan endo-1,3-xcex1-glucosidases (126.96.36.199), glucan 1,4-xcex2-glucosidases (126.96.36.199), glucan endo-1,6-xcex2-glucosidases (188.8.131.52), arabinan endo-1,5-xcex1-L-arabinosidases (220.127.116.11), lactases (22.214.171.124), chitosanases (184.108.40.206) and xylose isomerases (188.8.131.52).
Examples of commercially available carbohydrases include Alpha-Gal(trademark), BioTFeed(trademark) Alpha, Bio-Feed(trademark) Beta, Bio-Feed(trademark) Plus, Bio-Feed(trademark) Plus, Novozyme(trademark) 188, Celluclast(trademark), Cellusoft(trademark), Ceremyl(trademark), Citrozym(trademark), Denimax(trademark), Dezyme(trademark), Dextrozyme(trademark), Finizym(trademark), Fungamyl(trademark), Gamanase(trademark), Glucanex(trademark), Lactozym(trademark), Maltogenase(trademark), Pentopan(trademark), Pectinex(trademark), Promozyme(trademark), Pulpzyme(trademark), Novamyl(trademark), Termamyl(trademark), AMG(trademark) (Amyloglucosidase Novo), Maltogenase(trademark), Sweetzyme(trademark) and Aquazym(trademark) (all available from Novo Nordisk A/S). Further carbohydrases are available from other suppliers.
Examples of commercially available oxidoreductases (EC 1) include Gluzyme(trademark) (enzyme available from Novo Nordisk A/S). Further oxidoreductases are available from other suppliers.
Suitable transferases (EC 2) in the context of the invention are transferases in any of the following sub-classes:
transferases transferring one-carbon groups (EC 2.1); transferases transferring aldehyde or ketone residues (EC 2.2); acyltransferases (EC 2.3); glycosyltransferases (EC 2.4); transferases transferring alkyl oraryl groups, other that methyl groups (EC 2.5); and transferases transferring nitrogeneous groups (EC 2.6).
A preferred type of transferase in the context of the invention is a transglutaminase (protein-glutamine xcex3-glutamyltransferase; EC 188.8.131.52).
Examples of transglutaminases are described in WO 96/06931 (Novo Nordisk A/S).
The amount of enzyme to be incorporated in a granule of the invention will depend on the intended use of the granulate. For many applications, the enzyme content will be as high as possible or practicable.
The content of enzyme (calculated as pure enzyme protein) in a granule of the invention will typically be in the range of from about 0.5% to 20% by weight of the enzyme-containing granule.
When, for example, a protease (peptidase) is incorporated in granules according to the invention, the enzyme activity (proteolytic activity) of the finished granules will typically be in the range of 1-20 KNPU/g. Likewise, in the case of, for example, a-amylases, an activity of 10-500 KNU/g will be typical, whilst for lipases, an activity in the range of 50-400 KLU/g will normally be suitable.
Other Adjunct Ingredients
Where appropriate, various additives (adjuncts) may be incorporated together with the enzyme in a granule of the invention. Relevant adjuncts agents may include: metal compounds (e.g. salts and/or complexes of transition metals), solubilizers, activators, anti-oxidants, dyes, inhibitors, binders, fragrances, enzyme-protecting agents/scavengers, such as ammonium sulphate, ammonium citrate, urea, guanidine hydrochloride, guanidine carbonate, guanidine sulphonate, thiourea dioxide, monoethanolamine, diethanolamine, triethanolamine, amino acids such as glycine, sodium glutamate and the like, proteins such as bovine serum albumin, casein, surfactants, including anionic surfactants, ampholytic surfactants, nonionic surfactants, cationic surfactants and long-chain fatty acid salts, builders, alkalis or inorganic electrolytes, bleaching agents, blueing agents and fluorescent dyes, and caking inhibitors. Reference may be made to WO 92/00384 for a description of appropriate surfactants.
Granules incorporating such adjuvants may be made by methods well known to those skilled in the art of enzyme granulation, including fluidized bed spray-coating, pan-coating and other techniques for building up a granule by adding consecutive layers on top of a starting core material.
In addition to the process, according to the invention, for the production of enzyme-containing granules as described above, the present invention further relates to enzyme-containing granules obtained by, or obtainable by, an embodiment of the process.
Applications of Enzyme-Containing Granules of the Invention
Granulates (enzyme-containing granules) according to the present invention can be used for a variety of industrial applications. Particulary interesting applications include their use in detergents, in animal feed compositions, in products for the baking industry and in textile-treatment products, and the following list indicates types of enzymes which are most typically of interest in each of these fields of application:
Detergents: proteases, amylases (e.g. xcex1-amylases), cellulases, lipases, oxidoreductases;
Baking products: amyloglucosidases (glucoamylases, glucan 1,4-xcex1-glucosidases), bacterial xcex1-amylases, fungal xcex1-amylases, maltogenic amylases, glucose oxidases, proteases, pentosanases;
Animal feed compositions: bacterial xcex1-amylases, proteases, xylanases; phytases;
Textile-treatment products: cellulases, xcex1-amylases.
In a further aspect, the invention thus relates to detergent compositions (especially laundry and dishwashing detergent compositions) comprising enzyme-containing granules according to, or produced in accordance with, the invention.
In yet another aspect, the invention encompasses animal feed compositions comprising enzyme-containing granules according to, or produced in accordance with, the invention.
A still further aspect relates to compositions for baking comprising enzyme-containing granules according to, or produced in accordance with, the invention.
Moreover, the invention also relates to the use of enzyme-containing granules according to, or produced in accordance with, the invention as an enzyme-containing component in:
a detergent composition, e.g. for laundry washing or dishwashing;
an animal feed composition;
a composition for baking; or
a composition for textile treatment (e.g. for colour clarification or for dyeing).
Detergent Compositions
According to the invention, the enzyme-containing granules of the invention may typically be a component of a detergent composition, e.g., a laundry detergent composition or a dishwashing detergent composition. As such, they may be included in the detergent composition in the form of an uncoated granulate or coated granulate coated by methods known in the art. Examples of waxy coating materials are poly(ethylene oxide) products (polyethyleneglycol, PEG) with mean molecular weights of 1000 to 20000; ethoxylated nonylphenols having from 16 to 50 ethylene oxide units; ethoxylated fatty alcohols in which the alcohol contains from 12 to 20 carbon atoms and in which there are 15 to 80 ethylene oxide units; fatty alcohols; fatty acids; and mono- and di- and triglycerides of fatty acids. Examples of film-forming coating materials suitable for application by fluid bed techniques are given in patent GB 1483591.
The detergent composition of the invention may be in any convenient form, e.g. as powder, granules or paste.
The detergent composition comprises one or more surfactants, each of which may be anionic, nonionic, cationic, oramphoteric (zwitterionic). The detergent will usually contain 0-50% of anionic surfactant such as linear alkylbenzenesulfonate (LAS), alpha-olefinsulfonate (AOS), alkyl sulfate (fatty alcohol sulfate) (AS), alcohol ethoxysulfate (AEOS or AES), secondary alkanesulfonates (SAS), alpha-sulfo fatty acid methyl esters, alkyl- or alkenylsuccinic acid, or soap. It may also contain 0-40% of nonionic surfactant such as alcohol ethoxylate (AEO or AE), alcohol propoxylate, carboxylated alcohol ethoxylates, nonylphenol ethoxylate, alkylpolyglycoside, alkyldimethylamine oxide, ethoxylated fatty acid monoethanolamide, fatty acid monoethanolamide, or polyhydroxy alkyl fatty acid amide (e.g. as described in WO 92/06154).
In addition to the enzymes contained in the enzyme-containing granules of the invention, the detergent composition may additionally comprise one or more other enzymes, such as a pullulanase, esterase, lipase, cutinase, protease, cellulase, amylase, peroxidase or oxidase (e.g. a laccase).
Normally the detergent contains 1-65% of a detergent builder, but some dishwashing detergents may contain even up to 90% of a detergent builder, or complexing agent such as zeolite, diphosphate, triphosphate, phosphonate, citrate, nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTMPA), alkyl- or alkenylsuccinic acid, soluble silicates or layered silicates (e.g. SKS-6 from Hoechst).
The detergent builders may be subdivided into phosphorus-containing and non-phosphorous-containing types. Examples of phosphorus-containing inorganic alkaline detergent builders include the water-soluble salts, especially alkali metal pyrophosphates, orthophosphates, polyphosphates and phosphonates. Examples of non-phosphorus-containing inorganic builders include water-soluble alkali metal carbonates, borates and silicates as well as layered disilicates and the various types of water-insoluble crystalline or amorphous alumino silicates of which zeolites is the best known representative.
Examples of suitable organic builders include alkali metal, ammonium or substituted ammonium salts of succinates, malonates, fatty acid malonates, fatty acid sulphonates, carboxymethoxy succinates, polyacetates, carboxylates, polycarboxylates, aminopolycarboxylates and polyacetyl carboxylates.
The detergent may also be unbuilt, i.e. essentially free of detergent builder.
The detergent may comprise one or more polymers. Examples are carboxymethylcellulose (CMC), poly(vinylpyrrolidone) (PVP), polyethyleneglycol (PEG), poly(vinyl alcohol) (PVA), polycarboxylates such as polyacrylates, polymaleates, maleic/acrylic acid copolymers and lauryl methacrylate/acrylic acid copolymers.
The detergent composition may contain bleaching agents of the chlorine/bromine-type or the oxygen-type. The bleaching agents may be coated or incapsulated. Examples of inorganic chlorine/bromine-type bleaches are lithium, sodium or calcium hypochlorite or hypobromite as well as chlorinated trisodium phosphate. The bleaching system may also comprise a H2O2 source such as perborate or percarbonate which may be combined with a peracid-forming bleach activator such as tetraacetylethylenediamine (TAED) or nonanoyloxybenzenesulfonate (NOBS).
Examples of organic chlorine/bromine-type bleaches are heterocyclic N-bromo and N-chloro imides such as trichloroisocyanuric, tribromoisocyanuric, dibromoisocyanuric and dichloroisocyanuric acids, and salts thereof with water solubilizing cations such as potassium and sodium. Hydantoin compounds are also suitable. The bleaching system may also comprise peroxyacids of, e.g., the amide, imide, or sulfone type.
In dishwashing detergents the oxygen bleaches are preferred, for example in the form of an inorganic persalt, preferably with a bleach precursor or as a peroxy acid compound. Typical examples of suitable peroxy bleach compounds are alkali metal perborates, both tetrahydrates and monohydrates, alkali metal percarbonates, persilicates and perphosphates. Preferred activator materials are TAED or NOBS.
The enzymes of the detergent composition of the invention may be stabilized using conventional stabilizing agents, e.g. a polyol such as propylene glycol or glycerol, a sugar or sugar alcohol, lactic acid, boric acid, or a boric acid derivative such as, e.g., an aromatic borate ester, and the composition may be formulated as described in, e.g., WO 92/19709 and WO 92/19708. The enzymes of the invention may also be stabilized by adding reversible enzyme inhibitors, e.g., of the protein type as described in EP 0 544 777 B1.
The detergent may also contain other conventional detergent ingredients such as, e.g., fabric conditioners including clays, deflocculant material, foam boosters/foam depressors (in dishwashing detergents foam depressors), suds suppressors, anti-corrosion agents, soil-suspending agents, anti-soil-redeposition agents, dyes, dehydrating agents, bactericides, optical brighteners, or perfume.
The pH (measured in aqueous solution at use concentration) will usually be neutral or alkaline, e.g. in the range of 7-11.
Particular forms of laundry detergent compositions within the scope of the invention include:
1) A detergent composition formulated as a granulate having a bulk density of at least 600 g/l comprising
2) A detergent composition formulated as a granulate having a bulk density of at least 600 g/l comprising
3) A detergent composition formulated as a granulate having a bulk density of at least 600 g/l comprising
4) A detergent composition formulated as a granulate having a bulk density of at least 600 g/l comprising
5) A detergent composition formulated as a granulate having a bulk density of at least 600 g/l comprising
6) A detergent composition formulated as a granulate comprising
7) A detergent composition formulated as a granulate comprising
8) A detergent composition formulated as a granulate having a bulk density of at least 600 g/l comprising
9) Detergent formulations as described in 1)-8) wherein all or part of the linear alkylbenzenesulfonate is replaced by (C12-C18) alkyl sulfate.
10) A detergent composition formulated as a granulate having a bulk density of at least 600 g/l comprising
11) A detergent composition formulated as a granulate having a bulk density of at least 600 g/l comprising
12) Detergent formulations as described in 1)-11) which contain a stabilized or encapsulated peracid, either as an additional component or as a substitute for already specified bleach systems.
13) Detergent compositions as described in 1), 3), 5), 7) and 8) wherein perborate is replaced by percarbonate.
14) Detergent compositions as described in 1), 3), 5), 7), 8), 10) and 11) which additionally contain a manganese catalyst. The manganese catalyst may, e.g., be one of the compounds described in xe2x80x9cEfficient manganese catalysts for low-temperature bleachingxe2x80x9d, Nature 369, 1994, pp. 637-639.
Particular forms of dishwashing detergent compositions within the scope of the invention include:
1) Powder Automatic Dishwashing Composition
2) Powder Automatic Dishwashing Composition
3) Powder Automatic Dishwashing Composition
4) Powder Automatic Dishwashing Composition
5) Powder Automatic Dishwashing Composition
6) Automatic dishwashing compositions as described in 1), 2), 3) and 4), wherein perborate is replaced by percarbonate.
7) Automatic dishwashing compositions as described in 1)-4) which additionally contain a manganese catalyst. The manganese catalyst may, e.g., be one of the compounds described in xe2x80x9cEfficient manganese catalysts for low-temperature bleachingxe2x80x9d, Nature 369, 1994, pp.637-639.
All of the particular forms of washing and dishwashing detergent compositions listed above will, of course, additionally comprise minor amounts of granulate constituents (core material, coating constituents, etc.)
The enzyme-containing granules of the invention may be incorporated in concentrations corresponding to enzyme concentrations conventionally employed in detergents. It is at present contemplated that, in a detergent composition of the invention, the enzymes may be added in an amount corresponding to 0.00001-1 mg (calculated as pure enzyme protein) of enzyme per liter of wash/dishwash liquor.
Reference is made to WO 97/07202 (PCT/DK96/00341) for details concerning further types of detergent compositions relevant in the context of the present invention.
The present invention is further illustrated by the working examples described below, which are representative and are not intended to limit the scope of the invention in anyway. One skilled in the art will be capable of selecting other enzymes, cores, coating agents/adjuvants or methods on the basis of the teaching herein.
Enzyme Activity Assays
Proteolytic Activity (KNPU): In the present specification, proteolytic activity is expressed in Kilo Novo Protease Units (KNPU). The activity is determined relative to an enzyme standard, and the determination is based on the digestion of a dimethyl-casein (DMC) solution by the proteolytic enzyme under standard conditions (50xc2x0 C., pH 8.3, 9 min. reaction time, 3 min. measurement time). A brochure (AF 220/1) providing further details of the analytical method is available upon request from Novo Nordisk A/S, Bagsvaerd, Denmark.
Amylolytic activity (KNU) may be determined using potato starch as substrate. This method is based on the hydrolysis of modified potato starch by the enzyme, and the reaction is followed by mixing samples of the starch/enzyme solution with an iodine solution. Initially, a blackish-blue colour is formed, but during the breakdown of the starch the blue colour becomes weaker and gradually changes to a reddish-brown, which is compared to a coloured glass standard. One Kilo Novo alpha Amylase Unit (KNU) is defined as the amount of enzyme which, under standard conditions (37xc2x10.05xc2x0 C., 0.0003 M Ca2+, pH 5.6) dextrinizes 5.26 g starch dry substance Merck Amylum solubile.
A brochure (AF 9/6) describing this analytical method in more detail is available upon request from Novo Nordisk A/S, Denmark.
Lipolytic activity (LU) may be determined using tributyrin as substrate. This method is based on the hydrolysis of tributyrin catalyzed by the enzyme, and the consumption of alkali is measured as a function of time. One Lipase Unit (LU) is defined as the amount of enzyme which, under standard conditions (30.0xc2x0 C., pH 7.0; Gum Arabic as emulsifier and tributyrin as substrate) liberates 1 mmol of titratable butyric acid per minute. A brochure (AF 95/5) describing this analytical method in more detail is available upon request from Novo Nordisk A/S, Denmark.
Phytase activity (FYT) may be determined using Novo Nordisk analytical method KAL-SM-0403.01/01 (available upon request from Novo Nordisk A/S, Denmark).
Cores
Cassava starch cores: If nothing else is stated, cassava starch cores employed were obtained from Agro Comercial, Brazil.
Nonpareil cores (sugar-starch based): obtained from Crompton and Knowles, USA (xe2x80x9cSugar Spheres NF Mesh 35-40xe2x80x9d) or from NP Pharma.
Enzymes
Savinase(trademark) concentrate (water-based protease concentrate) was obtained from Novo Nordisk A/S, Denmark.
Phytase concentrate was obtained from Novo Nordisk A/S, Denmark.
Lipase (lipase variant HL9) was obtained as described in Example 3 of WO 97/07202.
Heubach method and Novo Nordisk attrition method
As already mentioned (vide supra), both the Heubach method and the Novo Nordisk attrition method are methods wherein a bed of granules is exposed to the action of rolling steel balls with simultaneous suction of air through the bed to collect dust and fragments created during the process. Brochures (EAL-SM-0289.01/01 and AF 225/2-GB, respectively) describing these methods in more detail are available upon request from Novo Nordisk A/S, Denmark.

Enzyme-containing granules and process for the production thereof


Some embodiments include a communication hub for presenting audio-visual data from electronic devices. Other embodiments of related systems and methods are disclosed.

When presenting audio-visual data via one or more audio-visual devices during a conference, it can be cumbersome and/or inconvenient for the participants of the conference to individually couple each electronic device of the multiple electronic devices to the one or more audio-visual devices in order to present the audio-visual data stored on the multiple electronic devices to the various participants of the conference. Accordingly, a need or potential for benefit exists for an apparatus or system that facilitates communication between the multiple electronic devices and the one or more audio-visual devices.
For simplicity and clarity of illustration, the drawing figures illustrate the general manner of construction, and descriptions and details of well-known features and techniques can be omitted to avoid unnecessarily obscuring the invention. Additionally, elements in the drawing figures are not necessarily drawn to scale. For example, the dimensions of some of the elements in the figures can be exaggerated relative to other elements to help improve understanding of embodiments of the present invention. The same reference numerals in different figures denote the same elements.
The terms "first," "second," "third," "fourth," and the like in the description and in the claims, if any, are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments described herein are, for example, capable of operation in sequences other than those illustrated or otherwise described herein. Furthermore, the terms "include," and "have," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, device, or apparatus that comprises a list of elements is not necessarily limited to those elements, but can include other elements not expressly listed or inherent to such process, method, system, article, device, or apparatus.
The terms "left," "right," "front," "back," "top," "bottom," "over," "under," and the like in the description and in the claims, if any, are used for descriptive purposes and not necessarily for describing permanent relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments of the invention described herein are, for example, capable of operation in other orientations than those illustrated or otherwise described herein.
The terms "couple," "coupled," "couples," "coupling," and the like should be broadly understood and refer to connecting two or more elements or signals, electrically, mechanically and/or otherwise. Two or more electrical elements can be electrically coupled together, but not be mechanically or otherwise coupled together; two or more mechanical elements can be mechanically coupled together, but not be electrically or otherwise coupled together; two or more electrical elements can be mechanically coupled together, but not be electrically or otherwise coupled together. Coupling can be for any length of time, e.g., permanent or semi-permanent or only for an instant.
"Electrical coupling" and the like should be broadly understood and include coupling involving any electrical signal, whether a power signal, a data signal, and/or other types or combinations of electrical signals. "Mechanical coupling" and the like should be broadly understood and include mechanical coupling of all types.
The absence of the word "removably," "removable," and the like near the word "coupled," and the like does not mean that the coupling, etc. in question is or is not removable.
The term "mobile electronic device" as used herein refers to at least one of a digital music player, a digital video player, a digital music and video player, a cellular phone (e.g., smartphone), a personal digital assistant, a handheld digital computer (e.g., a tablet personal computer), a laptop computer (e.g., a notebook computer, a netbook computer), or another portable device with the capability to present audio and/or visual data (e.g., images, videos, music, etc.). For example, a mobile electrical device can comprise the iPod® or iPhone® or iTouch® or iPad® or MacBook® product by Apple Inc. of Cupertino, Calif. Likewise, a mobile electrical device can comprise a Blackberry® product by Research in Motion (RIM) of Waterloo, Ontario, Canada, or a different product by a different manufacturer.
The term "computer network" as used herein can refer to a collection of computers and devices interconnected by communications channels that facilitate communications among users and allows users to share resources (e.g., an internet connection, an Ethernet connection, etc.). The computers and devices can be interconnected and/or implemented according to any one or any combination of wired and/or wireless network topologies (e.g., bus, star, tree, line, ring, mesh, daisy chain, hybrid, etc.) and/or protocols (e.g., personal area network (PAN) protocol(s), local area network (LAN) protocol(s), wide area network (WAN) protocol(s), cellular network protocol(s), Powerline network protocol(s), etc.), as desirable. Exemplary PAN protocol(s) can comprise Bluetooth, Zigbee, Wireless Universal Serial Bus (USB), Z-Wave, etc.; exemplary LAN and/or WAN protocol(s) can comprise Institute of Electrical and Electronic Engineers (IEEE) 802.3, IEEE 802.11, etc.; and exemplary cellular network protocol(s) can comprise Global System for Mobile Communications (GSM), General Packet Radio Service (GPRS), Code Division Multiple Access (CDMA), Evolution-Data Optimized (EV-DO), Enhanced Data Rates for GSM Evolution (EDGE), 3GSM, Digital Enhanced Cordless Telecommunications (DECT), Digital AMPS (IS-136/Time Division Multiple Access (TDMA)), Integrated Digital Enhanced Network (iDEN), etc. The components implementing the wired and/or wireless communication can be dependent on the network topologies and/or protocols in use, and vice versa.

Communication hub for presenting audio-visual data from electronic devices and method of providing and using the same


A rotary transformer includes a rotor core formed by stacking channel parts to form a required number of channels. Each channel part is formed by stacking two kinds of annular magnetic rings so that two rings having the same outside and inside diameters are placed at both sides of a ring having the same inside diameter as the two rings but a greater outside diameter than the two rings. A stator core is also formed by stacking channel parts to form the required number of channels. The channel part is formed by stacking two kinds of annular magnetic rings so that two rings having the same outside and inside diameters are placed on both sides of a ring having the same inside diameter with the two rings but smaller outside diameter than the two rings. A thin layer of glass can be used to bond the rings of the stator or rotor together.

This invention relates to a rotary transformer, and more particularly to a rotary transformer which can solve the problems associated with rotary transformers having channel grooves machined therein, which typically experience a high percentage of defective parts and low dimensional precision.
As shown in FIG. 1, a rotary transformer used for transmitting signals received from heads to a stator side circuit in an apparatus having rotating type magnetic heads, such as a VCR, camcorder, or digital audio tape recorder, includes a stator side core and a rotor side core, each of which cores has channel grooves 3 corresponding to the number of channels and short ring grooves 4 each for inserting a short ring.
The rotor 2 and the stator maintain a very small aperture on the order of a few tens of .mu.m between them, and the rotor 2 reads signals from the heads while being rotated, and transmits the signals to the stator 1.
Therefore, the dimensions of the rotor 2 and the stator 1 should be very precise, otherwise picture quality can be degraded due to noise caused in the course of the signal transmission and due to fluctuation in inductance.
A method for forming the rotary transformer having the foregoing structure is as follows.
First, inside and outside diameters of the cylindrical ferrite powder sintered bodies shown in FIGS. 2a and 2b are formed with a powder molding method so as to have about 1 mm machining allowance taking into account of many steps of machining.
Outside surfaces of the formed cylindrical sintered bodies are primarily ground with a centerless grinder, and the inside surfaces are rough ground with an internal grinder taking the ground outside surfaces as reference surfaces. The outside and inside surfaces are finally ground with a special purpose grinder.
By machining the channel grooves 3 and the short ring grooves 4 in the inside and outside surfaces of the machined cylindrical ferrite sintered bodies according to a number of required channels, the cores shown in FIGS. 3a and 3b are completed.
However, since the rotary transformer having the foregoing structure is formed by machining the channel grooves and short ring grooves after grinding surfaces of the cylindrical ferrite sintered bodies, it has problems in that it has a high percentage of defective and low preciseness of the dimension of the channel grooves due to the machining.
Further the rotary transformer has problems in that the productivity has been low since the core has been machined one by one in each machining, and the machining has been difficult in case diameter of the core is very small in the order of a few millimeters.

Rotary transformer and method for fabricating the same


In a towed array breakout of the type deployed from or retrieved by naval ssels a junction is defined between a fixed portion of an electrically conductive wire and a movable portion of the wire portion. A relatively hard potting material is provided around and defines the fixed portion of the wire. A coiled helically shaped portion of the same wire or a second wire is integrally joined to the first portion and defines the movable portion. This movable second portion is encased in a relatively soft urethane material so as to provide freedom in both a bending and tension mode. A third portion of the wire is connected to the opposite end of the coiled second portion. This structure affords strain relief at the junction between the fixed portion of the flexible conductor and the movable second portion.

(1) Field of the Invention
The present invention relates to providing strain relief at the end of a potted wire, and deals more particularly with providing flexibility for the wire immediately adjacent to a potted length of fixed wire in an assembly that provides for flexing and bending of a movable portion of the same wire immediately adjacent to the potted portion.
(2) Description of the Prior Art
Elastomers such as polyurethanes are frequently used in potting applications because of their ease of casting and molding to particular shapes, and because of their ability to resist environmental containments such as water and oils. More specifically, in shipboard applications, such urethanes are frequently used to pot and to waterproof electrical connections. In spite of the use of soft urethane sleeves on flexible electrical conductor wires, failure often occurs at the junction site between the flexible portion of the wire and the hard junction formed by the relatively hard potting material used to secure the fixed portion of the wire. The potting compound comprises a hard urethane or epoxy and is generally contained in a metal barrel that protects other electronic components. The prior art approach to protecting the wire protruding from the barrel at this junction site is to provide a soft urethane sleeve around the wire portion adjacent to the hard potted fixed wire portion.
The above described prior art approach to protecting the junction between a flexible wire and a potted portion such as would be connected to an electrical component in a towed sonobuoy array has been used in towed arrays by U.S. Naval vessels. Such assemblies generally include a towed array having hinged places where the array is designed to fold consisting of wires and electronics potted in both a high durometer stiff urethane or epoxy inside a metal barrel, and a low durometer soft urethane outside of this barrel. During handling such subassemblies are subjected to bending at severe angles, repeated flexing, and abrupt changes in tensile loads. Such severe handling of these subassemblies takes it's toll on the wires where the wires emerge from the relatively hard or stiff potting material. Although the soft polyurethane material generally provided in this area has been thought to alleviate such bending there is little strain relief afforded to the flexible wire at the juncture between it and the relatively hard or stiff potting material. After what can sometimes be a relatively short period of time in service, mechanical fatigue and consequent electrical failure of this flexible wire can occur. This phenomena has been experimentally duplicated in the laboratory and these tests correlate well with actual test results at sea.
Morais, U.S. Pat. No. 4,992,629 discloses a cable shock absorbing apparatus in which a coil spring is mounted in a housing. The cable extends through the housing and has a loop portion within the housing that cooperates with the spring. When the cable is tensioned the housing sections telescope outwardly stretching the spring. Removing the tension relaxes the spring to telescope the housing sections inwardly.

Strain relief for flexible wire at fixed junction

The United States of America as represented by the Secretary of the Navy


A non-invasive system and procedure for deriving the blood gas content for a patient. The system measures the volume and carbon dioxide concentration of the expiratory breath and discerns breath volumetric rate and gas content. This data is then processed to derive arterial blood gas levels of carbon dioxide. The processing shifts from the time to the volume domain and iteratively assesses the significance of numerous variables. The resulting relationship provides a fast and accurate measure of blood gas content for both healthy and diseased lung patients.

Brief Description of the Prior Art
Physicians and other health care providers often use elevated arterial pCO.sub.2 (PaCO.sub.2) as an indicator of incipient respiratory failure. In this regard, the determination of PaCO.sub.2 is useful in optimizing the settings on ventilators and detecting life-threatening changes in an anesthetized patient undergoing surgery. The traditional method for obtaining arterial blood gas values is to extract a sample of arterial blood and measure the partial pressure of carbon dioxide using a blood gas analyzer (PaCO.sub.2 ABG). Arterial puncture has inherent limitations: 1) arterial puncture carries a degree of patient discomfort and risk, 2) handling of the blood is a potential health hazard to health care providers, 3) significant delays are often encountered before results are obtained and, 4) measurements can only be made intermittently.
Continuous invasive monitoring requires in-dwelling arterial lines which entail inherent problems. These include sepsis, slow response times, and signal decay. The nature of this monitoring system excludes its use under routine care and is generally restricted to intensive care units within a hospital facility.
There have been attempts to assess PaCO.sub.2 levels indirectly, including a technique known as Capnography. The approach utilized in Capnography involves tracking patient exhale and measuring expiratory gas CO.sub.2 concentration against time during one or more respiratory cycles. The resulting relationship is plotted to create a graph depicting three distinct phases in breath CO.sub.2 gas concentration during the patient exhale cycle. (See, FIG. 1.) Typically, the three phases reflect the clearing of the conducting airways which do not normally participate in gas exchange (i.e., dead space) (phase I) followed by the exhalation of air from conducting airways dynamically mixed with lung gases from the active (alveoli) membrane surfaces within the lung that have undergone gas exchange with arterial blood (Phase II). The final phase (phase III) reflects the exhalation of unmixed gas from regions of the lung which normally are in active exchange with the alveoli tissue and thus closely resembles (in healthy patients) gas properties associated with arterial blood in contact with the lung for gas exchange (CO.sub.2 release and O.sub.2 absorption). In normal lungs, Phase III is substantially level (slope .apprxeq.0) since ventilated and perfused alveolar regions are closely matched. In a diseased lung, Phase III may not appear level due to a mismatch in ventilation and perfusion of this lung region. See, Table I below:
TABLE I ______________________________________ Phase I Represents CO.sub.2 -free gas expired from the airway conduction structures where gas exchange does not occur, Phase II The S-shaped upswing represents the transition from airway to alveolar gas, and Phase III The alveolar plateau representing CO.sub.2 rich gas from the alveoli. ______________________________________
In the past, capnography has utilized the peak or end-tidal (PetCO.sub.2) values as an estimate of PaCO.sub.2. PetCO.sub.2 is a measure of the mean alveolar partial pressure of carbon dioxide from all functional gas exchange units. PetCO.sub.2 obtained from capnography is a measure of mean alveolar pCO.sub.2 which approximates PaCO.sub.2 in normal lungs. Because CO.sub.2 readily diffuses across the alveolar-capillary membrane, the PetCO.sub.2 closely approximates the PaCO.sub.2 with normal ventilation-perfusion. The difference between PetCO.sub.2 and PaCO.sub.2 is primarily a function of the proportion of the lung where gas exchange does not occur (Fletcher, R., Johnson, G., and Brew, J., "The Concept of Deadspace with Special Reference to Single Breath Test for Carbon Dioxide," Br. J. Anaesth., 53, 77, 1981). In lung disease there often exists a proportional increase in the region of the lungs where gas exchange does not occur, resulting in a significant difference between peak CO.sub.2 obtained from capnography and PaCO.sub.2.
Other techniques have been utilized for assessing patient blood gas levels with mixed results. Transcutaneous sensors measure tissue pCO.sub.2 diffused through the heated skin but have practical and theoretical limitations. Oximetry is a widely used, non-invasive method for estimating the arterial oxygen carried on hemoglobin. For example, U.S. Pat. Nos. 4,759,369, 4,869,254 and 5,190,038 describe pulse oximeters which measure the percentage of hemoglobin which is oxygenated. However, neither measure the amount of dissolved oxygen present, nor the amount of oxygen carried when hemoglobin levels are reduced. Low hemoglobin levels are found when there is a significant blood loss or when there is insufficient red blood cell formation. Additionally, oximeter readings are specific to the point of attachment, which is typically the finger tip or ear lobe, and may not reflect the oxygen level of vital organs during conditions such as shock or hypothermia.
There remains a significant need in the art for an accurate, non-invasive, sensitive method for accurately determining the levels of arterial blood gases. As will be seen hereinafter, the instant invention sets forth a non-invasive system to overcome the problems of the prior art.

Non-invasive estimation of arterial blood gases


An optical fiber unit includes: a plurality of optical fibers; and at least two binding materials that bind the plurality of optical fibers. The two binding materials are wound around the plurality of optical fibers in an SZ shape and adhered to each other at reversed portions of the SZ shape to form an adhesive part. The adhesive part extends along a longitudinal direction where the optical fiber unit extends, and 0.15≤L/(P/2)≤0.8 is satisfied where L is a length of the adhesive part in the longitudinal direction and P is a binding pitch of the two binding materials in the longitudinal direction.

In the related art, as disclosed in Patent Document 1, an optical fiber unit formed by winding binding materials on a plurality of optical fiber cores or optical fiber strands (hereinafter, simply referred to as optical fibers). In the optical fiber unit, binding materials are wound, so it is possible to prevent the bundle of optical fibers from becoming loose, and it is also possible to improve the discrimination among the plurality of optical fiber units depending on the colors of binding materials.
In addition, Patent Document 2 proposes an optical fiber unit in which a plurality of binding materials are wound in an SZ shape on a bundle of optical fibers, and two binding materials are adhered to each other at reversed portions in the winding direction. According to this configuration, when the part at which the two binding materials are adhered to each other is peeled off, the binding around the peeled part is released and the binding at the other part is maintained. Thus, it is possible to improve workability of intermediate post-branching or the like of the optical fiber unit.
[Patent Document 1] Japanese Unexamined Patent Application, First Publication No. 2010-26196
[Patent Document 2] Japanese Unexamined Patent Application, First Publication No. 2012-88454
In the optical fiber unit described in Patent Document 2, since binding materials are adhered to each other at reversed portions, the adhesive part could be unexpectedly peeled off, so that the binding state tends to become unstable.

Optical fiber unit and optical fiber cable


An Al-based alloy represented by the general formula Al.sub.bal Ti.sub.a M.sub.b and Al.sub.bal Ti.sub.a M.sub.b Q.sub.c wherein M represents at least one element selected from among V, Cr, Mn, Co, Cu, Y, Zr, Nb, Mo, Hf, Ta and W; Q represents at least one element selected from Mg and Si; and a, b and c are, in percentages by weight, 7.ltoreq.a.ltoreq.20, 0.2.ltoreq.b.ltoreq.20 and 0.1.ltoreq.c.ltoreq.5. A compacted and consolidated material is produced by melting a material having the above alloy composition, rapidly solidifying the melt into powder or flakes; compacting the resultant powder or flakes; and subjecting the compacted powder or flakes to press forming and consolidating by a conventional plastic working. The aluminum-based alloy and the compacted and consolidated material thereof have a high strength, a good ductility and an excellent strength at high temperatures.

1. Field of the Invention
The present invention relates to a high-strength, heat-resistant aluminum-based alloy having a high strength and ductility and an excellent strength at high temperature, and a compacted and consolidated aluminum-based alloy material produced by compacting and consolidating the alloy and a process for producing the same.
2. Description of the Prior Art
An aluminum-based alloy having a high strength and a high heat resistance has hitherto been produced by the liquid quenching process or the like. In particular, an aluminum-based alloy produced by the liquid quenching process disclose in Japanese Patent Laid-Open No. 275732/1989 is in an amorphous or microcrystalline state and is an excellent alloy having a high strength, a high heat resistance and a high corrosion resistance.
Although the aluminum-based alloy disclosed in the above-described Japanese Patent Laid-Open No. 275732/1989 is an alloy having a high strength, a heat resistance and a high corrosion resistance, and exhibits an excellent workability when it is used as a high-strength material, there is room for improvement when the aluminum-based alloy is used as a material of which a high toughness and a high-temperature strength are required. Accordingly, an object of the present invention is to provide a high-strength aluminum-based alloy having an excellent toughness and a high-temperature strength, a compacted and consolidated material produced therefrom and a process for producing the same.

High-strength, heat-resistant aluminum-based alloy, compacted and consolidated material thereof, and process for producing the same


A unitary labeling apparatus for a container having a cap secured over an opening to an interior hollow, the apparatus including: a non-shrinkable base label suitable for being secured about a periphery of the container and to a portion of the cap; and, a shrinkable overlayer secured to the base label and suitable for being shrunk about the periphery of the container and a periphery of the cap; wherein, the unitary labeling apparatus is suitable for evidencing accessing of the container interior hollow via removal of the cap once secured about the container.

With an increasing interest in "out of package" containers, a need has arisen for a cost effective solution to address both labeling and tamper evidencing needs. Currently in many packaging operations a container is labeled with a pressure sensitive label, and then a separate clear shrinkable polyvinyl-chloride (PVC) shrink sleeve is applied as a "safety seal" tamper evidencing feature.

Labeling apparatus and method of making same