Transition metal complexes used as bleach catalysts of the formula (1)

The present invention relates to the use of certain transition metal complexes for increasing the bleaching action of peroxygen compounds during the bleaching of colored soilings both on textiles and also on hard surfaces, and to laundry detergents and cleaners which comprise complex compounds of this type.
Inorganic peroxygen compounds, in particular hydrogen peroxide and solid peroxygen compounds which dissolve in water to liberate hydrogen peroxide, such as sodium perborate and sodium carbonate perhydrate, have been used for a long time as oxidizing agents for disinfection and bleaching purposes. The oxidation effect of these substances depends heavily on the temperature in dilute solutions; thus, for example, using H2O2 or perborate in alkaline bleach liquors, a sufficiently rapid bleaching of soiled textiles is achieved only at temperatures above approximately 80xc2x0 C.
At lower temperatures, the oxidation effect of the inorganic peroxygen compounds can be improved by adding xe2x80x9cbleach activatorsxe2x80x9d. For this purpose, numerous proposals have been worked out in the past, primarily from the substance classes of N- or O-acyl compounds, for example polyacylated alkylenediamines, in particular tetraacetylglycoluril, N-acylated hydantoins, hydrazides, triazoles, hydrotriazines, urazoles, diketopiperazines, sulfurylamides and cyanurates, and also carboxylic anhydrides, in particular phthalic anhydride and substituted maleic anhydrides, carboxylic esters, in particular sodium nonanoyloxybenzenesulfonate (NOBS), sodium isononanoyloxybenzenesulfonate (ISONOBS) and acylated sugar derivatives, such as pentaacetylglucose. By adding these substances it is possible to increase the bleaching action of aqueous peroxide solutions to the extent that even at temperatures around 60xc2x0 C. essentially the same effects arise as with the peroxide solution on its own at 95xc2x0 C.
In the development of energy-saving washing and bleaching processes, use temperatures significantly below 60xc2x0 C., in particular below 45xc2x0 C. down to cold-water temperature, have gained in importance in recent years. At these low temperatures, the effect of the activator compounds known hitherto usually noticeably decreases. There has therefore been no lack of attempts to develop more effective activators for this temperature range although hitherto a convincing success has not been recorded.
A starting point for this arises from the use of transition metal salts and complexes thereof, as are described, for example, in EP 0 392 592, EP 0 443 651, EP 0 458 397, EP 0 544 490 or EP 0 549 271. EP 0 272 030 describes cobalt(II) complexes having ammonia ligands which, in addition, may have any further mono-, bi-, tri- and/or tetradentate ligands, as activators for H2O2 for use in textile detergents or bleaches. WO 96/23859, WO 96/23860 and WO 96/23861 describe the use of corresponding Co(III) complexes in compositions for automatic dishwashing. EP 0 630 964 discloses certain manganese complexes which, despite not having a marked effect with regard to a bleach boosting of peroxygen compounds and not decoloring textile fibers, are able to effect bleaching of soil or dye detached from the fiber and present in wash liquors. DE 44 16 438 discloses manganese, copper and cobalt complexes which can carry ligands from a large number of groups of substances and are reportedly used as bleach and oxidation catalysts. WO 97/07191 proposes complexes of manganese, iron, cobalt, ruthenium and molybdenum with ligands of the salene type as activators for peroxygen compounds in cleaning solutions for hard surfaces.
The aim of the present invention is to improve the oxidation and bleaching action of peroxygen compounds, in particular of inorganic peroxygen compounds, at low temperatures below 80xc2x0 C., in particular in the temperature range from about 15xc2x0 C. to 45xc2x0 C.
Surprisingly, it has now been found that certain transition metal complexes of ligands with an oximato or dioximato structure contribute significantly to the cleaning performance on colored soilings present on textiles or on hard surfaces.
The invention provides for the use of transition metal complexes having oxime ligands as bleach catalyst for peroxygen compounds, wherein the transition metal complexes have the formula (1)
M(L)nXmxe2x80x83xe2x80x83(1)
where
M is a metal atom from the group Mn, Fe, Co, Ni, Mo, W,
L is a ligand of the formula
R1R2Cxe2x95x90Nxe2x80x94O(H)z
R1 is C1-C22-alkyl, C2-C22-alkenyl or C5-C24-aryl,
R2 is H, C1-C22-alkyl, C2-C22-alkenyl, C5-C24-aryl or
where z=0 or 1,
X is a neutral or anion ligand from the group consisting of pyridines, imidazolines, methylimidazoles, picolines, lutidines, chloride, bromide, nitrate, perchlorate, citrate, hexafluorophosphate or anions of organic acids having C1-C22 carbon atoms, n is a number from 2 to 4 and m is a number from 0 to 4.
These transition metal complexes are used in laundry detergents and cleaners, in particular in the washing of textiles and in cleaners for hard surfaces, in particular for dishes, and in solutions for bleaching colored soilings.
Preference is given to using complexes with transition metal central atoms in oxidation states +2, +3 or +4, and complexes containing manganese or iron as central atoms. Corresponding manganese compounds have hitherto not been described in the literature.
The ligand (L) represents an oximato or dioximato ligand. Examples thereof are acetoxime, acetal oxime, salicyloxime and glyoxime, dimethylglyoxime, methylethylglyoxime, cyclohexanedione dioxime and other oximes or dioximes as described, for example, in A. Chakravorty, Coord. Chem. Rev. 13 (1974), 1-46 and I. W. Pang and D. V. Stynes, Inorg. Chem., 1977, 16, 590, G. N. Schrauzer and L. P. Lee, J.Am.Chem.Soc., 1970, 92, 1551. The oximes and dioximes can, as the person skilled in the art knows, be obtained by reacting the corresponding aldehydes, ketones or diketones with hydroxylamine.
Apart from the ligands (L) according to the formula I, the transition metal complexes to be used according to the invention can also carry further, usually simply constructed, ligands (X), in particular neutral ligands, or mono- or polyvalent anion ligands. Examples thereof are optionally substituted pyridines, imidazoles, methylimidazoles, picolines, imidazolines or lutidines or similar nitrogen-containing heterocycles. These heterocycles are preferably in their unsubstituted form. Also suitable here are nitrate, acetate, formate, citrate, perchlorate, ammonia and the halides, such as chloride, bromide and iodide, and complex anions, such as hexafluorophosphate or anions of organic C1-C22-carboxylic acids, such as acetates, propionates, butyrates, hexanoates, octanoates, nonanoate and laurate. The anion ligands serve to balance the charge between transition metal central atom and the ligand system. The presence of oxo ligands, peroxo ligands and imino ligands is also possible. These additional ligands can also have a bridging action, giving rise to polynuclear complexes having at least one ligand according to formula I.
Particularly preferred complexes are
a) [bis(cyclohexanone oxime)bis(cyclohexanone oximato)bis(pyridine)-manganese(II)]
b) [bis(diphenylglyoximato)bis(pyridine)manganese(II)]
Suitable peroxygen compounds are primarily all alkali metal perborate mono- and tetrahydrates and/or alkali metal percarbonates, and sodium is the preferred alkali metal. However, it is also possible to use alkali metal or ammonium peroxosulfates, such as, for example, potassium peroxomonosulfate (industrially: Caroat(copyright) or Oxone(copyright)). The concentration of inorganic oxidizing agent in the overall formulation of the laundry detergents and cleaners is 5-90%, preferably 10-70%.
The use amounts of peroxygen compounds are generally chosen so that between 10 ppm and 10% active oxygen, preferably between 50 ppm and 5000 ppm of active oxygen, are present in the solutions of the laundry detergents and cleaners. The amount of bleach-boosting complex compound used also depends on the intended use. Depending on the desired degree of activation, it is used in amounts such that 0.01 mmol to 25 mmol, preferably 0.1 mmol to 2 mmol, of complex per mole of peroxygen compound are used, although in special cases it is possible to exceed or fall short of these limits. Preferably 0.0025 to 0.25% by weight, in particular 0.01 to 0.5% by weight, of the above-defined bleach-boosting complex compound are present in laundry detergents and cleaners.
Additionally or alternatively, the laundry detergents and cleaners can comprise organic-based oxidizing agents in the concentration range 1-20%. These include all known peroxycarboxylic acids, e.g. monoperoxyphthalic acid, dodecanediperoxy acid or phthalimidoperoxycarboxylic acids, such as PAP and related systems, or the amido peracids as specified in EP-A-170 386.
The term bleaching here covers both the bleaching of soil on the surface of textiles, and also the bleaching of soil detached from the textile surface and present in the wash liquor. Analogous statements apply to the bleaching of soilings on hard surfaces.
Further potential uses are in the personal care sector, e.g. for the bleaching of hair and for improving the effectiveness of denture cleansers. In addition, the metal complexes described are used in commercial laundries, in the bleaching of wood and paper, the bleaching of cotton and in disinfectants.
Furthermore, the invention relates to a method of cleaning textiles and also of hard surfaces, in particular of dishes, using said complex compounds together with peroxygen compounds in aqueous solution optionally comprising further detergent or cleaner constituents, and to laundry detergents and cleaners for hard surfaces, in particular dishwashing detergents, preference being given to those for use in automatic processes which comprise complex compounds of this type.
The use according to the invention essentially consists, in the case of hard surfaces contaminated with colored soiling or in the case of soiled textiles, in providing conditions under which a peroxidic oxidizing agent and the complex compound can react with one another with the aim of obtaining secondary products which have a stronger oxidizing effect. Such conditions prevail particularly when the reactants encounter one another in aqueous solution. This can arise by separately adding the peroxygen compound and the complex to the aqueous solution of the laundry detergent and cleaner. However, the process according to the invention is particularly advantageously carried out using a laundry detergent or cleaner for hard surfaces which comprises the complex compound and optionally a peroxygen-containing oxidizing agent. The peroxygen compound can also be added to the solution separately without a diluent or, preferably, as an aqueous solution or suspension if a peroxygen-free laundry detergent or cleaner is used.
The laundry detergents and cleaners, which can be in the form of granules, pulverulent or tableted solids, as other moldings, homogeneous solutions or suspensions, can in principle comprise all ingredients known and customary in such compositions in addition to said bleach-boosting metal complex. The compositions can, in particular, comprise builder substances, surfactants, peroxygen compounds, additional peroxygen activators or organic peracids, water-miscible organic solvents, sequestering agents, enzymes, and specific additives with an action which is gentle on colors and fibers. Further auxiliaries, such as electrolytes, pH regulators, silver corrosion inhibitors, foam regulators and dyes and fragrances, are possible.
A hard-surface cleaner according to the invention can moreover comprise abrasive constituents, in particular from the group consisting of quartz flours, wood flours, plastic flours, chalks and micro glass beads, and mixtures thereof. Abrasive substances are preferably present in the cleaners according to the invention in amounts not exceeding 20% by weight, in particular from 5 to 15% by weight.
The laundry detergents and cleaners can comprise one or more surfactants, suitable surfactants being, in particular, anionic surfactants, nonionic surfactants, and mixtures thereof, and also cationic, zwitterionic and amphoteric surfactants. Such surfactants are present in laundry detergents according to the invention in amounts of preferably 1 to 50% by weight, in particular from 3 to 30% by weight, whereas in hard-surface cleaners, lesser amounts, i.e. amounts up to 20% by weight, in particular up to 10% by weight and preferably in the range from 0.5 to 5% by weight, are normally present. In cleaners for use in machine dishwashing processes, low-foam compounds are normally used.
Suitable anionic surfactants are, in particular, soaps and those which contain sulfate or sulfonate groups. Suitable surfactants of the sulfonate type are preferably C9-C13-alkylbenzenesulfonates, olefinsulfonates, i.e. mixtures of alkene- and hydroxyalkanesulfonates, and disulfonates, as are obtained, for example, from monoolefins with terminal or internal double bond by sulfonation with gaseous sulfur trioxide and subsequent alkaline or acidic hydrolysis of the sulfonation products. Also suitable are alkanesulfonates obtained from C12-C18-alkanes, for example by sulfochlorination or sulfoxidation with subsequent hydrolysis or neutralization. Also suitable are the esters of alpha-sulfofatty acids (ester sulfonates), for example the alpha-sulfonated methyl esters of hydrogenated coconut, palm kernel or tallow fatty acids which are prepared by sulfonation of the methyl esters of fatty acids of vegetable and/or animal origin having 8 to 20 carbon atoms in the fatty acid molecule, and subsequent neutralization to give water-soluble monosalts.
Further suitable anionic surfactants are sulfated fatty acid glycerol esters, which are mono-, di- and triesters, and mixtures thereof. Preferred alk(en)yl sulfates are the alkali metal and, in particular, the sodium salts of sulfuric monoesters of C12-C18-fatty alcohols, for example from coconut fatty alcohol, tallow fatty alcohol, lauryl, myristyl, cetyl or stearyl alcohol or of C8-C20-oxo alcohols and those monoesters of secondary alcohols of this chain length. Also preferred are alk(en)yl sulfates of said chain length which contain a synthetic straight-chain alkyl radical prepared on a petrochemical basis. 2,3-Alkyl sulfates, which are prepared, for example, in accordance with U.S. Pat. Nos. 3,234,158 and 5,075,041, are suitable anionic surfactants. Also suitable are the sulfuric monoesters of the straight-chain or branched alcohols ethoxylated with 1 to 6 mol of ethylene oxide, such as 2-methyl-branched C9-C11-alcohols having, on average, 3.5 mol of ethylene oxide (EO) or C12-C18-fatty alcohols having 1 to 4 EO.
Preferred anionic surfactants also include the salts of alkylsulfosuccinic acid, which are also referred to as sulfosuccinates or as sulfosuccinic esters and which are monoesters and/or diesters of sulfosuccinic acid with alcohols, preferably fatty alcohols and, in particular, ethoxylated fatty alcohols. Preferred sulfosuccinates contain C8-C18-fatty alcohol radicals or mixtures thereof. Other suitable anionic surfactants are fatty acid derivatives of amino acids, for example of N-methyltaurine (taurides) and/or of N-methylglycine (sarcosinates). Further suitable anionic surfactants are, in particular, soaps, for example in amounts of from 0.2 to 5% by weight. In particular, saturated fatty acid soaps, such as the salts of lauric acid, myristic acid, palmitic acid, stearic acid, hydrogenated erucic acid and behenic acid, and, in particular, soap mixtures derived from natural fatty acids, for example coconut, palm kernel or tallow fatty acids, are suitable.
The anionic surfactants, including the soaps, can be present in the form of their sodium, potassium or ammonium salts, and as soluble salts of organic bases, such as mono-, di- or triethanolamine. The anionic surfactants are preferably in the form of their sodium or potassium salts, in particular in the form of the sodium salts. Anionic surfactants are present in laundry detergents according to the invention preferably in amounts of from 0.5 to 10% by weight and, in particular, in amounts of from 5 to 25% by weight.
The nonionic surfactants used are preferably alkoxylated, advantageously ethoxylated, in particular primary, alcohols having, preferably, 8 to 18 carbon atoms and, on average, 1 to 12 mol of ethylene oxide (EO) per mole of alcohol, in which the alcohol radical may be linear or, preferably, methyl-branched in the 2-position, or may comprise a mixture of linear and methyl-branched radicals, as are usually present in oxo alcohol radicals. However, particular preference is given to alcohol ethoxylates with linear radicals from alcohols of a native origin having 12 to 18 carbon atoms, e.g. from coconut, palm, tallow fatty or oleyl alcohol, and, on average, 2 to 8 EO per mole of alcohol. Preferred ethoxylated alcohols include, for example, C12-C14-alcohols having 3 EO or 4 EO, C9-C11-alcohols having 7 EO, C13-C15-alcohols having 3 EO, 5 EO, 7 EO or 8 EO, C12-C18-alcohols having 3 EO, 5 EO or 7 EO and mixtures thereof, such as mixtures of C12-C14-alcohol with 3 EO and C12-C18-alcohol with 7 EO. The stated degrees of ethoxylation are statistical average values which, for a specific product, may be an integer or a fraction. Preferred alcohol ethoxylates have a narrowed homolog distribution (narrow range ethoxylates, NRE). In addition to these nonionic surfactants, it is also possible to use fatty alcohols having more than 12 EO. Examples thereof are (tallow) fatty alcohols having 14 EO, 16 EO, 20 EO, 25 EO, 30 EO or 40 EO.
The nonionic surfactants also include alkyl glycosides of the formula RO(G)X in which R is a primary straight-chain or methyl-branched, in particular methyl-branched in the 2-position, aliphatic radical having 8 to 22, preferably 12 to 18, carbon atoms and G is a glycose unit having 5 or 6 carbon atoms, preferably glucose. The degree of oligomerization x, which gives the distribution of monoglycosides and oligoglycosides, is any desired numberxe2x80x94which, being an analytically determined parameter, can also assume fractional valuesxe2x80x94between 1 and 10; x is preferably 1.2 to 1.4. Likewise suitable are polyhydroxyfatty acid amides of the formula (I)
in which the radical R1xe2x80x94CO is an aliphatic acyl radical having 6 to 22 carbon atoms, R2 is hydrogen, an alkyl or hydroxyalkyl radical having 1 to 4 carbon atoms and [Z] is a linear or branched polyhydroxyalkyl radical having 3 to 10 carbon atoms and 3 to 10 hydroxyl groups. The polyhydroxyfatty acid amides are preferably derived from reducing sugars having 5 or 6 carbon atoms, in particular from glucose.
The group of polyhydroxyfatty acid amides also includes compounds of the formula (II)
in which R3 is a linear or branched alkyl or alkenyl radical having 7 to 21 carbon atoms, R4 is a linear, branched or cyclic alkylene radical or an arylene radical having 6 to 8 carbon atoms and R5 is a linear, branched or cyclic alkyl radical or an aryl radical or an oxyalkyl radical having 1 to 8 carbon atoms, where C1-C4-alkyl or phenyl radicals are preferred, and [Z] is a linear polyhydroxyalkyl radical whose alkyl chain is substituted by at least two hydroxyl groups, or alkoxylated, preferably ethoxylated or propoxylated, derivatives of this radical. [Z] is here, too, preferably obtained by reductive amination of a sugar such as glucose, fructose, maltose, lactose, galactose, mannose or xylose. The N-alkoxy- or -N-aryloxy-substituted compounds can then be converted into the desired polyhydroxyfatty acid amides, for example in accordance with WO 95/07331 by reaction with fatty acid methyl esters in the presence of an alkoxide as catalyst.
A further class of preferred nonionic surfactants, which are used either as the sole nonionic surfactant or in combination with other nonionic surfactants, in particular together with alkoxylated fatty alcohols and/or alkyl glycosides, are alkoxylated, preferably ethoxylated or ethoxylated and propoxylated, fatty acid alkyl esters, preferably having 1 to 4 carbon atoms in the alkyl chain, in particular fatty acid methyl esters.
Nonionic surfactants of the amine oxide type, for example N-cocoalkyl-N,N-dimethylamine oxide and N-tallow-alkyl-N,N-dihydroxyethylamine oxide, and of the fatty acid alkanolamide type may also be suitable.
From the large group of cationic surfactants, particular preference is given to hydroxyalkyl quats of the general structures (III) and (IV).
where the radicals R1, R2, R3xe2x95x90C1-C22-alkyl and n=1 to 5.
Other suitable surfactants are xe2x80x9cgemini surfactantsxe2x80x9d. These are generally understood as meaning compounds which have two hydrophilic groups per molecule. These groups are usually separated from one another by a xe2x80x9cspacerxe2x80x9d. This spacer is usually a carbon chain which should be long enough for the hydrophilic groups to have a sufficient distance such that they can act independently of one another. Such surfactants are generally characterized by an unusually low critical micelle concentration and the ability to drastically reduce the surface tension of water. However, it is also possible to use gemini polyhydroxyfatty acid amides or poly-polyhydroxyfatty acid amides, as described in international patent applications WO 95/19953, WO 95/19954 and WO 95/19955. Further surfactant types can have dendrimeric structures.
A laundry detergent according to the invention preferably comprises at least one water-soluble and/or water-insoluble, organic and/or inorganic builder.
Suitable water-soluble inorganic builder materials are, in particular, alkali metal silicates and polymeric alkali metal phosphates, which can be in the form of their alkaline, neutral or acidic sodium or potassium salts. Examples thereof are trisodium phosphate, tetrasodium diphosphate, disodium dihydrogen diphosphate, pentasodium triphosphate, xe2x80x9csodium hexametaphosphatexe2x80x9d, and the corresponding potassium salts, or mixtures of sodium and potassium salts. Suitable water-insoluble, water-dispersible inorganic builder materials used are, in particular, crystalline or amorphous alkali metal alumosilicates, in amounts of up to 50% by weight. Of these, the crystalline sodium alumosilicates in laundry detergent quality, in particular zeolite A, P and optionally X, alone or in mixtures, for example in the form of a cocrystallisate of the zeolites A and X, are preferred. Their calcium-binding capacity, which can be determined in accordance with the instructions in German patent DE 24 12 837, is usually in the range from 100 to 200 mg of CaO per gram. Suitable builder substances are also crystalline alkali metal silicates, which can be present alone or in mixtures with amorphous silicates. The alkali metal silicates which can be used as builders preferably have a molar ratio of alkali metal oxide to SiO2 below 0.95, in particular of 1:1.1 to 1:12 and can be in amorphous or crystalline form. Preferred alkali metal silicates are the sodium silicates, in particular the amorphous sodium silicates having a molar ratio of Na2O:SiO2 of 1:2 to 1:2.8. Those with an Na2O:SiO2 molar ratio of from 1:1.9 to 1:2.8 can be prepared by the process of European patent application EP 0 425 427. The crystalline silicates used, which can be present alone or as a mixture with amorphous silicates, are preferably crystalline phyllosilicates of the formula Na2SixO2x+1.Y H2O, in which x, the xe2x80x9cmodulusxe2x80x9d, is a number from 1.9 to 4 and y is a number from 0 to 20, and preferred values for x are 2, 3 or 4. Crystalline phyllosilicates which fall under this formula are described, for example, in European patent application EP 0 164 514. Preferred crystalline phyllosilicates are those in which x in said formula assumes the values 2 or 3. Particular preference is given to both xcex4- and xcex2-sodium disilicates (Na2Si2O5.y H2O), where xcex2-sodium disilicate can be obtained, for example, according to the process described in international patent application WO 91/08171. xcex2-Sodium silicates with a modulus between 1.9 and 3.2 can be prepared in accordance with Japanese patent applications JP 04/238 809 or JP 04/260 610. Virtually anhydrous crystalline alkali metal silicates prepared from amorphous silicates and of the abovementioned formula in which x is a number from 1.9 to 2.1, which can be prepared as described in European patent applications EP 0 548 599, EP 0 502 325 and EP 0 425 428, can also be used. In a further preferred embodiment of such compositions, a crystalline sodium phyllosilicate with a modulus of from 2 to 3 is used, as can be prepared in accordance with the process of European patent application EP 0 436 835 from sand and soda. Crystalline sodium silicates with a modulus in the range from 1.9 to 3.5, as are obtainable in accordance with the processes of European patents EP 0 164 552 and/or EP 0 294 753, are used in a further preferred embodiment of compositions according to the invention. In a preferred embodiment of compositions according to the invention, a granular compound of alkali metal silicate and alkali metal carbonate, as listed, for example, in international patent application WO 95/22592 or as is commercially available, for example, under the name Nabion(copyright), is used. In cases where alkali metal alumosilicate, in particular zeolite, is present as additional builder substance, the weight ratio of alumosilicate to silicate, in each case based on anhydrous active substances, is preferably 1:10 to 10:1. In compositions which comprise both amorphous and crystalline alkali metal silicates, the weight ratio of amorphous alkali metal silicate to crystalline alkali metal silicate is preferably 1:2 to 2:1 and in particular 1:1 to 2:1.
Such builder substances are present in compositions according to the invention preferably in amounts of up to 60% by weight, in particular from 5 to 40% by weight.
The water-soluble organic builder substances include polycarboxylic acids, in particular citric acid and sugar acids, aminopolycarboxylic acids, in particular methylglycinediacetic acid, nitrilotriacetic acid and ethylenediaminetetraacetic acid, and polyaspartic acid.
Polyphosphonic acids, in particular aminotris(methylenephosphonic acid), ethylenediaminetetrakis(methylenephosphonic acid) and 1-hydroxyethane-1,1-diphosphonic acid, can likewise be used. Preference is also given to polymeric (poly)carboxylic acids, in particular the polycarboxylates of international patent application WO 93/16110 or of international patent application WO 92/18542 or of European patent application EP 0 232 202, accessible by oxidation of polysaccharides or dextrins, polymeric acrylic acids, methacrylic acids, maleic acids and mixed polymers thereof, which may also comprise small amounts of polymerizable substances without carboxylic acid functionality in copolymerized form. The relative molecular mass of the homopolymers of unsaturated carboxylic acids is generally between 5 000 and 200 000, that of the copolymers is between 2 000 and 200 000, preferably 50 000 to 120 000, in each case based on free acid. A particularly preferred acrylic acid-maleic acid copolymer has a relative molecular mass of from 50 000 to 100 000. Commercially available products are, for example, Sokalan(copyright) CP 5, CP 10 and PA 30 from BASF. Also suitable are copolymers of acrylic acid or methacrylic acid with vinyl ethers, such as vinyl methyl ethers, vinyl esters, ethylene, propylene and styrene, in which the proportion of acid is at least 50% by weight. Other water-soluble organic builder substances which may be used are terpolymers which contain, as monomers, two unsaturated acids and/or salts thereof, and, as a third monomer, vinyl alcohol and/or an esterified vinyl alcohol or a carbohydrate. The first acidic monomer or salt thereof is derived from a monoethylenically unsaturated C3-C8-carboxylic acid and preferably from a C3-C4-monocarboxylic acid, in particular from (meth)acrylic acid.
The second acidic monomer or salt thereof can be a derivative of a C4-C8-dicarboxylic acid, maleic acid being particularly preferred, and/or a derivative of an allylsulfonic acid which is substituted in the 2-position by an alkyl or aryl radical. Such polymers can be prepared, in particular, according to processes described in German patents DE 42 21 381 and DE 43 00 772, and generally have a relative molecular mass between 1 000 and 200 000. Further preferred copolymers are those which are described in German patent applications DE 43 03 320 and DE 44 17 734 and have, as monomers, preferably acrolein and acrylic acid/acrylic acid salts or vinyl acetate.
The organic builder substances can, in particular for the preparation of liquid compositions, be used in the form of aqueous solutions, preferably in the form of 30 to 50% strength by weight aqueous solutions. All said acids are usually used in the form of their water-soluble salts, in particular their alkali metal salts.
Such organic builder substances can, if desired, be present in amounts up to 40% by weight, in particular up to 25% by weight and preferably from 1 to 8% by weight. Amounts close to said upper limit are preferably used in pasty or liquid, in particular water-containing, compositions.
Suitable water-soluble builder components in hard-surface cleaners according to the invention are, in principle, all builders customarily used in compositions for machine dishwashing, for example the abovementioned alkali metal phosphates. Their amounts can be in the range up to about 60% by weight, in particular 5 to 20% by weight, based on the overall composition. Further possible water-soluble builder components are, as well as polyphosphonates and phosphonate alkyl carboxylates, for example organic polymers of native or synthetic origin of the polycarboxylate type listed above which, particularly in hard-water regions, act as cobuilders, and naturally occurring hydroxycarboxylic acids, such as, for example, mono-, dihydroxysuccinic acid, alpha-hydroxypropionic acid and gluconic acid. Preferred organic builder components include the salts of citric acid, in particular sodium citrate. Suitable as sodium citrate are anhydrous trisodium citrate and, preferably, trisodium citrate dihydrate. Trisodium citrate dihydrate can be used as a finely or coarsely crystalline powder. Depending on the pH ultimately set in the cleaners according to the invention, the acids corresponding to said cobuilder salts may also be present.
In addition to the complex compounds used according to the invention, it is possible to use conventional bleach activators, i.e. compounds which release peroxocarboxylic acids under perhydrolysis conditions. The customary bleach activators which contain O- and/or N-acyl groups are suitable. Preference is given to polyacylated alkylenediamines, in particular tetraacetylethylenediamine (TAED), acylated glycolurils, in particular tetraacetylglycoluril (TAGU), acylated triazine derivatives, in particular 1,5-diacetyl-2,4-dioxohexahydro-1,3,5-triazine (DADHT), acylated phenylsulfonates, in particular nonanoyl- or isononanoyloxybenzenesulfonate (NOBS and ISONOBS, respectively) or amide derivatives thereof, acylated polyhydric alcohols, as described for example in EP 170 386, in particular triacetin, ethylene glycol diacetate and 2,5-diacetoxy-2,5-dihydrofuran, and acylated sorbitol and mannitol, and acylated sugar derivatives, in particular pentaacetylglucose (PAG), pentaacetylfructose, tetraacetylxylose and octaacetyllactose, and acylated, optionally N-alkylated glucamine and gluconolactone. Open-chain or cyclic nitrile quats, as known from EP-A-303 520 and WO 98/23602, are also suitable for this intended use. It is also possible to use the combinations of conventional bleach activators known from German patent application DE 44 43 177.
The enzymes optionally present in the compositions according to the invention include proteases, amylases, pullulanases, cellulases, cutinases and/or lipases, for example proteases such as BLAP(copyright), Optimase(copyright), Opticlean(copyright), Maxacal(copyright), Maxapem(copyright), Durazym(copyright), Purafect(copyright) OxP, Esperase(copyright) and/or Savinase(copyright), amylases such as Termamyl(copyright), Amylase-LT, Maxamyl(copyright), Duramyl(copyright), Purafectel OxAm, cellulases such as Celluzyme(copyright), Carezyme(copyright), K-AC(copyright) and/or the cellulases known from international patent applications WO 96/34108 and WO 96/34092 and/or lipases, such as Lipolase(copyright), Lipomax(copyright), Lumafast(copyright) and/or Lipozym(copyright). The enzymes used can, as described, for example, in international patent applications WO 92/11347 or WO 94/23005, be adsorbed to carrier substances and/or embedded in coating substances in order to protect them from premature deactivation. They are present in laundry detergents and cleaners according to the invention preferably in amounts up to 10% by weight, in particular from 0.05 to 5% by weight, particular preference being given to using enzymes stabilized against oxidative degradation, as are known, for example, from international patent applications WO 94/02597, WO 94/02618, WO 94/18314, WO 94/23053 or WO 95/07350.
Machine dishwashing detergents according to the invention preferably comprise the customary alkali metal carriers, such as, for example, alkali metal silicates, alkali metal carbonates and/or alkali metal hydrogencarbonates. The customarily used alkali metal carriers include carbonates, hydrogencarbonates and alkali metal silicates with an SiO2/M2O molar ratio (M=alkali metal atom) of from 1:1 to 2.5:1. Alkali metal silicates can be present in amounts of up to 40% by weight, in particular 3 to 30% by weight, based on the overall composition. The alkali metal carrier system preferably used in cleaners according to the invention is a mixture of carbonate and hydrogencarbonate, preferably sodium carbonate and sodium hydrogencarbonate, which may be present in an amount of up to 50% by weight, preferably 5 to 40% by weight.
The invention further provides a composition for machine dishwashing, comprising 15 to 65% by weight, in particular 20 to 60% by weight, of water-soluble builder component, 5 to 25% by weight, in particular 8 to 17% by weight, of oxygen-based bleaches, in each case based on the overall composition, and 0.1 to 5% by weight of one or more of the above-defined cyclic sugar ketones. Such a composition preferably has low alkalinity, i.e. its percentage strength by weight solution has a pH of from 8 to 11.5, in particular 9 to 11.
In a further embodiment of compositions according to the invention for automatic dishwashing, 20 to 60% by weight of water-soluble organic builders, in particular alkali metal citrate, 3 to 20% by weight of alkali metal carbonate and 3 to 40% by weight of alkali metal disilicate are present.
In order to effect silver corrosion protection, silver corrosion inhibitors can be used in dishwashing detergents according to the invention. Preferred silver corrosion protectants are organic sulfides, such as cystine and cysteine, di- or trihydric phenols, optionally alkyl- or aryl-substituted triazoles, such as benzotriazole, isocyanuric acid, titanium, zirconium, hafnium, molybdenum, vanadium or cerium salts and/or complexes, and salts and/or complexes of the metals present in the complexes suitable according to the invention, with ligands other than those given in formula (I).
If the compositions foam excessively upon use, up to 6% by weight, preferably about 0.5 to 4% by weight, of a foam-regulating compound, preferably from the group consisting of silicones, paraffins, paraffin/alcohol combinations, hydrophobicized silicas, bisfatty acid amides and mixtures thereof and other further known commercially available foam inhibitors, can also be added. Preferably, the foam inhibitors, in particular silicone- and/or paraffin-containing foam inhibitors, are bonded to a granular water-soluble or -dispersible carrier substance. In this connection, particular preference is given to mixtures of paraffins and bistearylethylenediamide. Other possible ingredients in the compositions according to the invention are, for example, perfume oils.
The organic solvents which can be used in the compositions according to the invention, particularly if they are in liquid or paste form, include alcohols having 1 to 4 carbon atoms, in particular methanol, ethanol, isopropanol and tert-butanol, diols having 2 to 4 carbon atoms, in particular ethylene glycol and propylene glycol, and mixtures thereof and the ethers derivable from said classes of compound. Such water-miscible solvents are present in the cleaners according to the invention preferably in amounts not exceeding 20% by weight, in particular from 1 to 15% by weight.
To set a desired pH which does not arise by itself as a result of mixing the other components, the compositions according to the invention can comprise system- and environment-compatible acids, in particular citric acid, acetic acid, tartaric acid, malic acid, lactic acid, glycolic acid, succinic acid, glutaric acid and/or adipic acid and also mineral acids, in particular sulfuric acid or alkali metal hydrogensulfates, or bases, in particular ammonium or alkali metal hydroxides. Such pH regulators are present in the compositions according to the invention preferably in amounts not exceeding 10% by weight, in particular from 0.5 to 6% by weight.
The compositions according to the invention are preferably preparations in the form of powders, granules or tablets, which can be prepared in a manner known per se, for example by mixing, granulation, roll compaction and/or spray-drying the thermally stable components and mixing in the more sensitive components, including, in particular, enzymes, bleaches and the bleach catalyst. Compositions according to the invention in the form of aqueous solutions or solutions comprising other customary solvents are particularly advantageously prepared by simply mixing the ingredients, which can be added without a diluent or as a solution to an automatic mixer.
To prepare particulate compositions with increased bulk density, in particular in the range from 650 g/l to 950 g/l, a process known from European patent EP 0 486 592 and having an extrusion step is preferred. A further preferred preparation using a granulation process is described in European patent EP 0 642 576. The preparation of compositions according to the invention in the form of non-dusting, storage-stable flowable powders and/or granules with high bulk densities in the range from 800 to 1 000 g/l can also be carried out by, in a first process stage, mixing the builder components with at least some of the liquid mixture components, with an increase in bulk density of this premix, and then, if desired after intermediate drying, combining the other constituents of the composition, including bleach catalyst, with the premix obtained in this way.
To prepare compositions according to the invention in tablet form, preference is given to a procedure which involves mixing all of the constituents together in a mixer and compressing the mixture using conventional tableting presses, for example eccentric presses or rotary presses, using pressing forces in the range from 200xc2x7105 Pa to 1500xc2x7105 Pa. This thus gives without problems tablets which are resistant to breakage but which nevertheless dissolve sufficiently rapidly under use conditions and have flexural strengths of normally more than 150 N. A tablet prepared in this way preferably has a weight of 1-5 g to 40 g, in particular 20 g to 30 g, for a diameter of 3-5 mm to 40 mm.

Use of transition metal complexes having oxime ligands as bleach catalysts

Abstract: where

Abstract: L is a ligand of the formula

Abstract: where z=0 or 1,


A method of treatment of disorders of neurological origin and drug formulations for use in the method are disclosed. These conditions comprise fatigue and associated syndromes of pain, weakness and depressed mood which are associated with chronic fatigue syndrome, brain injury and stroke, stress, fibromyalgia, and irritable bowel syndrome. The treatment comprises administering to a patient in need thereof a selective inhibitor of noradrenaline reuptake combined with either phenylalanine or tyrosine in the same dosage form or the same pack.#

The present application claims priority to United Kingdom patent application 9924172.1, filed Oct. 12, 1999.
This invention relates to the treatment of neurological disorders and more particularly to the treatment of neurologically-related fatigue, brain injury, stress, and related conditions.
Some years ago one of us noted that combinations of various types of antidepressants, together with neurotransmitter precursors such as phenylalanine, tyrosine and tryptophan, could improve the symptoms of multiple sclerosis and a patent application covering this invention was filed (PCT/GB95/02361). Subsequently we and various associates also noticed that these same combinations could improve peripheral neuropathy, pain from peripheral neuropathy and pain of any type (PCT/GB97/01822 and PCT/GB97/02295). In each case vitamin B12, folic acid, pyridoxine and other nutrients could be added to the formulations.
We have continued to make clinical observations on the effects of various drugs and amino acids on multiple sclerosis and on pain and as a result have made new discoveries which extend the inventions disclosed in the above patent applications. In particular, we have found that the range of drugs and amino acid precursors which are most effective are those which specifically affect noradrenaline at nerve endings so activating noradrenergic systems, such as lofepramine, desipramine and reboxetine among the drugs and phenylalanine and tyrosine among the amino acids. Phenylanine and tyrosine are precursors of noradrenaline. Tryptophan, the serotonin precursor, and drugs which act prefentially on serotonin have some actions but are less effective. Other drugs which are effective in combination with phenylalanine or tyrosine are drugs which are combined inhibitors of both noradrenaline and serotonin uptake, such as venlafaxine, duloxetine or milnacipran, and drugs which are combined inhibitors of both dopamine and noradrenaline reuptake such as bupropion.
In addition to refining the list of the most effective drugs, the list of possible uses of the combinations has been expanded to include chronic stress, chronic fatigue syndrome, fibromyalgia, fatigue in association with migraine, fatigue in association with brain injuries or other forms of brain damage including stroke, and illnesses associated with chronic fatigue such as irritable bowel syndrome, and brain infections with any agent including viruses, prions or bacteria. A particularly important new use for the combinations of noradrenergic drug and noradrenaline precursor is the neurological rehabilitation of patients after any form of damage to the brain, including traumatic brain injuries and strokes.
Because of the anecdotal evidence of the benefits of lofepramine and phenylalanine, reported in earlier patent applications, we have conducted a substantial, randomised, placebo-controlled, double blind trial in 138 patients with multiple sclerosis (MS). Half the patients received 70 mg lofepramine and 500mg I-phenylalanine twice a day, while the other half received identical-appearing placebos. All patients in both groups received regular injections of vitamin B12. 44 patients had the relapsing/remitting type of MS, 35 had primary progressive disease, and 59 had secondary progressive disease. A wide range of disease severeites was exhibited by the patients: on the Kurtzke Extended Disability Symptom Scale (EDSS) about half the patients had seventies of 6.5 or more, with the other half 6.0 or less. Patients were assessed on various scales, but particularly the Kurtzke scale, and the Gulick MS Patient Symptom scale. The Kurtzke scale aims to provide a relatively objective assessment of the degree of disability as assessed by the neurologist. The Gulick scale assesses a range of symptoms assessed by the patient. These symptoms can be grouped into six factors (Gulick E E, Model confirmation of the MS-related symptom checklist. Nursing Res 1989; 38: 147-153): musculoskeletal (including weakness, spasms and balance problems): elimination (bowel and bladder): emotions (depression, anxiety and loneliness): sensory (pain, numbness, paraesthesia): head symptoms (visual, swallowing and memory): and fatigue. The trial lasted for six months and patients were assessed at baseline, 2 weeks, 4 weeks, 3 months and 6 months.
The results were clear cut and surprising and showed the best evidence ever obtained for a treatment for MS, especially given the relatively short duration of the trial. Interferons slow down the rate of deterioration in MS but do not produce any actual improvements in symptoms. As a result trials have to be two or three years long in order to show differences between active and placebo groups: those differences depend not on improvement in the interferon group but on deterioration in the placebo group. In contrast, lofepramine + phenylalanine produced actual improvements both on the Gulick and the Kurtzke scales. The placebo group showed a deterioration in the Kurtzke scale, and a small improvement on the Gulick scale. The results are summarised in table 1.
Table 1. The results of the trial for the Kurtzke disability and Gulick symptom scales. In the change from baseline line, a + sign indicates improvement and a xe2x88x92 sign indicates deterioration. In the difference between the two groups, a + sign indicates that active treatment with lofepramine and phenylalanine was better than placebo. There were 69 patients in each group.
Three particularly surprising and striking findings emerged from the results obtained with the Gulick scale. First, the effect was very rapid: there was a clear difference between active and placebo by 2 weeks, which reached a peak at 4 weeks and then stayed stable for the remaining five months of the trial. Second, the improvement was seen across all the sub-scales of the Gulick scale (overall 20.5% from baseline, musculoskeletal 15%, elimination 27%, emotions 31%, sensory 23%, head 27% and fatigue 21%): these are large and important effects which have a major impact on the quality of life of patients. Third, the effect on fatigue was particularly important to the patients since it was quick, substantial and a contrast to the interferons which often increase fatigue initially. Patients with MS consistently state that fatigue is the single most important symptom which affects their quality of life (J D Fisk et al. The impact of fatigue on patients with multiple sclerosis. Canadian Journal of Neurological Science 1994; 21: 9-14). We had previously noted an effect on fatigue in a few patients with MS (PCT/GB95/02361) but had not drawn particular attention to this, nor claimed treatment of fatigue, nor expected to see such a large, consistent and statistically significant effect on this important and difficult to manage symptom.
The anecdotal evidence indicating that noradrenaline precursors and noradrenergic drugs like lofepramine and desipramine are particularly effective, and the new and unexpected clinical trial evidence which clearly proves the efficacy, and shows that the effect on fatigue is very important, and that the effects on symptoms are astonishingly rapid and effective across all the symptom groups, has led us to extend our ideas and new applications of those ideas. In particular, the combination of the noradrenaline precursors, phenylalanine and tyrosine, coupled with a drug which either has as its sole action or a component of its action the inhibition of noradrenaline reuptake, is now seen to be valuable in the treatment of fatigue in any form, in the management of rehabilitation after stroke, in the treatment of stress in any form, and in the treatment of fibromyalgia and related disorders such as irritable bowel syndrome.
We can now, as a result of these entirely novel clinical trial findings, draw conclusions about mechanisms of action which lead to these novel applications. First, it is apparent that the system involved is dependent on noradrenaline and to a much smaller extent on serotonin: the greater impact of noradrenergic as opposed to serotoninergic drugs, and the greater effect of phenylalanine as opposed to tryptophan, indicate this. Second, the mechanism is extremely rapid and is too quick to involve any major neuroregeneration which is likely to take months or years if it occurs: the mechanism is therefore likely to involve changes in the function of an existing neuronal system within the brain and spinal cord. Third, the wide range of systems improved by the treatment includes neuronal systems supplying the head and neck, the skeletal muscles, the sensory system, the autonomic nervous system and higher cortical functions: the nerve cells involved in the therapeutic effect must therefore interact with almost all parts of the brain and spinal cord.
What parts of the central nervous system might fulfil the criteria required to explain the effects of lofepramine and phenylalanine? There are two closely related systems which precisely fit our entirely novel and unexpected observations. These are the Locus Coeruleus (LC) and the Lateral Tegmentum (LT) (R Y Moore and F E Bloom, Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Annual Review of Neuroscience 1979; 2: 113-168. B H Smith and W H Sweet, Monoaminergic regulation of central nervous system function: I. Noradrenergic systems. Neurosurgery 1978; 3: 109-119).
The LT and the LC are unique systems. They are both dependent on noradrenaline (NA, also known as norepinephrine) as their main neurotransmitter. The LC is a neuronal nucleus located in the brainstem reticular formation. The LT is a more diffuse system including a number of nuclei such as the dorsal motor vagus, the nucleus tractus solitarius and adjacent tegmentum, and the lateral tegmentum itself. The nerve fibres of the LC travel virtually throughout the whole central nervous system, including to the spinal cord, brainstem, cerebellum, thalamus, hypothalamus, basal telencephalon and the entire cortex. The LT neurons are somewhat less widely distributed but even so go to the spinal cord, brainstem, hypothalamus and basal telencephalon.
The real peculiarity of these systems, however, relates to (a) their astonishingly frequent neuronal branching so that a single LT or LC nerve cell may have axons which connect with millions of other nerve cells, (b) the diverse endings of branches from a single nerve cell so that one branch may go to the cerebellum, for example, while another goes to the cortex, (c) their lack of clear cut synaptic end targets, with each nerve cell making diffuse contact with millions of other cells, and (d) their release of noradrenaline from sites along all the branches of the axons and not just from the synaptic endings. Smith and Sweet vividly state xe2x80x9csingle axons may traverse several regions of the brain, making no specific synaptic connections in any one area, but spraying transmitter (noradrenaline) over several areasxe2x80x9d.
The axons of the LT and LC systems are very widely distributed, making contact with motor nerve systems, sensory nerve systems, pain systems and autonomic systems such as those regulating cardiovascular and respiratory functions, bladder and bowel functions, reproductive functions and stress responses.
It is therefore apparent that the LT and LC systems are primarily noradrenergic systems which are able to influence almost all parts of the rest of the nervous system simultaneously. They are thus very strong candidates for the rapid and completely generalised relief of symptoms obtained in response to lofepramine and phenylalanine in the trial we have just completed in MS.
One of the well-known and difficult to explain observations in MS is that the symptoms seen in the patients are often poorly correlated with the precise positions of the lesions in the central nervous system which are identified by magnetic resonance imaging. Some of the symptoms can be directly related to the lesions, but many of the more generalised symptoms and especially the autonomic symptoms and the fatigue are difficult to relate precisely to the specific points of damage. This situation is similar to that seen in a substantial number of other central nervous system (CNS) disorders. In stroke, head injury, or any form of specific localised damage to the brain, it has long been recognised that there are two syndromes: the first is localised and clearly related to the specific nerve cells damaged by the lesion: the second is much more generalised and includes widespread impairment of neuronal function and very frequently includes substantial subjective fatigue (J L Ingles et al, Fatigue after stroke, Archives of Physical Medicine and Rehabilitation 1999; 80: 173-177. M G Boyeson et al. Sparing of motor function after cortical injury. Archives of Neurology 1994; 51: 405-413. D M Feeney et al, Noradrenergic pharmacotherapy, intracerebral infusion and adrenal transplantation promote functional recovery after cortical damage. Journal of Neural Transplantation and Plasticity 1993; 4: 199-213.). These syndromes are in many ways similar to those which occur in response to prolonged and uncontrollable stress, and also in the rather mysterious syndrome known as chronic fatigue syndrome which is closely related to fibromyalgia and which is associated with a number of other medical conditions including irritable bowel syndrome, and esophageal reflux and related disorders (J M Weiss et al, Behavioral depression produced by an uncontrollable stressor: relationship to norepinephrine, dopamine and serotonin levels in various regions of rat brain. Brain Research Reviews 1981; 3: 167-205. D J Clauw, Fibromyalgia: more than just a musculoskeletal disease. American Family Physician 1995; 52: 843-851).
In all of these conditions there is emerging evidence that the LC and LT systems are dysfunctional. The reasons for the dysfunction may be various. Because the LT and LC neurons go almost everywhere in the CNS, local damage to any part of the CNS will inevitably damage some axons from LT and LC nerve cells. That damage may then impair the function of the LC and LT themselves, or at the least impair the function of the other parts of the brain innervated by the damaged nerves. For example, many LC neurons have branches going to both the cerebellum and the cerebral cortex. A stroke or injury or an MS lesion affecting the cerebellum may thus alter cortical function and vice versa. Because the LT and LC neurons are an important part of the response to stress, sustained stress may lead to damage to or temporary or permanent exhaustion of the system. Viral infection may damage the LT and LC systems directly and this, with chronic stress, may be related to some chronic fatigue and fibromyalgia syndromes.
We propose that what lofepramine and phenylalanine are doing is activating the LC and LT system. This explains the effects on fatigue and on the whole range of symptoms in MS, involving motor, sensory, autonomic and higher cerebral functions. Activation of the LC and LT systems also explains the relief of pain of all types since the LC and LT noradrenergic systems are particularly involved in the regulation of chronic pain (eg C J Glynn et al, Role of spinal noradrenergic system in transmission of pain in patients with spinal cord injury, Lancet 1986; ii: 1249-51. S V R Reddy et al. Spinal cord pharmacology of adrenergic agonist-mediated antinociception. Journal of Pharmacology and Experimental Therapeutics 1980; 213: 525-533). This mechanism indicates that the treatment will also be effective in chronic stress, chronic fatigue, in fibromyalgia and related conditions, in irritable bowel syndrome and in relieving the general fatigue and neurological symptoms which are seen not just in MS but in almost any illness which involves any form of damage to the brain or spinal cord.
Case History No. 1
An example of the use of our invention was a woman of 41 years of age who had been incapacitated for about 12 years by chronic fatigue syndrome associated with fibromyalgia and irritable bowel syndrome. Until the age of 29 she had been a relatively normal woman, married with two children. However she then experienced what appeared to be a mild attack of influenza. Instead of recovering quickly as usual, she became depressed and fatigued and unable to carry out her normal parttime work and care for her children in the usual way. Everything became an effort and she could sustain only short bursts of activity before having to rest. She also developed multiple aches and pains throughout her body, characteristic of fibromyalgia, and an irritable bowel in which painful spasms alternated with constipation. She was given almost all conceivable treatments over the years, including many types of non-steroidal anti-inflammatory drugs, both tricyclic and serotonin reuptake inhibiting and noradrenaline reuptake inhibiting antidepressants, and even steroids. Some of these treatments produced transient effects but these never lasted. She was then given combined treatment with lofepramine, 70 mg bd and L-phenylalanine, 500 mg bd. Over a period of 2-3 weeks she experienced a considerable improvement in fatigue, in fibromyalgia and in her irritable bowel. She and her family expected these effects to wear off but instead they persisted. After six months she was essentially back to her normal self.
The implications are important in stroke and brain injury which have remained depressingly resistant to the development of pharmacological interventions. Many recent trials of a wide variety of agents have failed to alter the outcome in stroke or brain injury. However, there are animal studies which are encouraging in this respect. In essence, experimental stroke is associated with inhibition of LC function and the generalised loss of motor function appears to be caused by a failure of the noradrenergic system (Boyeson et al and Feeney et al, above). Treatment with noradrenaline facilitates recovery in animals from such lesions and there is preliminary evidence that there may be beneficial effects in humans (Feeney et al and Boyeson et al, above and also, D M Feeney, From laboratory to clinic: noradrenergic enhancement of physical therapy for stroke or trauma patients. Brain Plasticity: Advances in Neurology 1997; 73: 383-394. M G Boyeson and K A Krobert, Cerebellar norepinephrine infusions facilitate recovery after sensorimotor cortex injury, Brain Research Bulletin 1992; 29: 435-439. M G Boyeson and D M Feeney, Intraventricular norepinephrine facilitates motor recovery following sensorimotor cortex injury. Pharmacology Biochemistry and Behavior 1990; 35: 497-501). Of particular interest, desipramine, which is a metabolite of lofepramine, is able to enhance LC function and recovery of motor function after brain lesions: in contrast, drugs acting on the serotonin system have much smaller effects. (M G Boyeson and R L Harmon, Effects of trazodone and desipramine on motor recovery in brain-injured rats. American Journal of Physical Medicine and Rehabilitation 1993; 72: 286-293. R J Valentino et al, Antidepressant actions on brain noradrenergic neurons. Journal of Pharmacology and Experimental therapeutics 1990; 253: 833-840. M G Boyeson et al. Comparative effects of fluoxetine, amitriptyline and serotonin on functional motor recovery after sensorimotor cortex injury. American Journal of Physical Medicine and Rehabilitation 1994; 73: 76-83).
These effects of noradrenergic compounds alone are important but relatively modest. Our concept of combining a noradrenergic drug like lofepramine or desipramine, together with a noradrenaline precursor such as phenylalanine or tyrosine, is much more effective. This is surprising because many people have tried to enhance noradrenaline synthesis by administering the precursors phenylalanine or tyrosine but have failed. Many studies have shown that in normal humans and animals the administration of phenylalanine or tyrosine has little or no effect on the synthesis of noradrenaline (J D Milner and R J Wurtman, Catecholamine synthesis: physiological coupling to precursor supply. Biochemical Pharmacology 1986; 35: 875-881.) As the Milner and Wurtman paper demonstrates, there is a very good reason for this: the end product of the reaction sequence, noradrenaline, feeds back to strongly inhibit the activity of tyrosine hydroxylase, a key rate-limiting enzyme in the synthesis of noradrenaline. As a result, under normal circumstances providing phenylalanine or tyrosine will not influence noradrenaline production to any substantial degree. However, the situation changes when noradrenergic systems are activated or stressed. Under these circumstances tyrosine hydroxylase becomes phosphorylated and resistant to feedback inhibition by noradrenaline. As a result, in this situation the administration of phenylalanine or tyrosine does indeed activate noradrenaline synthesis (Milner and Wurtman). We propose that this is the explanation for the strong interaction we have observed between lofepramine and phenylalanine. In MS, the LC and LT noradrenergic systems are activated and stressed leading to loss of the feedback control of noradrenaline synthesis. As a result phenylalanine can enhance noradrenaline synthesis and strongly interact with lofepramine which inhibits uptake of released noradrenaline and so activates noradrenergic systems. We propose that a similar release of feedback inhibition occurs in any situation of brain injury, brain viral or other infections, including bacterial and prion infections, or chronic stress and that as a result the combination of a noradrenaline precursor and a noradrenergic drug will be beneficial in fatigue of any sort including fatigue after stroke, brain injury, migraine, MS, viral and other infections and chronic stress. We also suggest that the combination of a noradrenaline precursor and a noradrenergic drug will substantially enhance the rate and the degree of recovery from stroke or other brain damage.
Case History No.2
An example of this treatment is that of a 65 year old man who was apparently healthy experienced a small stroke which temporarily led to some loss of function in his left arm and left. The major part of the deficit recovered within a matter of days and within about six months there was no evidence of any residual specific sensorimotor problem apart from slight left arm weakness. However, over the month or so following the initial stroke the man became seriously depressed and fatigued, a state which he had not experienced before. He found it difficult to summon the energy to do anything. He also experienced the classic signs of depression with an unduly gloomy view of the impact of the stroke on his future life, an inability to take interest in things which had previously been a major part of his life, a strong sense of guilt about not spending enough time with his family prior to the stroke, and early morning wakening. He was treated first with imipramine,then with fluoxetine and then with lofepramine without much success. Eventually 500 mg of L-phenylalanine taken twice daily in the morning and evening was added to his 70 mg bd dose of lofepramine. Within a week he began to fell better and within four weeks he appeared to be largely recovered. His energy had returned, he enjoyed his family and his view of his future prospects improved considerably. In this patient antidepressants alone were clearly inadequate to relieve either his depression or his fatigue but the addition of phenylalanine to lofepramine allowed resolution of most of his post-stroke problems.
MECHANISM
Phenylalanine
↓
Tyrosine
↓ Tyrosine hydroxylase
3-dihydroxyphenylalanine
↓
Dopamine
↓
Noradrenaline
This unique mechanism thus activates the brain LC and LT systems particularly well when there is a need for activation as demonstrated by removal of the feedback inhibition of noradrenaline synthesis. In contrast, in normal situations when feedback inhibition is fully operative, the combination will not exert adverse effects because then the phenylalanine or tyrosine will not be able to enhance noradrenaline synthesis. Because of a failure to understand this unique mechanism, although it has been proposed that phenylalanine and tyrosine may be used to treat depression, it has never been proposed that phenylalanine or tyrosine should be specifically combined with drugs which have specific effects on noradrenaline reuptake such as lofepramine, desipramine and reboxetine. Such combinations will be particularly effective in treating depression, especially when that depression is associated with chronic stress and abnormal function of the LC and LT systems.
The drugs which are most effective in the combination are those which have a large effect on the reuptake of noradrenaline at nerve endings and which at the same time have little effect or a much smaller effect on the uptake of serotonin. This can be demonstrated by studying the actions of the drugs on systems such as rat brain synaptosomes (C Bolden-Watson and E. Richelson, Blockade by newly developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sciences 1993; 52: 1023-1029. C Sanchez and J Hyttel, Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. Cellular and Molecular Neurobiology 1999; 19: 467-489). The most effective compounds will have a large effect on noradrenaline which is at the same time at least ten times larger than their effect on serotonin. Drugs which fall into this class include lofepramine, desipramine (also known as desmethylimipramine), nortriptyline, tomoxetine, maprotiline, oxaprotiline, levoprotiline, viloxazine and reboxetine. A second class of drugs which will have effects but which will be less active in selectively activating the LC and LT systems are the drugs which have combined actions on noradrenaline and serotonin reuptake or on noradrenaline and dopamine uptake. These drugs include venlafaxine, duloxetine, buproprion and milnacipran.
The key precursors which will be effective in a way which is appropriate to the state of the noradrenergic systems are the amino acids on the noradrenaline synthesis pathway which are before the rate-limiting regulated step of tyrosine hydroxylase. This means L-phenylalanine and L-tyrosine. The D forms of these amino acids may also have some activity since there is some recent evidence that they can be converted into the L-forms which are the specific noradrenaline precursors by enzymes which are present in the brain.
The noradrenergic drug and the precursor may be formulated together in the same dosage form or may be presented in separate dosage forms but in the same pack using methods familiar to those skilled in the art. The dosage forms may include tablets, coated tablets, hard or soft gelatin capsules, liquids, gels, creams, suppositories, pessaries and parenteral formulations.
Because there is recent evidence that many people with chronic depression, chronic fatigue or chronic stress, or with brain damage of any sort may have inadequate levels of essential nutrients, the combinations may also be formulated with appropriate essential nutrients. Nutrients which are particularly important in brain function include folic acid, vitamin B12, vitamin B6 and tetrahydrobiopterin and related compounds.

Treatment of fatigue, head injury and stroke

Abstract: The noradrenergic drug may be selected from lofepramine, desipramine or reboxetine. The selective inhibitor may be a combined inhibitor of both noradrenaline and serotonin reuptake such as venlafaxine, duloxetine or milnacipran, or an inhibitor of both noradrenaline and dopamine reuptake such as bupropion.


A music based video game in which a game player's singing performance is digitally sampled while the player performs a free-form vocal over a prerecorded musical composition. Aspects of the game player's free-form vocal performance are compared with predetermined criteria. For example, the vocal performance may be compared with tempo and key information to generate performance evaluation data. The performance evaluation data may be used to present performance feedback to the game player while the game player is singing.

The present invention relates generally to video games, and more particularly to a music based video game including vocals.
Video games provide a source of entertainment for many. Video games provide game players with different interactive challenges, many of which simulate interesting situations and scenarios that game players may not typically experience. Music video games, for example, often provide game players with the opportunity to participate in a live musical performance, and to be scored or graded on their performance.
In some music video games, a game player is presented lyrics to sing, along with possibly an indication of a pitch at which to sing the lyrics, with the pitch potentially being different for different portions of the lyrics. Along with the lyrics, the game player may also be presented with instrumental audio to accompany the lyrics. The game player's singing of the lyrics is generally received by a microphone and converted to electrical signals for processing by a game console.
However, merely singing predetermined lyrics of a song may not fully simulate a musical experience, for example, the creativity and originality which may be part of the musical experience.

This patent is subject to a terminal disclaimer.

Scoring of free-form vocals for video game


A conductive filler in the form of non-conductive particles coated with plural layers of metal plating is provided wherein the lower layer is of copper or copper alloy plating, and the uppermost layer is of gold plating. The conductive powder has a high conductivity, improved durability, especially oxidation resistance, and a relatively low specific gravity.

This invention relates to a conductive filler which is blended in rubber and resin compositions for imparting electrical conductivity.
It is known in the art that molded rubber parts as a whole can be made electrically conductive by blending a powder of conductive particles in rubber compositions, typically silicone rubber compositions and molding. Such conductive rubber parts are used in antistatic applications. The traditional conductive powder is carbon black. In recent years, conductive molded rubber parts are sometimes used for electrical connection on circuit boards in electronic equipment. In this application, high conductivity is required from the antistatic standpoint. More conductive additives, typically metal powders are then used as the conductive agent. The metal powders, however, have the problems that they are susceptible to ignition during handling and are readily oxidized to detract from conductivity, and most of them have a high specific gravity.
To overcome these shortcomings, it was recently developed to metallize core particles of resin or ceramic material. A typical powder takes the form of core particles which are coated with nickel by electroless plating and further on the outermost surface with gold by displacement plating. The coating of gold on the outermost surface cooperates with the underlying nickel to provide conductivity and oxidation resistance. The specific gravity is low since the metallization is limited to the surface. The cost is acceptable because of the thin buildup of gold.
Nevertheless, the conductivity of nickel/gold plated particles is insufficient in some applications or purposes. This is partly because the underlying nickel layer is usually a nickel-phosphorus alloy which has a high resistivity. It is thus desired to improve the conductivity of conductive particles (resulting from electroless plating) without a significant increase of material cost.
An object of the invention is to provide a conductive filler having a high conductivity, improved durability, especially oxidation resistance, and a relatively low specific gravity.
According to the invention, a layer of copper or copper alloy plating is formed on surfaces of non-conductive particles, a layer of nickel or nickel alloy plating is optionally formed thereon, and a layer of gold plating is formed as the uppermost layer. The resulting conductive particulate filler has a low resistivity, improved durability, and a lower specific gravity than wholly metal particles.
The electrically conductive filler of the invention is in the form of non-conductive particles or core particles which are coated on their surface with plural layers of metal plating. A lower layer of metal plating is formed of copper or copper alloy plating, and the uppermost layer of metal plating is formed of gold plating. Preferably a layer of nickel or nickel alloy plating intervenes between the lower layer of copper or copper alloy plating and the uppermost layer of gold plating. The intermediate layer prevents the gold plating layer from diffusing into the copper or copper alloy plating layer to form an alloy when heated.
The core material used herein to construct the non-conductive particles to be coated with metallizing layers is selected from a wide variety of materials including oxides such as silicon oxide, aluminum oxide, titanium oxide, zirconia, rare earth oxides, and yttrium oxide, naturally occurring compounds such as mica and diatomaceous earth, glasses such as sodium silicate glass, resins such as polyurethane, polycarbonate, phenolic resin, polyamide, polyimide, silicone resin, epoxy resin and polystyrene, and other electrically insulating materials. In a typical application, 100 parts by weight of a rubber composition, typically a silicone rubber composition or a resin composition, typically an epoxy resin composition is loaded with about 80 to 500 parts by weight of the inventive conductive filler, and the blend is milled prior to use. In order to prevent the plating from being stripped from the core particles during the milling step, the core particles should preferably have a certain rigidity. In this sense, an inorganic core material, especially silicon oxide is preferred. Core particles in excess of 150 xcexcm should desirably be excluded because they are likely to separate from the rubber or resin matrix even after milling. More desirably core particles in excess of 100 xcexcm are excluded. It is preferable to use core particles having a diameter of up to 150 xcexcm, more preferably up to 100 xcexcm, and most preferably 5 to 50 xcexcm. A particle shape more approximate to sphere is generally preferable. Particles of nearly spherical shape are most preferred since they are uniformly dispersed during milling.
Formed on surfaces of core particles is a layer of copper or copper alloy plating. The layer of copper or copper alloy plating is preferably formed by electroless or chemical plating.
Since the core particles are of insulating material, a catalyst must be applied thereto for initiating electroless plating. Catalyzing is carried out by prior art well-known methods, for example, a method of immersing in a tin (II) chloride solution and then in a palladium (II) chloride solution, and a method of immersing in a mixed solution of tin chloride and palladium chloride. To facilitate the application of catalyst, the core particles can be subjected to suitable treatments, for example, brief etching with suitable chemical agents, such as strong alkalis, mineral acids or chromic acid, treatment with chemical agents possessing both a functional group having affinity to the catalytic metal and a functional group having affinity to the core particles, such as silane coupling agents having an amino group, and mechanical treatments such as plasma treatment.
The electroless copper plating solution used for forming the copper or copper alloy plating layer may be any of well-known compositions, and commercially available compositions are acceptable. The plating conditions may be well-known ones. The electroless copper plating solution generally uses formaldehyde as a reducing agent although the use of hypophosphites and borides as the reducing agent is acceptable.
The copper or copper alloy plating layer is preferably formed of substantially pure copper. By the term xe2x80x9csubstantially pure,xe2x80x9d it is meant that copper may contain a minor amount of other elements as impurities. Preferably the copper or copper alloy plating layer has a thickness of 50 to 500 nm, and more preferably 75 to 400 nm. With a thickness below 50 nm, the metallized particle powder may become less conductive. A thickness in excess of 500 nm may not be cost effective since it brings about little further advantages and adds to the expense of metal material.
On core particles of a particular type, the adhesion of electroless copper plating is weak, as compared with electroless nickel plating, so that it may be strippable. In such a situation, another electroless plating layer other than copper or copper alloy may be formed as a primer layer underlying the copper or copper alloy plating layer.
The conductive filler of the invention is characterized in that a layer of copper or copper alloy plating is formed as the lower layer of metal plating (as mentioned just above) and a layer of gold plating is formed as the uppermost layer. To augment the adhesion of the gold plating layer to the copper or copper alloy plating layer, the copper or copper alloy plating layer is preferably surface processed. The surface processing may be done by any of plating treatment, blasting and plasma treatment although it is preferred to form an intermediate plating layer because replacement gold plating on copper proceeds at a very slow reaction rate and often ceases to proceed. In the event of copper being in direct contact with gold, there is a likelihood of interdiffusion between copper and gold to form an alloy when heat is applied during the step of molding the rubber or resin compound after milling. The diffusion and alloying can adversely affect the desired oxidation resistance. To prevent the undesired interdiffusion as well, it is recommended that a layer of nickel or nickel alloy plating intervene as an intermediate layer.
As the intermediate layer, a layer of nickel or nickel base alloy such as pure nickel, nickel-boron, nickel-phosphorus or nickel-boron-phosphorus is formed. Of these, a nickel-phosphorus alloy (phosphorus content 2 to 14% by weight) is most preferable because of ease of electroless nickel plating itself and uniform progress of subsequent replacement gold plating. The nickel salt for the electroless nickel plating may be any of well-known ones such as nickel sulfate, nickel chloride and nickel acetate, and used in a concentration of 0.01 to 0.5 mol/l of the plating bath. Too high a nickel concentration may allow a hydroxide to form due to pH changes and changes in the concentration of complexing agent, leading to a shortened bath life. At too low a nickel concentration, a more amount of solution must be replenished to bring about a substantial change of the plating bath volume. The phosphorus reducing agent used is hypophosphorous acid or an alkali metal or ammonium salt thereof, preferably in an amount of 0.1 to 5 mol per mol of the nickel salt.
Preferably the intermediate layer has a thickness of 15 to 200 nm, and more preferably 25 to 150 nm. With a thickness below 15 nm, the effects of the intermediate layer to facilitate replacement gold plating and prevent interdiffusion between gold and copper may become insufficient. Since the intermediate layer has little contribution to conductivity, a thickness in excess of 200 nm may merely increase the specific gravity of the power and the raw material cost.
The uppermost layer of gold plating should preferably have a thickness of at least 7 nm when the size and shape of particles, the gold content by chemical analysis, the constituents of the remaining plating layers and the specific gravity of core particles are taken into account. Below 7 nm, a continuous and dense gold film enough to provide oxidation resistance may not be obtained. The more preferred thickness is from 10 nm to 30 nm. A gold layer of more than 30 nm results in an increased specific gravity and an increased cost. It is not critical how to form the gold layer. Either electroless plating or electroplating may be used although the formation of the gold layer by replacement gold plating is preferred.
With respect to replacement gold plating, since the object to be plated is a powder rather than a large size molded part, it is preferred from the safety and hygienic standpoint to use gold (I) sulfite complex ions instead of gold cyanide complex ions which are customarily used in the prior art. The solvent for the gold salt is selected from water, ketones, and alcohols. The gold salt is preferably added in a concentration of 0.01 to 20% by weight.
It is not critical how to form the respective plating layers. The plating method is selected from several methods, for example, a method of premixing a metal ion, reducing agent, complexing agent, buffer agent, etc. to form a plating solution, adjusting the pH and temperature thereof, and directly admitting a powder into the plating solution; a method of admitting a slurry of a powder in water into the plating solution; and a method of dispersing a powder in a solution containing some plating solution components, and adding the remaining plating solution components thereto. The composition of plating solution may be selected from conventional bath compositions known for electroless nickel alloy plating, electroless copper plating and replacement gold plating.
The thus obtained conductive filler preferably has a resistivity of up to 15 mxcexa9-cm, more preferably 0.1 to 10 mxcexa9-cm, and most preferably 0.1 to 5 mxcexa9-cm. For the measurement of resistivity (or conductivity), specifically the measurement of resistance of a sample having a standardized volume and shape, constant current potentiometric measurement is conducted by the so-called four terminal method. Since the resistance to be measured is very low, a contact resistance and a thermally induced potential difference between contacts can be non-negligible error factors. It is thus desirable to minimize such error factors and compensate therefor by alternately inverting the current flow.
The conductive filler is advantageously used in various rubber and resin compositions, typically silicone rubber compositions and epoxy resin compositions.


The present invention is directed to an improved golf ball comprising at least one interior layer and/or a core comprising a silicone material. It is preferred to also utilize a multi-layer cover in conjunction with the silicone material(s). The resulting multi-layered golf ball of the present invention provides for enhanced distance without sacrificing playability or durability when compared to known multi-layer golf balls.

A number of two-piece (a solid resilient center or core with a molded cover) and three-piece (a liquid or solid center, elastomeric winding about the center, and a molded cover) golf balls have been produced by the present inventors and others. The different types of materials utilized to formulate the cores, covers, etc. of these balls dramatically alters the balls' overall characteristics. In addition, multi-layered covers containing one or more ionomer resins have also been formulated in an attempt to produce a golf ball having the overall distance, playability and durability characteristics desired.
Despite the great numbers of different materials and combinations of materials utilized in prior art golf balls, there still remains a need for an improved golf ball exhibiting superior properties.
The present invention is directed to new golf ball compositions, preferably utilized in conjunction with multi-layer covers, which provide for enhanced coefficient of restitution (i.e, enhanced resilience or carrying distance) and/or durability properties when compared to the balls found in the prior art. As such, the playability characteristics (i.e., "feel", "click", "spin", etc.) are not diminished.
These and other objects and features of the invention will be apparent from the following summary and description of the invention, the drawings and from the claims.


A gaming machine having a display and a game controller arranged to control images displayed on the display. The game controller is arranged to play a game wherein at least one random event is caused to be displayed on the display. If a predefined winning event occurs, the machine awards a prize. The display displays a spinning reel game, each reel of which carries a plurality of symbols, at least one of which is a mystery symbol, the identity of which, at least initially, is hidden. When the mystery symbol appears on the display in a predetermined position, it is caused, by the controller and subject to predetermined conditions, to move to a different position whereafter the identity of the mystery symbol is revealed to be another symbol which is a symbol of a set of symbols of the game.

This application claims priority to the Australian application PR3011 filed Feb. 9, 2001 entitled xe2x80x9cGAMING MACHINE WITH MYSTERY NUDGE SYMBOLxe2x80x9d.
This invention relates to a gaming machine. More particularly, the invention relates to a gaming machine and to an improvement to a game played on such a gaming machine.
Players who regularly play gaming machines quickly tire of particular games and therefore it is necessary for manufacturers of these machines to develop innovative game features which add interest to the games. In so doing, it is hoped to keep players amused and therefore willing to continue playing the game as well as to attract new players.
Also, with the growth that has occurred in the gaming machine market, there is intense competition between manufacturers to supply various existing and new venues. When selecting a supplier of gaming machines, the operator of a venue will often pay close attention to the popularity of various games with their patrons. Therefore, gaming machine manufacturers are keen to devise games which are popular with the players as a mechanism for improving sales, retaining customers and attracting new customers.
According to the invention, there is provided a gaming machine having a display means and a game control means arranged to control images displayed on the display means, the game control means being arranged to play a game wherein at least one random event is caused to be displayed on the display means and, if a predefined winning event occurs, the machine awards a prize, the gaming machine being characterized in that the display means displays a spinning reel game, each reel of which carries a plurality of symbols, at least one of which is a mystery symbol, the identity of which, at least initially, is hidden and further being characterized in that, when said at least one mystery symbol appears on the display means in a predetermined position, it is caused, by the control means and subject to predetermined conditions, to move to a different position whereafter the identity of the mystery symbol is revealed to be another symbol which is a symbol of a set of symbols of the game.
The at least one mystery symbol may, initially, be covered by a mystery-signifying representation such as a question mark representation or a representation of a pair of binoculars. Once the at least one mystery symbol has been moved, or nudged, to said different position, the mystery-signifying representation may be removed to reveal the other symbol.
Instead, once the at least one mystery symbol has been moved, or nudged, to its final position, the at least one mystery symbol may be transformed into the other symbol. The transformation from the at least one mystery symbol to the other symbol may be effected by the at least one mystery symbol simply being replaced by the other symbol. Instead, the transformation may be by means of an animation sequence from the at least one mystery symbol to said other symbol.
Those skilled in the art will appreciate that, in a spinning reel-type game, there are paylines on which, if a prize-winning combination of symbols appears when the reels stop spinning and the payline is active, a prize is awarded. An xe2x80x9cactivexe2x80x9d payline is one on which a player has made a wager. Each reel has a reel strip associated with it with each position on the reel strip being mapped to a predetermined position on its associated reel, at least one position on the reel strip being designated as a mystery symbol position.
The other symbol from the set of symbols of the game at the, or each, designated position may be predetermined. Instead, the at least one mystery symbol may, initially, be unidentified in the sense of not having any symbol from the set of symbols associated with it and only when the mystery symbol reaches its rest position is it converted by the control means into one of the other symbols.
The other symbol may be selected from one of (a) the entire set of symbols that is available on the reel strips and (b) a subset of the symbols. The subset of symbols is a set of special symbols such as, for example, a wild symbol, a scatter symbol, a top-paying symbol, a feature trigger symbol, or the like.
A prize may be paid for any prize-winning combination of symbols both before and after the at least one mystery symbol has been moved, or nudged, to its final position. Instead, the predetermined conditions may govern that the at least one mystery symbol moves, or is nudged, on to an active payline adjacent which the at least one mystery symbol is initially positioned only if it improves the prize applicable resulting from that combination of symbols which includes the other symbol revealed from the at least one mystery symbol. Still further, an initial prize may be paid and a further prize may be paid after the at least one mystery symbol has been moved and the other symbol revealed only if, as result of the move, the further prize is larger. Yet further, if an initial prize is payable before the at least one mystery symbol has been moved and the other symbol revealed and a further prize is payable after the at least one mystery symbol has been moved and the other symbol revealed, only the higher of the two prizes may be paid.
The predetermined conditions may further govern that, if the mystery symbol appears initially on an active payline of the game, no movement of the mystery symbol occurs.

Gaming machine with mystery nudge symbol

Aristocrat Technologies Australia PTY LTD


Torch for scuba diving comprising a body housing the batteries, a lamp and its electric circuitry, and a handle extending from said body. A box housing a display is mounted on the torch handle, which display is connected to a microcomputer coupled to the electric system of the torch and displaying both the torch duration in minutes and the indication of the lighting intensity selected by the user. A push-button turns on and regulates the lighting power of the torch. The box is pivoted on the end of the torch handle, and can be turned over from an operating position to a rest position in which the display is protected from possible shocks. The support pins of the box are preferably coupled to a general switch, so that by turning the box the torch is turned off.

The present invention relates to torches for scuba diving. The torches used at present are equipped with rechargeable batteries al ways with high powers, even in the range of 100 W.
These new-generation torches allow the user both to vary the light power of the torch, so as to suit it to the existing requirements, and to have an idea on the remaining duration of the torch, which, as far as highly sophisticated torches are concerned, can be carried out by means of several leds, so that the turning off of the leds one after the other indicates a decrease in the charge. This is mere theory, but as far as practice is concerned this indication is rather approximate and the user never knows the actual remaining duration of his/her torch.
Moreover, for building reasons said leds are always located on the back side of the cylindrical body of the torches, because this is the best portion where the led can be installed. However, when the user keeps the torch in his/her hand, he/she cannot see directly that portion and must turn the torch in order to see the bottom of said torch, which is not always easy to do.
The present invention aims at avoiding said and other disadvantages of the torches available at present.
According to a main feature of the invention, a display connected to a microcomputer is mounted onto the torch handle, said display being coupled to the electric system of the torch and displaying a whole series of information. For instance, it displays the present duration in minutes, and said display is constantly updated even in relation to the change in light intensity made by the user.
According to a further feature of the invention, a push-button for the regulation of light power is provided on the torch handle, and the set regulation appears on the display. Therefore, the user can always check on the torch display both the remaining duration of his/her torch and the light power set by means of said push button, as well as additional information, such as the indication that the torch batteries are under charge, etc.
According to another feature of the torch according to the invention, the display box, instead of being fixed onto the torch handle, is preferably supported on the end of said handle by means of two pins equipped with a snap regulation with an elastic coupling allowing its rotation of 180xc2x0 around one of its end cross axis, or alternatively said box can be supported by means of a middle pin, so that it can be turned of 180xc2x0 around its longitudinal axis, said pin or pins being coupled to the electric system of the torch, so that when the display is turned from a position which will be defined as active to a passive or rest position, the electric circuit between the torch batteries and the lamps is opened. Said features shows the following advantages:
(1) when the torch is not used the display is not endangered, since it is folded under the handle or turned towards the torch sheath, so that it is protected against possible shocks;
(2) said operation embodies a safety measure against the unintentional turning on of the torch, since the contact is disconnected and there is no danger that the torch loses its charge unintentionally.