Antibiotic 5-substituted-3-(2-aminoethylthio)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3 .2.0]hept-2-ene-2-carboxylic acids (I) are disclosed: ##STR1## wherein R is alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl or heteroaryl.

This invention relates to antibiotic 5-substituted-3-(2-aminoethylthio)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo(3 .2.0)hept-2-ene-2-carboxylic acids (I): ##STR2## Wherein R is substituted or unsubstituted: alkyl having 1-6 carbon atoms, trifluoromethyl, phenyl, phenylalkyl having 7-12 carbon atoms, cycloalkyl having 3-6 carbon atoms, cycloalkylalkyl having 3-6 ring carbon atoms, and 1-6 carbon atoms in the alkyl moiety, and heteroaryl having 4-6 atoms in the ring, one or more of which is selected from O, N or S; and wherein the substituent or substituents on the foregoing radicals are selected from: OH, COOH, Cl, F, Br, NH.sub.2, alkyl and alkoxyl having 1-3 carbon atoms.
This invention also relates to the pharmaceutically acceptable salt and ester derivatives of I; pharmaceutical compositions comprising I and such derivatives; and to methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.
There is a continuing need for new antibiotics, for unfortunately there is no static effectiveness of a given antibiotic because continued wide scale usage of any such antibiotic selectively gives rise to resistant strains of pathogens. In addition, the known antibiotics suffer from the disadvantage of being effective only against certain types of microorganisms. Accordingly, the search for new antibiotics continues.
Unexpectedly, it has been found that the compounds of the present invention are broad spectrum antibiotics, which are useful in animal and human therapy and in inanimate systems.
Thus, it is an object of the present invention to provide a novel class of antibiotics which are 5-substituted analogues of the antibiotic thienamycin. These antibiotics are active against a broad range of pathogens which representatively include both gram positive bacteria such as S. aureus, Strep. pyogenes and B. subtilis and gram negative bacteria such as E. coli, Proteus morganii, Serratia, Pseudomonas and Klebsiella. Further objects of this invention are to provide chemical processes for the preparation of such antibiotics and their non-toxic pharmaceutically acceptable salts; pharmaceutical compositions comprising such antibiotics; and to provide methods of treatment comprising administering such antibiotics and compositions when an antibiotic effect is indicated.
The compounds of the present invention (I, above) are conveniently prepared by the following scheme: ##STR3##
In words relative to the above diagram, the 4-substituted-4-(2-substituted-vinyl)azetidine-2-one, 4, starting material is prepared by reacting an R.sup.1 -oxy-3-substituted-butadiene, 1, with chlorosulfonylisocyanate 2. The reaction is conducted without solvent or may be run in solvent such as diethyl ether, ethyl acetate, chloroform, methylene chloride, or the like, at a temperature of from -78.degree. C. to 25.degree. C. for from a few minutes to 1 hour to provide 3. The radical R.sup.1 is an easily removable acyl blocking group such as an alkanoyl or aralkanoyl which bears no functional group or groups which might interfere with the desired course of reaction (1+2.fwdarw.3.fwdarw.4). Intermediate species 3 is converted to the sulfinamide by reduction which is then hydrolyzed to 4 at pH 6-8. Typically the reaction solution comprising 3 is contacted (5-30 minutes) with an aqueous solution (at 0.degree.-25.degree. C.) of a reducing agent such as sodium sulfite, thiophenol, or the like, at pH 6-8 to provide 4.
The reaction 4.fwdarw.5 is a reduction, and is preferably achieved by hydrogenation in a solvent such as ethyl acetate ether, dioxane, tetrahydrofuran (THF), ethanol or the like at 0.degree. to 25.degree. C. for from 5 minutes to 2 hours under 1 to 10 atmospheres of hydrogen in the presence of a hydrogenation catalyst such as platinum metal or oxide thereof such as 10% Pd/C or the like.
The de-blocking reaction 5.fwdarw.6 is usually desirable when R.sup.1 is acyl to permit the later alkylation, 7.fwdarw.8. The preferred de-blocking procedure is by alcoholysis wherein the solvent is a lower alkanol such as methanol, ethanol or the like in the presence of the corresponding alkali metal alkoxide, such as sodium methoxide. Typically, the reaction is conducted for from 5 minutes to 1 hour at a temperature of from -10.degree. to 25.degree. C.
Blocking groups R.sup.3 and R.sup.2 are established (6.fwdarw.7) to provide a suitably protected species for alkylation (7.fwdarw.8). There is no criticality in the choice of blocking groups, provided only that they do not interfere with the intended alkylation. R.sup.3 may be hydrogen, a triorganosilyl group such as trimethylsilyl or the like, or a cyclic ether such as 2-tetrahydropyranyl; R.sup.2 may also be a cyclic ether such as 2-tetrahydropyranyl; alternatively R.sup.3 and R.sup.2 may be joined together to form protected species such as 7a: ##STR4## For example, species such as 7a are conveniently prepared by treating 6 with 2,2-dimethoxypropane in the presence of a catalyst such as boron trifluoride etherate, toluene sulphonic acid, or the like in a solvent such as methylene chloride, ether, chloroform, dioxane or the like at a temperature of from -10.degree. C. to 35.degree. C. for from a few minutes to 1 hour.
The alkylation (7.fwdarw.8) is preferably conducted by treating 7 with a strong base such as lithium diisopropylamide, sodium amide, potassium hydride or the like in a solvent such as THF, glyme, ether, dimethylformamide (DMF), dimethylsulfoxide (DMSO) or the like at a temperature of from -78.degree. C. to 0.degree. C. The resulting anion is then treated with excess acetaldehyde to provide 8.
The reaction 8.fwdarw.9 establishes the blocking group R.sup.4 and is typically accomplished by treating 8 with a base such as an alkali metal hydroxide, lithium diisopropylamide,4-dimethylaminopyridine, or n-butyllithium in a solvent such as ether, THF, dioxane, DMF, DMSO or the like, followed by treatment with an acyl halide of choice such as alkanoyl, aralkanoyl or nuclear substituted aralkanoyl, or alkyl, aryl or aralkyl, substituted aralkyl or substituted aryl haloformate such as p-nitrobenzylchloroformate, o-nitrobenzylchloroformate, or the like, at a temperature of from -78.degree. C. to 25.degree. C. for from 1-24 hours.
The de-blocking reaction 9.fwdarw.10 is typically conducted by acid hydrolysis such as aqueous acetic acid at a temperature of from 25.degree. C. to 75.degree. C. for from 5 minutes to 3 hours.
The aldehyde intermediate 11 is prepared by treating 10 with an oxidizing agent such as CrO.sub.3.2(pyridine) in CH.sub.3 CN, 1:1 mixture of dimethylsulfoxide and acetic anhydride, cyclohexylcarbodiimide in DMSO or the like at a temperature of from 0.degree.-25.degree. C. for from 5 minutes to 1 hour. The resulting species 11 in a solvent such as acetonitrile, methylene chloride, chloroform or the like at a temperature of from -10.degree. to 25.degree. C. is treated with an excess of N-blocked cysteamine, HSCH.sub.2 --CH.sub.2 NHR.sup.5, in the presence of an acid catalyst such as boron trifluoride etherate, toluene sulphonic acid or the like to provide 12. Typically, the reaction requires from 1 to 60 minutes.
There is no criticality as to the identity of the N-protecting group, R.sup.5, or the cysteamine reagent and suitable groups are p-nitrobenzyloxycarbonyl, o-nitrobenzyloxycarbonyl, t-butyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, phthaloyl, or the like.
The vinyl sulphide 14 is obtained via intermediate 13 by treating 12 with a halogen such as chlorine or bromine (X=Cl or Br) in a solvent such as ether, methylene chloride, tetrahydrofuran, glyme or the like at a temperature of from -78.degree. to 30.degree. C. for from 1 to 30 minutes, followed immediately by treating with an olefin such as cyclohexene, isobutylene, or the like in the presence of base such as triethylamine, DBU, sodium hydride, or the like in a solvent such as DMF, glyme, THF, HMPA. The solution is held at -20.degree. to 25.degree. C. for from 1 to 8 hours to yield 14.
The vinyl sulphide species 14 is reacted with a diester of oxomalonic acid (or its monohydrate) to provide 15. There is no criticality as to the identity of the ester moiety, R.sup.6, of the oxomalonic acid. R.sup.6 may be a conventional, easily removable blocking group or it may be a pharmaceutically acceptable ester moiety. Suitable ester radicals R.sup.6 are p-nitrobenzyl, benzyl, o-nitrobenzyl, t-butyl, 2,2,2-trichloroethyl. The reaction 14.fwdarw.15 is typically conducted in a high boiling organic solvent such as benzene, toluene, cyclohexane, halo aromatic or the like at a temperature of from about 50.degree. C. to reflux for from 0.5 to 6 hours.
The halogenation reaction 15.fwdarw.16 is typically conducted in a solvent such as THF, glyme, ether, methylene chloride, chloroform or the like in the presence of a halogenating agent such as thionyl chloride, phosphorous pentachloride or the like in the presence of base such as pyridine at a temperature of from -20.degree. to 25.degree. C. for from 5 minutes to 3 hours. The selective reduction of 15.fwdarw.17 via 16 is completed by treating 16 with tributylphosphine, triphenylphosphine or the like in aqueous DMF or similar aqueous systems involving dioxane, THF, glyme, DMSO, or acetone in the presence of K.sub.2 HPO.sub.4 at a temperature of from about 0.degree.-50.degree. C. for from 10 minutes to 5 hours.
Species 17 is halogenated by the previous procedure (12.fwdarw.13), but omitting the addition of the cyclohexene or other olefin, to provide the dihalo species 18. Species 18 is treated with a base such as triethylamine, sodium hydride or potassium hydride in a solvent such as DMF, acetonitrile, methylene chloride, chloroform, glyme or the like at a temperature of from about -78.degree. to 25.degree. C. for 1 to 5 hours to provide 19. Species 19 is converted to 20 on treatment with a strong base such as 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU), 1,5-diazabicyclo[3.4.0]non-5-ene(DBN), or the like in a solvent such as DMSO, acetone, chloroform, DMF, THF, glyme or the like or on treatment with AgF in pyridine at a temperature of from 0.degree.-40.degree. C. for from 1/4 to 24 hours. The reaction 20.fwdarw.21 is conducted by treating 20 with an aromatic base such as pyridine, s-collidine or lutidine, in the presence of a displacing agent such as lithium iodide, lithium bromide, sodium bromide, or the like at a temperature of from about 80.degree.-150.degree. C. for from 15 minutes to 2 hours. An aqueous work up of the resulting reaction mixture provides 21. Isomerization of the double bond 21.fwdarw.22 is accomplished by treating 21 in a solvent such as DMF, DMSO, ethyl ether, THF, glyme, methylene chloride with a strong base such as diisopropylamine, DBU, DBN, or the like at a temperature of from 0.degree. to about 25.degree. C. for from a few minutes to 2 hours or until equilibrium has been established as determined by examination of sample aliquots by ultraviolet absorption or by thin layer chromatography. The final reaction 22.fwdarw.I (by hydrogenolysis of the blocking groups) is accomplished by treating 22 in a solvent such as dioxane, ethanol, THF or the like or an aqueous mixture thereof in the presence of a Platinum metal catalyst such as Pd/C under a hydrogen pressure of from 1-4 atmospheres for from 0.5 to 8 hours at a temperature of from about 0.degree.-25.degree. C.
The above-described total synthesis may also advantageously start with a 4-substituted-4-vinyl azetidinone (23), below rather than the enol acylate azetidinone (4, above). The following scheme illustrates this 4-substituted-4-vinyl-azetidinone embodiment of the present invention; notice that it ties into the above scheme at species 14. ##STR5##
In words relative to the above reaction diagram, the 4-substituted-4-vinyl azetidinone 23 is silylated to provide the N-silyl species 24. The groups R' on the silyl radical are loweralkyl having from 1-6 carbon atoms especially preferred triorganosilyl groups are trimethylsilyl and t-butyl-dimethylsilyl. Typically the silylation (23-24) is achieved by treating 23 in a solvent such as DMF, DMSO, HMPA or the like with the silylating agent of choice, dimethyl t-butylsilyl chloride, and a base such as Et.sub.3 N, pyridine, N,N-dimethylaniline and the like at a temperature of from -10.degree. to 30.degree. C. for from 1 to 8 hours. Species 24 is alkylated to form 25 by treatment with acetaldehyde in the presence of base. This reaction 24.fwdarw.25 is conducted exactly as described above for the alkylation 7.fwdarw.8. The O-protecting group is established in the reaction 25.fwdarw.26. The protecting group R.sup.4 is as previously defined and the reaction 25.fwdarw.26 is exactly analogous to the above described reaction 8.fwdarw.9. The removal of the N-triorganosilyl group is accomplished in reaction 26.fwdarw.27 by mild acid catalyzed solvolysis. The halo sulfide species 28 is obtained from 27 by treating 27 in a solvent such as methylene chloride, THF, glyme, or the like with the reagent XSCH.sub.2 CH.sub.2 NHR.sup.5 wherein R.sup.5 has previously been defined and X is halogen such as chloro or bromo at a temperature of from -50.degree. C. to 50.degree. C. for from 1 to 16 hours. The final sulfide intermediate 14, which is common to the above illustrated scheme of total synthesis is obtained from 28 by elimination of HX on treatment of 28 with a base such as 1,5-diazabicyclo (5.4.0)undec-5-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene, (DBN), 1,4-diazabicyclo[2.2.2]octane, (DABCO), or silver fluoride in a solvent such as DMSO, pyridine, DMF, HMPA or the like at a temperature of from -20.degree. to 50.degree. C. for from 1/4 to 16 hours.
The products of this invention (I) form a wide variety of pharmacologically acceptable salts with inorganic and organic bases; these include, for example, metal salts derived from alkali or alkaline earth metal hydroxides, carbonates or bicarbonates and salts derived from primary, secondary or tertiary amines such as monoalkylamines, dialkylamines, trialkylamines, loweralkanolamines, di-loweralkanolamines, lower alkylenediamines, N,N-diaralkyl lower alkylenediamines, aralkylamines, amino substituted lower alkanols, N,N-di-lower alkylamino substituted lower alkanols, amino-, polyamino- and guanidino-substituted lower alkanoic acids and nitrogen-containing heterocyclic amines. Representative examples include salts derived from sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium hydroxide, calcium carbonate, trimethylamine, triethylamine, piperidine, morpholine, quinine, lysine, protamine, arginine, procaine, ethanolamine, morphine, benzylamine, ethylenediamine, N,N'-dibenzylethylenediamine, diethanolamine, piperazine, dimethylaminoethanol, 2-amino-2-methyl-1-propanol, theophylline, N-methylglucamine and the like. Acid addition salts, e.g., with hydrochloric, tartaric, hydrobromic, sulfuric nitric, toluene-p-sulphonic and methane sulphonic acids may also be employed.
The salts can be mono-salts such as the monosodium salt obtained by treating one equivalent of sodium hydroxide with one equivalent of the product (I), also mixed di-salts. Such salts may be obtained by treating one equivalent of a base having a divalent cation, such as calcium hydroxide, with one equivalent of the product (I). The salts of this invention are pharmacologically acceptable non-toxic derivatives which can be used as the active ingredient in suitable unit-dosage pharmaceutical forms. Also, they may be combined with other drugs to provide compositions having a broad spectrum of activity.
The compounds of the present invention are valuable antimicrobial substances which are active against various gram-positive and gram-negative pathogens. Thus the free acid, free base, and especially the salts thereof such as amine and metal salts, particularly the alkali metal and alkaline earth metal salts, are useful bactericides and can be used for removing susceptible pathogens from dental and medical equipment, for separating microorganisms, and for therapeutic use in humans and animals. For this latter purpose pharmacologically acceptable salts with inorganic and organic bases such as those known in the art and used for the administration of penicillins and cephalosporins can be utilized. For example, salts such as alkali metal and alkaline earth metal salts, and primary, secondary and tertiary amine salts can be used for this purpose. These salts can be combined with pharmaceutically acceptable liquid and solid vehicles to form suitable dosage unit forms such as pills, tablets, capsules suppositories, syrups, elixirs and the like which can be prepared in accordance with procedures well known in this art.
The novel compounds are valuable antibiotics active against various gram-positive and gram-negative bacteria, and accordingly, find utility in human and veterinary medicine. The compounds of this invention can therefore be used as antibacterial drugs for treating infections caused by gram-positive or gram-negative bacteria, for example against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Bacillus subtilis, Salmonella typhosa, Pseudomonas and Bacterium proteus. The antibacterials of the invention may further be utilized as additives to animal feedingstuffs, for preserving foodstuffs and disinfectants. For example, they may be employed in aqueous compositions in concentrations ranging from 0.1 to 100 parts of antibiotic per million parts of solution in order to destroy and inhibit the growth of harmful bacteria on medical and dental equipment and as bactericides in industrial application, for example in waterbased paints and in the white water of paper mills to inhibit the growth of harmful bacteria.
The products of this invention may be used alone or in combination as an active ingredient in any one of a variety of pharmaceutical preparations. These antibiotics and their corresponding salts may be employed in capsule form or as tablets, powders or liquid solutions or as suspensions or elixirs. They may be administered orally, intravenously or intramuscularly.
The compositions are preparably presented in a form suitable for absorption by the gastro-intestinal tract. Tablets and capsules for oral administration may be in unit dose presentation form, and may contain conventional excipients such as binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers for example, lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine; lubricants, for example, magnesium stearate, talc, polyethylene glycol, silica; disintegrants, for example, potato starch or acceptable wetting agents such as sodium lauryl sulphate. The tablets may be coated according to methods well known in the art. Oral liquid preparations may be in the form of aqueous or oily suspension, solution, emulsions, syrups, elixirs, etc. or may be presented as a dry product, for reconstitution with water or other suitable vehicles before use. Such liquid preparations may contain conventional additives such as suspending agents, for example, sorbitol syrup, methyl cellulose, glucose/sugar syrup, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminum stearate gel or hydrogenated edible oils, for example almond oil, fractionated coconut oil, oily esters, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoates or sorbic acid. Suppositories will contain conventional suppository bases, e.g., cocoa butter of other glyceride.
Compositions for injection may be presented in unit dose form in ampules, or in multidose containers with an added perservative. The compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in powder form for reconstitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use.
The compositions may also be prepared in suitable forms for absorption through the mucous membranes of the nose and throat or bronchial tissues and may conveniently take the form of powder or liquids sprays or inhalants, lozenges, throat paints, etc. For medication of the eyes or ears, the preparations may be presented as individual capsules, in liquid or semi-solid form, or may be used as drops etc. Topical applications may be formulated in hydrophobic or hydrophilic bases as ointments, creams, lotions, paints, powders, etc.
Also, in addition to a carrier, the instant compositions may include other ingredients such as stabilizers, binders, antioxidants, preservatives, lubricators, suspending agents, viscosity agents or flavoring agents and the like. In addition, there may also be included in the composition other active ingredients to provide a broader spectrum of antibiotic activity.
For veterinary medicine the composition may, for example, be formulated as an intramammary preparation in either long acting or quick-release bases.
The dosage to be administered depends to a large extent upon the condition of the subject being treated and the weight of the host, the route and frequency of adminstration, the parenteral route being preferred for generalized infections and the oral route for intestinal infections. In general, a daily oral dosage consists of from about 5 to about 600 mg. of active ingredient per kg. of body weight of the subject in one or more applications per day. A preferred daily dosage for adult humans lies in the range of from about 15 to 240 mg. of active ingredient per kg. of body weight.
The instant compositions may be administered in several unit dosage forms as, for example, in solid or liquid orally ingestible dosage form. The compositions per unit dosage, whether liquid or solid may contain from 0.1% to 99% of active material, the preferred range being from about 10-60%. The compositions will generally contain from about 15 mg. to about 1500 mg. of the active ingredient; however, in general, it is preferable to employ a dosage amount in the range of from about 250 mg. of 1000 mg. In parenteral administration the unit dosage is usually the pure compound in a slightly acidified sterile water solution or in the form of a soluble powder intended for solution.

5-Substituted-3 -(2-aminoethylthio)-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en e-2-carboxylic acid


In a trunked communication system using intelligent repeaters (101), each intelligent repeater performs a series of tests (602, 606, 610, 614, and 618) on its own functionality. The results of these tests are transmitted (622) to a resource manager, which is one of the intelligent repeaters at a communications site. Using the results of these tests, the resource manager then selects one or more of the intelligent repeaters to perform the functions of authorization, resource allocation (708), and logging of communications (713).

Trunked communication systems are known to comprise a plurality of communication units, a limited number of communication resources that are transceived via a predetermined number of repeaters, or base stations, and a communication resource allocator that allocates the limited number of communication resources among the plurality of communication units. The communication units may be portable radios and/or mobile radios. The communication resources may comprise a TDM (time-division multiplexed) bus, a carrier frequency, a pair of carrier frequencies, or any RF (radio frequency) transmission means.
Generally, trunked two-way communication systems provide mobile and portable communication units with wireless services similar to many wired communication networks. Such examples include full-duplex telephone voice communication, two-way mobile-to-mobile group dispatch communication, and two-way mobile-to-dispatcher group dispatch communication. A typical trunked communication system site, where each different site has a different physical location, is composed of a number of full-duplex repeaters, each coupled to a variety of devices to support interconnection to the public telephone network, mobile-to-mobile calling, and to one or more dispatcher console positions. These devices typically provide a centralized control for the repeaters. For example, a single central controller provides radio channel signalling encode and decode functions, authorization functions, resource determination functions, and communication activity logging. A single telephone interconnect switch typically provides the repeaters with an interface to one or more telephone lines to support telephone interconnect communication. In systems employing a single device that is shared among the repeaters, a failure of the single device may render one or more of the desired services or functions inoperable, thus impairing communications in the system. Placing redundant devices within the system is expensive and an inefficient use of space and resources.
Because breaks in communications must be avoided, a method of providing centralized control of repeaters without wasteful redundancy is desired.

Resource management by an intelligent repeater


A gas sensor for detecting a gas component from a food item includes a sensing layer having an electrical resistance value that varies in accordance with the concentration and type of the gas component generated from the food item to thereby sense the gas component, first and second electrodes coupled across the sensing layer and connected to a power supply, a heater for heating the gas sensor to a temperature of sensing operation, and a switch connected to an adjustable voltage supply for controlling whether the heater is operated in a first temperature range or in a second temperature range. The sensing layer includes a mixture of SnO.sub.2 and WO.sub.3 in a predetermined ratio.

1. Field of the Invention
The present invention relates to a gas sensor, and more particularly to a gas sensor for sensing fruits or vegetables and a method of manufacturing the same.
2. Discussion of the Related Art
An effective sensor for sensing an inherent smell component of food (such as fruits and vegetables) is yet to be developed. Among the sensors in existence, the sensitivity for sensing the inherent smell component of the food had been too low to sense fruits and vegetables being put into or out of a container. Already-developed sensors merely sense the gas produced when the food (fruits and vegetables) decays or its freshness degrades.
Generally, when vegetables such as radish, Welsh onion, carrot, or lettuce are put in a storage compartment, the vegetables produce reducing gases, such as sulfuretted hydrogen (H.sub.2 S), methyl-mercaptan (CH.sub.3 SH), dimethyl-sulfide ((CH.sub.3).sub.2 S), and dimethyl-disulfide ((CH.sub.3).sub.2 S.sub.2), as the storage time grows.
If the vegetables are stored for a long time as described above, the sulfuric compound gases (reducing gases) are generated due to the degraded freshness. Thus, these gases are bonded with oxygen ions adsorbed on the surface of the gas sensor to generate conducting electrons as in the following reaction formula, thereby changing an electric conductivity on the surface of a sensing layer of the gas sensor: EQU R+O=RO+e.sup.-
Since the reaction of this formula is active in the vicinity of a metal catalyst on the surface of a sensing layer of the gas sensor, it is very important as to which catalyst of a certain component is added and how much is added. Conventionally, a palladium (Pd) catalyst of 1 wt % is added, and SnO.sub.2 is utilized as the sensing layer.
The above-mentioned conventional gas sensor for sensing gases produced due to the degraded freshness from prolonged storage will be described with reference to accompanying drawings. FIGS. 1a-1c is a view showing a structure of a conventional gas sensor for sensing the freshness of food, and FIG. 2 shows a process of manufacturing the gas sensor for sensing the freshness of food.
In manufacturing a gas sensor for sensing the freshness of the food, SnO.sub.2 powder is adequately mixed with Pd powder, which is finely ground to be subjected to a heat treatment at 700.degree. C. for about 5 hours. Then, the heat-treated powder mixture is finely ground further, and mixed with an organic material consisting of ethyl-cellulose and alpha-terpinol to create a paste. The mixture in the paste is coated to have a proper size and thickness on an electrode plane of alumina substrate 1 formed with electrodes 2 and a heater 3 via a screen printing method, thereby forming a sensing layer 4.
Thereafter, a drying process is performed; the gas sensor is sintered at 600.degree. C. for 10 minutes; a lead wire is attached; and a packaging process is performed. Thus, the gas sensor is completed.
FIGS. 1a-1c illustrate a situation where the heater is formed on the bottom plane. FIG. 3 is a circuit diagram for showing the operation of the conventional gas sensor. An operation of the conventional gas sensor for sensing the freshness of the food is carried out as follows.
The gas sensor reacts with the sulfuric compound to change electric conductivity. At this time, a resistance variation Rm is supplied to a microprocessor 5 as a voltage variation value in accordance with a resistance dividing ratio with a fixed resistor R.sub.L.
In this operation, microprocessor 5 compares the input voltage value with a pre-programmed value to determine the freshness of the vegetables in the storage compartment. Then, once the freshness begins degrading, the rate of freshness degradation is maximally retarded by a temperature control, a humidity control, a pressure control, a quantity control of oxygen/ozone, a quantity control of an anion, etc.
However, the conventional gas sensor and the freshness maintaining apparatus for using the same have the following problems. First, the conventional gas sensor which senses the freshness of the food, such as fruits and vegetables, has low sensitivity in sensing the inherent smell component of the fruits and vegetables, so that it is not distinguishable whether the fruits or vegetables are being put into or being put out from the storing compartment. Moreover, since the putting in or putting out of the fruits and vegetables cannot be distinguished, it is controlled by recognizing that the food, such as the fruits or vegetables, in the storage compartment is as good despite the fact that there is no food in the storing compartment. Consequently, the power consumed by a refrigerator is unnecessarily increased.

Gas sensor for detecting gases generated from food products


An improved package for pulverulent egg preparations, said package being intended for the preparation of egg-based food products without having to manipulate fresh eggs.

1. Object of the Invention
An improved package for pulverulent egg preparations intended to prepare food containing egg without having to manipulate fresh eggs and losing their characteristics, starting from pulverulent egg to which a certain amount of water is added, so that a product suitable for its use in food is obtained.
2. Description of the State of the Art
Several different forms of packages for pulverulent egg preparations exist, as well as different methods to produce it according to different processes and it always being necessary to add water prior to consumption of the product.
Until now, pulverulent egg has been marketed in large packages and their contents are poured into another container of greater dimensions to which water is then added. This system is rather uncomfortable, since a certain amount of pulverulent egg is lost as it remains stuck to the inside surface of the package or during pouring a certain amount of egg falls outside and cannot be used. Moreover, there is another important problem to obtain the best flavour and harnessing of the product, like adding water, since adding the exact and correct amount of this liquid is quite difficult. Another drawback is to make the mixture, a rather difficult action due to the amount of product and the size of the package, making a perfect homogenisation of the product very complicated.
The same problems arise when packing the pulverulent egg in separate containers, mainly due to the users""s ignorance of the exact amount of water that should be added to the pulverulent egg.
A container for concentrated egg products has already been disclosed in the British patent GB 2227004, where a bag is described for the individual preparation of a pasty, non-pulverulent concentrated egg. In spite of reducing the aforementioned problems, this patent still leaves several problems without solution, like the fact that its preparation in a plastic bag is exclusively thought to prepare the mixture and consume the product directly, without possibility of storage. Moreover, the created liquid cannot be easily stored due to the instability of the bag, the impossibility of covering the bag making contamination possible once the latter has been opened and the product mixed and moreover, the preparation of the mixture is difficult since the type of package prevents stirring of the product, making homogenisation difficult, causing a difficult solution of the pasty egg. Another added problem of this package is the existence of several level marks on its outside which makes the consumer doubt when adding the water to make the mixture, besides making different types of mixture possible when there only exists one proportion of the mixture which is perfect, permitting an optimum harnessing of the egg properties.
To solve the aforementioned problems, the present invention has been developed, an improved package for pulverulent egg preparations.
The present invention, an improved package for pulverulent egg preparations perfectly solves the aforementioned drawbacks due to its design.
Basically, the package permits a hygienic manipulation of the pulverulent egg without the need to remove it from its original container, hence preventing contamination thereof, which may be produced with previous pulverulent or pasty egg package systems, since in them it was necessary to remove the egg from its container or the container was not very robust, permitting spillage thereof.
This package is made of a resistant material, whether plastic or glass, allowing easy maintenance in the refrigerator once the mixture has been made, until its expiry date. In other words, it allows storage of the product and it is not necessary to use it immediately as was the previous case. In this way, the mixture characteristics are maintained, as fresh egg, but without need to manipulate it.
The product is especially intended for the food industry whether confectioners, restaurants or at home, permitting a fast and perfect preparation of liquid egg, which latter may be used in different foods but always with the security that the product is not contaminated.
Besides the pulverulent egg, there may be different ingredients or flavours inside the package, their applications being the same as unshelled eggs, like omelettes, sponges, mayonnaise, battering and others. The pulverulent egg, due to its characteristics, and mainly to its low water content, allows its preservation for a long period of time from the manufacturing date, so that it may be recovered at any time.
The package contents, the pulverulent egg, is produced by the automatic shelling of eggs, which prior to their homogenisation and pasteurisation are desiccated by atomisation. After this, the product is subjected to strict physico-chemical and bacteriological tests.
The preparation method of the final product as from the improved package containing the pulverulent egg is simply and fast, obtaining a liquid egg suitable for its consumption. To prepare the final product, it is only necessary to open the hermetically closed package and add water until the horizontal mark appearing on it, so that no doubt may exist regarding the exact amount of water to obtain optimum product conditions. Once the water has been added, it is necessary to mix both ingredients, the water and the pulverulent egg and for this, it is only necessary to close the package again and shake it, without having to move it with a utensil, it being sufficient to shake the container.
Following this method the liquid product obtained is the same as liquid egg obtained from shelling eggs and homogenising the yolk and white thereof by beating, the amount of water to add being the same as that for eggs in the preparation phase of pulverulent egg in the desiccation stage.
By this method of preparation and using this package, an improved preservation of the prepared product is obtained compared with previous systems. The preservation of unprepared egg, that is, in the closed package is greater than that of an egg with the shell when this is not refrigerated, supporting high temperatures without the product suffering.
Due to the package characteristics, the product preparation is very simple without needing to weight nor measure quantities of water, simply having to add water until the measure indicated on the package. For later consumption of the mixture, some egg shaped marks exist on the side of the package, each mark being equivalent to one beaten egg. In this way, the preparation of a mixture is simple with a determined number of eggs different from the capacity of the improved package.
Due both to the pulverulent product and its later packaging and preservation in the container object of the present invention, total bacteriological stability is obtained assuring that during the useful life there is no proliferation of undesirable and pathogenic germs frequently found in egg shell and which during manual shelling of eggs may pass to the non-pasteurised liquid egg.

Package for pulverulent egg preparations


A method for detecting the commencement of opening of the nozzle needle of an injector of an injection system. In the detection method, the coil of the solenoid injector has a voltage applied to it which is so low that the armature is moved toward the nozzle needle at such a low speed that the abutment causes a stoppage of the armature movement, without the nozzle needle being opened. In this case, the idle travel is overcome, but no injection process is initiated. The abutment of the armature against the nozzle needle is detected, in the current profile, as the commencement of opening of the nozzle needle.

The detection of the commencement of the opening of the nozzle needle or of the point in time of the abutment of the armature on the nozzle needle is based on several principles. The eddy-current driven coupling between the mechanics (armature and injector needle) and the magnetic circuit (coil) generates a feedback signal based on the displacement of the mechanics. A speed-dependent eddy current is induced in the armature as a result of the displacement of the nozzle needle and of the armature, which also causes a reaction on the electromagnetic circuit. Depending on the speed of displacement, a voltage is induced in the electromagnet that is superimposed on the activation signal. The utilization of said effect requires the superimposition of the basic electrical variables voltage or current with the signal change owing to the armature and/or the needle displacement to be suitably separated and then to be further processed. In doing so, the characteristic signal shape in the voltage or current signal is analyzed in relation to the point in time of occurrence.
The following methods for detecting a characteristic signal profile during the opening process are known:
Current Measurement Method
This method requires active influencing of the current profile (the standard activation form) in order to ensure that the magnetic circuit is not saturated. With said measurement techniques, a needle stop measurement signal can only be detected in the event of full drive.
Voltage Measurement
This type of measurement is not possible with the standard activation form because voltage imposition overwrites all characteristics. In doing so it is assumed therefrom that the electromagnetic circuit is controlled with sample-and-hold activation with a boost phase.
If the injector is activated with the standard voltage profile, the nozzle needle is opened very rapidly. No signal is generated in this case because the nozzle needle abutment takes place at a point in time at which the magnet circuit is saturated. There is therefore no signal available for detecting the commencement of the opening of the nozzle needle.
The nozzle needle abutment can only be detected if an activation profile is used with which the nozzle needle abutment takes place when the magnetic circuit is not in saturation. This can be achieved by reducing the needle opening rate, wherein however operation with such a detection profile cannot be carried out permanently because the reduced nozzle needle speed can result in a lower injection quality (atomization, emissions etc.). With such a procedure, the quality of the injection would therefore have been affected.
These and other previously known methods for generally determining the opening or closing time of an electromagnetically driven device use either a measurement channel for the determination of injector opening and closing (current/voltage measurement), with intervention into the energization during the detection of opening, or current measurement alone for detection of the opening and closing times. The intrusive intervention into the basic activation of the coil and the limitations associated therewith, result in altered injection behavior.

Method and device for detecting the commencement of opening of a nozzle needle


A system and method for producing a wide range of metallic appearances using halftones of a nano-particle metallic ink, such as, for example, nano-silver, are presented. In exemplary embodiments of the present invention, a nano-particle metallic ink, such as, for example, nano-silver, can be made to produce a range of appearances from, for example, bright silver to dull oxidized aluminum, by changing halftone level of the silver inks, changing the substrate surface properties and introducing small amounts of other colored inks, such as process or spot, in either an underprinting or overprinting of the metallic ink. In exemplary embodiments of the present invention, InkJet printing of a single metal-pigmented ink can be effected, and its metallic appearance can very quickly be adjusted to match a given package design.

Current commercial offerings of metal-pigmented inks cannot be successfully used in a proofing application except as transferred via thermal transfer. This is because metallic pigments are produced as flakes which have a large aspect, their length to width, may be tens, or even hundreds, of microns in size. This makes it very difficult to pass the metal flake through the narrow orifice of a typical inkjet head. Similarly, toner based digital proofing systems rely on electrostatic or electro-dynamic forces to hold the toner particles on the image drum. However, metal flakes are conductive and thus bleed the charges off, allowing the toner to fall off of the image drum before printing can occur. There have been no commercial solutions known to the inventors that have addressed these problems.
On the other hand, thermal transfer uses a plastic donor sheet on which a clear resin coating with dispersed pigment has been cast. The print heads contain heating elements that raise the temperature of the coating until it becomes fluid and then is transferred by contact with the receiving sheet. These thermal transfer films are produced in much the same way as paint films and the metallic flakes are dispersed into the polymeric resin before being cast onto the plastic sheets. The thermal transfer method is very slow and very expensive (proofs cost near $100.00 each for A3 format) and the imaging systems for applying the donor to a substrate can also be rather expensive (over $10,000). Such a system can be, for example, a proofing printer such as the Kodak Approval NX and XP, shown at, for example, http://graphics.kodak.com/US/en/product/proofing/kodak_approval/default.htm?_requestid=5068.
Moreover, when using such thermal transfer technology, the level of brightness must be developed on the donor roll. This requires development and warehousing of multiple donor rolls with varying metallic pigments. For example, paint coatings have five or six levels. Converters that produce brochures for the automotive industry generally offer three levels, bright, medium and dull—giving appearances from that of the shiny front side of a sheet of foil down to an unpolished metal sheet.
What is needed in the art is an inexpensive method to vary the appearance of metallic inks for use in proofing applications that can be easily iteratively repeated, so as to fully match a desired package or other substrate design.

Halftone printing of metal-pigmented inks to produce various metallic appearances


A method for locating a sound source by maximizing a directed response strength calculated for a plurality of vectors of the interauricular time differences forming a set comprises: a first subset of vectors compatible with sound signals from a single sound source at an unlimited distance from the microphones; and a second subset of vectors not compatible with sound signals from a signal sound source at an unlimited distance from the microphones. Each vector of the first subset is associated with a direction for locating the corresponding single sound source, and each vector of the second subset is associated with the locating direction of a vector of the first subset closest thereto according to a predefined metric. A humanoid robot including: a set of at least three microphones, arranged on a surface higher than the head of thereof; and a processor for implementing one such method is provided.

A robot may be qualified humanoid provided that it possesses certain attributes of the appearance and functionalities of a human: a head, a trunk, two arms, optionally two legs, etc. Generally, it is required that a humanoid robot be able to interact with human beings as "naturally" as possible, by sensing the presence of a person, by understanding his language, by engaging him in conversation, etc. The ability to be able to localize sound sources is very useful, or even necessary, to achieve this aim. Specifically, such an ability may allow a humanoid robot to determine the direction from which a sound is coming and to turn his head in that direction; if the sound was produced by a person, the robot may then activate a face recognition software package, configure optimally a voice recognition system, follow with "his gaze" the movements of this person, etc.
A plurality of methods and systems for finding the spatial localization of a plurality of sound sources are known in the prior art. These methods and systems are generally based on a plurality of microphones that are not or not very directional and on digital processing of the signals captured by said microphones.
The paper by J. DiBiase et al. "Robust localization in reverberant rooms" in "Microphone Arrays: Signal Processing Techniques and Applications" edited by M. S. Brandstein and D. B. Ward by Springer-Verlag, 2001, Berlin, Germany, describes three principal approaches to localizing a sound source.
A first approach uses spectral estimation techniques based on the correlation matrix of the signals captured by the microphones. Methods based on this approach tend to be sensitive to modelling errors and very demanding of computational power. They are mainly suitable for narrow-band signals.
A second approach is based on the estimation of time shifts between the sound signals received by pairs of microphones ("Time Difference Of Arrival" or TDOA techniques). These estimations are used, with the knowledge of the positions of the microphones, to calculate hyperbolic curves, the intersection of which gives the position of the source. The time shifts may especially be estimated by the PHAT-GCC (for "Phase Transform—Generalized Cross-Correlation") method, which exploits the calculation of an intercorrelation—or cross correlation—between signals previously "whitened" by filtering. The PHAT-GCC method is described in more detail in the paper by Ch. H. Knapp and G. C. Carter "The Generalized Correlation Method for Estimation of Time Delay", IEEE Transaction on Acoustics, Speech and Signal Processing, Vol. ASSP-24, No. 4, August 1976 pp. 320-327. These methods are computationally light but they are not robust to correlated noise originating from multiple sources and are subject to "false positives". Furthermore, they are not very robust to reverberation, with the exception of the PHAT-GCC method.
A third approach consists in synthesizing an orientable acoustic beam by adding the signals captured by the various microphones, to which signals a variable time shift has been applied, and in identifying the orientation of the beam that maximizes the power of the composite signal thus received. Methods based on this approach tend to be not very robust to reverberation and noise, excepting certain variants that are however very demanding of computational power.
The paper more particularly describes a method combining the synthesis of an orientable acoustic beam and a generalized intercorrelation with phase transformation. This method is denoted SRP-PHAT (for "Steered Response Power—PHAse Transform"). Relative to the PHAT-GCC method, it is more robust to noise but more sensitive to reverberation.

Method for locating a sound source, and humanoid robot using such a method


Described are compositions of stable nanoparticulate cinacalcet or a salt thereof, and methods of making and using them. The compositions exhibit an improved dissolution rate, improved bioavailability, and reduced difference in absorption when administered orally under fed as compared to fasting conditions.

A. Background Regarding Cinacalcet
Cinacalcet hydrochloride is a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. It is sold as Sensipar® in the USA and Australia, and Mimpara® in Europe. Its empirical formula is C22H22F3N.HCl with a molecular weight of 393.9 g/mol (hydrochloride salt) and 357.4 g/mol (free base). It has one chiral center having an R-absolute configuration. The R-enantiomer is the more potent enantiomer and has been shown to be responsible for pharmacodynamic activity (Sensipar® prescribing information; www.sensipar.com/professional/pdf/sensipar_pi.pdf, accessed Jun. 11, 2008). The structural formula of cinacalcet hydrochloride is shown below:

Cinacalcet HCl reduces iPTH, serum calcium, serum phosphorus, and the calcium-phosphorus product in patients with chronic kidney disease and secondary hyperparathyroidism who are receiving dialysis, and reduces elevated serum calcium associated with primary hyperparathyroidism and parathyroid carcinoma. Cinacalcet was approved in the US on 8 Mar. 2004 (NDA No. 021688) where it is sold under the tradename Sensipar® and in the European Union on 22 Oct. 2004 (MA EU/1/04/292/001-012) where it is sold as Mimpara®. Sensipar®/Mimpara® is indicated for the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease on dialysis. Sensipar® is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma. In January 2008, Kirin Pharma (now Kyowa Hakko Kirin) launched cinacalcet, as Regpara™, for the treatment of secondary hyperparathyroidism. In June 2008, cinacalcet was approved in the EU for the treatment of hypercalcemia in primary hyperparathyroidism.
In patients with secondary hyperparathyroidism and end-stage renal disease on dialysis, cinacalcet is to be administered orally starting at 30 mg, once daily. The dose should be titrated every 2 to 4 weeks up to 180 mg daily, to achieve a target PTH level. For patients with parathyroid carcinoma the recommended starting oral dose of Sensipar® is 30 mg twice daily. This should be titrated every 2 to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily and 90 mg three or four times daily as necessary to normalize serum calcium levels.
Cinacalcet is administered orally, and concomitant administration with food affects its bioavailability. Studies have confirmed this fact. Specifically, a study comparing the absorption of a single oral dose of cinacalcet HCl (Sensipar®/Mimpara® (90 mg) following (i) a high-fat, high-caloric meal, (ii) a low-fat, low-caloric meal, and a (iii) 10-hour fast, showed that the mean (90% confidence intervals) AUC[infinity] following high- and low-fat meals was increased by 68 (48 to 89) % and 50 (33 to 70) %, respectively, relative to fasting. The difference in mean AUC∞ between high- and low-fat meals was small [12 (9.9-26) %]. Moreover, the mean tmax of cinacalcet was prolonged in fasting subjects (6 h) in relation to high-fat (4 h) and low-fat (3.5 h) fed subjects. The mean t1/2[beta] was similar between treatment conditions. See American J. of Therapeutics, 14:235-240 (May/June 2007). Thus, administration of cinacalcet with either high- or low-fat meals results in significant increases in exposure, relative to administration under fasting conditions. This change in exposure requires that the medication be taken with food or shortly after a meal. If a patient does not take their dose exactly as indicated sub-therapeutic levels of cinacalcet can occur. A recommendation that cinacalcet to be taken with food or shortly after a meal is included in the labeling information issued by the FDA and EMEA in respect of the Sensipar® and Mimpara® products respectively (see FDA 2004 label information and EMEA 2004 Summary of Product Characteristics, available on the relevant agency's website). In the case of the US product the most recent revision of the label information (19 Dec. 2008) maintains this recommendation. The absolute bioavailability of cinacalcet in fasted subjects has been estimated at 20-25% (EMEA 2004 Summary of Product Characteristics for Mimpara®)
More generally, cinacalcet is used to treat hyperparathyroidism (elevated parathyroid hormone levels) Torres PU, "Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease". Journal of renal nutrition: the official journal of the Council on Renal Nutrition of the National Kidney Foundation 16 (3): 253-8. (2006), and the symptoms thereof. Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH). Parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels. Overactivity of one or more of the parathyroid glands causes high calcium levels (hypercalcemia) and low levels of phosphate in the blood. Hyperparathyroidism may be a consequence of parathyroid tumors and chronic renal failure.
Cinacalcet HCl is a white to off-white, crystalline solid soluble in methanol or 95% ethanol, but only slightly soluble in water. As such, the dissolution rate and bioavailability of known cinacalcet formulations are not optimal. The effectiveness of cinacalcet may be enhanced if it could be formulated to be taken without food, thus decreasing the likelihood of patient compliance problems. Furthermore a formulation that enhances the bioavailability of cinacalcet would facilitate reduction of the dosage strength with the possibility of achieving a better safety profile.
U.S. Pat. No. 6,011,068, U.S. Pat. No. 6,031,003, U.S. Pat. No. 6,211,244 and U.S. Pat. No. 6,313,146 are listed in respect of Sensipar® in the FDA's list of Approved Drug Products with Therapeutic Equivalence Evaluations (otherwise known as the "Orange Book"; see www.fda.gov/cder/ob/default.htm—accessed 5 May, 2009). Collectively these patents cover the cinacalcet compound per se, pharmaceutical compositions comprising cinacalcet and various uses including those listed in the Orange Book, namely: reducing parathyroid hormone level; modulating parathyroid hormone secretion; treating hyperparathyroidism; and reducing serum ionized calcium level.
B. Background Regarding Nanoparticulate Active Agent Compositions
Nanoparticulate active agent compositions, first described in U.S. Pat. No. 5,145,684 ("the '684 patent"), are particles comprising a poorly soluble therapeutic or diagnostic agent having adsorbed onto, or associated with, the surface thereof a non-crosslinked surface stabilizer. The '684 patent does not describe nanoparticulate compositions of cinacalcet.
Methods of making nanoparticulate active agent compositions are described in, for example, U.S. Pat. Nos. 5,518,187 and 5,862,999, both for "Method of Grinding Pharmaceutical Substances;" U.S. Pat. No. 5,718,388, for "Continuous Method of Grinding Pharmaceutical Substances;" and U.S. Pat. No. 5,510,118 for "Process of Preparing Therapeutic Compositions Containing Nanoparticles." These do not describe nanoparticulate compositions of cinacalcet.
Nanoparticulate active agent compositions are also described, for example, in U.S. Pat. No. 5,298,262 for "Use of Ionic Cloud Point Modifiers to Prevent Particle Aggregation During Sterilization;" U.S. Pat. No. 5,302,401 for "Method to Reduce Particle Size Growth During Lyophilization;" U.S. Pat. No. 5,336,507 for "Use of Charged Phospholipids to Reduce Nanoparticle Aggregation;" U.S. Pat. No. 5,340,564 for "Formulations Comprising Olin 10-G to Prevent Particle Aggregation and Increase Stability;" U.S. Pat. No. 5,346,702 for "Use of Non-Ionic Cloud Point Modifiers to Minimize Nanoparticulate Aggregation During Sterilization;" U.S. Pat. No. 5,352,459 for "Use of Purified Surface Modifiers to Prevent Particle Aggregation During Sterilization;" U.S. Pat. No. 5,429,824 for "Use of Tyloxapol as a Nanoparticulate Stabilizer;" U.S. Pat. No. 5,560,931 for "Formulations of Compounds as Nanoparticulate Dispersions in Digestible Oils or Fatty Acids;" U.S. Pat. No. 5,565,188 for "Polyalkylene Block Copolymers as Surface Modifiers for Nanoparticles;" U.S. Pat. No. 5,569,448 for "Sulfated Non-ionic Block Copolymer Surfactant as Stabilizer Coatings for Nanoparticle Compositions;" U.S. Pat. No. 5,571,536 for "Formulations of Compounds as Nanoparticulate Dispersions in Digestible Oils or Fatty Acids;" U.S. Pat. No. 5,573,783 for "Redispersible Nanoparticulate Film Matrices With Protective Overcoats;" U.S. Pat. No. 5,580,579 for "Site-specific Adhesion Within the GI Tract Using Nanoparticles Stabilized by High Molecular Weight, Linear Poly(ethylene Oxide) Polymers;" U.S. Pat. No. 5,585,108 for "Formulations of Oral Gastrointestinal Therapeutic Agents in Combination with Pharmaceutically Acceptable Clays;" U.S. Pat. No. 5,587,143 for "Butylene Oxide-Ethylene Oxide Block Copolymers Surfactants as Stabilizer Coatings for Nanoparticulate Compositions;" U.S. Pat. No. 5,591,456 for "Milled Naproxen with Hydroxypropyl Cellulose as Dispersion Stabilizer;" U.S. Pat. No. 5,622,938 for "Sugar Based Surfactant for Nanocrystals;" U.S. Pat. No. 5,718,388 for "Continuous Method of Grinding Pharmaceutical Substances;" U.S. Pat. No. 5,834,025 for "Reduction of Intravenously Administered Nanoparticulate Formulation Induced Adverse Physiological Reactions;" U.S. Pat. No. 6,264,922 for "Nebulized Aerosols Containing Nanoparticle Dispersions;" U.S. Pat. No. 6,267,989 for "Methods for Preventing Crystal Growth and Particle Aggregation in Nanoparticle Compositions;" U.S. Pat. No. 6,270,806 for "Use of PEG-Derivatized Lipids as Surface Stabilizers for Nanoparticulate Compositions;" U.S. Pat. No. 6,316,029 for "Rapidly Disintegrating Solid Oral Dosage Form;" U.S. Pat. No. 6,375,986 for "Solid Dose Nanoparticulate Compositions Comprising a Synergistic Combination of a Polymeric Surface Stabilizer and Dioctyl Sodium Sulfosuccinate;" U.S. Pat. No. 6,428,814 for "Bioadhesive Nanoparticulate Compositions Having Cationic Surface Stabilizers;" U.S. Pat. No. 6,431,478 for "Small Scale Mill;" U.S. Pat. No. 6,432,381 for "Methods for Targeting Drug Delivery to the Upper and/or Lower Gastrointestinal Tract;" U.S. Pat. No. 6,592,903 for "Nanoparticulate Dispersions Comprising a Synergistic Combination of a Polymeric Surface Stabilizer and Dioctyl Sodium Sulfosuccinate," U.S. Pat. No. 6,582,285 for "Apparatus for sanitary wet milling;" U.S. Pat. No. 6,742,734 for "System and Method for Milling Materials;" U.S. Pat. No. 6,745,962 for "Small Scale Mill and Method Thereof;" U.S. Pat. No. 6,811,767 for "Liquid droplet aerosols of nanoparticulate drugs;" U.S. Pat. No. 6,908,626 for "Compositions having a combination of immediate release and controlled release characteristics;" U.S. Pat. No. 6,969,529 for "Nanoparticulate compositions comprising copolymers of vinyl pyrrolidone and vinyl acetate as surface stabilizers;" U.S. Pat. No. 6,976,647 for "System and Method for Milling Materials;" U.S. Pat. No. 6,991,191 for "Method of Using a Small Scale Mill;" U.S. Pat. No. 7,198,795 for "In vitro methods for evaluating the in vivo effectiveness of dosage forms of microparticulate of nanoparticulate active agent compositions;" U.S. Pat. No. 7,244,451 for "Methods of making nanoparticulate drug compositions comprising copolymers of vinyl pyrrolidone and vinyl acetate as surface stabilizers"; U.S. Pat. No. 7,288,267 for "Bioadhesive nanoparticulate compositions having cationic surface stabilizers"; U.S. Pat. No. 7,320,802 for "Methods of treatment using nanoparticulate fenofibrate compositions;" U.S. Pat. No. 7,390,505 for "Nanoparticulate topiramate formulations;" U.S. Pat. No. 7,459,283 for "Nanoparticulate compositions having lysozyme as a surface stabilizer;" U.S. Pat. No. 7,521,068 for "Dry powder aerosols of nanoparticulate drugs;" U.S. Pat. No. 7,695,739 for "In vitro methods for evaluating the in vivo effectiveness of dosage forms of microparticulate or nanoparticulate active agent compositions;" U.S. Pat. No. 7,713,551 for "Gel stabilized nanoparticulate active agent compositions;" U.S. Pat. No. 7,763,278 for "Nanoparticulate polycosanol formulations and novel polycosanol combinations;" U.S. Pat. No. RE41,884 for "Reduction of intravenously administered nanoparticulate-formulation-induced adverse physiological reactions;" U.S. Pat. No. 7,825,087 for "Nanoparticulate and controlled release compositions comprising cyclosporine;" U.S. Pat. No. 7,842,232 for "Sterilization of dispersions of nanoparticulate active agents with gamma radiation;" U.S. Pat. No. 7,850,995 for "Bioadhesive nanoparticulate compositions having cationic surface stabilizers;" U.S. Pat. No. 7,879,360 for "Nanoparticulate compositions having a peptide as a surface stabilizer;" U.S. Pat. No. 7,910,577 for "Injectable nanoparticulate olanzapine formulations;" U.S. Pat. No. 7,927,627 for "Nanoparticulate fibrate formulations;" and U.S. Pat. No. 7,931,917 for "Nanoparticulate fibrate formulations," all of which are specifically incorporated by reference. These patents do not describe nanoparticulate compositions of cinacalcet.
In addition, U.S. Patent Publication Nos. 20080152585 for "Low viscosity liquid dosage forms"; 20080124393 for "Controlled release nanoparticulate compositions"; 20080025807 for "System and Method for Milling Materials"; 20080003295 for "Bioadhesive nanoparticulate compositions having cationic surface stabilizers"; 20070141159 for "Methods of Making Nanoparticulate Compositions Comprising Copolymers of Vinyl Pyrrolidone and Vinyl Acetate as Surface Stabilizers"; 20070110776 for "In vitro methods for evaluating the in vivo effectiveness of dosage forms of microparticulate or nanoparticulate active agent compositions;" 20020012675 A1 for "Controlled Release Nanoparticulate Compositions," 20040195413 A1, for "Compositions and method for milling materials," 20040173696 A1 for "Milling microgram quantities of nanoparticulate candidate compounds," 20020012675 A1 for "Controlled Release Nanoparticulate Compositions;" 20050238725 for "Nanoparticulate compositions having a peptide as a surface stabilizer;" 20050147664 for "Compositions comprising antibodies and methods of using the same for targeting nanoparticulate active agent delivery;" 20050031691 for "Gel stabilized nanoparticulate active agent compositions;" 20040258757 for "Liquid dosage compositions of stable nanoparticulate active agents;" 20040195413 for "Compositions and method for milling materials;" 20040156895 for "Solid dosage forms comprising pullulan;" 20040105889 for "Low viscosity liquid dosage forms;" 20040105778 for "Gamma irradiation of solid nanoparticulate active agents;" 20040015134 for "Drug delivery systems and methods;" 20030215502 for "Fast dissolving dosage forms having reduced friability;" 20030185869 for "Nanoparticulate compositions having lysozyme as a surface stabilizer;" 20030137067 for "Compositions having a combination of immediate release and controlled release characteristics;" 20030108616 for "Nanoparticulate compositions comprising copolymers of vinyl pyrrolidone and vinyl acetate as surface stabilizers;" 20030087308 for "Method for high through put screening using a small scale mill or microfluidics;" 20030023203 for "Drug delivery systems & methods;" 20020179758 for "System and method for milling materials; 20010053664 for "Apparatus for sanitary wet milling," 20110064803 for "Nanoparticulate and controlled release compositions comprising vitamin k2;" 20110027371 for "Nanoparticulate statin formulations and novel statin combinations;" 20110008435 for "Nanoparticulate and Controlled Release Compositions Comprising Aryl-Heterocyclic Compounds;" 20100316725 for "Reduction of flake-like aggregation in nanoparticulate active agent compositions;" 20100260859 "Controlled-release clozapine compositions;" 20100260858 for "Drug delivery composition;" 20100247636 for "Nanoparticulate and controlled release compositions comprising nilvadipine;" 20100221327 for "Nanoparticulate azelnidipine formulations;" 20100028439 for "Nanoparticulate stabilized anti-hypertensive compositions;" 20090304801 for "Aerosol and injectable formulations of nanoparticulate benzodiazepine;" 20090297596 for "Nanoparticulate and Controlled Release Compositions Comprising a Platelet Aggregation Inhibitor;" 20090291142 for "Nanoparticulate bicalutamide formulations;" 20090269400 for "Nanoparticulate and Controlled Release Compositions Comprising a Cephalosporin;" 20090252807 for "Nanoparticulate and Controlled Release Compositions Comprising Prostaglandin Derivatives;" 20090238884 for "Compositions for site-specific delivery of imatinib and methods of use;" 20090155331 for "Injectable nanoparticulate olanzapine formulations;" 20090074873 for "Nanoparticulate beclomethasone dipropionate compositions;" 20090035366 for "Nanoparticulate benzothiophene formulations;" 20080317843 for "Nanoparticulate formulations of modafinil;" 20080279929 for "Nanoparticulate and Controlled Release Compositions Comprising Cefditoren;" 20080254114 for "Controlled Release Compositions Comprising Heterocyclic Amide Derivative Nanoparticles;" 20080248123 for "Nanoparticulate anticonvulsant and immunosuppressive compositions;" 20080226734 for "Combination of a narcotic and non-narcotic analgesic;" 20080220074 for "Gamma radiation sterilized nanoparticulate docetaxel compositions and methods of making same;" 20080213378 for "Nanoparticulate statin formulations and novel statin combinations;" 20080213374 for "Nanoparticulate sorafenib formulations;" and 20080171091 for "Nanoparticulate compositions of immunosuppressive agents," describe nanoparticulate active agent compositions and are specifically incorporated by reference. These patent application publications do not describe nanoparticulate compositions of cinacalcet.
Amorphous small particle compositions are described, for example, in U.S. Pat. No. 4,783,484 for "Particulate Composition and Use Thereof as Antimicrobial Agent;" U.S. Pat. No. 4,826,689 for "Method for Making Uniformly Sized Particles from Water-Insoluble Organic Compounds;" U.S. Pat. No. 4,997,454 for "Method for Making Uniformly-Sized Particles From Insoluble Compounds;". These are also specifically incorporated herein by reference. These patents do not describe nanoparticulate compositions of cinacalcet.
The present invention relates to nanoparticulate cinacalcet compositions, such as nanoparticulate cinacalcet HCl, which addresses the needs described above by providing nanoparticulate cinacalcet compositions which overcome the shortcomings of known non-nanoparticulate cinacalcet formulations.


A device for regulating the discharge of bones and other hard, objectionable material from processed food includes a flow control device contained within a housing applied to the discharge line downstream of a grinding apparatus. The device has a reciprocating valve element having an elongated cylindrical valve head with a groove formed therein at an angle to the longitudinal axis of the valve element. This groove is constantly contacted by the discharge product flow stream in open and closed positions of the valve.

The present invention relates generally to a bone elimination apparatus, and more specifically, to a means for regulating the discharge of bones and other hard materials from a bone elimination apparatus.
In the food processing industry animal carcasses or remnants are used to produce ground food material. After choice and select portions of the animal are removed from the carcasses, some useable portions of food remain on the carcasses. This useable material may be recovered from the carcasses by subjecting the carcasses to a grinding process. In such processes, the animal carcasses are inserted into a grinding apparatus where the useable food material is processed into a ground form, while the remaining bone and hard tissues are separated and discharged from the grinding apparatus to waste.
Bone elimination devices are well known in the food processing industry. For the most part, these devices are used in association with a grinding apparatus of the type having a tubular grinding chamber with a rotating compression screw or auger extending within the grinding chamber. Food parts, such as carcasses or remnants, are placed into the chamber where the auger contacts and drives the food material through the tube, forming a food material mass in the grinding chamber. The auger may include a series of grinding blades which cut the useable material from the carcasses and may also press it against a perforated portion of the grinding chamber. The auger compresses the food material against the perforations and forces the useable, ground food material out of the grinding chamber through the perforations while retaining the bones and connective tissues in the grinding chamber.
The bones and hard tissue are heavier than the useable soft material of the carcasses so that during the grinding process, this heavier material tends to collect along the auger shaft where it is pushed down the length of the grinding chamber to the end of the grinding chamber. This unusable material is typically discharged through a tube extending out of the meat grinding chamber to a waste collection point. Examples of bone removal equipment having a structure as noted above are fully described in U.S. Pat. Nos. 4,536,920 issued Aug. 27, 1985 and Re. 31,631, issued Jul. 17, 1984.
The equipment described in these two patents utilize an orifice of decreasing size which collects the bones and hard material for discharge and expels them through a discharge opening. Depending on the type of food material being processed, some useable food material may remain on the carcasses or remnants. Other patents describe devices which are suitable for recovering useable food material which still may be attached on the unusable hard portions of the carcasses after a first grinding. Such an apparatus is described in U.S. Pat. No. 5,251,829, issued Oct. 12, 1993 to Weiler and Company of Whitewater, Wis. This patent describes a bone collector assembly in which an additional, or secondary, grinding chamber is located downstream of the primary grinding chamber. This secondary grinding chamber has an additional auger and knife assembly which grinds the hard material discharged from the first grinding chamber a second time, thereby increasing the yield of the useable food material from carcasses.
In using an apparatus of the type described in the above-mentioned '829 patent, it has come to be appreciated that occasionally relatively large amounts of food material are discharged from the grinder apparatus in sporadic spurts as a result of the overall backpressure within the system. When food material is discharged from such a grinding apparatus in large spurts, the backpressure of the system is reduced, and useable food material may be easily ejected out of the grinder along with the unusable material. When large amounts of useable material are discharged in this manner, some food processors may reintroduce the expelled material back into the grinding apparatus for regrinding in an attempt to recover additional useable material. When this reintroduction occurs, the likelihood is increased that some of the hard unusable portions of the food material may be ground into the useable food material, leading to an inferior quality of the ultimate processed food product.
The present invention is therefore directed to a solution to this problem by providing a means to increase the backpressure of the grinding system which regulates the discharge of bones and hard materials from the grinder, thereby substantially eliminating the need to regrind discharged material and reducing the likelihood of reintroducing bone and foreign objects into the processed food material.
In accordance with the present invention, a discharge valve means is provided within the discharge tube of a food grinder which provides control over the flow and backpressure of the grinding apparatus. The valve means is contained within a housing adapted for connection to the discharge opening of a food grinding apparatus. The valve means includes a valve element slidably mounted therein between inlet and outlet openings of the housing. Movement of the valve element occurs along the longitudinal axis of the housing. The valve element includes a valve head or plug for sealing the inlet of the control housing which consequently seals the discharge of the grinding apparatus. The walls of the inlet opening of the control housing serve as the valve seat and cooperate with a multi-surfaced portion of the valve head to regulate a precise flow rate of discharge out of the system so as to remove only rejectable material from the grinder product flow stream.
The multiple surfaces of the valve head serve to increase the overall surface area of the valve head (as compared to a valve element having a constant planar pressure surface profile) in contact with the grinder product flow stream. In a preferred profile, the valve may include a circular groove which extends lengthwise within the valve head at an angle from its axis to define a variable discharge passage in the valve head, such that as the system pressure increases, the valve opening incrementally increases to reduce back pressure on the system so that substantially only rejectable food material is removed from the grinder product flow stream.
Accordingly, it is an object of the present invention to provide a means for regulating the discharge of bones and other hard material from a food material grinder.
It is another object of the present invention to provide a means for increasing the backpressure of a food material grinding apparatus having a bone discharge device which incorporates a flow control means into the bone discharge line of the grinding apparatus which regulates the amount of unusable material discharged from the grinding apparatus, which discharge is regulated solely by the flow of unusable material exiting from the grinding apparatus and not by any external regulation means.
It is still another object of the present invention to provide a means for providing a controlled backpressure on a discharge line of a food material grinding apparatus and thereby regulating the discharge of bones and unusable food material out of the grinding apparatus, wherein the means includes a discharge flow control valve disposed within a bone discharge line, the valve having a valve element which contains a groove of variable size, the size of the groove depending upon the movement of the valve element within the housing in response to the grinding apparatus backpressure, which groove is in contact with the grinding apparatus product flow stream.
Yet another object of the present invention is to provide a bone discharge regulating device for use on a food material grinder having a bone elimination and discharge component, wherein the device is mounted in a discharge line of the bone elimination and discharge component and includes a valve element having a multiple surface profile in contact with the product flow stream, the valve element including a reciprocatable plunger element disposed in the discharge line, the plunger element having a longitudinal groove extending therein, the groove presenting a valve opening which has a specific size at an open position of the valve and which steadily decreases as the valve closes, thereby providing a variable opening within the plunger element which permits bone material to pass through the discharge line through the plunger element groove.
Another object of the present invention is to provide a means for controlling the flow of waste material out of a food grinding apparatus which substantially reduces the overall amount of material discharged to waste from the grinding apparatus while removing substantially all of the bones, hard material and foreign objects from the food material being processed.
These and other objects, features and advantages of the present invention will be clearly understood through a consideration of the following detailed description.


The invention relates to a drilling-resistance measuring device (10) and to a method for material testing in a humid environment or underwater. The drilling-resistance measuring device (10) comprises a housing (1), in which a drive and a drill chuck (3) coupled to the drive are arranged, in which drill chuck a drilling needle (4) is or can be releasably held, wherein the housing (1) has a drilling-needle outlet opening (5′) enclosed by a drilling-needle outlet guide (5), through which drilling-needle outlet opening the drilling needle (4) extends out of the housing (1). The drilling-resistance measuring device (10) comprises at least one water-tight bellows (6), which is arranged in the interior of the housing (1) around the drilling needle (4) between the drill chuck (3) and the drilling-needle outlet guide (5), wherein moisture or water can enter the bellows (6) through the drilling-needle outlet opening (5′).

The invention concerns a drilling resistance measuring device for material testing that is provided for work and use in humid environment, in particular also under water. The drilling resistance measuring device comprises a housing in which a drive and a drill chuck, coupled with the drive and provided with a drilling needle detachably arranged therein, are arranged, wherein the housing comprises a drilling needle outlet opening which is surrounded by a drilling needle outlet guide and through which the drilling needle extends out of the housing.
For performing drilling resistance measurements by means of which material properties in the interior of test bodies are derived, drilling resistance measuring devices with thin drilling tools or drilling needles are used. The drilling needle is moved by a drive of the drilling resistance measuring device and driven into the test body wherein, for example, the power input or the current consumption of the drive is used as a measure for the drilling resistance of the test body upon penetration or removal of the drilling needle and correlated, for example, with the penetration depth of the drilling needle so that the material properties in the interior of the test body can be assessed.
In case of measurements in humid environment, for example, in pouring rain or under water, penetration of moisture or water into the drilling resistance measuring device is to be prevented in order to avoid damaging the drive.
DE 100 31 334 A1 discloses in this context a drilling resistance measuring device that comprises an outlet opening for the drilling needle and means for generating an increased gas pressure in the interior of the drilling resistance measuring device so that the pressure present in the interior of the drilling resistance measuring device corresponds to a simultaneously measured outer pressure and no water can penetrate into the interior of the drilling resistance measuring device. The means for generating an increased inner gas pressure can be a pressurized gas line coupled with the interior of the drilling resistance measuring device or an attached gas cartridge.
Based on this prior art, it is the object of the present invention to provide a drilling resistance measuring device that is functioning in humid environment and under water independent of a pressurized gas source.

Drilling-resistance measuring device for use underwater


A method and an apparatus for electrokinetically decontaminating the soil contained in a radioactive waste drum are disclosed. The radioactively contaminated soil is put into drums, and the drums are carried to a temporary storage or to a disposal site. If the extremely low level radioactive soil is decontaminated rather than carrying the soil to the temporary storage or to a disposal site, and if the decontaminated soil is returned to the nature, then the limited storage capacity can be saved. Further, if a high level radioactive soil is treated to a low level one, and if thus a low level radioactive soil is stored in a storage, then the safety is improved. In the present invention, electrodes are buried into the contaminated soil contained in a radioactive waste drum, and a dc current is supplied, so that the radioactive nuclide and impurities can be removed by the electroosmosis and the electromigration. The anode includes: (1) at least 3 or more metal tubes made of titanium or zircaloy and having a diameter of 5 cm or less; (2) at least 6 or more metal rods made of stainless steel, titanium, or zircaloy; and (3) stainless steel sieves. The cathode is a tube made of carbon steel, stainless steel, or palladium, and has a diameter of 10 cm or less.

1. Field of the Invention
The present invention relates to a method and an apparatus for electro-kinetically decontaminating the soil contained in a radioactive waste drum.
2. Description of the Prior Art
Patent applications for the technique similar to the present invention have been filed since 1989, and the last patent was issued in 1998 under U.S. Pat. No. 5,725,752.
Between 1981 and 1985 in the United States, there were developed a method for extracting water from a sludge by using a dynamic electric current, a method for drying wet soil, and a method for adjusting the water flow amount or for reversing the water flow direction. Patents were issued for these techniques (U.S. Pat. Nos. 4,305,800, 4,382,341, and 4,479,857). Between 1976 and 1993 in Japan, a method for extracting water from soil was developed, and patents were issued (02136435 JP A1). Besides the environmental industries, the Hewlett-Packard company utilized the electroosmosis to develop an ink distribution unit for the ink jet printer. Patent applications for this technique were filed in the U. S. and Japan.
To describe the patents related to the present invention, R. F. Probstein et al. filed a patent application in 1989, and obtained a patent in 1991 (U.S. Pat. No. 5,074,986). The technique was on decontaminating the soil site, and the title of the invention was "Electroosmosis Techniques for Removing Materials from Soil". The main claim was on electrically decontaminating the contaminated soil site, and the related claims were on the voltage gradients, on the electrodes, and on the purging liquid supply method.
Almost simultaneously with R. F. Probstein et al., Y. B. Acar et al. obtained a patent (U.S. Pat. No. 5,137,608) under the title of "Electrochemical Decontamination of Soils or Slurries". The total number of claims were 33, and the technique was on an inert anode (containing graphite) and a non-reactive cathode (containing graphite). The object to be decontaminated is metals (such as Pb ions), organic materials, and radioactive nuclides. The Pb ions are recovered at the cathode. The main electrochemical process within the soil includes the steps of: (1) transmitting direct electric current through the soil between an inert anode and non-reactive cathode; (2) supplying a first liquid which comprises water to the soil near said anode; and (3) introducing a nutrient into the soil thorough electroosmosis.
J. P. Bibler obtained in 1993 a patent under the title of "Method and Apparatus for Removing Ions from Soil" (U.S. Pat. 5,190,628). The technique is on selectively removing ions from the soil. That is, a permeable membranes impregnated with an ion exchange resin that is specific to one or more species of chemical ions are inserted into ground. Then electrodes are installed near the membrane, and a voltage is supplied to them. Preferably, the resin exchanges ions of sodium or hydrogen for ions of metal that it captures from soil area. When the permeable membrane is saturated with the metal ions, the potential applied across electrodes is discontinued and membranes are preferably removed from soil for storage or recovery of the ions. The claims state the following matters. That is, there is provided a method for removing one or more species of ions from an area of soil groundwater. That is, (1) placing at least two electrodes in spaced relation with respect to each other and to said area of soil; (2) placing a permeable barrier adjacent each of said at least two electrodes and said area of soil, said barrier adapted to pass said groundwater, said barrier carrying an ion exchange resin, said resin being selective for said at least one species of ions; and (3) applying a potential across said electrodes, said potential causing said at least one species of ions to migrate with respect to said electrodes, thereby allowing said ion exchange resin carried in said permeable barrier to capture said species. The main species removed is assumed to be a mercury ion, and at least two titanium electrodes are installed. The first and second membranes are spaced approximately 10 feet apart and said electric potential is approximately 60 volts DC.
H. R. Chang et al. obtained a patent in 1993 under the title of "Surfactant Augmented In-situ Removal of Poly-chloro-benzenes from Soil by Electroosmosis" (U.S. Pat. No. 5,240,570). In this method, the contaminants such as poly-chloro-benzenes are electro-osmotically extracted from soil at the contamination site. By adding a low concentration surfactant solution, the decontamination capability is reinforced.
R. A. Jacobs obtained a patent in 1995 under the title of "Removal of Contaminant Material from a Soil Site" (U.S. Pat. No. 5,415,744). In this method, at least one anode is positioned in the soil site, and a plurality of cathodes are disposed around the anode. Then a voltage gradient is established between the anode and the cathodes. Owing to the electroosmosis, the solution at the anode moves to the cathodes. That is, the contaminant materials are moved together with the solution, and are removed at the cathodes. The total number of the claims was 19, and the method includes the steps of: (1) positioning one anode at a first location within said soil site; (2) positioning a plurality of only cathodes at second locations around said anode; (3) establishing voltage gradients between said anode and the said plurality of cathodes; (4) supplying a non-contaminated solution to the anode so as to make the solution and the contamination substances move toward the cathodes; and (5) removing said material from said cathodes. Here, the number of the cathodes should be at least three, and the cathodes should be disposed symmetrically relative to the anode. The cathodes are disposed in a circular form. At the step 5, the solution together with the contamination substances can be removed through separate paths for the respective cathodes, or can be combinedly removed.
W. Pool of Netherlands obtained a patent in 1995 under the title of "Process for the Electroreclamation of Soil Material" (U.S. Pat. No. 5,433,829). The content of this invention is similar to the other ones, but is characterized in that: (1) one or more anodes and one or more cathodes are used, and different levels of voltages are applied between different electrodes; and (2) the contaminants are removed both at the anode and at the cathode unlike the other inventions. The total number of claims was 11. Claim 1 defines as follows. That is, an anode and a cathode are installed within a soil which is contaminated with heavy metals and cyanides. Then an electric current is made to flow between the electrodes so that the contaminants would be gathered to the electrodes. Specifically, claim 1 includes the steps of: (1) inserting an electrode into a porous container to make the electrode serve as an anode (or a cathode) so as to make an electric current flow between this electrodes and another electrode (cathode or anode); (2) installing the electrode into the soil; (3) injecting an electrolytic solution into the electrodes through a cathode circulation system and through an anode circulation system; (4) supplying a dc current to the electrodes to make the contamination substances move to the electrodes (electro-migration); and (5) removing the contamination substances from the anode and the cathode.
Further, continuous adjustments are carried out on the pH level of the circulation system, the electrical conductivity, temperature and current density within the solution. Other claims contain the following contents. That is, an acid is added to adjust the acidity of the solution so as to improve the decontamination effect. The anode is made of a noble metal, and the cathode is made of graphite. The heavy metals to be removed are ions of Cu, Pb, Zn, Ni, Co, Fe, Sr, Mg and Ca. In this method, the migration of the contaminants can also be prevented by the application of electrical method.
R. J. Griffith et al. obtained a patent in 1996 under the title of "Electric Field Method And Apparatus for decontaminating Soil" (U.S. Pat. No. 5,584,980). The subject matter of this invention is as follows. That is, an in-situ decontamination is carried out by using a plurality of adjacent electrodes. This invention offers a low cost decontamination. The total number of claims is 33, and claim 1 includes the steps of: (1) arranging a plurality of small adjacent electrodes in one rows into the soil to form a planar anode; (2) arranging a plurality of small adjacent electrodes in one row into the soil to form a planar cathode; (3) making the distance between the electrodes within one row become 50% as large as the distance between the rows; (4) supplying voltages to the anodes; (5) directing a first fluid containing an additive to the anode assemblies to make the solution move to the cathode based on the electroosmosis; (6) making the remaining solution flow faster than the electroosmotic flow so as to recover it.
In claim 2, a second solution having an additive is injected to the cathode, and the solution coming from the anode is recovered. Besides, the claims contain the following contents. That is, the waste solution is treated to reuse it. The method is applied to the region of soil. The anodes are arranged alternately with the cathodes. A permeable geomembrane is used. Two cylindrical electrodes are coaxially used, so that a solution channel can be formed.
J. G. Sunderland et al. of England obtained patents in 1998 under the title of "Electrokinetic Decontamination of Land" (U.S. Pat. No. 5,725,752, and EP 0 724 492 B1). The subject matter of this invention is as follows. That is, the soil is decontaminated by applying a DC electric field across electrodes. At least one anode and at least one cathode are installed in or on said soil, and then, a dc electric current is supplied. Here, a typical anode assembly for use in the method of the invention comprises the carbon felt anode material wrapped around a suitable current feeder and one or more electrolyte feed means. And, the cathode assembly for use in accordance with the method of the invention comprises a cathode, which may be, for example of stainless steel or alternatively a carbon felt material like the anode, within a porous housing, the housing allowing the passage of electrolyte therethrough. This is an in-situ decontamination method using an electrode group, and its cost is very low. The total number of claims is 16, and claim 1 is characterized as follows. That is, at least one anode is installed within the soil, and a DC current is supplied to it, so that oxygen would be produced. The anode is wrapped with a carbon fiber, and the carbon fiber directly contacts with the soil. In claim 2, a cathode is disposed within a porous housing through which the electrolyte can pass. The porous cathode housing is made of a ceramic material, a microporous polymer material or a dense cloth. -The anode is made of carbon, active carbon, or carbon fiber. When a DC current is supplied to it, a colloidal carbon is formed, and moves together with the water owing to the electric field. An electrolyte is supplied through tiny channels which are formed within the carbon anode layer. The cathode is made of stainless steel, nickel, carbon felt and titanium suboxide. The additive for improving the decontamination efficiency is composed of water soluble electrolytes, non-ionic surfactants, cationic surfactants, complexing agents, polyelectrolyte leachants, inorganic acids and organic acids. Between the anode and the cathode, there is at least one bore hole. And, at least one bore hole is positioned outside of an area between the cathode and the electrode.
Yamazaki Teruhiko and Katsura Tsutomu filed patent applications respectively in 1991 and 1993 (19910831 JP 03-244356, and 19930206 JP 05-42197). The titles were "Method for Disposing Polluted Soil, And Its Equipment" and "Method And Device for Treating Water-containing Soil On Site by Electroosmosis".
Orito Shigeru filed a patent application in 1995 (19950411 JP 07-110103), and the title of the invention was "Electrochemical Treatment". In this invention, without using a complicated apparatus, a contaminated soil or sludge is separated and treated. That is, the contaminated soil or sludge is put into between an anode and a cathode, and a solution is let to flow on it, while supplying electric current. Then the harmful substances move between the anode and the cathode. These substances are extracted and electrolyzed.
Takagi Kazuhiro at al. filed a patent application in 1995 (19951227 JP 07-341207), and the title of the invention was "Method for Removing Salt from Saline Soil". The subject matter of the invention is as follows. That is, when electroosmotically decontaminating the soil, metal components are deposited on the electrode, and this problem is solved. That is, the deposition of the metals is inhibited by adding a complexing agent into the solution.
Further, it was found that Monsanto Company (St. Louis) filed a patent application (Application No. 95-70601, and Laid-open No. 96-703390) in Korea. This is same as U.S. Pat. No. 5,476,992 (In-Situ Remediation of Contaminated Heterogeneous Soil). It is found that the total number of claims is 3 in a Korean patent, and claim 1 defines that a chemical agent is added to clean a contaminated soil. Claim 2 defines that an electrical method is employed to clean a contaminated soil. Claim 3 defines that a water pressure flow is induced based on the water pressure gradient to clean a contaminated soil. Particularly, in claim 2, a dc current is supplied between a first electrode and a second electrode for the following purposes. (1) An electroosmotic flow is induced from the second electrode to the first electrode, or (2) ionic migration occurs toward the electrode having the opposite charges, or (3) ionic contamination substances are made to migrate from the second electrode to the first electrode by electroosmosis and toward the electrode having the opposite charges by electromigration. Here, (a) The first electrode is disposed at a first edge of the contaminated soil area, and the second electrode is disposed at the opposite edge of the contaminated soil area. (b) Th e first electrode is disposed at an edge of the low transmissive soil area.

Method for electro-kinetically decontaminating soil contained in a radioactive waste drum, and apparatus therefor