Novel 2-aza-bicyclo[2.2.2]octanes substituted in the 2-position are effective as NMDA NR2B antagonists useful for relieving pain.

Field of the Invention
This invention relates to novel 2-aza-bicyclo[2.2.2]octanes. In particular, this invention relates to novel 2-aza-bicyclo[2.2.2]octanes substituted in the 2-position that are effective as NMDA NR2B antagonists useful for relieving pain.
Ions such as glutamate play a key role in processes related to chronic pain and pain-associated neurotoxicityxe2x80x94primarily by acting through N-methyl-D-aspartate (xe2x80x9cNMDAxe2x80x9d) receptors. Thus, inhibition of such actionxe2x80x94by employing ion channel antagonists, particularly NMDA antagonistsxe2x80x94can be beneficial in the treatment and control of pain.
Known NMDA antagonists include ketamine, dextromophan, and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (xe2x80x9cCPPxe2x80x9d). Although these compounds have been reported (J. D. Kristensen, et al., Pain, 51:249-253 (1992); K. Eide, et al., Pain, 61:221-228 (1995); D. J. Knox, et al., Anaesth. Intensive Care 23:620-622 (1995); and M. B. Max, et al., Clin. Neuropharmacol. 18:360-368 (1995)) to produce symptomatic relief in a number of neuropathies including postherpetic neuralgia, central pain from spinal cord injury, and phantom limb pain, widespread use of these compounds is precluded by their undesirable side effects. Such side effects at analgesic doses include psychotomimetic effects such as dizziness, headache, hallucinations, dysphoria, and disturbances of cognitive and motor function. Additionally, more severe hallucinations, sedation, and ataxia are produced at doses only marginally higher than analgesic doses. Thus, it would be desirable to provide novel NMDA antagonists that are absent of undesirable side effects or that produces fewer and/or milder side effects.
NMDA receptors are heteromeric assemblies of subunits, of which two major subunit families designated NR1 and NR2 have been cloned. Without being bound by theory, it is generally believed that the various functional NMDA receptors in the mammalian central nervous system (xe2x80x9cCNSxe2x80x9d) are only formed by combinations of NR1 and NR2 subunits, which respectively express glycine and glutamate recognition sites. The NR2 subunit family is in turn divided into four individual subunit types: NR2A, NR2B, NR2C, and NR2D. I. Ishii, et al., J. Biol. Chem., 268:2836-2843 (1993), A. Wenel, et al., NeuralReport, 7:45-48 (1995), and D. J. Laurie et al., Mol. Brain Res., 51:23-32 (1997) describe how the various resulting combinations produce a variety of NMDA receptors differing in physiological and pharmacological properties such as ion gating properties, magnesium sensitivity, pharmacological profile, as well as in anatomical distribution.
For example, while NR1 is found throughout the brain, NR2 subunits are differentially distributed. In particular, it is believed that the distribution map for NR2B lowers the probability of side effects while producing pain relief. For example, S. Boyce, et al., Neuropharmacology, 38:611-623(1999) describes the effect of selective NMDA NR2B antagonists on pain with reduced side-effects. Thus, it would be desirable to provide novel NMDA antagonists that target the NR2B receptor.
International Patent Publication WO94/21615 describes benzimidazole-piperidine compounds utilized as dopamine D4 antagonists. Phenol compounds described as NMDA antagonists are described in U.S. Pat. Nos. 5,306,723 and 5,436,255, and in International Patent Publications WO91/17156, WO92/19502, WO93/02052, WO94/29571, WO95/28057, WO96/37226, and EP 04422506. Benzyl piperidines substituted with phenols or imidazoles are described in Z. -L. Zhou, et al., J. Medicinal Chemistry, 42:2993-3000(1999); T. F. Gregory, et al., Poster #94, 218th National Meeting American Chemical Society, New Orleans, La., Aug. 22-26, 1999. Other NMDA NR2B selective compounds are described in European Patent Publication EP 787493 and British J. Pharnacol., 123:463(1998). However, there continues to be a need for novel NMDA antagonists that target the NR2B receptor.
The present invention relates to 2-aza-bicyclo[2.2.2]octanes substituted in the 2-position with benzimidazoles, imidazopyridines, phenols or imidazoles either directly or through a C1-C4alkyl, cycloalkyl, hydroxyalkyl, alkoxy or aminoalkyl chain. The present invention also forms novel pharmaceutical compositions utilizing these novel compounds. Further, this invention includes novel methods to treat pain by utilizing the novel compounds.
In one aspect, the compounds of this invention are represented by Formula (I):
or pharmaceutically acceptable salts thereof, wherein
R1 is 2-benzimidazole, 4-imidazole, 2-imidazopyridine, 2-indole, 2-quinazoline, or 4-phenol;
R2 is phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, C1-C4alkyl, trifluoromethyl, hydroxy, or carboxy;
L1 is C1-C4alkyl, C1-C4alkenyl, C1-C4alkynyl, C1-C4alkoxy, aminoC1-C4alkyl, hydroxyC1-C4alkyl, carbonyl, cycloC3-C6alkyl or aminocarbonyl;
L2 is phenylmethyl or phenylmethylaminocarbonyl, optionally substituted with chloro, fluoro, bromo, or methyl; and
optionally substituted at any of the 3, 5, 6, 7, or 8 positions independently with X, wherein X is hydroxy, amino, C1-C4alkylamino, di(C1-C4)alkylamino, C1-C4alkyl, ester, carbamate, carbonate, or ether.
In an embodiment, the compound of this invention is represented by Formula (I) or a pharmaceutically acceptable salt thereof, wherein
R1 is 2-benzimidazole;
R2 is phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, C1-C4alkyl, trifluoromethyl, hydroxy, or carboxy;
L1 is C1-C4alkyl, C1-C4alkenyl, C1-C4alkynyl, C1-C4alkoxy, aminoC1-C4alkyl, hydroxyC1-C4alkyl, carbonyl, cycloC3-C6alkyl or aminocarbonyl;
L2 is phenylmethyl or phenylmethylaminocarbonyl, optionally substituted with chloro, fluoro, bromo, or methyl; and
optionally substituted at any of the 3, 5, 6, 7, or 8 positions independently with X, wherein X is hydroxy, amino, C1-C4alkylamino, di(C1-C4)alkylamino, C1-C4alkyl, ester, carbamate, carbonate, or ether.
In another embodiment, the compound of this invention is represented by Formula (I) or a pharmaceutically acceptable salt thereof, wherein
R1 is 2-imidazopyridine;
R2 is phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, C1-C4alkyl, trifluoromethyl, hydroxy, or carboxy;
L1 is C1-C4alkyl, C1-C4alkenyl, C1-C4alkynyl, C1-C4alkoxy, aminoC1-C4alkyl, hydroxyC1-C4alkyl, carbonyl, cycloC3-C6alkyl or aminocarbonyl;
L2 is phenylmethyl or phenylmethylaminocarbonyl, optionally substituted with chloro, fluoro, bromo, or methyl; and
optionally substituted at any of the 3, 5, 6, 7, or 8 positions independently with X, wherein X is hydroxy, amino, C1-C4alkylamino, di(C1-C4)alkylamino, C1-C4alkyl, ester, carbamate, carbonate, or ether.
As used herein, xe2x80x9calkylxe2x80x9d as well as other groups having the prefix xe2x80x9calkxe2x80x9d such as, for example, alkoxy, alkanoyl, alkenyl, alkynyl and the like, means carbon chains which may be linear or branched or combinations thereof. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, sec- and tert-butyl, pentyl, hexyl, heptyl and the like. xe2x80x9cAlkenylxe2x80x9d, xe2x80x9calkynylxe2x80x9d and other like terms include carbon chains containing at least one unsaturated Cxe2x80x94C bond.
The term xe2x80x9ccycloalkylxe2x80x9d means carbocycles containing no heteroatoms, and includes mono-, bi- and tricyclic saturated carbocycles, as well as fused ring systems. Such fused ring systems can include one ring that is partially or fully unsaturated such as a benzene ring to form fused ring systems such as benzofused carbocycles. Cycloalkyl includes such fused ring systems as spirofused ring systems. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, decahydronaphthalene, adamantane, indanyl, indenyl, fluorenyl, 1,2,3,4-tetrahydronaphalene and the like. Similarly, xe2x80x9ccycloalkenylxe2x80x9d means carbocycles containing no heteroatoms and at least one non-aromatic Cxe2x80x94C double bond, and include mono-, bi- and tricyclic partially saturated carbocycles, as well as benzofused cycloalkenes. Examples of cycloalkenyl include cyclohexenyl, indenyl, and the like.
Unless otherwise stated, the terms xe2x80x9ccarbonylxe2x80x9d and xe2x80x9caminocarbonylxe2x80x9d include short C1-C2 termini. The terms include, for example, xe2x80x94CH2CONHxe2x80x94, xe2x80x94CH2COxe2x80x94, xe2x80x94C2H4CONHCH2xe2x80x94, and xe2x80x94CH2COC2H4xe2x80x94.
Unless otherwise stated, the term xe2x80x9ccarbamatexe2x80x9d is used to include xe2x80x94OCOOC1-C4alkyl, xe2x80x94NHCOOC1-C4alkyl, and xe2x80x94OCONHC1-C4alkyl.
The term xe2x80x9chalogenxe2x80x9d includes fluorine, chlorine, bromine and iodine atoms.
The term xe2x80x9cSEMxe2x80x9d is used to describe xe2x80x94CH2xe2x80x94Oxe2x80x94CH2CH2xe2x80x94Si(CH3)3.
The term xe2x80x9cC0xe2x80x9d means that the carbon is not present. Thus, xe2x80x9cC0-C5xe2x80x9d means that there are from none to five carbons presentxe2x80x94that is, five, four, three, two, one, or no carbons present.
The term xe2x80x9coptionally substitutedxe2x80x9d is intended to include both substituted and unsubstituted. Thus, for example, optionally substituted aryl could represent a pentafluorophenyl or a phenyl ring.
Compounds described herein contain one or more asymmetric centers and may thus give rise to diastereomers and optical isomers. The present invention includes all such possible diastereomers as well as their racemic mixtures, their substantially pure resolved enantiomers, all possible geometric isomers, and pharmaceutically acceptable salts thereof. The above Formula I is shown without a definitive stereochemistry at certain positions. The present invention includes all stereoisomers of Formula I and pharmaceutically acceptable salts thereof. Further, mixtures of stereoisomers as well as isolated specific stereoisomers are also included. During the course of the synthetic procedures used to prepare such compounds, or in using racemization or epimerization procedures known to those skilled in the art, the products of such procedures can be a mixture of stereoisomers.
The term xe2x80x9cpharmaceutically acceptable saltsxe2x80x9d refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids. When the compound of the present invention is acidic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic bases, including inorganic bases and organic bases. Salts derived from such inorganic bases include aluminum, ammonium, calcium, copper (ic and ous), ferric, ferrous, lithium, magnesium, manganese (ic and ous), potassium, sodium, zinc and the like salts. Particularly preferred are the ammonium, calcium, magnesium, potassium and sodium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, as well as cyclic amines and substituted amines such as naturally occurring and synthesized substituted amines. Other pharmaceutically acceptable organic non-toxic bases from which salts can be formed include ion exchange resins such as, for example, arginine, betaine, caffeine, choline, N,Nxe2x80x2-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine and the like.
When the compound of the present invention is basic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. Such acids include, for example, acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic acid and the like. Particularly preferred are citric, hydrobromic, hydrochloric, maleic, phosphoric, sulfuric, and tartaric acids.
The pharmaceutical compositions of the present invention comprise a compound represented by Formula I (or pharmaceutically acceptable salts thereof) as an active ingredient, a pharmaceutically acceptable carrier and optionally other therapeutic ingredients or adjuvants. The compositions include compositions suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The pharmaceutical compositions may be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy.
In practice, the compounds represented by Formula I, or pharmaceutically acceptable salts thereof, of this invention can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral or parenteral (including intravenous). Thus, the pharmaceutical compositions of the present invention can be presented as discrete units suitable for oral administration such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient. Further, the compositions can be presented as a powder, as granules, as a solution, as a suspension in an aqueous liquid, as a non-aqueous liquid, as an oil-in-water emulsion or as a water-in-oil liquid emulsion. In addition to the common dosage forms set out above, the compound represented by Formula I, or pharmaceutically acceptable salts thereof, may also be administered by controlled release means and/or delivery devices. The compositions may be prepared by any of the methods of pharmacy. In general, such methods include a step of bringing into association the active ingredient with the carrier that constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both. The product can then be conveniently shaped into the desired presentation.
Thus, the pharmaceutical compositions of this invention may include a pharmaceutically acceptable carrier and a compound or a pharmaceutically acceptable salt of Formula I. The compounds of Formula I, or pharmaceutically acceptable salts thereof, can also be included in pharmaceutical compositions in combination with one or more other therapeutically active compounds.
The pharmaceutical carrier employed can be, for example, a solid, liquid, or gas. Examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid. Examples of liquid carriers are sugar syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen.
In preparing the compositions for oral dosage form, any convenient pharmaceutical media may be employed. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like may be used to form oral liquid preparations such as suspensions, elixirs and solutions; while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like may be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solid pharmaceutical carriers are employed. Optionally, tablets may be coated by standard aqueous or nonaqueous techniques A tablet containing the composition of this invention may be prepared by compression or molding, optionally with one or more accessory ingredients or adjuvants. Compressed tablets may be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent. Each tablet preferably contains from about 1 mg to about 500 mg of the active ingredient and each cachet or capsule preferably containing from about 1 to about 500 mg of the active ingredient.
Pharmaceutical compositions of the present invention suitable for parenteral administration may be prepared as solutions or suspensions of the active compounds in water. A suitable surfactant can be included such as, for example, hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Further, a preservative can be included to prevent the detrimental growth of microorganisms.
Pharmaceutical compositions of the present invention suitable for injectable use include sterile aqueous solutions or dispersions. Furthermore, the compositions can be in the form of sterile powders for the extemporaneous preparation of such sterile injectable solutions or dispersions. In all cases, the final injectable form must be sterile and must be effectively fluid for easy syringability. The pharmaceutical compositions must be stable under the conditions of manufacture and storage; thus, preferably should be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g. glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof.
Pharmaceutical compositions of the present invention can be in a form suitable for topical use such as, for example, an aerosol, cream, ointment, lotion, dusting powder, or the like. Further, the compositions can be in a form suitable for use in transdermal devices. These formulations may be prepared, utilizing a compound represented by Formula I of this invention, or pharmaceutically acceptable salts thereof, via conventional processing methods. As an example, a cream or ointment is prepared by mixing hydrophilic material and water, together with about 5 wt % to about 10 wt % of the compound, to produce a cream or ointment having a desired consistency.
Pharmaceutical compositions of this invention can be in a form suitable for rectal administration wherein the carrier is a solid. It is preferable that the mixture forms unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art. The suppositories may be conveniently formed by first admixing the composition with the softened or melted carrier(s) followed by chilling and shaping in moulds.
In addition to the aforementioned carrier ingredients, the pharmaceutical formulations described above may include, as appropriate, one or more additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface-active agents, thickeners, lubricants, preservatives (including anti-oxidants) and the like. Furthermore, other adjuvants can be included to render the formulation isotonic with the blood of the intended recipient. Compositions containing a compound described by Formula I, or pharmaceutically acceptable salts thereof, may also be prepared in powder or liquid concentrate form.
The activity of selected compounds to inhibit NR1A/2B NMDA receptor activation measured as NR1A/2B receptor-mediated Ca2+ influx is assessed by the following procedure:
NR1A/2B receptor transfected L(tk) cells are plated in 96-well format at 3xc3x97106 cells per plate and grown for onexe2x80x94two days in normal growth media (Dulbeccos MEM with Na pyruvate, 4500 mgglucose, pen/strep, glutamine, 10% FCS and 0.5 mg/ml geneticin). NR1A/2B-expression in these cells is induced by the addition of 4nM dexamethasone in the presence of 500 xcexcM ketamine for 16-24 hours. After receptor induction cells are washed using a Labsystem Cellwasher two times with assay buffer (Hanks balanced salt solution (HBSS-Mg++ free) containing 20 mM HEPES, 0.1% BSA, 2 mM CaCl2 and 250 xcexcM probenecid). The cells of each 96 well cell plate are loaded with the Ca++ sensitive dye Fluo-3 (Molecular Probes, Inc.) at 4 xcexcM in assay buffer containing 0.5% FBS, and 0.04% pluronic F-127 (Molecular Probes, Inc.) for 1 h at 37xc2x0 C. avoiding light. The cells are then washed with the Cellwasher four times with assay buffer leaving them in 100 xcexcl buffer. Test compounds in solution are pipetted by FLIPR (Fluorometric Imaging Plate Reader) into each test well for a 2 min pretreatment. During this time the fluorescence intensity is recorded (excitation at 488 nm and emission at 530 nm). The glutamate/glycine 50 xcexcL agonist solution (final concentration 1 xcexcM/1 xcexcM) is then added by FLIPR into each well already containing 150 xcexcL of buffer (containing the test compound or vehicle) and the fluorescence is continuously monitored for 10 min. The end point fluorescence values are used to determine an IC50 value comparing the agonist-stimulated signal for the vehicle alone sample and that for the cells incubated with each concentration of test compound.
The radioligand binding assay is performed at room temperature in 96-well microtiter plates with a final assay volume of 1.0 mL in 20 mM Hepes buffer (pH 7.4) containing 150 mM NaCl. Solutions of test compounds were prepared in DMSO and serially diluted with DMSO to yield 20 xcexcL of each of 10 solutions differing by 3-fold in concentration. Non-specific binding (NSB) using hot AMD-1 (10 xcexcM final concentration) and total binding (TB) by using DMSO (2% final concentration). A solution of NR1A/NR2B receptors (40 pM final concentration) and tritiated AMD-2 (1 nM final concentration) were added to the test compounds. After 3 h of incubation at room temperature, samples are filtered through Packard GF/B filters (presoaked in 0.05% PEI, polyethyleninine Sigma P-3143) and washed 10 times with 1 mL of cold 20 mM Hepes buffer per wash. After vacuum drying of the filter plates, 40 xcexcL of Packard Microscint-20 was added and bound radioactivity determined in a Packard TopCount. The apparent dissociation constant (Ki), the maximum percentage inhibition (% Imax), the minimum percentage inhibition (% Imin) and the hill slope (nH) were determined by a non-linear least squares fitting the bound CPM data to Equation #1 below.
Equation#1:       CPM              xe2x80x83            Bound    =                              (          SB          )                                  (                                    %                                            I                max                                      -                          %                                            I                min                                              )                            (                  I          +                                    (                                                [                  Drug                  ]                                /                                  (                                                            Ki                                                                    [                                                                              L                            -                            844                                                    ,                          345                                                ]                                                              /                                          K                      D                                                        )                                            )                        nH                          )              +    NSB    +                  (        SB        )                          (                  1          -                      %                                      I              max                                      )
where, KD is the apparent dissociation constant for the radioligand for the receptor as determined by hot saturation and SB is the specifically bound CPM determined from the difference of TB and NSB.
Compounds AMD-1 and AMD-2 can be synthesized in accordance with the following general reaction schemes.
In accordance with scheme 1, hydrogen chloride is bubbled through a solution of the appropriately substituted benzonitrile 1 in methanol at room temperature. The volatiles are removed under reduced pressure and the resulting residue is triturated with ether and filtered to yield the desired imidate 2. Imidate 2 is dissolved in methanol at ambient temperature, treated with amine 3 at ambient temperature and stirred under argon. The volatiles are removed under reduced pressure and the residue purified by preparative HPLC or trituration with ether to afford amidine Ia.
In accordance with scheme 2, at room temperature under argon, amine 3a is dissolved in ether and was treated with 1-M hydrogen chloride in ether (1 equiv.) in a single portion. The resulting precipitate is stirred vigorously for 10 minutes. The volatiles are removed under reduced pressure. The residue is suspended in toluene, cooled to 0xc2x0 C. under argon, treated with 2.0-M trimethylaluminum (1.05 equiv.) in a dropwise manner, and stirred for 45 minutes at room temperature to afford intermediate 6 (not isolated). Compound 6 is added to a solution of nitrile 1 in toluene. The reaction is heated to 80xc2x0 C without stirring in a sealed tube for 18 h, cooled to ambient temperature, poured onto a silica gel column and eluted with methanol/dichloromethane to give the amidine 4.
Tritiated AMD-1 was prepared by the following procedure: A mixture of AMD-1, hydrochloride salt, (5 mg, 0.012 mmol) in dioxane (0.2mL) containing triethylamine (4 xcexcL) was treated with hexamethylditin (5 xcexcL), a catalytic amount of palladium catalyst and heated at 100xc2x0 C. for 45 minutes. The reaction was cooled to room temperature, filtered through a glass wool plug, rinsed with methanol and concentrated in vacuo to give 10.7 mg of a brown oil. The oil was dissolved in methylene chloride and passed through a small silica column eluting with methylene chloride followed by 5% methanol/methylene chloride. Fractions containing the trimethylstannane (Rf 0.26 in 10% methanol/methylene chloride) were pooled and concentrated in vacuo to give 4.5 mg of the trimethylstannane as a clear colorless oil.
This material was further purified by HPLC (C18 Econosil, 10xc3x97250 mm, 20 minute linear gradient, 30% MeCN:70% H2O (0.1% TFA) to 90% MeCN, 3 mL/min, 254 nm, retention time 15 minutes) to give 3 mg of the trimethylstannane.
A Na125I shipping vial (10 mCi, Amersham) was charged with a stir bar, an iodobead, 50 xcexcL of methanol and stirred five minutes at room temperature. A solution of the trimethylstannane (0.1 mg) in 50 xcexcL of methanol containing 5 xcexcL of trifluoroacetic acid was added and the reaction was stirred for five minutes. The 20 reaction was quenched with 50 xcexcL of ammonium hydroxide and purified by HPLC (C18 Vydac protein and peptide column, 4.6xc3x97250 mm, 20 minute linear gradient, 30% MeCN:70% H2O (0.1% TFA) to 90% MeCN, 1 mL/min, retention time 11 minutes). Fractions containing the radioactive product were pooled and concentrated in vacuo to give 989 xcexcCi of [125I]AMD-1 with a specific activity of 898 Ci/mmol as measured by UV absorbance at 272 nm.
Tritiated AMD-2 was prepared by the following procedure: The phenol of AMD-2 (2 mg, 0.008 mmol) dissolved in dimethylformamide (0.6mL) and potasium carbonate (1.2 mg) for 1 hr. High specific activity tritiated methyl iodide (50mCi, 0.0006 mmol, in toluene 1 mL, American Radiolabeled Chemicals) was added at room temperature and stirred for 2 hours. The reaction mixture was filtered using a Whatman PTFE 0.45 xcexcm syringeless filter device to remove any insoluable potassium carbonate, washed with Abs. ethanol (2 mL, Pharmco), and the combined filtrates were concentrated to dryness at room temperature using a rotary evaporator; this also removed any unreacted tritiated methyl iodide. The residue was purified by HPLC chromatography on a Phenomenx Luna C8 semi-prep column (Luna 5 micro C8(2), 250xc3x9710.0 mm) using a gradient system of 20/80 acetonitrile/water with 0.1% trifluoroacetic acid to 100% acetronitrile with 0.1% trifluoroacetic acid in 20min. Total activity of the product was 8 mCi. Further purification was effected by absorption onto a Waters C-18 Sep-pak column (Waters Sep-Pak PLUS C18) and elution with water followed by absolute ethanol. The product was diluted with absolute ethanol (10 mL) before submission for final analysis.
The compounds of this invention exhibit less than 50 xcexcM in the FLIBR and binding assays. Thus, the compounds and pharmaceutical compositions of this invention have been found to exhibit biological activity as NMDA NR2B antagonists. Accordingly, another aspect of the invention is the treatment of pain, migraine, depression, anxiety, schizophrenia, Parkinson""s disease, or strokexe2x80x94maladies that are amenable to amelioration through inhibition of NMDA NR2B receptorsxe2x80x94by the administration of an effective amount of the compounds of this invention.
The following examples are provided to more fully illustrate the present invention, and are not to be construed as limiting the scope of the claims in any manner.


A method is provided for degradation-compensated evaluation of detection signals of a sensor arrangement operating on the principle of luminescence quenching, which arrangement has a luminophore that degrades over time, an excitation radiation source, and at least one optical sensor. The luminophore radiates, in accordance with a response characteristic of the sensor arrangement, in reaction to irradiation with a predefined modulated excitation radiation and as a function of the extent of an interaction of the luminophore with a quencher substance that quenches the luminescence of the luminophore. A response radiation is detected by the at least one optical sensor. The sensor arrangement outputs a detected intensity value representing an intensity of the response radiation and a detected phase value representing a phase difference of the response radiation with respect to the modulation of the excitation radiation. A predetermined calibration value correlation is identified in consideration of the reference response characteristic.

The present invention relates to a method for degradation-compensated evaluation of detection signals of a sensor arrangement operating on the principle of luminescence quenching. The present invention furthermore relates to an evaluation apparatus embodied to carry out such a method.
A sensor arrangement operating according to the principle of luminescence quenching comprises a luminophore, an excitation radiation source, and at least one optical sensor. As a reaction to irradiation with a predefined modulated excitation radiation, the luminophore radiates, in accordance with a response characteristic typical of the sensor arrangement, a response radiation that is detected by the at least one optical sensor. The response radiation depends not only on the excitation radiation of the excitation radiation source, but also on the extent to which the luminophore interacts with a quencher substance. The quencher substance, for instance oxygen, has the property of quenching a luminescence of the luminophore. The luminophore luminescence brought about by the excitation radiation therefore decays more quickly in the presence of the quencher substance that interacts with the luminophore than would be the case in the absence of the quencher substance. The response characteristic in this context is the material-immanent correlation, dependent on the extent of interaction with the quencher substance, between the excitation radiation and the response radiation of the predefined luminophore.
As a rule, such sensor arrangements are used instrumentally not only to detect but to quantify the presence of a specific quencher substance. If, for example, oxygen is a quencher substance for a predefined luminophore, the sensor arrangement can be used to ascertain the oxygen content or oxygen concentration in a test fluid that is to be tested. For this, the test fluid must be brought into luminescence-quenching interaction with the luminophore, for example, in the case of collisional quenching, into physical contact with the luminophore.
The luminescence quenching produced by the quencher substance causes a change, as a function of the concentration of the quencher substance in the test fluid, in a phase angle of a phase shift between the modulated excitation radiation and a response radiation that is thus necessarily also modulated. Using a form of the Stern-Volmer equation (known per se) which takes into account the phase angle between the excitation radiation and response radiation, it is possible to determine, from a phase angle of the response radiation which is identified for a known excitation radiation, a concentration of the quencher substance, for instance in the form of a partial pressure of the quencher substance in the test fluid.
The luminescence quenching produced by the quencher substance causes, for a predefined excitation radiation, a change in an intensity of the response radiation which depends on the concentration of the quencher substance in the test fluid. Using a form of the Stern-Volmer equation which takes into account the intensity of the response radiation, it is again possible to determine, from an intensity of the response radiation which was identified for a known excitation radiation, a concentration of the quencher substance.
Detection signals of the sensor arrangement therefore represent, as a rule, either a phase angle or an intensity of the response radiation.
Based on a calibration of the sensor arrangement carried out before a concrete detection operation, it is possible very generally to associate, with a detection signal that is based on the response radiation detected by the optical sensor, a result value that represents the desired result, for example a concentration of a predetermined quencher substance in a test fluid, for instance the oxygen partial pressure in a test fluid. What is identified in the context of calibration of the sensor arrangement is therefore very generally a calibration value correlation that links values of the detection signal, based on the response radiation, to result values.
The objective of an evaluation of detection signals of a sensor arrangement operating according to the principle of luminescence quenching is to ascertain the result value that is the goal of the detection operation.
It is problematic in this context that a luminophore degrades over time, for instance by so-called "bleaching." Assuming a constant excitation radiation and constant concentration of the quencher substance in the test fluid, the response radiation of the luminophore radiated in reaction to the excitation radiation changes as degradation of the luminophore used in a sensor arrangement progresses. In the terminology used above, this means that the material-immanent response characteristic of the luminophore changes in degradation-related fashion.
In the present Application, a reference to degradation of the luminophore is equivalent to a reference to degradation of the sensor arrangement.
As degradation of the luminophore progresses, the difference between the response characteristic currently existing at the respective detection time, and the reference response characteristic which previously existed during calibration and on which the (still valid) calibration value correlation is based, increases. As a consequence, the result values that are determined based on current detection signals, and on the basis of a calibration at a time in the past, increasingly deviate from the true value, for example (in the case of bleaching, which constitutes a very common form of degradation) toward detection values that are too low. Because the luminescence quenching property of the luminophore means that decreasing detection values are associated with rising quencher-substance concentrations as result values, degradation of the luminophore as a rule leads to the identification of result values that are quantitatively too high.
The calibrated sensor arrangement, when used as intended in order to determine result values on the basis of the respectively valid response characteristic, always supplies some detection value and as a consequence, on the basis of the respectively valid calibration value correlation, some result values from the detection values. For the user of the sensor arrangement, it is not possible in the existing art to recognize whether an identified high result value results from degradation of the luminophore, or from an actually high concentration of the quencher substance.
One approach to avoiding degradation-related errors in the identification of result values is to calibrate the sensor arrangement as frequently as possible, and thus adjust the reference response characteristic that is the basis of the calibration to the current response characteristic that changes as a result of degradation of the luminophore. This quite considerably decreases the productivity of the sensor arrangement, however, because of the time required for calibration.
Another approach is to correct the result values that are incorrect due to degradation. A proposal for doing so is known from EP 2 887 054 A1.
The teaching of this document is to take into account in correcting fashion a degradation of the luminophore in the Stern-Volmer equation used for evaluation of the sensor arrangement detection signal, the Stern-Volmer equation being used in a form that uses the detected phase angle as an argument.
EP 2 887 054 A1 proposes to modify both the baseline phase value of the Stern-Volmer equation, i.e. the phase angle that is identified in the absence of the quencher substance using a new, undegraded luminophore, and the Stern-Volmer constant used in the equation, by means of respective aging factors. The aging factors are in turn dependent on the modulation frequency of the excitation radiation. They must be empirically ascertained very laboriously for each sensor type (because of their dependence on the sensor structure), and for several modulation frequencies of the excitation radiation (because of their frequency dependence).
The Stern-Volmer equations used in accordance with EP 2 887 054 A1 are degradation-corrected using exponential functions, different exponential functions, constituting correction factors, being multiplied by the baseline phase value and by the Stern-Volmer constant. The respective aging factors are part of the exponents of the exponential functions. Because of the equation structure resulting therefrom, degradation correction according to EP 2 887 054 A1 requires laboriously numerically solving an equation system for each detection operation, which either requires provision of an evaluation apparatus having unusually high computation performance or, in a context of conventional computation performance, delays the detection operation until the desired result value has been obtained. The degradation correction proposed in EP 2 887 054 A1 is furthermore dependent on the operating duration of the sensor, which in reality is not necessarily the case.

Method for degradation-compensated evaluation of luminescence sensor detection signals, and evaluation apparatus therefor


A contact guide member extends transversely to the contact fingers on the contact carrier of electrical switching apparatus and has spaced openings through which the contact fingers extend and are held in spaced relation. The contact finger guide member is positioned to isolate the arc toes adjacent the free ends of the contact fingers from the main contacts and the contact springs in order to protect the latter items from the arc gases and debris generated during arcing. The openings in the contact finger guide member are elongated to permit differentially pivoting of the contact fingers, but not axial movement. The contact finger guide member slides in a pocket molded in the end face of the contact carrier and is captured by and moves with the contact fingers.

1. Field of the Invention
This invention relates to electrical switching apparatus, and in particular, to such apparatus with multiple contact fingers and to a contact finger guide which maintains spacing between the contact fingers during current interruption and blocks passage of arcing gasses back along the contact fingers.
2. Background Information
Electrical switching apparatus for power distribution systems includes devices such as, for instance, circuit breakers, network protectors, transfer switches and disconnect switches. A common type of power air circuit breaker has a molded casing housing multiple pole assemblies all driven by a common operating mechanism. Each pole includes a contact arm carrier pivoted by the operating mechanism between open and closed positions. The contact arm carriers support contact arms having movable contacts which engage stationary contacts with the contact arm carrier in the closed position. Typically, the contact arm is made up of a number of contact arm laminations or contact fingers mounted on a common pivot pin on the carrier. Contact springs bias the contact fingers against the stationary contacts in the closed position to provide contact pressure and to accommodate for wear.
There is a need to locate the contact fingers laterally against magnetic loads during short circuit conditions. The contact fingers tend to sway from side to side due to the magnetic effects of adjacent poles which are out of phase. This allows the moving contacts to slide on the stationary contacts. During interruption, when the contact fingers are arcing, magnetic forces tend to pull the ends of the fingers together, toward the center of the pole. The fingers may bend, touch at their tips, and even weld together, losing their independent action. Separating fins may be molded into the carrier, but they are difficult to mold and often break during interruption. The taper required to mold them limits their effectiveness in locating the contact fingers. Also, there is a need to protect the contact springs from arc generated debris, which can collect between coils, limiting spring travel after interruption. The contact carrier partially shrouds the springs, but there must be enough clearance to allow the fingers to pivot to the fully compressed position.
There is a need therefore for an improved electrical switching apparatus with plural, parallel spaced contact fingers arranged to prevent bending and welding together of the contact fingers during arcing.
There is a further need for such an improved electrical switching apparatus which protects the contact springs and main contacts from arc gases and debris generated at separate arcing contacts.
There is an associated need for such electrical switching apparatus which achieves these results with simple, economical arrangements of the parts.

Electrical switching apparatus with contact finger guide


A method for accessing shared memory cards from each of plural processor cards is disclosed. The shared memory cards are composed of a shared memory card of an operating system and a shared memory card of a standby system in a redundant configuration, and each of plural processor cards individually access the shared memory cards. Each of the plural processor cards is connected to the shared memory card of the operating system and the shared memory card of the standby system in a point-to-point structure via corresponding serial buses and executes data transmission on a one to one basis to/from the shared memory card of the operating system and the shared memory card of the standby system.

1. Field of the Invention
The present invention generally relates to a method for accessing shared memories and a multiprocessor system using the accessing method in a distributed processing system in which various operations are processed by using plural processors.
2. Description of the Related Art
Recently, the development of the CDMA (code division multiple access) communication system has rapidly progressed and a processor system, which can operate in high-volume traffic corresponding to the expansion of mobile phone services and the popularization of data communications of huge amount of audio and video data in a wireless network, has been required. The processor system is generally realized by a multiprocessor system (for example, refer to Patent Document 1).
FIG. 1 is a block diagram showing a conventional multiprocessor system having shared memory cards. In the multiprocessor system shown in FIG. 1, n processor cards 101a to 101n, shared memory cards 104 and 105, and bus control cards 106 and 107 are connected to a global bus 108 in a multi-connection structure.
In the shared memory cards 104 and 105 in a redundant configuration, the same information which is common to the processor cards 101a to 101n is stored. The bus control cards 106 and 107 have a function to adjust the global bus 108 which the processor cards 101a to 101n use to access the shared memory cards 104 and 105. The processor cards 101a to 101n renew a common resource in the shared memory cards 104 and 105 while executing requested processes.
[Patent Document 1] Japanese Laid-Open Patent Application No. 2001-166960
However, corresponding to the expansion of services in an IDC (Internet data center) and communication services in the 3G, a large amount of communication data must be processed at high speed. However, in a multiprocessor system which processes large amounts of data by a distributed processing system, the conventional technology has difficulty in expanding the services due to limitations in increasing the throughput.
In the conventional multiprocessor system which includes shared memory cards shown in FIG. 1, in which the processor cards 101a to 101n and the shared memory cards 104 and 105 are connected by the global bus 108 in the multi-connection structure, as one of methods to increase the throughput, there is a method to add a new processor card. However, when a processor card is newly added, signal quality is degraded due to the increase of the connecting workload on the global bus 108. Consequently, there is a limitation to increasing the number of processor cards.
As a different method, there is a method to increase the throughput of the global bus 108. However, there is a limitation to increasing the throughput of the global bus 108 due to a limitation of the protocol of the global bus 108.
In addition, since the plural processor cards 101a to 101n are connected to the global bus 108 in order to access the shared memory cards 104 and 105, when the global bus 108 is hung up by some problem of a processor card 101x, other processor cards cannot access the shared memory cards 104 and 105.
Consequently, in the conventional multiprocessor system which requires large throughput, there are surely limitations for the throughput. In addition, when one of the processor cards has some trouble, the trouble interferes with processes in the other processor cards.

Method for accessing shared memories and multiprocessor system using the method


A system, handheld devices, and methods for space equipment tracking and control. The system tracks and controls items, people and their interactions. The handheld mobile wireless device provides item specific information, instruction, and supervision. A plurality of handheld devices is configured to be used by different people, and communicate with a central database. A handheld device comprises a camera for scanning an image of an item of space equipment, a display for displaying information, and a wireless network connection to the database for sending and receiving data. The system recognizes the item of space equipment and identifies a person. The database includes information regarding people and their roles, permissions, and authorized or assigned tasks; space equipment and tools; item specific instructions; and the handheld devices. An observer, or the system, can monitor the performance of the tasks, and provide corrective feedback.

1. Field of Invention
The present invention relates to object recognition and control, in particular the invention relates to space equipment recognition and control including mobile wireless devices for use by a space exploration organization.
2. Description of Prior Art
Various space exploration organizations develop space equipment. Initially only NASA and the Russian Soviet Space programs had the resources to develop space flight and the require equipment. More recently other space exploration or space launch companies exist. For example, Space Exploration Technologies Corporation (SpaceX) was founded in 2002, Alliant Techsystems Inc (ATK Aerospace Systems) develops space launch equipment, and Orbital Sciences Corporation (OSC) develops satellites and launch systems.
Various attempts have been made to label objects with labels that can be read automatically by a computing machine. Barcodes have proven to be an effective scheme for achieving these purposes. Originally, linear or one-dimensional barcodes such as the Universal Product Code (UPC) were used. The UPC was the first commercially successful model and enjoyed widespread universal use.
Later a two-dimensional or matrix code was developed. These are similar to one-dimensional codes, but represent more data per unit area and traditionally utilize square pixels. While the UPC represents a serial number, matrix codes can represent text, URLs, or other data. The Quick Response Code (QR Code or QRC) is one of the most popular types of two-dimensional codes and is often used with smart phones.
More recently, a third-generation barcode called the High Capacity Color Barcode (HCCB) was developed. This two-dimensional barcode uses multi-colored triangles for an increase in data density, but still represents the same types of data.
Bar code readers are typically connected to computer systems and databases to keep track of sales or inventory.
These conventional methods have many drawbacks and limitations including the inability to identify individuals in various disciplines and roles and correlate relationships, tasks, permissions, etc. with other objects and/or individuals. In addition, these methods lack the ability to provide and present training, instructional and other information in various forms for maintenance and other purposes.
There is a need for mobile wireless handheld devices to be able to recognize various items of space equipment and people and to provide for training, instruction, tracking, monitoring, and observation, which is authorized, and item specific. Further there is a need to be able to confirm that maintenance or use procedures are performed properly while they are being performed.

This patent is subject to a terminal disclaimer.

Space equipment recognition and control using handheld devices


A storage device including a lid and a plurality of shelf members, pivotally mounted to a frame member. The lid, the base, and the plurality of shelf members form pairs of opposed cooperating rack assemblies. Each pair of cooperating rack assemblies is adapted to hold articles stored in the storage device in an offset nesting relationship until use.

1. Field of the Invention
This invention relates to storage devices, and more particularly to improved storage devices to temporarily store parts in storage racks ready for transport and eventual use by workers on assembly lines. Most particularly, the present invention relates to an improved storage device to temporarily store automobile steering wheels in storage racks ready for shipment to and installation by automotive assembly line workers in automobiles during the assembly process.
2. Description of the Prior Art
The problem of how to efficiently and safely store a sufficient number of steering wheels beside an automobile assembly line has been present ever since the invention of the automotive assembly line. Current methods now in use are neither space efficient, nor safe.
Currently, storage racks having a number of vertical spindles are used. These storage racks are provided with heavy weighted bases to militate against movement. Vertical rods over which the steering wheel hubs are placed extend upwardly from the bases. A number of steering wheels, alternated with spacers to prevent contact of the wheels with each other, and prevent scuffing, are placed seriatim on the spindles. The spindles may also be mounted on wheeled frames.
When so mounted, due to stacking requirements, they are limited to thirty inches in height. This height limit provides a severe limit to the number of steering wheels which can be place on each rack.
To increase the number of steering wheels that can be stored, the vertical spindles are often times placed in a matrix arrangement, and this poses a serious health problem. As steering wheels are removed from any particular spindle, the worker must reach farther and farther down the spindle to remove the next steering wheel. Since the worker is bending over in the midst of many spindles, frequent eye injuries occur when the worker's head or eye comes in contact with the top of one spindle, while the worker is bending over to pick a steering wheel off another spindle. These accidents are so frequent that this type of device has been referred to in the art as an "eye poker."
In addition, serious ergonomic problems, in the form of back problems, have come about because of all the bending which the worker needs to do, and because of the particular direction of bending. For all these reasons, the search for a safer, more efficient and less expensive method of storing steering wheels next to automotive assembly lines has been one of long standing.
The prior art has revealed many types of racks for storage of many types of parts. Racks, such as those disclosed in U.S. Pat. No. 870,835 to Charles H. Loew, and U.S. Pat. No. 1,856,935 to Giles M. Turner, show racks having a plurality of swingable supports or shelves pivotably mounted on a central frame member. However, even though these devices maintain a plurality of shelves in a parallel spaced relationship, they are not directed to the particular problems associated with steering wheel storage, and do not serve to hold the parts in an offset nesting relationship for easy access by the assembly line worker.
Likewise, patents such as U.S. Pat. Nos. 2,716,495 to C. E. Prevette et al., 2,982,419 to R. A. Shiels, and 3,762,572 to Clarence H. Hager, disclose a plurality of shelf means pivotally supported near their rear edges, and thus, are somewhat similar to the present invention. None of these patents, and in fact no patents found during a search of the prior art, is specifically directed to the problems of steering wheel storage.


A digital camera to which a storage medium can be connected, includes a profile information storer and a profile information reader. The profile information storer stores profile information representing a storage medium user in the storage medium connected to the digital camera. The profile information reader reads the profile information.

1. Field of the Invention
The present invention relates to a digital camera and a digital camera system, especially to a digital camera having a user identifying function, and to a digital camera system including such a digital camera and a storage medium.
2. Description of the Related Art
Generally, in digital cameras, a storage medium is connected to a digital camera and is used for storing photographed images. A storage medium in which images are stored, is detached from the digital camera and photographed images stored therein are replayed on a computer.
In the case where a digital camera to which a storage medium is attached, is used by a plurality of users, the storage medium used by one user may be initialized by another user and image data stored in the storage medium may be deleted.


A recording apparatus includes a support drum that rotates while supporting a recording medium on a support surface thereof. A guide axis extends in parallel with a rotation axis of the support drum along the support surface. A carriage that is guided by the guide axis moves back and forth along the support surface. A recording head for ejecting ultraviolet curing type ink toward a recording medium is supported on the support surface. The recording head has head units and is mounted on the carriage. Each head unit ejects a different type of ultraviolet curing type ink to a different position along an extending direction of the guide axis. An ultraviolet emission unit of the recording apparatus includes ultraviolet light sources that generate ultraviolet light having at least an intensity, wavelength, or emission time that is different from those of the other ultraviolet light sources.

1. Technical Field
The present invention relates to a recording apparatus and a liquid ejecting apparatus. In particular, the present invention relates to a recording apparatus and a liquid ejecting apparatus using ultraviolet curing type ink.
2. Related Art
There is a recording apparatus or a liquid ejecting apparatus for forming an image or a pattern on a recording medium by using ultraviolet curing type ink. The ultraviolet curing type ink has the property in which it takes a long time to be cured till ultraviolet is emitted and the property in which curing is immediately completed when ultraviolet is emitted, which are preferable for print ink. In addition, the ultraviolet curing type ink has an advantage in that it imposes a small environmental burden as no solvent is vaporized in the process of curing.
Further, the ultraviolet curing type ink has excellent properties. For example, the ultraviolet curing type ink shows high adherence property to a various recording mediums due to the composition of vehicle, is scientifically stable after curing, has high adhesiveness, drug tolerability, weather resistance, abrasion resistance, and the like, and can be withstood to outdoor condition. Consequently, an image can be formed not only on a thin sheet-like recording medium such as a paper, a resin film, a metallic foil, and the like but also on a label surface of an optical recording medium, a textile product, and the like having a three dimensional surface shape to some extent.
As for the method for adhering ultraviolet curing type ink on a recording medium, application, printing, and the like are exemplified. However, it is expected that ultraviolet curing type ink is utilized for an ink jet type recording apparatus in which any image or patter can be formed with high accuracy without a lithographic plate. In the ink jet type recording apparatus, an image can be recorded on any area also to a long recording medium or a recording medium having a large area by using a nozzle whose size is limited by the combination of reciprocating movement of a recording head for ejecting ink and movement of a recording medium in the direction perpendicular to the direction of the reciprocating movement of the recording head.
In JP-A-2004-155046, an ink jet recording apparatus is described. In the ink jet recording apparatus, an ultraviolet curing agent is included in ink and ultraviolet is emitted on a recording surface right after recording, thereby improving quick-drying of recording surface. To be more specific, it is described that ultraviolet curing type ink is used as ink and the ink adhered on a recording medium is immediately cured to fix thereon by ultraviolet lumps disposed at the both ends of a recording head in the main scanning direction in an ink jet printer.
Further, in JP-A-2005-324443 and JP-A-2005-125513, there is described an image forming apparatus having a recording head for ejecting ink that is cured by ultraviolet emission and an ultraviolet emission unit coupled to the recording head and in which an image support body, the recording head, and the ultraviolet emission unit are relatively moved. In the image forming apparatus described in the patent documents, an input digital image is formed by scanning of a plurality of recording head on the record support body and ink is independently cured by ultraviolet emission for every scan. Further, in JP-A-2004-042548, it is described that an ultraviolet emission device is independently provided for every color in the recording apparatus that ejects ultraviolet curing type ink having a different color to each other from nozzles to perform color printing.
The ultraviolet curing type ink has different transmittance property to ultraviolet depending on the type, for example the color, of the ink, so that curing speed is also different. Further, the transmittance property to ultraviolet is also changed in accordance with the thickness of ultraviolet curing type ink adhered on a recording medium. Consequently, when recording operation is performed by using different type of inks for color printing or the like, there is a case in that curing of a specific type of ink takes a long time. However, when the ink which is not yet cured is mixed on the surface of a recording medium, bleeding occurs in an image after curing, thereby deteriorating image quality.
Further, when ultraviolet is emitted for the ink which is most difficult to cure, there is a case that not only emission energy is uselessly consumed, but also curing speed of another type of ink becomes too fast. The ultraviolet curing type ink itself is cured and fixed, so that the volume of the ink does not decrease after adhesion. Consequently, when the curing speed is too fast, the ink is cured to rise from the surface of a recording medium and the surface texture becomes coarse.
It is proposed that the mutual difference of the property of the type of the ultraviolet curing type ink is compensated by, for example, adjusting the composition of the ultraviolet curing component contained in the ink. However, the difference is not compensated. Further, it is proposed that an ultraviolet emission device is independently provided in accordance with the ink ejected from each of recording heads. However, there occurs problems in that the weight and the size of the carriage becomes too large, the scale of the device becomes large, and the improvement of operational speed is restricted in the structure in which a recording head and a plurality of ultraviolet emission devices are mounted on a plurality of carriages.

Recording apparatus and liquid ejecting apparatus


A device for cutting the paper sleeve of defective filter cigarettes for recycling tobacco has at least one knife roller having a plurality of knife disks spaced from one another at a distance that is smaller than a diameter of the cigarettes. Each knife disk has a circumferential edge with a plurality of teeth. A conveyor belt feeds the cigarettes to the knife roller such that the cigarettes are essentially oriented parallel to the conveying direction. The conveyor belt and the knife roller are synchronized such that a circumferential velocity of the knife disks corresponds to the conveying velocity of the conveyor belt. As an alternative, the knife disks can be provided with a continuous circular dulled circumferential cutting surface. It is then necessary that the conveyor belt and the knife roller are synchronized such that a circumferential velocity of the knife disks is greater than the conveying velocity of the conveyor belt.

The present invention relates to a device for cutting the paper sleeve of defective filter cigarettes for recycling the tobacco, the device having a conveyor belt for feeding the cigarettes to a roller for opening the paper sleeves such that the cigarettes are essentially oriented parallel to the conveying direction.
From German Offenlegungschrift DE-OS 38 39 431 a device for recycling of tobacco from defective cigarettes is known in which the cigarettes which are essentially oriented parallel to the conveying direction are fed into a roller system by a conveyer belt which is wetted with water, wherein the roller system comprises at least one cutting roller with revolving knife rings. This cutting roller comprises either a plurality of knife rings which, in the form of closed individual rings, are arranged at an acute angle relative to the roller axis or with a coilshaped cutting knife extending over the entire length of the roller. In this manner it is ensured that the wetted paper sleeves of the cigarettes which are entering in axial orientation into the roller system are gently crushed without damaging the long fibers of the tobacco.
This known device has been successfully used in practice, however, an attentive and expensive service and cleaning is required since wet tobacco clumps are susceptible to molding.
It is therefore an object of the present invention to provide a device for cutting the paper sleeve of defective filter cigarettes of the aforementioned kind, in which the wetting of the transported goods is avoided and which is suitable for recycling the tobacco of defective filter cigarettes.

Device for cutting the paper sleeve of defective filter cigarettes


A ducted fan includes a fan that generates an airflow that flows substantially parallel with the axis of the rotating shaft of the fan; a duct, arranged around the fan, that extends in the direction of the rotating shaft of the fan and includes an airflow inlet defined by the upstream end and an airflow outlet defined by the downstream end, and that has a ramp portion formed in the inner face of the airflow inlet; an airflow guide portion, provided at the airflow outlet, that introduces air from outside of the duct to a position downstream of the airflow outlet; and a negative-pressure forming portion, provided at the downstream end of the airflow guide portion. The negative-pressure forming portion generates a negative pressure near the downstream end of the airflow guide portion when air passes by the negative-pressure forming portion.

1. Field of the Invention
The invention relates to a ducted fan that produces thrust through the rotation of a fan arranged in a duct.
2. Description of the Related Art
Using a ducted fan as a thrust producing device for a vertical take-off and landing aircraft has been proposed.
Japanese Patent Application Publication No. JP-A-2005-145264 describes a vertical take-off and landing aircraft. In the described vertical take-off and landing aircraft, the magnitude of negative pressure, which is formed when air flows, is changed in a lip portion through which air is introduced into a duct of a ducted fan. Thus, the magnitude of a thrust produced is flexibly controlled.
Japanese Patent Application Publication No. JP-A-03-70699 also describes a vertical take-off and landing aircraft. According to Japanese Patent Application Publication No. JP-A-03-70699, the pitch angle of a blade of a ducted fan and the speed of an engine that drives the ducted fan are controlled. Thus, the magnitude of a thrust produced is flexibly controlled.
However, the following phenomenon may occur in a ducted fan mounted in an aircraft. If a crosswind blows against the side face of the ducted fan during flight, the airflow going into the duct and the crosswind join together at an air-introduction portion of a portion of the duct, the portion being exposed to the crosswind (hereinafter, such air-introduction portion will be referred to as a "front air-introduction portion"). As a result, the flow speed of the air entering the air-introduction portion increases.
Accordingly, a negative pressure formed at the front air-introduction portion is greater than a negative pressure formed in an air-introduction portion of another portion of the duct, the portion not being exposed to the cross wind (hereinafter, such air-introduction portion will be referred to as a "rear air-introduction portion").
Accordingly, the front air-introduction portion is attracted in the direction, in which the negative pressure is applied, more strongly than the rear air-introduction portion is. Therefore, a moment, which is applied in the direction in which the front portion of the ducted fan moves upward, may be produced.
An airflow outlet is formed in the lower portion of the ducted fan. The airflow, which has passed through the duct, comes out of the airflow outlet. In an area downstream of the airflow outlet, the airflow coming out of the duct and the crosswind join together, and the direction of the airflow on the downstream end of the duct (hereinafter, such airflow will be referred to as the "descending airflow") approaches the direction of the crosswind.
Because the direction of the descending airflow is influenced by the crosswind, the descending airflow proceeds through the area downstream of the duct so as to pass over the airflow outlet. This interrupts the flow path along which the airflow comes vertically out of the airflow outlet of the duct.
As a result, the air cannot smoothly flow out of the duct, which may decrease the flow speed of the airflow coming out of the duct. In particular, decreases in the flow speed of the airflow coming out of the rear airflow outlet decrease the thrust applied to the rear portion of the duct. This may make it difficult to produce a moment that is applied in the direction in which the rear portion of the duct moves upward.
Hereafter, the above-described phenomenon, which is caused when the ducted fan is exposed to the crosswind, will be described in detail with reference to FIGS. 1 and 2.
FIG. 1 illustrates the airflows that are generated around a ducted fan 200 and in a duct 7 when a crosswind 13 blows against the side face of the ducted fan 200 from the outside of the ducted fan 200. The arrows in FIG. 1 indicate the directions of airflows. To facilitate the understanding of the directions of the airflows, the fan provided in the duct 7 is not shown in FIG. 1.
First, the airflows near an airflow inlet 8 will be described with reference to FIG. 1. An airflow 14 generated due to the turning motion of the fan and the crosswind 13 join together in a front airflow inlet 8a to generate a combined airflow 18. The combined airflow proceeds faster than the airflow 14 flowing through a rear airflow inlet 8b.
Next, the airflows near an airflow outlet 10 will be described with reference to FIG. 1. An airflow 20 coming out of the airflow outlet 10 and the crosswind 13 join together, which causes the direction of a descending airflow 19 to approach the direction of the crosswind 13.
Because the direction of the descending airflow 19 is influenced by the crosswind 13, the descending airflow 19 proceeds through the area downstream of the duct 7 so as to pass over the airflow outlet 10. This interrupts the flow path along which the airflow 20 comes vertically out of the airflow outlet 10.
As a result, the air does not flow smoothly out of the airflow outlet 10.
FIG. 2 illustrates the flow speed distribution of the airflows generated around the ducted fan 200 and in the duct 7, the directions and magnitudes of thrusts produced by the airflows, and the directions and the magnitudes of moments produced by the thrusts, in the case where the crosswind 13 blows against the side face of the ducted fan 200 from the outside of the ducted fan 200.
Due to the above-described airflows near the airflow inlet 8, the negative pressure formed at a ramped portion 9a, which is formed on the inner face of the front portion the duct 7 (hereinafter, referred to as a "front ramp portion 9a"), is greater than the negative pressure formed at a ramp portion 9b, which is formed in the inner face of the rear portion of the duct 7 (hereinafter, referred to as a "rear ramp portion 9b"). Accordingly, a force 15 for attracting the front ramp portion 9a is stronger than a force 16 for attracting the rear ramp portion 9b, whereby the front ramp portion 9a is attracted in the direction, in which the negative pressure is applied, more strongly than the rear ramp portion 9b is. Thus, a moment 17, which is applied in the direction in which the front ramp portion 9a moves upward, is produced.
A flow speed distribution area 21 is formed in the duct 7 and on the downstream end of the duct 7. In the flow speed distribution area 21, the airflows proceed at flow speeds equal to or higher than a predetermined value.
Due to such airflows, a thrust 22a is applied to the front portion of the duct 7 (hereinafter, such thrust will be referred to as a "front fan thrust"), and a thrust 22b is applied to the rear portion of the duct 7 (hereinafter, such thrust will be referred to as a "rear fan thrust"). Thus, a moment 23, which is applied in the direction in which the rear portion of the duct 7 moves upward, is produced.
As shown in FIG. 2, the moment 23 is not great enough to completely offset the moment 17, which is applied in the direction in which the front ramp portion 9a moves upward. Accordingly, if the ducted fan 200 is exposed to the crosswind 13, a moment, which is applied in the direction in which the front portion of the duct 7 moves upward (hereinafter, such moment will be referred to as a "pitch-up moment"), is ultimately produced.
As described so far, in the ducted fan according to the related art, the pitch-up moment, which is applied in the direction in which the front portion of the duct moves upward, may be produced when the ducted fan is exposed to the crosswind.


A rotary actuator and a method of providing kinesthesia using a magnetorheological fluid are provided. The method includes generating a solenoid which generates a magnetic field, thereby forming flux lines, in response to a current being applied thereto. A cylindrical rotor surrounds inner, outer and top surfaces of the solenoid, is freely rotatable about a rotary shaft disposed in an opened central portion thereof. A cylindrical housing surrounds inner, outer and bottom surfaces of the solenoid, and engages with the rotor. The magnetorheological fluid is disposed inside gaps among the solenoid, the rotor and the housing, and generates magnetic chains along the flux lines in response to the magnetic field. The thickness of walls of the rotor which surround the inner and outer surfaces of the solenoid decreases in the top-to-bottom direction. A space having a predetermined width is defined around the rotary shaft.

An actuator is a type of motor that is responsible for moving or controlling a mechanism or system, and extensively includes various types of motors that using electricity, hydraulic power, compressed air, or the like. Typically, an actuator is operated by a source of energy such as an electric current, hydraulic fluid pressure or pneumatic pressure; and converts that energy into motion. Recently, many actuators, which are provided on the physical body of a user to provide kinesthesia, are being developed. Most actuators that have been developed to date use a vibration motor or either a hydraulic or pneumatic pump to provide kinesthesia to the human body (see Korean Patent Application Nos. 10-2001-0057470 and 10-2007-0132361). Specifically, either a plurality of vibration motors known in the art is equipped within clothes or air is blown into pneumatic windbags in order to apply pressure to the skin.
However, these actuators of the related art which are intended to provide kinesthesia have the following problems. These actuators suffer from limitations in use and space owing to their bulky volume and heavy weight, and their applications are limited to specific and restricted fields. In particular, the use of miniaturized and light-weight actuators is required in order to provide kinesthetic haptic feedback to fingers or the like on which the actuators are disposed. It is required to develop a single module actuator that consumes little power, is small-sized and slim, and is applicable to a variety of environments.
The above information is presented as background information only to assist with an understanding of the present disclosure. No determination has been made, and no assertion is made, as to whether any of the above might be applicable as prior art with regard to the present disclosure.

Rotary actuator and method of providing kinesthesia using a magnetorheological fluid


An assembly for feeding and milking animals. The assembly is provided with a feeding system comprising a movable feed platform and a drive unit for driving the feed platform, a number of feeding places being provided on the feed platform. The assembly also includes a milking system for, in particular automatically, milking animals on the feed platform, which milking system comprises a number of sets of teat cups. An area where the animals are allowed to move freely communicates via an entrance with the feed platform, the width of the entrance being sufficiently large to enable simultaneous access of several animals to the feed platform. The entrance is free from a closing device.

1. Field of the Invention
The invention relates generally to feeding and milking assemblies and more particularly to feeding and milking assemblies in which the animals are located on a movable feed platform. The invention further relates to a method of milking an animal using such a movable feed platform.
2. Description of the Related Art
Methods and devices are known for milking animals in which the animals are located on movable platforms. Such known devices are generally provided with individual stalls or confining elements to prevent movement of the animals on the platform. Additionally, the animals are generally not free to board the platform themselves but must be led or driven there by a herdsman or the like. In certain cases the animals are effectively housed on the platform semi-permanently and may only be led off for brief intervals. Such devices may suffer from the disadvantage that a dairy animal finds it unpleasant to be milked in a closed area, such as the stalls provided on the platform which limit the freedom of movement of a dairy animal to a high extent. Furthermore, dairy animals appear to experience walking to and boarding the platform as unpleasant and may therefore by very unwilling to be led to or from the platform, which may result in problems to get an animal onto or from the platform, leading to insufficient occupation of the platform and thus reduced milk production. In addition some animals may find the extreme long stay on the platform as unpleasant, as a result of which they might be very unwilling to be led to the platform. Devices of this type are shown in U.S. Pat. No. 2,358,000, U.S. Pat. No. 3,103,912, U.S. Pat. No. 4,508,058 and US-A1-2002/0033138.
Another device is known from FR-A-2,649,858. The housing system as used in FR-A-2,649,858 is not explicitly described, but since the animals have to enter the circular platform from within the platform it is most likely that the animals have to be led from the outside of the platform towards the inside. In addition the assembly known from FR-A-2,649,858 also suffers from the disadvantage that a dairy animal to be milked is in a closed area, such as the stalls provided on the platform disclosed therein which limit the freedom of movement of a dairy animal to a high extent. Each stall is closed by two gates, so that this also restricts the free movement of animals since an animal has to board the platform at a specific position. Furthermore, dairy animals appear to experience walking to and boarding the platform as unpleasant and may therefore by very unwilling to be led to the platform, which may result in problems to get an animal onto or from the platform, leading to insufficient occupation of the platform and thus reduced milk production.
A further method of milking an animal is known from international patent application WO 02/19807 and the article "Rund und ohne Futtertisch", DLZ Agrarmagazin, of March 2002, pages 120 and 121. Herein a platform is described, which is provided with individual milking stalls, each milking stall comprising the associated teat cups and its own feed trough. The access to and the exit from the platform is controlled by means of a number of controlled gates. When the animals are to be milked, automatic driving devices are used to drive the cows towards the platform. During milking the rotational speed of the platform is adjusted in such a way that an animal will spend approximately 10 to 15 minutes on the platform (i.e. one rotation of the platform will take 10 to 15 minutes). When there is no need for milking, the platform is used as a feed platform. In this case the automatic driving devices are not used, but the controlled gates are. Moreover, the rotational speed of the platform is adjusted in such a way that one rotation will take approximately 30 minutes. Although this known method may be expected to provide an enhanced efficiency when milking large herds, it has a number of drawbacks limiting its efficiency. It has been found that the use of automatic driving devices leads to unrest with some of the dairy animals, and these animals may then be inclined to consider the platform as unpleasant. This unrest will not only result in a reduced milk yield with some animals, but these animals will also be inclined not to go to the platform voluntarily. Consequently, when there is no need for milking, and the platform is used as a feed platform, these animals will walk more slowly to the platform or even block the gates. This may lead to further unrest and to insufficient feed consumption, which is undesirable, of course. A further drawback of this known method is that the dairy animals are not able to go voluntarily to the platform for being milked.

Assembly for and a method of feeding and milking animals


In a system providing for user access of secure resources upon user authentication by a remote authentication server, a successful user authentication is saved locally for use when the authentication server is not available. The successful user authentication returns an authenticated credential which is stored on the local client utilizing a security method such as Public Key Infrastructure which prevents tampering with the credential. If a gateway machine provides connectivity between the client and the authentication server, the credential is also stored on the gateway.

As computer networks proliferate and the use of the internet, intranets and other remote methods of providing computer resources and services become more popular, the problem of authenticating users becomes more and more important. It is imperative for providers of resources such as banking services, databases holding personal or other sensitive information and internal company resources, for example, to be able to reliably identify users attempting to access their resources. As such, well known standards and methods have been developed to provide for user authentication. Many such standards and methods involve the remote exchange of some type of user authentication credential.
A user attempting to access a secure resource might be asked to enter some identifying information, such as a user id and/or a password. Behind the scenes and transparent to the user, the user's system would send the identifying information to an authentication server connected to the user's system via a network, such as the internet. Assuming the authentication server recognizes the identifying information as associated with an authorized user, an authenticated credential would be returned to the user's system, with which the user would be allowed to access the requested resource. The nature of the identifying information and the methods used by the user's system and the authentication server to verify the user's right to access the resource can all be in accordance with any one of the well-known standards regarding such functions. These methods and standards are easily identified by those skilled in the relevant arts.
One popular standard that has been developed for remote authentication of users is the Light-weight Directory Access Protocol (LDAP). LDAP may be used to authenticate users to access resources that may reside locally or remotely to the user. Typically, especially in small business environments, the LDAP server is located remotely from the user. Utilizing a remote LDAP server provided through a service provider allows the small business to save the cost of providing its own local LDAP servers. Connectivity to the LDAP server is provided via the internet, an intranet or other computer network. FIG. 1 shows one possible LDAP configuration. The user's system (or client) 10 is located on a local area network (LAN) 20 to which resources 30 are also connected. These resources can include various media such as databases or world-wide web content or computer-implemented services such as banking services, training courseware, etc. Some of these resources 30 may be secure resources, the use of which requires user authentication. The client 10 is also connected to a computer network 40, such as the internet or an intranet, via a secure gateway machine 50. The gateway machine 50 may provide connectivity to the network for other clients (not shown) as well. The presence of the gateway 50 is optional as the client 10 may be connected directly to the computer network 40. Also connected to the network 40 is an LDAP server 60 for providing LDAP user authentication services for the client 10 and other systems utilizing its services (not shown) and other secure resources (30) which may be accessed by the client 10.
In order to access resources 30 which require user authentication, the client 10 must contact the LDAP server 60 and receive an authenticated credential. When the LDAP server is unavailable, such as when any of the connections between the client and the LDAP server are down (i.e., the client-gateway connection, the gateway-network connection or the network-LDAP server connection) or when the LDAP server or the gateway machine is down, user authentication is not possible and the user is unable to access the desired secure resource(s). In the case of a business environment, this can cause serious productivity losses.
In some instances, some resources 30 may be located on the client machine 10. Authentication of the user by the LDAP server 60 would still be required before the user could access such resources. In the case where the client 10 is a mobile computer, the client will often be disconnected from the network. In such an instance, the user would be unable to access the secure resources on the mobile client because there would be no connectivity to the LDAP server. Again, serious productivity losses could result.
For these reasons, and others readily identified by those skilled in the art, it would be desirable to develop techniques to allow user's some access rights to secure resources when a remote authentication server is unavailable while maintaining a high degree of trust.

Remote authentication caching on a trusted client or gateway system


An applicator for a syringe is provided that includes a hub configured to be disposed at least partially within a nozzle of the syringe and defining a fluid passage therethrough, with one or barbs on the hub that frictionally and sealingly engage an interior of the nozzle in a manner minimizing void space associated with waste of deliverable material, and an applicator tip extending distally from the hub. The barb(s) may have varying diameters in order to enable the applicator to be engaged and utilized with syringes having different diameter nozzles. Further the fluid passage through the hub and applicator tip is dimensioned to minimize the volume of material that is retained within the applicator after use, thereby increasing the volume of material that can dispensed from the syringe for use in a procedure or procedures and minimize waste.

In various types of medical and dental procedures it is often necessary for an individual to dispense an amount of a fluid onto a surface being treated. The fluids can have various purposes, such as to sterilize, anesthetize, clean or treat in some manner the surface being examined during the procedure.
In order to precisely deliver the fluids onto the surface for the desired purpose, a number of different delivery systems have been developed. One such delivery system is a syringe. The syringe is formed with a barrel containing an amount of the fluid to be dispensed and a nozzle at one end of the barrel from which the fluid is expelled from the barrel. Opposite the nozzle, a plunger is slidably positioned within the barrel and includes a bung that contacts the fluid within the barrel. The plunger can be moved within the barrel in order to compress the fluid via the bung to urge or force the fluid from within the barrel out of the syringe through the nozzle. The amount of fluid dispensed from the nozzle is controlled by the force applied to the fluid via the plunger, and thus the individual can determine the amount of fluid to be dispensed.
With these syringes, a suitable applicator, such as a those including a needle extending outwardly from a plastic assemblage, among others, is secured to the nozzle opposite the barrel to direct the flow of fluid from the nozzle and inject or apply various medical materials and medicaments. To secure the applicator to the nozzle, a suitable engagement structure is formed on the nozzle that is engageable with a complementary structure disposed on the applicator. Typically these "applicators" are called "applicator tips" (these words are used interchangeably throughout the document).
By far the most common syringe and applicator connection is formed by the luer taper in which the syringe nozzle is formed with a 6% tapered surface on the exterior of the nozzle tip that allows for a fluid tight connection when mated with an applicator that has an assemblage with an interior surface having a complementary 6% taper. The assemblage also includes an engagement structure, to facilitate a lock or a slip connection with the nozzle. In the luer lock connection, an exterior flange on the assemblage is engaged with threads located on the exterior of the nozzle or on the interior surface of a sheath spaced from and surrounding the nozzle. In the luer slip connection, the friction between the interior 6% taper surface of the assemblage and the exterior 6% taper surface of the nozzle hold the applicator on the nozzle, optionally in conjunction with a locking member on the assemblage that engages the nozzle.
As shown in FIG. 1, the current construction of a currently-available tip/hub 17 forming the part of the applicator that is used to connect the applicator to a syringe 15 is configured to fit over and around the distal tip/nozzle 15x of the syringe at its distal end and results in a significant amount of unintended waste of the material to be dispensed from the syringe. Although the entire syringe barrel is not expressly illustrated in this prior art drawing, those of skill in the art will readily appreciate how the hub 17 fits with the distal tip/nozzle 15x of a standard syringe 15 that includes a distal-extending lip 15y around that tip 15x. More specifically, the portion of the hub of the applicator that extends between the distal terminus of a syringe nozzle 17a and a proximal end 17c of a needle as indicated in FIG. 1 essentially functions as a reservoir 17b for unused material within the applicator. When the syringe's plunger 15w is pressed completely into the barrel of the syringe 15, any material to be dispensed from the barrel is urged out to and through the applicator 17. However, because the material exiting the needle must be acted upon by additional material positioned between the needle and the plunger and being pressed by the plunger, when the plunger has reached the limit of its movement within the barrel, the material remaining in the hub (between the plunger 15w and proximal needle end 17c) cannot be pressed out through the needle, and thus is wasted. Although the actual volume of the material remaining unused in the hub is relatively small, in numerous procedures where a single syringe is used repetitively to dispense the material through a number of successively applied applicators, this can result in a significant amount of material wasted. As an example, dental practitioners will typically use 35 mg of a bioceramic, such as BC sealer, available from Brasseler (Savannah, Ga.), to fill voids during an endodontic procedure and/or an apicoectomy surgical procedure. The barrel of the syringe of the BC sealer contains 2 g of bioceramic, which directly translates to 57 procedures that can theoretically be performed using the amount of bioceramic contained within the syringe. However, this analysis does not take into consideration the amount of material wasted within each applicator, which is replaced for each procedure for obvious hygienic and other purposes, although the syringe is able to be used across multiple procedures. Nevertheless, testing on syringes including these amounts of material and using conventional applicators having the hubs shown in FIG. 1 have shown that approximately 82 mg of material remains unused within the hub per procedure, thereby limiting the dental practitioner to 17 actual procedures per syringe. Compared to the amount of material actually used in a typical procedure (i.e., 35 mg), 2.3× that amount of material is left unusable within the applicator. For every one procedure performed, therefore, the dental professional wastes 2.3 procedures within each applicator with a cost in price and materials associated with losing about 40 procedures.
One prior art attempt to address this issue is disclosed in U.S. Patent Application Publication No. US2016/0008545, entitled Low Waste Syringe And Needle Assemblage, the entirety of which is expressly incorporated herein by reference except that terms defined herein shall weigh over any definitions in said reference. In the '545 application, the low waste needle syringe includes a syringe tip that is formed with an outward taper of its inner diameter in order to mate with a complementary frusto-conical member of a needle assembly. The smooth outer surface of the frusto-conical member contacts the smooth inner surface of the tip to align a needle base with the exterior of the tip. The base includes threads that engage a flange on the exterior of the tip in a manner to secure the base to the syringe tip. While reducing the volume of interior of the needle assembly, and thus reducing the amount of unused material remaining within the needle assembly after use, the structure of the needle assembly requires a specific configuration for the tip that differs significantly from existing syringe configurations, as it requires the syringe to include a mating/reverse frusto-conical shape to receive and contactingly mate with the '545 publication's tip. As such, the needle assembly disclosed therein needs a custom/complementary syringe design that does not encompass the vast majority of existing commercially available syringe designs.
Accordingly, it is desirable to develop an applicator for attachment to common/commercially available syringes, which applicator is configured for significantly reducing the amount of unused material retained within the applicator after use. It is also desirable that the applicator include a universal connector that can be utilized with syringes having different nozzle or syringe tip configurations.