Disclosed are methods for treating or preventing inflammatory bowel disease (IBD) using amide and related compounds. Pharmaceutical compositions containing amide compounds which are useful for the treatment or prophylaxis of IBD are also disclosed.

1. Field of the Invention
This invention relates to the treatment of inflammatory bowel disease (IBD). More specifically, this invention is directed to methods for treating or preventing IBD using amide compounds. This invention is also directed to pharmaceutical compositions containing amide compounds which are useful for the treatment or prophylaxis of IBD.
2. State of the Art
The term inflammatory bowel disease (xe2x80x9cIBDxe2x80x9d) describes a group of chronic inflammatory disorders of unknown causes involving the gastrointestinal tract (xe2x80x9cGI tractxe2x80x9d). The prevalence of IBD in the US is estimated to be about 200 per 100,000 population or approximately 500,000 people. Patients with IBD can be divided into two major groups, those with ulcerative colitis (xe2x80x9cUCxe2x80x9d) and those with Crohn""s disease (xe2x80x9cCDxe2x80x9d).
In patients with UC, there is an inflammatory reaction primarily involving the colonic mucosa. The inflammation is typically uniform and continuous with no intervening areas of normal mucosa. Surface mucosal cells as well as crypt epithelium and submucosa are involved in an inflammatory reaction with neutrophil infiltration. Ultimately, this situation typically progresses to epithelial damage with loss of epithelial cells resulting in multiple ulcerations, fibrosis, dysplasia and longitudinal retraction of the colon.
CD differs from UC in that the inflammation extends through all layers of the intestinal wall and involves mesentery as well as lymph nodes. CD may affect any part of the alimentary canal from mouth to anus. The disease is often discontinuous, i.e., severely diseased segments of bowel are separated from apparently disease-free areas. In CD, the bowel wall also thickens which can lead to obstructions. In addition, fistulas and fissures are not uncommon.
Clinically, IBD is characterized by diverse manifestations often resulting in a chronic, unpredictable course. Bloody diarrhea and abdominal pain are often accompanied by fever and weight loss. Anemia is not uncommon, as is severe fatigue. Joint manifestations ranging from arthralgia to acute arthritis as well as abnormalities in liver function are commonly associated with IBD. Patients with IBD also have an increased risk of colon carcinomas compared to the general population. During acute xe2x80x9cattacksxe2x80x9d of IBD, work and other normal activity are usually impossible, and often a patient is hospitalized.
Although the cause of IBD remains unknown, several factors such as genetic, infectious and immunologic susceptibility have been implicated. IBD is much more common in Caucasians, especially those of Jewish descent. The chronic inflammatory nature of the condition has prompted an intense search for a possible infectious cause. Although agents have been found which stimulate acute inflammation, none has been found to cause the chronic inflammation associated with IBD. The hypothesis that IBD is an autoimmune disease is supported by the previously mentioned extraintestinal manifestation of IBD as joint arthritis, and the known positive response to IBD by treatment with therapeutic agents such as adrenal glucocorticoids, cyclosporine and azathioprine, which are known to suppress immune response. In addition, the GI tract, more than any other organ of the body, is continuously exposed to potential antigenic substances such as proteins from food, bacterial byproducts (LPS), etc.
Once the diagnosis has been made, typically by endoscopy, the goals of therapy are to induce and maintain a remission. The least toxic agents which patients are typically treated with are the aminosalicylates. Sulfasalazine (Azulfidine), typically administered four times a day, consists of an active molecule of aminosalicylate (5-ASA) which is linked by an azo bond to a sulfapyridine. Anaerobic bacteria in the colon split the azo bond to release active 5-ASA. However, at least 20% of patients cannot tolerate sulfapyridine because it is associated with significant side-effects such as reversible sperm abnormalities, dyspepsia or allergic reactions to the sulpha component. These side effects are reduced in patients taking olsalazine. However, neither sulfasalazine nor olsalazine are effective for the treatment of small bowel inflammation. Other formulations of 5-ASA have been developed which are released in the small intestine (e.g. mesalamine and asacol). Normally it takes 6-8 weeks for 5-ASA therapy to show full efficacy.
Patients who do not respond to 5-ASA therapy, or who have a more severe disease, are prescribed corticosteroids. However, this is a short term therapy and cannot be used as a maintenance therapy. Clinical remission is achieved with corticosteroids within 2-4 weeks, however the side effects are significant and include a Cushing goldface, facial hair, severe mood swings and sleeplessness. The response to sulfasalazine and 5-aminosalicylate preparations is poor in Crohn""s disease, fair to mild in early ulcerative colitis and poor in severe ulcerative colitis. If these agents fail, powerful immunosuppressive agents such as cyclosporine, prednisone, 6-mercaptopurine or azathioprine (converted in the liver to 6-mercaptopurine) are typically tried. For Crohn""s disease patients, the use of corticosteroids and other immunosuppressives must be carefully monitored because of the high risk of intra-abdominal sepsis originating in the fistulas and abscesses common in this disease. Approximately 25% of IBD patients will require surgery (colectomy) during the course of the disease.
Oxygen-derived free radicals such as HOxe2x80xa2, the superoxide anion and other reactive oxygen species such as HOCl, have emerged as a common pathway of tissue injury in a wide variety of diseases whose underlying cause is an inappropriately vigorous and sustained immune response (failure to control or down regulate response to the initial, appropriate stimulus). Examples of other diseases, in addition to IBD and arthritis, where this mechanism appear to be the operative cause are ARDS, septic shock, asthma, diabetes, multiple sclerosis, uveitis, etc. Typically, both a cytokine-mediated immune response and a nonspecific inflammatory cascade are involved in the primary inappropriate response with both responses mediated through active oxygen species (oxidative stress). The inappropriate secondary response, also mediated through oxidative stress) may involve tissue damaging oxidation by neutrophils and tissue macrophages.
Various approaches have been taken to suppress this inappropriate inflammatory response. Small molecule inhibitors of the various leukotriene, PAF and cyclooxygenase pathways have shown only limited efficacy, perhaps because blocking only one of many pathways does not provide a sufficiently large decrease in overall oxidative stress. Another approach has been the use of antibodies or cloned receptor molecules which target specific proteins in the inflammatory cascade such as IL-1, IL-6 or TNF-xcex1. However, this approach is practical only for acute conditions, like septic shock or ARDS, where IV administration and antibody formation against the therapeutic protein is less of a concern. For a chronic condition like IBD, an orally active small molecule that is fully active when dosed once-a-day would be the preferred method of treatment.
Another approach to mitigating the oxidative stress resulting from an inflammatory response is to employ nitrone-related therapeutics (NRTs). The prototype NRT is xcex1-phenyl-t-butyl nitrone (PBN) shown below.
NRTs represent a new category of therapeutics with the inherent capacity to overcome the shortcomings of other previously studied compounds. Among other properties, NRTs such as PBN are believed to trap free radicals (Rxe2x80xa2) by adding the radical to form a more unreactive nitroxyl free radical.
Nitrones were first used as analytical tools capable of reacting with highly reactive radicals to yield free radical adducts that are much less reactive. In many cases, the free radical/nitrone adduct complex is stable enough to allow in vivo isolation and quantitation using electron spin resonance (ESR). The concept of using nitrones as therapeutics in, for example, neurodegenerative diseases resulted from the observations that nitrones, such as PBN, trap reactive oxygen species and/or secondary free radicals following ischemia. The therapeutic effects of nitrones may result because the nitrones convert highly reactive radicals into much less reactive products. Certain NRTs have been shown to protect experimental animals from ischemia/reperfusion injury (stroke). NRTs, administered chronically, reverse the age-associated increase in oxidatively damaged protein and the age-associated decrease in the activity of the oxidative-sensitive enzyme, glutamine synthetase, in the brain.
Accompanying the NRT-mediated changes in oxidized protein and glutamine synthetase activity is a significant improvement in the performance of animals in behavioral tests measuring short-term spatial memory. For example, it has been shown that prototype NRTs mitigate the effects of this inflammatory cascade in a number of in vivo models. Of particular interest is the consistent and well documented protection shown by PBN against the lethality induced by LPS in various rodent models of septic shock. Remarkably, PBN has also been shown to increase the life span of senescence-accelerated mice by one third, perhaps by mitigating free radical damage. PBN has also been shown to block inducible nitric oxide synthetase (xe2x80x9ciNOSxe2x80x9d), the enzyme responsible for producing large amounts of the highly damaging NOxe2x80xa2. Thus, PBN can both trap HOxe2x80xa2 and suppress formation of NOxe2x80xa2, potentially neutralizing the effects of the two agents considered to be the most damaging to tissue.
When evaluating the prospects of using an anti-oxidant to successfully treat IBD, it is perhaps also useful to consider that the anti-oxidant defense of the human colon is relatively deficient compared to human liver (mucosal levels of SOD, catalase and GSH representing 8%, 4% and 40%, respectively of liver levels), thus leaving the colon particularly sensitive to oxidative stress. A considerable number of chemical modifications have been made to increase NRTs suitability as therapeutic agents. The effects of intrinsic chemical reactivity and radical trapping ability have been examined by substituting the phenyl ring with electron donating or electron withdrawing substituents. More water soluble analogues have also been made which, for example, have a carboxylate or sodium sulfonate group on the phenyl ring. In addition, lipophilic analogues have been made with functional group substitutions on either the phenyl ring or the nitronyl nitrogen. The alkyl nitrogen substituent has also been varied through the standard straight chain and branched C3-C5 substituents. Nitrone isosteres and related compounds have also targeted and examined for efficacy. This approach has led to various classes of compounds, such as substituted ureas, amides, thioamides, azoxy derivatives, sulphones, and hydroxamic acids. Among these, some benzamide compounds substantially similar in structure to some nitrones, such as PBN, have been shown to have activity in the treatment of Parkinson""s disease, HIV dementia, and related conditions.
As a final aspect of background, in evaluating the effectiveness of compounds in the treatment of IBD, an in vivo model based upon trinitrobenzene sulfonic acid (xe2x80x9cTNBSxe2x80x9d) is used.
References relating to the above-mentioned subjects include:
Glickman, RM (1994) Inflammatory Bowel Disease in Harrison""s Principles of Internal Medicine (McGraw Hill, New York, N.Y.) Chapter 255: 1403-1416.
Calkins, B M, Mendeloff, A l (1986) Epidemiology of Inflammatory Bowel Disease, Epidemiology Review 8: 60-90.
Levin, B. (1992) Inflammatory Bowel Disease and Colon Cancer, Cancer (Supplement), 70: 1313-1316.
Crotty, B. (1994) Ulcerative Colitis and Xenobiotic Metabolism, Lancet, 343: 35-38.
Hanauer, S B, Baert, F. (1994) Medical Therapy of Inflammatory Bowel Disease, Med Clin North Am, 78: 1413-1426.
MacDermott, R P (1994) Alterations in the Mucosal System in Ulcerative Colitis and Crohn""s Disease, Med Clin North Am, 78: 1207-1231.
Hanauer, B. (1993) Medical Therapy of Ulcerative Colitis, Lancet, 342: 412-417.
Winrow, V R, Winyard, P G, Morris, C J, Blake, D R (1993) Free radicals in Inflammation: Second Messengers and Mediators of Tissue Destruction, Br Med Bull 49: 506-522.
Floyd, R A and Carney, J., Nitrone Radical Traps (NRTs) Protect in Experimental Neurodegenerative Diseases, in Neuroprotective Approaches to the Treatment of Parkinson""s Disease and Other Neurodegenerative Disorders (Olanow, C W, Jenner, P and Youssim E, Eds.) Academic Press, New York, N.Y., in press.
Cao, X. and Phillis, J W (1994) a-Phenyl-N-tert-butyl-nitrone Reduces Cortical Infarct and Edema in Rats Subjected to Focal Ischemia. Brain Res. 644: 267-272.
Zhao, Q., Pahlmark, K., Smith, M.-J., and Siesjo, B. (1994) Delayed Treatment with the Spin Trap a-phenyl-n-tert-butyl nitrone (PBN) Reduces Infarct Size Following Transient Middle Cerebral Artery Occlusion in Rats. Acta Physiol. Scad. 152: 349-350.
Oliver, C N, Starke-Reed, P E, Stadtman, E R, Carney, J M and Floyd, R A (1990) Oxidative Damage to Brain Proteins, Los of Glutamine Synthetase Activity and Production of Free Radicals During Ischemia Induced Injury to Gerbil Brain. Proc. Natl. Acad. Sci. USA 87: 5144-5147.
Carney, J M, Starke-Reed, P E Oliver, C N, Landrum, R W, Cheng, M S, Wu, J F and Floyd, R A (1991) Reversal or age-related increase in brain protein oxidation in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-xcex1-phenylnitrone. Proc. Natl. Acad. Sci., 88: 3633-3636.
Novelli, GP (1992) Oxygen Radicals in Experimental Shock: Effects of Spin-Trapping Nitrones in Ameliorating Shock Pathophysiology, Critical Care Medicine, 20: 499-507.
Hamburger, S A, McCay, P B (1989) Endotoxin-Induced Mortality in Rats is Reduced by Nitrones, Circulatory Shock, 29: 329-334.
Progrebniak, H W, Merino, M J, Hahn, S M, Mitchell, J B, Pass, H I (1992) Spin Trap Salvage from Endotoxemia: The Role of Cytokine Down-Regulation, Surgery, 112: 130-139.
McKechnie, K., Furman, B L, Paratt J R (1986), Modification by Oxygen Free Radical Scavengers of the Metabolic and Cardiovascular Effects of Endotoxin Infusion in Conscious Rats, Circulatory Shock 19: 429-439.
Edamatsu,R, Mori,A., Packer, L (1995) The Spin Trap N-tert-xcex1-phenyl-butylnitrone Prolongs the Life Span of the Senescence Accelerated Mouse, Biochem Biophys Res Comm 211: 847-849.
Miyajima, T., Kotake, Y. (1995) Spin Trapping Agent, Phenyl N-Tert_Butyl Nitrone, Inhibits Induction of Nitric Oxide Synthase in Endotoxin-Induced Shock in Mice, Biochem Biophys Res Commun, 215: 114-121.
Boettner, GR (1987) ESR Parameters of Spin Adducts, Free Radical Biology, 3: 259-303.
Harris, M L, Schiller, H J, Reilly, P M, Donowitz, M, Grisham, M B, Bulkley (1992), Free Radicals and Other Reactive Oxygen Metabolites in Imflammatory Bowel Disease: Cause, Consequence or Epiphenomenom, Pharmacol. Ther., 53: 375-408.
Grisham M B, MacDermott, R P, Deitch E A (1990), Oxidant Defence Mechanisms in the Human Colon, Inflammation, 14: 669-680.
Elson, C O, Startor, R B, Tennyson, G S, Ridell, R H (1995), Experimental Models of Inflammatory Bowel Disease, Gastroenterology, 109: 1344-1367.
Yamada, T, Marshall, S, Specian, R D, Grisham, M B (1992) A Comparative Analysis of Two Models of Colitis in Rats, Gastroenterology, 102: 1524-1534.
Wallace, J A, MacNaughton, W K, Morris, G P, Beck P L (1989) Inhibition of Leulotriene Synthesis Markedly Accelerates Healing in a Rat Model of Inflammatory Bowel Disease, Gastroenterology, 95: 29-35.
Higa, A. McKnight, G W, Wallace, J L (1993) Attenuation of Epithelial Injury in Acute Experimental Colitis by Immunomodulators, Eur. J. Pharmacol|. 239: 171-178.
Castro, G A, Roy, S A, Stockstill, R D (1974) Trichinella Spiralis: Peroxidase Activity in Isolated Cells from the Rat Intestine, Exp. Parasitol., 36: 307-315.
It has now been found that certain amide compounds are effective for the treatment and prophylaxis of IBD.
Accordingly, in one of its composition a spects, this invention provides a pharmaceutical composition for the treatment or prophylaxis of inflammatory bowel disease comprising a pharmaceutically acceptable carrier and an effective inflammatory bowel disease-treating amount of a compound selected from the group consisting of:
N-tert-butyl 3-trifluoromethylbenzamide,
N-cyclopentyl 4-trifluoromethylbenzamide,
N-cyclobutyl 4-trifluoromethylbenzamide,
N-cyclopropyl 4-trifluoromethylbenzamide,
N-phenyl 4-trifluoromethylbenzamide, and pharmaceutically acceptable salts thereof.
Another aspect of this invention is directed to methods for treating a patient suffering from or susceptible to an inflammatory bowel condition. Accordingly, this invention provides a method for treating a patient suffering from or susceptible to an inflammatory bowel condition comprising administering to said patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective inflammatory bowel condition-treating amount of a compound selected from the group consisting of:
N-tert-butyl 3-trifluoromethylbenzamide,
N-cyclopentyl 4-trifluoromethylbenzamide,
N-cyclobutyl 4-trifluoromethylbenzamide,
N-cyclopropyl 4-trifluoromethylbenzamide,
N-phenyl 4-trifluoromethylbenzamide, and pharmaceutically acceptable salts thereof.
In still another of its method aspects, this invention provides a method for treating or preventing inflammatory bowel disease comprising:
(a) identifying a patient suffering from or susceptible to an inflammatory bowel condition; and
(b) administering to said patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective inflammatory bowel condition-treating amount of a compound selected from the group consisting of:
N-tert-butyl 3-trifluoromethylbenzamide,
N-cyclopentyl 4-trifluoromethylbenzamide,
N-cyclobutyl 4-trifluoromethylbenzamide,
N-cyclopropyl 4-trifluoromethylbenzamide,
N-phenyl 4-trifluoromethylbenzamide, and pharmaceutically acceptable salts thereof.
In the methods of this invention, the pharmaceutical compositions may be administered orally, parenterally, or rectally. The methods of this invention are be effective where the inflammatory bowel condition is ulcerative colitis or Crohn""s disease.
In one embodiment of the above methods, the pharmaceutical composition is preferably administered as an oral dose in an amount of from 0.1 to about 150 mg/kg of patient weight.
In another embodiment of the above methods, the pharmaceutical composition is preferably administered intravenously in an amount of from about 0.01 mg/kg/hour to about 100 mg/kg/hour of patient weight for at least about 1 hour.
In still another embodiment of the above methods, the pharmaceutical composition is preferably administered rectally in an amount of from 1 to about 150 mg/kg of patient weight.
In one of its composition aspects, this invention is also directed to novel amide compounds. Accordingly, this invention is directed to each of the following compounds:
N-tert-butyl 3-trifluoromethylbenzamide,
N-cyclopentyl 4-trifluoromethylbenzamide,
N-cyclobutyl 4-trifluoromethylbenzamide, and pharmaceutically acceptable salts thereof.
The treatment methods and pharmaceutical compositions of this invention employ one or more amides or related compounds as the active agent. For the purposes of this invention, the amide compounds are named using conventional amide nomenclature, i.e., the substituents on the amide nitrogen atom are given the N- prefix. For example, N-cyclopentyl 4-trifluoromethylbenzamide has the formula:
In some cases, the amides of this invention may contain one or more chiral centers. Typically, such compounds will be prepared as a racemic mixture. If desired, however, such compounds can be prepared or isolated as pure stereoisomers, i.e., as individual enantiomers or diastereomers, or as stereoisomer-enriched mixtures. All such stereoisomers (and enriched mixtures) of the amide of formula I are included within the scope of this invention. Pure stereoisomers (or enriched mixtures) may be prepared using, for example, optically active starting materials or stereoselective reagents well known in the art. Alternatively, racemic mixtures of such compounds can be separated using, for example, chiral column chromatography, chiral resolving agents and the like.
When describing the compounds, pharmaceutical compositions and methods of this invention, the following terms have the following meanings unless otherwise specified.
xe2x80x9cTrifluoromethylxe2x80x9d refers to the group xe2x80x9cxe2x80x94CF3xe2x80x9d.
xe2x80x9cPharmaceutically acceptable saltxe2x80x9d refers to salts which are acceptable for administration to mammals including, by way of illustration, alkali and alkaline earth metal salts and addition salts of free acids and amines. Such pharmaceutically acceptable salts may be derived from a variety of organic and inorganic counter-ions well known in the art and include, by way of example only, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, and the like; and when the molecule contains a basic functionality, salts of organic or inorganic acids, such as hydrochloride, hydrobromide, tartrate, mesylate, acetate, maleate, oxalate and the like.
The term xe2x80x9cpharmaceutically acceptable cationxe2x80x9d refers to a pharmaceutically acceptable cationic counterion of an acidic functional group. Such cations are exemplified by sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium cations, and the like.
The compounds of this invention can be prepared from readily available starting materials using the following general methods and procedures. It will be appreciated that where typical or preferred process conditions (i.e., reaction temperatures, times, mole ratios of reactants, solvents, pressures, etc.) are given, other process conditions can also be used unless otherwise stated. Optimum reaction conditions may vary with the particular reactants or solvent used, but such conditions can be determined by one skilled in the art by routine optimization procedures.
Additionally, as will be apparent to those skilled in the art, conventional protecting groups may be necessary to prevent certain functional groups from undergoing undesired reactions. The choice of a suitable protecting group for a particular functional group as well as suitable conditions for protecting and deprotecting various functional groups are well known in the art. For example, numerous protecting groups, and their introduction and removal, are described in T. W. Greene and G. M. Wuts, Protecting Groups in Organic Synthesis, Second Edition, Wiley, New York, 1991, and references cited therein.
In a preferred method of synthesis, the amide compounds of this invention are prepared by coupling a carboxylic acid halide of formula I:
wherein R1 is 3-trifluoromethylphenyl or 4-trifluoromethylphenyl, and X is halo, preferably chloro or bromo, with an amine of formula II:
xe2x80x83R2xe2x80x94NH2xe2x80x83xe2x80x83II
wherein R2 is tert-butyl, cyclopentyl, cyclobutyl or cyclopropyl, under conventional reaction conditions.
The coupling reaction is typically conducted by contacting the carboxylic acid halide I with an excess, preferably about 1.1 to about 3 equivalents per carbonyl halide group, of amine II. This reaction is typically conducted at a temperature of from about xe2x88x9210xc2x0 C. to about 30xc2x0 C. for about 1 to about 24 hours. Typically, the reaction is conducted in an inert diluent such as dichloromethane, chloroform, benzene, toluene, acetonitrile, tetrahydrofuran and the like.
Preferably, the coupling reaction is conducted in the presence of a suitable base to scavenge the acid generated during the reaction. Suitable bases include, by way of example, triethylamine, diisopropylethylamine, N-methylmorpholine and the like. Alternatively, an excess of amine II may be used to scavenge the acid generated during the reaction.
Upon completion of the coupling reaction, the amide is recovered by conventional methods including precipitation, chromatography, filtration, distillation and the like. If a protecting group has been employed, the protecting group is then removed using conventional procedures.
The carboxylic acid halides employed in the coupling reaction are either commercially available or can be prepared from commercially available starting materials and reagents using conventional procedures. For example, carboxylic acid halides can be readily prepared from the corresponding carboxylic acid by contacting the carboxylic acid with an inorganic acid halide, such as thionyl chloride, phosphorous trichloride, phosphorous tribromide or phosphorous pentachloride, or alternatively, with oxalyl chloride under conventional conditions. Generally, this reaction is conducted using about 1 to 5 molar equivalents of the inorganic acid halide or oxalyl chloride, either neat or in an inert solvent, such as carbon tetrachloride, at temperature in the range of about 0xc2x0 C. to about 80xc2x0 C. for about 1 to about 48 hours. A catalyst, such as N,N-dimethylformamide, may also be used in this reaction.
Preferred carboxylic acid halides for use in this invention include 3-trifluoromethylbenzoyl chloride and 4-trifluoromethylbenzoyl chloride.
The amines of formula II are also either known compounds or compounds that can be prepared from known starting material and reagents by conventional procedures. Examples of suitable amines for use in this reaction include, but are not limited to, tert-butylamine, cyclopentylamine, cyclobutylamine and cyclopropylamine.
Alternatively, the amides of this invention can be prepared by coupling a carboxylic acid (i.e., a compound of formula I where X is OH) with an amine of formula II using conventional coupling reagent, such as dicyclohexyl-carbodiimide and the like, or N,Nxe2x80x2-carbonyldiimidazole. This reaction can be conducted with or without the use of well known additives such as N-hydroxysuccinimide, 1-hydroxybenzotriazole, etc. which are known to facilitate the coupling of carboxylic acids and amines.
When used as pharmaceuticals, the compounds employed in this invention are typically administered in the form of a pharmaceutical composition. Such compositions can be prepared using procedures well known in the pharmaceutical art and comprise at least one active compound.
Generally, the compounds of this invention are administered in a pharmaceutically effective amount. The amount of the compound actually administered will typically be determined by a physician, in the light of the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered, the age, weight, and response of the individual patient, the severity of the patient""s symptoms, and the like.
The compound(s) is typically formulated into a pharmaceutical composition suitable for oral, parenteral (e.g. intravenous or intramuscular injection), or rectal (e.g. suppository) administration.
The compositions for oral administration can take the form of liquid solutions or suspensions, powders, tablets, capsules or the like. In such compositions, the amide compound is usually a minor component (0.1 to about 50% by weight) with the remainder being various vehicles or carriers and processing aids helpful for forming the desired dosing form. A liquid form may include a suitable aqueous or nonaqueous vehicle with buffers, suspending dispensing agents, colorants, flavors and the like.
A solid form may include, for example, any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose; a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, sugar, methyl salicylate, or orange flavoring.
Injectable compositions are commonly based upon injectable sterile saline or phosphate-buffered saline or other injectable carriers known in the art. Again, the active amide compound is typically a minor component, often being from about 0.05 to 10% by weight, with the remainder being the injectable carrier and the like.
Rectal administration is usually by suppository. Suppositories are generally made with a base component of cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weights, or fatty acid esters of polyethylene glycol. The active amide compound is usually a minor component, often from about 0.05 to 20% by weight, with the remainder being the base component.
The components for orally administrable, injectable compositions and suppositories are merely representative. Other materials as well as processing techniques and the like are set forth in Part 8 of Remington""s Pharmaceutical Sciences, 18th edition, 1990, Mack Publishing Company, Easton, Pa., 18042, which is incorporated herein by reference.
One can also administer the compounds of the invention in sustained release forms or from sustained release drug delivery systems. A description of representative sustained release materials can be found in the incorporated materials in Remington""s Pharmaceutical Sciences.
The conditions treated with the pharmaceutical compositions of this invention generally include IBD and the various symptoms which fall within a definition of IBD. The formulations are administered to achieve a therapeutic effect. For those compounds that exhibit a long residency in the body, a once-a-day regimen is possible. Alternatively, multiple doses, such as up to three doses per day, typically, may offer more effective therapy. Thus, a single dose or a multidose regimen may be used.
In any event, the pharmaceutical composition is administered in such a manner so that compound is delivered into the patient""s bloodstream. One excellent mode for accomplishing this is intravenous administration. Intravenous dose levels for treating IBD range from about 0.01 mg/kg/hour of active amide compound to about 100 mg/kg/hour, all for from about 1 to about 120 hours and especially 1 to 96 hours. A preloading bolus of from about 50 to about 5000 mg may also be administered to achieve adequate steady state levels. Other forms of parenteral administration, such as intramuscular injection can be used, as well. In this case, similar dose levels are employed.
With oral dosing, one to three oral doses per day, each from about 0.1 to about 150 mg/kg of active compound are employed, with preferred doses being from about 0.15 to about 100 mg/kg.
With rectal dosing, one to three rectal doses per day, each from about 1 to about 150 mg/kg of active compound are employed, with preferred doses being from about 1 to about 100 mg/kg.
In any treatment regimen, the health care professional should assess the patient""s condition and determine whether or not the patient would benefit from treatment. Some degree of routine dose optimization may be required to determine an optimal doing level and pattern.
A positive dose-response relationship has been observed. As such and bearing in mind the severity of the side effects and the advantages of providing maximum possible amelioration of symptoms, it may be desired in some settings to administer large amounts of active compound, such as those described above.
The following formulation examples illustrate representative pharmaceutical compositions of this invention. The present invention, however, is not limited to the following pharmaceutical compositions.
A compound of formula I is admixed as a dry powder with a dry gelatin binder in an approximate 1:2 weight ratio. A minor amount of magnesium stearate is added as a lubricant. The mixture is formed into 240-270 mg tablets (80-90 mg of active compound per tablet) in a tablet press.
A compound of formula I is admixed as a dry powder with a starch diluent in an approximate 1:1 weight ratio. The mixture is filled into 250 mg capsules (125 mg of active compound per capsule).
A compound of formula 1(125 mg), sucrose (1.75 g) and xanthan gum (4 mg) are blended, passed through a No. 10 mesh U.S. sieve, and then mixed with a previously made solution of microcrystalline cellulose and sodium carboxymethyl cellulose (11:89, 50 mg) in water. Sodium benzoate (10 mg), flavor, and color are diluted with water and added with stirring. Sufficient water is then added to produce a total volume of 5 mL.
The compound of formula I is dissolved in a buffered sterile saline injectable aqueous medium to a concentration of approximately 5 mg/mL.

Amide therapeutics and methods for treating inflammatory bowel disease


The present invention provides a nonaqueous electrolyte secondary battery porous layer which improves an initial battery characteristic immediately after initial charge and discharge of a nonaqueous electrolyte secondary battery. In the nonaqueous electrolyte secondary battery porous layer in accordance with an aspect of the present invention, a standard deviation of bursting strength is 0.6 or more and 11.0 or less.

Nonaqueous electrolyte secondary batteries, particularly lithium ion secondary batteries, have a high energy density and are therefore in wide use as batteries for personal computers, mobile phones, portable information terminals, and the like. Such nonaqueous electrolyte secondary batteries have recently been developed as on-vehicle batteries.
As a member of such a nonaqueous electrolyte secondary battery, a separator having excellent heat resistance is under development. As the separator which excels in heat resistance, a separator including a porous layer which contains a heat-resistant component is known.
Patent Literature 1 discloses a bursting strength of a nonwoven fabric for a separator in an alkaline battery.

Nonaqueous electrolyte secondary battery porous layer


In one example, an apparatus and method are provided for rendering map images. In one example, an apparatus (e.g., a map server) includes logic for causing the transfer of tiled vector image data in response to a map request, wherein the vector data is associated with stored map data divided into a plurality of tiles. The tiled vector image data is transferred to a remote device (e.g., a client device) for rendering of the map image. Additionally, the vector image data may comprise one or more attributes associated therewith, the one or more attributes configurable by a receiving device. For example, the map image may be rendered (e.g., customized) based on one or more local attributes to vary the language used, colors, how items in the map are displayed, and other imaging characteristics of the map image.

1. Field
The present invention relates generally to systems and methods for rendering large images, such as maps, in client-server systems, and in one particular example, to client-side rendering of a map image according to received tiled vector image data.
2. Related Art
Various map and geographic information systems are known in the art. For example, various Web-based mapping services operating to deliver map image data to clients via a Web browser are known. Generally, the map image data may span large geographic areas and may be displayed in several discrete zoom levels. The map image data may further include various additional services, such as street names, addresses, and businesses for display with or overlaying the map image.
In a typical client-server environment, such as a Web based mapping service, map images are generally rendered on the server side in response to a user request for a map image and transferred to the client for display. For example, in response to a user request for a map image, a map server renders the appropriate image data for the location and zoom level associated with the request, renders the image data, and communicates the image data to the client (e.g., as JPEG or bitmap data). The image data is generally communicated to the client as raster image data, e.g., data for displaying an image as a collection of independently controlled dots or pixels arranged in rows and columns, which together form an image of the desired map. Raster image data may include bitmap data for producing the desired image, the bitmap data including a collection of pixels that represent an aerial or satellite photograph, graphical image, or the like of a geographical location (e.g., a city or neighborhood).
Map servers generally store terabytes or more of data associated with large map images and for transfer to clients (in some examples, however, the map data is not stored physically with the map server; rather, the map data is accessed by the map server from a local or remote database). The loading or rendering of map data for delivery to a client in response to a request is generally computationally burdensome on the server side, the client-side, or both. Accordingly, current Web based map image systems, e.g., based on rastor image data, generally suffer from several drawbacks. For example, zooming (or scaling) of the map image generally requires additional map data to be retrieved by the map server for display, and as such, generally requires greater storage and computational demands on the server to store and render each offered zoom level. Accordingly, as a client changes the zoom or pans within the map, there is often a time lag in the display of the map as the map server accesses, renders, and transfers the new map data corresponding to the new zoom level or view to the client.
Further, rastor images are generally optimized for display on a client display device such as a computer monitor or handheld device screen (e.g., at a resolution of approximately 1280×1024 and about 80-100 pixels per inch); however, such resolution optimized for display on a monitor is generally well below a desired resolution for printing. For example, typical printer resolution may be on the order of 600 dots per inch or greater such that printing a map rendered at a relatively low resolution (e.g., 80-100 pixels per inch) used for display results in relatively low quality printed image (compared with the printer's capability). Increased image resolution described for printing, however, would further burden the server, client, or both during map image rendering operations.
Accordingly, it is desired to provide a system and method for rendering images such as map images in a fast and efficient manner; for example, with reduced computational and storage demand on the server. Additionally, it is desirable to provide a system and method for rendering images that may be zoomed more efficiently and printed at higher resolution by a client.

Method of client side map rendering with tiled vector data


To minimize the variability in the emitted light color and improve the unevenness of color tone, a light emitting device comprises a light emitting element and a fluorescent substance that is excited by the light emitting element, wherein the light emitting element has an emission spectrum in a region from ultraviolet to visible light of short wavelengths, and the fluorescent substance has an emission spectrum that includes two or more emission peaks with at least two peaks of the two or more peaks being in the relation of complementary colors of each other.

The present invention relates to a light emitting device that uses a light emitting element and a fluorescent substance and can be used for such applications as illumination, display, indicator and other light sources, and particularly to a white light emitting device that uses a fluorescent substance that is excited by the light emitted by a semiconductor light emitting element and emits light having a spectrum in the visible region.
Various semiconductor light emitting elements have been developed such as light emitting diode and laser diode. These semiconductor light emitting elements are replacing part of electric bulbs and cold cathode ray tubes as light sources for display, back light and indicator, by taking advantage of such features as the capability to run on low voltage, small size, light weight, small thickness, long life, high reliability and low power consumption.
In recent years, such light emitting devices have been developed as nitride semiconductor is used as the light emitting element that can efficiently emit light in a region raging from ultraviolet to visible light of short wavelengths. Such LEDs capable of emitting blue or green light with 10 candela or higher luminous intensity have been commercialized by using light emitting elements having quantum well structure with activation (light emission) layer made of nitride semiconductor (for example, mixed crystal of InGaN).
It has also been made possible to carry out color mixing including white color by combining the light emitted by such an LED chip (light emitting element) and the light emitted by a fluorescent substance that is excited by the light of the LED chip thereby to produce fluorescence.
Such light emitting diodes are disclosed, for example, in Japanese Non-examined Patent Publication No. 152609/1993, Japanese Non-examined Patent Publication No. 153645/1997 and Japanese Non-examined Patent Publication No. 10-242513/1998.
Specifically, the light emitting element is caused to emit ultraviolet rays or blue light of relatively short wavelengths in the visible region, and the fluorescent substance is excited by the light of this light emitting element so as to emit visible light of wavelengths longer than the light emitted by the light emitting element. The constitution that employs color mixing of the light emitted by the light emitting element (visible light) and the light emitted by the fluorescent substance has an advantage that the structure can be simplified and the output power can be increased, although color drift is likely to occur. When a light emitting element that emits ultraviolet rays is used, on the other hand, such a constitution is employed as fluorescent substances capable of emitting light of red, green and blue colors so as to produce white light are used, so that the color can be adjusted relatively easily since only the light emitted by the fluorescent substances is used. When a light emitting element that emits ultraviolet ray is used, in particular, mass productivity can be improved since deviation of wavelength of the light emitted by the semiconductor light emitting element can be accommodated somewhat and the chromaticity can be determined only by the color of light emitted by the fluorescent substance.
However, in the light emitting device of the prior art where two or more kinds of fluorescent substance are used and a desired color is produced by color mixing of the light emitted by the fluorescent substances, intensity ratio of light emitted by two fluorescent substances changes due to difference in the excitation spectrum between the two fluorescent substances, when emission wavelength of the light emitting element used in excitation changes.
As a result, in the light emitting device of the prior art where two or more kinds of fluorescent substance are used, it has been difficult to satisfactorily suppress the variation of chromaticity of the light emitting device since variability in the emission wavelength of light emitting element affects the chromaticity of the light emitting device.
For the semiconductor light emitting element to be used as light source including illumination by making use of the advantage thereof, the light emitting device of the prior art is not satisfactory and it is required to increase the luminance and improve the mass productivity.
There has not been known any fluorescent substance that can be excited by near ultraviolet rays or visible light of short wavelengths so as to emit red light with sufficient luminance.
Therefore, there is such a case as the proportion of mixing the red light emitting fluorescent substance must be increased, which results in a decrease in the relative luminance. When the fluorescent substance is excited by near ultraviolet rays, variability in the wavelength of light emitted by the light emitting element may lead to a decrease in the luminance of red light emitted by the fluorescent substance due to the shift in the wavelength of light that excites the fluorescent substance, thus resulting in a change in chromaticity of light emitted by the light emitting device.
Also in case the fluorescent substance is excited by a fluorescent substance emitted by the light emitting element, it is desired that a required color can be achieved by controlling the composition of the fluorescent substance in order to improve the mass productivity.

This patent is subject to a terminal disclaimer.


A rubber endless track belt assembly for use in a crawler type track mechanism, which has a rubber endless track belt and a plurality of metal cores embedded at an equal spaced distance to one another in the belt along the longitudinal direction thereof. Each of the metal cores is provided with a pair of intermediate guide lugs spaced apart from each other and projecting outwardly on the inner peripheral side of the belt, a pair of wing portions each projecting horizontally in the transverse direction of the belt and embedded therein, and a pair of flat surface zones to which bogie wheels are thrustedly and rotatingly contacted, each of which zones being formed between the guide lug and the wing portion so as to extend in the longitudinal direction of the belt over the width of the wing portion and to be exposed on the inner peripheral side of the belt.

1. Field of the Invention
This invention relates to an endless track belt assembly for use in a crawler type track mechanism, more particularly to an endless track belt assembly having a rubber endless track belt and a plurality of metal cores of which their respective lower parts are embedded at an equal spaced distance to one another in the rubber endless track belt along the longitudinal direction of the belt.
2. Description of the Prior Art
Heretofore, as a crawler type track mechanism, in construction machines, metallic endless track belt assemblies have been exclusively used. On the other hand, rubber endless track belt assemblies have been used in cultivation machines.
In the metallic endless track belt assembly 1, a plurality of center-flanged bogie wheels 2 or side-flanges bogie wheels 3 used exclusively for the metallic endless track belt assembly 1 have been associated therewith as shown in FIGS. 1A and 1B. On the other hand, in the rubber endless track belt assembly 1'in which a plurality of metal cores 6 are embedded in a rubber endless track belt 4 except for their respective guide lugs 7, a plurality of center-flanged bogie wheels 2 or outside-contacted bogie wheels 5 used exclusively for the rubber endless track belt assembly 1' have been associated therewith as shown in FIGS. 2A and 2B.
In FIGS. 2A and 2B, reference numeral 8 represents a plurality of steel cords embedded in the rubber endless track belt 4 and extending in the longitudinal direction of the belt 4 to reinforce the same.
In recent years, however, it has appeared that the rubber endless track belt assembly has been often used in construction machines also. In case the side-flanged bogie wheels are associated with the rubber endless track belt assembly, it tends to cause a bad condition called a "pitting phenomenon (water insect phenomenon)" on the contact surface of the rubber endless track belt, because outer peripheral surfaces of side flanges of each of the side-flanged bogie wheels are directly thrust-contacted to the contact surface. Therefore, the rubber endless track belt assembly cannot be used for a long time.
On the other hand, in case the center-flanged bogie wheels are associated with the rubber endless track belt assembly, it does not tend to cause the above-described problem, but the following inconveniences are caused.
Namely, since the rubber endless track belt assembly 1' is made to contact at respective top surfaces m, m of the guide lugs 7, 7 of the metal core 6 with roll-contact surface parts of the center-flanged bogie wheel 2 as shown in FIG. 2A, the distance h between the top surfaces m, m of the guide lugs 7, 7 and the steel cords 8 becomes large, and further it is necessary to enlarge the distance g (shown in FIG. 3) between respective guide lugs of two metal cores adjacent to each other embedded in the rubber endless track belt 4.
As a result, the rubber endless track belt assembly causes fluctuation vibrations at non-contacted portions thereof to the bogie wheels and so called as an "inward bending phenomenon" thereat also when the rubber endless track belt assembly is run on a projection such as, for example, a stone, etc. In case of the inward bending phenomenon, thus bent, non-contacted portion between two metal cores adjacent to each other is opened so that one of the center-flanged bogie wheels falls in that portion. As a result, both the guide lugs of such two metal cores adjacent to each other are forcibly kicked off by the "falled-in" bogie wheel when it gets off from the opened portion of the rubber endless track belt assembly, so that the metal cores are peeled off from the rubber endless track belt thereby deteriorating the durability of the rubber endless track belt assembly.
In order to prevent the aforementioned inconveniences from the rubber endless track belt assembly, it is thought to make all of the guide lugs in T-shape and to elongate the longitudinal length f of the top surface m of each guide lug as shown in FIG. 3. In such a structure of the guide lug, however, the distance g between respective guide lugs of two metal cores adjacent to each other is shortened, so that around the periphery of a drive or idler sprocket wheel respective of both edges of the guide lugs adjacent to one another in the longitudinal direction of the belt assembly cause a collision phenomenon. Therefore, the length f of the top surface m of each guide lug can not be enlarged more than a predetermined limited length, so that a reduction of vibrations and an effective prevention of the inward bending phenomenon themselves have their limitations.
In the case where case the outside-contacted bogie wheels are associated with the rubber endless track belt assembly, the aforementioned inconveniences of using the center-flanged bogie wheels do not occur because the roll-contact surface parts of each of the outside-contacted bogie wheels are directly contacted to the inner peripheral surface of the rubber endless track belt. However, the outside-contacted bogie wheels can not be associated with the metallic endless track belt assembly and tend to cause the above-described pitting phenomenon on the contact surface of the rubber endless track belt thereby deteriorating the durability of the rubber endless track belt assembly.


There is disclosed an image forming apparatus that has two operation panels—a standard operation panel and an optional operation panel. The image forming apparatus has a standard mode and a professional mode which provide different displays on the operation panels. In addition, custom displays may be stored and recalled by the users.

1. Field of the Invention
The present invention relates to operation panels of image forming apparatuses that have functions such as a copying machine function, a printer function, a fax machine function etc.
2. Description of Related Art
Conventionally, in a compound machine that has a copy machine function, a printer function, and a fax machine function, there has been a technique to enable another operation panel that is loaded as optional equipment to operate in conjunction with an operation panel that is included as standard equipment when such an optional operation panel is loaded. Also, there has been a technique to display detailed description of functions that are configured when various settings are set through the operation panel of a copy machine to which an information equipment that has a display function is connected.
However, aforementioned conventional equipment can display only items and contents that are predefined such as print menu list and detailed description of functions when another panel is loaded as extended equipment.
Therefore, selecting menu items can be difficult for users who do not have enough understanding of the functions of the image forming apparatus because information necessary for them may not be displayed, or, on the other hand, selecting menu items each time could be bothersome for users who often use the image forming apparatus and have a lot of knowledge on its functions because totally unnecessary information for them may be displayed. As described above, there have been various problems depending on the users' level of knowledge on the operation of the image forming apparatus.

User interface for image forming apparatus


An optoelectronic component includes a semiconductor chip, and a phosphor at least partly surrounding the semiconductor chip, wherein 1) the semiconductor chip emits a primary radiation in a short-wave blue spectral range at a dominant wavelength of less than approximately 465 nm, and wherein the phosphor converts at least part of the primary radiation into a longer-wave secondary radiation in a green spectral range at a dominant wavelength of approximately 490 nm to approximately 550 nm, and 2) a mixed light composed of primary radiation and secondary radiation has a dominant wavelength at wavelengths of approximately 460 nm to approximately 480 nm such that luminous flux of the mixed light is up to 130% greater than luminous flux of an optoelectronic component without a phosphor having the same dominant wavelength of 460 nm to 460 nm.

Known optoelectronic components comprise semiconductor chips which emit electromagnetic radiation in the blue spectral range having a wavelength of less than approximately 480 nm. The semiconductor chips have to emit electromagnetic radiation having the longest possible wavelength to achieve high lumen values. This has the disadvantage that the radiation power of a semiconductor chip that emits in the blue spectral range decreases greatly as the wavelength increases.
It could therefore be helpful to provide an optoelectronic component which comprises semiconductor chips having a high radiation power and at the same time emits light in the long-wave blue spectral range.


An automatic volume control system and method for use in a multimedia computer system having at least one speaker and at least one audio generating device accumulates a status of the audio generating device to determine if it is on or off. The system recognizes an audio mute event notification signal from a notification device, such as an incoming telephone call notification signal, and selectively generates a control signal for use in varying the volume to the at least one speaker in response to the detection of the notification signal to selectively control audio from the audio generating device. The system also accommodates multiple audio generating devices. The system analyzes the location of the telephone, speakers and audio generating devices to determine the type of action that is necessary.

Conventional multimedia computer systems typically have speakers for limited stereo audio capabilities. The user can manually adjust volume control and can have limited manual equalization adjustment capabilities for on-board CD players or television cards. Such systems may also allow for manual adjustment of volume control for personal computer based telephone answering systems. Known television cards for personal computers typically route the television audio signals directly to the television speakers without providing any audio control.
Standards are being developed for universal serial bus (USB) hub controllers that multiplex differing buses to interface with a computer. With such USB's, many devices can be connected to a personal computer. Where a single multimedia computer system controls multiple audio generating devices that are not necessarily on-board the computer, such as CD players, digital versatile or video disc (DVD's) players, VCR's, and television monitors, the location of each audio generating device can vary such that the devices can be in separate rooms throughout a home or office building. Where multiple speakers are coupled to the computer through an audio card, groups of speakers can also be located in different locations throughout the home or office building. Also, facsimile/modem and telephone answering systems can also be connected to the computer where different telephone lines can be coupled through a common modem in a computer.
When multiple audio generating devices are operational, such as when a movie is being watched on a DVD player in one room and a television is being watched in another room, and the telephone rings, the volume from the movie (speakers) or television can often be excessively loud so that the ring is not heard. Also, if the ring is heard, a person wishing to converse on the telephone has to manually reduce the volume or leave the room with the telephone to avoid being inundated by the loud audio. The problem is compounded when multiple telephones are located in a home or office building and multiple audio generating devices can be operational at the same time.
Consequently, there exists a need for an automatic volume control/pause control system and method for use in multimedia computer systems that substantially overcomes one or more of these problems. It would be advantageous if such a system could selectively generate an audio volume control signal for any of a determined number of audio generating devices upon detection of an audio mute notification signal. In addition, such a system should be able to determine which telephone is ringing to determine whether volume control should be instituted. When the volume must be controlled, the system should also determine whether the volume should be adjusted or whether another volume control mechanism should be employed. Moreover, the system should recognize priority incoming calls as requiring differing volume control strategies.

Automatic volume control system and method for use in a multimedia computer system


A method and device for protecting slot-in optical disc drive are provided. A first sensing switch is for detecting the action of an unloading unit, a second sensing switch is for detecting the action of a receiving unit, and a third sensing switch is for detecting the action of a positioning bar. A disc is inserted as the optical disc drive is at the initial state, and the states of the first, second and third sensing switches are detected. The transmission unit is activated to automatically load the disc as all sensing switches are turned on, and whether the state of the third sensing switch changes is checked. When the state of the third sensing switch changes, the extraction of the disc is detected, so the transmission unit is immediately reversed to execute the unloading of the disc, so as to protect the optical disc drive.

1. Field of the Invention
The invention relates in general to an optical disc drive, and more particularly to a method and a device for protecting slot-in optical disc drive by automatically extracting a disc when the abnormal extraction of the disc is detected in the course of loading the disc.
2. Description of the Related Art
Normally, optical disc drives are divided into tray type optical disc drive and slot-in optical disc drive according to the way of loading/unloading a disc. According to loading/unloading way of the tray type optical disc drive, the disc is placed in a receiving space of a tray, and the tray is moved into or extracted from the optical disc drive. As for the slot-in optical disc drive, the loading/unloading mechanism automatically sucks in the disc and further guides the disc to be positioned when the disc is disposed at the entrance of the optical disc drive or unloads the disc. The slot-in optical disc drive is user-friendly and is easy to be thinned.
In the course of loading a disc to a conventional slot-in optical disc drive, the user holds the disc and directly inserts the disc into the entrance of the optical disc drive. Then, the user pushes the disc into the optical disc drive. When the disc activates the detecting mechanism of the optical disc drive and the inserting depth of the disc is detected, the optical disc drive activates its transmission motor to drive the loading/unloading mechanism to automatically load the disc into the optical disc drive and further guides the disc to a predetermined position. Then, the loading/unloading mechanism uplifts a traverse having a spindle motor until the spindle motor is able to retain the disc by the central hole of the disc and to rotate the disc for the data to be retrieved.
In the course stated above, the disc is gradually moved into the optical disc drive. Before the disc is positioned, the disc is partly exposed outside the optical disc drive, and the user may extract the disc from the optical disc drive at any time. If the disc is extracted by the user after the transmission motor is already activated by the optical disc drive, the traverse, which is automatically uplifted would scratch or damage the disc that has not been completely extracted since the loading/unloading mechanism continues the loading of the disc at fast speed. This is because when the disc is extracted, the optical disc drive still continues to drive the loading/unloading mechanism to load the disc at a fast speed. Furthermore, the force to extract the disc will cause the guiding rod of the loading/unloading mechanism to be curved or deformed and make the optical disc drive jammed or damaged.
To prevent the damage caused by abnormal operation, as disclosed in the prior art of the Taiwanese Patent Publication No. 093115463, a releasing mechanism is disposed on the guiding rod of the loading/unloading mechanism. When the force received by the guiding rod is over a predetermined limit, the releasing mechanism releases a locking mechanism, such that the receiving end of the guiding rod can rotate freely to avoid the deformation of the guiding rod. However, the releasing mechanism does not stop the transmission motor, and if the user extracts the disc too late, the traverse that is uplifted fast will still scratch or damage the disc. Beside, the above protection mechanism is disposed on the guiding rod, which is narrow and small, not only making the manufacturing and assembly of the optical disc drive more difficult and costive but also not favoring the miniaturization of the optical disc drive. Thus, the manufacturer of slot-in optical disc drive still has many problems to resolve regarding the protection during abnormal operation.

Method and device for protecting slot-in optical disc drive


A keyboard contains an input device comprising a linear strip of sensitive material the approximate width of the human finger integrated into the left or right side of the keyboard. The strip is linearly sensitive in only one direction and not to any other direction, such as from left to right. A user operates the device by touching it with his or her finger and varies the input by changing the position along the strip and the pressure of his or her finger.

1. Field of the Invention
The invention relates generally to user input devices. More particularly, the present invention relates to a simple computer touch input device providing input information corresponding to position and pressure.
2. Description of the Related Art
Conventional input devices are inefficient and require a user to utilize skill and dexterity in order to operate. In particular, keyboards require a modicum of typing skills and fine-motor devices such as miniature trackballs and the IBM trackpoint (pencil-eraser-look-alike) device are difficult to use and may be impossible or uncomfortable for people with slight disabilities.
Even simple devices tend to have disadvantages. For example, a mouse can be used to point to and click on items displayed on a screen. The mouse is typically restricted to operate merely as a pointing device, with the user moving the mouse with the right hand and either doing nothing with the left hand or pressing a small number of modifier keys. The non-dominant hand (typically the left hand) is underutilized during graphical interaction with the display of a computer screen. Unfortunately, using two mice simultaneously requires an unusually high level of both manual and cognitive dexterity.
Other pointing devices, such as pressure-sensitive touch tablets, also require a certain degree of manual and cognitive dexterity and can be disadvantageous for the further reason that they are bulky and relatively expensive. In particular, three-dimensional input devices, such as flying mouses which are intended to be lifted off of the table to indicate a position in the Z-axis are difficult to use.
Consequently, there is a need for an input device which is easier for users to use than a mouse, has a predictable and close location, and is easier to manipulate, especially when inputting three-dimension position data.


Disclosed are a means and a method for the placement of insulated electrical wires beneath the human scalp in such a way that they will experience no flexing after implantation thus disallowing wire breakage. Specifically, this intracranial system uses wires to connect a control module containing various electronic systems to brain electrodes. These wires are placed in grooves that are made by a surgeon in an outer portion of the patient's cranium by means of a specially shaped burr rotated at high speed by means of a router. At the end of the groove, the surgeon would drill a burr hole in the cranium at the site where a brain electrode is to be placed. A distal portion of each electrical wire would be in the form of a helical coil; one helical coil would be placed in each burr hole. The grooves and burr holes could be filled with an adhesive filler type of material to form a smooth outer surface for the cranium. Also, a special cap could be placed over the burr hole. The function of the cap would be to form a smooth outer surface for the cranium. The electrodes at the end of the wires could be placed at various locations such as deep into the brain, on the brain surface, or in close proximity to the brain.

Electrodes are often placed in close proximity to the brain or deep into the brain structures. Wires to connect these brain electrodes to amplifiers, stimulators or other electronic equipment typically are placed through the patient's skin or scalp. It is conceived that intracranial systems will become available in the near future for the treatment of various neurological disorders that originate in the brain. It is therefore important to be able to provide electrical wire connections to such electrodes without subjecting such wires to frequent bending that might lead to wire breakage.

Means and method for the placement of brain electrodes


A method for processing an interrupt message in a system having a plurality of processors arranged into at least two partitions. The interrupt message is decoded to identify an interrupt source. If the interrupt source is not in an interrupt set, the interrupt is dropped. If the interrupt source is in a local partition, the interrupt is delivered. If the interrupt source is in the interrupt set and not in the local partition, the interrupt is processed in accordance with at least one of a target enable register and a vector enable register.

In a computer system having processors and peripheral devices, such as a memory or other input/output device, interrupts may be used to request a processor to perform a task with regard to the peripheral device or to execute certain instructions. The processor receives an interrupt request including an interrupt vector where the interrupt vector identifies the instructions or task to be performed by the processor.

Hewlett-Packard Development Company, L.P.


The present invention is directed to a device for delivering a sealant to a tissue, comprising a sealant compartment, a cooling gas compartment, and a heater, all disposed inside a unified housing; with heater configured for rendering the sealant liquid or semi-liquid or molten and flowable; with sealant compartment configured for expressing the sealant in a flowable form from device via an exit nozzle; with gas compartment configured for expressing a cooling gas via a gas expression port; with exit nozzle and gas expression port co-directed into the same direction.

Various substances and compositions have been employed to control bleeding from cut bone surfaces. One class of materials used for the control of this type of hemorrhage is called bone wax. Bone waxes are used for controlling hemorrhages from the cut surfaces of bones, such as those of the ribs, by applying the wax as a putty over the cut surface so that the material mechanically occludes and seals the open ends of the bleeding osseous vessels. Bone waxes used in surgery are frequently prepared from refined beeswax which has been admixed with nonabsorbable and water insoluble hydrocarbons and vegetable oils. Some wax formulations can have relatively poor adhesion properties, and the hard brittle state of the wax at room temperatures may require softening and kneading prior to application.
U.S. Pat. No. 4,439,420 by Mattei, et al. titled "Absorbable hemostatic composition" discloses an absorbable hemostatic composition for use in the control of osseous hemorrhage, comprising: (i) a component (A) comprising either a biocompatible fatty acid salt alone, which comprises between 45% and 80% by weight based on the weight of the total composition; or a mixture of said fatty acid salt with a biocompatible in vivo absorption enhancing agent, in which said mixture comprises between 35% and 45% by weight of said fatty acid salt based on the weight of the total composition, and between 25% and 35% by weight of said absorption enhancing agent, based on the weight of the total composition; and (ii) a component (B) comprising a body absorbable biocompatible base selected from the group consisting of ethylene oxide/propylene oxide block copolymers, polyethylene glycols and methoxypolyethylene glycols, triglycerides and fatty acid esters, the cation of said fatty acid salt being selected from the group consisting of calcium, magnesium, zinc, aluminum, lithium and barium, the fatty acid anion being saturated or unsaturated and containing from 10 to 22 carbon atoms in the chain, said composition having a putty-like consistency at room temperature, and a tackiness sufficient for it to adhere readily to a bloody bone surface.
U.S. Pat. No. 8,801,723 titled "Minimally invasive surgical applicator", discloses an apparatus for the application of a surgical material or substance at an elevated temperature, comprising: a) an applicator body, said body comprising: (i) a rear grip, (ii) a chamber for receiving said surgical material or substance, wherein the chamber for receiving surgical material or substance comprises a cover, wherein the chamber cover is a hatch, and (iii) a bayonet; b) a trigger assembly, pivotally actuable on the applicator body; c) an extrusion rod for engagement with said applicator body; d) a tip attached to the bayonet, wherein the tip comprises an angle of inclination of between 0-45 degrees relative to longitudinal axis of the bayonet; and e) a heating assembly for warming the surgical material or substance above room temperature, wherein the heating assembly comprises a heating element and a power source operably connected to said heating element, wherein the heating element is disposed about or along at least 10 percent of the length of the bayonet.
Utility Model publication CN201431481Y "Detachable medical bone wax injection device/A detachable medical bone wax spraying device discloses a detachable medical bone wax spraying device, comprising a nozzle, a spring, an indicator lamp, a temperature sensor, a power supply, a sealing ring and sealing cushions, wherein the device is assembled by a melter and a pressurizer, which are connected with the nozzle in turn.
U.S. Patent Application publication No. 2016/0278786 titled "BONE WAX DISPENSER" discloses a dispenser comprising: a tubular housing; an adjustable base configured to move from one end of the tubular housing to a second end of the tubular housing; and bone wax disposed within the tubular housing.
European Patent Application publication EP2506893A2 titled "ADHESIVE DELIVERY DEVICES, SYSTEMS AND METHODS" discloses an adhesive material injection system for delivering adhesive to a patient site comprising: adhesive material; and a delivery device comprising: a housing; and a nozzle, said nozzle comprising a proximal end and a distal end wherein the adhesive material is configured to exit said nozzle distal end.
U.S. Patent Application publication No. 2009/0220686A1 titled "COMPRESSED AIR SPRAY GLUE GUN" discloses a spray gun for spraying an adhesive material comprising: an adhesive pathway for receiving the adhesive material; a heating element for melting the adhesive material into an adhesive stream which flows within the adhesive pathway; an air pathway for an air stream; and a nozzle comprising an end of the adhesive pathway and an end of the air pathway, wherein the adhesive pathway and the air pathway are configured at the nozzle such that the air stream and adhesive stream exit the nozzle in a substantially laminar direction relative to one another.
U.S. Patent Application publication No. 2008/0073448A1 titled "ANTI-STRINGING APPLICATOR" discloses an applicator for applying a substance, the applicator comprising: a nozzle adapted to deliver the substance; and a gas port configured to be enveloped by the substance and to deliver a gas flow to disrupt a flow of the substance.
U.S. Pat. No. 6,783,534 titled "Bone wax applicator" discloses a bone wax applicator, comprising means for providing a force, a cylinder having a piston end and an outlet end, a piston coupled to said means for providing a force and disposed within said cylinder for close sliding fit therein and for movement between said cylinder piston end and said cylinder outlet end in response to said force, said cylinder having an access opening, an access opening cover moveable between open and closed positions, an open wax transport tube connected at one end to said cylinder outlet end and having an opposing free end, said opposing free end having a discharge opening, and a dissector tip attached to said opposing free end adjacent said discharge opening.
U.S. Pat. No. 8,147,246 titled "Surgical bone wax applicator" discloses a surgical bone wax applicator, comprising: one or more layers of absorbent material; a mass of bone wax deposited on a surface of the absorbent material so that the bone wax adheres to the material; an electrical heating element comprising an electrically resistive heating wire or conductor that extends within the absorbent material in the vicinity of the mass of bone wax, and the heating wire has an associated pair of electrical contact terminals that are exposed on the applicator for connecting the heating wire to an outside voltage source; and the heating wire is constructed and arranged to heat and soften the mass of bone wax when the electrical contact terminals of the heating wire are connected to the outside voltage source and a determined current flows through the heating wire.

Surgical delivery devices for meltable bone wax or bone putty


A system providing self-service access to locked merchandise comprising: (a) providing a fixture that restricts access to the locked merchandise, wherein the fixture can automatically lock or unlock, allowing or restricting access to the locked merchandise; (b) providing a means of uniquely identifying an individual attempting to access the merchandise; (c) measuring a set of behaviors of the individual during any time the fixture is an open mode; (d) assessing whether the set of behaviors of the individual are suspicious or not relative to a set of suspicious event thresholds; (e) storing the individual and their set of behaviors as accessible records in at least one database; and (f) providing an algorithm which determines future access privileges of the individual to the enclosure based on a set of variables.

There is a universal paradox in retail stores, the better you protect your merchandise from theft, the greater the impact this protection has on product sales. In their effort to reduce theft of merchandise, retailers place restrictions on access to merchandise, impacting the vast majority of legitimate shoppers. The typical outcome is retailers inconvenience 99% of legitimate shoppers to stop theft from the 1% who come into their stores to steal. For example, a common method of reducing theft in a retail environment is to secure high-value merchandise by locking it up in a cabinet or other limited access merchandise fixture that makes it difficult for legitimate shoppers to access the product. To complete a purchase, the shopper must locate a store associate to unlock the fixture, gain access to the merchandise, and ultimately purchase the desired item(s). This process is not only costly and labor intensive for retailers, but it's time consuming, frustrating, and inconvenient, for the shopper, which nearly always leads to a horrible customer experience. This locked fixture approach has existed for year, virtually unchanged, and remains a significant problem for retailers. The primary goal of this invention is to modernize this outdated approach and to provide retailers with a means of protecting merchandise from theft, while creating virtually open access to this high value merchandise by legitimate shoppers, arguably providing retailers with the best of both worlds.
The recent trend of people willing to trade privacy for convenience is advantageous to the invention. More and more people willingly surrendering personal information to more easily access their phones, ATM's, board airplanes and other services. This invention capitalizes on this trend by requiring shoppers to provide personal identifying information in exchange for the convenience of unfettered access to merchandise. A typical example would be a shopper desiring to purchase high-value merchandise secured inside a locked liquor cabinet. Without this invention, the shopper would have to track down a store associate who has to locate the key to open the cabinet and access the goods. This cumbersome, time consuming, and inconvenient process typically results in a loss of 25% to 50% of sales; all this to thwart theft from 1% of the shoppers. Using this invention, a shopper approaching the same locked liquor cabinet is identified by some means, such as facial recognition, the use of the retailer's app or some form of customer loyalty information, and the cabinet automatically unlocks. So long as this same shopper doesn't exhibit suspicious behavior, as described in this disclosure, the cabinet automatically opens each time this shopper returns.
While locking or otherwise securing merchandise reduces or even eliminates theft, it also suppresses legitimate sales due to the inconvenience of or even inability of the shopper to obtain required assistance when and where needed. This inconvenience causes a significant percentage of shoppers to abandon the purchase. The value of these lost sales often exceeds the savings realized by preventing theft. Even worse, shoppers significantly inconvenienced in a store often adversely impacts loyalty (i.e., a regular shopper may choose to switch to a competitive store for future shopping trips), representing a far larger loss than the missed sale of the protected item.
Given this tension between theft and sales losses, retailers often choose sales preservation over loss prevention. It is simply more financially advantageous to suffer theft losses rather than sales losses caused by securing theft-prone merchandise. This invention fundamentally eliminates this tension. It allows product protection from theft even while enabling free access to merchandise by trusted customers. In short, retailers no longer have to choose between protecting products from theft and reducing sales. Instead, legitimate shoppers are provided ready access to protected merchandise while such automatic access is denied to individuals deemed "untrusted" by the retailer. The self-service system described in this invention enables retailers to implement effective loss prevention measures which no longer adversely impacts merchandise sales or the shopping experience. Further, the invention supports loss prevention measures that mitigate both opportunistic shoplifting (typically an individual stealing an item) as well as multi-item sweeps (theft of many items at the same time) typically committed by booster teams as part of large-scale organized retail crime operations.
While the above antitheft scenario inspired the invention, it can also be used advantageously in other situations in which identified individuals that exhibit desired behaviors are rewarded with unfettered access to merchandise or other privileges.
In addition to the sales recovery and customer experience advantages provided by the invention, there are significant labor savings achieved by allowing customers to self-service locked merchandise. A typical transaction requiring a store associate to respond to a customer request to unlock a case can require up to 10 minutes of "task interruption" time for the store associate. From responding to the customer, locating the key, unlocking the cabinet and allowing the customer to shop the case, and then returning to tasking, this often takes 10 minutes. 10 minutes of store associate time is equivalent to ˜$2.50. This cost along with the lost productivity can easily eliminate any profit from merchandise sold in the locked fixture.
Finally, lost keys and re-keying of locked cases is a real problem in retail. Employees misplace keys, they bring them home after their shift, and the mechanism eventually wears our. This not only causes lost sales due to then inability to access the merchandise, but the cost of re-keying fixtures is significant.

System providing self-service access to locked merchandise


A system for monitoring a circuit breaker that includes a monitoring device in electronic communication with the circuit breaker and a receiving device located separately from the monitoring device. The monitoring device receives data from the circuit breaker and wirelessly transmits at least a portion of the data such as one or more phase currents measured from a network which the circuit breaker protects, an ambient temperature within the circuit breaker, and/or data relating to a trip condition of the circuit breaker. The receiving device receives the transmitted data and displays all or a portion thereof. The monitoring device also includes a display that displays all or a portion of the data.

1. Field of the Invention
The present invention relates to circuit interrupters and in particular to a system for monitoring a circuit breaker wherein data is collected and wirelessly communicated to a separately located receiving device.
2. Background Information
Molded case circuit breakers are well known in the art as exemplified by U.S. Pat. Nos. 6,747,534 and 6,140,897, owned by the assignee hereof, the disclosures of which are incorporated herein by reference. Molded case circuit breakers include a set of separable main contacts, one of which is usually fixed and one of which is movable for automatically opening upon the occurrence of an overload or short circuit electrical current in the network which the circuit breaker is provided to protect. In addition, electronic molded case circuit breakers have trip units, which are often removeably insertable in the circuit breaker case. A trip unit includes a microprocessor, such as a microcontroller, and is adapted to automatically open the circuit breaker contacts under certain conditions. One such condition is what is known as short tripping of the circuit breaker, and occurs when the amount of current flowing through the separable main contacts of the circuit breaker is so high as to represent a potential catastrophic failure and which therefore requires exceedingly quick opening action of the circuit breaker. A second condition is what is known as long tripping, and occurs in response to a relatively low amount of overload current, which eventually will cause overheating of the electrical wires in the circuit to be protected, but which does not necessitate the instantaneous action a short circuit requires and thus does not require the magnetic tripping described above. In either case, one or more current transducers measure the current flowing through the breaker, and the measured currents are provided to the trip unit microprocessor. Algorithms executed by the microprocessor analyze the measured currents and, when a short trip or long trip condition is detected, the microprocessor causes an actuator to open the contacts and thus trip the breaker. Other types of tripping conditions are also known in the art, such as ground fault tripping and over temperature tripping.
Furthermore, it is desirable to be able to monitor certain conditions of a circuit breaker such as a molded case circuit breaker during operation. Such conditions may include, without limitation, causes of trips, breaker temperature, and phase current magnitudes. Typically, a number of molded case circuit breakers, such as 16 or more, are mounted in a single panel. In such situations, it is cost prohibitive and an inefficient use of space to run wires from the breakers to a central location on the panel or elsewhere to transfer the monitored data for subsequent use. Thus, there is a need for a relatively inexpensive and efficient device and system for monitoring certain breaker conditions.

System for wireless monitoring of circuit breakers


The invention relate generally to a tightening mechanism for a bottle filling and capping system, and a bottle neck configuration. More specifically, the invention includes a machine for tightening plastic caps onto the threaded necks of plastic bottles, and bottle neck configuration that facilitates the capping process, both of which result in a simple and effective capping operation. A conveying assembly moves the bottle in a circular path where the neck of the bottle and the cap are brought together by moving the bottle under a cap that is loosely held at a particular elevation and angle by a feeder mechanism. The conveying system constricts the rotational movement of the bottle, and a neck support stabilizes the neck of the bottle vertically, as the cap is pressed onto the neck initially by a roller. A capping station in a bottle filling line is comprised of a spring biased toothed finger that engage the peripheral edge of the caps as the bottles are conveyed through the machine. Depending on various factors such as the number and circumferential length of the threads on the cap and bottle a second roller and second toothed finger will be used to complete the tightening process. When a capped bottle exits the capping station, the cap is fully engaged with the bottle in that it is tightened and in its final position relative to the bottle.

The capping system shown and described is for use in applying threaded caps onto the threaded necks of containers for beverages, such as milk, other dairy products and juice.
Bottlers of dairy and juice drinks often use blow-molded containers to deliver their beverage products to consumers. To reduce the amount of plastic used in such bottles, for cost and environmental reasons, the bottles have become increasingly thinner; and this progression has tended to make the bottles more flexible and difficult to control, particularly prior to being capped, i.e., in an unsealed condition (either filled or empty). This has made the capping process more difficult, and has required that the bottle be better supported during the capping operation in order to prevent buckling of the bottle as the cap is applied.
A problem with some capping machines is that they have complex capping stations with several large and expensive components, such as multiple rotary capping heads like those that are shown in FIG. 1 of U.S. Pat. No. 4,308,707; FIG. 2 of U.S. Pat. No. 5,218,811; and FIGS. 1 and 2 of U.S. Pat. No. 5,012,630. Some prior art capping stations include pivoting toothed fingers with vertical serrations that engage similarly configured serrations on a bottle cap. An example is U.S. Pat. No. 4,922,684 (hereinafter the '684 patent). But, the system of the '684 patent as a number of drawbacks, including inferior horizontal support for the neck of the bottle during the capping process, no vertical support (other than the bottle's own buckling strength) for the bottle neck during initial placement of the cap onto the bottle, and difficulty in adjusting the force applied by the toothed finger.
The capping system shown and describe herein includes a tightening mechanism for a bottle filling and capping machine, and a bottle neck configuration that receives a support in the form of hook providing both vertical and lateral support during the application process, all of which result in a simple and effective capping operation. A conveying assembly moves the bottle in a defined bottle pathway where the neck of the bottle and the cap are brought together by moving the bottle under a cap feeder that is loosely places a cap onto the bottle a particular elevation. The rotational movement of the bottle during installation of the threaded cap is generally prevented by either weight of the bottle applying a frictional force to a conveyor, or by restraint against rotation based on interference between the bottle and a guide rail, or a combination of these and other means for preventing or limiting rotation of the bottle as a threaded cap is applied to the neck. A neck support stabilizes the neck of the bottle vertically and laterally, as the cap is pressed onto the neck initially by a roller. A capping station in a bottle-filling line further includes a spring biased toothed finger that engages the peripheral edge of the caps as the bottles are conveyed through the machine. Depending on various factors such as the pitch, number and circumferential length of the threads on the cap and bottle a second roller and second toothed finger may be used to complete the tightening process. When a capped bottle exits the capping station, the cap is fully engaged with the bottle in that it is tightened and in its final position relative to the bottle. An additional optional feature of the system described herein is that the pressure applied by the toothed finger is adjustable. Finally, an important aspect of the system is that the bottle neck it shaped to include a groove that receives in a close-fitting way the support or hook that provides both lateral and vertical support to the bottle during the simplified capping operation.


Request processing is optimized. The request has elements. The method, computer program and database system includes selecting an access path for the request taking into consideration a stored actual request element cost, processing the request using the selected access path, producing one or more actual request element costs, and storing the one or more actual request element costs.

A database management system is accessed and managed through "requests." A request can be a query, through which the database is accessed, or an instruction to execute a utility, such as a load command. Most database management systems use an optimizer to select an access plan, or query execution plan, for a database request and most optimizers rely on a cost model, where cost is associated with the amount of a resource, such as CPU or I/O, that must be devoted to a task, to choose the best access plan to execute any given request. Most cost models rely on a mathematical construct that uses estimates of the numbers of rows (cardinalities) which will result at each step of the access plan. The estimates are often based on assumptions regarding the contents of the database tables.


A flow control assembly for regulating fluid flow in a wellbore is disclosed. A remote-open ICD is opened in response to swelling of a swellable actuator. The swellable actuator can move a flow regulator radially, circumferentially, etc., such that flow is allowed through the regulator. Alternately, the swellable actuator can move one or more valve members to an open position thereby allowing fluid to flow across the valve and to the flow regulator. The swellable actuator can be swelled in response to introduction of chemicals or heat. A guide mechanism can be used to control swelling of the actuator or movement of the regulator device or valve member.

Without limiting the scope of the present inventions, their background is described with reference to Inflow Control Devices (ICDs) and design improvements thereto. Inflow Control Devices are designed to improve completion performance and efficiency by balancing inflow throughout the length of a completion. Differences in influx from the reservoir can result in premature water/gas breakthrough, leaving valuable resources in the ground. Typical applications include wells experiencing "heel-toe" effects, breakthrough of water/gas, permeability differences, and water challenges in high viscous oil reservoirs. Another benefit of this technology is that it can balance the fluid injected into the formation in injection wells. U.S. Pat. Nos. 7,469,743 and 7,802,621, the entire disclosures of which are incorporated herein by reference for all purposes, disclose ICDs for sand control screens.
An example of an inflow control device is commercially available from Halliburton Energy Services, Inc. under the trade mark EquiFlow® Inflow Control Device. The EquiFlow® ICD consists of an annular chamber on a standard oilfield tubular. If screen is required, the reservoir fluid is produced from the formation, through the sand screen and into the flow chamber. The flow continues through a set of tubes, which creates a pressure drop, and then into the pipe through a set of ports. Tube length and ID are designed to give the pressure drop needed for optimum completion efficiency. EquiFlow® Adjustable ICDs are pre-configured with a set of tubes that may be re-configured on the rig to change the pressure drop. A slidable housing provides flow tube access. Typically, multiple tubes per ICD are used. Disclosure regarding the EquiFlow® ICD is available on-line.
In many applications, it is beneficial to run the ICD in a closed position during installation. This allows for circulation of fluid down to the shoe and up the annular space outside of a sand screen without using a wash pipe. It is also possible to pressurize the completion to activate other components, like open hole packers. A delayed opening valve has been developed as well. This valve is activated by applying a high tubing pressure to shear a mechanism. Halliburton Energy Services, Inc. manufactures and markets a remotely-opened valve for use with ICDs which holds internal pressure when closed, but opens the screen to full production flow after sufficient internal pressure is applied and released. A remote-open valve is typically installed on each joint of screen, with the valves in the closed position as the screens are run into the well. The valves are sealed to internal pressure only, allowing the screens to fill with well fluid when they are run into the well. When the valves are closed, the entire completion assembly including the screens can be pressurized internally to pressure test the tubing, and pressure can be applied to set downhole devices, such as packer or other operational tools in the completion string. The valve mechanism is made up of a collet and ball assembly with the collet held in a run-in position by an externally inserted shear pin. When enough pressure is applied, the shear pin shears, the collet shifts and locks in an open position while still holding tubing pressure. The number of remote-open valve units is determined by the flow rate required or desired.
U.S. Pat. No. 7,762,341, the entire disclosure of which is incorporated herein by reference for all purposes, discloses a flow control device utilizing a reactive media, comprising a flow path associated with a production control device (e.g., sand screen and ICD); an "occlusion member" (e.g., piston) positioned along the flow path that moves between an open position and a closed position, the occlusion member being activated by a change in a pressure differential in the flow path; and a "reactive media" (e.g., a water swellable material or an oil swellable material) disposed along the flow path that changes a pressure differential across at least a portion of the flow path by interacting with a selected fluid (e.g., water, of a sufficient concentration or amount, encountered by the production control device) to thereby actuate the occlusion member.
U.S. Pat. App. Pub. No. 2011/0067886, the entire disclosure of which is incorporated herein by reference for all purposes, discloses a completion assembly with a valve assembly for regulating fluid flow in a wellbore. The completion assembly can include a base pipe with a sand screen. A flow control housing is disposed on one end of the sand screen. A first tubular port in the base pipe leads into the flow control housing, and a second tubular port is also formed in the base pipe. A flow path is formed within the flow control housing and communicates with both the base pipe and the inner annulus of the screen assembly. A valve assembly is located in the flow control housing and is in fluid communication with both the inner annulus and the base pipe. The valve assembly is positionable between multiple positions for controlling the flow through the flow control flow path in response to fluid pressure applied to the second tubular port.
Therefore, it will be appreciated that advancements in the art of inflow control devices are desirable, and such advancements are also beneficial in a wide variety of circumstances.

Remote-open inflow control device with swellable actuator