A therapeutic composition is provided that comprises a 1-R1-phenyl, 4-R2-phenyl substituted 1,2,3,6-tetrahydropyrimidine-2-one sensory nerve receptor agonist in a therapeutically effective amount. The sensory nerve receptor agonist may be represented by the general formula 1-[R1-phenyl]-4-[R2-phenyl]-1,2,3,6-tetrahydropyrimidine-2-one wherein: R1 is -hydroxy, -chloro, -fluoro, -alkyl, -acetoxy, -trifluoromethyl; and R2 is -nitro, -chloro, -fluoro, -alkyl, -trifluoromethyl. Therapeutic compositions of the invention reduce pain, itch, and a sense of discomfort, when formulated for topical delivery to the human lips, mouth, and to the anorectal area.

Not applicable.
1. Field of the Invention
This invention generally relates to therapeutic compositions formulated for topical delivery to the surfaces of the human lips, mouth, and the anorectal area. This invention more particularly relates to a class of chemicals that activate receptors on sensory nerve endings at or near the entrance and exit of the human gastrointestinal tract and therapeutic use of these chemicals for pain and inflammation. The particularly preferred embodiment compositions are formulated as an ointment, cream, paste, aerosol or suppository and comprise xe2x80x9cicilinxe2x80x9d, a 1,2,3,6-tetrahydropyrimidine-2-one compound.
2. Description of Related Art
Background on Icilin. 1,2,3,6-Tetrahydropyrimidine-2-one compounds were described in U.S. Pat. No. 3,821,221(inventors C. Podesva and J.M. Do Nascimentoet al, Jun. 28, 1974). These compounds were thought to have depressant and/or stimulant effects on the central nervous system. In 1972, an abstract described a compound in this series called AG-3-5 (1[2-hydroxyphenyl]4-[3-nitrophenyl]-1,2,3,6-tetrahydropyrimidine-2-one). This prototype elicited a syndrome of xe2x80x9cwet dog shake behaviorxe2x80x9d in rats and monkeys accompanied by hyperthermia, hyperactivity and ptosis. Wei (Chemical stimulants of shaking behavior. Journal of Pharmacy and Pharmacology 28: 722-724, 1976) provided the first detailed report of the actions of AG-3-5 in animals and noted that shaking behavior similar to those of a dog when wet could be evoked in various laboratory animals such as the rat, mouse, cat, dog, gerbils, guinea pigs and hamsters.
Subsequently, Wei (Pharmacological aspects of shaking behavior produced by AG-3-5, TRH, and morphine withdrawal. Federation Proceedings 40: 1491-1496, 1981) reported that 0.1 mg of AG-3-5, dissolved in propylene glycol, applied to the dorsum of the tongue elicited prickling sensations of cold and ingestion of 6 mg mixed in orange juice, on one occasion out of three, produced sensations of coolness on the cheeks and on the inner surfaces of the arms and legs. It was hypothesized that AG-3-5 may produce specific activation of receptors for cold, and that stimulation of these receptors accounted for the shaking seen in laboratory animals. In a subsequent publication (E. T. Wei and D. A. Seid. AG-3-5: A chemical producing sensations of cold. Journal of Pharmacy and Pharmacology 35: 110-112, 1983) the effects of AG-3-5 on shaking behavior in the rat were compared to those of menthol and AG-3-5 was shown to be 400 times more potent than menthol on a molar basis on this behavioral endpoint. AG-3-5 was less toxic than menthol, as measured by the oral median lethal dose in rats. AG-3-5 was named icilin because of its cold-producing properties.
Recently, two independent groups simultaneously cloned a biological macromolecule (called a receptor) from trigeminal sensory neurons of the rat. These receptors belong to the transient receptor potential (TRP) family of ion channels and responded to cold temperature and to menthol. Using a sample provided by Wei, McKemy et al. (Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416: 52-58, 2002) showed that icilin was about 200 times more potent than menthol in eliciting ion channel current changes in the cloned and transfected TRP(M8) receptor. The ion permeability changes elicited in transfected cells were more robust with icilin than those elicited by menthol, and the presence of extracellular calcium was required for activity. Menthol currents did not require extracellular calcium.
The chemical structure of icilin bears little similarity to that of menthol; the former chemical being a pyrimidine-2-one attached to two phenyl rings, and the latter a cyclohexanol derivative. Activation of the TRP(M8) receptor on the neuronal membrane may lead to depolarization of the sensory nerve ending and send action potentials towards the spinal cord and brain that are eventually recognized as psychic signals of skin stimulation.
Background on Pain and Inflammation of the Oral and Anal Areas.
The mouth is the entrance to the gastrointestinal tract and the anus is the exit. At the point of entrance and exit, the surfaces change from thicker skin to thinner skin, and then to mucous membrane. The border between the skin and mucous membrane is called a mucocutaneous junction. The anatomy of the lips illustrates this transition. The lips present three surfaces and a core. The external surface is thin skin with hair follicles, sebaceous glands, and sweat glands. The second surface is the transition zone or vermilion border; it has no hair follicles or sweat glands and is the external border of the lips. The lips have a pinkish red color due to underlying rich blood capillary network and its forms a transition from keratinized to nonkeratinized epithelium. The inner surface of the lips and mouth is nonkeratinized stratified squamous epithelium and the underlying tissue contains numerous small mucous glands and mucoserous salivary (labial) glands. The central core of the lips is composed of striated muscle embedded in elastic fibroconnective tissue.
The perineum is the skin between the anus and the genitalia and has the typical keratinized epithelium of normal skin. The anatomy of the anus is similar in histology to the lips. The anal epithelium (skin) extends about 1.5 cm inside from the anal verge (external edge) and transits from keratinized to nonkeratinized epithelium at the dentate line, the part that demarcates the anus from the rectum. The rectal surface is a mucous membrane and is not keratinized.
The skin epithelia of the lips and anus and surrounding tissues are densely innervated with sensory nerve fibers and these afferent (A delta and C) fibers code for pain and temperature signals. When the lips or anus, or the tissues surrounding, are injured, the subsequent inflammation stimulates the somatosensory nerve endings and the result is pain and sometimes itch. By contrast, the visceral sensory nerve endings that innervate the mucous membrane of the inner lips, mouth, and rectum do not transmit discrete, localized signals of pain, but are sensitive to stretch. Stimulation of rectal nerve endings produces a sense of distension, an urge to have a bowel movement, flatulence, and, if the stimulation is excessive, rectal pain and discomforts.
Inflammatory Conditions of the Lips and Mouth. The skin and mucosa of the lips are demarcated by the vermilion border. The mucosa seen on viewing the face is keratinized and dry; the mucosa of the inner aspect of the lips is nonkeratinized and moist. Branches of the 5th cranial nerve (trigeminal) innervate these tissues. Non-specific disorders can cause inflammation around the mouth and lips. These include immunological disorders, such as pemphigus, pemphigoid, lichen planus; infections, such as venereally transmitted warts (condyloma cuminatum) and herpes simplex; metaplasia, such as dyskeratosis; and physical causes, such as lip and mouth surgery, sunlight, and wind. Some common conditions affecting the surface of the mouth and lips are:
Angular Cheilitisxe2x80x94Chelitis is the technical term for inflammation of the lips. Angular cheilitis occurs at the corners of the lips. This lesion is seen as dry, scaly, red skin and there may be a fissure or slit in the mucocutaneous junction, causing severe pain when the mouth is opened wide. Angular cheilitis may be caused by dry weather, too much sunlight, allergic reactions, or excessive salivation. Cheilitis is also seen more frequently in persons who have reduced immune function, viral infections, or persistent yeast infection. Other forms of inflammation of the lips are cracking exfoliative cheilitis, cheilitis glandularis, and cheilitis granulomatosa.
xe2x80x9cCold soresxe2x80x9d or herpes labialis, are the result of an infection with a common virus known as herpes simplex. The sores begin as a group of small red bumps that blister. Itching and burning of the area precedes the prodroma phase (the time for onset of sores). The blisters begin to dry up after a few days and form a yellow crust. The crust then falls off and the redness slowly goes away. The whole process takes about 10 to 14 days. The sores frequently occur on the vermilion border and on the corners of the lips. Infections are more common in immunodeficient individuals, and the blisters themselves are infectious.
xe2x80x9cCanker soresxe2x80x9d or recurrent apthous ulcers, are inflammatory spots found on the inside linings of the lips and cheeks and in movable parts of the mouth such as the tongue. The small reddish swellings may be painful, especially if they occur in parts of the mouth in contact with the chewing of food. The sores generally heal within 2 weeks. The causes of canker sores are not known, but the incidence of occurrence may be as high as 20 to 25%.
Stomatits, or inflammation of the inner mouth, can occur after infections, or when cancer chemotherapeutic drugs are administered (a condition that is also called mucositis), or when the head and neck are irradiated for cancer treatment.
Inflammatory Conditions of the Anorectal Area. The area between the anus and the genitalia is called the perineum. The anus is the orifice at the terminus of the intestinal tract. Just behind the anus is the anal canal wherein lies the exterior sphincter and the interior sphincter. A sphincter is a circular muscle that constricts and relaxes. Anal sphincters constrict to retain feces and expand to allow it and flatus to pass during defecation. The anal canal is the first 2 inches of skin after the anus; it is closed while at rest and open during defecation. It leads to the rectum, the cavity that runs vertically from the end of the colon to the anal canal. The rectum is approximately 5 inches long and 1.5 inches wide. It stores feces prior to defecation. The term xe2x80x9canorectal areaxe2x80x9d is defined herein to include the perineum, anus and rectum of a human. More particularly, the term includes the external anus, the internal anus and the lower rectum.
The nerve supply of the anorectal area controls its sensory and motor functions. The inferior rectal nerve, a branch of the pudendal nerve, innervates the lower portion of the anal canal and the external sphincter. These tissues have somatosensory nerve endings, responding to pain, touch and temperature. By contrast, the hypogastric nerve (a visceral nerve because it is part of the autonomic nervous system) innervates the upper portion of the anal canal, internal sphincter and rectum. The sensory nerve endings of the hypogastric nerve respond to distension and transmit visceral afferent signals, including pressure, pain and temperature, to the spinal cord, but discrete sensations are not localized. Instead, over-stimulation of the visceral sensory nerve endings evokes a sense of bloat, distension, cramping, and an urge to defecate.
Many agents or conditions can cause injury to the tissues of the anorectal area and produce pain and inflammation. The primary symptoms are pain and itch but if the inflammation extends to the lower bowel mucosa (rectum, colon, ileum) and its nerve endings, there are also distressing sensations of visceral discomfort. Some of the pathological conditions are described below.
Perineal Dermatitis. Inflammation of perineal skin occurs when urine or feces, because of incontinence, irritates the skin. Pads (e.g. diapers) or other containment devices for incontinence may exacerbate inflammation by causing perspiration and prolonging contact of irritants with tissues. The dermatitis that results causes itch, pain, infections and may lead to ulceration of the skin. Treatment using cleansers, moisturizers, moisture barriersxe2x80x94including ointments, creams, powders, pastes, and lipid barrier films, are discussed by Gray et al. (Perineal Skin Care for the Incontinent Patient. Advances in Skin and Woundcare 15: 170-177, 2002), incorporated herein by reference. An ointment, powder, aerosol or paste containing icilin will alleviate pain and itch of such conditions in the elderly and in the infant (e.g. diaper rash) and facilitate therapeutic management.
Anal Fissure. A fissure is a break or slit in tissue usually at the junction of skin and mucous membrane (mucocutaneous junction). If the fissure occurs on the corner of the mouth, it is called angular cheilitis and opening the mouth can cause pain. An anal fissure is a small tear in the skin of the anus. The fissure can bleed, itch, and become extremely sore during and after defecation, making bowel movements, sitting, and sex painful. Anal sex without lubrication, a hard bowel movement, and inflammation of anal tissue can cause a fissure. Some heal within a couple of weeks, especially if therapeutic cream, warm baths, and stool softeners are used. Others require surgical correction of the tear but this is associated with a subsequent risk of incontinence. Ointments for the treatment of anal fissure have been described in a patent from Cellegy U.S. Pat. No. 6,391,869, incorporated herein by reference. These ointments contain, as active ingredients, substances that release nitric oxide and increase cyclic AMP of smooth muscle cells in the internal anal sphincter. The nitric oxide relaxes the sphincter smooth muscle and the reduced tension decreases pain signals from the fissure.
Hemorrhoids. Hemorrhoids are swollen veins that may protrude outside the anus or reside inside the anal canal. The veins may become inflamed, blocked, or broken and cause fecal contamination of perianal skin. Hence, hemorrhoids may bleed and cause pain and itching because of incontinence and excessive wiping (pruritus ani). Risk factors for hemorrhoids include strenuous or frequent bowel movements that raise intra-abdominal pressure and impede venous return. Related risk factors for developing hemorrhoids are birth trauma and lifting weights.
Sexually Transmitted Diseases. A number of sexually transmitted diseases (STD) can have local effects on tissues in the anorectal region, producing pain, itch, redness and blisters. These STD include:
Herpes simplex virus (HSV) is an infection of the skin and genital mucosa (mucous membrane) causing recurring sores and pain
Gonorrhea: inflammation of genital mucosa, causing infectious and painful discharge
Human papillomavirus (HPV) causes genital and anal warts
Proctitis is inflammation of the lining of the rectum. Proctitis can be short term (acute) or long term (chronic). Proctitis has many causes. It may be a side effect of autoimmune diseases of the lower bowel, such as ulcerative colitis and Crohn""s disease. Sexually transmitted diseases may cause proctitis. Proctitis is frequently a side-effect of radiation used to treat prostate cancer or cancer of the female organs. The rectum resides just behind the prostate in the male and the vagina and uterus in the female, so when these organs are irradiated, the bowel wall is injured. Radiation proctitis is manifested as the new growth of many tiny blood vessels on the epithelial surface of the rectum. These blood vessels are fragile and bleed with minimal trauma, resulting in blood in the stool. If the bleeding is severe, anemia or a low red cell blood count can occur. Other causes of proctitis include traumatic rectal injury, allergies, and malfunction of the nerves in the rectum.
Pathogenic organisms that may cause anorectal inflammation are Salmonella, Shigella, Campylobacter, Entamoeba histolytica, Giardia lamblia, Mycobacterium avium-intracellulare, Cryptosporidium, Microsporidium, and Cytomegaolvirus. Patients infected with human immunodeficiency virus or receiving immunosuppressive drugs are especially susceptible to infectious agents attacking the lower gut lining and surrounding tissues.
The most common manifestation of proctitis is a frequent or continuous sensation of an urge to have a bowel movement. This distressing but ineffectual urge to empty the rectum is called tenesmus. Other symptoms include constipation, a feeling of rectal fullness, left-sided abdominal pain, passage of mucus through the rectum, rectal bleeding, and anorectal pain. Proctitis because it leads to bleeding, some incontinence, and inflammation will produce subjective discomfort, pain, and itch in the entire anorectal area.
Physicians diagnose proctitis by looking inside the rectum with a proctoscope or a sigmoidoscope. Redness, bleeding, or increased growth of blood vessels are indices of inflammation. A biopsy of tissue from the rectum may confirm the presence of inflammatory cells, diseases, or infections. Treatment depends on the cause of proctitis. For example, the physician may prescribe antibiotics for proctitis caused by bacterial infection. If the inflammation is caused by ulcerative colitis or Crohn""s disease, the physician may recommend a drug such 5-aminosalicyclic acid or a glucocorticosteroid. These drugs may be applied directly to the area, as a suppository, or taken orally as a pill. Radiation proctitis may also be treated with analgesics and loperamide, an anti-diarrhea drug with localized actions.
In one embodiment of the present invention, a composition is provided that comprises a 1-R1-phenyl, 4-R2-phenyl substituted 1,2,3,6-tetrahydropyrimidine-2-one sensory nerve endings receptor agonist, preferably formulated as a topical ointment, cream, lotion, lozenge, paste, powder, aerosol, suppository or enema, that is therapeutically effective, such as to relieve pain, when delivered to the lips, mouth, anus and surrounding tissues. The sensory nerve endings receptor agonist may be represented by the general formula 1-[R1-phenyl]-4-[R2-phenyl]-1,2,3,6-tetrahydropyrimidine-2-one wherein: R1 is -hydroxy, -chloro, -fluoro, -alkyl (with about 2 to 4 carbons), -acetoxy, -trifluoromethyl; and R2 is -nitro, -chloro, -fluoro, -alkyl, -trifluoromethyl.
A particularly preferred sensory nerve endings receptor agonist embodiment is called xe2x80x9cicilinxe2x80x9d and a particularly preferred composition comprises icilin formulated as an ointment, cream or suppository. Icilin formulated and administered as an ointment or cream offers improved therapeutic benefit for the treatment of inflammation of the lips, anorectal area and surrounding tissues. The inventive compositions can also be applied to and/or carried on a suppository, such as for treatment of hemorrhoids, or formulated for administration as an aerosol.
A particularly preferred method of treating cheilitis, perineal inflammation (irritant dermatitis), or anal fissures in a human comprises topically administering a composition comprising 1-[2-hydroxyphenyl]4-[3-nitrophenyl]-1,2,3,6-tetrahydropyrimidine -2-one or an analog, wherein the 1-[2-hydroxyphenyl]-4-[3-nitrophenyl]-1,2,3,6-tetrahydropymidine-2-one or an analog preferably in an amount of at least about 1 to 8% by weight of the composition, more preferably about 3% of the composition.
The further advantages and aspects of the present invention will be understood by reading the following detailed description and the accompanying claims.
I have found that icilin and related analogs elicit sensations of cold and anesthetic action when applied topically to the surfaces of the lips and anus, and in surrounding tissues. The effects of cold and numbing are also felt on the inside of the mouth and the tongue; that is, on mucous membranes. These actions can counteract the pain and itch produced in these tissues by inflammation, much like the effects of ice applied to injury.
Uses of Icilin Compounds in Treatment of Inflammation of the Lips, Mouth, and the Anorectal Area. In the parent patent submission, of which this is a continuation-in-part, I described examples whereby topical applications of icilin produced cold sensations on skin and mucous membranes. The somatosensory nerve endings of the lips, mouth, and anorectal area contain receptors that recognize signals coding for pressure, cold and heat/pain. The receptors are coupled to specific cation channels on the nerve membrane and these receptors, when stimulated, cause afferent neuronal transmission to the spinal cord and brain. The specific cold receptor is called TRP(M8) receptor and has a unique molecular composition. The specific receptor for heat/pain has another configuration and is called the vanilloid receptor.
It is recognized for a long time that ice has anti-inflammatory properties and reduces pain (analgesia). Topical application of ice has been used for reducing the discomfort of cold sores on the lips and for the pain of anal fissures, but repeated applications of ice are inconvenient for these conditions. While it is tempting to attribute the actions of ice solely to stimulation of the TRP(M8) receptor, this conclusion is not warranted because: a) ice also causes constriction of blood vessels, b) ice reduces the metabolic activity of cells and may inhibit the release of inflammatory substances (mediators) and c) ice may affect activity of other receptors, as well as affect the process of neurotransmission itself, and the like. Thus, the effects of ice on sensory perception and on inflammation are an empirical observation.
Icilin and related analogs, applied locally as an ointment or cream, or delivered via a suppository or aerosol, produce sensations of cold and reduces the sensations of pain and irritation. These actions attenuate the symptomatic discomforts of cheilitis, stomatitis, mucositis, proctitis and perineal inflammation. The sensory effects of icilin compounds are the basis and mechanisms for its use in treatment of pain, itch and inflammation of the skin, lips; mucous lining of the mouth and anorectal area Without being bound by theory, I hypothesize that the target of icilin actions may be the TRP(M8) receptor, but suspect that at the molecular level other receptors are being affected as well. The observations of the beneficial actions of icilin and related compounds are empirical findings.
The word xe2x80x9cagonistxe2x80x9d was introduced by Reuse (xe2x80x9cComparisons of various histamine antagonists. British Journal of Pharmacology vol.3, pgs. 174-180, 1948) to denote a chemical that activates biological events. A sensory nerve ending is the part of the nerve that, when activated, initiates events that convey signals to the spinal cord and brain. These signals may be translated to sensory experience. Thus, a sensory nerve ending receptor agonist is a chemical that acts on targets on the sensory nerve ending to produce changes in sensation.
Delivery of Icilin Compounds to Targets. Compositions and therapeutic methods in accordance with this invention utilize a 1-R1-phenyl, 4-R2-phenyl substituted 1,2,3,6-tetrahydropyrimidine-2-one sensory nerve endings receptor agonist, preferably of the general formula 1-[R1-phenyl]-4-[R2-phenyl]-1,2,3,6-tetrahydropyrimidine-2-one wherein: R1 preferably is -hydroxy, -chloro, -fluoro, -alkyl (with about 2 to about 4 carbon atoms)-acetoxy, -trifluoromethyl; and R2 preferably is -nitro, -chloro, -fluoro, -alkyl (with about 2 to 4 carbons), -trifluoromethyl. I refer to the particularly preferred compound and its analogs as xe2x80x9cicilinxe2x80x9d and its analogs as xe2x80x9cicilin analogsxe2x80x9d. Formula 1 illustrates the general formula and icilin is represented by Formula 2.
Formula 1: 1-R1-phenyl, R2-phenyl, substituted 1,2,3,6-tetrahydropyrimidine-2-one.
Formula 2: Icilin, 1-[2-hydroxy]-4-[3-nitrophenyl]-1,2,3,6-tetrahydropyridimine-2-one.
Icilin is a lemon yellow crystalline powder with a molecular weight of 311 Daltons and a melting point of 229 to 231xc2x0 C. The powder is without odor and non-irritating, meaning that it does not elicit any smell or unpleasant sensations upon contact with the surfaces of the human body. The compound is stable at room temperature. Icilin is readily soluble in organic solvents such as dimethylsulfoxide, nitromethane, dimethylacetamide and, after warming, in propanediols; slightly soluble in ethanol and acetone; and virtually insoluble in water. Thus, icilin would be considered as a lipophilic, hydrophobic compound that is not easily miscible with aqueous systems. Analogs of icilin, for example, with acetyoxy, ethyl, fluoro, or trifluoromethyl substitutions, retain similar chemical and physical properties and are included within the scope of this invention.
Methods suitable for the preparation of the Formula 1 and Formula 2 compounds are described by Podesva and Do Nascimento, U.S. Pat. No. 3,821,221, issued Jun. 28, 1974, incorporated herein by reference, and are exemplified by Example A hereinafter. Further, the examples 1-6 show the effects of topical application of icilin on skin and mucous membranes to relieve pain of angular cheilitis and pain and itch of hemorrhoidal discomfort. Icilin, administered via a suppository or as an enema, reduces anorectal pain.
Formulation of Icilin Compounds for Topical Delivery to Targets. Pharmaceutical carriers or vehicles suitable for the topical administration of icilin and combinations provided herein to the lips, mouth, or anorectal area include any such carriers known to those skilled in the art to be suitable for the particular mode of administration. The effective concentration may be determined empirically by testing the compounds using in vitro and in vivo systems. Thus, methods for preparing solutions, emulsions and suspensions, using standard methods for formulated Medical Topicals are well known to the art (J. G. Nair, Chapt. 39: Solutions, Emulsions, Suspensions and Extracts, pg. 721-752 and L. H. Block, Chapt. 44, Medicated Topicals, pg. 836-857, in xe2x80x9cRemington, the science and practice of pharmacy,xe2x80x9d Alfonso R. Gennaro, Chairman of the editorial board and editor. 20th ed. Baltimore, Md.: Lippincott Williams and Wilkins, 2000). The recipes for ointment preparation are also on the Internet (www.pharmlabs.unc.edu) site of the School of Pharmacy, University of North Carolina, Chapel Hill. The selected icilin compound of this invention may be dispersed in various vehicles as an emulsion wherein it is either in a suspension or is solubilized, and is in either the aqueous or the oil phase.
The rate of drug absorption across the skin surface is dependent on drug concentration in the formulation, its solubility and its oil/water partition co-efficient. The physical form of icilin to be delivered to the receptors of the sensory nerve endings is optimized by design for penetration of barriers, receptor activation, and sufficient duration of action. Although icilin may be administered as a solution, for example dissolved in a solvent such as propylene glycol, it is more preferably suspended in this solvent as a solid and admixed as an emulsion in an ointment or cream. Before formulation, icilin may be milled to a fine particle size, modified by recrystallization to a particle with maximal surface area, incorporated onto nanospheres, or incorporated into nanoparticles or liposomes, to maximize biological activity and duration of action using such methods as are now known in the art.
Compositions of the present invention with icilin and/or icilin analogs may be formulated as liniments (defined as a preparation that may be liquid or semiliquid intended for external application) or more preferably as ointments or creams. Standard ointment formulations may be used for delivery to the lips and anorectal surfaces. Thus, particularly preferred embodiments of this invention are wherein icilin is used in a non-irritating ointment, cream or lotion. In Example A, I describe a 2% solution of icilin formulated in an Aquaphor(copyright) ointment and used it for investigation. The ingredients in the commercially available Aquaphor(copyright) ointment are petrolatum, mineral oil, ceresin, lanolin alcohol, pathenol, glycerin and bisabolol. This product is quite similar in consistency to pure petrolatum (Vaseline(copyright)), but somewhat less viscous, and is non-irritating. The details for preparation of the ointment are given in Example A. It is to be understood that the concentration ranges set forth herein are exemplary only and are not intended to limit the scope or practice of the claimed formulations.
The Formula I compounds are typically included at concentration of 0.1% w/w up to 20% w/w. Preferable concentrations are in the range of 0.5% w/w to about 20% w/w, more preferably 1% w/w to 20% w/w, yet more preferably greater than about 1% w/w to about 10% w/w, and most preferably greater than 1% w/w up to about 5% w/w. Aqueous suspensions and formulations contain 1% w/w or more.
The U.S. Pharmacopoeia recognizes four general classes of ointment bases. The formulation in Example A is in the category of xe2x80x9cAbsorption Bases (Anhydrous)xe2x80x9d. Another ointment in the xe2x80x9cAbsorption Bases (water in oil type)xe2x80x9d would be composed of icilin, 1.0 to 8% by weight, and containing emulsifying wax, white petrolatum, purified water and propylene glycol, butylated hydroxyanisole, propyl gallate, citric acid and lactic acid. Other ingredients in a topical ointment formulation may include lanolin, paraffin wax, vegetable oils, such as peanut or castor oil, aloe vera, and sorbital sequioleate. A lotion containing icilin, 0.3 to 2% by weight, may be composed of a smooth, homogeneous, opaque emulsion composed of benzyl alcohol 2% (wt/wt) as preservative, emulsifyng wax, glycerin, isopropyl palmitate, lactic acid, purified water, and polyethylene glycol 400. A more viscous ointment may contain these ingredients: a homogeneous melt of 50% methyl salicylate, 25% white beeswax, 25% anhydrous lanolin to which is added 3% by weight of icilin. The mixture is warmed and then allowed to solidify. A soft ointment results having a soothing effect on the anorectal area. Further, icilin may also be formulated in Hydrophilic Petrolatum USP, using 30 g cholesterol, 30 stearyl alcohol, 80 g white wax, 860 g white petrolatum, combined with 20 g icilin in 110 ml propylene glycol.
There are standard procedures for the actual mixing and preparing ointments with petrolatum or oleaginous bases. The finely powdered icilin is levigated thoroughly with a small quantity of the base to form a concentrate. The concentrate then is diluted geometrically with the remainder of the base to form a uniformly dispersed ointment in a petrolatum or oleaginous base.
The solvent used for wetting, suspending or dissolving icilin may be a nonaqueous pharmacologically approved solvent with non-irritating properties. Suitable organic materials useful as the solvent or a part of a carrier system are as follows: propylene glycol, polyethylene glycol (M.W. 200-600), polypropylene glycol (M.W. 425-2025), glycerine, sorbitol esters, butanediol and mixtures thereof. Other examples include ethoxydiglycol, and 1-methyl-2-pyrrolidone, purified water, saline solution, polyethylene glycol, glycerine, glycerine polymethacrylate, white ointment, petroleum jelly (petrolatum), lanolin, beeswax, cholesterol alone or in combination. The preferred vehicle for levigation use in this invention is a propanediol, containing in the finished product 1 to 8% of Formula 1 compounds by weight. In certain situations, aqueous suspensions, gels, pastes, foams, aerosols, and sprays may also be considered for topical administration.
For longer term application of icilin to the anorectal area or for the inner lining of the mouth, a suppository or a paste may be used. Thus, for example, icilin may be incorporated into a mucoadhesive polymer such as polyvinylpyrrolidone, polycarbophil or sodium alginate, for use as a suppository. The suppository may be applied as a liquid at room temperature, which then gels in the anorectal surface at body temperature and adheres to the mucous membrane. Other examples of formulations for delivery of drugs to the anorectal area are described in U.S. Pat. No. 6,391,869, incorporated herein by reference.
For mucoadhesive pastes to be applied to the lining of the mouth or to the gums, one may use Orabase(copyright). Chemically Orabase(copyright) consists of plasticized hydrocarbongel, guar gum, carboxymethylcellulose, tragacanth gum and pectin. Orabase(copyright) is an adhesive-vehicle preparation and was designed for the purpose of retaining topically applied drugs on the oral mucous membranes. Studies with this preparation indicate that it adheres to the oral mucosa for 2 hours or longer, the duration being dependent on the degree of mobility of the oral tissues, the washing action of saliva and the amount of vehicle applied. Other oral mucoadhesive compounds are described in U.S. Pat. No. 6,319,513.
For certain inflamed body parts, such as the lining of the mouth and the surfaces of wounds on the skin, the preferred delivery mechanism may be the use of an aerosol. An aerosol has been defined as a colloidal system consisting of very finely divided liquid or solid particles dispersed in or surrounded by a gas. Thus, a gas, typically air, is used to deliver icilin compounds in solution or as solid particles to biological targets in skin or mucous membranes.
An aerosol dosage form has the advantages of: a) ease of use, for example, the absence of need of cotton swab or other applicators, b) simple dose titration to individual needs, for example, when used for pain from mucositis in the mouth, c) no danger of contamination of the medication, as the unused portion is sealed in the package, d) rapid onset of action, for example, if the drug is formulated in solution, and e) reasonable control of dosage by selecting the proper nozzle valve and container. The aerosol may be used to deliver icilin compounds and compositions as a spray, foam or semi-solid. Methods for aerosol delivery and formulations are described by Sciarra et al., Chpt. 50, xe2x80x9cAerosolsxe2x80x9d in xe2x80x9cRemington, the science and practice of pharmacy,xe2x80x9d Alfonso R. Gennaro, Chairman of the editorial board and editor. 20th ed. Baltimore, Md. Lippincott Williams and Wilkins, 2000, incorporated here by reference.
For the icilin compounds, specialized propellant gases are typically not required for delivery of drug to skin and mucous membrane surfaces, and a simple manual air pump is likely to suffice. Such dispensers, used for buccal and nasal spray delivery, are well known to the art and available commercially. For example, Nature Well uses a 10-ml spray bottle to deliver Migra Spray(copyright) to the buccal mucosa, using digital pressure for generating the airflow.
For icilin compounds and compositions applied to mucous membranes such as the oral cavity or the anogenital region, a preferred formulation is an emulsion with oil/water foam characteristics, similar to quick-breaking shaving foam. This avoids a xe2x80x9cwetxe2x80x9d dripping solution applied to the skin surface. Such a formulation may be achieved by dissolving icilin compounds in propylene glycol, then adding additional substituted glycols and glycol derivatives, then adding glycerin and purified water and appropriate preservatives. A thickener may be added if the spray is used to deliver drug to skin ulcers or wounds, such as, for example, occurs after traumatic injury, burns, or ulcers from pressure or endocrine disorders (e.g. diabetic skin ulcers). For delivery into the oral cavity, however, a water/oil formulation, that is, a formulation with a higher percentage of water, would preferably deliver aerosol foam more rapidly to the target.
The concentrations of icilin compound in aerosol preferably range from 1% to 20% depending on the severity of the pain or itch condition that is being experienced. For example, for sunburns of the lips and face, a concentration of about 2 to 4% icilin emulsion/foam may be sufficient for rapid pain relief. On the other hand, when used for relieving the pain of wound debridement in a bun patient or for treating a soldier who has been wounded in a blast injury and recovering from surgery, a 10% icilin emulsion/foam would provide more long-lasting relief.
Compositions of the present invention with icilin and/or icilin analogs for the lips and anus may preferably further comprise a single pharmaceutical or a combination of pharmaceuticals (wherein the pharmaceutical has some desired biological activity). The use of an icilin product in combination with one or more pharmaceutical agents is particularly useful to facilitate therapy of the lips or anorectal disorder.
Thus, an antifungal agent may be used for yeast infections of the lips or anus. An anti-viral agent, such as acyclovir or docosanol, maybe combined with icilin for treatment of cold sores on the lips. A smooth muscle relaxant such as minoxidil may be combined with icilin for the treatment of anal fissures. A gel containing a growth factor (Regranex(copyright)) may be formulated with icilin to treat skin ulcers or anal fistulae.
Additional pharmaceuticals that may be used in combination with icilin include anti-inflammatory analgesic agents, anti-inflammatory steroidal agents, antihistamines, sympathomimetic amine vasoconstrictors, smooth muscle relaxants, menthol and menthol analogs, local anesthetics, antibiotics and keratolytics.
Examples of anti-inflammatory analgesic agents include methyl salicylate, monoglycol salicylate, aspirin, indomethacin, diclofenac, ibuprofen, ketoprofen, naproxen, pranoprofen, fenoprofen, sulindac, fenclofenac, clidanac, flurbiprofen, fentiazac, bufexamac, piroxicarn, pentazocine, etc.
Examples of steroidal anti-inflammatory agents include hydrocortisone, prednisolone, dexamethasone, triamcinolone acetonide, fluocinolone acetonide, hydrocortisone acetate, prednisolone acetate, methylprednisolone, dexamethasone acetate, betamethasone, betamethasone valerate, flumetasone, fluticasone, budesonide, fluorometholone, beclomethasone diproprionate, etc.
Examples of antihistamines include diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine, chlorpheniramine maleate, promethazine hydrochloride, etc.
Examples of sympathomimetic amine vasoconstrictors include phenylephrine hydrochloride and oxymetazoline.
Examples of local anesthetics include dibucaine hydrochloride, dibucaine, lidocaine hydrochloride, lidocaine, benzocaine, pramoxine hydrochloride, tetracaine, tetracaine hydrochloride, oxyprocaine hydrochloride, mepivacaine, and piperocaine hydrochloride.
Examples of smooth muscle relaxants include nitric oxide donors, such as minoxidil, isorbide dinitate, and phosphodiesterase inhibitors, such as aminophylline. Other examples of smooth muscle relaxants that may be given in combination with icilin to achieve relaxation of the internal anal sphincter in anal fissures are described in U.S. Pat. No. 6,391,869.
Examples of antibiotics include neomycin and the anti-viral agent docosanol (Abreva(copyright)), and examples of keratolytics include such agents as, alpha-hydroxy acids, glycolic acid and salicylic acid.
Examples of menthol analogs include WS-3 and WS-23, both menthol analogs having Generally Recognized As Safe status by regulatory authorities; WS-158 and other phosphine oxide menthol analogs; menthone glycerol ketal, menthyl lactate, menthoxypropane-1,2-diol and cyclic alpha-keto enamines such as 4-methyl-3-(1-pyrrolidinyl)-2-[5H]-furanone.
Other drugs that may be used in combination are Protopic(copyright) tacrolimus) and Elidel(copyright) (pimecrolimus), both of which are topical immunosuppressive drugs used in the treatment of dermatitis.
Without limiting the present invention, a number of examples are now described. In the below experimental section, Example A describes a preparation and formulation of icilin and analogs, while Examples 1-6 describe therapeutic uses of the invention with human subjects.

1,2,3,6-tetrahydropyrimidine-2-one compositions and therapeutic methods therewith for pain and inflammation


A blood storage system. The system has a collection bag for red blood cells; an oxygen/carbon dioxide depletion device; a storage bag for red blood cells; and tubing connecting the collection bag to the depletion device and the depletion device to the storage bag. The depletion device includes a receptacle of a solid material having an inlet and an outlet adapted to receiving and expelling a flushing gas; a plurality of hollow fibers or gas-permeable films extending within the receptacle from an entrance to an exit thereof. The hollow fibers or gas-permeable films are adapted to receiving and conveying red blood cells.

1. Field
The present disclosure relates to a storage blood system having an oxygen/carbon dioxide depletion device and a blood storage bag for the long-term storage of blood. More particularly, the present disclosure relates to a blood storage system that is capable of removing oxygen and carbon dioxide from the red blood prior to storage and during storage, as well as maintaining oxygen and/or carbon dioxide depleted states during storage, thereby prolonging the storage life and minimizing deterioration of the deoxygenated red blood.
2. Background of the Art
Adequate blood supply and the storage thereof is a problem facing every major hospital and health organization around the world. Often, the amount of blood supply in storage is considerably smaller than the need therefor. This is especially true during crisis periods such as natural catastrophes, war and the like, when the blood supply is often perilously close to running out. It is at critical times such as these that the cry for more donations of fresh blood is often heard. However, unfortunately, even when there is no crisis period, the blood supply and that kept in storage must be constantly monitored and replenished, because stored blood does not maintain its viability for long.
Stored blood undergoes steady deterioration which is, in part, caused by hemoglobin oxidation and degradation and adenosine triphosphate (ATP) and 2-3,biphosphoglycerate (DPG) depletion. Oxygen causes hemoglobin (Hb) carried by the red blood cells (RBCs) to convert to met-Hb, the breakdown of which produces toxic products such as hemichrome, hemin and free Fe3+. Together with the oxygen, these products catalyze the formation of hydroxyl radicals (OH.cndot.), and both the OH.cndot. and the met-Hb breakdown products damage the red blood cell lipid membrane, the membrane skeleton, and the cell contents. As such, stored blood is considered unusable after 6 weeks, as determined by the relative inability of the red blood cells to survive in the circulation of the transfusion recipient. The depletion of DPG prevents adequate transport of oxygen to tissue thereby lowering the efficacy of transfusion immediately after administration (levels of DPG recover once in recipient after 8-48 hrs). In addition, these deleterious effects also result in reduced overall efficacy and increased side effects of transfusion therapy with stored blood before expiration date, but possibly older than two weeks are used. Reduction in carbon dioxide content in stored blood has the beneficial effect of elevating DPG levels in red blood cells.
There is, therefore, a need to be able to deplete oxygen and carbon dioxide levels in red blood cells prior to storage on a long-term basis without the stored blood undergoing the harmful effects caused by the oxygen and hemoglobin interaction. Furthermore, there is a need to store oxygen and carbon dioxide depleted red blood cells in bags containing or bag surrounded by a barrier film with oxygen and carbon dioxide depletion materials. Furthermore, there is a need to optimize ATP and DPG levels in stored red blood cells by varying the depletion or scavenging constituents prior to and/or during storage depending upon the needs of the recipient upon transfusion. Furthermore, the blood storage devices and methods must be simple, inexpensive and capable of long-term storage of the blood supply.

This patent is subject to a terminal disclaimer.

Blood storage bag system and depletion devices with oxygen and carbon dioxide depletion capabilities


A system for humidifying respiratory gases has a humidification apparatus, a humidification chamber, a heating apparatus and a sensor. The sensor is configured to determine a characteristic of the gases flow and communicate this to a controller which controls the power supplied to the heating apparatus with respect to information regarding the characteristic of the gases flow. A structure partially encloses the humidification chamber and allows energy loss through a wall of the humidification chamber. The humidification chamber may have features to promote heat loss through the wall of the chamber.

A humidification apparatus is used to provide heated and humidified respiratory gases to a patient via a patient interface. Respiratory gases delivered to a patient at 100% relative humidity and 37° C. mimic the transformation of air that occurs as the respiratory gases pass through the upper airway to the lungs. This may promote efficient gas exchange and ventilation in the lungs, aid defense mechanisms in the airway and increase patient comfort during treatment.
Respiratory gases entering a humidification apparatus are heated and humidified by passing over the surface of the liquid within the humidification chamber. Thus, they are substantially saturated with vapour when they flow out of the humidification chamber through the outlet port. A controller determines the amount of power to supply to the heater so that the respiratory gases comprise a predetermined characteristic such as temperature, humidity or flow at the outlet port. The characteristic can be measured by one or more sensors at the outlet port. Therefore, the humidification apparatus heats and humidifies the respiratory gases so that they are substantially saturated and comprise a predetermined characteristic as they exit the humidification apparatus.


A cover for preventing the unwanted discharge of concrete mixer chute residues from the chute, has a water impermeable cap with side panels which are gathered at the one end with an elastic band for retaining he cap in place, and which has a strong elastic retention means for holding the entire cap in place on the chute against the force of dislodging concrete particles.

1. Field of the Invention
The present invention relates to protective devices and, in particular to devices for preventing the spillage of concrete residues from the chutes of vehicle mounted concrete mixers.
2. Prior Art
Vehicle mounted cement mixers are an important part of virtually all construction projects. The mixers are loaded at a fixed base then, while in transit to the job site, mix the loaded ingredients. Upon arrival at the site, the mix is ready for application.
The most common method of discharging the mix is by way of a vehicle mounted discharge chute which is hinged and which is moveable to the exact location for placement of the mix. The mix is then flowed, pushed, scooped, or raked into a form where it then hardens, with or without further processing.
In the past, operation of concrete mixers employed to deliver concrete mix to construction sites have used various techniques to minimize the spillage of concrete residues during return to the mixer's fixed base.
Sometimes, the residue is washed out of the chute onto the ground in the vicinity of the site. This technique suffers from the obvious drawback that concrete residues are left behind, remaining at the washout site contaminating the environment and, at best, leaving behind a hardened, "poisoned" patch which cannot support vegetation.
The practice of washing out the chute has been proscribed by local ordinances in many communities and is considered, even when not specifically outlawed, to be an unwelcome and unsatisfactory practice.
Another technique sometimes employed is the rinsing of the chute back into the mixer tank. Although preferable to washing out onto surface soil, the technique suffers from the fact that the wash water dilutes the contents of the tank, eventually making the remainder of the load unsuitable for further use.
Of all the prior techniques, the one which is the most objectionable is to attempt to forego any washout by merely leaving the residue resting precariously in the discharge chute while the mixer is returning to its final base. The residue left in the chute is susceptible to being dislodged and then falling onto the pavement.
It is of course illegal to drop such items onto the pavement at any time. Moreover, concrete residues which have fully hardened are hazardous projectiles which all too often create damage to property in the form of broken windshields, dented or marred sheet metal, and, even worse, injury and death to persons who are struck by the flying debris.
Concrete particles as large as 4 kg. are known to form regularly in discharge chutes which have not been washed down prior to returning to streets and highways.
In addition to the risks of actual contact, drivers who are behind a truck from which residue falls will frequently make violent and unpredictable evasive maneuvers which, although successful in avoiding the concrete residue itself, result in a more violent impact with another vehicle or a stationary object. Sometimes, multiple car accidents involving numerous injuries and even death are the result.
In some regions, mixer drivers are subject to misdemeanor negligence charges for dropping mixer chute residues on public roads.
Accordingly, a need exists for an apparatus which can reliably contain concrete mixer chute residues and prevent them, when dislodged, from finding their way onto the streets and highways.


The application relates to a data reading circuit of an embedded flash memory cell. The data reading circuit a switch circuit, a current clamp circuit, a current mirror circuit, a reference current source, a precharge circuit and a comparison circuit; the switch circuit includes a transmission gate, one end of the transmission gate is connected with a drain of the embedded flash memory cell, and the other end of the transmission gate is connected with a detection end of the current clamp circuit; a response end of the current clamp circuit is connected with a data node; the current mirror circuit is connected with the reference current source and the data node; an output end of the precharge circuit is connected with the data node; one input end of the comparison circuit is connected with the data node, and the other input end is connected with reference voltage.

Embedded flash memory cell (eflash), due to its low cost, low power consumption, fast access speed and other performance advantages, has occupied an increasingly important position in the field of nonvolatile memories. With the development of science and technology, the application of data storage media has changed from some traditional nonvolatile memories to flash memories. Large-capacity solid-state memory devices, with flash memories as main storage media, have become one of the mainstream solutions to data storage up to now.
Generally, a flash memory cell includes a floating gate structure. By applying different operating voltage to a control gate, an intermediate electrode and a source in the flash memory cell, the reading operation, writing operation and erasing operation of the flash memory cell are realized. Content stored in the flash memory cell depends on a state of the floating gate structure that stores electrons. If the floating gate structure has no electrons, the data in the flash memory cell is 1; if the floating gate has electrons, the data in the flash memory cell is 0.
When the data in the flash memory cell is read, first reading voltage is applied to the middle electrode of the flash memory cell through a word line (WL), and second reading voltage is applied to a drain through a bit line BL. When the flash memory stores data as 1 (i.e., the floating gate is in the state without electrons), large current will be generated between the source and the drain of the flash memory cell due to the movement of a large amount of electrons. When the flash memory stores data as 0 (i.e., the floating gate is in the state that electrons are stored), the electrons in the floating gate structure absorb the voltage applied to the intermediate electrode, so that the electrons conducted in drain-source channel are reduced, resulting in small current. By determining the magnitude of the current flowing through the flash memory cell, the data stored in the flash memory cell can be determined.
In the related arts, a reading circuit for reading the data in the flash memory cell includes a switch module, a reference current source module, and a voltage comparison module. One end of the switch module is connected with the flash memory cell, the other end is connected with the reference current source module to form a data node, and one input end of the voltage comparison module is connected with the data node. During the operation of reading the data, the switch module is in an on state, a reference current source provided by the reference current source module is compared with the current in the flash memory cell, the data node is charged or discharged according to a comparison result to increase or decrease the voltage of the data node, and the voltage comparison module determines the voltage of the data node and outputs a determination result.
However, for an eflash in a 55 nm process, its core device voltage is 1.2V+/−10%, and threshold voltage is 0.6V for high-threshold N channels under the worst situation. When the traditional reading circuit works for a reading operation, it is necessary to apply switch control voltage (VDD) to the switch module to make the switch module on, so as to transmit 0.6V voltage to the bit line BL. When the switch control voltage is less than 1.2V, and for example, the switch control voltage is 1.05V, the switch module cannot be on, that is, the switch module cannot transmit 0.6V voltage to the bit line BL, such that the reading circuit fails.

Data reading circuit of embedded flash memory cell

Shanghai Huahong Grace Semiconductor Manufacturing Corporation


This is a method of forming a bipolar transistor comprising: forming a subcollector layer, having a doping type and a doping level, on a substrate; forming a first layer, of the same doping type and a lower doping level than the subcollector layer, over the subcollector layer; increasing the doping level of first and second regions of the first layer; forming a second layer, of the same doping type and a lower doping level than the subcollector layer, over the first layer; increasing the doping level of a first region of the second layer which is over the first region of the first layer, whereby the subcollector layer, the first region of the first layer and the first region of the second layer are the collector of the transistor; forming a base layer over the second layer of an opposite doping type than the subcollector layer; and forming an emitter layer of the same doping type as the subcollector layer over the base layer. Other devices and methods are also disclosed.

Without limiting the scope of the invention, its background is described in connection with, bipolar transistors as an example.
Heretofore, in this field, GaAs/AlGaAs heterojunction bipolar transistors (HBT) have been fabricated using mesa technology in which the collector, base and emitter epi layers are subsequently grown during a single epitaxial deposition run. The emitter and base epi layer are selectively removed using two etch steps for making contact to the base and collector areas, respectively. These etches result in steps in the GaAs ranging in height between 0.4 and 2.0 microns for a typical mesa HBTs. Although high quality HBTs can be fabricated in this manner, the resulting mesa structure results in very severe topography making it difficult to incorporate a multilevel metal system as required for high levels of integration.
Planar heterojunction bipolar transistors have been fabricated as elements of integrated circuits in the emitter down configuration (See U.S. Pat. No. 4,573,064). This avoids the mesa topography but this technology requires all of the NPN transistors to be connected in the common emitter configuration which severely limits its applications for analog/linear ICs.
Although a single epitaxial deposition run as used in the foregoing mesa HBTs and emitter-down HBTs does simplify the fabrication process, it limits the types of structures which can be integrated together on a single chip.
An alternative has been to grow an emitter epilayer onto an implanted base with Zn as the base dopant because of the high mass and low implant range. However, implanted Zn is difficult to activate at low temperatures. Raising the temperature high enough for good activation results in excessive diffusion due m the large diffusion coefficient for Zn, significantly increasing the base width and lateral dimensions and degrading the frequency response. Additionally, this process integrates only a single type of device, the NPN HBT.
Improved performance as well as increased circuit flexibility has been made possible by integrating both NPN and PNP bipolar transistors on the same chip. Silicon digital circuits make use of vertical NPN switching transistors and PNP transistors for input logic, current sources and level shifting. Silicon linear circuits are routinely using integrated NPN and PNP transistors for improved circuit performance.

Enhanced performance bipolar transistor process


A stirling engine with mechanical output through a main shaft (71) has piston(s) (44) reciprocable in cylinder bore(s) (41). Each piston is guided on a fixed piston guide (52) which extends into but not through the piston. This guidance holds the piston clear of mechanical contact with the cylinder bore (41). A separate seal is provided between the piston and the bore. Internal guidance of the piston permits a guidance arrangement where clearances change very little or not at all with changes in temperature of the engine.

The invention is applicable particularly but not exclusively to Stirling engines of the multi-cylinder double-acting type. Typical engines of this type have a hot working chamber at one end, normally the upper end and a cold working chamber at the other end of each cylinder separated by the piston, each of these hot and cold working chambers being connected respectively to a cold or hot working chamber of another cylinder. In this way, four closed working volumes are established in each of which the required working fluid is permanently entrapped. Conventional lubricants can not normally be used within the working volume because the lubricant carbonises and carbonised deposits interfere with heat transfer capability.
Differential thermal expansion between a piston and its cylinder in a Stirling engine can be a particularly severe problem. Pistons are normally supported to slide in a bore by axially spaced annular bearing pads which operate in an oil free environment and normally have a high expansion coefficient. The cylinder in the region of the upper bearing pad is normally liquid cooled and so does not experience wide temperature differences or large degrees of expansion. It may also be convenient to make it from a ferrous metal which has a relatively low expansion coefficient. In contrast, the piston may need to operate over a much wider range of temperatures and may be of light alloy with high expansion coefficient. The relatively high expansion of the piston itself and of a bearing pad carried on the piston can be such as to require excessive clearance between the piston and cylinder at low temperatures. The extent of this clearance can be such as to allow substantial angular movement of the piston. A Stirling engine piston often carries a high crown known as a displacer which runs close to but does not contact the cylinder. Lateral movement of the displacer on tilting of the piston, is magnified by its distance from the bearing pads and there can be a risk of inadvertent contact by the displacer with the cylinder wall at low temperatures. Misalignment caused by large clearances can also lead to high wear rates due to edge loading.
If the engine over-heats and clearances diminish to the extent that friction increases, the piston temperature tends to rise more than the cylinder temperature, tending to result in seizure. To guard against this problem during over-heating, a still larger clearance is required at low temperature. Achieving a satisfactory seal in conjunction with low wear and low friction between the piston and cylinder over a complete range of working temperatures and clearances can also be difficult to achieve and has been a major factor in limiting the commercial success of Stirling engines. The problem is even greater with engines requiring a mechanical drive connection to the piston than with free piston engines because a mechanical drive normally involves a side load on the piston.
The arrangement of guiding a piston in a cylinder by annular pads on the piston engaged with the cylinder wall can thus be disadvantageous in a Stirling engine with a mechanical coupling. An object of the present invention is to provide a piston guide arrangement in which these problems are reduced.


A method and apparatus for improving the water balance in a power unit by providing the exhaust gas from the cathode side of the fuel cell as a feed gas to the combustion system condensing at least a portion of water present in the effluent from the combustion system in a condenser, and then transferring water vapor from the uncondensed portion of the effluent from the condenser to the gas fed to the cathode side of the fuel cell. Water from the exhaust gas from the cathode side of the fuel cell is either captured in the condenser, or is reused in the feed gas of the cathode side of the fuel cell. By humidifying the air fed into system with the water vapor present in the exhaust gas, water is not lost from the system. Instead, the air is being fed into the system is humidified with this water, which in turn allows the humidifier to operated at higher temperatures and/or use smaller radiators and fans and/or draw less parasitic power, thereby increasing overall system efficiency.

The need for mobile electrical power generation systems has traditionally been satisfied with generators powered by internal combustion engines fueled with material such as gasoline or diesel fuel. While these systems have proven reliable and efficient in numerous applications, they are not suitable in certain other applications. For example, in many military applications the requirement that a single fuel source power both a vehicle and an auxiliary power system prevents the use of off-the-shelf internal combustion gasoline generator systems. Additionally, issues related to the noise and vibration generated by internal combustion systems can render their use unacceptable in particular situations.
One alternative to typical internal combustion systems are fuel cell-based electrical power generation systems. Of particular interest are polymer electrolyte membrane (PEM) fuel cells used in conjunction with steam reforming systems. Combining a PEM fuel cell with a steam reforming system, these systems provide a mobile source of electricity that is quiet, efficient, and capable of being powered by a variety of hydrocarbon fuel streams.
Generally speaking, fuel cells generate water and electricity as outputs. In addition, combustion processes such as those used to heat a steam reformer generate water vapor. However, steam reforming systems use water as an input. Therefore, power generation systems that combine fuel cells with steam reforming systems must have water available as an input, or make efficient use of water formed in the fuel cell and reformer combustor. Operation of these power generation systems in environments with high temperatures requires efficient use and recovery of water. Maintaining a positive water balance, where water condensed and recovered exceeds that being fed to the process, becomes more and more difficult for high ambient temperatures (i.e. >40° C.) due to the close approach temperatures that must be achieved in the radiator and condenser. The result is that a system designed to reach water balance at high ambient temperature will have very large radiators and have a significant parasitic penalty for radiator fan power. At some point, maintaining positive water balance is simply not possible regardless of radiator size.
Accordingly, there exists a need for methods and apparatus that allow a power unit for generating electrical power that has a steam reforming system and a fuel cell to conserve water available to the power unit. There is a further need to increase the efficiency of a power unit for generating electrical power that has a steam reforming system and a fuel cell.

Method and apparatus for improving water balance in fuel cell power unit


Methods, apparatus, and systems, including computer programs encoded on a computer storage medium, manage metadata for virtual volumes. In some implementations, a method includes: loading into memory at least a portion of metadata for a virtual volume (VV) that spans data extents of different persistent storage devices, wherein the metadata comprises virtual metadata block (VMB) descriptors and virtual metadata blocks (VMBs); mapping an address of the VV to a VMB number and an index of an extent pointer within a VMB identified by the VMB number, wherein the extent pointer indicates an extent within one of the different persistent storage devices; locating a VMB descriptor in the memory based on the VMB number; and locating the identified VMB in the memory or not in the memory based on the located VMB descriptor.

The present disclosure describes systems and techniques relating to metadata management for virtual volumes.
A storage server system, such as a SAN (Storage Area Network) or NAS (Network-Attached Storage), has the primary purpose of providing shared storage that can be accessed by computers attached to the server through a network. A typical storage server is designed to serve as storage to many (10s or 100s or even 1000s) computers.
Modern storage servers provide virtualized storage to its users in the form of "virtual volumes". A virtual volume hides the way the physical storage is organized and presents a uniform, virtually contiguous storage to the outside world. In other words, what a computer attached to the storage server sees as a physically contiguous space is really composed of many physically disparate chunks of storage. The virtual volume concept provides flexibility to the storage server in order to serve as storage to many computers.
In order to provide the virtualized view to the outside world, the storage server maintains metadata that translates the virtualized storage to its physical counterpart. For example, for each virtual volume, the storage server can employ a tree structure, such as a B-Tree, to keep track of the metadata that translates from an address in the virtual volume to an address in that virtual volume's physical counterpart.


A guidewire having a first end and a second end, and comprising two or more guidewire modules. Each guidewire module has a first end and a second end. Each guidewire module is configured to be attachable to a second guidewire module by at least one of: attaching the first end of the guidewire module with the second end of the second guidewire module, and attaching the second end of the guidewire module with the first end of the second guidewire module.

The present invention relates generally to the field of surgical tools and implements, and more particularly to guidewires for use in surgical and related healthcare settings.
Guidewires are used in many surgical procedures carried out in a healthcare setting. For example, in orthopedic trauma surgery, guidewires are often used to connect two fragments of a bone fracture. The guidewire allows for guided tool and implant insertion into the bone through the sliding of cannulated tools and implants over the guidewire connecting the two bone fragments.
Guidewires are typically made of stainless steel and designed to be disposable, though some are designed of different materials and/or designed to be reusable. They may come equipped with one of a variety of tips, depending on the guidewire's purpose. Guidewires also come in various lengths and diameters, depending on where in a patient's skeletal anatomy the guidewire is to be used. Additionally, guidewires may be contoured in the operating room by surgical staff to suit a need of the a patient (e.g., to help a surgeon find a canal of a fragment of a fractured implant).
However, some procedures require longer guidewires which can range up to 100 cm (approximately 40 inches), making them awkward to transport. Moreover, maneuvering longer guidewires in small or cramped conditions can be difficult and threaten the sterility of the guidewire. As such, a guidewire with, e.g., customizable length and/or tip options would be desirable in many healthcare settings.


A magnetron has an anode cylinder, a plurality of vanes arranged radially within the anode cylinder, a magnetic piece disposed at an open end section of the anode cylinder, an anode vacuum container including a metal container disposed to cover an upper surface of the magnetic piece, a cathode disposed along a central axis of the vacuum container, and an antenna externally discharging microwaves. The magnetic piece and the metal container are placed, in that order, on a shelf formed inwardly on a thin end section projecting from the open end section of the anode cylinder. When tightly welding the thin end section, a predetermined number of projections, projecting inwardly from the thin end section of the anode cylinder, loosely secure an outer perimeter bend of the metal container. The metal container is then accurately tightly welded to the anode cylinder without the metal container shifting off-center.

The present invention relates to a method for making magnetrons. More specifically, the present invention relates to a method for making magnetrons used in radars, microwave heating devices, e.g., microwave ovens, or the like.
Referring to FIG. 4, a conventional magnetron includes a plurality of vanes 52 formed within a cylindrical anode cylinder 51. An anode vacuum container 55 includes a magnetic piece 53 and a metal container 54 disposed at the open end section of the anode cylinder 51. A cathode 57, disposed along the center axis of vacuum container 55, includes a top hat 56a, an end hat 56b, and a filament 56c. An antenna 58 extracts a microwave, e.g., at 2450 MHZ, generated in the hollow space. In this magnetron, the thermoelectrons discharged by filament 56c spin inside the active space formed between vanes 52 and filament 56c, generating a microwave. This microwave, flowing along a vane 52, is transferred to antenna 58 connected to vain 52. The microwave is then discharged externally through antenna 58.
Anode cylinder 51 and metal container 54 are bonded by tightly welding thin end section 59 of anode cylinder 51. Referring to FIG. 5(a), before the welding operation, thin end section 59 of anode cylinder 51 has a roughly even thickness between end 59a and base section 59b. Magnetic piece 53 and metal container 54 are placed on an inner shelf 60 of thin end section 59.
Referring to FIGS. 4 and 5(b), thin end section 59 of anode cylinder 51 is melted by welding to form a tight bond with outer perimeter bend 54a of metal container 54.
If a slight gap forms between the inner wall surface of thin end section 59 of anode cylinder 51 and outer perimeter bend 54a of metal container 54 due to dimensional tolerances, misalignment of the parts, or the like, this gap will remain, even after the tight welding. This can lead to reduced sealing properties. Discarding such assemblies results in increases material costs, while performing repairs of these assemblies increases the number of steps involved in the procedure.
To prevent these gaps, the parts may be formed with shapes that provide alignment relative to each other. If alignment between the parts is not possible, dedicated tools or equipment may be used to secure the parts while welding. However, with each of these methods there is an increase in production costs.
It is an object of the present invention to provide a method for making a magnetron which overcomes the foregoing problems.
More specifically, it is an object of the present invention to provide a method for making magnetrons that easily improves the quality of the tight welding operation.
Briefly stated, the present invention provides a magnetron having an anode cylinder, a plurality of vanes arranged radially within the anode cylinder, a magnetic piece disposed at an open end section of the anode cylinder, an anode vacuum container including a metal container disposed to cover an upper surface of the magnetic piece, a cathode disposed along a central axis of the vacuum container, and an antenna externally discharging microwaves. The magnetic piece and the metal container are placed, in that order, on a shelf formed inwardly on a thin end section projecting from the open end section of the anode cylinder. When tightly welding the thin end section, a predetermined number of projections, projecting inwardly from the thin end section of the anode cylinder, loosely secure an outer perimeter bend of the metal container. The metal container is then accurately tightly weld to the anode cylinder without the metal container shifting off-center.
According to an embodiment of the present invention, a method for making magnetrons includes a magnetron having an anode cylinder, a plurality of vanes arranged radially within the anode cylinder, a magnetic piece disposed at an open end section of the anode cylinder, an anode vacuum container including a metal container disposed to cover an upper surface of the magnetic piece, a cathode disposed along a central axis of the vacuum container, and an antenna externally discharging microwaves. The magnetic piece and the metal container are placed, in that order, on a shelf formed inwardly on the thin end section projecting from the open end section of the anode cylinder. When tightly welding the thin end section, a predetermined number of projections projecting inwardly from the thin end section of the anode cylinder is used to loosely secure an outer perimeter bend of the metal container.
According to another embodiment of the present invention, a method for making magnetrons includes providing a magnetron having an anode cylinder, a plurality of vanes arranged radially within the anode cylinder, a magnetic piece disposed at an open end section of the anode cylinder, an anode vacuum container including a metal container disposed to cover an upper surface of the magnetic piece, a cathode disposed along a central axis of the vacuum container, and an antenna externally discharging microwaves. The magnetic piece and the metal container are placed, in that order, on a shelf formed inwardly on the thin end section projecting from the open end section of the anode cylinder. When tightly welding the thin end section, a ring-shaped projection, projecting inward from the thin end section of the anode cylinder, is used to loosely secure an outer perimeter bend of the metal container.
The above, and other objects, features and advantages of the present invention will become apparent from the following description read in conjunction with the accompanying drawings, in which like reference numerals designate the same elements.


Disclosed are an impedance matching method, an impedance matching apparatus for the same, and a record medium. The impedance matching apparatus includes an impedance matching part connected to an antenna to transmit/receive a radio wave and including at least one variable capacitor, a detector to detect transmit power and reflected power reflected by the antenna, and a controller to set a first searching region within a whole variation range of the variable capacitor, to detect an optimal impedance matching point within the first searching region by using at least one of the transmit power and the reflected power, and to set a next searching region about the optimal impedance matching point to search for a final impedance matching point within the whole variation range of the variable capacitor.

An antenna circuit of a mobile communication terminal allows an antenna to transmit or receive predetermined radio signals.
In order to optimize the transmit/receive radiation performance of the antenna, impedance matching must be exactly performed.
Therefore, the antenna circuit includes capacitors and inductors, and the impedance of the antenna is matched in the optimal status by adjusting values of the capacitors and the inductors.
In general, the impedance matching of the antenna is achieved in a state that the mobile communication terminal is positioned in a free space.
Meanwhile, the mobile communication terminal may be used by a user in a state that the user handholds the body of the mobile communication terminal and adheres a speaker to the ear of the user due to the mechanical characteristic of the mobile communication terminal, or may be used by the user through an ear-phone in a state that the body of the mobile communication terminal is put into a pocket or a bag of the user.
As the user uses the mobile communication terminal by gripping the mobile communication terminal with the hand of the user and closely touching the speaker to the ear of the user, or as the user uses the mobile communication terminal put into the pocket or the bag, the conditions for the impedance matching of the antenna may vary, so that the transmit/receive radiation performance of the antenna subject to impedance matching in the free space may be degraded.
Therefore, the mobile communication terminal employs an adaptive tuning antenna circuit to automatically adjust the impedance of the antenna when the conditions for the impedance matching of the antenna vary, so that the antenna has the optimal transmit/receive radiation performance.
The adaptive tuning antenna circuit must detect the impedance variation of the antenna to maintain the transmit/receive radiation performance of the antenna in the optimal state.
To this end, the adaptive tuning antenna circuit includes a coupler to detect reflected power and forward power output from the coupler, and to change the capacitance of a variable capacitor according to the reflected power and the forward power, so that impedance matching can be performed.
According to the related art, as shown in FIG. 1, after sequentially scanning the whole variable region of the variable capacitor, a point representing the best RF performance is selected and adapted, thereby performing impedance matching.
However, if the whole region of the variable capacitor is scanned as described above, a point representing the inferior RF performance is inevitably scanned, so that the transmit/receive radiation performance may be degraded.

Impedance matching method, impedance matching apparatus for the same, and record medium


A Ga—Sb—Ge family of phase change memory materials is described, including GaxSbyGez, wherein a Ga atomic concentration x is within a range from 20% to 45%, a Sb atomic concentration y is within a range from 25% to 40% and a Ge atomic concentration z is within a range from 25% to 55%, is described wherein the material has a crystallization transition temperature Tx greater than 360° C. Adding impurities including one or more element selected from silicon Si, carbon C, oxygen O and nitrogen N, can also increase the crystallization transition temperature Tx to temperatures greater than 400° C., and also reduce reset current.

Field of the Invention
The present technology relates to high density memory devices based on phase change based memory materials.
Description of Related Art
Phase change based memory materials, like chalcogenide based materials and similar materials, can be caused to change phase between an amorphous state and a crystalline state by application of electrical current at levels suitable for implementation in integrated circuits. The generally amorphous state is characterized by higher electrical resistivity than the generally crystalline state, which can be readily sensed to indicate data. These properties have generated interest in using programmable resistive material to form nonvolatile memory circuits, which can be read and written with random access.
In phase change memory, data is stored by causing transitions in an active region of the phase change material between amorphous and crystalline states. For a one bit cell, the difference between the highest resistance R1 of the low resistance crystalline set state and the lowest resistance R2 of the high resistance amorphous reset state defines a read margin used to distinguish cells in the crystalline set state from those in the amorphous reset state. The data stored in a memory cell can be determined by determining whether the memory cell has a resistance corresponding to the low resistance state or to the high resistance state, for example by measuring whether the resistance of the memory cell is above or below a threshold resistance value within the read margin.
Phase change materials used for memory operations can be characterized by a number of different performance specifications including set and reset speeds, data retention, endurance, reset current and the probability that data stored using the material will survive solder bonding. The speed is a function of the pulse lengths required to cause the set and reset operations, as well as other factors. The data retention is a function, typically, of the tendency of the phase change material in the amorphous phase to crystallize over time and temperature so as to lose data. The endurance is a function of the phase change material tendency to become hard to set or hard to reset as the material is exposed to many set/reset cycles. The reset current has a value which is desirably low, but must be sufficient to cause heating in the active area sufficient to cause the phase transition, and can be higher as the resistance level of the set state is lower. The solder bonding specification refers to a difficulty that arises with phase change materials on integrated circuits that are mounted by solder bonding. The solder bonding process exposes the integrated circuit to elevated temperatures, which can exceed the crystallization transition temperature for the phase change materials. Thus, prior art phase change designs could not be programmed before being mounted by solder bonding.
It is desirable therefore to provide a phase change memory material with a higher crystallization transition temperature to prevent undesired transformation from the amorphous reset state to the crystallized set state at elevated operation temperatures. It is further desirable that the phase change memory material maintain a large difference between the range of reset state resistance values and the range of set state resistance values. It is also desirable that the phase change memory material retains fast set and reset speeds. It is also desirable that a phase change memory material have relatively higher resistance in the crystallized set state phase, to reduce the reset current. Furthermore, it is desirable that a phase change memory material have a crystallization transition temperature high enough to withstand solder bonding without loss of data.


A system, method, and program for optimally caching in a memory system an overlay instance. The system includes a local memory and a rasterizing processor coupled to the local memory. Responsive to receipt of a presentation requirement specifying an overlay stored in a memory device, the rasterizing processor determines whether an overlay instance for the overlay is cached in a memory system. Responsive to the overlay instance not being cached in the memory system, the rasterizing processor generates a new overlay instance for the overlay and caches the new overlay instance in the memory system. Responsive to the overlay instance being cached in the memory system, the rasterizing processor produces another overlay instance tailored to the presentation requirements, compares the another overlay instance to the cached overlay instance and then caches into the memory system only one overlay instance among the another overlay instance and the cached overlay instance that best presents the overlay. The rasterizing processor discards the other overlay instance.

1. Technical Field
The present invention relates in general to document presentation, and, in particular, to caching rasterized data used in document presentation.
2. Description of the Related Art
A document is generally a data collection created by an application program, such as a word processing application, that is logically subdivided into pages. A page comprises objects, such as text, images, graphical objects, and display elements, that are to be displayed on one side of a sheet, subject to various formatting specifications, such as size, margins, font, color, depth, etc. When printed, document pages are presented on sheets, which are presentation units generally having at least two sides (e.g., a front side and a back side). Each side of a sheet may contain one or more pages.
A document is generally a piece of work created by a computer application program, such as a word processing document created by a word processing application. The work for a document typically comprises one or more sheets. A sheet is a presentational unit within the document in which each sheet has at least two sides (e.g., a front side and a back side). An exemplary sheet is a sheet of paper having a front side of the paper and a back side of the paper among various sheets of paper in a paper stack. A sheet may contain one or more pages. A page comprises objects, such as text, images, graphical objects, and display elements, that are displayed on one side of a sheet, subject to various formatting specifications, such as size, margins, font, color, depth, etc. A page may also include one or more overlays.
An overlay is a pre-defined page or part of a page that a host processor of a print server loads and sends to a local memory system of a printer. An overlay may include text, images, graphics, bar codes, and/or other objects. Overlays are stored in a memory system until they are deactivated. In contrast, if pages are stored, the pages are saved in the local memory system only until they are printed. Overlays are typically used to present fixed data on a document that does not move with respect to the sheets.
An overlay may be included in a page by specifying in the data for the page a command to include the overlay (e.g., an xe2x80x9cinclude overlayxe2x80x9d command). A rasterizer for the printer receives the data for the page and responds to the xe2x80x9cinclude overlayxe2x80x9d command by retrieving the stored overlay from the local memory system. The rasterizer processes and rasterizes the overlay, creating rasterized data specifying the usage of the overlay. An xe2x80x9coverlay instancexe2x80x9d is the data specifying a particular usage of the overlay.
The overlay instance is typically cached into a memory system for future use. However, a particular cached overlay instance can only be used again if the same overlay is placed at the same location and same side of a sheet. If the overlay is to be presented at a different location or side of a sheet, then the rasterizer must re-rasterize the overlay to create a new overlay instance, and the new overlay instance is then cached into the memory system. Thus, several overlay instances for the same overlay end up being cached into the memory system when the data stream specifies that the overlay be placed at different locations and/or on various sides of sheets. Furthermore, in a conventional parallel rasterizer which has a master processor and several satellite processors coupled to the master processor, each satellite processor has to save and maintain its own overlay instances for the same overlay.
The creation and storage of various overlay instances for the same overlay results in the inefficient use of the rasterizer and memory space. Therefore, the present invention recognizes that the conventional method of caching overlay instances for an overlay in a memory system needs to be improved. In addition, it would be desirable to reduce or eliminate redundant processing of overlay data by the rasterizer.
A system, method, and program for optimally caching in a memory system an overlay instance. The system includes a local memory and a rasterizing processor coupled to the local memory. Responsive to receipt of a presentation requirement specifying an overlay stored in a memory device, the rasterizing processor determines whether an overlay instance for the overlay is cached in a memory system. Responsive to the overlay instance not being cached in the memory system, the rasterizing processor generates a new overlay instance for the overlay and caches the new overlay instance in the memory system. Responsive to the overlay instance being cached in the memory system, the rasterizing processor produces another overlay instance tailored to the presentation requirements, compares the another overlay instance to the cached overlay instance and then caches into the memory system only one overlay instance among the another overlay instance and the cached overlay instance that best presents the overlay. The rasterizing processor discards the other overlay instance.

System, method, and program for optimally caching overlay instances in a memory system

International Business Machines Corporation


Optical scanning device 1 according to the present invention includes: main movable portion 10; a pair of torsionally deformable main torsion beams 21 and 22 arranged opposite to each other at both ends of main movable portion 10 and swingably supporting main movable portion 10; and main driving unit 30 that drives main movable portion 10 to oscillate. Main movable portion 10 includes mirror unit 11 having reflection surface 11a for reflecting light, and a pair of permanent magnets 12 and 13 arranged opposite to each other to sandwich mirror unit 11, each permanent magnet extending along oscillation axis X-X of main movable portion 10. Main driving unit 30 includes yoke unit 31, 32, and 33 arranged along oscillation axis X-X of main movable portion 10 to surround permanent magnets 12 and 13, and coil 34 wound on yoke unit 31, 32, and 33 and configured to be energized to magnetize yoke unit 31, 32, and 33, thereby generating magnetic fields to be applied on permanent magnets 12 and 13.

The optical scanning device that scans light by causing a mirror to oscillate is widely used in a digital copying machine, a laser printer, a barcode reader, a scanner, or a projector. With the recent development of a microfabrication technology, an optical scanning device, which illustrates the aforementioned device, and to which MicroElectro Mechanical Systems (MEMS) technology of is applied, has become a focus of attention.
The optical scanning device based on MEMS technology, in which a mirror mechanism can be integrally formed in a semiconductor process, is accordingly advantageous in that the device can be miniaturized. However, when a mirror size (chip size) increases, a cost problem occurs. Specifically, one wafer is expensive and, in view of yield or the number of chips actually produced therefrom, it is difficult to manufacture MEMS chips of 1 cm or more at low cost. Thus, the optical scanning device is not so suitable for use in high resolution projectors where a sufficiently large mirror size is required.
On the other hand, the optical scanning device based on MEMS technology has the following advantages. In such an optical scanning device, the mirror having both ends supported by beams that are made of an elastic member oscillates about an oscillation axis along the beams by a driving force such as an electrostatic force or an electromagnetic force, and accordingly optical scanning is carried out. Thus, unlike an optical scanning device of a type in which a polygon mirror or a galvano-mirror is rotated by a motor, a mechanical driving mechanism such as a motor is not necessary. As a result, the structure is simpler and assembling performance is higher, thereby contributing to lower costs. As compared with the aforementioned optical scanning device, the oscillation angle of the mirror can be set relatively large. This is important for realizing a projector that is capable of displaying an image on a large screen.
Thus, there is a demand for image display devices, such as projectors, that feature a large screen display and high resolution, that can be realized by applying the aforementioned advantages of the optical scanning device based on the MEMS technology to an optical device that has a large size mirror.
In the optical scanning device based on the MEMS technology, in many cases, to increase the oscillation angle of the mirror, a resonant mirror driven by the resonance frequency of the structure is used. The resonance frequency fr of the mirror is given byfr=(2π)−1(k/Im)1/2  (1)where k is a torsion spring constant of a torsion beam for supporting the mirror, and Im is the moment of inertia of the mirror.
When a driving force applied to the mirror is represented by T, the oscillation angle θ of the mirror is given byθ=QT/k  (2)where Q is a quality factor of the system, and typical values in air and vacuum are respectively about 100 and 1000.
In the resonant mirror, in many cases, high-speed vibration of about several 10 kHz as a resonance frequency fr is required. Accordingly, as the torsion beam, a torsion beam having a large torsion spring constant k, i.e., a hard torsion beam, is used (see Equation (1)). In such a case, the torsion spring constant k cancels out the quality factor Q of the mirror. As a result, oscillation angle θ of the mirror given by Equation (2) depends on driving force T. Thus, a large driving force is necessary to increase oscillation angle θ of the mirror.
On the other hand, in a certain type of optical scanning device of a certain type, a mirror is configured to be non-resonantly driven (i.e., DC-driven). In the case of this non-resonant mirror, oscillation angle θ of the mirror is given byθ=T/k  (3)where T and k are respectively a driving force applied to the mirror and torsion spring constant.
According to Equation (3), oscillation angle θ can be increased to some extent by increasing driving force T or decreasing torsion spring constant k. However, when torsion spring constant k is decreased, resonance frequency fr is decreased according to Equation (1). In such a case, since the resonance frequency approaches a driving frequency (normally, 60 Hz) in a non-resonant mode, a resonant waveform is superimposed on the driving waveform of the mirror. To prevent this, resonance frequency fr must be set to about 1 kHz or higher. As a result, torsion spring constant k cannot be greatly reduced. Thus, in the non-resonant mirror, as in the case of the resonant mirror, to increase oscillation angle θ of the mirror, the driving force must be greatly increased.
As described above, irrespective of the resonant type or the non-resonant type, to achieve a large oscillation angle of the mirror in the optical scanning device, it is important to secure a large driving force. In this regard, the use of a magnetic-force type driving device that generates a driving force with the aid of a permanent magnet and a coil is advantageous. The magnetic-force type driving devices are largely classified into the following two types depending on the arrangement of the permanent magnet and the coil.
(1) Movable Coil (MC) Type
For example, each of Patent Literatures 1 and 2 discloses a MC type driving coil in which a coil is mounted on a movable portion. A plurality of permanent magnets is disposed around the movable portion, and the movable portion is driven by Lorentz force applied on the coil when current is supplied to the coil.
(2) Movable Magnet (MM) Type
In a MM type driving device, a configuration where at least one permanent magnet is mounted on the plate surface of a platelike movable portion is frequently used. A coil is disposed near the movable portion, and the movable portion is driven by the magnetic interaction of the permanent magnet and the coil when current is supplied to the coil.
In such a driving device, various ideas for efficiently generating driving forces have been offered.
For example, Patent Literature 3 discloses a driving device including a coil disposed at a position facing the surface of a movable plate (movable portion) where a permanent magnet is mounted to incline according to the oscillation angle of the movable plate. Thus, even when the movable plate is deflected, a sufficiently large magnetic field is applied to the permanent magnet.
Patent Literature 4 discloses an optical scanner that includes a permanent magnet disposed on the rear surface of a mirror plate (movable portion) so that the magnetization direction can be horizontal, and a fixed yoke that houses a coil. The permanent magnet is held between the ends of the fixed yoke. Accordingly, a magnetic field applied to the permanent magnet through the fixed yoke can be relatively increased.