Methods, kits, apparatus, and compositions for inhibiting a cerebral neurovascular disorder or a muscular headache in a human patient are provided. The methods comprise intranasally administering to the patient a pharmaceutical composition comprising a local anesthetic, and preferably a long-acting local anesthetic ingredient. A composition useful for practicing the methods of the invention is described which comprises at least one local anesthetic in a pharmaceutically acceptable carrier, wherein the composition is formulated for intranasal delivery. Cerebral neurovascular disorders include migraine and cluster headache. Muscular headaches include tension headaches and muscle contraction headaches. A kit comprising the composition and an intranasal applicator and a method of systemically delivering a pharmaceutically active agent to an animal are also included in the invention. Apparatus for delivering or applying the compositions of the invention or for performing the methods of the invention are also described.

This invention relates to compositions, kits, methods, and apparatus for inhibiting muscular headaches and cerebral neurovascular disorders including, but not limited to, neurovascular headaches, migraines, cluster headaches, tinnitus, cerebrovascular spasm, ischemic disorders, and seizures.
Headache is a common symptom of numerous diseases and disorders including, but not limited to, migraine, muscle tension, systemic or intracranial infection, intracranial tumor, head injuries, severe hypertension, cerebral hypoxia, certain diseases of the eyes, nose, throat, teeth, and ears, and head pain for which no cause can be determined.
Infrequent headaches can often be determined to result from causes attributable to a particular experience of a patient, such as fatigue, fever, alcohol ingestion, muscle contraction, tension, or the like. The cause of persistent or recurrent headaches is often difficult to determine. Persistent or recurrent headaches include, but are not limited to, muscular headaches, such as tension or muscle contraction headaches, and neurovascular headaches, such as migraines and cluster headaches.
Cerebral neurovascular disorders (CNvDs) are characterized by one or more disturbances in the normal functioning of at least one component of the cerebral vascular or nervous system in a human. CNvDs include, for example, migraine, cluster headaches, other headaches of neurovascular etiology, tinnitus, and cerebrovascular spasm. Human patients afflicted with a CNvD experience a single episode of the disorder, recurrent episodes, persistent episodes, or some combination of these patterns. An individual episode is designated an acute CNvD.
Many CNvDs, such as cerebral vascular accidents, reversible ischemic neurological defects, and transient ischemic attacks (TIA), are associated with functional cerebral ischemia. These are often nonhemorrhagic and of thrombotic, embolic, and vasospastic etiologies. Furthermore, intracranial vasospasm commonly afflicts patients who have experienced an acute cerebral ischemic event such as a stroke and is often problematic following thrombolytic therapy. Numerous symptoms occur during and after acute cerebral ischemic events. Indeed, neurovascular headaches have a vasomotor component to them, which may be responsible for certain or many of the symptoms experienced by patients who are afflicted with prolonged or recurrent neurovascular headaches such as migraines and cluster headaches.
It has been theorized that headaches of neurovascular etiology, such as migraines, for example, result from release of neurotransmitters by trigeminal nerves, which innervate cerebral blood vessels (Moskowitz et al., 1979, Lancet 2:883-885). When disturbed, the trigeminal ganglion is capable of antidromic release of excitatory and other neurotransmitters that initiate sterile inflammation (Demarin et al., 1994, Funct. Neurol. 9:235-245; Moskowitz, 1984, Ann. Neurol. 16:157-168; Moskowitz, 1993, Neurol. 43(Suppl. 3):S16-S20). Studies of trigeminal stimulation, cerebral blood flow, and neuropeptides in animal models and in humans provide support for this theory (Goadsby et al., 1993, Ann. Neurol. 33:48-56; Goadsby et al., 1991, Headache, 31:365-370; Goadsby et al., 1990, Ann. Neurol. 28:183-187; Edvinsson et al., 1994, Cephalalgia 14:88-96). It has been postulated that changes in cerebral blood flow that are triggered by trigeminal stimulation are mediated by the sphenopalatine ganglion (hereinafter, the xe2x80x9cSPGxe2x80x9d) Goadsby et al., 1987, Am J. Physiol. 22:R270-R274; Lambert et al. 1984, J. Neurosurg. 61:307-315; Walters et al., 986, Stroke 17:488-494; Suzuki et al., 1989 Neuroscience 30:595-604).
Another theory posits that nitric oxide is a causative molecule of headaches of neurovascular etiology (Olesen et al., 1995, Cephalalgia 15:94-100). Because the SPG and related postsynaptic and neurovascular structures contain many cells which express nitric oxide synthetase, the SPG mediates the changes in cerebral blood flow that are triggered by trigeminal stimulation, according to this model.
Regardless of whether a neurotransmitter, nitric oxide, both, or neither are the causative agent of headaches of neurovascular etiology, it is clear that the SPG and other dorsonasal nerve structures are key complex structures for targeting the treatment of headaches of neurovascular origin, such treatment including, but not being limited to the treatment of the pain associated with such headaches. Methods of treating headaches of neurovascular etiology which have been described in the prior art have not provided sustained and effective relief from acute neurovascular headache episodes.
Migraine
Migraine is a disorder characterized by persistent headache, which may be severe, which may be associated with visual and gastrointestinal disturbances, and which may also be recurrent. In certain cases, visual changes (designated xe2x80x9cauraxe2x80x9d by some practitioners) or other symptoms precede the onset of a migraine. Such prodromal symptoms may be due to intracranial vasoconstriction. The precise etiology of migraine is unknown. Reported evidence suggests that a genetically transmitted functional disturbance of intra- and extracranial circulation may be involved. Regional alterations in cerebral blood flow attributable to intracranial arterial vasodilation are known to accompany headache associated with migraine. Some investigators have attributed head pain associated with a migraine to substances released as a result of or associated with dilation of scalp arteries during an acute migraine episode (e.g. Berkow et al., ed., 1992, The Merck Manual of Diagnosis and Therapy, Merck Research Laboratories, Rahway, N.J., pp. 1425-1426).
Prodromal symptoms of an acute migraine episode include, but are not limited to, depression, irritability, restlessness, anorexia, scintillating scotomas, visual changes such as perception of stars or zig-zag lines, paresthesias, and hemiparesis. These prodromal symptoms may disappear shortly before the migraine is manifested, or may persist until or after the onset of the migraine.
The head pain associated with migraine may be unilateral or generalized. Nausea, vomiting, and photophobia often accompany migraines. Symptoms generally follow a pattern in an individual patient, except that unilateral head pain may not always be on the same side. Patients afflicted with migraine may experience migraines with a frequency between daily and only once in several months. An untreated acute migraine episode may endure for a long period, such as hours or days.
Various nonspecific medical and surgical procedures have been recommended to decrease the frequency of recurrence of migraines. Such procedures include surgery, counseling, participation of the patient in biofeedback procedures, and administration of methysergide, propanolol, a calcium channel blocker such as verapamil, an ergotamine preparation such as dihydroergotamine, or a serotonin receptor agonist such as sumatriptan. Some procedures to decrease the frequency of recurrence of migraines may offer benefit to certain patients, but are not useful for alleviating the pain associated with an acute migraine episode once it has begun.
Treatments which have been recommended for the treatment of an acute migraine episode include administration of aspirin, codeine, a serotonin agonist such as sumatriptan, ergot, ergotamine, caffeine, a narcotic, butorphanol tartrate, meperidine, or a combination of these compounds. Administration of any combination of these compounds has not offered satisfactory or sustained relief from the pain or other symptoms associated with an acute migraine episode in many patients. Furthermore, numerous side effects have been reported to accompany administration of these compounds, including dizziness, nausea, somnolence, fatigue, chest pain, cardiac infarction, hypertension, hypertensive crisis, chest-, face-, and neck-hyperemia, gastrointestinal upset, sedation, drug dependence, and the like. In addition, certain of these compounds are contraindicated for numerous patients such as pregnant women, nursing women, patients using monoamine oxidase inhibitors, patients having a history of ischemic heart disease, ulcer, gastritis, kidney disease, liver disease, and other diseases.
Currently popular migraine treatments involve administration of a pharmaceutically active agent which interacts with a serotonin receptor on cerebral arterial surfaces (Goadsby, 1995, In: Migraine: Pharmacology and Genetics, Sandler et al., Eds., pp. 67-81; Cambridge et al., 1995, Brit. J. Pharmacol. 114:961-968; Ferrari et al., 1995, Euro. J. Neurol. 2:5-21). Serotonin receptor agonists include sumatriptan (Imitrex(trademark), Glaxo Wellcome Inc., Research Triangle N.C.), zolmitriptan (Zomig(trademark), Zeneca Pharmaceuticals, Wilmington, Del.), and rizatriptan (Maxalt(trademark), Merck and Co., West Point, Pa.). Serotonin receptor agonists are believed to produce relief from an acute migraine episode by causing resumption of regulated cranial blood flow, thereby halting the acute migraine episode. (Hamel et al., 1993 Mol. Pharmacol. 44:242-246). However, administration of serotonin receptor agonists is inefficient via intravenous, oral, and intrarectal gavage routes. These routes of administration result in systemic agonist distribution, which increases the availability of the agonist to hepatic tissue and to other sites where the agonists are metabolized. Furthermore, systemic distribution of one of an agonist results in distribution of the agonist to sites where the agonist produces undesirable side effects (Saper, 1997, Headache 37(Suppl. 1):S1-S14). Therefore, it would be advantageous to administer an agent which does not require systemic delivery.
Intranasal administration of lidocaine for the relief of pain associated with migraines has been investigated in a non-controlled study by Kudrow et al. (1995, Headache, 35:79-82). In that study, many patients experienced no relief and were on migraine prophylactic medication. In a controlled study, Maizels and co-workers evaluated the effectiveness of intranasally-administered lidocaine, a shorter-acting local anesthetic, for treatment of acute migraine episodes (Maizels et al., 1996, J. Amer. Med. Assoc. 276:319-321). High concentrations of lidocaine administered intranasally decreased head pain within fifteen minutes in 55% of the patients so treated. However, significant pain and associated symptoms persisted in many of these patients following treatment. A significant number of patients required further treatment with other types of migraine medication to attain acceptable relief. Furthermore, the acute migraine episode frequently rebounded or relapsed early after treatment, usually within the first hour.
Cluster Headaches
A cluster headache comprises a headache which is characterized by recurrent episodes of unilateral excruciating pain, usually occurring on the same side of the head of a patient. These headaches are typically oculofrontal or oculotemporal, with occasional radiation to the upper jaw, and are described as being of a boring, non-throbbing nature. Associated with the head pain are one or more autonomic accompaniments, including conjunctival injection, nasal congestion, lacrimation, rhinorrhea, body temperature elevation, vasodilation on the same side as that on which the pain is experienced, and edema beneath the eye. A cluster headache is usually of short duration, persisting for between fifteen and ninety minutes, and tends to occur in clustersxe2x80x94typically a few times a day for a period of six to twelve weeks. Months or years may pass between the clusters of headaches. Because headaches which appear to be identical to spontaneous cluster headaches may be induced by subcutaneous injection of histamine diphosphate, cluster headaches are also known as histamine headaches. Headaches having sensory similarity to cluster headaches may also be induced by administration of nitroglycerin to a human patient, for example by sublingual administration of 0.4 milligrams of nitroglycerin.
Methods which have been investigated for treating cluster headaches include administration of methysergide, a vasoconstrictor, a corticosteroid, oxygen, indomethacin, and intranasal administration of cocaine, which is a toxic shorter-acting local anesthetic with pronounced central effects and a vasoconstrictor, or lidocaine, which is also a shorter-acting local anesthetic (Barre, 1982, Headache, 22:69-73; Kittrelle et al., 1985, Arch. Neurol. 42:496-498). These investigations highlight that shorter-acting local anesthetics were effective to abort pain associated with a single individual headache episode that is only one of several headache episodes comprising a cluster headache, sometimes referred to as a cluster period. Large amounts of drug and repeated dosings were required to achieve these results. However, no investigation was made by those investigators of the ability of these shorter-acting local anesthetics to provide relief from all, or even more than one, of the typically short-duration headaches associated with a single cluster headache period. Clinically, intranasal administration of lidocaine has proven to be disappointing and is not widely used, nor is it included in recognized cluster headache treatment protocols.
Tinnitus
More than 37 million Americans are afflicted with tinnitus. Tinnitus is a condition characterized by a ringing, buzzing, roaring, or clicking sound perceived by a patient, a person observing the patient, or both, which seems to originate from the ear of the patient. Objective tinnitus is characterized by noise originating from the ear of a patient which can be perceived by a person examining the patient, while noise associated with subjective tinnitus can be perceived only by the patient. There are currently no truly effective treatment options available for tinnitus, which has been associated with instances of suicide in patients afflicted therewith. Treatment methods which have been attempted include surgical decompression of the eighth nerve, use of specialized hearing aids which mask the tinnitus, and infusion of drugs directly into areas of the brain involved in auditory sensory processing. None of these treatment methods has proven routinely effective.
Intra- and Extracranial Vasospasm
Intra- and extracranial vasospasm, hereinafter referred to as xe2x80x9ccerebrovascular spasm,xe2x80x9d results from contraction of smooth muscle tissue of a cerebral blood vessel. Cerebrovascular spasm interferes with cerebral blood supply and is associated with numerous symptoms, including muscle paralysis, visual changes, speech changes, and numerous ischemic symptoms of stroke. Vascular muscle tone is modulated by neural, humoral and local factors.
Disorders Manifested During or After and Associated with an Acute Ischemic Event
Causes of acute ischemic events include occlusive (i.e. thrombotic or embolic) processes, as well as vasospastic and other physiological processes and disorders, following the onset of which the affected tissue is insufficiently supplied with oxygenated blood. Manifestations during or after such events include, for example, tissue damage or death, vasospasm, vasodilation, vasomotor instability, muscle weakness, dysphasia, dysphonia, cognitive impairment, autonomic imbalance, and the like. These disorders may be alleviated by increasing oxygenated blood supply to the ischemic tissue. Increased blood supply to ischemic cerebral tissue may be effected, for example, by inducing dilation of an occluded cerebral blood vessel. Further by way of example, such increased blood supply may be effected by dilation of cerebral blood vessels proximal to an occluded vessel by increasing the flow of oxygenated blood or by increasing the pressure gradient across the occlusion, thereby decreasing the amount of watershed ischemia, decreasing the amount of damaged cerebral tissue, and increasing the amount of cerebral tissue which may be salvaged. Furthermore, facilitating venous drainage, by venodilation, decreases venous back pressure and increases forward flow of oxygenated blood.
Prior art methods of treating such disorders exhibit serious limitations. Thrombolytic therapy, for instance, is known to be effective to decrease the severity of cerebral damage caused by certain occlusive strokes if the therapy is performed soon enough after the onset of the occlusion. However, cerebrovascular spasm frequently follows, and decreases the success of the procedure and adversely affects patient outcome. A method of reducing the severity of an acute cerebral ischemic event by increasing early blood flow to the ischemic area and decreasing vasospasm is needed.
Anatomy of the Nasal Cavity
The structures associated with the nasal cavity are described, for example, in Williams et al. (eds., 1980, Gray""s Anatomy, 36th ed., W. B. Saunders Co., Philadelphia, 1062-1065), especially at FIGS. 3.78, 3.79, 3.80, 7.239, and 7.240 and the accompanying text. FIG. 1 herein is a diagram depicting the approximate location of the SPG in relation to the nasal cavity of a human.
The SPG is, in some texts, designated the xe2x80x9cpterygopalatine ganglion.xe2x80x9d The position, origin, branches, and distribution of the SPG may be understood by examining FIGS. 7.177, 7.178, 7.179, and 7.181 and the accompanying text in Williams et al. (supra).
As the cited figures and text describe, the SPG is located below a region of epithelium in the posterior portion of the nasal cavity, inferior to and including the spheno-ethmoidal recess, and is therefore not readily accessible via the nostril.
Ropivacaine is a recently introduced amino amide local anesthetic that is commercially available as the S(levo)-enantiomer (Lee et al., 1989, Anesth. Analg. 69:736-738). Ropivacaine allows differential nerve block and exhibits intermediate distribution and clearance and a better systemic toxicity profile compared with other similar relatively long acting potent local anesthetics. In addition, ropivacaine also exhibits inherent vasoactive properties (deJong, 1995, Reg. Anesth. 20:474-481; Santos et al., 1990, Anesth. Analg. 70:262-266). Ropivacaine-HCl is commercially available as 0.25%, 0.5%, 0.75% and 1.0% (w/v) solution (Naropin(trademark), Astra USA, Inc., Westborough, Mass.), and has been described, for example in international patent application publication number WO 85/00599.
Local anesthetics are known to block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of nerve impulses, and by reducing the rate of rise of the action potential of the nerve. In general, the progression of anesthesia is related to the diameter, degree of myelination, and conduction frequency and velocity of affected nerve fibers. Generally, the order of loss of nerve function is as follows: (1) sympathetic and parasympathetic function, temperature and pain, and (2) touch, and, where applicable, (3) proprioception, and (4) skeletal muscle tone.
The rate of systemic absorption in a patient of a local anesthetic is dependent upon the total dose, the concentration, and the identity of the local anesthetic administered to the patient, the route of administration, the vascularity of the site of administration, and the presence or absence of vasoconstrictors such as epinephrine in the anesthetic composition. A dilute concentration of epinephrine (e.g. 1:200,000 or 5 micrograms per milliliter) usually reduces the rate of absorption and peak plasma concentration of the local anesthetic, sometimes prolonging the duration of the anesthetic effect.
The duration of the anesthetic effect at a given site of administration of a local anesthetic is dependent upon the total dose, the concentration, and the identity of the local anesthetic administered to the patient, the rate of systemic absorption, and often the presence or absence of a vasoconstricting or other agent in the anesthetic composition.
Systemic administration of a local anesthetic is not a practical method for delivery of the local anesthetic to provide lasting relief of headache pain in a human patient, due to known adverse reactions, occasionally including acute emergencies, associated therewith.
There remains a significant unmet need for effective methods of treating acute CNvDs such as persistent and recurrent headaches of neurovascular etiology, including migraines and cluster headaches. Particularly needed are compositions and methods which are effective for inhibiting an acute neurovascular headache episode.
Muscular Headaches
Muscular headaches are very common in the adult population. It is estimated that between about 3% and about 5% of patients who experience a muscular headache are afflicted with chronic muscular headaches, by which is meant that the muscular headache occurs more than fifteen days per month for a period of at least about six months. Analgesic addiction is a recognized problem in the treatment of patients afflicted with chronic muscular headaches.
Muscular headaches may be acute, as is the case for typical episodic tension headaches, which are related to contraction of muscles of the head and neck. Sustained contractions of skeletal muscles of the head, neck, face, and shoulders are associated with concurrent local chemical changes within skeletal muscle, and may give rise to pain. The pain may be localized or it may be referred, which means that the pain is perceived at a body location different than the location of muscle contraction. Muscle contraction headaches may also be chronic and associated with depression or with one or more other psychological problems. Muscle contraction headaches may also be associated with anatomic factors such as cervical arthritis, temporomandibular joint disorders, irritating lesions, pressure and mechanical stress, eye strain, or emotional stress or disorders.
Muscular headaches, including muscle contraction headaches and tension headaches, are recognized as the most common category of recurring head pain. In distinction from migraines, they are usually bilateral, often with occipital nuchal, temporal, or frontal predominance or with diffuse extension over the top of the cranium. The pain may be located in the back of the head and neck as well. Unlike migraine pain, the pain associated with a muscular headache is usually described as squeezing and vise-like in nature. Nausea, photophobia, and phonophobia are not generally associated with muscular headache episodes. The onset of a muscular headache episode is more gradual than the onset of a migraine or cluster headache episode, and muscular headache episodes are not generally associated with auras or prodromal symptoms. The onset of muscular headache episodes does not appear to be associated with physical activity by the patient. Once established, a muscular headache episode may persist, perhaps with minimal fluctuations in intensity, for weeks or months. Muscular headache is recognized as being present all day, day after day.
Although patients afflicted with migraine may be awaked from sleep, patients afflicted with a chronic muscular headache generally sleep undisturbed and perceive development or intensification of the headache soon after waking. About a third of patients afflicted with a muscular headache exhibit symptoms of depression. Migraine headaches may be complicated by tension headaches which persist and arouse fears of mass lesions, thereby leading to the performance of unnecessary diagnostic workups in many patients.
Muscular headaches are recognized as being a distinct class of headaches, distinguishable from headaches such as migraines or cluster headaches.
Muscular headaches are, in part, related to sustained contraction of the skeletal muscles of the scalp, face, neck, and shoulders. Sustained muscle contraction is related to local pathology, central influences, and multisystem modulation, and involves gamma efferent neuronal muscle spindle activation. Related monosynaptic conduction through the ventral horn augments both efferent neuronal discharge and muscle contraction. A cycle of pain, muscle spasm, local chemical changes, neural excitability, skeletal muscle blood vessel compression or spasm, and anxiety ensues. All types of persistent headaches lead to sustained cranial muscle contraction, but pain resulting from this type of sustained contraction is typified by an aching sensation, rather than by the characteristic squeezing pain associated with muscular headaches. Sometimes, surface electromyograph recordings of the craniocervical muscles show no evidence of persistent contraction. It is therefore widely suspected that muscular headaches are not caused solely by sustained cranial muscle contraction.
Generally, the pain associated with a muscular headache episode is mild to moderate in severity, although the pain becomes severe in many patients. Relaxation, massage, and common analgesic medications such as aspirin and acetaminophen are often effective to alleviate mild muscular headache pain. Codeine or other narcotic preparations, tranquilizers, and antidepressants are sometimes administered to patients experiencing more severe muscular headache pain. Unfortunately, many of these patients develop physical dependence on these agents and must be followed closely because of a significant incidence of addiction.
Nonetheless, the musculature of the head, neck, jaw, or upper back is tense and tender in many or most patients afflicted with a muscular headache, and one or more trigger points, or muscle knots, are often present. Cervical spine arthritis and temporomandibular joint disorders may contribute to the development of a muscular headache.
Treatments which have been recommended for the treatment of muscular headaches include reassurance and psychological support, massage of the head and neck, application of hot and cold packs, transcutaneous electrical neural stimulation, physical support (e.g., use of orthopedic pillows and the like), administration of aspirin compounds, acetaminophen compounds, non-steroidal anti-inflammatory drugs, tricyclic antidepressants, narcotic analgesics, oral muscle relaxants, with or without tranquilizers, muscle relaxants, and other analgesic compounds. These treatments are generally effective for alleviating mild- to moderate-intensity acute muscular headaches.
Some patients afflicted with either severe or chronic muscular headaches sometimes experience relief from their acute symptoms using these known treatments. However, many do not. Furthermore, over time, many patients who initially respond to one or more of these therapies become less responsive to these therapies, possibly because they develop a tolerance to known medications, or because the disease process progresses or increases. Additionally, symptoms may be influenced by psychological factors which may remain constant or worsen. The side effects which accompany administration of known medications are significant and may become more severe over time.
There remains a significant unmet need for effective compositions and methods of treating muscular headaches, including inhibiting muscle contraction headaches and tension headaches. The present invention provides compositions and methods which satisfy this need.
Systemic Delivery of a Pharmaceutically active agent
Numerous pharmaceutically active agents are useful when delivered systemically to a human patient. Systemic delivery of such agents can sometimes be effected by oral administration of a composition comprising the agent. However, many pharmaceutically active agents are degraded by, or otherwise react with acids, proteins, or other agents located in, the human gastrointestinal tract or the human liver or circulatory system, with the result that the agent loses its pharmaceutical usefulness. For this reason, many pharmaceutically active agents may not practically be administered by an oral route to achieve systemic delivery of the agent. In addition, gastrointestinal absorption of an orally administered medication may be impaired in a distressed patient, such as a patient experiencing a migraine or any severe headache.
Pharmaceutically active agents intended for systemic delivery to a human may be administered via an intravenous route using well known methods. However, such methods cause discomfort to the patient and often can be performed only in conjunction with frequent or continuous supervision by a medical professional.
Methods of topically administering compositions to a human tissue to achieve systemic delivery of a pharmaceutically active agent which is a component of the composition are known, including the use of transdermal or transmucosal pastes, cremes, liquids, solids and semisolids impregnated with the composition, and the like. Systemic delivery of a pharmaceutically active agent effected by topical administration methods are limited by the ability of the agent to diffuse through the tissue to which the composition is applied to reach blood vessels where the agent is absorbed and taken up for systemic delivery.
A significant, unmet need remains for compositions and methods which can be used to systemically deliver or to enhance systemic delivery of a pharmaceutically active agent to a human and which overcome the limitations of known systemic delivery compositions and methods.
The present invention provides compositions and methods which satisfy the needs described herein.

Apparatus for administering composition for inhibiting cerebral neurovascular disorders and muscular headaches


A data transmission system includes a visual interface device and an operation device. The visual interface device includes a display panel and a control unit. The control unit receives display data and transmission data, and transmits the display data and the transmission data to the display panel. The operation device includes a capturing unit. A coupling signal containing the display data and the transmission data is coupled from an electrode of the display panel to the operation device when the visual interface unit is in operation, and the operation device utilizes the capturing unit to retrieve the transmission signal from the coupling signal.

Field of Invention
The invention relates to a data transmission system.
Related Art
In recent years, for increasing the applications of consumer electronic devices, some companies add the near field communication (NFC) (or short range wireless communication) function into an electronic device. Commands, music, pictures, business card, data or files can be transmitted from one electronic device to another electronic device without establishing a physical connection by the NFC (or near wireless communication). Except providing convenient data transmission between electronic devices, it also enable the application of electronic device in more areas, such as access control system, tickets, credit card payment, or receiving advertising messages, such as receiving coupons form store's screen via Bluetooth communication.
It is an inevitable trend for an electronic device to be equipped with near field communication function. Therefore, communication industries actively research and develop to provide an electronic device with a new structure near field communication function.


Seat covers are sewn inside-out and then inverted to fit over a frame. Inversion is accomplished by threading the sewn seat cover over a pair of generally parallel arms. The sewn seat cover is generally in the form of a pocket. The closed end of the pocket is engaged by the blunt edge of a plate. The plate pushes the closed end between the arms forcing the structure of the pocket to ride up and over the top of the arms and downward between the two arms thereby inverting the seat cover to a right side out condition.

Modern motorized vehicle seats have a wear surface of fabric, leather, or the like consisting of a plurality of panels of material sewn together in conventional construction. The sewn edges of the panels are hidden from view of the user of the seat, but the sewing process itself is accomplished by conventional commercial grade sewing machines which sew all of the seat cover parts together with the sewing taking place while the wear surface of the seat cover is in inverted condition. After sewing, the seat cover has front and back panels joined together along three sides with the fourth side open to slide over the frame. The sewn panels form a pocket-like structure. The seat cover as sewn must be inverted to get the wear surface to the exterior of the pocket formed in the sewing operation.
It is conventional to sew, adhesively bond, or otherwise secure foam rubber padding, etc. to the front panel of the seat cover prior to the time the front and back panels are sewn together. The padding is to provide comfort for the user of the seat. A problem is created by the fact that the padding is secured to the front panel of the seat cover, in that, the volume of the padding bulges into the pocket making a tight fit and making it physically difficult to invert the seat cover to operative position. Heretofore, in this industry the inversion has taken place by a hand operation which is time consuming, physically exhausting, an altogether labor intensive feature of the manufacturing process.
A review of product inverting apparatus has been made and U.S. Pat. No. 4,249,972 is illustrative. It shows apparatus for inverting inside-out girdles using two upstanding arms over which the girdle is threaded. A plate descends downward between two upstanding arms and pushes the closed end of the girdle downward between the two arms to invert the girdle structure.
U.S. Pat. No. 3,125,261 shows similar structure to that of the patent mentioned above except that the structure reciprocates in horizontal fashion rather than vertical fashion.
In U.S. Pat. No. 4,739,910 an apparatus and method are shown for inverting a pair of training pants for children. It uses a cone-shaped structure over which the training pants are fitted and a probe which pushes within the cone-shaped structure from the narrowest end to invert the training pants as the probe pushes to the interior of the cone.
U.S. Pat. No. 3,310,207 shows apparatus for inverting a pillowcase which includes a couple of arms which project to the closed end of the pillowcase and then some mechanism grasps the collar at the open end and pulls it longitudinally toward the closed end.
U.S. Pat. No. 3,103,302 shows an apparatus for inverting hosiery which uses a piston and cylinder combination actuated by a foot peddle to assist in the inversion process.
As a result of the problem in the industry and the research performed in seeking a solution, it was concluded that new and original apparatus was required to accomplish the desired result.

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The present invention relates to a new process for the synthesis of alkyl phosphinic acids, and more particularly to a coupling reaction between an alkylhalide and a hypophosphorous acid derivative in the presence of an amine and an amineoxide.

Reactions between an alkyl halide and the hypophosphorous acid derivative, bis(trimethylsilyl)hypophosphite, is previously known from K. Issleib et al., Z. anorg. Chem. 530 (1985), pp. 16-28.
A radical initiated reaction between a hypophosphorous acid and an alkene is disclosed in Deprèle, S., et al., J. Org. Chem., 2001, 66, 6745-6755. The reaction is a radical addition of hypophosphites to olefins and the radical reaction is initiated by trialkylboranes and oxygen.
Winqvist A., et al., Eur. J. Org. Chem., 2002, 1509-1515, describe, inter alia, synthesis of phosphinic acids from alkyl halides and bis(trimethylsilyl)hypophosphite. The publication describes the influence of the temperature during the reaction.
WO 01/41743 discloses (aminopropyl)methylphosphinic acids and the synthesis thereof starting from protected aminopropylhalides and a hypophosphorous acid derivative.
U.S. Pat. No. 2,724,718 and U.S. Pat. No. 4,632,741 disclose the synthesis of phosphinate salts through a radical addition of a hypophosphite salt to olefins by means of irradiation with UV light in the presence of a photoinitiator.
EP 1055676 discloses a process for the preparation of dialkylphosphinic acids by free radical-initiated reaction with olefins.
Many initiators in the collection of suitable radical initiators require heat addition for initiating the reaction. Also oxygen can be used as an initiator for a radical reaction. However, some of the hypophosphorous acid derivatives are pyrophoric and therefore oxygen is not a suitable initiator in large-scale production. One such example is the hypophosphorous acid derivative bis(trimethylsilyl)hypophosphite.
Chemical radical initiators would be possible for initiating the reaction between an alkyl halide and a hypophosphorous acid derivative. Most often, when such initiators are used, the reaction is started by raising the temperature of the reaction mixture. However, temperature is also a critical parameter for reduction of the amount of by-products, the lower temperature the lower amount of by-products. The disadvantage of lowering the temperature is that also the reaction rate is reduced at a low temperature, and this has implications for the result and the yield of the desired product. Therefore, there is a need for a process where the amount of by-products obtained are kept low in parallel with a fast and efficient reaction rate.
WO 2006/038870 discloses that UV-light can catalyze the reaction between alkyl iodides and BTHP in the formation of alkyl phosphinic acids. The use of UV-light is convenient on lab-scale, but it has proven to be difficult to find viable technical solutions on larger scales.
Outline of the Invention
The present invention relates to a new process for the synthesis of alkyl phosphinic acids starting from alkyl halides and a hypophosphorous acid derivative in the presence of an amine and an amineoxide.
More particularly, the present invention relates to a process for the synthesis of a compound of formula I
wherein
R1 is selected from hydrogen; C1-C10-alkyl; C1-C10-alkoxy; fluorine; and chlorine;
R2 is selected from hydroxy; fluorine; chlorine; oxo; and C1-C10-alkoxy;
R3 is selected from hydrogen and C1-C6-alkyl;
R4 is selected from hydrogen and C(O)R5;
R5 is selected from C1-C10 alkyl and C1-C10 alkoxy;
comprising reacting a compound of formula II

R6 is selected from hydrogen; C1-C10-alkyl; C1-C10-alkoxy; fluorine; and chlorine;
R7 is selected from hydroxy; fluorine; chlorine; oxo; and C1-C10-alkoxy;
R8 is selected from hydrogen and C1-C6-alkyl;
R9 is selected from hydrogen and C(O)R10;
R10 is selected from C1-C10 alkyl and C1-C10 alkoxy; and
X is iodide or bromide;
with a compound of formula III
wherein
to R11 and R12 are each and independently selected from C1-C10 alkyl and Si(R13)3;
and
R13 is a C1-C6 alkyl;
in the presence of an amine and an amineoxide.
When the substituent R2 and/or R7 is oxo, then this substituent is bound to the carbon atom by a double bond. In this case, no hydrogen atom is bound to said carbon atom.
In another embodiment, the compound of formula II is prepared by reacting another compound of formula II, wherein X is mesyloxy, with one or more halides.
In another embodiment, the halides are selected from sodium iodide and tetrabutylammonium iodide.
In another embodiment, the compound of formula I is

In another embodiment, the compound of formula II is

In another embodiment, the compound of formula III is bis(trimethylsilyl)hypophosphite.
In another embodiment, the amine is selected from hexamethyldisilazan, N-methylmorpholine, trimethylamine, triethylamine, diisopropylethylamine, and 2,2,6,6-tetramethylpiperidine.
In another embodiment, the amineoxide is selected from trimethylamineoxide, N-methylmorpholineoxide (NMM-oxide) and 2,2,6,6-tetramethylpiperidineoxy radical (TEMPO).
In another embodiment, the reaction is performed in the presence of toluene, tetrahydrofuran, acetonitrile, ethyl acetate or in a mixture thereof.
In another embodiment, the reaction is performed at a temperature of from −70° C. to 20° C.
In another embodiment, the reaction is performed at a temperature of from −70° C. to 0° C.
As used herein:
ACN refers to acetonitrile;
BTHP refers to bis(trimethylsilyl)hypophosphite;
DIPEA refers to diisopropyl ethyl amine;
EtOAc refers to ethyl acetate;
HPLC refers to high performance liquid chromatography;
IPC refers to in-process control;
MEK refers to methyl ethyl ketone;
NMM refers to N-methylmorpholine;
PEG refers to polyethylene glycol;
QI refers to tetrabutylammonium iodide;
TEMPO refers to 2,2,6,6-tetramethylpiperidineoxy radical;
THF refers to tetrahydrofuran;
TLC refers to thin layer chromatography.
According to the present invention, NMM is used in the reaction mentioned above as a base forming a precipitate with the hydrogen iodide generated in the reaction. NMM-oxide is used as a catalyst. Process development based on these findings resulted in a method that gives reproducible results on 1000-L scale, resulting in a shorter reaction time and a slightly higher yield.
Unless otherwise stated the term "C1-C10 alkyl" as used throughout this specification includes linear or branched C1-C10 alkyl. Examples of C1-C10 alkyl include, but are not limited to, C1-C6 alkyl such as methyl, ethyl, propyl, n-propyl, isopropyl, butyl, iso-butyl, sec-butyl, tert-butyl, pentyl and hexyl.
Unless otherwise stated, the term "alkoxy" denotes an O-alkyl, wherein alkyl is as defined above. The term "C1-C10 alkoxy" as used throughout this specification includes linear or branched C1-C10 alkoxy. Examples of C1-C10 alkoxy include, but are not limited to, C1-C6 alkoxy such as methoxy, ethoxy, propoxy, n-propoxy, and tert-butoxy.
The synthesis of the phosphinic acids according to the present invention can be performed at temperatures at or below approximately room temperature, i.e. at a temperature of or below 20° C. The effect of lowering the temperature is that the various side reactions and the amount of by-products limiting the yield of the reaction can be reduced. According to one embodiment of the invention, the reaction mixture is held at a temperature of approximately 0° C. By lowering the reaction temperature to approximately −70° C. an increased yield can be achieved. Dehalogenation is a side reaction, which occurs. However, the dehalogenation is suppressed by lowering the temperature, and thus, the production of the sideproducts is suppressed.
An alkyl phosphinic acid is produced according to the present invention by adding the alkyl halide dissolved in a solvent which may be organic to a cooled solution comprising the hypophosphorous acid derivative in an inert environment, i.e. an environment free from oxygen attained by using nitrogen or argon.
The components for forming the hypophosphorous acid derivative, i.e. the hypophosphite to group, are, for example, ammonium hypophosphite and hexamethyldisilazan, ammonium hypophosphite, DIPEA and trimethylsilyl chloride. They are mixed in a vessel until the reaction is completed, the reaction mixture is then cooled and kept in an environment free from oxygen.
For example, when BTHP is being used as the hypophosphorous acid derivative, the first step of the synthesis for obtaining alkylphosphinic acids is the formation of BTHP. The formation of the hypophosphorous acid derivative just before the addition of the alkyl halide is an advantage since the hypophosphorous acid derivative is highly pyrophoric. The alkyl halide is then added and the reaction is thereafter initiated by NMM and NMM-oxide. The completion of the reaction is measured by, for example, HPLC or TLC.
During the process of the invention, a neutralisation of the hydrogen halide formed during the reaction can be performed by having a base present during the synthesis of the phosphinic acid. The base is suitably an amine such as hexamethyldisilazan, N-methylmorpholine, trimethylamine, triethylamine, or DIPEA.
The reaction is conducted in an aprotic organic solvent, for example, toluene, THF, EtOAc, acetonitrile, MEK, or in a mixture thereof.
The compound formed is recovered by extraction in a polar solvent such as ethyl acetate, isopropanol, n-butanol or a mixture thereof.
By mixture thereof is meant a mixture of two or more of said solvents.
The compounds synthesised according to the claimed process of the present invention can form salts with bases. Salts with bases are, for example, alkali metal salts, e.g. sodium or potassium salts, or those with ammonia or organic amines.
The process according to the present invention is an efficient as well as an economical process for the preparation of alkylphosphinic acids. The following Examples will further illustrate the invention, but are not intended to limit the scope of the invention as described herein or as claimed below.

Process for the synthesis of alkyl phosphinic acids by initiation of an amine and an amineoxide


A method of fabricating a connecting rod (6) out of composite material using three-dimensional fabric of woven reinforcing fibers, the connecting rod (6) extending in a main direction. The method comprises the steps of: cutting out one or more base pieces (7, 8) from a three-dimensional fabric; cutting out one or more reinforcing pieces (9, 10) from a three-dimensional fabric; installing the various pieces (7, 8, 9, 10) on a support in order to shape them; securing the various pieces (7, 8, 9, 10) to one another by stitching (12, 13, 14, 15) using reinforcing fibers in order to constitute a reinforcing fiber preform; installing the preform on a mandrel; and injecting resin into the preform and polymerizing the resin.

Such a connecting rod, shown in FIG. 1 with the reference 1, has a generally tubular hollow main body 2 extending along a general direction AX and extended at each of its ends by respective two-lug clevises, these clevises being given references 3 and 4.
In a method known from patent document FR 2 893 532, the connecting rod is fabricated using a piece of reinforcing fiber fabric that is cut to have a shape as shown in FIG. 2. This shape comprises a central portion for the hollow main body 2 and four extensions, each corresponding to a respective one of the clevis lugs.
The fabric used is a three-dimensional woven fabric of carbon fibers, i.e. a fabric of relatively large thickness made up of reinforcing fibers that are woven together in three dimensions. By way of example, such a three-dimensional fabric corresponds to a 2.5 D type fabric.
Such a fabric has a plurality of layers of longitudinal fibers, and a plurality of layers of transverse fibers that are woven together in such a manner that the fibers extending in one direction are interlinked with the fibers in a plurality of other layers in order to constitute a non-separable fabric.
The fabric may optionally be reinforced in the clevises: some of the fibers of the various layers are then no longer interlinked in the clevises so as to leave layers that are not mutually interlinked. This makes it possible to insert additional layers in the clevises in order to increase their thickness.
Additional fibers extending substantially perpendicularly to the plane of the layers may subsequently be stitched through the various layers making up the clevises in order to secure them to one another.
Fabricating such a clevis consists in folding the piece of fabric shown in FIG. 2, which piece of fabric is optionally reinforced in its clevises, by applying it onto a mandrel or the like and then bringing together its two opposite edges. The edges can then be connected together, e.g. by stitching, prior to injecting resin into the reinforcing fiber fabric and heating the assembly in order to polymerize the resin.
The nominal thickness of the wall forming the connecting rod is limited by the thickness of the three-dimensional fabric that is used for making it, given that deciding to use a thick fabric increases the cost of such a fabric very considerably, in particular because it involves reducing the speed of weaving very considerably.
In practice, given current sales costs, it is not possible to envisage using a fabric having a thickness of more than two or three centimeters. It can be understood that such a limitation on thickness puts a limitation on the forces that can be accepted by the connecting rod in question as a whole, and also by its clevises.

Composite connecting rod having an increased mechanical strength


Nano- to microscale liquid coacervate particles are provided. The liquid coacervate particles are produced by a process including stimulating a population of liquid droplets containing one or a mixture of components to induce a phase separation point of a first component, and maintaining stimulation at the phase separation point to form a coacervate domain of the first component within each of the droplets to form the liquid coacervate particles. The self-assembled nano, meso, micro and macro liquid coacervate particles and related coated substrates can have utility in drug delivery, bioanalytical systems, controlled cell culture, tissue engineering, biomanufacturing and drug discovery.

Multi-phase compartments are ubiquitous within biological cells, provide a powerful method for segregation of biomolecules, and are universal motifs in synthetic polymeric particle fabrication. Unfortunately, a broad platform for the in vitro programming of complex and hierarchical multi-phase structures has remained elusive. Techniques such as layer-by-layer deposition, molecular self-assembly, and microfluidic emulsion templating enable a high degree of control over the layering of distinct liquid or polymeric phases. However, these approaches have been limited to varying extents by: the need for complex and specialized fluidic devices, low fabrication throughput, limitations in achievable particle size, and constraints on material components due to assembly requirements. Thus, both current microfluidic and existing bulk techniques for fabrication of hierarchical liquid-liquid, gel and particle systems are severely lacking in scalability, size control, ease of fabrication, and morphological diversity.

Programmable liquid, gel and biohybrid compartments and methods of use


An adjustable hinge device is provided for a foldable apparatus in accordance with the present invention. The foldable apparatus, such as a portable mobile phone, comprises a cover and a body connected by the hinge so as to make the cover rotatable relative to the body between a fully opened position and a fully closed position. When the cover rotates to the fully opened position, a maximum opening angle is defined. According to the relative movement between a rotatable portion and a fixed portion of the adjustable hinge, the maximum opening angle can be adjusted to fit different requirements.

A hinge is often used to connect a cover with the body of a foldable apparatus. There are many foldable mobile phones using hinges to connect their bodies and covers. A foldable mobile phone usually has a smaller volume than others not foldable.
In the prior art, the maximum opening angle, defined by the cover and the body, is not adjustable. According to different demands of various users, for example, different users having different facial sizes, an adjustable maximum opening angle is required to accommodate the various users.


Devices, systems, software, and methods for control of light emitting diodes (LEDs) via an LED driver circuit that receives a dimmed AC input signal from a dimmer and generates an output signal to power and dim an LED element. The LED driver circuit comprises a dimmed input sense circuit, a microcontroller, and a power supply circuit. The power supply circuit generates a power supply from the dimmed AC input signal for powering the LED driver circuit. The dimmed input sense circuit detects an incoming duty cycle (Din) of the dimmed AC input signal. The microcontroller stores one or more dimming level parameters, receives the detected incoming duty cycle (Din) from the dimmed input sense circuit, and generates an output duty cycle (Dout) based on the detected incoming duty cycle (Din) and the one or more dimming level parameters. The LED driver circuit generates the output signal using the generated output duty cycle (Dout) for powering the LED element at a generated dimming level.

Technical Field
The present invention relates generally to lighting control. More particularly, the invention relates to devices, systems, software, and methods for control of light emitting diodes (LEDs).
Background Art
Increasingly, light emitting diodes (LEDs) are providing lighting to commercial and residential structures. These LED lamps and fixtures provide many benefits over conventional lighting technologies, such as higher efficiency, increased lifetime, and relatively safer materials.
An LED driver is an electrical device that regulates power to the LED. LED drivers receive line voltages and convert them to the low voltages typically required by LEDs. There are many types of LED drivers. LED drivers may be internal or external to the LED lamp or fixture and may supply either a constant voltage or a constant current to the lamp or fixture. Certain drivers allow dimming of LEDs, thereby providing a range of lighting levels as well as energy saving opportunities and increased lifetime of the LED.
Traditional phase controlled two-wire LED drivers receive a phase controlled dimmed signal from a dimmer and dim the LED lamps using a dimming scheme based on inhibiting the LED power supply. The lower incoming root mean square (RMS) power is used as raw power delivery that is directly translated to the outbound power delivered into the LED element. In other implementations, a pulse width modulation (PWM) circuitry is included at the front end of the LED driver that applies pulse width modulation directly to the incoming phase controlled dimmed signal and feeds that to the LED element. These implementations, while inexpensive, create several problems.
The power delivered into the LED element is inconsistent causing inconsistent light output and dimming levels. At very low dimming levels, this inconsistency will cause the power supply of the LED driver to sometimes turn on, and at other times turn off. If the power supply is turned off, there will be a period of time where the light will be visibly out. This may cause the LEDs to experience undesired behaviors, such as perceivable flickering or even "dropout" periods. The LEDs may also "pop on" because of this power supply design. Additionally, the LEDs may be at their max brightness well before full power is delivered to them.
Further, dimming LEDs in this manner causes a non-linear relationship between intended brightness and actual LED lumen output. Particularly, in practice the incoming phase controlled dimmed signal is not a perfect sine wave. The wave line suffers from noise that may cause significant fluctuation in voltage levels. At very low dimming levels, and thereby low voltage levels, the noise may cause the LED to turn on at a much lower voltage level than intended. This scheme also produces instability back towards zero cross circuitry. The noise may cause the wave to cross zero voltage at multiple points. In determining the zero cross, the wrong zero cross point may be used, causing a shift in the time cycle. Even a small shift may cause instability in dimming levels, resulting in unwanted flickering.
Accordingly, there is now a need for improved drivers of LED lamps.
Additionally, replacement or reprogramming of constant current LED controls is inconvenient due to configuration requirements. Constant current LED drivers need to be tailored specifically to the LED element to which they are attached. This configuration is typically done one of three ways. LED drivers may be factory configured by ordering them specifically with their current rating. LED drivers may be software programmable at the fixture manufacturer. Lastly, a resistor may be placed on a set of jumpers to configure the current levels.
There is also an issue of LED driver failures in the field. Digital Addressable Lighting Interface (DALI) LED drivers (and ballasts) are soft-addressed, which means that replacement necessitates a commissioning agent to readdress the new device. This is inconvenient and costly to users.
Therefore, there is now a need for improved configuration of LED drivers.

Light emitting diode driver and method of controlling thereof having a dimmed input sense circuit


In injection of steam, gas, liquid or a powdered or granulate product into a fluid in an injection apparatus having a substantially disc-shaped rotor (53), a product inlet (50) and a central product outlet (57), the injection is carried out in an annular injection zone above the disc-shaped rotor (53) at a distance from both the circumference and the center of the rotor (53). The fluid product which may be a liquid with considerable variation of dry solids content and viscosity is exposed to a radial displacement effect as well as a tangential dispersion effect.

1. Field of the Invention
The invention relates to a method of injecting a product into a first fluid, whereby in an injection apparatus having a substantially disc-shaped rotor, a radial displacement effect is imparted to the first fluid, said product being injected into a limited intermediate zone above the disc-shaped rotor displaced from both the center and the circumference of the rotor, in which zone the first fluid is exposed to a tangential dispersion effect in addition to said displacement effect.
2. Description of the Related Art
Such an injection method is known from published international patent application WO 94/13395.
Without in any manner being restricted thereto, the method according to the invention has substantial fields of application in, partly, heat treatment of liquids by injection of steam. For example, bactericidal UHT treatment of milk products or pregelatinization of starch products, partial injection of gases, for example CO.sub.2 or nitrogen into such liquids which are subsequently to be spray dried with the aim of reducing the density of a powder product obtained by the spray drying, partial injection of a liquid, for example water, into certain fatty or oily products with a view to reduction of the fat content and partly mixing of a solid product in powder or granulate form into a liquid.
In connection with the spray drying of food products, for example milk products or fruit juice, it is known from U.S. Pat. Nos. 3,185,580 and 3,222,193 to inject a gas directly into an elongated mixing pipe through which the liquid starting material flows before supply to an atomizer in the spray drying apparatus. This type of gas injection is not suitable for heat treatment at higher temperatures, as it will inevitably lead to burning. Actually, the above patents also direct that a heat treatment of the product, for example for pasteurization purposes, be made in a conventional preheater.
U.S. Pat. No. 3,182,975 describes an apparatus for heat treatment of milk products at an increased temperature after prior preheating by injection of steam into a mixing chamber to which the product to be treated is supplied. Steam injection is carried out by means of a propeller-like rotor with perforated tubular blades where the steam extravasates on the back of the rotor blades seen in the direction of rotation at a relatively low pressure, whereby the pressure is increased through the mechanical influence from the rotation of the rotor. The intention is to obtain a rapid heating without burning.
SU patent specification No. 578046 describes another method of heat treatment of milk products where the product is also supplied to a mixing chamber by a propeller-like rotor. In the '046 specification the steam supply is made via a distributor system with annular distributing conduits arranged concentrically in relation to the rotor and controlled by means of a valve arrangement so that the steam in the central area of the chamber is supplied at a relatively low temperature and pressure, and in the peripheral area at a substantially increased temperature and pressure. The intention is to obtain a very rapid heating to sterilization level after a preheating in the central area. In this construction, however, the strong heat influence at the periphery involves a considerable risk of burning.
It is known from US patent specification No. 4,479,908 to inject gas into a fluid product of a higher density by a method in which a strong turbulence and high flow velocity are imparted to the fluid product by passing it through a conduit part with a curved wall in connection with a constricted flow section where the gas injection takes place through an adjustable nozzle. According to the patent, the method may also be used for heat treatment of milk products by injection of steam at a temperature of about 170.degree. C.
CH patent specification No. 531363 describes an apparatus for mixing a liquid raw material with a gas, for example with a view to foaming. Mixing takes place in a mixing chamber by means of a rotor disc with projecting teeth moving between stationary teeth in a surrounding stator part, the rotor disc performing an eccentric circulatory movement about the axis of the stator frame.
Similar embodiments of mixing heads with a rotor provided with teeth engaging with teeth in a stator system where the sets of teeth may be arranged in several steps mutually displaced in the radial and axial directions are known from DE patent No. 3127684, EP patent application No. 0253139 and published international patent application No. WO 91/07221.
Whereas, in the two latter mixing methods the supply of the fluid product to be treated, and the injection of gas take place at the same place in the mixing chamber, preferably in its central part, the method disclosed in DE-C-3127684 provides for injection of the gas into a working space displaced from the inlet and outlet and delimited by projecting toothed rims from the rotor and stator, respectively.

Method for injecting a product into a fluid, and an apparatus for carrying out the method


A gas/air mixer for injecting gas into the intake air stream of an internal cumbustion engine using a combination of radial holes and radial tubes located around the perimeter of an air flow passage. The gas/air mixer includes an intake air passage which has a combination of radial holes and radial tubes arranged so that the gas is injected into the air stream. The gas passage contains gas which is at a higher pressure than the intake air. The gas flows around an annulus which distributes the gas to all the radial holes and radial tubes. The size of the intake air passage, the number and size of the radial holes, and the number, size and length of the radial tubes can be varied in any combination to achieve adequate gas/air mixing for the particular engine application. This combination can even include a device that contains all radial holes or all radial tubes. The distance that the gas is injected into the air stream is small at the radial holes and larger at the radial tubes.

As different types of fuel systems are being developed to enhance the efficiency of internal combustion engines and allow for cleaner operation, manufactures are challenged to incorporate these new and improved fuel systems into an engine having a simplified design to minimize cost and complexity. One element that directly effects the efficiency at which an internal combustion engine operates is the device which controls the mixture of gas and air being fed into the engine for combustion. A design which is easy to manufacture yet meets or exceeds industry standards for gas fueled engines is currently sought by engine manufacturers.
Many different designs of gas/fuel mixers have been developed in order to enhance fuel efficiency. For example, U.S. Pat. No. 5,058,625 to Kaiser et al. discloses a valve for the intermittent introduction of fuel wherein the feeding means for supply fuel comprises inflow conduits extending into an intake passage and controlled by a rotating valve means which intermittently opens and closes the inflow conduits. Gas/air mixers such as those disclosed in Kaiser, however, are very complex and have different moving parts which could breakdown, increase the cost of repair and cause undesirable downtime. Moreover, the device disclosed in Kaiser does not appear to provide a structure that uniformly mixes gas with intake air. A non-uniform mixture could undesirably effect combustion.
A more simpler gas/air mixer design is shown in U.S. Pat. No. 5,150,690 to Carter et al. This design includes a flow control system having a gas-air mixer located in an intake air duct with a fuel diffuser tube extending across the intake air duct. The fuel diffuser tube has a plurality of openings through which the supplied fuel mixes with the air being drawn into the engine. This design, however, suffers from a similar deficiency discussed above with respect to Kaiser. Although Carter et al. discloses a gas/air mixer having a simpler design than that illustrated in Kaiser, the fuel diffuser tube extends across the center of the intake air duct, resulting in fuel being distributed only to the center of the air flow path which could affect the uniformity of the gas/air mixture at time of combustion.
An improved gas/air mixer design which appears to provide greater uniformity than the references discussed above is found in U.S. Pat. No. 4,872,440 to Green. This reference discloses an air/fuel mixing device for an internal combustion engine wherein the feeding means comprises circular apertures in an annular gas feeding device. The air/fuel mixer design of Green, however, is very complex in that the device has many different parts, some movable, which again creates a greater likelihood of breakdown resulting in costly repair and downtime. Furthermore, the complexity of the device increases manufacturing costs of the gas/air mixer and ultimately, the internal combustion engine.
A gas/air mixing device which appears to overcome the noted deficiencies of the above references is disclosed in U.S. Pat. No. 4,991,561 to Gerassimov et al. This reference is directed to a gas-air mixer including an inlet and outlet diffuser connected by a collar having uniformly shaped feeding channels which terminate in an annular channel around the diffusers connected to a gas supply. The feeding channels for the gas supplied through the annular channel are disclosed as slots which may be widened or narrowed to control the amount of gas mixed with the air in the inlet diffuser. Although Gerassimov et al. appears to disclose a gas/air mixer having greater simplicity and possibly greater gas/air uniformity than the patents discussed above, the reference includes moving parts which increase manufacturing costs and decreases the reliability of the device.
The inventors have recognized the need for a device having a simplistic design that improves the gas/air mixture by increasing its uniformity. In essence, increased uniformity results in optimal combustion and overall efficiency of the internal combustion engine. Moreover, a gas/air mixer having a simple design reduces manufacturing costs, decreases the chance of breakdown and prevents unnecessary downtime.


The present invention relates to nitrile rubber polymers having lower molecular weights and narrower molecular weight distributions than those known in the art. The present invention also relates to a process for the manufacture of said nitrile rubber and the use of said nitrile rubber for the manufacture of shaped articles.

Nitrile rubber (NBR), a co-polymer comprising at least one conjugated diene, at least one unsaturated nitrile and optionally further comonomers, is a specialty rubber, which has good chemical resistance, and excellent oil resistance. Coupled with the high level of mechanical properties of the rubber (in particular the high resistance to abrasion) it is not surprising that NBR has found widespread use in the automotive (seals, hoses, bearing pads), electrical (cable sheathing), mechanical engineering (wheels, rollers) and footwear industries, amongst others.
Commercially available NBR is manufacture by emulsion polymerization. The monomers are emulsified in water, a free radical-generating catalyst is added and the mixture is agitated whilst a constant temperature is maintained. After the desired degree of polymerization is reached, a shortstop and stabilizers are added to the reaction system causing termination of the polymerization process. Generally, NBR obtained by this process has a Mooney viscosity in the range of from 30 to 90, an Mw in the range of from 250,000 to 350,000, an Mn in the range of from 80,000 to 150,000 and a polydispersity index greater than 3.2.
In addition, so-called "liquid NBR" having a very low Mooney viscosity and a low molecular weight can be produced be adding the shortstop agent early in the reaction process. As in the case of regular NBR, the resulting liquid NBR has a polydispersity greater than 3.0.
Karl Ziegler's discovery of the high effectiveness of certain metal salts, in combination with main group alkylating agents, to promote olefin polymerization under mild conditions has had a significant impact on chemical research and production to date. It was discovered early on that some "Ziegler-type" catalysts not only promote the proposed coordination-insertion mechanism but also effect an entirely different chemical process, that is the mutual exchange (or metathesis) reaction of alkenes according to a scheme as shown in FIG. 1.
Acyclic diene metathesis (or ADMET) is catalyzed by a great variety of transition metal complexes as well as non-metallic systems. Heterogeneous catalyst systems based on metal oxides, sulfides or metal salts were originally used for the metathesis of olefins. However, the limited stability (especially towards hetero-substituents) and the lack of selectivity resulting from the numerous active sites and side reactions are major drawbacks of the heterogeneous systems.
Homogeneous systems have also been devised and used to effect olefin metathesis. These systems offer significant activity and control advantages over the heterogeneous catalyst systems. For example, certain Rhodium based complexes are effective catalysts for the metathesis of electron-rich olefins.
The discovery that certain metal-alkylidene complexes are capable of catalyzing the metathesis of olefins triggered the development of a new generation of well-defined, highly active, single-site catalysts. Amongst these, Bis-(tricyclohexylphosphine)-benzylidene ruthenium dichloride (commonly know as Grubb's catalyst) has been widely used, due to its remarkable insensitivity to air and moisture and high tolerance towards various functional groups. Unlike the molybdenum-based metathesis catalysts, this ruthenium carbene catalyst is stable to acids, alcohols, aldehydes and quaternary amine salts and can be used in a variety of solvents (C6H6, CH2Cl2, THF, t-BuOH).
The use of transition-metal catalyzed alkene metathesis has since enjoyed increasing attention as a synthetic method. The most commonly used catalysts are based on Mo, W and Ru. Research efforts have been mainly focused on the synthesis of small molecules, but the application of olefin metathesis to polymer synthesis has allowed the preparation of new polymeric material with unprecedented properties (such as highly stereoregular poly-norbornadiene).
The utilization of olefin metathesis as a means to produce low molecular weight compounds from unsaturated elastomers has received growing interest. The principle for the molecular weight reduction of unsaturated polymers is shown in FIG. 2. The use of an appropriate catalyst allows the cross-metathesis of the unsaturation of the polymer with the co-olefin. The end result is the cleavage of the polymer chain at the unsaturation sites and the generation of polymer fragments having lower molecular weights. In addition, another effect of this process is the "homogenizing" of the polymer chain lengths, resulting in a reduction of the polydispersity. From an application and processing stand point, a narrow molecular weight distribution of the raw polymer results in improved physical properties of the vulcanized rubber, while the lower molecular weight provides good processing behavior.
The so-called "depolymerization" of copolymers of 1,3-butadiene with a variety of co-monomers (styrene, propene, divinylbenzene and ethylvinylbenzene, acrylonitrile, vinyltrimethylsilane and divinyldimethylsilane) in the presence of classical Mo and W catalyst system has been investigated. Similarly, the degradation of a nitrile rubber using WCl6 and SnMe4 or PhC≡CH co-catalyst was reported in 1988. However, the focus of such research was to produce only low molecular fragments, which could be characterized by conventional chemical means and contains no teaching with respect to the preparation of low molecular weight nitrile rubber polymers. Furthermore, such processes are non-controlled and produce a wide range of products.
The catalytic depolymerization of 1,4-polybutadiene in the presence of substituted olefins or ethylene (as chain transfer agents) in the presence of well-defined Grubb's or Schrock's catalysts is also possible. The use of Molybdenum or Tungsten compounds of the general structural formula {M(═NR1)(OR2)2(═CHR); M═Mo, W} to produce low molecular weight polymers or oligomers from gelled polymers containing internal unsaturation along the polymer backbone was claimed in U.S. Pat. No. 5,446,102. Again, however, the process disclosed is non-controlled, and there is no teaching with respect to the preparation of low molecular weight nitrile rubber polymers.

This patent is subject to a terminal disclaimer.


A temporal protection layer is employed to a wafer backside for use of micro-electro-mechanical systems (MEMS). The formation of the temporal protection layer prevents the wafer backside from scratch in process of transferring system for IC manufacturers. With regard to low cost and easy forming and removing, an oxide layer is used as the temporal protection layer. The throughput and yield rate of the wafer production are improved by the use of the temporal protection layer.

1. Field of the Invention
The present invention generally relates to a method for protecting the backside of a wafer in process of transferring for IC manufacturers. In particular, the present invention relates to a method for protecting the backside of a wafer with micro-electro-mechanical systems (MEMS) thereon.
2. Description of the Prior Art
In common IC fabrications (fabs), the front-side or topside of a wafer is mainly concerned due to all IC devices and elements constructed on the topside of the wafer. Thereof the wafer uses to be delivered with touching of backside of wafer transfer systems, for example, robot, picker and etc. In another word, the process of fabricating IC will be continued even if the backside of the wafer is scratched slightly by an operator and wafer transfer systems. But it is necessary that there is no breakdown of the wafer due to scratches even though after high temperature process, and damage the IC devices on and within the wafer.
Oppositely, both topside and backside of a MEMS (micro-electro-mechanical systems) wafer are concerned on application. There may be IC devices, micro-electro elements or micro-mechanical elements on the both sides on a MEMS wafer. On other applications, there may be other devices assembled with the backside of the MEMS wafer, such as ink jet print-head chips of the MEMS wafer. Accordingly, the backside of the MEMS wafer should be regarded as important as the topside of the MEMS wafer. Unfortunately, the most of transfer wafer systems in IC fabs are in touch with the backside of MEMS wafers when delivering MEMS wafers as well as those general wafers, so as to result in the damage or scratch on the backside of MEMS wafer. The damaged and scratched MEMS wafers make process of fabricating MEMS fail then the wafers must to be scraped. There is much lost of throughput and yield rate of MEMS products due to these issues.

Processing method for protection of backside of a wafer


One feature pertains to a method for implementing a physically unclonable function (PUF). The method includes providing an array of magnetoresistive random access memory (MRAM) cells, where the MRAM cells are each configured to represent one of a first logical state and a second logical state. The array of MRAM cells are un-annealed and free from exposure to an external magnetic field oriented in a direction configured to initialize the MRAM cells to a single logical state of the first and second logical states. Consequently, each MRAM cell has a random initial logical state of the first and second logical states. The method further includes sending a challenge to the MRAM cell array that reads logical states of select MRAM cells of the array, and obtaining a response to the challenge from the MRAM cell array that includes the logical states of the selected MRAM cells of the array.

1. Field
Various features relate to physically unclonable functions (PUFs), and in particular to PUFs based on the initial logic states of an array of magnetoresistive random-access memory (MRAM) cells.
2. Background
An on-chip PUF is a chip-unique challenge-response mechanism exploiting manufacturing process variations inside integrated circuits (ICs). When a physical stimulus (i.e., challenge) is applied to the PUF, the PUF generates a response in an unpredictable but repeatable way due to the complex interaction of the stimulus with the physical microstructure of the device employing the PUF. This exact microstructure depends on physical factors introduced during manufacture of the device employing the PUF, which are unpredictable. The PUF's "unclonability" means that each device employing the PUF has a unique and unpredictable way of mapping challenges to responses, even if one device is manufactured with the same process as another seemingly identical device. Thus, it is practically infeasible to construct a PUF with the same challenge-response behavior as another device's PUF because exact control over the manufacturing process is infeasible.
MRAM is a non-volatile random-access memory that, unlike conventional RAM, stores data not as electric charge but instead as electron spin within magnetic storage elements. FIG. 1, comprising FIGS. 1A and 1B, illustrates a schematic diagram of at least a portion of a spin transfer torque (STT) MRAM circuit cell 100 found in the prior art. The MRAM cell 100 shown in FIGS. 1A and 1B is an example of an "in-plane" STT MRAM cell. The MRAM cell 100 includes a free layer 102, a reference layer (also known as "pinned reference layer") 104, a tunnel junction layer 106, and an anti-ferromagnetic (AFM) pinning layer 108. The free layer 102 is a ferromagnetic layer whose magnetic polarity is not fixed but is instead free to change direction in response to an external magnetic field (not shown). The reference layer 104 includes a first ferromagnetic layer 105 and a second ferromagnetic layer 107 that have opposite magnetic polarities. By contrast to the free layer 102, the reference layer 104 has a magnetic polarity that is fixed such that the magnetic polarities of the first and second ferromagnetic layers 105, 107 do not change direction in the presence of the aforementioned external magnetic field. The AFM pinning layer 108 is an anti-ferromagnetic layer that controls the magnetic polarities of the reference layer 106.
Situated in between the free layer 102 and the reference layer's first ferromagnetic layer 104 is the tunnel junction layer 106. The tunnel junction layer 106 is made of a very thin insulating material, such as magnesium oxide (MgO). The tunnel junction layer 106 is so thin that electrons may actually flow through (e.g., tunnel through) the layer 106 despite the layer 106 being an insulator. The magnetic polarity direction of the free layer 102 relative to the first ferromagnetic layer 105 (e.g., parallel to each other or antiparallel to each other) represents one of two different logical data bit states (e.g. data bit "1" or data bit "0"). In the example illustrated in FIG. 1A, the parallel orientation is shown with the free layer 102 having a magnetic polarity direction that is the same as the magnetic polarity direction of the first ferromagnetic layer 105. By contrast, FIG. 1B illustrates the antiparallel orientation with the free layer 102 having a magnetic polarity direction that is the opposite of the magnetic polarity direction of the first ferromagnetic layer 105.
A signal line voltage VSL applied to the MRAM cell 100 controls the flow of current ISL through the MRAM cell 100. For example, applying a voltage VSL that exceeds the transition voltage VT of the cell 100 causes the current ISL to flow in the direction shown in FIG. 1A and also causes the magnetic polarity of the free layer 102 to change direction into a parallel orientation. That is, the magnetic polarity direction of the free layer 102 is parallel to the magnetic polarity of the first ferromagnetic layer 105. To change the magnetic polarity direction of the free layer 102 back to an antiparallel orientation, a signal line voltage VSL that exceeds VT is applied in the orientation shown in FIG. 1B to cause the current ISL to flow in the opposite direction. In one example, the parallel state may be considered the first logical state representing a data bit "0," and the antiparallel state may be considered the second logical state representing a data bit "1."
FIG. 2 shows a top perspective schematic view of a portion of the in-plane MRAM cell 100 found in the prior art that is undergoing a manufacturing process step. During manufacture of the cell 100, an annealing process step is performed that initializes all of the MRAM cells 100 in the MRAM cell array (array not shown) to a first logical state, e.g., state "1." Specifically, an external magnetic field along the MRAM cell's "easy axis" is applied during the annealing process step to initialize the MRAM cells 100 of the array. The "easy axis" is the preferred/relaxed direction of an MRAM cell free layer's magnetic polarity. For example, the easy axis of the in-plane MRAM cell 100 shown in FIG. 2 is the free layer's 102 long axis 203, which is parallel to the x-axis labeled in FIG. 2. Application of the annealing process step in the presence of the external magnetic field causes all of the MRAM cells 100 in the array to have a homogenous state (e.g., all in the first logical "1" state) prior to any logical state transition (as described with reference to FIGS. 1A and 1B) that may occur during typical use.
FIG. 3 shows a top perspective schematic view of a portion of a perpendicular MRAM cell 300 found in the prior art. Like the in-plane MRAM cell 100 shown in FIGS. 1A and 1B, the perpendicular MRAM cell 300 of FIG. 3 includes a free layer 302 and a reference layer 304. The relative orientation (parallel or antiparallel) of the magnetic polarity of the free layer 302 with respect to the reference layer 304 dictates the logical state (e.g., logical "0" or "1") of the MRAM cell 300. The magnetic polarities of the perpendicular MRAM cell's 300 free layer 302 and reference layer 304 are typically oriented along a direction parallel to its perpendicular axis 303 (e.g., parallel to the y-axis shown in FIG. 3). The perpendicular MRAM cell 300 shown is similarly undergoing an annealing process that initializes the MRAM cell 300 (and all other MRAM cells in the array (array not shown)) to a first logical state, e.g., state "1." An external magnetic field is applied during the annealing process step along the MRAM cell's 300 easy axis to initialize the MRAM cells 300 of the array. In the example shown in FIG. 3, the easy axis of the perpendicular MRAM cell 300 is the perpendicular axis 303, which is parallel to the y-axis shown in FIG. 3. Application of the annealing process step in the presence of the external magnetic field causes all of the MRAM cells 300 in the array to have a homogenous state (e.g., all in the first logical "1" state) prior to any logical state transition (as described with reference to FIGS. 1A and 1B) that may occur during typical use.
There exists a need for methods and apparatuses that implement PUFs based on MRAM cells. Specifically, there exists a need to provide methods and apparatuses that may implement PUFs based on the initial logic states of MRAM cell arrays. Such MRAM based PUFs may provide a secure means to uniquely identify electronic devices, such as integrated circuits, and/or provide secure cryptographic keys for cryptographic security algorithms.

Physically unclonable function based on the initial logical state of magnetoresistive random-access memory


A method for transferring data, by establishing network links between a private and a public network. Each link is associated with a respective unique public-network-address. Each session of one or more data packets within the private network is allocated an extended-private-address, the private network being adapted to transfer each data packet in a respective session using at least part of the extended-private-address as an identifying private-network-address. For each session the extended-private-address is translated to an extended-public-address, which includes one of the unique public-network-addresses. The data packets of each session are conveyed between the private and public networks via the link associated with the public-network-address of the respective session, and are transmitted within the public network using at least part of the extended-public-address as an identifying public-network-address.

Data networks which are coupled to each other frequently require implementation of network address translation (NAT) as the data transfers between networks. Address translation is necessary when all addresses within the coupled networks are not unique, and "Traditional NAT" is an accepted protocol in the art which describes translation of network addresses. The protocol combines and updates earlier protocols and is described by Srisuresh et al. in Request for Comments (RFC) 3022 of the Internet Engineering Task Force (IETF) Network Working Group (January, 2001), which is incorporated herein by reference. Traditional NAT provides a mechanism for transparently connecting a private network having private addresses to an external public network with globally unique registered addresses.
FIG. 1 is a block diagram that schematically illustrates operation of RFC 3022, as is known in the art. A private network 22 is coupled via an address translator 24 to an external public network 26. The coupling from translator 24 to network 26 is via a router 25 in the external network. Address translator 24, which typically comprises software components operating in network 22, translates between internal private addresses of network 22 and unique global addresses suitable for use within network 26. The translation is implemented by translator 24 for data transferring in both directions between the two networks. Traditional NAT translates both Internet Protocol (IP) addresses, and Transmission Control Protocol/User Datagram Protocol (TCP/UDP, referred to collectively as TU) port numbers used by these addresses.
The translation is performed by translator 24 forming a binding between local private addresses and allocated external addresses, the binding being determined when an outgoing data transfer session initiates from a private host. (Data transfer sessions are described in more detail below.) The binding takes the form of a mapping between a first ordered pair (source private IP address, source private TU port) and a second ordered pair (assigned external IP address, assigned external TU port). The first ordered pair is effectively a single extended address which is used for data transfer/routing within network 22. The second pair is effectively a single extended address used for data transfer/routing in network 26. The binding is maintained in a table generated by translator 24, and is used for incoming data transfer to the private host, where the ordered pairs are used to generate the destination addresses.
Using address translation allows private network 22 to continue using its private addresses, while enabling the private network to communicate with an external network, where the private addresses might cause conflicts if not translated.
Srisuresh et al., in RFC 2663 of the IETF Network Working Group (August, 1999), which is incorporated herein by reference, clarifies terms used in NAT, and also enlarges on translation processes. RFC 2663 refers to Basic NAT and Network Address Port Translation (NAPT) protocols, which are incorporated into and superceded by Traditional NAT, described above. In section 2.3 of RFC 2663, a session is defined as the set of traffic that is managed as a unit for translation. Traffic of a session is composed of a sequence of one or more packets, and TCP/UDP sessions are uniquely identified by the ordered tuple of (source IP address, source TCP/UDP port, destination IP address, destination TCP/UDP port).
As explained in section 2.4, servers "listen" for incoming connections, typically on the set of port numbers 0-1023. Typically, clients trying to initiate a connection use a source TU port number in the range 1024-65535. However, these ranges are not universally accepted, and instances where a client initiates a connection using a source port number in the range 0-1023, and/or where servers listen on port numbers in the range 1024-65535, are known.
FIG. 2 is a schematic diagram showing headers of TCP/IP and UDP/IP data packets, as are known in the art. A TCP/IP packet header comprises an IP header 27 and a TCP header 28. The IP header comprises source and destination addresses. The TCP header comprises source and destination ports, as well as other fields including a flags field and a checksum field. The flags field includes ACK, SYN, RST, and FIN bits. These are respectively used as an acknowledgement of receipt of a packet, a synchronization bit used at the initiation of a connection, a reset bit indicating that a receiver should delete the connection without further interaction, and a control bit which indicates that a sender will send no more data. The checksum field is used as a check on correct data receipt, and is a sum evaluating all data of a packet, including the IP and TCP headers.
A UDP/IP packet header comprises the IP header 27 and a UDP header 30. The UDP header comprises source and destination ports, and a checksum field, which is substantially similar to the checksum field of the TCP header.
Sections 2.5 and 2.6 of RFC 2663 respectively describe methods for determining a start and a finish of a specific session of data packet transfer. A TCP session start can be recognized by the presence of the SYN bit and absence of the ACK bit in a received data packet. "The end of a TCP session can be detected when FIN is acknowledged by both halves of the session, or when either half receives a packet with an RST bit in the TCP flags field." Once these end sections have been detected, RFC 2663 states that, to cover retransmissions due to dropped packets, ". . . a session can be assumed to have been terminated . . . after a period of 4 minutes subsequent to this detection." RFC 2663 also advocates using garbage collection, as a means of detecting when a TCP connection has terminated without the translation device (translator 24 of FIG. 1) being aware of the termination.
For non-TCP sessions, including UDP sessions, RFC 2663 states "there is no deterministic way of recognizing the start of a UDP based session or any non-TCP session. A heuristic approach would be to assume the first packet with hitherto nonexistent session parameters as constituting the start of a new session . . . . In the case of UDP-based sessions, there is no single way to determine when a session ends."
RFC 2663 also suggests using timing to terminate sessions, e.g. by assuming that "TCP sessions that have not been used for say, 24 hours, and non-TCP sessions that have not been used for a couple of minutes, are terminated." Alternatively or additionally, "Another way to handle session terminations is to timestamp entries and keep them as long as possible and retire the longest idle session when it becomes necessary."
In section 4.1.2 of RFC 2663, the authors state that the Basic NAT and NAPT protocols can be combined so that a pool of external addresses are used in conjunction with port translation.
In order to increase the rate at which communications are transferred between points, it is known in the art to use multiple links in parallel. For example, in place of the point-to-point protocol (PPP) that provides a single link for digital packet communications between computers, the PPP Multilink Protocol may be used. This protocol is described by Sklower et al., in RFC 1990 of the IETF Network Working Group (August, 1996), which is incorporated herein by reference.
FIG. 3 is a block diagram that schematically illustrates operation of RFC 1990, as is known in the art. As for the PPP protocol, two software components, a multilink manager 33 and a multilink manager peer 34, are required. The multilink connection between the two components is set up by manager 33 transmitting a Link Control Protocol (LCP) request to manager peer 34. Once manager peer 34 acknowledges that it is able to accept the multilink connection, transfer of data packets via the parallel multilinks is possible. The transfer occurs by manager 33 fragmenting data into sequenced packets, which are then sent to peer 34, where the sequenced packets are reassembled into the original data. The PPP Multilink Protocol provides a framework for tracking the data fragments sent on each link of the multilink, and for insuring that the fragments are reassembled in their correct order at manager peer 34.
FIG. 4 is a block diagram that schematically illustrates combination of the processes of address translation and multilink transfer, as is known in the art. In transferring data from private network 22 to external network 26, address translation is first performed in translator 24, and then the data is transferred via multilink manager 33, after the latter has set up a multilink with multilink manager peer 34.

Extended internet protocol network address translation system


An inhaler or container holster which is strapped around a user's wrist and ready to use, End hook and loop fasteners on a wrist band hold an inhaler band to the user's wrist band while a second set of hook and loop end fasteners on an inhaler band hold the inhaler, The wrist band is generally perpendicular to the inhaler band which either totally or partially encircles and holds the canister containing the inhaler. The canister's end segments may be additionally secured to the inhaler band by elastic strap assemblies attached to the inhaler band which loop around the top and bottom of the canister at opposite ends. Ventolin or any other asthma or any other medication may be placed in the inhaler or container.

Persons with respiratory difficulties, such as asthma, often need the use of an inhaler to provide relief from breathing problems. This inhaler with its solution (e.g., Ventolin ) should be readily accessible to the user and is usually carried in one's pocket or purse to insure the same easy accessibility. However, when a person is exercising there may be no pockets in their shorts for the inhaler necessitating its being carried in their sock or hand while attempting to exercise or left with a friend or coach. While these attempts to provide ready inhaler accessibility to exercising asthma suffers have some merit, the present invention provides a better more accessible solution by providing for a wrist held inhaler that can be carried by the user and used without taking the inhaler out of its wrist mount all as more fully described hereafter.