A phacoemulsification tip having a crimped or swaged distal tip. Swaging of the distal end of a phacoemulsification tip produces more efficient cutting during torsional vibration of the tip by increasing the cutting surface area.

This invention relates generally to the field of phacoemulsification and more particularly to torsional phacoemulsification cutting tips.
The human eye in its simplest terms functions to provide vision by transmitting light through a clear outer portion called the cornea, and focusing the image by way of the lens onto the retina. The quality of the focused image depends on many factors including the size and shape of the eye, and the transparency of the cornea and lens.
When age or disease causes the lens to become less transparent, vision deteriorates because of the diminished light which can be transmitted to the retina. This deficiency in the lens of the eye is medically known as a cataract. An accepted treatment for this condition is surgical removal of the lens and replacement of the lens function by an IOL.
In the United States, the majority of cataractous lenses are removed by a surgical technique called phacoemulsification. During this procedure, a thin phacoemulsification cutting tip is inserted into the diseased lens and vibrated ultrasonically. The vibrating cutting tip liquefies or emulsifies the lens so that the lens may be aspirated out of the eye. The diseased lens, once removed, is replaced by an artificial lens.
A typical ultrasonic surgical device suitable for ophthalmic procedures consists of an ultrasonically driven handpiece, an attached cutting tip, and irrigating sleeve and an electronic control console. The handpiece assembly is attached to the control console by an electric cable and flexible tubings. Through the electric cable, the console varies the power level transmitted by the handpiece to the attached cutting tip and the flexible tubings supply irrigation fluid to and draw aspiration fluid from the eye through the handpiece assembly.
The operative part of the handpiece is a centrally located, hollow resonating bar or horn directly attached to a set of piezoelectric crystals. The crystals supply the required ultrasonic vibration needed to drive both the horn and the attached cutting tip during phacoemulsification and are controlled by the console. The crystal/horn assembly is suspended within the hollow body or shell of the handpiece by flexible mountings. The handpiece body terminates in a reduced diameter portion or nosecone at the body's distal end. The nosecone is externally threaded to accept the irrigation sleeve. Likewise, the horn bore is internally threaded at its distal end to receive the external threads of the cutting tip. The irrigation sleeve also has an internally threaded bore that is screwed onto the external threads of the nosecone. The cutting tip is adjusted so that the tip projects only a predetermined amount past the open end of the irrigating sleeve. Ultrasonic handpieces and cutting tips are more fully described in U.S. Pat. Nos. 3,589,363; 4,223,676; 4,246,902; 4,493,694; 4,515,583; 4,589,415; 4,609,368; 4,869,715; 4,922,902; 4,989,583; 5,154,694 and 5,359,996, the entire contents of which are incorporated herein by reference.
In use, the ends of the cutting tip and irrigating sleeve are inserted into a small incision of predetermined width in the cornea, sclera, or other location. The cutting tip is ultrasonically vibrated along its longitudinal axis within the irrigating sleeve by the crystal-driven ultrasonic horn, thereby emulsifying the selected tissue in situ. The hollow bore of the cutting tip communicates with the bore in the horn that in turn communicates with the aspiration line from the handpiece to the console. A reduced pressure or vacuum source in the console draws or aspirates the emulsified tissue from the eye through the open end of the cutting tip, the cutting tip and horn bores and the aspiration line and into a collection device. The aspiration of emulsified tissue is aided by a saline flushing solution or irrigant that is injected into the surgical site through the small annular gap between the inside surface of the irrigating sleeve and the cutting tip.
One phacoemulsification tip that has gained widespread acceptance has a belled or flared distal end. Such a tip is described in U.S. Pat. No. 4,816,018 (Parisi). Such a design allows for larger lens material purchase as well as increased holding force when vacuum is applied to the tip while maintaining a smaller bore in the shaft of the tip. This combination of features increases anterior chamber stability, by reducing sudden outflow from the anterior chamber when the distal end becomes occluded and this occlusion breaks.
Another phacoemulsification tip is an angled or "bent" tip with or without a flared distal end. These tips are described in U.S. Pat. No. 6,039,715 (Mackool), U.S. Pat. No. 5,653,724 (Imonti) and U.S. Pat. No. 5,154,694 (Kelman). These tips have a predominantly straight shaft with the far distal portion of the shaft being bent on an angle. Bent tips are used by a great many surgeons, and are particularly useful when used in conjunction with a oscillatory phacoemulsification handpiece, such as those described in U.S. Pat. No. 6,352,519 (Anis, et al.) and U.S. Pat. No. 6,602,193 (Chon) and commercially available as the NeoSoniX® handpiece from Alcon Laboratories, Inc., Fort Worth, Tex., however; some surgeons are reluctant they feel that due to the proximal location of the bend it is more difficult to judge the position of the proximal cutting edge based on the extrapolation of the sleeved portion of the tip.
The inventors have discovered that swaged phacoemulsification tips are particularly advantageous when used in combination with torsional ultrasound handpiece. Torsional ultrasound handpieces are more fully disclosed in U.S. Pat. No. 6,077,285 (Boukhny). Therefore, a need continues to exist for a swaged phacoemulsification tip.


Disclosed are ophthalmic compositions comprising ketotifen and pharmaceutically acceptable salts thereof, as well as methods for making such compositions.

The present invention describes an autoclavable ophthalmic composition comprising an ophthalmic drug and in particular an ophthalmic drug. The invention further describes a method for stabilizing such compositions and the use of said stabilizers.
Drug safety is a permanent issue in drug regulatory affairs. A recent European regulation requires that a final ophthalmic composition must be autoclaved before use, and consequently, before sale. Autoclaving improves drug safety since the pathogenic germs are killed thereby.
JP 62/277323 describes for example a method for producing eye drops containing ketotifen fumarate, which eye drops might further contain a preservative such as benzalkonium chloride. In order to stabilize such a composition, JP 62/277323 proposes to add a polyvalent alcohol such as a saccharide and other alcohols such as glycerol or propylene glycol. The composition described is not stable if autoclaved.
Therefore the problem to be solved consists of providing in particular an aqueous ophthalmic composition comprising an ophthalmic drug, in particular selected from ketotifen and dexamethasone, which substantially prohibits decomposition when subjected to standard autoclaving conditions.
This problem had unexpectedly been solved by the addition of a stabilizer which is selected from the group consisting of EDTA, Dequest and Desferal. Preference is given to EDTA and Dequest and more particular to EDTA.
Another unexpected finding of the present invention is a synergistic effect, namely the effect of improved preservative efficacy if a preservative is added to said stabilized composition. This means that the amount preservative necessary to ensure shelf life and muti-dose sterility may be reduced very significantly, which in turn may strongly improve ocular tolerability of an addressed ophthalmic composition.
Consequently, the invention relates to an ophthalmic composition in accordance to the main claim. It further relates to the objects of all dependent and independent claims disclosed infra, in particular to a method of stabilizing an ophthalmic drug by adding a particular stabilizer during autoclavation.
According to the invention an ophthalmic composition is advantageously applied topically to the eye, especially in the form of a solution, a suspension or a gel. Such compositions comprise an ophthalmically effective ingredient and in particular ketotifen or dexamethasone, for example, in a range of from approximately 0.000001 to approximately 10.0% by weight, preferably from approximately 0.00001 to approximately 1.0% by weight, or more preferably in the range of from approximately 0.0001 to approximately 0.1% by weight and most preferably in the range of from 0.001 to 0.1% by weight. The dose of the active ingredient may depend on various factors, such as mode of administration, requirement, age and/or individual condition.
Other customary pharmaceutically acceptable excipients and additives known to the person skilled in the art are used in corresponding ophthalmic composition. Such compositions are prepared in a manner known per se, for example by mixing an active ingredient with the corresponding excipients and/or additives to form corresponding ophthalmic compositions.
Carriers used in accordance to the present invention are typically suitable for topical or general administration, and are for example water, mixtures of water and water-miscible solvents, such as C1- to C7-alkanols, vegetable oils or mineral oils comprising from 0.5 to 5% by weight hydroxyethylcellulose, ethyl oleate, carboxymethyl-cellulose, polyvinyl-pyrrolidone and other non-toxic water-soluble polymers for ophthalmic uses, such as, for example, cellulose derivatives, such as methylcellulose, alkali metal salts of carboxy-methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, methylhydroxypropyl-cellulose, hydroxypropylcellulose, chitosan and scleroglucan, acrylates or methacrylates, such as salts of polyacrylic acid or ethyl acrylate, polyacrylamides, natural products, such as gelatin, alginates, pectins, tragacanth, karaya gum, xanthan gum, carrageenin, agar and acacia, starch derivatives, such as starch acetate and hydroxypropyl starch, and also other synthetic products, such as poloxamers, e.g. Poloxamer F127, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether, polyethylene oxide, preferably cross-linked polyacrylic acid, such as neutral Carbopol, or mixtures of those polymers. Preferred carriers are water, cellulose derivatives, such as methylcellulose, alkali metal salts of carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, methylhydroxypropylcellulose and hydroxypropylcellulose, neutral Carbopol, or mixtures thereof. The concentration of the carrier is, for example, from 0.1 to 100000 times the concentration of the active ingredient.
Solubilizers may be used for an ophthalmic composition of the present invention as well, and are, for example, tyloxapol, fatty acid glycerol polyethylene glycol esters, fatty acid polyethylene glycol esters, polyethylene glycols, glycerol ethers, polysorbate 20, polysorbate 80 or mixtures of those compounds. A specific example of an especially preferred solubilizer is a reaction product of castor oil and ethylene oxide, for example the commercial products Cremophor EL(copyright) or Cremophor RH40(copyright). Reaction products of castor oil and ethylene oxide have proved to be particularly good solubilizers that are tolerated extremely well by the eye. Another preferred solubilizer is tyloxapol. The concentration used depends especially on the concentration of the active ingredient. The amount added is typically sufficient to solubilize the active ingredient. For example, the concentration of the solubilizer is from 0.1 to 5000 times the concentration of the active ingredient.
Buffers, tonicity enhancing agents and preservatives different from quaternary ammonium salts may be used in an ophthalmic composition of the present invention too.
Examples of buffer substances are acetate, ascorbate, borate, hydrogen carbonate/carbonate, citrate, gluconate, lactate, phosphate, propionate and TRIS (tromethamine) buffers. Tromethamine and borate buffer are preferred buffers. The amount of buffer substance added is, for example, that necessary to ensure and maintain a physiologically tolerable pH range. The pH range is typically in the range of from 4 to 9, preferably from 4.5 to 8.5 and more preferably from 5.0 to 8.2.
Tonicity enhancing agents may also be present in an above composition and are, for example of ionic and/or non-ionic type. Examples of ionic tonicity enhancers are e.g. alkali metal or earth metal halides, such as, for example, CaCl2, KBr, KCl, LiCl, Nal, NaBr or NaCl, Na2SO4 or boric acid. Non-ionic tonicity enhancing agents are, for example, urea, glycerol, sorbitol, mannitol, propylene glycol, or dextrose. Typically, a sufficient amount of tonicity enhancing agent may be added to impart to an above ophthalmic composition an osmolality of approximately from 50 to 1000 mOsmol, preferred from 100 to 400 mOsmol, more preferred from 200 to 400 mOsmol and even more preferred from 250 to 350 mOsmol.
Preservatives may be present in an above composition too. A preservative may typically be selected from a quaternary ammonium compound such as benzalkonium chloride, benzoxonium chloride or the like. Benzalkonium chloride is better described as: N-benzyl-Nxe2x80x94(C8-C18alkyl)-N,N-dimethylammonium chloride. Examples of preservatives different from quaternary ammonium salts are alkyl-mercury salts of thiosalicylic acid, such as, for example, thiomersal, phenylmercuric nitrate, phenylmercuric acetate or phenylmercuric borate, parabens, such as, for example, methylparaben or propylparaben, alcohols, such as, for example, chlorobutanol, benzyl alcohol or phenyl ethanol, guanidine derivatives, such as, for example, chlorohexidine or polyhexamethylene biguanide, sodium perborate, Germal(copyright)II or sorbic acid. Preferred preservatives are quaternary ammonium compounds, in particular benzalkonium chloride, alkyl-mercury salts and parabens. Where appropriate, a sufficient amount of preservative is added to the ophthalmic composition to ensure protection against secondary contaminations during use caused by bacteria and fungi.
Another object of the present invention are autoclavable ophthalmic compositions in accordance to the specification and the claims, but with the proviso that the preservative is absent. Such compositions are in particular useful for the so called unidose forms.
An above ophthalmic composition may comprise further non-toxic excipients, such as, for example, emulsifiers, wetting agents or fillers, such as, for example, the polyethylene glycols designated 200, 300, 400 and 600, or Carbowax designated 1000, 1500, 4000, 6000 and 10000. Other excipients that may be used if desired are listed below but they are not intended to limit in any way the scope of the possible excipients. Such excipients are especially antioxidants, such as ascorbic acid, acetylcysteine, cysteine, sodium hydrogen sulfite, butyl-hydroxyanisole, butyl-hydroxytoluene or alpha-tocopherol acetate. The amount and type of excipient added is in accordance with the particular requirements and is generally in the range of from approximately 0.0001 to approximately 90% by weight.
Further excipients may be comprised in an above concerned ophthalmic composition, which may in particular function as a combined stabilizer/solubilizer. Such a combined additional stabilizer/solubilizer is for example a cyclodextrin. A preferred cyclodextrin is in particular selected from the group of xcex1-cyclodextrin, xcex2-cyclodextrin, xcex3-cyclodextrin, hydroxypropyl-xcex2-cyclodextrin, hydroxypropyl-xcex3-cyclodextrin, dimethyl-xcex2-cyclodextrin and dimethyl-xcex3-cyclodextrin. The amount is generally in the range of from approximately 0.01 to approximately 90% by weight, more preferably in the range of from 0.1-20% by weight.
Alkyl means throughout this invention an alkyl group having up to and including 18, more preferably 12 and even more preferably 7 C-atoms, and is either a linear or a branched alkyl group.
Examples for alkyl are methyl, ethyl, propyl, butyl, iso-propyl, t-butyl, neo-pentyl, octyl or dodecyl.
The term weight % used herein refers to the weight % of the total weight of an addressed composition or object.
The above is in particular useful for ophthalmic drugs. Examples of such ophthalmic drugs are antazolin, betaxolol, bupivacaine, carbachol, carteolol, chloramphenicol, chlortetracycline, cromolyn sodium, dexamethasone, dichlorphenamide, dipivefrin, ephedrine, erythromycin, fluoromethalone, indomethacin, ketotifen, levobunolol, levocabastine, lidocaine, lignocaine, lomefloxacin, medrysone, methazolamide, naphazoline, natamycin, neomycin, noradrenaline, ofloxacin, oxybuprocaine, physostigmine, pilocarpine, polymyxin B, prednisolone, scopolamine, sorbinil, sulfacetamide, tamoxifen, tetracaine, tetracycline, timolol, trifluridine, tropicamide, vidarabine, and ophthalmically acceptable salts, and mixtures thereof.
More preferred ophthalmic drug are selected from antazolin, betaxolol, chloramphenicol, dexamethasone, fluoromethalone, ketotifen, lomefloxacin, ofloxacin, pilocarpine, timolol and ophthalmically acceptable salts, and mixtures thereof.
Strongly preferred are ketotifen and dexamethasone.
The term ketotifen relates to the basic compound itself as well to any pharmaceutically acceptable salt thereof. A preferred pharmaceutically acceptable salt of ketotifen is for example a hydrochloride, a hydrobromide, a hydrogen maleate, a hydrogen sulfate and a hydrogen fumarate. A more preferred example is a hydrochloride and a hydrogen fumarate. Most preferred is a hydrogen fumarate.
Similarly, the term dexamethasone relates also e.g. to dexamethasone-21-acetate, dexamethasone-21-phosphate disodium salt, dexamethasone-21-dihydrogen phosphate disodium salt and the like. All these are known to the skilled person in the art and are specifically disclosed in Merck Index, 12th edition, page 498, No. 2986.
The term autoclaving relates to a standardized thermal heating procedure characterized by the following parameters:
Heating a test composition to 120xc2x0 C. or more for a period of 15 minutes or more, wherein said composition is aqueous. Said aqueous composition is kept in a closed vessel, which vessel is typically a plastic or glass bottle. A preferred bottle material is polypropylene (PP). The pressure during autoclaving is typically 1 bar or more.
The autoclaving (autoclavation) may preferably range from 120-150xc2x0 C., more preferably from 120-140xc2x0 C.; the time needed may preferably range from 15-120 minutes, more preferably from 15-60 minutes; and the pressure applied may preferably range from 1-20 bar, more preferably from 1-10 bar, and even more preferably form 1-5 bar.
The term Dequest as used within the present invention relates to chelating agents having phosphonic acid or phosphonate groups. A preferred group of such chelating agents are organophosphonates, particularly amino tri(lower alkylene phosphonic acids). A variety of such chelating agents are commercially available from Monsanto Company, St. Louis, Mo., and are sold under the trademark DEQUEST(copyright). Examples of such compounds include, without limitation, diethylene triamine penta(methylene phosphonic acid); hexamethylene-diaminetetra (methylenephosphonic acid); ethylenediaminetetra (methylenephosphonic acid); and aminotrimethylene phosphonates. A particularly preferred chelating agent is diethylene triamine penta(methylene phosphonic acid), sold under the trademark DEQUEST(copyright) 2060. Mixtures of such Requests mentioned above may be comprised too.
Within the terms of the present invention, EDTA relates to ethylendiamine tetraacetic acid itself as well to its various salts, namely e.g. to monosodium, disodium and/or potassium salts. EDTA may also be referred to as edetate. Mixtures of EDTA""s may be comprised too.
Desferal relates within the present terms to deferoxamine itself (see Merck Index 12th edition, page 483, No. 2914) as well to its salts, e.g. hydrochloride, methanesulfonate and the like. Derivatives thereof, such as N-acetyldeferoxamine may also be comprised. Mixtures of such deferoxamines may be comprised too.
Typical examples which illustrate the present invention, but are not intended to limit it in any way, are described below.

Autoclavable pharmaceutical compositions containing a chelating agent


This invention is for a vertical axis wind turbine apparatus supported in a tower with wind diverter doors for controlling the air impinging on the turbine blades. The diverter doors are closable in high wind conditions to seal off the wind turbine to protect the turbine against damage.

Wind turbines are generally classified into two groups based upon the orientation of the turbine axis of rotation. There are horizontal axis wind turbines and vertical axis wind turbines. Horizontal wind turbines are the traditional image when thinking of windmills. The rotor shaft and an electric generator are generally mounted atop a tower and are connected to a gear box that converts the slow rotation of the blades into a faster rotation for the electric generator. Horizontal axis wind turbines have the disadvantages of needing to be readjusted to face the wind with every shift of the wind direction and requires gearing, braking and feathering controls to transfer the torque to an off-axis generator and means to keep the rotational speeds within acceptable limits. These turbines are equipped with high wind shutdown features to avoid over speed damage. Vertical axis wind turbines, on the other hand, have blades mounted to a vertically extending rotor shaft and are favored in areas where winds constantly shift direction because the blades are not required to be rotated to face into the wind and where low winds occur because they require a slower wind speed to start generating electricity.
Each group of wind turbines has advantages and disadvantages. The main disadvantage of vertical axis wind turbines is drag created as the blades rotate into the wind even while a lift is being created on the opposite side. The turbulent winds located near the ground can cause excessive noise as well as torque and strain on the main rotor shaft and bearings. Other disadvantages are that they have only about half the efficiency of the horizontal axis wind turbines in large part because of the additional drag that they have as the blades rotate in to the wind.
The present invention overcomes disadvantages of vertical axis wind turbines by utilizing a tower configuration in which the wind driven blades and turbine are inside a tower frame. The tower frame has diverter doors that reduce the draft of the blades as they rotate into the wind. The doors transfer the load of the blades to the tower and off the axis. This increases bearing life and ease in maintenance and repairs. Diverter doors also control the quantity of wind to the blades and therefore can increase wind to the blades in low wind conditions and will decrease wind in high wind conditions using computer control motors on the diverter doors. The tower configuration with the diverter doors, which can be fully closed, allows for greater protection against high wind conditions. The tower configuration with diverted doors allows the vertical axis wind turbine to be configured for a multi-megawatt generation and allows the turbines blades, which can increase torque and allow for a gear box ratio to increase the speed of the generator. In addition, the increased torque and weight transfer of the axis to the tower allows the axis to be fitted with a fly wheel which limits over torque from gusts of wind and allows continuous electrical generation during lull periods. The rigid tower and diverter doors allow the wind turbine to be used in hurricanes and other high wind conditions by closing the diverter doors and the rigid frame.
The present wind turbine can be installed in a city or urban environment and allows for ease in connection to an electrical grid and the transfer of electricity to the consumer.
In the past, there have been a wide variety of vertical axis wind generators including the following U.S. patents. The Rice U.S. Pat. No. 6,984,899 is a vertical axis windmill for the generation of electric power utilizing wind which maintains a relatively constant rotational frequency of the shaft of the windmill. It uses two wind foils which extend radially outward from the blades to provide a scoop for pulling in more air than would normally be received by the blades. The wind foils direct the flow to the power producing part of rotation of the blades and close to control the wind flow to the blades.
The Elder U.S. Pat. No. 6,448,669 is for a vertical axis water turbine used to convert water kinetic energy into mechanical energy. A vertical axis wind turbine is mounted so that wind is compressed and directed to the rotor blades by a plurality of fixed stator blades. The Kato U.S. Patent Application Publication No. US 2009/0167027 is for a blade for a windmill and a windmill and wind power generator of the vertical axis type. The Tsipov U.S. Pat. No. 6,962,478 is for a vertical axis windmill having a wind turbine mounted inside a frame. A plurality of gate elements which are turnably connected to the frame are for the closing and opening of the openings in the frame by wind flowing substantially in a horizontal plane. The Williams U.S. Patent Application Publication No. 2009/0097960 is for a vertical axis windmill assembly.
The Kariya U.S. Patent Application Publication No. 2008/0131281 is for a vertical axis windmill with a guiding device which includes vertical plates which are fixed on the bottom of the base structure to the top of the rotor in an annular array. The Uchiyama U.S. Pat. No. 7,417,334 is for a wind power generation system which uses a permanent magnets and coils for generating electric power.
The Valsamidis U.S. Pat. No. 5,380,149 is for a wind turbine cross wind machine which has a circumferential arrangement of guide vanes around a centrally located rotor and having an arrangement of turbine blades in the middle so that the guide vanes can guide the wind falling upon a counteracting rotor blades towards the direction of rotor rotation.
The Taylor U.S. Pat. No. 6,015,258 and the Teasley et al. U.S. Pat. No. 4,318,019, and the Townsend U.S. Pat. No. 5,632,599 each teach wind turbine rotor blade designs.
The Rowe U.S. Pat. No. 6,740,989 is for a vertical axis wind turbine which has vanes surrounding a turbine rotor with each vane creating a turbulent swirling boundary layer on the vane surface that rotates in the direction that draws and redirects air flow into the air flow channels defined by the stator vanes. It is then compressed by the narrowing of the channels and directed to rotor blades to drive the turbine.
The Roberts U.S. Pat. No. 6,465,899 is for an omni-directional vertical-axis wind turbine. The Ouellet U.S. Pat. No. 5,126,584 is for a windmill having a stator and a rotor. The stator surrounds and supports the rotor and has equally spaced vanes having a stationary shutter surrounding a movable inner shutter capable of pivoting around the longitudinal axis.
The present invention is for a vertical axis wind turbine for generating electricity which has a vertically extending wind turbine having its rotor shaft connected through a gear box to an electric generator and which has a plurality of diverter doors which are movable to control the air flow to and from the wind turbine which doors are closable to protect the wind turbine to protect against winds exceeding a predetermined velocity.


Desoxypeganine and its pharmaceutically acceptable acid addition salts are useful in treating nicotine dependence.

This application is a 371 of PCT/EP00/00975 filed Feb. 8, 2000.
The present invention relates to the novel use of a little-known active compound for the treatment of nicotine dependence.
In particular, the present invention is directed at pharmaceutical use in formulations by means of which deoxypeganine or one of its pharmaceutically acceptable acid addition salts is delivered in a controlled, e.g. continuous, manner for the treatment of nicotine dependence.
Dependence on nicotine fulfils all of the criteria of drug dependence defined by the WHO:
compulsive use
psychoactive effects
influence on the behavior
stereotypical consumption habits
abstinence symptoms on withdrawal or development of tolerance.
Smoking is thus not a xe2x80x9cbad habitxe2x80x9d and cannot be suppressed in all cases by willpower alone. Pharmacologists have found nicotine receptors in the brain which are a biological explanation for the fact that so many smokers relapse again and again in spite of strong motivation and good psychological support.
This knowledge led in 1975 to a completely new therapeutic approach, the supply of nicotine by chewing gum. Initially greeted enthusiastically, the system, however, very soon showed weak points. Thus, fault was found with the bitter taste and the low social acceptance of the chewing gum. Misuse in these systems also definitely occurs due to overdosage.
All these disadvantages led to the development of transdermal systems which contain nicotine, as are described, for example, in German Patent DE 36 29 304 and U.S. Pat. No. 4,597,961.
In the transdermal administration of nicotine, taste does not play a part, use is invisible, the release of the active compound takes place without substitutive oral gratification and plasma peaks are avoided.
Side effects observed are skin irritation at the application sites, reddening, slight swelling and itching, which in some cases led to the abandonment of the therapy.
A disadvantage of this nicotine therapy is moreover that in this type of treatment the extreme toxicity of the nicotine is not taken into account.
There is therefore a need for medicaments which safely suppress the symptoms of nicotine dependence without, however, the therapeutic doses of the active compound having a toxicity which is comparable to that of nicotine.
Up to now, substances from the following groups have been employed for the treatment of nicotine dependence:
natural substances without nitrogen, e.g. xcex3-pyrones, citric acid, acetic acid, camphor, glucose, vitamins, terpenes and others
alkaloids having a different spectrum of action, e.g. lobeline, caffeine, galanthamine and Apocynaceae alkaloids
tricyclic antidepressants such as, for example, fluoxetine
clonidine
pyrrolopyrimidine
It is recognized even from the different nature of the therapy principles that an effective medicament for the treatment of nicotine dependence has still not been found which is not as toxic as nicotine.
The object of the invention is therefore the provision of a pharmaceutical in an oral, transdermal or otherwise parenteral formulation which releases this pharmaceutical in a form which is as controlled as possible and guarantees that the desire for nicotine is decreased. The term parenterally should thus include all administration forms apart from oral administration, such as rectal, intravenous, intramuscular, intraperitoneal and nasal administration.
This object is achieved in a surprising manner according to the invention by the use of deoxypeganine and/or one of its pharmaceutically acceptable acid addition salts for the treatment of nicotine dependence.
This achievement is all the more surprising as deoxypeganine has in fact been investigated in detail in the former Soviet Union and its pharmacological actions have been intensively researched, but the use according to the invention of a deoxypeganine-containing formulation for the treatment of nicotine dependence has not been described up to now.
On account of its pharmacological properties, deoxypeganine belongs to the group of reversibly acting cholinesterase inhibitors, is closely related to physostigmine and neostigmine in its actions, but is distinguished by particular specific properties. Deoxypeganine as a matter of fact inhibits not only acetylcholinesterase, but also monoamine oxidase.
This advantage offsets its somewhat lower cholinesterase inhibitory action (in comparison to physostigmine) based on the unit of weight.
In contrast to neostigmine, deoxypeganine crosses the blood-brain barrier and antagonizes the cerebral actions of cholinergic toxins.
Deoxypeganine is obtained by isolation from the harmel peganum (Peganum harmala) or by synthesis.
Pharmaceutical forms which release active compounds in a controlled manner are already known in the prior art. The administration of pharmaceutically active compounds by means of such formulations can take place orally, transdermally or otherwise parenterally. In medicaments of this type, the deoxypeganine can be present as such or in the form of pharmaceutically acceptable acid addition salts, e.g. as a hydrohalide, in particular hydrochloride or hydrobromide, or as a salt of another pharmaceutically acceptable acid. These agents as a rule furthermore contain excipients, such as vehicles, flow-improving agents, solvents and oils, whose nature and amount varies depending on the presentation form. In general, the content of active compound in the medicament, calculated as free deoxypeganine, is between 0.1 and 50% by weight, preferably between 2 and 15% by weight.
Some formulations for oral administration suitable in the context of the present invention will be described briefly.
In such a formulation, the pharmaceutical active compound is encapsulated, for example, in a semipermeable membrane, such as, for example, in cellulose acetate. A tiny hole is drilled in the capsule material using a drill or laser. Water is absorbed by the capsule material in the body of the patient who is being treated. The pharmaceutical active compound is driven through the small opening by osmotic pressure in the desired gradual, constant and controlled manner. Such systems are described, for example, in U.S. Pat. No. 3,760,805 and U.S. Pat. No. 3,987,790. In these systems, the pharmaceutical active compounds can be present in solid form or absorbed on ion exchanger resins.
Another system for oral administration is described by Sheth and Leeson in U.S. Pat. No. 4,137,300. This patent describes a formulation which contains a wax matrix.
The active compounds of the present invention are administered in a fitting and suitable manner by means of appropriate formulations. The solid active compounds can be administered in solution or as a suspension. The solution or suspension medium can be aqueous or organic. Suitable solution or suspension media for deoxypeganine are, for example, water, silicone fluid or mineral oil.
In order to simplify the administration of a compound by means of a formulation as described above, a flow-improving agent can be added to the system. Some suitable flow-improving agents for oral formulations include, for example, polyethylene glycol, hydroxy-propylmethylcellulose and sugar.
In a formulation for the transdermal administration of compounds according to the present invention, the pharmaceutical active compound can be contained in a matrix from which it is released in the desired gradual, constant and controlled manner. The permeability of the matrix during the release of the compound is based on diffusion. A system of this type is described in the German Patent 33 15 272 (U.S. Pat. No. 4,769,028). This system consists of an impermeable back layer, a specially constructed supersaturated active-compound reservoir associated therewith, made of a polymer matrix, a contact-adhesive layer permeable to the active compound, associated with the reservoir, and a protective layer covering the contact-adhesive layer, which can be removed again for use. Systems in which the reservoir layer has such a high intrinsic tackiness that it is simultaneously the contact-adhesive layer are also possible.
German Patent DE 38 43 239 (U.S. Pat. No. 5,089,267) describes such a system.
If the active compound is absorbed through the skin, the patient to be treated in this manner receives a controlled and predeterminable supply of the active compound.
Other suitable transdermal formulations are described in U.S. Pat. Nos. 3,742,951, 3,797,494, 3,996,934 and 4,031,894. These formulations fundamentally consist of a back layer which is one of the surfaces, an adhesive layer permeable to the active compound, which is the other surface, and finally a reservoir which contains the active compound between the two layers forming the surface. Alternatively to this, the active compound can also be contained in a multiplicity of microcapsules which are distributed in the permeable adhesive layer. In each case, the active compound is continuously released from the reservoir or the microcapsules by a membrane into the adhesive layer permeable to the active compound, which is in contact with the skin or mucous membrane of the patient to be treated. In the case of microcapsules, the capsule material can also act as a membrane.
Formulations which are suitable for the otherwise parenteral administration of deoxypeganine and its salts are those which make a depot action of the active compound possible. In this context, the formulation is applied as an injection solution on a nonaqueous basis. The possible solvents are known to the person skilled in the art. Examples which may be mentioned are the vegetable oils which individual pharmacopeias prescribe, such as peanut oil, olive oil, almond oil, sunflower oil, soybean oil and sesame oil. Castor oil often shows a particularly favorable solubility for medicaments; in addition oils of animal origin are also suitable.
The oils are physiologically indifferent and highly tolerable. The prerequisite for this is that they are specially purified and have low acid and peroxide counts. As intravenous administration is not possible because of the lack of miscibility with the blood serum and can lead to pulmonary embolism, their use is possible only for intramuscular and subcutaneous injection preparations. Oily solutions and suspensions remain at the site of administration for a very long time (often up to 1 month) and release the active compounds over a prolonged period.
The dose of deoxypeganine or its pharmaceutically acceptable acid addition salts must be so high and take place over such a long time that a lasting action is obtained, and needs individual adjustment.

Pharmaceutical composition containing deoxypeganine for the treatment of nicotine dependence


A predetermined number of erasable blocks positioned at a start of a volume area in a semiconductor memory card are provided so as to include volume management information. A user area following the volume management information includes a plurality of clusters. A data length NOM of an area from a master boot record and partition table sector to a partition boot sector is determined so that the plurality of clusters in the user area are not arranged so as to straddle erasable block boundaries. Since cluster boundaries and erasable block boundaries in the user area are aligned, there is no need to perform wasteful processing in which two erasable blocks are erased to rewrite one cluster.

1. Field of the Invention
The present invention relates to an access apparatus for accessing a semiconductor memory card having internal nonvolatile memory such as EEPROM (electrical erasable programmable read-only memory), a computer-readable recording medium for recording an initialization program for a semiconductor memory card, an initialization method, and a semiconductor memory card, and in particular to an improvement for raising the efficiency with which data can be rewritten in the nonvolatile memory.
2. Description of the Background Art
Semiconductor memory cards have the advantage of being small and lightweight, and are well on the way to consolidating their position as the recording medium of choice in a wide variety of technical fields. A semiconductor memory card has an internalized nonvolatile memory known as EEPROM, which is accessed by a connected device, enabling the semiconductor memory card to be used as a recording medium. Data can be directly written into blank EEPROM sectors in the same way as for magnetic or optical discs. However, when EEPROM sectors already contain data, this data has to be deleted, returning the sectors to a blank state, before new data can be written into the sectors. In the type of EEPROM known as NAND (Not And) used in many semiconductor memory cards, the operation for returning sectors to a blank state has to be performed on 32 sectors at one time (in this nonvolatile memory, a group of 32 sectors is known as an erasable block). Consequently, the semiconductor memory card contains a specialized internal control circuit for realizing memory management using erasable blocks as access units. Status control of erasable blocks, and reading and writing of data to/from erasable blocks, is managed by this control circuit.
This means that the semiconductor memory card has a unique hardware structure (physical layer) that is completely different from that used in magnetic and optical discs. However, a layer model shown in FIG. 1A is formed from physical, file system and application layers, in the same way as in a magnetic or optical disc. FIG. 1B shows a detailed layout of the physical layer. In the drawing, the physical layer includes a volume area, in which a plurality of erasable blocks are arranged. Each erasable block is formed from 32 sectors and has a data length of 16 KB. The layout of the file system layer shown in FIG. 1C is what is commonly known as a FAT (file allocation table) file system. In a FAT file system, management of the volume area is performed in units known as clusters. Volume management information is arranged at the start of the volume area, and a user area for recording user data is arranged directly following the volume management information. The volume management information includes a master boot record, a partition table, a partition boot sector, a duplexed file allocation table (FAT), and a root directory entry. The duplexed FAT shows links between the plurality of clusters included in the volume area. This kind of file system layer enables data to be stored in the application layer in a hierarchical structure formed from directories and files. By installing a layer model, the access apparatus can access a semiconductor memory card with the same procedure used to access a recording medium such as a magnetic or optical disc, without needing to pay attention to differences in the physical layer.
However, a user has many opportunities to determine the data size of the volume area when data is stored in the volume area of the file system. When the size of the volume area is changed in response to a user request, the number of clusters included in the volume area increases or decreases accordingly. If the number of clusters is increased or decreased, the FAT formed from entries corresponding to these clusters also increases or decreases, respectively, as does the size of the volume management information in which the FAT is included. If the size of the volume management information is increased or decreased, a start address of the user area following the volume management information will also be changed. The start address of the user area changes according to the size of the volume area. Consequently, the start addresses of each cluster also change according to the size of the user area.
If the start address of each cluster changes according to the size of the user area, clusters may straddle the boundaries between two erasable blocks, and the end portion of the volume management information may be arranged in the same erasable block as a cluster positioned at the start of the user area. FIG. 1D shows the layout of the volume area when the end portion of the volume management information and the cluster positioned at the start of the user area are in the same erasable block. If clusters are arranged as shown in the drawing, and a user wishes to modify data stored in a particular cluster, the two erasable blocks in which the cluster is arranged have to be read and then returned to a blank state. However, nonvolatile memory is formed from a memory component that includes a floating gate buried in an insulating layer. This memory component can only be erased a few tens of thousands of times, so if the phenomenon in which two erasable blocks have to be erased to modify one cluster frequently occurs, the lifespan of the nonvolatile memory will be significantly reduced.
Generally speaking, when 32 sectors are managed as one cluster, writing data into a cluster can be completed in 32xc3x97200 xcexcs (200 xcexcs is the time required to write each sector), provided that the write destination has already been erased. However, if the write destination has to be erased before data can be written, a 2 ms erasure period is added. If the cluster straddles the boundary between two erasable blocks, both blocks need to be erased, and erasing the write destination takes 4 ms. As a result, the time taken to write data is markedly lengthened.
An object of the present invention is to provide an access apparatus that achieves a reduction in the processing time required to modify erasable blocks, as well as forming a data storage format in a semiconductor memory card that enables a nonvolatile memory having a longer lifespan to be realized.
The type of semiconductor memory card known as a secure digital (SD) memory card has made great strides toward resolving the aforementioned problems of reduction in processing time and nonvolatile memory longevity for the following reasons. In an SD memory card, an area known as the protected area, which cannot be used by the general user, is provided. This protected area is used to store secret information, such as an encryption key used for encrypting data, billing information used to bill a user when a copyrighted material is reproduced, and the like. The amount of data which needs to be kept secret varies according to the type of application program used, so that the size of the protected area has to change according to the type of application program. If the size of the protected area is changed, this means that the layout of the volume area also changes in response to the type of application program. If the layout of the volume area changes in this way, a layout in which clusters straddle the boundaries between erasable blocks is often generated, so achievement of the above-mentioned object is particularly desirable.
In order to achieve the above-mentioned object, the semiconductor memory card access apparatus may have the following structure. The access apparatus performs file access on a semiconductor memory card that has a memory area comprising of a plurality, of sectors by managing data in each group of 2j sectors (j being 0 or a positive integer) as a cluster, and managing one or more clusters as a file. Here, each group of 2i consecutive sectors in the memory area forms a block (i being 0 or a positive integer), which is the smallest unit on which data erasure can be performed. The access apparatus includes a calculation unit, a reserving unit, and a recording unit. The calculation unit calculates a size of volume management information based on a number of clusters in the memory area that are to be managed. Here, the volume management information includes a file allocation table that indicates, for each file, links between clusters corresponding to the file. The reserving unit reserves a first area for recording the volume management information, and a second area for recording user data. The first area has a data size larger than the calculated volume management information, and is formed from mxc3x972j sectors (m being a positive integer), while the second area is formed from sectors following the first area. The recording unit records volume management information in the first area, and user data in the second area, and manages the volume management information and the user data as clusters. In this access apparatus, an area in the volume area having m clusters (m is a positive integer) is reserved for recording volume management information, so there is no possibility of any cluster being stored straddling two erasable blocks. Cluster boundaries can be aligned with erasable block boundaries, and the boundary of the volume management information can be aligned with an erasable block boundary. Consequently, only one erasable block needs to be erased when a cluster is rewritten or overwritten, and the number of times that erasable blocks have to be erased can be reduced. If the number of block erasures is reduced, the semiconductor memory card can write data in a shorter time, and the lifespan of the nonvolatile memory itself can be increased.
Here, the volume management information may include in addition to the file allocation table, a master boot record, a partition table, partition boot sector information, and a root directory entry. Furthermore, the recording unit records the master boot record and the partition table in a first sector of the first area, skips a predetermined number of sectors and then records the partition boot sector information, the file allocation table, and the root directory entry in subsequent sectors. As a result, an end of the first area can be aligned with an end of the root directory entry. The number of sectors between the master boot record showing the start of the drive, and the partition boot sector showing the front of the partition area, can be adjusted, so the volume management information can be restricted to a first area formed from m clusters, and compatibility with devices that use a FAT file system preserved.
Here, the calculation unit may calculate a sum SUM by totaling a number of sectors used to record the partition boot sector information, the file allocation table, and the root directory entry. The reserving unit reserves the first area by calculating the value of m based on an {equation 1} NOM+SUM=2jxc3x97m. Here, NOM is a number of sectors. The recording unit calculates the predetermined number of sectors by subtracting 1 from the number of sectors NOM. Even if the size of the file allocation table changes, a first area which is larger than the size of the volume management information and is an integral multiple of erasable block size is reserved. As a result, a necessary minimum size for the first area can be reserved, no matter how the size of the file allocation table is calculated.
Here, the recording unit may set the predetermined number of sectors in the partition table recording the volume management information. In this structure, even if the size of the first area changes, causing the start address of the second area to change, a number of sectors, obtained by subtracting 1 from the number of sectors NOM, is set in the partition table, so the access apparatus can access the user area accurately by referring to the partition table.

Semiconductor memory card access apparatus, a computer-readable recording medium, an initialization method, and a semiconductor memory card

Matsushita Electric Industrial Co., Ltd.


A capsulated body having a facility, which acquires biomedical information through endoscopic examination or the like, incorporated therein is inserted into a duct within a living body. Whether the capsulated body has halted for a certain period of time is detected from the time-varying position of the capsulated body or a time-passing change in an image. If it is judged that the capsulated body has halted at a stenosed region or the like, the fact is notified so that the capsulated body can be collected immediately.

1. Field of the Invention
The present invention relates to capsulated medical equipment that is shaped like a capsule and that moves within a body cavity to perform examination or the like.
2. Description of the Related Art
In recent years, endoscopes and other medical equipment have been proposed for examining an intracavitary region or the like. Moreover, ordinary endoscopes are such that an insertion unit alone is inserted into a body cavity in order to perform endoscopic examination or the like. Medical equipment including a capsulated body that is shaped like a capsule and inserted into a body cavity in order to perform examination or the like has been disclosed in, for example, Japanese Unexamined Patent Application Publication No. 2001-91860.
In this type of capsulated medical equipment, the capsulated body may presumably be clogged at a stenosed region within a body cavity. If the capsulated body is clogged, it must be collected as soon as possible.
However, the related art described in the foregoing publication has not disclosed a countermeasure permitting early-stage detection of the clogged state of the capsulated body.
Moreover, a publication No. WO99/30610 of an unexamined international application under PCT discloses a related art that detects whether the acceleration in an axial direction is equal to or smaller than a predetermined value. If the acceleration is equal to or small than the predetermined value, a powering unit is disconnected for fear redundant image data may be acquired.
The above related art does not detect the clogged state of the capsulated body.


A heat exchanger comprises a plurality of first heat exchange tubes extending through the exchanger, and through a plurality of laterally extending heat exchanger chambers, each chamber having at least one entry from a first chamber and at least one exit to a second axially adjacent chamber, and each chamber having a plurality of transverse interconnecting zones, each of which is defined by at least two of said tubes, and at least one first zone has an entry to said first chamber and at least one second zone, different from said first zone, has an exit to said second chamber. Also included is a vessel for mixing or distributing streams of a first fluid passing axially from an upstream to a downstream location, which comprises transverse baffles across said vessel in at least two successive rows, which rows of baffles define an open transverse chamber, the baffles in successive rows having a different spatial distribution across the vessel. Preferably the apparatus has the heat exchanger with the distributor downstream of it, and the whole apparatus is a compact reformer.

The present invention relates to an apparatus for heat exchange between fluids and/or for mixing of fluids, those fluids being different and/or at different temperatures.
In many process operations there are heat exchangers involving transfer of heat from a first to a second fluid. The exchange may be to cool exhaust gases from a combustion reaction and/or to preheat gases prior to reaction. The two fluids may move in countercurrent or cocurrent directions and may move with one fluid in a core and the other in a surrounding shell, or one may move in a tube or tubes passing thorough a chamber containing the other fluid. In EPA-450872 a compact reformer has reaction tubes for an exothermic reaction inside a chamber packed with catalyst for an endothermic reaction. The exiting endothermic reaction products in the chamber preheat the exothermic reactants passing in a core and surrounding annulus inside the chamber. In EPA-643618 and EPA-703823 the endothermic reaction occurs in the tubes and the exothermic reaction in the chamber, and the exothermic reactants are preheated by passage in annuli surrounding the exit endothermic tubes. In EPA-703823 one preheated exothermic reactant, usually air, passes into the reaction chamber through a perforated distribution plate, which forms a wall of air which moves up the chamber until it meets the preheated fuel outlets at which time autoignition occurs to produce flames which pass around and along the endothermic tubes to effect reaction therein. The exiting combustion gases from the exothermic reaction preheat the incoming endothermic reactant.
The above arrangements do not give as uniform preheating of the exothermic reactants as may be desired, nor as uniform a temperature distribution of the air entering the reaction chamber as may be desired.
The present invention concerns apparatus for and methods of obtaining greater uniformity in the preheating and/or temperature distribution.
The present invention provides a heat exchanger, which comprises a plurality of first heat exchange tubes extending through the exchanger, and through a plurality of laterally extending heat exchanger chambers, each chamber having at least one entry from a first chamber and at least one exit to a second axially adjacent chamber, and each chamber having a plurality of transverse interconnecting zones, each of which is defined by at least two of said tubes, and at least one first zone has an entry to said first chamber and at least one second zone, different from said first zone, has an exit to said second chamber.
The present invention provides a heat exchanger, which comprises a plurality of first heat exchange tubes extending through the exchanger and through a plurality of laterally extending heat exchanger chambers comprising a first chamber and a second and third chamber axially adjacent thereto and on either side thereof, each chamber being separated from each adjacent chamber by a partition, in which are a plurality of discrete openings, and each chamber having a plurality of transverse interconnecting zones, each of which is defined by at least three of said tubes, a first partition and a second partition opposing said first partition, and with said openings in different zones and a passage through said zones between at least one first opening in a first partition and at least one second opening in said first partition, and at least a third and a fourth opening in said second partition.
The present invention also provides a process for effecting heat exchange between a first fluid passing through a vessel and a second fluid in a plurality of first tubes extending through said vessel and through a plurality of laterally extending heat exchange chambers, each chamber having a plurality of transverse interconnecting zones, which comprises passing at least one stream of said first fluid into a first chamber, effecting contact of said fluid and more than one of said tubes and then passing a stream of said fluid subsequent to said contact from said first chamber into a second chamber axially adjacent to said first chamber, so that said fluid passes through said chambers in an axial and lateral direction.
The present invention also provides a process for effecting heat exchange in a vessel between a first fluid passing through a plurality of laterally extending heat exchange chambers in said vessel in mutual axial relation in said vessel and a second fluid passing in a plurality of first tubes, which extend through said vessel and through said chambers, each chamber having a plurality of transverse interconnecting zones, which comprises passing at least two streams of said first fluid into different zones in a first chamber, effecting contact of each of said first streams and more than one of said tubes to give second and third streams, mixing said second and third stream in a different zone to produce a mixed stream and passing said mixed stream from said different zone into a second chamber axially adjacent to said first chamber, so that said fluid passes through said chambers in an axial and lateral direction.
The heat exchanger is a hollow vessel containing the plurality of chambers and the heat exchange tubes. The vessel may be of curved, e.g. circular, or ellipsoidal, or rectilinear e.g. square or rectangular cross section, and may have a longitudinal axis substantially normal to its radial axis, as in a right cylinder. Preferably its height to width ratio is 10:1 to 2:1. The vessel may be of metal, e.g. steel, or insulating material, e.g. brick or stone, construction and especially in the case of a metal walled vessel, may have an insulating external layer.
The first heat exchanger tubes are of heat conducting material such as carbon fiber reinforced material or ceramics but preferably of metal, especially high temperature resistant steel. The tubes may be dispersed in the vessel in a random or regular array, in particular in at least 2 such as 2-6 rows, in which the tubes in adjacent rows may be in line or offset with respect to one another. The tubes may be parallel in one or two directions, so any tube is a member of two rows, the axis of one row being normal to the axis of the adjacent row or at 45xc2x0 to said latter axis; the axis of one row may also be normal to the axis of the next row beyond the adjacent row. Thus the tubes may be in rectilinear rows, each tube being a constant distance from each of its 4 nearest neighbouring tubes or having 8 nearest neighbours, 4 of these at one distance and the next 4 at a longer distance. The tubes may also be in non rectilinear arrays. There may be at least 2, e.g. at least 10, first heat exchange tubes such as 2-5000, preferably 10-576, first heat exchange tubes in the vessel. They may be distributed in a square or rectangular pattern in the vessel, preferably in a square pattern and with the number of tubes in each row the same or alternating by one. They may be in a triangular pitch or a rectilinear pitch, e.g. square pitch, the rows in the rectilinear pitch being optionally parallel to or at 30-60xc2x0, e.g. 45xc2x0, to the walls of a notional or actual sheath surrounding the outermost of the tubes in the array in the vessel.
The first tubes may extend through the vessel reactor linearly, especially in a direction parallel to the longitudinal axis of the vessel, in particular for right cylindrical vessels. For rectangular vessels the tube axis is usually parallel to a longitudinal edge. Advantageously the tubes pass through opposed faces, e.g. top and bottom of the vessel. However the tubes may also pass at any angle through one of said opposed faces, rather than substantially normal thereto, and may pass through a side face of the vessel. The tube may also pass in a non-rectilinear fashion, e.g. in a curved fashion, which may be in a single plane, as in an arc of constant or varying radius, or in a serpentine fashion, e.g. a sinusoidal fashion, or the tube may be in more than one plane, e.g. in a regular or irregular helix.
The exchanger usually has insulation either surrounding the external wall of the vessel and/or in a layer on the inside of that wall.
The vessel is subdivided axially with a plurality of laterally extending chambers, each chamber usually extending across the full internal width of the vessel. There may be at least 2, such as at least 5, such chambers especially 2-200 or 10-60. The first tubes pass through more than one chamber, especially through each chamber. The chambers preferably extend laterally normal to the longitudinal axis of at least one tube passing through it, in particular all of said tubes, and/or extend laterally normal to the longitudinal axis of the vessel, especially both. The relative height (axial length) of the chamber to the lateral width of zones in said chamber i.e. the gap between said first tubes is usually up to 10:1, e.g. 0.1:1 to 10:1, such as up to 5.0:1, e.g. 0.2-3.0:1, 0.2-0.8:1 or 1-2:1. Advantageously the individual chambers are substantially parallel to one another, so the first and second partitions which constitute floors and ceilings of each chamber are preferably substantially parallel.
Each chamber is subdivided into a number of transverse zones (e.g. at least 10 zones such as 10-1000), the relation of which to each other and other chambers will be described with reference to the first chamber, and the second and third, chambers adjacent to it on either side.
The first chamber has among its zones, at least two and preferably 6, such as 6-50 entry zones, in which each zone has an opening to entry from the second chamber and at least two, and preferably at least 6, such as 6-50, exit zones, in which each zone has an opening to exit into the third chamber. The relation between the number of zones to the number of tubes may be up to 2:1, e.g. 0.5-2.2:1, while the ratio between the number of entry zones to the number of exit zones in any one chamber is usually 0.5-2:1, e.g. 0.1-1.2:1, preferably substantially 1:1. The zones usually extend in both lateral directions throughout the chamber and substantially all the chamber has been divided into zones. The zones usually interconnect with each other in the chamber and the majority especially substantially all, usually interconnect with zones in neighbouring chambers as described further below. Ignoring the space between the outermost tubes and the walls of the vessel, each zone is defined by the walls of at least 3 or 4 tubes passing through the chamber. The zone is defined by at least 3 tubes when these are arranged in a triangular pattern and by at least 4 tubes when these are in a square or rectangular pattern. Irregular patterns of tubes can require at least 3-6 tubes to define a zone. Each zone has at least 1 and usually 2 tubes common to its neighbouring zone.
A first zone has an entry from the next (e.g. second) chamber and a second zone has an exit to the other adjacent (e.g. third) chamber. No zone has both such an entry and such an exit, so the first and second zones are different. At least one first entry zone may be adjacent to at least one second exit zone, or may be spaced from the second zone by at least one, e.g. 1-4, but especially 1 third zone, which has neither such entry nor such exit. Thus advantageously an entry zone may be spaced by a third zone from an exit zone, which is itself spaced by a further third zone from a further entry zone; thus 6 zones in question are preferably in a straight line across the width of the chamber. Alternatively an entry zone may be adjacent to an exit zone, itself adjacent to a further entry zone, all the zones preferably in a straight line across the chamber. Preferably the entry and exit zones in each of the second, first and third zones are in the same plane, so the first fluid moves up the vessel in that plane. When the exit zone is surrounded by 2 or more entry zones in one, e.g. the first chamber, then the overall effect is to mix the portions of the first fluid entering the first chamber via the entry zones and eject them through the exit into the next, e.g. third chamber, whereupon a portion passes to one exit zone in that chamber and another portion passes to another exit zone in that chamber. In this way the fluid is divided, mixed and redivided and remixed with the same or different streams of fluid, in each case with contact of 2 or more tubes in each zone. By this means the temperature of fluid in each chamber progressively becomes more uniform as the fluid moves up the vessel from chamber to chamber.
In each chamber there are usually at least 4 zones in any linear direction, and especially 0-3 zones, e.g. 0-1 zones, between each entry zone and each exit zone. In particular at least one entry zone is spaced from the vessel wall by at least one, e.g. 1-3, such as 1 tube, and especially at least one, e.g. 1-3, such as 1 zone; the nearest exit zone from said entry zone is also preferably spaced from the vessel wall by at least one, e.g. 1-3, such as 1 tube or especially at least one, e.g. 1-3, such as 1 zone. In addition each chamber preferably has at least 2 entry zones spaced apart and at least 2 exit zones spaced apart, all in a straight line across the chamber in particular with 0 or 1 zones between each entry and exit zone.
The first heat exchange tubes may be the only ones passing through the chambers, but preferably there is at least one second heat exchange tube passing through the chambers. The diameters, cross section shapes and areas of the first and second (and any subsequent tubes) may be the same or different; preferably the first tubes are larger and may be for countercurrent heat transfer to the first fluid passing through the vessel while the second tubes may be smaller and for cocurrent heat transfer from the first fluid or countercurrent radiation heat transfer from the first tubes. The second and further tubes may be symmetrically disposed with respect to said first tube, e.g. equidistant to two or more first tubes. The second and further tubes may be arranged regularly as described above with the first tubes: in particular the first and second tubes are in rows which are parallel in two directions to one another. Thus, preferably there is a first regular array of said first exchange tubes and a second regular array of second heat exchange tubes axially extending through the exchanger and preferably of different diameter from said first exchange tubes. The second tubes are preferably in alternate rows with the first tubes, in line therewith or especially offset therefrom, i.e. with each tube of one kind at the center of a square (in plan view) with 4 nearest neighbours of another kind at the corners of the square. The second tubes may alternate with first tubes in 2 directions normal to one another or only in one of those directions. The tube center/tube center spacing between the first tubes in any direction may be the same or different from that spacing between the second tubes in that direction and that spacing between the first and second tubes may be the same or different from either of the above spacings. Preferably all these tube center/tube center spacings are substantially the same. The ratio of the number of first tubes to second tubes may be 1:3 to 3:1, especially 10-14 to 14-10, or substantially 1:1. The first tubes may be arranged with a triangular pitch with the second tubes in each alternate triangle, or may be in a rectilinear, especially square pitch.
The presence of first and second heat exchange tubes passing through the heat exchanger chambers is a particularly important aspect of the invention especially in the method of the invention in which a first fluid passes through the chambers, and a second fluid passes through the first tubes, while a third fluid passes through the second tubes, the direction of flow of the second fluid is counter current to that of the third fluid, and to the overall axial flow of the first fluid.
At least one of the first and second heat exchange tubes, preferably the first tubes and optionally both, is provided with means for enlarging the effective external surface area thereof. The enlargement means may be integral with the tube, or non integral therewith but in direct thermal contact with the tube; both kinds of enlargement means may be present if desired. The enlargement means is usually one or more fins or ribs on the tube, the fins or ribs being continuous or discontinuous through the chamber. They may be straight or curved e.g. spiral or helical along the tube length in the chamber. The non integral enlargement means may be in the form of a heat conducting body having one or more fin or rib, said body being extended round the tube in the chamber, with or without attachment to the tube. Conveniently the non integral means may have a fin or rib extending outwardly from, e.g. normal to, a base, which may have a flat surface for contacting the tube; thus this means may be a flexible elongate body of T-shaped cross section tightly wound round the tube to provide good thermal contact between the tube and the base and hence provide heat to the fin or rib.
In the method of the invention, a second fluid, e.g. a gas or a liquid or mixture thereof, moves in the first tubes and heat is transferred between the tube walls and the first fluid (e.g. a gas or liquid or mixture thereof) passing through the zones in each chamber. A first stream of the first fluid may enter the first chamber, contact at least 2 of the tubes in the zones and pass into the second chamber; alternatively, or in addition, a first and second stream of the first fluid may separately enter the first chamber, each stream contacting at least one tube and then the first and second streams may mix and pass to the second chamber. Preferably each stream entering an entry zone in one chamber contacts at least 4, e.g. at least 8, heat exchange tubes before it leaves that chamber. Preferably the first fluid passes through successive chambers countercurrent to a second fluid passing through the first tubes, while especially a third fluid passes in the second tubes cocurrent with the first fluid and countercurrent to the second fluid.
Advantageously the first and second fluids are gases and the third is a gas or a liquid, (especially when the second tube diameter is smaller than that of the first tube). In particular the second fluid is an endothermic reaction product, e.g. from steam reforming of a gaseous hydrocarbon, e.g. of 1-4 carbons such as methane, or a partial oxidation of such a hydrocarbon, while the first fluid is a gas comprising molecular oxygen such as air and the third fluid is a fuel, e.g. hydrogen or a gaseous hydrocarbon of 1-5 carbons such as methane, ethane, propane or butane or carbon monoxide. Advantageously heat is transferred from the second fluid via first tubes to the first fluids, and hence from first fluid to third fluid (via second tubes) especially to preheat the air and fuel before entering a combustion region of the vessel, the combustion heating up the endothermic reaction. If desired the first tubes may contain heat transfer solids, e.g. inert solids such as ceramic material and/or solid catalyst for the endothermic reaction. At least some of the heat transfer between the first tube and the second tube in the chambers is usually by radiation, e.g. at least 5% or 20%, such as 5-10%, 10-50%, or 20-40%, such as about 30%, the rest being primarily by convection.
Preferably in the process the first fluid passes through at least 1 and especially at least 2 successive chambers in one plane, e.g. 5-30 chambers, and then through at least 1 especially at least 2 successive chambers in a different plane, particularly at 45-135xc2x0 to the first plane, e.g. substantially normal to it, e.g. a further 1-30 chambers; thereafter the plane of movement may be changed again, e.g. as before at least once more, such as 1-5 times further. If desired the plane of movement may be changed at a more frequent rate with increasing distance from the entry of first fluid.
The percentage of the entry and exit openings in any chamber to the total area of that chamber (i.e. including tubes) is usually 5-25%, e.g. 10-20%, while the percentage of the entry and exit openings in any chamber to the total area of that chamber excluding the tubes (i.e. the total area of the zones) is usually 25-50.
In the apparatus of the invention the individual chambers may have complete partitions, also called barriers herein, between them apart from the entry and exit openings mentioned above, so they have substantially complete floors and ceilings. The barriers may be otherwise impermeable to first fluid forcing all that fluid to pass from entry to exit zones before passing to the next chamber. However, if desired at least a portion, especially substantially all, of at least one barrier between successive chambers, especially substantially all such barriers, are foraminous, with the percentage of the area of the holes to the total area of the barrier of 10-70%, especially 30-60%. Such perforated barriers allow some passage of the first fluid from each chamber to the next other than via the entry and exit zones to reduce the back pressure and render the flow distribution even compared to use of solid barriers. Preferably however, the barriers are incomplete but not foraminous.
The entry and exit openings may be in the form of slots in sheets or plates, or spaces between separate baffles. The barriers may be of a regular or irregular shape with straight or curved sides, so that the entries and exits may be of circular, ellipsoid, rectangular, square or other cross section. One barrier may completely cover the roof of one or more zones; in particular there may be one or a series of barriers across the width of the vessel. Thus there may be a series of rows of barriers of similar shape, e.g. with parallel longitudinal or laterally extending sides; those may thus be the baffles mentioned above. The second tubes may pass through at least two and especially substantially all of these barriers with parallel lateral extending sides but preferably pass through only a proportion of said barriers especially at regular intervals, in particular through alternate barriers. When a series of successive chambers has parallel sided baffles, the sides of the baffles may be coplanar through at least 2 successive chambers, e.g. substantially all, or the sides may be parallel to those of the baffles in the next chamber but the sides may overlap (when viewed in plan view). There is thus effectively no axial line of sight between successive chambers, thereby forcing the first fluid to move laterally as well as axially between successive chambers especially in a serpentine manner. While baffles in one chamber may have sides parallel to the corresponding baffles in the adjacent chamber and/or axially colinear with those in the subsequent chamber, so that there may be 5-30 of such chambers, it is preferable periodically to have a series of baffles for first successive chambers with such parallel sides and then a series of baffles for the next successive chambers with mutually parallel sides, but at an angle, e.g. 45-135xc2x0 such as substantially normal to those in the first series. This change for the next successive chambers may be repeated one or more times, each group of chambers having 1-50, e.g. 5-30, chambers. In this way portions of the first fluid move through the vessel in one plane, prior to moving through the vessel in a different plane usually normal to the first. Thus there may be an exchanger which comprises in successive chambers a first series of barriers with sides parallel in one direction and then a second series of barriers with sides parallel in a different direction; the first and second series of barriers may alternate. When there are first and second tubes there are preferably baffles between alternate rows of first tubes in said first chamber and baffles between different alternate rows of first tubes in said second chamber, said second tubes passing through said baffles.
The first chamber may have a first partition which is a floor (or roof to the second chamber) with 2 transverse parallel sided slots, and a second partition which is a roof (or floor to the third chamber) with 3 transverse parallel sided slots, the sides being axially coplanar with those in the first chamber, while for the floor of the second chamber there are 3 such slots etc; after this series of such chambers the next plane of the sides changes for the next series again with an alternating 2, 3, 2, 3 number of slots. Generically the numbers of slots may alternate by one between each successive chamber. The slots may thus go North/South for a series, then East/West, then North/South again. With the above arrangements of slots, the effect is preferably that the heat exchanger vessel when viewed in plan view has a regular pattern of tubes with baffles through which first tubes pass and with an arrangement of second tubes, slots and baffles through which the second tubes pass or are tangential thereto, the overall effect being that there is effectively no line of sight through the heat exchanger, so that the first fluid can only pass with axial and lateral motion, rather than axial alone.
Advantageously the heat exchange tubes are inside a reactor with 2 walls, preferably concentric walls. While both may be load bearing, advantageously the outer one is more load bearing than the inner one. The inner wall acts like a shroud or envelope surrounding all of the tubes to provide an annulus between the two walls, e.g. outer wall and shroud. The inner wall, e.g. shroud, is usually of heat conducting material, e.g. metal or carbon fiber reinforced material, and may be in contact with one or more heat exchange tubes, but preferably is spaced from each tube. The inner wall may be of the same axial cross section shape as the outer reactor wall, e.g. concentric circles, but preferably the axial sections shapes are different, e.g. the outer wall is circular and the inner one is ellipsoidal or rectangular, such as square. The shroud may also hold in place in the reactor the barriers or partitions present between the chambers, and hence may help to locate the tubes.
This annulus in the reactor between shroud and reactor wall can contain heat insulation, e.g. ceramic material, but preferably provides a preheating zone for first fluid prior to entry into the heat exchanger chambers at their upstream end; this zone also reduces the heat loss from the reactor by capturing the heat from the shroud and reusing it. The reactor wall may be provided at one or more locations, at least one of which is distant from upstream heat exchanger chambers and near to the downstream heat exchangers, with at least one orifice for entry of the first fluid, e.g. air, and especially fluid under compression, said orifice(s) being in the reactor wall of the annulus. There may be more than 1 orifice, especially 2-6, in particular spaced symmetrically about the longitudinal axis of the reactor, usually in a plane normal to that axis. The shroud or envelope at its end near to the upstream heat exchange chambers may have at least one entry location into that (or those) heat exchange chamber(s) in particular 1-3 entries, e.g. one, into the one or more of the 3 most upstream heat exchange chambers, especially the most upstream chamber. Thus in use the air, e.g. compressed air, enters the reactor through the orifice(s) into the annulus, passes through the annulus, where via the shroud it is in cocurrent heat exchange relationship with the first tubes and/or countercurrent heat relationship to the first fluid moving through the heat exchanger chambers; the first fluid may be preheated to at least 100xc2x0 C. in this way before entry into the heat exchanger chamber from the annulus.
In one embodiment the process of the present invention also includes preheating the first fluid outside the heat exchanger chamber by heat exchange with first fluid inside said chambers, to give a preheated first fluid prior to entry of the preheated first fluid into heat exchanger chambers; advantageously the preheating is in a direction countercurrent to the direction of movement of first fluid in said chambers. In particular the first fluid is passed through an annulus between the shroud and reactor wall, the shroud providing an envelope surrounding the tubes.
The benefits of the heat exchanger and process of the invention may include a better heat distribution across the width of the vessel to the first fluid when leaving the exchanger, e.g. at the top, and/or to the second fluid when leaving the exchanger, e.g. at the bottom, through the first tubes. In a further aspect the present invention also provides a vessel for mixing or distributing streams of a first fluid passing axially from an upstream to a downstream location, which comprises transverse baffles across said vessel in at least two successive rows, which rows of baffles define an open transverse chamber, the baffles in successive rows having a different spatial distribution across the vessel. This arrangement of baffles may be present in a heat exchanger of the invention preferably after the first fluid has passed through the heat exchanger. Alternatively other heat exchanger systems may be used in combination with the above arrangement of baffles. The baffles can act as spoilers to break up the flow of the first fluid and distribute or mix it.
The arrangement of baffles may be used as a mixing device for fluids, different in temperature and/or composition, e.g. for mixing at least two different fluids, or one fluid in at least 2 streams at different temperatures. Preferably it is for mixing fluids at different temperatures, such as ones obtained from contact of one or more fluids with heat exchange surfaces, in particular ones extending through the vessel as in the first tubes in the above mentioned published references. If one of the tubes is at a different temperature from the rest, then first fluid passing it will be at a different temperature from the rest leading to lack of uniformity at the top of the heat exchanger, which this aspect of the present invention seeks to remedy with the special arrangement of baffles to give a substantially uniform temperature and composition fluid across the width of the vessel.
The arrangement of baffles is preferably used in a distribution device for fluids, e.g. ones having different axial velocities, in order to provide a flow of fluid across a wide area, e.g. the vessel width, of substantially constant velocity. The first fluid may first contact the baffles in one or more than one stream, e.g. a stream emanating from contact of one or more fluids with heat exchange surfaces, in particular ones extending through the vessel as in the first tubes of the previous apparatus of the present invention. Preferably the fluid is air and the baffles provide a flow of air across the vessel of substantially constant velocity, e.g. as a wall of air, in particular when the air meets the fuel burners in the apparatus of the invention.
The vessel may as described above in respect of the heat exchanger in terms of shape and construction, though need not have the first (and other tubes) in it. Thus in the upstream location in the vessel the 2 streams of fluid may just have been passed into the vessel, or may be separate from but on top of a heat exchanger with heat exchange surfaces, that heat exchanger being inside the vessel or outside it but with free movement of fluid from the exchanger into the vessel. In the former case, with baffles and exchanger in the same vessel, the heat exchange surfaces may extend through the region of the vessel containing the transverse baffles or may be absent therefrom, e.g. stop in the vessel below the baffles.
The baffles may be impermeable to the fluids, but preferably are foraminous, the total area of the holes in the baffles being 10-60%, e.g. 30-50%, of the total area of the baffles, and the size of the individual holes being preferably on average less than one fifth of the size of any heat exchange tubes passing through them, e.g. one twentieth to one fifth of the size. Advantageously the holes are all substantially the same size, especially in any particular row, though the holes in successive rows may be also of the same size or of progressively increasing or especially progressively decreasing size.
The shapes of the individual baffles may be as described above for the barriers in the heat exchanger.
The baffles are preferably in a vessel with at least some tubes passing through them, the spatial relationship between the vessel and the tubes being preferably as described above in relation to the heat exchanger and tubes. In particular the vessel may have first tubes passing through it in one regular array, and second tubes passing through it in a different way; the description above provides further details on the spatial arrangement of the tube arrays. The first and second tubes may be in rows parallel to one another or at 30-60xc2x0, e.g. 45xc2x0 to one another. In particular, a pair of rows of first tubes is preferably spaced by a row of second tubes and/or vice versa, especially when the first and second tubes are in parallel rows in two directions at right angles. Preferably each first tube is surrounded by 4 second tubes and each second tube is surrounded by 4 first tubes (apart from tubes adjacent to the vessel wall). The relation between the tubes and the baffles is preferably as follows. The second tubes may pass between, but preferably pass through, at least some of the baffles. The baffles may have laterally extending parallel sides, extending across substantially the internal width of the vessel and are located between at least some of the first tubes, e.g. 2-4. The sides of the baffles in a first row are usually at an angle, e.g. 45-135xc2x0, or substantially normal to the sides of the baffles in a second adjacent row. Preferably the number of baffles in one row is one more or less than the number in the adjacent row. Advantageously with respect to a first row of baffles first and second tubes are in parallel rows interspaced between one another, and rows of parallel sided baffles have alternate rows of second tubes passing through them, while with respect to a second row of baffles adjacent to said first row of baffles, rows of parallel sided baffles in said second row have each row of second tubes passing through them and each row of first tubes passing between them, the direction of the sides of said baffles in the second row being substantially at right angles to the direction of the sides of the baffles in the first row; especially with respect to a third row of baffles adjacent to said second row of baffles, rows of parallel sided baffles in said third row have each row of second tubes passing through them and each row of first tubes passing between them, the direction of the sides of said baffles in the third row being substantially at right angles to the direction of the sides of the baffles in the second row, but substantially in the same direction as the sides in the first row. In particular the vessel has in combination the first, second and third row of baffles as described in the previous sentence; especially the 3 successive rows of baffles are perforated and are each disposed with respect to the tubes and the walls of the vessel such that in axial view the overall effect of the 3 rows is to appear to occupy at least 80% of the cross sectional area of the vessel, excluding the tubes.
The method of distributing according to the invention comprises a method of passing a first fluid axially through a vessel from an upstream to downstream location, wherein the fluid passes axially around successive rows of baffles laterally extending across the vessel, each successive row being in a different spatial relationship across the vessel, so that at least some of said fluid has lateral as well as axial movement. When more than one stream of said first fluid is passed into the vessel, the streams may be distributed separately in the method of the invention, but preferably the at least partly distributed streams, e.g. after the first row of baffles may be mixed, so the baffles overall effect a method of mixing. In particular at least a portion of a first stream of fluid passes axially between first tubes in a first row, and then passes axially and laterally between first and second tubes in a second row, and optionally through at least one perforated baffle in said second row, and preferably at least a portion of said first stream passes axially and laterally between first and second tubes in a third row and optionally through at least one perforated baffle in said third row.
In preferred aspects of the invention the heat exchanger of the invention has the distributor of the vessel of the invention downstream, e.g. on top of it. Extending in the vessel beyond the last baffle in a downstream direction are preferably the second tubes upon the end of each of which is mounted a fuel burner, e.g. a jet nozzle; advantageously the burner ends are in a transverse plane normal to the longitudinal axis of the heat exchange/mixer/vessel. The distributor and/or mixer arrangement of baffles provides a uniform temperature and velocity distribution of first fluid, e.g. air, which moves subsequently in the vessel up towards the burners while the air and fuel ignite (usually auto-ignite) producing elongate flames, which move around and along the first tubes so that the first tubes, which for the endothermic reaction, are immersed in a sea of flame. The exiting combustion gases from the burning in the vessel leave the vessel, optionally via an accelerated movement through an annulus of upwardly converging diameter, the annulus surrounding the incoming first tubes; in this way the endothermic reactants are preheated and then heated by the combustion of the exothermic reactants. The combined heat exchanger, mixer/distributor combustion vessel, (including burners), together with their associated first and second tubes can form a compact reformer for reforming hydrocarbons to carbon monoxide and hydrocarbon with maximum internal heat distribution and minimum temperature for the exiting endothermic and exothermic reaction products. If desired the heat exchanger, mixer and tubes may be supported in the external apparatus via means to absorb elongations and stresses due to expansion e.g. bellows on the tube sheets used to support the tubes.

Heat exchange apparatus and method of use

BP Exploration Operating Company Limited