This invention relates to compositions comprising (a) film formers and (b) microencapsulated biocides that are free of heavy metals and to methods for making such compositions. This invention further relates to antifouling compositions and antifouling coatings.

The invention relates to the use of microencapsulated heavy-metal-free biocides in antifouling coating compositions.
Antifouling coatings for preventing infestation by algae, barnacles, tube worms, mussels or other marine organisms on the surface of articles which come into contact with sea water or brackish water have been used for a long time. Infestation growth is a severe problem especially in the case of ships, since, for example, the frictional resistance is increased and, as a consequence of the increased energy consumption and frequent spells in dry dock, the operating costs are significantly heightened.
A distinction can be made between antifouling coatings which include biocides and those which are biocide-free. Biocide-free antifouling coatings possess anti-adhesion properties, which are intended to prevent the attachment of marine organisms. The effectiveness of the prior art biocide-free antifouling coatings, however, is limited, so that mechanical cleaning of the ship""s hull or of the underwater construction becomes necessary within relatively short periods of time. More effective are antifouling coating which comprise biocides which kill the infestation-forming organisms. Customary antifouling biocides are organotin compounds. Copper antimony and bismuth compounds have also been proposed, these, however, are less effective. The night part of the prior art biocide-containing antifouling coatings is their low environmental compatibility. Antifouling biocides which contain heavy metals are particularly problematic, since they cause contamination of the sea water and of the sea bed, especially in the area of harbours.
In contradistinction to these biocides which comprise heavy metals, heavy-metal-free biocides, which are generally of lower ecotoxicity, since they can frequently be broken down into non-toxic metabolites in sea water, do not have a good long-term action, since, apparently, the active substance is degraded prematurely while still in the coating.
The object of the present invention is therefore to provide a highly effective antifouling coating which has good long-term action and improved environmental compatibility.
It has now been found that antifouling coatings with heavy-metal-free biocides exhibit an improved long-term action if the biocide is in microencapsulated form.
The invention therefore provides antifouling compositions and antifouling coatings based on film-formers and biocides, which are characterized in that the biocides are microencapsulated.
Suitable biocides are preferably heavy-metal-free algicides, fungicides, insecticides, molluscicides and bactericides.
Triazoles:
Azaconazole, bromuconazole, cyproconazole, dichlobutrazol, diniconazole, hexconazole, metconazole, penconazole, propiconazole, tebuconazole, amitrole, azocyclotin, epoxyconazole, bitertanol, difenoconazole, fenbuconazole, fenchlorazole, fenethanil, fluquinconazole, flusilazole, flutriafol, imibenconazole, isozofos, myclobutanil, paclobutrazol, (xc2x1)-cis-1-(4-chlorophenyl)-2-( 1H-1,2,4-triazol-1-yl)-cycloheptanol, tetraconazole, triadimefon, triadimenol, triapenthenol, triflumizole, triticonazole, uniconazole and their metal salts and acid adducts.
Imidazoles:
Imazalil, pefurazoate, prochloraz, triflumizole.
Thiazolecarboxanilides, such as 2xe2x80x2,6xe2x80x2-dibromo-2-methyl-4-trifluoromethoxy-4xe2x80x2-trifluoromethyl-1,3-thiazole-5-carboxanilide and their metal salts and acid adducts.
Succinate dehydrogenase inhibitors, such as:
Fenfuram, furcarbanil, cyclafluramid, furmecyclox, seedvax, metsulfovax, pyrocarbolid, oxycarboxin, Shirlan, mebenil (mepronil), benodanil, flutolanil (Moncut);
Naphthalene derivatives, such as:
Terbinafine, naftifine, butenafine;
Sulphenamides, such as dichlofluanid, tolylfluanid, folpet, fluorfolpet; captan, captofol;
Benzimidazoles, such as carbendazim, benomyl, furathiocarb, fuberidazole, thiophonatmethyl, thiabendazole or salts thereof;
Morpholine derivatives, such as tridemorph, fenpropimorph, falimorph, dimethomorph, dodemorph; aldimorph, fenpropidin and their salts with arylsulphonic acids, such as p-toluenesulphonic acid and p-dodecylphenyl-sulphonic acid;
Dithiocarbamates, cufraneb, ferbam, mancopper, mancozeb, maneb, metam, metiram, thiram zeneb, ziram:
Benzothiazoles, such as 2-mercaptobenzothiazole;
Benzamides, such as 2,6-dichloro-N-(4-trifluoromethylbenzyl)-benzamide;
Boron compounds, such as boric acid, boric esters, borax;
Formaldehyde and formaldehyde donor compounds, such as benzyl alcohol mono-(poly)-hemiformal, oxazolidines, hexa-hydro-S-triazines, N-methylolchloracetamide, paraformadehyde, nitropyrine, oxolic acid, tecloftalam;
Tris-N-(cyclohexyldiazeniumdioxy)-aluminium, N-(cyclo-hexyldiazeniumdioxy)-tributyl, K salts;
N-Methylisothiazolin-3-one, 5-chloro-N-methylisothiazolin-3-one, 4,5-dichloro-N-octylisothiazolin-3-one, N-octyl-isothiazolin-3-one, 4,5-trimethylene-isothiazolinone, 4,5-benzisothiazolinone;
Aldehydes, such as cinnamaldehyde, formaldehyde, glutardialdehyde, xcex2-bromo-cinnamaldehyde; thiocyanates, such as thiocyanatomethylthiobenzothiazole, methylenebisthiocyanate, and the like;
Quaternary ammonium compounds, such as benzyldimethyltetradecylammonium chloride, benzyldimethyldodecylammonium chloride, didecyldimethylammonium chloride;
Iodine derivatives, such as diiodomethyl p-tolyl sulphone, 3-iodo-2-propinyl alcohol, 4-chlorophenyl-3-iodopropargyl formal, 3-bromo-2,3-diiodo-2-propenyl ethylcarbamate, 2,3,3-triiodoallyl alcohol, 3-bromo-2,3-diiodo-2-propenyl alcohol, 3-iodo-2-propinyl n-butylcarbamate, 3-iodo-2-propinyl-n-butylurea, 3-iodo-2-propinyl n-hexylcarbamate, 3-iodo-2-propinyl cyclohexylcarbamate, 3-iodo-2-propinyl phenylcarbamate;
Phenol derivatives, such as tribromophenol, tetrachlorophenol, 3-methyl-4-chlorophenol, 3,5-dimethyl-4-chlorophenol, phenoxyethanol, dichlorophen, o-phenylphenol, m-phenylphenol, p-phenylphenol, 2-benzyl-4-chlorophenol and their alkali metal salts and alkaline earth metal salts.
Microbicides having an activated halogen group, such as chloroacetamide, N-methylolchloroacetamide, bronopol, bronidox, tectamer such as 2-bromo-2-nitro-1,3-propanediol, 2-bromo-4xe2x80x2-hydroxy-acetophenone, 2,2-dibromo-3-nitrilo-propionamide, 1,2-dibromo-2,4-dicyanobutane, xcex2-bromo-xcex2-nitrostyrene;
Pyridines, such as 1-hydroxy-2-pyridinethione (and the Na, Fe, Cu, Mn, Zn salts thereof), tetrachloro-4-methylsulphonylpyridine, pyrimethanol, mepanipyrim, dipyrithione;
Dialkyldithiocarbamates, such as Na salts of dialkyldithiocarbamates, tetramethylthiuram disulphide, potassium N-methyl-dithiocarbamate;
Nitriles, such as 2,4,5,6-tetrachloroisophthalonitrile, disodium cyano-dithioimidocarbamate;
Quinolines, such as 8-hydroxyquinoline and the Cu salts thereof;
Mucochloric acid, 5-hydroxy-2(5H)-furanone;
4,5-Dichlorodithiazolinone, 4,5-benzodithiazolinone, 4,5-trimethylenedithiazolinone, 4,5-dichloro-(3H)-1,2-dithiol-3-one, 3,5-dimethyl-tetrahydro-1,3,5-thiadiazine-2-thione,
N-(2-p-Chlorobenzoylethyl)-hexaminium chloride, potassium N-hydroxymethyl-Nxe2x80x2-methyl-dithiocarbamate,
2-Oxo-2-(4-hydroxy-phenyl)acethydroximic acid chloride,
Phenyl 2-chloro-cyano-vinyl sulphone,
Phenyl 1,2-dichloro-2-cyano-vinyl sulphone.
Furthermore, highly effective compositions are also prepared with the following active substances:
Fungicides:
Methyl (E)-methoximino[xcex1-(o-tolyloxy)-o-tolyl]acetate, methyl (E)-2-{2-[6-(2-cyanophenoxy)-pyrimidin-4-yl-oxy]phenyl}-3-methoxyacrylate,
Acypetacs, 2-aminobutane, ampropylfos, anilazine, benalaxyl, bupirimate, chinomethionat, chloroneb, chlozolinate, cymoxanil, dazomet, diclomezine, dichloram, diethofencarb, dimethirimol, diocab, dithianon, dodine, drazoxolon, edifenphos, ethirimol, etridiazole, fenarimol, fenitropan, fentin acetate, fentin hydroxide, ferimzone, fluazinam, flurormide, flusulfamide, flutriafol, fosetyl, fthalide, furalaxyl, guazatine, hymexazol, iprobenfos, iprodione, isoprothiolane, metalaxyl, methasulfocarb, nitrothal-isopropyl, nuarimol, ofurace, oxadiyl, perflurazoate, pencycuron, phosdiphen, pimaricin, piperalin, procymidone, propamocarb, propineb, pyrazophos, pyrifenox, pyroquilon, quintozene, tar oils, tecnazene, thicyofen, thiophanate-methyl, tolclofos-methyl, triazoxide, trichlamide, tricyclazole, triforine, vinclozolin.
Insecticides:
Phosphates, such as azinphos-ethyl, azinphos-methyl, xcex1-1(4-chlorophenyl)-4-(O-ethyl, S-propyl)phosphoryloxy-pyrazole, chlorpyrifos, coumaphos, demeton, demeton-S-methyl, diazinon, dichlorvos, dimethoate, ethoate, ethoprophos, etrimfos, fenitrothion, fenthion, heptenophas, parathion, parathion-methyl, phosalone, phoxim, pirimiphos-ethyl, pirimiphos-methyl, profenofos, prothiofos, sulfprofos, triazophos and trichlorphon;
Carbamates, such as aldicarb, bendiocarb, xcex1-2-(1-methylpropyl)-phenyl methylcarbamate, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, cloethocarb, isoprocarb, methomyl, oxamyl, pirimicarb, promecarb, propoxur and thiodicarb;
Organosilicon compounds, preferably dimethyl(phenyl)silyl-methyl 3-phenoxybenzyl ethers such as dimethyl-(4ethoxyphenyl)-silylmethyl 3-phenoxybenzyl ether, or
(dimethylphenyl)-silyl-methyl 2-phenoxy-6-pyridylmethyl ethers, such as e.g. dimethyl-(9-ethoxy-phenyl)-silylmethyl 2-phenoxy-6-pyridylmethyl ether or [(phenyl)-3-(3-phenoxyphenyl)-propyl](dimethyl)-silanes, such as e.g. (4-ethoxyphenyl)-[3-(4-fluoro-3-phenoxyphenyl-propyl]dimethyl-silane, silafluofen;
Pyrethroids, such as allethrin, alphamethrin, bioresmethrin, byfenthrin, cycloprothrin, cyfluthrin, decamethrin, cyhalothrin, cypermethrin, deltamethrin, alpha-cyano-3-propancarboxylate, fenpropathrin, fenfluthrin, fenvalerate, flucythrinate, flumethrin, fluvalinate, permethrin, resmethrin and tralomethrin;
Nitroimines and nitromethylenes, such as 1-[(6-chloro-3-pyridinyl)-methyl]-4,5-dihydro-N-nitro-1H-imidazole-2-amine (imidacloprid), N-[(6-chloro-3-pyridyl)methyl-]N2-cyano-N1-methylacetamide(NI-25);
Abamectin, AC 303, 630, acephate, acrinathrin, alanycarb, aldoxycarb, aldrin, amitraz, azamethiphos, bacillus thuringiensis, phosmet, phosphamidon, phosphine, prallethrin, propaphos, propetamphos, prothoate, pyraclofos, pyrethrins, pyridaben, pyridafenthion, pyriproxyfen, quinalphos, RH-7988, rotenone, sodium fluoride, sodium hexafluorosilicate, sulfotep, sulphuryl fluoride, tar oils, teflubenzuron, tefluthrin, temephos, terbufos, tetrachlorvinphos, tetramethrin, O-2-tert-butyl-pyrimidin-5-yl-o-isopropyl-phosphorothiate, thiocyclam, thiofanox, thiometon, tralomethrin, triflumuron, trimethacarb, vamidothion, verticillium lacanii, XMC, xylylcarb, benfuracarb, bensultap, bifenthrin, bioallethrin, MERbioallethrin (S)-cyclopentenyl isomer, bromophos, bromophos-ethyl, buprofezin, cadusafos, calcium polysulphide, carbophenothion, cartap, chinomethionat, chlordane, chlorfenvinphos, chlorfluazuron, chlormephos, chloropicrin, chlorpyrifos, cyanophos, beta-cyfluthrin, alpha-cypermethrin, cyophenothrin, cyromazine, dazomet, DDT, demeton-S-methylsulphon, diafenthiuron, dialifos, dicrotophos, diflubenzuron, dinoseb, deoxabenzofos, diaxacarb, disulfoton, DNOC, empenthrin, endosulfan, EPN, esfenvalerate, ethiofencarb, ethion, etofenprox, fenobucarb, fenoxycarb, fensulfothion, fipronil, flucycloxuron, flufenprox, flufenoxuron, fonofos, formetanate, formothion, fosmethilan, furathiocarb, heptachlor, hexaflumuron, hydramethylnon, hydrogen cyanide, hydroprene, IPSP, isazofos, isofenphos, isoprothiolane, isoxathion, iodfenphos, kadethrin, lindane, malathion, mecarbam, mephosfolan, mercurous, chloride, metam, Metarthizium, anisopliae, methacrifos, methamidophos, methidathion, methiocarb, methoprene, methoxychlor, methyl isothiocyanate, metholcarb, mevinphos, monocrotophos, naled, Neodiprion sertifer NPV, nicotine, omethoate, oxydemeton-methyl, pentachlorophenol, petroleum oils, phenothrin, phenthoate, phorate;
Molluscicides:
Fentin acetate, metaldehyde, methiocarb, niclosamide, thiodicarb, trimethacarb;
Algicides:
Dichlororphen, endothal, fentin acetate, quinoclamine;
Herbicides:
Diuron, dichlorophen, endothal, fentinacet, quinochlamine.
Suitable biocides are preferably algicides, such as diuron, dichlorophen, endothal, fentin acetate, quinoclamine, molluscicides, such as fentin acetate, metaldehyde, methiocarb, niclosamide, thiodicarb and trimethacarb, fungicides, such as dichlofluanid, tolylfluanid, iodopropargyl butylcarbamate, fluorfolpet and azoles, such as tebuconazole or customary antifouling active substances, such as 2-(N,N-dimethylthiocarbamoylthio)-5-nitrothiazyl, tetrabutyldistannoxane, 2-tert-butylamino-4-cyclopropylamino-6-methylthio-1,3,5-triazine, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, 2,4,5,6-tetrachloroisophthalonitrile, tetramethylthiuram disulphide, 2,4,6-trichlorophenylmaleimide, 2,3,5,6-tetrachloro-4-(methylsulphonyl)-pyridine, diiodomethyl paratryl sulphone, thiabendazole, tetraphenylboron pyridine salt, sodium salt of 2-pyridinethiol 1-oxide.
Other biocides preferred in accordance with the invention are benzothiophen-2-carboxamide S,S-dioxides of the formula (1)
in which
R1 represents optionally substituted alkyl, represents alkenyl or alkinyl, represents in each case optionally substituted cycloalkyl or cycloalkylalkyl, or represents in each case optionally substituted aralkyl, aralkenyl, aralkinyl or aryl,
R2 represents hydrogen or represents optionally substituted alkyl or
R1 and R2 together with the nitrogen atom to which they are attached represent an optionally substituted heterocycle and
R3, R4, R5 and R6 independently of one another each represent hydrogen, halogen, cyano, nitro, alkyl, alkoxy, alkylthio, halogenoalkyl, halogenoalkoxy or halogenoalkylthio, especially the compound N-cyclohexylbenzothiophen-2-carboxamide S,S-dioxide.
Particularly good effects are also obtained with active-substance combinations preferably of the specified biocides.
Particular preference is given to those biocides which are biodegradable.
The term biodegradable for the purposes of the invention is used for those biocides which have a half life of less than 180 days in sea water at 25xc2x0 C., preferably less than 90 days. The mechanism of the degradation reaction is not critical for the inventive effect. It may be chemical degradation by, for example, hydrolysis or oxidation, photochemical degradation, or biological degradation by microorganisms.
Examples of suitable degradable biocides can be found, for example, within the group of the phenoxyacetic acids, ureas, thioureas, thiocarbamates, sulphamides and halogenoaromatic compounds.
Preferred active substances are:
Suitable materials for the microencapsulation of the biocides are the materials known for this purpose, especially polymers. Examples of suitable polymers are polyesters, natural and synthetic polyamides, melamine resins, polyurethanes, polyureas, polysiloxanes, poly(meth)acrylates, and copolymers of (meth)acrylic acid and (meth)acrylic ester. In many cases it is advantageous to employ crosslinked polymers. As a natural polyamide, gelatine is particularly suitable. It is employed in particular as the coacervate and complex coacervate. Gelatine-containing complex coacervates for the purposes of the invention are, in particular, combinations of gelatine and synthetic polyelectrolytes. Suitable synthetic polyelectrolytes are copolymers with incorporated units of, for example, maleic acid, acrylic acid, methacrylic acid, acrylamide and methacrylamide. Gelatine-containing capsules can be crosslinked with customary curing agents such as, for example, formaldehyde or glutaraldehyde.
The microencapsulated biocide can be in the form of a single biocide particle enveloped by a polymer shell. Alternatively, there may be a polymer particle in which a large number of biocide particles are enclosed or in which the biocide is present in molecularly disperse form. The microencapsulation of isolated biocide particles can be carried out by known methods, for example by applying a finished polymer from solution by precipitating the polymer or evaporating the solvent. It is also possible to produce the polymer on the surface of the biocide particle by means of assembly reactions, such as addition polymerization, polyaddition or polycondensation.
The preparation of polymer particles comprising a large number of enclosed biocide particles can be carried out, for example, by melt compounding with subsequent comminution. Another very suitable process for preparing biocide-containing polymer particles is bead addition polymerization. In this procedure, liquid mixtures of monomers and biocide are broken up into small droplets and cured, giving spherical particles in which the active substance is enclosed. Suitable monomers for preparing biocide-containing bead addition polymers are, for example, the following monofunctional monomers and multifunctional monomers, which generally act as crosslinkers: styrene, vinyltoluene, chlorostyrene, chloromethylstyrene, acrylic acid, methacrylic acid, acrylates, methacrylates, acrylonitrile, methacrylonitrile, acrylamide, methacrylamide, vinyl chloride, vinylidene chloride, vinyl acetate, divinylbenzene, diethylene glycol divinyl ether, 1,7-octadiene, 1,5-hexadiene, ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, trimethylolpropane trimethachrylate and allyl methacrylate.
It has been found that antifouling coatings with bead addition polymers comprising active substance permit high filling levels and have very good processing properties.
The average particle size of the microencapsulated biocides is from 0.1 to 200 xcexcm, preferably from 0.2 to 20 xcexcm.
The proportion of the micro-encapsulated biocides is from 1 to 50, preferably from 2 to 40% by weight, based on the antifouling coating.
Suitable binders are the film forming binders known for coatings. By way of example there may be mentioned: polyesters polyacrylates, polyurethanes, polyamides, chlorinated rubbers, polyvinyl chloride and polysiloxanes. Also highly suitable are so-called 2-component systems, in which the binder is produced from two reactive components in the coating. Preferred 2-component systems are, for example, polyurethanes formed from a polyester- or polyetherdiol and a diisocyanate. Through the incorporation of polysiloxane units into, for example, a polyetherdiol it is possible to produce polyurethanes having anti-adhesion properties. Binders which consist predominantly of polysiloxane units are available both as condensation-crosslinking 1-component systems and as addition-crosslinking 2-component systems. The binders can be processed from organic solvents or as an aqueous dispersion. Examples of suitable organic solvents are aliphatic hydrocarbons, especially petroleum fractions, aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ketones, esters and ethers.
In addition to the microencapsulated heavy-metal-free biocides and the organopolysiloxanes, the antifouling coating compositions of the invention may generally include, as well as the binders, customary auxiliaries such as, for example, fillers, solvents, plasticizers, dyes, pigments, catalysts, inhibitors, tackifiers, coatings additives and/or common dispersing or formulating auxiliaries. In addition to the heavy-metal-free biocides it is also possible, of course, for heavy-metal-containing biocides to be present as well, such as, for example, N-(cyclo-hexyldiazeniumdioxy)-tributyltin bis-N-(cyclohexyldiazeniumdioxy)-copper; metal soaps, such as tin, copper, and zinc naphthenate, octoate, 2-ethylhexanoate, oleate, phosphate and benzoate, metal salts, such as copper hydroxycarbonate, sodium dichromate, potassium dichromate, potassium chromate, copper sulphate, copper chloride, copper borate, zinc fluorosilicate, copper fluorosilicate, copper salt of 2-pyridine-thiol 1-oxide; oxides, such as tributyltin oxide, Cu2O, CuO and ZnO; Ag, Zn or Cu-containing zeolites alone or enclosed in polymeric active substances, although in this case the ecological advantage is limited.
The examples which follow are intended to illustrate the invention. The invention is not limited to the examples. All references to parts and percentages are by weight unless otherwise indicated.


Non-invasive methods for determining blood flow distribution in a region of interest are provided. The method includes illuminating a region of interest of a subject with a coherent light source; sequentially acquiring at least two speckle images of the region of interest, wherein sequentially acquiring the at least two speckle images comprises acquiring the at least two speckle images in synchronization with motion of the heart of the subject; and electronically processing the at least two acquired speckle images based on the temporal variation of the pixel intensities in the at least two acquired speckle images to generate a laser speckle contrast imaging (LSCI) image, determine distribution of blood flow speed in principal vessels and quantify perfusion distribution in tissue in the region of interest from the LSCI image. The LSCI image enables detection of different blood flow speeds.

Revascularization is an interventional procedure for the provision of a new, additional, or augmented blood supply to a body part or organ. Revascularization typically involves a thorough analysis and/or diagnosis and treatment of the existing diseased vasculature of the affected organ. In some instances, revascularization can be aided by the use of different imaging modalities, such as magnetic resonance imaging (MRI), positron emission tomography (PET) scan, computed tomography (CT) scan, and X ray fluoroscopy.
Revascularization is designed to improve blood flow to tissues perfused by the principal arterial vessel(s) supplying that tissue. Revascularization may be needed, for example, due to an obstruction in the native arterial vessel supplying that tissue. Coronary artery bypass grafting (CABG) is a revascularization procedure that may be used to increase blood flow to ischemic myocardium by bypassing the native coronary obstructions.
There are two measurement components to the revascularization evaluation, blood flow in the principal arterial supply and quantitative perfusion in the tissue. Conventional methods for measurement of blood flow and perfusion are limited, despite the benefit these measurements would bring to the clinical evaluation of the quality of the revascularization procedure.
Some conventional interoperative methods of measuring blood flow are based on ultrasound detection of blood flow in the graft conduits, but not the native principal arterial vessel(s). Some conventional angiographic evaluation methods include conventional coronary angiography performed in a hybrid operating room setting at the time of surgery. Recently, Novadaq Technologies, Inc. of Toronto, Canada has introduced fluorescence imaging that uses both angiographic image evaluation and quantitative perfusion evaluation to CABG.
However, ultrasound detection typically requires physical contact between the graft vessel and a probe. Furthermore, ultrasound detection typically relies on proper placement of the probe around the vessel to obtain accurate measurement of flow speed and can be unreliable, measurement to measurement.
Coronary angiography typically requires radiation and administration of toxic image contrast agent. Furthermore, hybrid operating rooms used for coronary angiography can be relatively expensive, making this method unavailable to many patients undergoing CABG.
Fluorescence imaging typically requires injection of non-toxic dye into the patient. Furthermore, fluorescence imaging typically cannot provide information to directly determine the speed of blood flow in principal vessels. Despite the above, there remains a need for alternative methods of determining blood flow.

Methods, systems and computer program products for non-invasive determination of blood flow distribution using speckle imaging techniques and hemodynamic modeling


A method for treating obsessive-compulsive disorders, somatoform disorders, dissociative disorders, eating disorders, impulse control disorders, and autism is disclosed. These disorders are treated by administering an effective amount of a D1/D5 antagonist.

This invention is directed to the treatment of a group of disorders marked by repetitive, intrusive thoughts and/or ritualistic behaviors, i.e., obsessive-compulsive disorder, somatoform disorders, dissociative disorders, eating disorders, impulse control disorders, and autism.
Obsessive-compulsive disorder (xe2x80x9cOCDxe2x80x9d), recognized to be among the most common of all psychiatric disorders, occurs in 2 to 3% of the U.S. population. OCD is characterized by anxiety-provoking and intrusive thoughts (e.g., fear of contamination and germs, doubt and uncertainty about future harm, need for symmetry, etc.) which lead to ritualistic and/or irrational behavior (e.g., constant checking, washing, touching, counting, etc.). See Hollander, et al., J. Clin Psychiatry 57 (Suppl. 8), pp. 3-6 (1996).
Somatoform disorders (e.g., body dysmorphic disorder and hypochondriasis) are characterized by abnormal preoccupation with one""s appearance or physical condition. For example, body dysmorphic disorder is a preoccupation with an imagined or slight defect in appearance. Many sufferers of body dysmorphic disorder are severely debilitated by their abnormal preoccupation, with significant impairment in social, occupational, or other important aspects of daily life. See Phillips, J. Clin Psychiatry 57 (suppl. 8), pp. 61-64 (1996). Hypocondriasis is characterized by a persistent conviction that one is, or is likely to become ill. Many hypochondriacs are unable to work or engage in ordinary activities due to their preoccupation with illness.
Dissociative disorders (e.g., depersonalization) are characterized by sudden temporary alterations in identity, memory, or consciousness, segregating normally integrated memories or parts of the personality from the dominant identity of the individual. Depersonalization disorder, which is a dissociative disorder, is characterized by one or more episodes of depersonalization (feelings of unreality and strangeness in one""s perception of the self or one""s body image).
Eating disorders (e.g., anorexia nervosa, bulimia, and binge eating) are characterized by abnormal compulsions to avoid eating or uncontrollable impulses to consume abnormally large amounts of food. These disorders affect not only the social well-being, but the physical well-being of sufferers.
Impulse control disorders (e.g., pathological gambling, compulsive buying, sexual compulsions and kleptomania) are characterized by a preoccupation with, and an inability to refrain from repeatedly engaging in various behaviors that are either socially unacceptable, or abnormally excessive by societal norms.
Autism is a disorder characterized by a preoccupation with one""s own self and a severe impairment of the ability to perceive or react to outside stimuli in a normal fashion. Many autistics are incapable of even communicating with others.
In view of the tragic and debilitating effects of these disorders, there is a strong need for a drug therapy which can effectively treat such disorders.
There have been some reports that certain D1 antagonists: inhibit L-DOPA-induced self-mutilatory behavior in neonatal-6-hydroxypropamine lesioned rats; are able to block amphetamine-induced locomotor activity and apomorphine-induced stereotypy in rats; inhibit grooming and oral activities induced by the administration of D1 agonists to marmosets; inhibit apomorphine induced stereotypy in mice; and reverse extrapyramidal side effects in monkeys treated with haloperidol. See Criswell, et al., Neuropsychopharmacology, 7 (2) pp. 95-103 (1992); Kerkman, et al., European Journal of Pharmacology, 166 (3) 481-91 (1989); Gnanalingham, et al., Psychophamacology, 117 (4), pp. 403-12 (1995); Acri, et al., Drug Dev. Res. 37 (1), pp. 39-47 (1996); McHugh, et al., European Journal of Pharmacology 202, pp. 133-134 (1991); Coffin, et al., Neurochem. Int., Vol. 20, Suppl., pp. 141S-145S (1992); Waddington, Gen. Pharmac. Vol. 19, No. 1, pp. 55-60 (1988); and Beaulieu, Can. J. Neurol. Sci., 14: 402-406 (1987).
The present invention provides a method for treating a human suffering from obsessive compulsive disorder, a somatoform disorder, a dissociative disorder, an eating disorder, an impulse control disorder, or autism by administering an effective amount of a D1/D5 antagonist.
As used herein, the following terms have the meanings set forth below.
xe2x80x9cD1/D5 antagonistxe2x80x9d is a compound that selectively binds to the D1 receptors and/or the D5 receptors in the brain, thereby decreasing or preventing dopamine access to these sites. A compound xe2x80x9cselectively bindsxe2x80x9d to the D1 and/or D5 receptors when it exhibits greater binding to either the D1 or D5 receptors than it does to the D2 receptors. D1/D5 antagonists include compounds that bind only to the D1 receptor (pure D1 antagonists), only to the D5 receptor (D5 antagonists), as well as compounds that bind to both the D1 and D5 receptors.
Non-limitative examples of D1/D5 antagonists include: SCH 39166 [(xe2x88x92)-trans-6,7,7a, 8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5-H-benzo[d]naphtho{2,1-b}azepine HCl]; SCH23390 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol maleate]; BTS-73-947 [(S)-1-(1 -(2-chlorophenyl)cyclopropyl)-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline]; A-69024 [1-(2-bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline]; JHS-271 [8-chloro-3-[6-(dimethylamino)hexyl]-2,3,4,5-tetrahydro-5-phenyl-1H-3-Benzazepin-7-ol]; JHS-198 [8-chloro-3-[6-(dimethylamino)hexyl]-2,3,4,5-tetrahydro-5-phenyl-1H-3-Benzazepin-7-ol in a 1:1 complex with cyanoborane]; JHS-136 [8-chloro-3-[4-(dimethylamino)butyl]-2,3,4,5-tetrahydro-5-phenyl-1H-3-Benzazepine-7-ol]; and NNC-22-0010 [S(+)-8-chloro-5-(5-bromo-2,3-dihydrobenzofuran-7-yl)-7-hydroxy-3-methyl-2,3,4,5-tetrahydro-1H-3-Benzazepine]. The foregoing D1/D5 antagonists can be prepared by known methods, e.g., by the methods described in U.S. 5,302,716, WO 93/13073, WO 93/1702, WO 95/25102, and J. Med. Chem 38 (21) pp. 4284-93 (1995), the contents of which are incorporated herein by reference. SCH 39166 and SCH 23390 are particularly preferred, with SCH 39166 being most preferred.
It will be appreciated by those skilled in the art that the doses effective for treating obsessive-compulsive disorder, somatoform disorders, dissociative disorders, eating disorders, impulse control disorders, and autism will vary depending on the particular individual treated, and the relative severity of the disorder. The D1/D5 antagonists are preferably administered at daily doses of 0.01 to 500 mg/kg of bodyweight, more preferably 0.01 to 150 mg/kg, most preferably 0.01 to 10 mg/kg. The daily dose may be administered in a single dose, or divided equally into several doses.
For preparing pharmaceutical compositions with the D1/D5 antagonists used in this invention, inert, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, dispersible granules, capsules, cachets and suppositories. The powders and tablets may be comprised of from about 5 to about 70 percent active ingredient. Suitable solid carriers are known in the art, e.g. magnesium carbonate, magnesium stearate, talc, sugar, lactose. Tablets, powders, cachets and capsules can be used as solid dosage forms suitable for oral administration.
For preparing suppositories, a low melting wax such as a mixture of fatty acid glycerides or cocoa butter is first melted, and the active ingredient is dispersed homogeneously therein as by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool and thereby solidify.
Liquid form preparations include solutions, suspensions and emulsions. As an example may be mentioned water or water-propylene glycol solutions for parenteral injection.
Liquid form preparations may also include solutions for intranasal administration.
Aerosol preparations suitable for inhalation may include solutions and solids in powder form, which may be in combination with a pharmaceutically acceptable carrier, such as an inert compressed gas.
Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for either oral or parenteral administration. Such liquid forms include solutions, suspensions and emulsions.
The D1/D5 antagonists may also be deliverable transdermally. The transdermal compositions can take the form of creams, lotions, aerosols and/or emulsions and can be included in a transdermal patch of the matrix or reservoir type as are conventional in the art for this purpose.
Preferably, the D1/D5 antagonists are administered orally.

Method of treating obsessive compulsive disorders, somatoform disorders, dissociative disorders, eating disorders, impulse control disorders, and autism


A base for rendering a gas-fired water heater, having a lower combustion chamber, explosion-proof, is described. The base has elevating supports which are provided with securement means in an upper portion thereof for securing same to a bottom end of a gas water heater housing whereby to support the gas water heater elevated from a floor surface. One or more vapour detectors are associated with the base to detect the presence of combustible vapours. The vapour detectors are connected to a switch to shut off a gas burner and pilot in the combustion chamber before the combustible vapours reach the flame of the gas burner and/or pilot through combustion chamber air supply passages in a lower end of the gas water heater housing. The temperature in the chamber is lower than the temperature of ignition of gas vapour.

The present invention relates to a base for rendering a gas-fired water heater explosion-proof by elevating the water heater and its combustion chamber from a floor surface and by using vapour detector(s) to detect the presence of combustible vapours before they can reach the combustion chamber.
Gas water heaters are provided with a combustion chamber in the lower part thereof where a gas burner is located to heat the bottom tank wall of the water heater to produce hot water. The combustion chamber has openings whereby to admit fresh air for mixture with the gas to produce a combustible product. These gas water heaters can be hazardous if they are utilized in areas where there is a risk that combustible vapours may propagate in the area of the air supply to the burners. Usually, combustible vapours will accumulate on a floor surface, because they are heavier than air, and slowly build up and rise thus creating a large cloud of ignitable gas vapours. If such a cloud of vapour propagates to the combustion chamber of a gas water heater it will ignite and cause a very serious explosion and usually destroy the gas water heater and fragment the gas line to add further fuel to the fire. Needless to say, such explosion would be disastrous to any person in the immediate vicinity of the gas water heater and cause a building fire.
Gas water heaters can be installed in garages. However, in garages fumes are usually released by automobiles due to gas leakage or the storage of paint or the use of glues and other such combustible vapour generating products that we usually find in work areas of a garage. The basement of a residence is also another hazardous location where dangerous products are stored. In the past, various attempts have been made to deal with this problem but to date none has proven satisfactory.
It is known to provide sealed combustion chambers and provide duct work whereby to admit fresh air from the outside into these chambers for the combustible products. We usually find such installations in gas fireplaces and these fire places are usually installed close to an outside wall for this purpose. The chimney duct work of these gas appliances are usually formed by concentric piping wherein the centre pipe is used as a flue and the annular channel thereabout formed by the spaced outer pipe acts as the fresh air intake to the combustion chamber. This process in water heater is known as xe2x80x9cdirect vent water heaterxe2x80x9d and has been widely used for more than six years. Wall distance from the appliance is the limitation of the application.
There is currently millions of gas water heaters in operation and most of these are fed combustible air through the base of the housing of the water heater and they are subjected to the above-mentioned problems.
It is a feature of the present invention to provide a base for rendering a gas water heater substantially explosion-proof.
Another feature of the present invention is to provide a base which is adaptable to existing water heaters whereby to provide a retrofit to elevate the water heaters from a floor support surface and wherein vapour detectors are associated with the base to render the water heater substantially explosion-proof by early switching off the gas supply and extinguishing the burner, the pilot flames and cooling the components in the combustion chamber.
Another feature of the present invention is to provide a base and a connector whereby to secure the base to existing gas water heaters to support the water heaters elevated from a floor support surface and wherein detecting and switching means is provided to shut off the gas supply to the burner of the combustion chamber and pilot and burner flames upon detection of combustible vapours.
According to the above features, from a broad aspect, the present invention provides a base for rendering a gas-fired water heater, having a lower combustion chamber, explosion-proof. The base has elevating support means to support the water heater elevated from a floor surface. One or more vapour detectors are associated with the base to detect the presence of combustible vapours. The vapour detectors are connected to switching means to shut-off a gas burner and pilot in the combustion chamber before the combustible vapour reach the gas burner and pilot through combustion chamber air supply passages in a lower end of the gas water heater housing.

Elevating base for gas-fired water heater


The invention provides a method of forming a polyurethane foam suitable for use as a wound-contacting layer, said method comprising: mixing 1 part by weight of an isocyanate-capped prepolymer having from 0.5 to 4.8 meq. NCO groups/g with from 0.4 to 1.0 parts by weight of water and an effective amount of a nonvolatile pharmaceutically acceptable acid to form a prepolymer mixture; allowing said prepolymer mixture to cure to form a foamed product; followed by drying the foamed product. The invention also provides acidified polyurethane foams obtainable by this method, and wound dressings comprising such foams.

This invention relates to polyurethane foams, and more particularly to a method of making conformable, high-density polyurethane foams for use in wound dressings. The invention also relates to a wound dressing having a wound-contacting layer formed from such a foam.
Polyurethane foams have been proposed for a number of uses in the prior art. For example, U.S. Pat. No. 3,903,232 discloses hydrophilic cross-linked polyurethane foams which are said to be useful for external body cleaning, for internal body usage and as absorptive products such as diapers. The foams are prepared by reacting particular isocyanate-capped polyoxyethylene polyols having an isocyanate functionality greater than 2 with large amounts of an aqueous reactant, preferably water.
EP-A-0171268 discloses a dressing for use in deep wounds, which dressing comprises individual pieces of absorbent hydrophilic foam contained within a porous bag formed from an apertured polymeric film. The absorbent foam is preferably a hydrophilic polyurethane foam which can be made from HYPOL (Registered Trade Mark) isocyanate-capped polyether prepolymer marketed by W.R. Grace and Co., and non-ionic surfactants.
According to EP-A-0171268, the fact that the foam is present in the form of individual pieces confers on the dressing the property of being able to conform to the contours of a wound cavity both on initial application of the dressing and subsequently following absorption of body fluids. It is said that existing commercially available foams, if used as a single piece, have too high a density to possess the required degree of conformability.
U.S. Pat. No. 4,339,550 discloses a hydrophilic foam composition which is prepared by the xe2x80x9cin situxe2x80x9d reaction of an isocyanate-capped polyether prepolymer having a functionality of from about 2 to about 8, water, and a chemically compatible, essentially non-polar, volatile organic compound. The foam is stated to be capable of achieving a sustained, controlled release of the volatile materials from the foamed structure. Suitable xe2x80x9ccontrol releasexe2x80x9d ingredients include polyols, such as propylene glycol and glycerine.
EP-A-0335669 discloses a hydrophilic foam composition comprising the xe2x80x9cin situxe2x80x9d reaction product of an isocyanate-capped polyether prepolymer, a hydrophilic agent capable of absorbing water, an adjuvant comprising an alcohol, a wetting agent and water. One application which is proposed for the foam composition is in the manufacture of wound dressings. The composition is said to carry the adjuvant releasably, so that at least a portion of the adjuvant is released into an external liquid (e.g. wound exudate) with which the foam composition comes into contact.
A wide range of prepolymer, hydrophilic agents, adjuvants and wetting agents are proposed in EP-0335669. Suitable prepolymers are said to include prepolymers having an NCO content as high as 2.55 meq/g or as low as 0.5 to 0.9 meq/g. Water soluble monohydric, dihydric and polyhydric alcohols are all said to be suitable adjuvants, but glycerol is preferred, and the majority of the examples involve the use of glycerol. The sole example in which a monohydric alcohol is employed as the adjuvant involves the use of a prepolymer having an NCO content of 1.6 meq/g. The resulting product is said not to be acceptable because of xe2x80x9cgross porosityxe2x80x9d.
EP-A-0541391 describes a method of forming a polyurethane foam suitable for use as a wound-contacting layer, the method comprising mixing 1 part by weight of an isocyanate-capped prepolymer having from 0.5 to 1.2 meq NCO groups/g with from 0.4 to 1.0 parts by weight of water in the presence of from 0.05 to 0.4 parts by weight of a C1 to C3 monohydric alcohol, and then drying the product such that the amount of water-soluble alcohol remaining in the product is less than 1% by weight. The resulting foam has high density and conformability.
GB-A-1417962 discloses a non-reticulated polyurethane foam material, the foam cells adjacent to at least one surface of which are irreversibly partially collapsed relative to foam cells remote from said surface. The specification notes that polyurethane foam can be reversibly deformed or compressed to reduce the thickness up to a certain extent, but the original thickness will be recovered upon washing or steam heating. In contrast, the xe2x80x9cirreversibly partially collapsedxe2x80x9d cells are formed by applying a greater degree of compression, but not so great a degree of compression as to cause the cells to collapse completely or fuse.
According to GB-A-2253628, the foams disclosed in GB-A-1417962 are suitable for the treatment of moderately exuding wounds, but they may not have sufficient absorbency to absorb all the exudate from heavily exuding wounds. GB-A-2253628 further reports that an attempt to increase the absorbency of the known foam by incorporating an alginate during manufacture of the foam was unsuccessful. The alginate was said to be degraded, with consequent impairment of its absorbent and haemostatic properties. A deterioration in the appearance of the foam was also noted. However, GB-A-2253628 teaches that alginate may be used to enhance the absorbency of a polyurethane foam, after the foam has already been formed. Thus, the specification discloses a polyurethane foam which is impregnated with alginate, for example by spreading an alginate gel onto the surface of the foam, or immersing the foam in a solution of alginate.
In contrast to the teaching of GB-A-2253628, we have found that alginates can advantageously be incorporated during the production of polyurethane foams, if the foam is formed by mixing an isocyanate-capped prepolymer with a relatively small amount of water. Although the addition of alginate does not substantially increase the absorbency of the polyurethane foam (as measured on a weight per weight basis), it has been found that polyurethane foams containing alginate generally have smaller, more uniform cells, and higher densities.
Accordingly, the present invention provides a method of forming a polyurethane foam suitable for use as a wound-contacting layer, the method comprising mixing one part by weight of an isocyanate-capped prepolymer having from 0.5 to 4.8 meq NCO groups/g with from 0.4 to 1.0 parts by weight of water, characterised in that the mixture further contains from 0.2 to 20% by weight of alginic acid or a salt thereof Preferably, the alginic acid or alginate salt is present in an amount of from 0.5 to 10% by weight, more preferably 0.5 to 5% by weight, e.g. from 0.75 to 2.5% by weight.
In particularly preferred embodiments, the isocyanate-capped prepolymer has from 0.5 to 1.2 meq. NCO groups/g.
Preferably, the step of mixing is carried out in the presence of from 0.05 to 0.4 parts by weight of a C1 to C3 monohydric alcohol. Subsequent drying of the foam preferably results in a product containing less than 1% by weight of the monohydric alcohol.
The use of a relatively small amount of water in accordance with the present invention produces an initial reaction mixture of relatively high initial viscosity. Carbon dioxide formed by hydrolysis of isocyanate end groups is therefore trapped, producing a foamed hydrogel.
The present invention also provides a polyurethane foam which is suitable for use as a wound-contacting layer, the foam having a density of at least 0.28 g/cm3, and containing from 0.2 to 20% by weight of alginic acid or a pharmaceutically acceptable salt thereof, generally uniformly distributed throughout said foam.
Foams produced according to the method of the invention preferably have a density of at least 0.3 g/cm3. Particularly preferred foams have a density in the range 0.3 to 1.0 g/cm3, e.g. about 0.5 g/cm3.
The foams of the invention also preferably have an elongation at break of at least 150%, and more preferably at least 300%. Particularly preferred foams according to the invention have an elongation at break in the range from 500 to 2000%.
Depending on the proportions of other additives, the foam s of the invention have an absorbency of at least 3 g saline/g, preferably at least 5 g/g, and more preferably from 8 to 20 g/g. The foams are thus highly absorbent, yet conformable.
The foams of the invention also have the property of swelling and expanding when water is absorbed. This is particularly advantageous in a wound contact layer, because the swelling of the foam causes it to move inwards towards the wound bed thus filling the wound cavity. This encourages the wound to heal from the base upwards and outwards, and it discourages epithelialization over the wound surface before the bed has been filled with granulation tissue .
The degree of swelling of the foams of the present invention on complete saturation with an aqueous medium is typically at least 100% (expressed in terms of increase in volume), and preferably at least 200%. Preferred foams swell by 400 to 800%. Despite this high degree of swelling, however the foams of the invention retain their integrity even after absorption of large quantities of water.
Moreover, the foams are found to have a morphology which is particularly appropriate for low adherence wound dressings. The foams are open-celled, the cells being very regular in size and shape, with very smooth edges to the pores in the walls of the cells. Typically, the cells of the foams of the invention have an average diameter in the range 0.1 to 0.6 mm.
The prepolymer which is used in the method of the invention is preferably an isocyanate-capped polyether, such as an ethyleneoxy/propyleneoxy copolymer. A particularly suitable prepolymer is that available under Trade Mark HYPOL Hydrogel.
Although the preferred methods of the invention comprehend the use of any of methanol, ethanol or propanol, the use of methanol is particularly preferred. All three alcohols reduce the rate of reaction between the isocyanate-capped prepolymer and water, but the effect of methanol is more marked. A reduction of the reaction rate is desirable in order to facilitate mixing of the various components and spreading of the reaction mixture into a layer of suitable thickness for curing. In addition, the monohydric alcohol serves to end cap some of the NCO end groups, preventing reaction with water to form the urea linkage. This also gives a more flexible, conformable foam.
More preferably, one part by weight of the isocyanate-capped prepolymer is mixed with water in the presence of from 0.05 to 0.25 parts by weight of methanol or from 0.1 to 0.3 parts by weight of ethanol.
It will be appreciated that other components may be added to the reaction mixture in the method of the invention, in order to give desired properties to the product. In particular, it is preferable to include a small proportion (e.g. up to 30% by weight of the wet composition) of a rubber, which may be either natural or synthetic. This has the effect of increasing the cure time for the polyurethane, and increases extensibility, strength and tack.
Most importantly, it substantially reduces shrinkage of the gel on drying, and it also improves bubble formation, producing more regular, smaller bubbles.
Preferably, the rubber is added in the form of a latex, ie. a suspension or emulsion of the rubber in an aqueous medium. The latex will generally comprise 40 to 70% solids by weight, e.g. 50 to 60% by weight. If the foam is to be used as a wound contact layer, the rubber must of course be pharmaceutically acceptable.
Acrylic-based rubbers are particularly preferred. These are commercially available in the form of latexes, such as PRIMAL B-15J and RHOPLEX N-560 (Registered Trade Marks), manufactured by the Rohm and Haas company.
In addition to the methanol or ethanol other alcohols, and particularly polyols, may be included in the reaction mixture to produce a softer, more conformable foam. For example, a polyol sold by Bayer AG under the Registered Trade Mark Levagel may be used. However, traces of such alcohols are likely to remain in the free form after the foaming reaction, and these traces may be difficult to remove from the foam merely by heating. The use of higher boiling alcohols is therefore preferably avoided if the foam is to be used as a wound contact layer, because of the likelihood that such alcohols will be leached from the foam during use of the dressing. When used as or in wound dressings, the foams of the invention contain less than 1% by weight of water soluble alcohols, and more preferably less than 0.1% by weight. It is particularly preferred that the foams of the invention are essentially free of water soluble alcohols (e.g. less that 0.01% by weight).
For use as a wound-contact layer, the foams of the invention may also include topical medicaments and antiseptics, such as silver sulfadiazine, povidone iodine, chlorhexidine acetate and chlorhexidine gluconate, as well as other therapeutically useful additives such as polypeptide growth factors and enzymes.
The present invention also provides a wound dressing comprising a wound contact layer formed from a polyurethane foam as described above, in conjunction with a water-repellant or water-impermeable backing layer. It is greatly preferred that the backing layer also be moisture vapour permeable, as well as being extensible and conformable. A particularly suitable material is a high density polyurethane foam, such as MEDFIX 4003 or 4005 (Registered Trade Mark). These are polyurethane foams of a blocked toluene diisocyanate nature, and are predominantly closed cell.
A particularly advantageous presentation for the dressing of the invention is as an island of wound-contact material on a backing layer, wherein at least the marginal portions of the backing layer are coated with adhesive. Any medically accepted, skin friendly adhesive is suitable, including acrylic, hydrocolloid, polyurethane and silicone based adhesives.
The adhesive may be applied either continuously or discontinuously over the marginal portions of the backing layer. Preferably, however, the adhesive is applied continuously over the whole of the backing layer if the backing layer is not itself impermeable to bacteria, so as to ensure that the backing layer/adhesive combination is impermeable to bacteria
It is also preferred that the combination of adhesive and backing layer have a minimum moisture vapour permeability of 400 g/m2/24 hrs, and preferably at least 700 g/m2/24 hrs.
The preferred adhesive is a polyurethane gel material known as LEVAGEL (Registered Trade Mark) and marketed by Bayer AG. This adhesive is made up of three components, namely a modified diphenylmethane diisocyanate, high molecular weight polyhydroxy polyether and a catalyst (dibutyltindilaurate). These three components may be mixed such that the gel contains 4-10 parts (preferably 4.6-6.4 parts) of the modified diphenylmethane diisocyanate, 99.9-99.9975 parts, (preferably 99.94-99.995 parts) of the polyhydroxy polyether and 0.0025-0.1 parts (preferably 0.005-0.06 parts) of the catalyst.
The gel may be mixed by the methods given in U.S. Pat. No. 4,661,099 and applied by conventional coating methods to the backing. The thickness of the gel layer may be between 0.01 mm and 1.0 mm, and preferably between 0.05 mm and 0.5 mm, giving a coating weight of between 25 g/m2 and 250 g/m2.
The dressing may also contain a wicking layer between the wound contact layer and the backing layer. Such a wicking layer provides absorbency, but more importantly it encourages moisture to move from the wound facing side of the dressing to the back of the dressing where it escapes out of the dressing through the breathable backing. It should have good wicking properties so that moisture can be spread over as large a surface area as possible, thus increasing evaporation The overall effect of this layer is to draw moisture from the wound facing layer, thus decreasing the chances of wound maceration, and to increase evaporation through the backing of the dressing
The wicking layer may be formed of several plies (which may or may not be the same) if desired, but it is preferred that the total thickness of the wicking layer does not exceed 1 mm. It is also preferred that the wicking layer be substantially the same size and shape as the wound-facing layer, or slightly smaller than the wound-facing layer.
Suitable materials for the wicking layer include nonwoven, woven and knitted fabrics. Nonwoven viscose fabrics such as those conventionally used for making nonwoven surgical swabs are preferred, but it will be understood that many alternative fabrics particularly other cellulosic fabrics) could be used in their place.
The dressings of the invention will generally be sterile and enclosed in a conventional bacteria-proof envelope. Sterilization may conventionally be carried out using xcex3-irradiation, but other sterilization methods such as electron beam sterilization may also be used.
The effect of addition of a nonvolatile acid on experimental curing rates of polyurethane foams for use in wound dressings is shown by the following specific embodiments, which are non-limiting examples for the purpose of illustration only.
Methanol (6 g) was added to HYPOL (Registered Trade Mark) Hydrogel prepolymer (50 g; NCO content 0.5-1.2 meq/g) in a disposable cup and mixed thoroughly for a few seconds. Water (32 g) and Latex (12 g) were then added to the HYPOL mixture and stirred vigorously. The foaming mixture was poured onto release paper and spread using a stainless steel hand spreader set at a gap of 2.2 mm. The foam was left to cure and the foam sheet and release paper were placed in an oven (80xc2x0 C.-100xc2x0 C.) for 30 min to drive off the water. After cooling, the foam, was lifted from the release paper, allowed to shrink, and replaced on the same paper. The foam was then kiss-cut to size and shape.
The procedure of Example 1 was repeated, but with the addition of varying amounts of sodium alginate and calcium alginate, as set out in the following Table. The Table also shows the absorbency of the foams produced, as determined by the following method:
A sample of foam (approximately 3 g) is prepared and weighed, then placed in a pre-weighed cylindrical wire mesh basket (5 cm diameter, 9 cm depth; 9 cm mesh size). The basket is formed from galvanised steel wire (approx. 0.95 mm thickness), and is closed at one end. The basket and sample are then completely submerged in 0.9% saline solution for 1 hour. The basket is removed from the saline solution, and allowed to drain for 15 seconds, with the closed end down. The basket is then weighed in order to determine the weight of the saturated sample.
It will be seen that the addition of comparatively small amounts of sodium or calcium alginate results in a modest increase in absorbency (on a weight per weight basis), but absorbency decreases with greater quantities of alginate. More importantly, however, the addition of alginate gives rise to smaller and more uniform pores in the foam. This can be seen in the accompanying figures which are scanning electron micrographs at xc3x9720 magnification.

Polyurethane foams for use in wound dressings


A mini clean room for preventing wafer pollution includes a robot arm, a clean room body slidably disposed on the robot arm and at least one lock unit which is rotatably connected with the clean room body. During operation, the robot arm extends out of the clean room body to carry a wafer waiting to be processed, and then moves back into the clean room body which can provide an isolated and protected space for the wafer to avoid that the wafer is polluted. The present invention also discloses a method of using a mini clean room for preventing wafer pollution.

1. Field of the Invention
The present invention relates to a sealing protection structure and using method thereof, and more particularly to a mini clean room for preventing wafer pollution and using method thereof.
2. Description of Related Art
At present, a semiconductor process includes various complex procedures, such as repeated oxidation, diffusion, lithography, etching, physical or chemical vapor deposition and so on. For improving precision of semiconductor processes, almost all procedures are designed to be performed under automatic control. Please refer to FIG. 1 illustrating a robot arm carrying a wafer. After the wafer 4a is processed on machine station 1a in one procedure, the robot arm 3a receives the wafer 4a and carries it to another machine station 2a for the next procedure. Owing to the robot arm 3a, dust and errors caused by manual operation, which influence the yield of the wafer manufacturing process, can be avoided.
However, the transportation of the robot arm has the shortcomings as follows:
1. When the robot arm takes the wafer out of one machine station, the wafer carried by the robot arm is completely exposed to the environment, so it is possible that particles in the atmosphere pollute the wafer on the robot arm during transportation.
2. If the wafer becomes polluted during transportation by the robot arm, this will influence the next production step.
The inventors of the present invention believe that the shortcomings described above can be improved and suggest the present invention which is of a reasonable design and is an effective improvement based on deep research and thought.

Mini clean room for preventing wafer pollution and using method thereof


Method for the preparation of citalopram comprising reaction of a compound of Formula (IV)

The present invention relates to a method for the preparation of the well known antidepressant drug citalopram, 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile.
Citalopram is a well known antidepressant drug that has now been on the market for some years and has the following structure:
It is a selective, centrally acting serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, accordingly having antidepressant activities. The antidepressant activity of the compound has been reported in several publications, eg. J. Hyttel, Prog. Neuro-Psychopharmacol. and Biol. Psychiat., 1982, 6, 277-295 and A. Gravem, Acta Psychiatr. Scand., 1987, 75, 478-486. The compound has further been disclosed to show effects in the treatment of dementia and cerebrovascular disorders, EP-A 474580.
Citalopram was first disclosed in DE 2,657,013 corresponding to U.S. Pat. No. 4,136,193. This patent publication describes the preparation of citalopram by one method and outlines a further method which may be used for preparing citalopram.
According to the process described, the corresponding 1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile is reacted with 3-(N,N-dimethylamino)propyl-chloride in the presence of methylsulfinylmethide as condensing agent. The starting material was prepared from the corresponding 5-bromo derivative by reaction with cuprous cyanide.
According to the method, which is only outlined in general terms, citalopram may be obtained by ring closure of the compound:
in the presence of a dehydrating agent and subsequent exchange of the 5-bromo group with cyano using cuprous cyanide. The starting material of Formula II is obtained from 5-bromophthalide by two successive Grignard reactions, i.e. with 4-fluorophenyl magnesium chloride and N,N-dimethylaminopropyl magnesium chloride, respectively.
A new and surprising method and an intermediate for the preparation of citalopram were described in U.S. Pat. No. 4,650,884 according to which an intermediate of the formula
is subjected to a ring closure reaction by dehydration with strong sulfuric acid in order to obtain citalopram. The intermediate of Formula III was prepared from 5-cyanophthalide by two successive Grignard reactions, i.e. with 4-fluorophenyl magnesium halogenide and N,N-dimethylaminopropyl magnesium halogenide, respectively.
Further processes are disclosed in International patent application Nos. WO 98019511, WO 98019512 and WO 98019513. WO 98019512 and WO 98019513 relate to methods wherein a 5-amino-, 5-carboxy- or 5-(sec. aminocarbonyl)phthalide is subjected to two successive Grignard reactions, ring closure and conversion of the resulting 1,3-dihydroisobenzofuran derivative to the corresponding 5-cyano compound, i.e. citalopram. International patent application No. WO 98019511 discloses a process for the manufacture of citalopram wherein a (4-substituted-2-hydroxymethylphenyl-(4-fluorphenyl)methanol compound is subjected to ring closure and the resulting 5-substituted 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran converted to the corresponding 5-cyano derivative which is alkylated with a (3-dimethylamino)propylhalogenide in order to obtain citalopram.
Finally, methods of preparing the individual enantiomers of citalopram are disclosed in U.S. Pat. No. 4,943,590 from which it also appears that the ring closure of the intermediate of Formula III may be carried out via a labile ester with a base.
With respect to the above methods for the preparation of citalopram the process comprising exchange of the 5-bromo group with cyano proved not to be very convenient in commercial scale, since it was the yield was rather low, the product was impure and in particular that it was difficult to separate the resulting citalopram from the corresponding 5-bromo compound.
It has now been found that citalopram may be obtained in a high yield as a very pure produce by a new catalytic process in which 5-bromo or 5-chloro is exchanged with 5-cyano in 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-isobenzofuran thus avoiding the extensive work up of the old cyanide exchange process.
Accordingly, the present invention relates to a novel method for the preparation of citalopram comprising reaction of a compound of Formula IV
wherein R is Cl or Br with a with a cyanide source, for example KCN, NaCN or (Rxe2x80x2)4NCN where (Rxe2x80x2)4 indicates four groups which may be the same or different and are selected from hydrogen and straight chain or branched C1-6 alkyl, in the presence of a nickel catalyst and isolation of the corresponding 5-cyano compound, i.e. citalopram
as the base or a pharmaceutically acceptable salt thereof.
In a further aspect the invention relates to the above process in which the compound of Formula IV is the S-enatiomer.
In yet another aspect, the present invention relates to an antidepressant pharmaceutical composition comprising citalopram manufactured by the process of the invention.
By the process of the invention citalopram is obtained as a pure product in high yield thus reducing costly purification processes. Furthermore, the reaction may be carried out in more convenient solvents, at a low temperature and at a low excess of CNxe2x88x92 compared to the known cyano exchange process. The process has environmental advantages in that it only uses small amounts of heavy metals. Finally, this process gives an improved crystalline product enabling easy conversion to desired salts.
The cyanide source used may be any useful source. Preferred sources are KCN, NaCN or (Rxe2x80x2)4NCN where (Rxe2x80x2)4 is as defined above. The cyanide source is used in a stoichiometric amount or in excess, preferably 1-2 equivalents are used per equivalent starting material of Formula IV. (Rxe2x80x2)4N+ may conveniently be (Bu)4N+. The cyanide compound is preferably NaCN or KCN or Zn(CN)2.
The nickel catalyst may be any suitable Ni(0) or Ni(II) containing complex which acts as a catalyst, such as Ni(PPh3)3, ("sgr"-aryl)-Ni(PPh3)2Cl, etc. The nickel catalysts and their preparation are described in WO 96/11906, EP-A-613720 or EP-A-384392.
In one embodiment of the invention the reaction is carried out in the presence of a catalytic amount of Cu+ or Zn2+.
In a particularly preferred embodiment a Nickel(0) complex is prepared in situ before the cyanation reaction by reduction of a Nickel(II) precursor such as NiCl2 or NiBr2 by a metal, such as zinc, magnesium or mangan in the presence of excess of complex ligands, preferably triphenylphosphin.
The Ni-catalyst is conveniently used in an amount of 0.5-10, preferably 2-6, most preferably about 4-5 mol %.
Catalytic amounts of Cu+ and Zn2+, respectively, means substoichiometric amounts such as 0.1-5, preferably 1-3%. Any convenient source of Cu+ and Zn2+ may be used. Cu2+ is conveniently used as the Zn(CN)2 salt or formed in situ by reduction of a nickel (II) compounds using zinc.
In a preferred embodiment of the invention, R is chloro.
In a particularly preferred embodiment of the invention a compound of Formula IV wherein R is Cl is reacted with NaCN or KCN in the presence of a Ni(PPh3)3 which is preferably prepared in situ as described above
The intermediate of Formula IV wherein R is bromo or chloro may be prepared from bromo- and chlorophthalide, respectively, as described in DE 2,657,013 and the corresponding U.S. Pat. No. 4,136,193.
The reaction may be performed in any convenient solvent, preferably acetonitril, propionitrile, THF and ethylacetate.
Other reaction conditions, solvents, etc. are conventional conditions for such reactions and may easily be determined by a person skilled in the art.
The compound of general Formula I may be used as the free base or as a pharmaceutically acceptable acid addition salt thereof. As acid addition salts, such salts formed with organic or inorganic acids may be used. Exemplary of such organic salts are those with maleic, fumaric, benzoic, ascorbic, succinic, oxalic, bismethylenesalicylic, methanesulfonic, ethanedisulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, p-aminobenzoic, glutamic, benzene sulfonic and theophylline acetic acids, as well as the 8-halotheophyllines, for example 8-bromotheophylline. Exemplary of such inorganic salts are those with hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric and nitric acids.
The acid addition salts of the compounds may be prepared by methods known in the art. The base is reacted with either the calculated amount of acid in a water miscible solvent, such as acetone or ethanol, with subsequent isolation of the salt by concentration and cooling, or with an excess of the acid in a water immiscible solvent, such as ethylether, ethylacetate or dichloromethane, with the salt separating spontaneously.
The pharmaceutical compositions of the invention may be administered in any suitable way and in any suitable form, for example orally in the form of tablets, capsules, powders or syrups, or parenterally in the form of usual sterile solutions for injection.
The pharmaceutical formulations of the invention may be prepared by conventional methods in the art. For example, tablets may be prepared by mixing the active ingredient with ordinary adjuvants and/or diluents and subsequently compressing the mixture in a conventional tabletting maschine. Examples of adjuvants or diluents comprise: Corn starch, potato starch, talcum, magnesium stearate, gelatine, lactose, gums, and the like. Any other adjuvant or additive colourings, aroma, preservatives etc. may be used provided that they are compatible with the active ingredients.
Solutions for injections may be prepared by solving the active ingredient and possible additives in a part of the solvent for injection, preferably sterile water, adjusting the solution to the desired volume, sterilisation of the solution and filling in suitable ampoules or vials. Any suitable additive conventionally used in the art may be added, such as tonicity agents, preservatives, antioxidants, etc.

Abstract: wherein R is Cl or Br with a cyanide source in the presence of a nickel catalyst and isolation of the corresponding 5-cyano compound, i.e. citalopram.


An Internet download enhancement system for downloading a file comprising an application arranged to initiate a download process and receive a downloaded file over one of a narrow band download path and a broadband broadcast download path, wherein modules in communication with the application are arranged to provide selectable download options among the available download paths. The selectable download options are based at least on an unused bandwidth of one or more of the download paths, thereby enabling the input of a selected download option. The modules are arranged in response to the input to cause a download process to download files over one of the narrow band download path and the broadband broadcast download path and then to output the downloaded file to application.

The invention relates generally to methods of data transfer and specifically to the transfer of data packets over a broadcast radio frequency channel coordinated with a separate point-to-point digital data transfer system, such as a telephone modem-linked Internet access.
The xe2x80x9cInternetxe2x80x9d (also referred to as the World Wide Web) is a global network of interconnected data links by which various types of data service or functionalities are available to individuals accessing the network via a computer. Both the data service locations and the individuals have unique network addresses on the Internet. Data service or access to the Internet is provided by Internet Service Providers (ISP""s) to residential and commercial subscribers. Each subscriber gains access to the Internet in the form of a separate operative session. Such sessions operate simultaneously and independently of each other. Each subscriber at a respective address can initiate a session through the use of a computer connected to an ISP at its respective address on the Internet. The ISP provides a competitively priced package of functionalities tailored to one or more types of subscribers, including at least basic access to the Internet. Additional services that are frequently made available include electronic mail, access to one or more Internet search engines, known as browsers, chat rooms, news features, weather information, and advertising space. Such functional features appear on the subscriber""s computer screen as choices and, when selected, connect to the source providing that feature, so that the selected functional feature appears on the subscriber""s screen. Because there is a basic access to all Internet addresses, the subscriber can contact and interact with any Internet address to obtain information or a file from that address, more commonly known as xe2x80x9cdownloading the filexe2x80x9d from that address. A typical subscriber session is an electronic communication with the ISP requesting a selected functionality, and also through the ISP to various other network locations on the Internet which provide selected additional functionalities or files which can be downloaded to the subscriber""s computer.
Typically, most electronic data traffic in a given subscriber session consists of a dialog of inquiries and responses paced at the timing of human discourse. While graphics data accompanies much of this traffic, the relative size of each portion of the dialog compared to the movement of substantially large files of data is small. On occasion, the subscriber may request receipt of a large file containing any of numerous data-types, e.g., it can have a particular digital format and a narrowly tailored application. A large file can be an exceptionally large text file, or it can be a file representing a scanned photograph, a video recording in the form of a sequence of video frames, or a file containing computer-executable code such as a software application, computer game, or operating system component. Thus, it can be appreciated that data transfers requested by typical subscribers on the Internet are bursty, i.e., small or large amounts of data are requested, followed by little or no data requests for periods of time.
One major problem with downloading large files from the Internet is the capacity of the network to convey large files at speeds acceptable to the Internet subscriber. Capacity is defined by the available bandwidth of the particular network route over which the files are transmitted, and low available bandwidth results in longer download times. An additional consideration is the manner in which both the subscriber""s computer and the source of the transmitted file are connected to the Internet. While each network link comprising the particular route the file travels between source and subscriber destination has an associated bandwidth, both the initial and the final link between the ISP and the subscriber can be the most troublesome. When a modem connection to a public-switched telephone line is employed, communication though the data network is constrained to data rates in the tens of kilobits per second (e.g., 11, 16 or 56 kbits per second) or low hundreds of kilobits per second in the case of a hard-wire equivalent integrated services digital network (ISDN) line. As an alternative, cable television providers offer a high speed connection service through a cable modem. However, use of a cable modem is expensive because the cable connection is priced at premium levels. A cable modem connection is a full-time connection, not an on-demand connection, as opposed to a modem connected to a telephone line.
Various methods have been proposed to shorten the time required to download large data files by utilizing more than one data path. For example, U.S. Pat. No. 5,181,107 to Rhodes, discloses an information service distribution system wherein a terminal device connected to a television network and to a point-to-point, public-switched telephone line. A subscriber requests a menu of information services (or already has a menu from a previous request) over the telephone line. After appropriate identification has been made for billing purposes, the subscriber can request a selection from the menu (or pay for additional use of a previous selection), such as a video game, dating services, shopping selection, etc., stored in a remotely located information services storage center. In response to the request conveyed over the telephone link, the center transmits files encoded as digital bit streams over a television broadcast channel. While menus are received and decoded by all subscribers, only the requested file is decoded at the requesting subscriber location. There are several drawbacks to this system. For example, the system is restricted to selections from a fixed menu; selected information service is displayed/interacted with only on the subscriber""s television set; there is no access to all downloadable files available on the Internet; and there is no choice between point-to-point and broadcast downloading paths.
U.S. Pat. No. 5,768,539 to Metz et al., discloses a downloading generating system that utilizes a broadband digital broadcast channel and a separate narrow band two-way data communications channel. The digital broadcast network includes provision for downloading executable applications software over one broadcast channel and video programming over a second broadcast channel. The two channels can be multiplexed on a single transport stream. The narrow band two-way data communications capability is for signaling interactive text services such as video file requests. The system includes a set-top device at the subscriber location which, when instructed by the subscriber, transmits data request signals over a narrow band two-way data channel provided by a public switched telephone network or alternatively, by a coaxial cable, e.g., a cable television network cable. The data requests are relatively short messaging-type communications which can be accommodated on the available narrow band two-way data channel. The data provider, which can be an ISP, responds by downloading both packets of executable code and the requested video data file in the form of compressed data for a plurality of video frames to the subscriber over the digital broadband channels. The downloaded executable code, along with a resident software application, are stored and executed in a protected memory device that includes an operating system in the subscriber""s set-top terminal. The set-top terminal can emulate a CATV tuner/decoder for channel selections. Execution of the downloaded code received over the first broadcast channel in turn controls selective capture and presentation of audio and video segments received over the second digital broadcast channel. The billing and other administrative data is communicated to the subscriber over the narrow band two-way data channel.
The Metz et al. system is principally directed toward video-on-demand wherein a known library of video programming is maintained for on-demand download requests by subscribers. While this arrangement enables the transport of digital program information over a relatively fast digital broadcast channel, it is limited to first downloading executable control code into the memory of a subscriber""s set-top terminal, and then utilizing that executable control code to control the operation of the set-top terminal to identify and receive a specific data-type, i.e., the audio and video segments of the program information, as distinguished form any executable computer control code. A disadvantage of the system disclosed in the Metz et al. Patent is that it does not offer the capability of downloading generally any file obtainable from any source on the Internet to a specified subscriber on a demand basis. In addition, executable code must be downloaded over the broadband network to the subscriber to enable the subscribers computer to identify and download the accompanying digital program information.
Internet subscribers generally require, on an on-demand basis, the download of one or more large data files of a wide variety of data-types, where the data file could be obtained from any source connected to the Internet. A common complaint by Internet subscribers is that the data transfer rate over telephone lines, a procedure now commonly in use, is slow. Further, complicating the picture, as computers make increasing use of graphics and audio/video segments, the size of downloaded data files will continue to grow. However, the faster ISDN lines needed to handle large files are expensive to install and maintain.
Downloading operating systems such as the above-described system of Metz et al., do not provide general access to available files on the Internet in combination with a choice of download resources, i.e., over slower (and cheaper) telephone lines, or over faster (and more expensive) broadcast channels. A low cost system is needed that significantly reduces download response time Internet subscribers while enabling such users to use the narrow band communications resources provided by a public-switched, point-to-point telephone lines for communicating request-response type Internet communications between the subscriber and the subscriber""s ISP. A further need is for such a low cost system that provides an option of sharing the use of a high data rate broadcast data channel for downloading substantially large amount of data, regardless of its data-type and source on the lntemet.
In accordance with this invention, a system for enhancing the process of downloading files from the Internet, includes a low cost data receiver for receiving radio frequency signals, a digital data demodulator and software components located both at an ISP and at the subscriber""s location, that together enable an Internet subscriber to select and communicate a choice of available high speed and low speed download paths for downloading a data file from a downloading source to the subscribers computer. The high speed download path option may comprise one or more broadcast data channels, such as, or example, a digital television broadband broadcast channel. The relatively slower low speed download path option may comprise a narrow band, two-way, point-to-point data channel, such as, for example, a public-switched telephone line.
The broadcast data channel transmits alternatively any one or more types of a stream of digital data packets forming part of a broadcast signal. The point-to-point data transfer channel may be a telephone modem link, such as a public-switched telephone modem link, connected between a subscriber-located computer and an ISP. The data receiver is any data receiving means, e.g., a radio frequency receiving means such as a high definition digital television (HDTV) tuner, analog television tuner, radio tuner or satellite receiver. The demodulator is a system for demodulating digital data from the data receiver and transferring the demodulated data to software residing in the subscriber-located computer.
To accomplish this arrangement, a high speed link is provided between an Internet service provider (ISP) and one or more broadcast data channel providers, and a separate well known lower speed link is provided between the ISP and the subscriber. A third link receivable by all subscribers (and non-subscribers who lack the appropriate data receiver and therefore cannot detect the presence of the downloaded file contained within the broadcast signal), is a broadcast channel originating from the broadcast channel provider.
The option of sharing the use of a high data rate broadcast data channel provided by a broadcast channel provider, for downloading substantially large amounts of data, regardless of its data-type and source on the Internet, depends in part on the availability of the unused portion of the broadcast data channel, i.e., the unused bandwidth. Content providers, such as the NATIONAL BROADCAST CORPORATION(trademark), Inc., which own and operate numerous television broadcast stations in major metropolitan areas, are implementing a capability for broadcasting digital television signals over a television channel allocated to them by the Federal Communications Commission (FCC). The television channels are connected to the television subscriber by numerous well known methods, for example by television transmission or by cable television network providers. The FCC permits the use of the 19.3 Mbit/second data rate digital signal to include both audio and video information with unused bandwidth to be made available for other purposes. According to the present invention, one such purpose is to provide the extra data bandwidth to the ISP, thereby providing an additional revenue stream to the broadcaster from the otherwise unused portion of the data bandwidth. The above-described large data files downloaded from an ISP to one of many Internet subscribers, who receive Internet connectivity services from that ISP, advantageously can be communicated over the bandwidth available on the digital broadcast channel.
When a subscriber in networked communication with an ISP that provides Internet connection service to the subscriber over a narrow band two-way data channel transmits a request to download a large data file (which may originate from any addressable location on the Internet), software located at the ISP queries an updated broadcast channel availability status file to determine unused bandwidth availability for one or more broadcast channels. The ISP-located software communicates this availability over the narrow band two-way telephone channel to software resident in the subscriber""s computer, which displays information including the size of the desired file to be downloaded, the computed download time and associated cost for the broadband digital broadcast download path option. The software resident in the subscriber""s computer also displays similar narrow band download information, along with options for the subscriber to select the desired download method. If the slower, narrow band, two-way, point-to-point data channel is selected, a software module located at the ISP detects this selection and directs other software located at the ISP to encode and then download the desired data file over the narrow band route, which connects to Internet application software residing in the subscriber""s computer. If the faster broadcast channel option is selected, a software module located at the ISP encodes the file with a subscriber-specific identification and then (after obtaining the file from its Intemet address source) directs the desired data file to be transmitted over a high speed network link between the ISP and the broadcast channel provider, where a separate software module introduces the desired data file into the television broadcast data channel to be transmitted as part of the broadcast signal. The subscriber is billed for use of the broadcast channel. While the desired data file can be received by all broadcast channel receivers, only those with data receivers of the present invention can detect the desired data file, and only the requesting subscriber""s data receiver will identify and store the subscriber-specific encoded file. The file can be encrypted prior to transmission and decrypted upon receipt, thereby preserving privacy. The digital data demodulator of the present invention, also located at the subscribers location, demodulates the received and identified digital data, and transfers it to the subscribers computer for storage and access by the Intemet application and other applications, as necessary, thus completing the download process of the Intemet download enhancement system.