This invention is directed to a composition comprising expandable cross linked polymeric microparticles having an unexpanded volume average particle size diameter of from about 0.05 to about 10 microns and a cross linking agent content of from about 9,000 to about 200,000 ppm of labile cross linkers and from 0 to about 300 ppm of non-labile cross linkers and to the use of the composition for modifying the permeability of subterranean formations and increasing the mobilization and/or recovery rate of hydrocarbon fluids present in the formations.

This invention provides compositions and methods for the recovery of hydrocarbon fluids from a subterranean reservoir. More particularly, this invention concerns expandable cross-linked polymeric microparticle compositions that modify the permeability of subterranean formations and increase the mobilization and/or recovery rate of hydrocarbon fluids present in the formations.
In the first stage of hydrocarbon recovery the sources of energy present in the reservoir are allowed to move the oil, gas, condensate etc. to the producing wells(s) where they can flow or be pumped to the surface handling facility. A relatively small proportion of the hydrocarbon in place can usually be recovered by this means. The most widely used solution to the problem of maintaining the energy in the reservoir and ensuring that hydrocarbon is driven to the producing well(s) is to inject fluids down adjacent wells. This is commonly known as secondary recovery.
The fluids normally used are water (such as aquifer water, river water, sea water, or produced water), or gas (such as produced gas, carbon dioxide, flue gas and various others). If the fluid encourages movement of normally immobile residual oil or other hydrocarbon, the process is commonly termed tertiary recovery.
A very prevalent problem with secondary and tertiary recovery projects relates to the heterogeneity of the reservoir rock strata. The mobility of the injected fluid is commonly different from the hydrocarbon and when it is more mobile various mobility control processes have been used to make the sweep of the reservoir more uniform and the consequent hydrocarbon recovery more efficient. Such processes have limited value when high permeability zones, commonly called thief zones or streaks, exist within the reservoir rock. The injected fluid has a low resistance route from the injection to the production well. In such cases the injected fluid does not effectively sweep the hydrocarbon from adjacent, lower permeability zones. When the produced fluid is re-used this can lead to fluid cycling through the thief zone to little benefit and at great cost in terms of fuel and maintenance of the pumping system.
Numerous physical and chemical methods have been used to divert injected fluids out of thief zones in or near production and injection wells. When the treatment is applied to a producing well it is usually termed a water (or gas etc.) shut-off treatment. When it is applied to an injection well it is termed a profile control or conformance control treatment.
In cases where the thief zone(s) are isolated from the lower permeability adjacent zones and when the completion in the well forms a good seal with the barrier (such as a shale layer or xe2x80x9cstringerxe2x80x9d) causing the isolation, mechanical seals or xe2x80x9cplugsxe2x80x9d can be set in the well to block the entrance of the injected fluid. If the fluid enters or leaves the formation from the bottom of the well, cement can also be used to fill up the well bore to above the zone of ingress.
When the completion of the well allows the injected fluid to enter both the thief and the adjacent zones, such as when a casing is cemented against the producing zone and the cement job is poorly accomplished, a cement squeeze is often a suitable means of isolating the watered out zone.
Certain cases are not amenable to such methods by virtue of the facts that communication exists between layers of the reservoir rock outside the reach of cement. Typical examples of this are when fractures or rubble zones or washed out caverns exist behind the casing. In such instances chemical gels, capable of moving through pores in reservoir rock have been applied to seal off the swept out zones.
When such methods fail the only alternatives remaining are to produce the well with poor recovery rate, sidetrack the well away from the prematurely swept zone, or the abandon the well. Occasionally the producing well is converted to a fluid injector to increase the field injection rate above the net hydrocarbon extraction rate and increase the pressure in the reservoir. This can lead to improved overall recovery but it is worthy of note that the injected fluid will mostly enter the thief zone at the new injector and is likely to cause similar problems in nearby wells. All of these are expensive options.
Near wellbore conformance control methods always fail when the thief zone is in widespread contact with the adjacent, hydrocarbon containing, lower permeability zones. The reason for this is that the injected fluids can bypass the treatment and re-enter the thief zone having only contacted a very small proportion, or even none of the remaining hydrocarbon. It is commonly known amongst those skilled in the art, that such near wellbore treatments do not succeed in significantly improving recovery in reservoirs having crossflow of the injected fluids between zones.
A few processes have been developed with the aim of reducing the permeability in a substantial proportion of the thief zone and, or at a significant distance from the injection and production wells. One example of this is the Deep Diverting Gel process patented by Morgan et al (1). This has been used in the field and suffered from sensitivity to unavoidable variations in quality of the reagents which resulted in poor propagation. The gelant mixture is a two component formulation and it is believed that this contributed to poor propagation of the treatment into the formation.
The use of swellable cross linked superabsorbent polymer microparticles for modifying the permeability of subterranean formations is disclosed in U.S. Pat. Nos. 5,465,792 and 5,735,349. However, swelling of the superabsorbent microparticles described therein is induced by changes of the carrier fluid from hydrocarbon to aqueous or from water of high salinity to water of low salinity.
We have discovered novel polymeric microparticles in which the microparticle conformation is constrained by reversible (labile) internal crosslinks. The microparticle properties; such as particle size distribution and density, of the constrained microparticle are designed to allow efficient propagation through the pore structure of hydrocarbon reservoir matrix rock, such as sandstone. On heating to reservoir temperature and/or at a predetermined pH, the reversible (labile) internal crosslinks start to break allowing the particle to expand by absorbing the injection fluid (normally water).
The ability of the particle to expand from its original size (at the point of injection) depends only on the presence of conditions that induce the breaking of the labile crosslinker. It does not depend on the nature of the carrier fluid or the salinity of the reservoir water. The particles of this invention can propagate through the porous structure of the reservoir without using a designated fluid or fluid with salinity higher than the reservoir fluid.
The expanded particle is engineered to have a particle size distribution and physical characteristics, for example, particle rheology, which allow it to impede the flow of injected fluid in the pore structure. In doing so it is capable of diverting chase fluid into less thoroughly swept zones of the reservoir.
The rheology and expanded particle size of the particle can be designed to suit the reservoir target, for example by suitable selection of the backbone monomers or comonomer ratio of the polymer, or the degree of reversible (labile) and irreversible crosslinking introduced during manufacture.
Accordingly, in its principal embodiment, this invention is directed to a composition comprising highly cross linked expandable polymeric microparticles having an unexpanded volume average particle size diameter of from about 0.05 to about 10 microns and a cross linking agent content of from about 9,000 to about 200,000 ppm of labile cross linkers and from 0 to about 300 ppm of non-labile cross linkers.
Definitions of Terms
xe2x80x9cAmphoteric polymeric microparticlexe2x80x9d means a cross-linked polymeric microparticle containing both cationic substituents and anionic substitutents, although not necessarily in the same stoichiometric proportions. Representative amphoteric polymeric microparticles include terpolymers of nonionic monomers, anionic monomers and cationic monomers as defined herein. Preferred amphoteric polymeric microparticles have a higher than 1:1 anionic monomericationic monomer mole ratio.
xe2x80x9cAmpholytic ion pair monomer: means the acid-base salt of basic, nitrogen containing monomers such as dimethylaminoethylacrylate (DMAEA), dimethylaminoethyl methacrylate (DMAEM), 2-methacryloyloxyethyldiethylamine, and the like and acidic monomers such as acrylic acid and sulfonic acids such as 2-acrylamido-2-methylpropane sulfonic acid, 2-methacryloyloxyethane sulfonic acid, vinyl sulfonic acid, styrene sulfonic acid, and the like.
xe2x80x9cAnionic monomerxe2x80x9d means a monomer as defined herein which possesses an acidic functional group and the base addition salts thereof. Representative anionic monomers include acrylic acid, methacrylic acid, maleic acid, itaconic acid, 2-propenoic acid, 2-methyl-2-propenoic acid, 2-acrylamido-2-methyl propane sulfonic acid, sulfopropyl acrylic acid and other water-soluble forms of these or other polymerizable carboxylic or sulphonic acids, sulphomethylated acrylamide, allyl sulphonic acid, vinyl sulphonic acid, the quaternary salts of acrylic acid and methacrylic acid such as ammonium acrylate and ammonium methacrylate, and the like. Preferred anionic monomers include 2-acrylamido-2-methyl propanesulfonic acid sodium salt, vinyl sulfonic acid sodium salt and styrene sulfonic acid sodium salt. 2-Acrylamido-2-methyl propanesulfonic acid sodium salt is more preferred.
xe2x80x9cAnionic polymeric microparticlexe2x80x9d means a cross-linked polymeric microparticle containing a net negative charge. Representative anionic polymeric microparticles include copolymers of acrylamide and 2-acrylamido-2-methyl propane sulfonic acid, copolymers of acrylamide and sodium acrylate, terpolymers of acrylamide, 2-acrylamido-2-methyl propane sulfonic acid and sodium acrylate and homopolymers of 2-acrylamido-2-methyl propane sulfonic acid. Preferred anionic polymeric microparticles are prepared from about 95 to about 10 mole percent of nonionic monomers and from about 5 to about 90 mole percent anionic monomers. More preferred anionic polymeric microparticles are prepared from about 95 to about 10 mole percent acrylamide and from about 5 to about 90 mole percent 2-acrylamido-2-methyl propane sulfonic acid.
Betaine-containing polymeric microparticlexe2x80x9d means a cross-linked polymeric microparticle prepared by polymerizing a betaine monomer and one or more nonionic monomers.
xe2x80x9cBetaine monomerxe2x80x9d means a monomer containing cationically and anionically charged functionality in equal proportions, such that the monomer is net neutral overall. Representative betaine monomers include N,N-dimethyl-N-acryloyloxyethyl-N-(3-sulfopropyl)-ammonium betaine, N,N-dimethyl-N-methacryloyloxyethyl-N-(3-sulfopropyl)-ammonium betaine, N,N-dimethyl-N-acrylamidopropyl-N-(2-carboxymethyl)-ammonium betaine, N,N-dimethyl-N-acrylamidopropyl-N-(2-carboxymethyl)-ammonium betaine, N,N-dimethyl-N-acryloxyethyl-N-(3-sulfopropyl)-ammonium betaine, N,N-dimethyl-N-acrylamidopropyl-N-(2-carboxymethyl)-ammonium betaine, N-3-sulfopropylvinylpyridine ammonium betaine, 2-(methylthio)ethyl methacryloyl-S-(sulfopropyl)-sulfonium betaine, 1-(3-sulfopropyl)-2-vinylpyridinium betaine, N-(4-sulfobutyl)-N-methyldiallylamine ammonium betaine (MDABS), N,N-diallyl-N-methyl-N-(2-sulfoethyl) ammonium betaine, and the like. A preferred betaine monomer is N,N-dimethyl-N-methacryloyloxyethyl-N-(3-sulfopropyl)-ammonium betaine.
xe2x80x9cCationic Monomerxe2x80x9d means a monomer unit as defined herein which possesses a net positive charge. Representative cationic monomers include the quaternary or acid salts of dialkylaminoalkyl acrylates and methacrylates such as dimethylaminoethylacrylate methyl chloride quaternary salt (DMAEA.MCQ), dimethylaminoethylmethacrylate methyl chloride quaternary salt (DMAEM.MCQ), dimethylaminoethylacrylate hydrochloric acid salt, dimethylaminoethylacrylate sulfuric acid salt, dimethylaminoethyl acrylate benzyl chloride quaternary salt (DMAEA.BCQ) and dimethylaminoethylacrylate methyl sulfate quaternary salt; the quaternary or acid salts of dialkylaminoalkylacrylamides and methacrylamides such as dimethylaminopropyl acrylamide hydrochloric acid salt, dimethylaminopropyl acrylamide sulfuric acid salt, dimethylaminopropyl methacrylamide hydrochloric acid salt and dimethylaminopropyl methacrylamide sulfuric acid salt, methacrylamidopropyl trimethyl ammonium chloride and acrylamidopropyl trimethyl ammonium chloride; and N,N-diallyldialkyl ammonium halides such as diallyldimethyl ammonium chloride (DADMAC). Preferred cationic monomers include dimethylaminoethylacrylate methyl chloride quaternary salt, dimethylaminoethylmethacrylate methyl chloride quaternary salt and diallyldimethyl ammonium chloride. Diallyldimethyl ammonium chloride is more preferred.
xe2x80x9cCross linking monomerxe2x80x9d means an ethylenically unsaturated monomer containing at least two sites of ethylenic unsaturation which is added to constrain the microparticle conformation of the polymeric microparticles of this invention. The level of cross linking used in these polymer microparticles is high, compared to conventional super-absorbent polymers, to maintain a rigid non-expandable microparticle configuration. Cross linking monomers according to this invention include both labile cross linking monomers and non-labile cross linking monomers.
xe2x80x9cEmulsionxe2x80x9d, xe2x80x9cmicroemulsionxe2x80x9d and xe2x80x9cinverse emulsionxe2x80x9d mean a water-in-oil polymer emulsion comprising a polymeric microparticle according to this invention in the aqueous phase, a hydrocarbon oil for the oil phase and one or more water-in-oil emulsifying agents. Emulsion polymers are hydrocarbon continuous with the water-soluble polymers dispersed within the hydrocarbon matrix. The emulsion polymer are optionally xe2x80x9cinvertedxe2x80x9d or converted into water-continuous form using shear, dilution, and, generally an inverting surfactant. See U.S. Pat. No. 3,734,873, incorporated herein by reference.
xe2x80x9cFluid mobilityxe2x80x9d means a ratio that defines how readily a fluid moves through a porous medium. This ratio is known as the mobility and is expressed as the ratio of the permeability of the porous medium to the viscosity for a given fluid.
1.  λ  =            k      x              η      x
for a single fluid x flowing in a porous medium.
When more than one fluid is flowing the end point relative permeabilities must be substituted for the absolute permeability used in equation 1.
2.      λ    x    =            k      rx              η      x
for a fluid x flowing in a porous medium in the presence of one or more other fluids.
When two or more fluids are flowing the fluid mobilities may be used to define a Mobility ratio
3.  M  =                    λ        x                    λ        y              =                            η          y                                  k          rx                                      η          x                                  k          ry
The mobility ratio is of use in the study of fluid displacement, for example in water flooding of an oil reservoir where x is water and y is oil, because the efficiency of the displacement process can be related to it. As a general principle at a mobility ratio of 1 the fluid front moves almost in a xe2x80x9cPlug flowxe2x80x9d manner and the sweep of the reservoir is good. When the mobility of the water is ten times greater than the oil viscous instabilities, known as fingering, develop and the sweep of the reservoir is poor. When the mobility of the oil is ten times greater than the water the sweep of the reservoir is almost total.
xe2x80x9cIon-pair polymeric microparticlexe2x80x9d means a cross-linked polymeric microparticle prepared by polymerizing an ampholytic ion pair monomer and one more anionic or nonionic monomers.
xe2x80x9cLabile cross linking monomerxe2x80x9d means a cross linking monomer which can be degraded by certain conditions of heat and/or pH, after it has been incorporated into the polymer structure, to reduce the degree of crosslinking in the polymeric microparticle of this invention. The aforementioned conditions are such that they can cleave bonds in the xe2x80x9ccross linking monomerxe2x80x9d without substantially degrading the rest of the polymer backbone. Representative labile cross linking monomers include diacrylamides and methacrylamides of diamines such as the diacrylamide of piperazine, acrylate or methacrylate esters of di, tri, tetra hydroxy compounds including ethyleneglycol diacrylate, polyethyleneglycol diacrylate, trimethylopropane trimethacrylate, ethoxylated trimethylol triacrylate, ethoxylated pentaerythritol tetracrylate, and the like; divinyl or diallyl compounds separated by an azo such as the diallylamide of 2,2xe2x80x2-Azobis(isbutyric acid) and the vinyl or allyl esters of di or tri functional acids. Preferred labile cross linking monomers include water soluble diacrylates such as PEG 200 diacrylate and PEG 400 diacrylate and polyfunctional vinyl derivatives of a polyalcohol such as ethoxylated (9-20) trimethylol triacrylate.
The labile cross linker is present in an amount of from 9000 to about 200,000 ppm, preferably from about 9000 to about 100,000 ppm and more preferably from about 20,000 to about 60,000 ppm based on total moles of monomer.
xe2x80x9cMonomerxe2x80x9d means a polymerizable allylic, vinylic or acrylic compound. The monomer may be anionic, cationic, nonionic or zwitterionic. Vinyl monomers are preferred, acrylic monomers are more preferred.
xe2x80x9cNonionic monomerxe2x80x9d means a monomer as defined herein which is electrically neutral. Representative nonionic monomers include N-isopropylacrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, dimethylaminopropyl acrylamide, dimethylaminopropyl methacrylamide, acryloyl morpholine, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate, dimethylaminoethylacrylate (DMAEA), dimethylaminoethyl methacrylate (DMAEM), maleic anhydride, N-vinyl pyrrolidone, vinyl acetate and N-vinyl formamide. Preferred nonionic monomers include acrylamide, N-methylacrylamide, N,N-dimethylacrylamide and methacrylamide. Acrylamide is more preferred.
xe2x80x9cNon-labile cross linking monomerxe2x80x9d means a cross linking monomer which is not degraded under the conditions of temperature and/or pH which would cause incorporated labile cross linking monomer to disintegrate. Non-labile cross linking monomer is added, in addition to the labile cross linking monomer, to control the expanded conformation of the polymeric microparticle. Representative non-labile cross linking monomers include methylene bisacrylamide, diallylamine, triallylamine, divinyl sulfone, diethyleneglycol diallyl ether, and the like. A preferred non-labile cross linking monomer is methylene bisacrylamide.
The non-labile cross linker is present in an amount of from 0 to about 300 ppm, preferably from about 0 to about 200 ppm and more preferably from about 0 to about 100 ppm based on total moles of monomer. In the absence of a non-labile cross linker, the polymer particle, upon complete scission of labile cross linker, is converted into a mixture of linear polymer strands. The particle dispersion is thereby changed into a polymer solution. This polymer solution, due to its viscosity, changes the mobility of the fluid in a porous medium. In the presence of a small amount of non-labile cross linker, the conversion from particles to linear molecules is incomplete. The particles become a loosely linked network but retain certain xe2x80x98structurexe2x80x99. Such xe2x80x98structuredxe2x80x99 particles can block the pore throats of porous media and create a blockage of flow.
Preferred Embodiments
In a preferred aspect, the polymeric microparticles of this invention are prepared using an inverse emulsion or microemulsion process to assure certain particle size range. The unexpanded volume average particle size diameter of the polymeric microparticle is preferably from about 0.1 to about 3 microns, more preferably from about 0.1 to about 1 microns.
Representative preparations of cross-linked polymeric microparticles using microemulsion process are described in U.S. Pat. Nos. 4,956,400, 4,968,435, 5,171,808, 5,465,792 and 5,737,349.
In an inverse emulsion or microemulsion process, an aqueous solution of monomers and cross linkers is added to a hydrocarbon liquid containing an appropriate surfactant or surfactant mixture to form an inverse monomer microemulsion consisting of small aqueous droplets dispersed in the continuous hydrocarbon liquid phase and subjecting the monomer microemulsion to free radical polymerization.
In addition to the monomers and cross linkers, the aqueous solution may also contain other conventional additives including chelating agents to remove polymerization inhibitors, pH adjusters, initiators and other conventional additives.
The hydrocarbon liquid phase comprises a hydrocarbon liquid or mixture of hydrocarbon liquids. Saturated hydrocarbons or mixtures thereof are preferred. Typically, the hydrocarbon liquid phase comprises benzene, toluene, fuel oil, kerosene, odorless mineral spirits and mixtures of any of the foregoing.
Surfactants useful in the microemulsion polymerization process described herein include sorbitan esters of fatty acids, ethoxylated sorbitan esters of fatty acids, and the like or mixtures thereof. Preferred emulsifying agents include ethoxylated sorbitol oleate and sorbitan sesquioleate. Additional details on these agents may be found in McCutcheon""s Detergents and Emulsifiers, North American Edition, 1980.
Polymerization of the emulsion may be carried out in any manner known to those skilled in the art. Initiation may be effected with a variety of thermal and redox free-radical initiators including azo compounds, such as azobisisobutyronitrile; peroxides, such as t-butyl peroxide; organic compounds, such as potassium persulfate and redox couples, such as sodium bisulfite/sodium bromate. Preparation of an aqueous product from the emulsion may be effected by inversion by adding it to water which may contain an inverting surfactant.
Alternatively, the polymeric microparticles cross linked with labile cross links are prepared by internally cross linking polymer particles which contain polymers with pendant carboxylic acid and hydroxyl groups. The cross linking is achieved through the ester formation between the carboxylic acid and hydroxyl groups. The esterification can be accomplished by azeotropic distillation (U.S. Pat. No. 4,599,379) or thin film evaporation technique (U.S. Pat. No. 5,589,525) for water removal. For example, a polymer microparticle prepared from inverse emulsion polymerization process using acrylic acid, 2-hydroxyethylacrylate, acrylamide and
2-acrylamido-2-methylpropanesulfonate sodium as monomer is converted into cross linked polymer particles by the dehydration processes described above.
The polymeric microparticles are optionally prepared in dry form by adding the emulsion to a solvent which precipitates the polymer such as isopropanol, isopropanol/acetone or methanol/acetone or other solvents or solvent mixtures that are miscible with both hydrocarbon and water and filtering off and drying the resulting solid.
An aqueous suspension of the polymeric microparticles is prepared by redispersing the dry polymer in water.
In another embodiment, this invention is directed to a method of modifying the permeability to water of a subterranean formation comprising injecting into the subterranean formation a composition comprising cross linked polymeric microparticles having a cross linking agent content of from about 0.9 to about 20 mole percent of labile cross linkers and from 0 to about 300 ppm of non-labile cross linkers wherein the microparticles have a smaller diameter than the pores of the subterranean formation and wherein the labile cross linkers break under the conditions of temperature and pH in the subterranean formation to form expanded microparticles.
The composition then flows through the a zone or zones of relatively high permeability in the subterranean formation under increasing temperature conditions, until the composition reaches a location where the temperature or pH is sufficiently high to promote expansion of the microparticles.
Unlike conventional blocking agents such as polymer solutions and polymer gels that cannot penetrate far and deep into the formation, the composition of this invention, due to the size of the particles and low viscosity, can propagate far from the injection point until it encounters the high temperature zone.
Also, the polymeric microparticles of this invention, due to their highly crosslinked nature, do not expand in solutions of different salinity. Consequently, the viscosity of the dispersion is not affected by the salinity of the fluid encountered in the subterranean formation. Accordingly, no special carrier fluid is needed for treatment. Only after the particles encounter conditions sufficient to reduce the crosslinking density, is the fluid rheology changed to achieve the desired effect.
Among other factors, the reduction in crosslinking density is dependent on the rate of cleavage of the labile crosslinker. In particular, different labile crosslinkers, have different rates of bond cleavage at different temperatures. The temperature and mechanism depend on the nature of the cross-linking chemical bonds. For example, when the labile crosslinker is PEG diacrylate, hydrolysis of the ester linkage is the mechanism of de-crosslinking. Different alcohols have slightly different rates of hydrolysis. In general, methacrylate esters will hydrolyze at a slower rate than acrylate esters under similar conditions. With divinyl or diallyl compounds separated by an azo group such as the diallylamide of 2,2xe2x80x2-Azobis(isbutyric acid), the mechanism of de-crosslinking is elimination of a nitrogen molecule. As demonstrated by various azo initiators for free radical polymerization, different azo compounds indeed have different half-life temperatures for decomposition.
In addition to the rate of de-crosslinking, we believe that the rate of particle diameter expansion also depends on the total amount of remaining crosslinking. We have observed that the particle expands gradually initially as the amount of crosslinking decreases. After the total amount of crosslinking passes below a certain critical density, the viscosity increases explosively. Thus, by proper selection of the labile cross-linker, both temperature- and time-dependent expansion properties can be incorporated into the polymer particles.
The particle size of the polymer particles before expansion is selected based on the calculated pore size of the highest permeability thief zone. The crosslinker type and concentration, and hence the time delay before the injected particles begin to expand, is based on the temperature both near the injection well and deeper into the formation, the expected rate of movement of injected particles through the thief zone and the ease with which water can crossflow out of the thief zone into the adjacent, lower permeability, hydrocarbon containing zones. A polymer microparticle composition designed to incorporate the above considerations results in a better water block after particle expansion, and in a more optimum position in the formation.
In a preferred aspect of this embodiment, the composition is added to injection water as part of a secondary or tertiary process for the recovery of hydrocarbon from the subterranean formation.
In another preferred aspect of this embodiment, the injection water is added to the subterranean formation at a temperature lower than the temperature of the subterranean formation.
The composition is added in an amount of from about 100 to 10,000 ppm, preferably from about 500 to about 1500 ppm and more preferably from about 500 to about 1000 ppm based on polymer actives.
In another preferred aspect of this embodiment, the diameter of the expanded polymeric microparticles is greater than one tenth of the controlling pore throat radius of the rock pores in the subterranean formation.
In another preferred aspect of this embodiment, the diameter of the expanded polymeric microparticles is greater than one fourth of the controlling pore throat radius of the rock pores in the subterranean formation.
In another preferred aspect of this embodiment, the subterranean formation is a sandstone or carbonate hydrocarbon reservoir.
In another preferred aspect of this embodiment, the composition is used in a carbon dioxide and water tertiary recovery project.
In another preferred aspect of this embodiment, the composition is used in a tertiary oil recovery process, one component of which-constitutes water injection.
In another embodiment, this invention is directed to a method of increasing the mobilization or recovery rate of hydrocarbon fluids in a subterranean formation comprising injecting into the subterranean formation a composition comprising polymeric microparticles according to claim 1 wherein the microparticles have a smaller diameter than the pores of the subterranean formation and wherein the labile cross linkers break under the conditions of temperature and pH in the subterranean formation to decrease the mobility of the composition.
In another aspect of this embodiment, the composition is added to injection water as part of a secondary or tertiary process for the recovery of hydrocarbon from the subterranean formation.
In another aspect of this embodiment, the injection water is added to a producing well. Use of the composition of this invention in a producing well increases the oil-to-water ratio of the produced fluid. By injecting a composition comprising the polymeric microparticles of this invention and allowing the particles to expand, the water producing zones can be selectively blocked off.
In another aspect of this embodiment, the injection water is added to the subterranean formation at a temperature lower than the temperature of the subterranean formation.
In another aspect of this embodiment, the subterranean formation is a sandstone or carbonate hydrocarbon reservoir.
The foregoing may be better understood by reference to the following examples, which are presented for purposes of illustration and are not intended to limit the scope of this invention.

Composition and method for recovering hydrocarbon fluids from a subterranean reservoir


Co-administration of a channel blocking epithelial sodium channel (ENaC) blocker in conjunction with a mineralocorticoid receptor inhibitor makes it possible to achieve desired lowering of blood pressure with use in the range of 20% to 75% or less of the presently used dosage of the mineralocorticoid receptor inhibitor (MRI), thus avoiding many of the deleterious side effects usually associated with administration of an MRI. As little as 10% of the usual dosage of MRI may, in some cases, be efficacious. The most commonly used ENaC blocker now in use is amiloride. The most commonly used inhibitors of the mineralocorticoid receptor are precursors of canrenone.

This invention relates to the control of hypertension in patients suffering from aldosteronism and conditions wherein aldosterone may be elevated secondary to pathophysiological conditions as seen in patients with cardiac insufficiency such as in post-myocardial infarction. Simultaneous administration of an epithelial sodium channel (ENaC) blocker in combination with an agent that inhibits the mineralocorticoid receptor provides a new and effective means of treatment.
Aldosterone is involved in salt and water homeostasis. The main effect is thought to involve genomic mechanisms. These mechanisms are thought to be mediated by the mineralocorticoid receptor. However, the existence of plasma membrane steroid receptors has also been postulated.
The mineralocorticoid hormone aldosterone has the ability to cause an increase the reabsorption of salt and water. A part of this process appears to involve the stimulation of amiloride-sensitive sodium channels in the cortical collecting duct of the kidney. The classical mechanism of this regulation is that aldosterone activates a cytosolic mineralocorticoid receptor that, in turn, has genomic effects resulting in increased transcription of the genes that produce serum-glucocorticoid-regulated kinase SGK and Na+xe2x80x94K+ ATPase. A compelling reason for suspecting a genomic mechanism of regulation is that in vitro effects of aldosterone are not acute, but rather take as long as four hours to develop and can be blocked by inhibitors of transcription and translation. It is important to consider that the vast majority of experiments to elucidate the mechanism of action of aldosterone have been carried out on model systems such as rat tissue and cells and A6 epithelial cells derived from Xenopus lavis. The mechanism of action of aldosterone in other species, including humans, is more complex than in those model systems.
A body of evidence has been accumulating that suggests that in species other than the rat, aldosterone produces acute effects at picomolar concentrations. For example, rapid aldosterone-mediated effects on cellular processes in human smooth muscle cells and human lymphocytes have been observed when the mineralocorticoid receptor has been inhibited with spironolactone. Spironolactone is converted in the body to canrenone, the active metabolite, a compound of the formula:
or to the canrenoic acid ion in the body. Canrenone, too, has been used as an aldosterone antagonist. (See U.S. Pat. No. 2,900,383, which is incorporated herein by reference in its entirety.).
Several articles compare use of spironolactone and amiloride in treatment of patients. For example, Jeunemaitre, et al. teaches use of, in the alternative, spironolactone, hydrochlorothiazide/amiloride combination or cyclothiazide/triamterene combinations in treatment of patients with elevated blood pressure. (See American Journal of Cardiology, 62 (16), pp 1072-7 (Nov. 15, 1988.) There is no suggestion therein to use spironolactone with amiloride.
Millar, et al report a study comparing amiloride and spironolactone (British Journal of Clinical Pharmacology, 18(3), pp. 369-75 (September, 1984)). (See, also, Clinical Pharmacology and Therapeutics, 27 (4), pp 533-43 (April, 1980).).
The administration of spironolactone in accord with present dosage standards, whether used alone or using previously taught combinations, is known to cause several serious and uncomfortable side effects, including dangerous alterations in blood potassium causing hyperkalemia. Endocrine disturbances, including enlargement of breasts in males, also occur.
Co-administration of a channel blocking epithelial sodium channel (ENaC) blocker in conjunction with a mineralocorticoid receptor inhibitor makes it possible to achieve desired lowering of blood pressure with use in the range of 20% to 75% or less of the presently used dosage of the mineralocorticoid receptor inhibitor (MRI), thus avoiding many of the deleterious side effects usually associated with administration of an MRI. Usually the dosage of MRI is about 20% to 50% of that required when administered without an ENaC blocker, though as little as 10% of the usual dosage of MRI may, in some cases, be efficacious. When used at the lower levels, it is possible to avoid or decrease the more serious and/or distressing untoward reactions to the MRI.
It is the purpose of this invention to provide means for treatment/control of hypertension in patients suffering from aldosteronism, including conditions wherein elevated aldosterone levels may be secondary to other pathophysiological processes such as heart failure.
The rational for inhibiting the effects of aldosterone in patients with post-myocardial heart failure is that subsequent to damage to the heart muscle, the ability of the heart to function as an efficient pump is reduced. This reduction in pumping efficiency is the source of reduced cardiac output. When the body senses a reduction in cardiac output, the renin-angiotensin-aldosterone axis is activated as a compensatory mechanism. Activation of this mechanism causes the blood vessels to constrict and the blood volume to increase by retention of salt and water. This compensatory attempt by the body to adjust for the reduced cardiac output puts more strain on the damaged heart. Ultimately, the feed-back mechanism meant to protect the organism causes the damaged heart to be damaged further. Reducing the effects of salt and water retention resulting from the increased aldosterone breaks the feed-back cycle, thereby reducing the workload for the heart and preserving cardiac function. It has now been found that simultaneous administration of an epithelial sodium channel (ENaC) blocker in combination with an agent that inhibits the mineralocorticoid receptor (an aldosterone antagonist) as disclosed herein provides a new and effective means of treatment for patients suffering from untoward effects of both primary and secondary aldosteronism.
The most commonly used ENaC blocker is amiloride. However, related compounds may be used in practice of the invention. Some pteridines have been shown to have properties similar to amiloride. The most common substituted pteridine in use is triamterene. Similarly, other mineralocorticoid receptor inhibitors such as analogues of spironolactone, including as those identified in this disclosure, may be used in practice of the invention. It is possible, when using the combination therapy, to reduce the amount of the MRI by 25% to 90%. For example, spironolactone is usually given at dosage of 25 to 100 mg. When used with a ENaC blocker such as amiloride, the dosage of as little as 5 mg. may be used. An aspect of the invention comprises compositions containing an ENaC blocker in combination with much smaller doses of an MRI than was previously delivered to have clinical significance.
Materials and Methods:
Principal Cell Preparation
Collecting ducts were manually dissected from sagittal slices obtained from 50 gram Sprague Dawley rats and 0.5 Kg New Zealand White rabbits. The dissected collecting ducts were suspended in RPMI 1640 culture medium supplemented with 1.5 mg/ml collagenase A (Boehringer Mannheim, Mannhein, Germany). The collecting ducts were enzymatically digested for 1.5 hours to isolate individual cells. The digested cells were washed in serum-free RPMI and placed in a perfusion chamber mounted on the stage of an inverted microscope. The whole-cell patch clamp configuration was established and initial current measurements were made in un-supplemented RPMI. The bath solution was changed (by perfusion of the entire bath chamber) to RPMI supplemented with aldosterone (100 nM), vasopressin (250 nM), amiloride (2 xcexcM), spironolactone (1 xcexcM), or various combinations of these compounds. To block the cytosolic mineralocorticoid receptor, some cells were suspended in RPMI supplemented with spironolactone for 1 hour prior to whole-cell patch clamping.
Preparation of Lymphocytes
Human and canine lymphocytes were isolated from peripheral blood samples by differential centrifugation over ficoll paque (Pharmacia Biotech, Uppsala, Sweden). The cells were washed and re-suspended in serum-free RPMI. Subsequently, suspended cells were placed in the perfusion chamber. Whole-cell patch clamp and testing of aldosterone were carried out using identical techniques and protocols as described for principal cells. Rabbit, rat and mouse lymphocytes were obtained by mincing sections of spleen and manually freeing the cells by agitation. The cell suspensions were then centrifuged over ficoll paque and treated identically to the lymphocytes obtained from peripheral blood. All procedures were carried out under the guidelines for animal use and with institutional board approval for human use.
Studies were conducted using both whole cell patch clamp and single channel patch clamp techniques. Whole-cell clamped rabbit principal cells were exposed to 100 nM aldosterone. Positive identification of these cells was determined by the response to either aldosterone, or, if the cells failed to respond to aldosterone, a positive response to vasopressin. No cells failed both tests. Upon entering the bath, the aldosterone induced a specific activation of the inward currents at hyperpolarized membrane potential clamp voltages. The activated currents were subsequently inhibited completely with 2 xcexcM amiloride (in the continued presence of aldosterone), confirming that the activated currents were amiloride-sensitive. The average current-voltage relations for the current activated by aldosterone and the current inhibited by amiloride after aldosterone activation was studied. The current voltage relations showed inward current up to (+40 mV). ENa+ was approximately +60 mV with the ionic gradients present. The activated current was carried exclusively by sodium. In a separate set of experiments rabbit principal cells were re-suspended in RPMI supplemented with 1 xcexcM spironolactone for 1 hour prior to use for whole-cell patch clamp. This concentration is sufficient to inhibit completely the mineralocorticoid receptor. It was found that spironolactone had no effect on the inward currents. However, even with mineralocorticoid receptor inhibition, 100 nM aldosterone specifically activated the inward currents. These studies indicate that the acute activation of ENaC by aldosterone did not utilize the mineralocorticoid receptor and was, therefore, non-genomic.
In contrast to the findings in the rabbit principal cells, aldosterone had no acute affect on principal cells isolated from the collecting ducts of rats. Since aldosterone had no effect, the expression of ENaC and the cell type (principal cell) was confirmed in every study by subsequent acute specific activation of the amiloride sensitive inward currents by 250 nM vasopressin. The same protocol was carried out on rabbit principal cells. Once ENaC was activated by aldosterone, subsequent stimulation with vasopressin did not activate the inward currents any further, i.e., there was no synergistic effect of the two ENaC agonists, implying that they activated the same set of channels.
Studies were done to evaluate the average current activated by these ENaC agonists measured at EK+. At this potential (xe2x88x9280 mV) there can be no potassium current. Thus, all of the current activated by aldosterone or vasopressin must be sodium current. In the absence of aldosterone, or if aldosterone activation was inhibited, vasopressin activated the inward currents. Statistical analysis of the mean current showed that for rat principal cells, aldosterone did not alter the current, but vasopressin increased it significantly, while amiloride restored the current to the basal level. For the rabbit principal cells, aldosterone significantly increased the current, vasopressin had no additional effect, and amiloride returned the conductance to the basal level. Also, the basal conductance and the activated conductance in rat and rabbit principal cells were not significantly different between the species.
The hypothesis that aldosterone-mediated non-genomic activation of ENaC utilized methylation rather than protein Kinase A-mediated phosphorylation to induce channel activation was tested. It was found that methyl esterification was independent of vasopressin-stimulated cAMP-mediated signal transduction.
Further studies that were conducted that directly demonstrated the findings on intact rabbit cortical collecting ducts helped to resolve an apparent contradiction. A considerable delay (2-4 hours) was observed when the in vitro effect of aldosterone was measured using intact renal collecting duct segments. In the present study aldosterone-stimulated ENaC activation was observed within seconds. The only obvious difference between former studies and the present study was that it was possible to control the cytosolic (ATP), whereas in intact collecting duct segments the cellular ATP is controlled by cellular metabolism. Full ENaC activation was only observed in rabbit principal cells when the pipette solutions were supplemented with a minimum of 2 mM ATP.
The xe2x80x9craggedxe2x80x9d morphology of the whole-cell currents in principal cells and lymphocytes has generated some concern about the identity of the channels that are activated by aldosterone. To address this concern, single channel characteristics of the sodium conductors expressed by human lymphocytes were studied. It was found that conductance was the same as the channel conductance reported for human ENaC expressed in Xenopus oocytes.
To test the amiloride sensitivity of the single channels, outside-out patches were formed because amiloride only interacts with the outside surface of the channels. A xe2x80x9crundownxe2x80x9d phenomena typical of ENaC in the inside-out patch experiments was noted. Incomplete inhibitory action of amiloride on these channels at an amiloride concentration close to IC50 for amiloride and ENaC (75 nM) was found. When the amiloride concentration was increased to 2 xcexcM, single channel activity was completely abolished.
When the cells were treated with 100 nM aldosterone, a somewhat different channel behavior was observed. In outside-out patches, the unitary conductance was unchanged, but the channels opened and closed in groups. Single channel activity was virtually abolished when amiloride (2 xcexcM, final concentration) was added to the bath solution. Hence, it was demonstrated that this single channel behavior produced the xe2x80x9craggedxe2x80x9d whole-cell currents that are characteristic of the sodium conductance of principal cells and lymphocytes by reconstructing the whole-cell currents from single channel recordings.
Finally, it should be mentioned that the vast majority of patches ( greater than 80%) were devoid of single channel activity in cells that were not pretreated with aldosterone. These single channel findings are completely consistent with the whole-cell findings, and establish, by biophysical characteristics, that the channels that are activated by aldosterone are ENaC.
The direct electrophysiological findings from these studies address three major issues concerning the role of aldosterone in the regulation of Na+ currents by principal cells. First, the findings demonstrate directly an acute, non-genomic activation of an amiloride-sensitive sodium conductance (ENaC) in renal principal cells of the rabbit. In contrast, the findings also show that aldosterone fails to activate any current in principal cells of rats. Because the kidneys of both species are used extensively to study renal salt and water regulation, this difference has wide-ranging implications for understanding of the role of aldosterone in controlling sodium reabsorption in the collecting duct. For example, based on numerous previous studies indicating that aldosterone increases expression of epithelial sodium channels by interaction with the cytosolic mineralocorticoid receptor, inhibition of this receptor by spironolactone has been the recognized treatment for primary aldosteronism. However, these new studies show that aldosterone has the ability to activate nascent channels in the presence of spironolactone. Thus, a more effective therapy involves administration of an epithelial sodium channel (ENaC) blocker in combination with an agent that inhibits the mineralocorticoid receptor. One such combination is spironolactone and amiloride as a preferred treatment for patients suffering from aldosteronism where surgery is not warranted or cannot be performed, and in patients suffering from heart failure such as that seen in post-myocardial infarction.
Some previous studies utilizing rabbit cortical collecting ducts showed delayed effects of aldosterone on sodium conductance but failed to show the immediate effect that was demonstrated in the whole-cell studies of the effects as described. Hence, the therapy taught herein was not suggested by the previous findings. Since some of the studies measured trans-epithelial potential (TEP) and could demonstrate an acute change in TEP induced by vasopressin but not by aldosterone, the prior findings suggested that aldosterone did not produce an acute ENaC activation in rabbit CCD, contrary to the whole-cell clamp findings presented herein. The re-supplying cytosolic ATP, by using ATP-supplemented pipette solutions, made it possible to replete ATP to a sufficient concentration. This is not possible in intact collecting ducts in vitro. These findings show that the appropriate level of ATP was essential for signal transduction between aldosterone and ENaC to produce non-genomic ENaC activation. This demonstrates directly that aldosterone-stimulated signal transduction for ENaC regulation requires ATP from a depletable pool, but vasopressin-stimulated signal transduction for ENaC activation may utilize ATP from a pool that is not depleted. This line of reasoning reconciles the difference between the whole-cell clamp findings and the findings obtained in intact collecting ducts, because in intact tubules the in vitro metabolism may not be robust enough to continuously provide the cellular concentrations of ATP that are required for aldosterone-mediated ENaC regulation.
While spironolactone is exemplified as the more commonly used MRI, canrenone or other agents of the formula:
wherein R1 is a protective group such as a carbonyl or carboxyl, or a sulfur-containing analogue of such groups which, when removed during metabolism, converts to the canrenone of Formula I, would be appropriate for use in compositions and in the method of this invention. For example, in the case of spironolactone, R1 is SCOCH3. However, other compositions containing as an active agent the analogue wherein R1 is COCH3 are also known and can be used in accord with the teachings herein. For example, R1 may be a thio group, a carbonyl or a carboxyl group having 1-10 carbon atoms. R1 may, for example, be SCOxe2x80x94R2, COR2 or COOR2 wherein R2 is alkyl, phenyl, phenylalkyl or alkenyl having 1-10 carbons, wherein the alkyl and alkenyl groups may be branched and phenyl may have an alkyl substituent. Any R2 may, additionally, be substituted with 1-2 halo, amino or alkoxy moieties. Any metabolic precursor of canrenone would clearly be useful for purposes of the invention.
For purposes of treating hypertension in patients suffering from aldosteronism, various active agents which are epithelial sodium channel (ENaC) blockers can be given in combination with agents that inhibit the mineralocorticoid receptor. The range of dosage for co-administration may be within the parameters of dosage presently used when the active agents are administered separately for purposes of inhibiting mineralocorticoid receptor activity or as ENaC blockers.
It would be preferable to combine the active agents in one dosage form, if possible. For example, in a preferred embodiment of the invention, compositions containing 5 mg to 20 mg. spironolactone and 1 mg to 5 mg of amiloride would be administered twice daily to the average adult person. However, the combination therapy makes it possible to use far less of the spironolactone, as little of 5 mg. in adults and 1 mg. for children. The form of the composition would be determined by the condition of the patient and the particular agents administered. Preferred dosage would be 2-15 mg. spironolactone and 0.5 to 5 mg. amiloride.

Methods of treatment using an epithelial sodium channel blocker and an inhibitor of the mineralocorticoid receptor


A mobile station (4) in a satellite mobile telephone system predicts when it will move into another cell on the basis of one set of broadcast information thereby reducing the overall processing burden. The mobile station (4) can predict with a useful degree of certainty which broadcast control channel (BOCH) frequencies it should listen on when it wakes up on the basis of a stored map of the relative positions of cells. The broadcast information is valid for a predetermined time interval. Upon waking up, the mobile station (4) determines present time within the predetermined time interval and uses the broadcast information as well as the present time within the predetermined time interval to predict the time at which the mobile telephone will leave the cell.

Known satellite mobile telephone systems include the Inmarsat-M system, the IRIDIUM™ system described in, for example EP-A-0365885, the ICO™ system described in, for example, GB-A-2295296 and the ODYSSEY™ system described in, for example, EP-A-0510789. Whilst each of these systems is cellular in nature, they differ from terrestrial systems in that the cells move relative to the Earth's surface because each cell is defined by a beam from an orbiting satellite.
To extend battery life during the idle mode of a satellite mobile telephone, the mobile telephone is desirably powered down for 95% to 98% of the time. Periodically, the mobile telephone wakes up briefly to determine if broadcast control channels from satellites can be received. If so the mobile telephone checks for an incoming call. In idle mode, the mobile telephone needs to know when to hand over to another beam from the same or a different satellite, i.e. when to start listening to another broadcast control channel.
If a mobile telephone does not know the time of the next handover or the new broadcast control channel, it must frequently search a number of frequencies, for example 8. In particular, if on wake-up the broadcast control channel is found to be weak or absent, the mobile telephone has no way of knowing whether the signal is being blocked or interfered with or whether it is now being serviced by another beam.
It is desirable for a mobile telephone to check only two or three broadcast control channel frequencies (one from a primary satellite and one or two from secondary satellites) instead of all possible frequencies. This minimises "on time" during each wake-up while maintaining the desired low duty cycle. Frequent wake-ups are desirable to minimise the time taken to detect incoming calls and the return of signals after an outage.
It is an aim of the present invention to overcome this problem.

This patent is subject to a terminal disclaimer.

Satellite mobile telephone cell departure prediction


Method for gluing plastic labels (15) formed of a film (12) of BI-oriented polypropylene covered on each from a layer of acrylic material (13,14), to hydrorepellent containers by using application apparatus for water based glue paper labels; one of layers (13,14) is printed by means of inks (16) for non absorbing materials, covered by a layer of overprinting paint (17).

The present invention relates to processes allowing for the application of plastic labels onto hydrorepellent containers of the type, for example, made of plastic, metal or glass, using apparatus designed originally for sticking traditional paper labels onto substrates using water based glues. The processes include further that said plastic labels be printed with inks for non absorbing supports, wherein the inks contain oxidising additives which tend to effect rapid drying thereof, and the inks tend to be stable when in contact with the water based glues.
Modem processes for sticking paper labels to containers of various type use machines or apparatus which employ, generally, a so-called xe2x80x9clabel reservoirxe2x80x9d, which comprises ordered piles of overlaid and pre-cut labels suitably placed therein to contain them on the apparatus or sticking machines. Within such machines or apparatus, the labels are taken from the reservoir by a picking means and carried towards rolls wetted by glue and a carousel provided with pads suitable to spread the glue, in example vinyl one, on the back of the label. The glue is drawn from tanks, the so-called xe2x80x9cglue reservoirsxe2x80x9d of the application machines or apparatus. The labels, wetted by glue, are then transported to containers onto which they are applied by means of an application mechanism generally comprising pincers which take up the labels and lay them down on the surface of the containers. The label machines or apparatus are also provided with means, such as pads, for applying suitable pressure to the applied label and making uniform the adhesion of the label to the container.
The types of conventional apparatus for the application of labels as described above are denominated xe2x80x9cwet typexe2x80x9d or xe2x80x9cwater based typexe2x80x9d, as compared to xe2x80x9cdry typexe2x80x9d machines which provide for the application of labels having on the rear side an adhesive (self-adhesive labels). In xe2x80x9cdry typexe2x80x9d machines the label reservoir is made of rolls of paper web with silicone on which the labels to be applied on the containers are pre-cut. Examples of xe2x80x9cdry-typexe2x80x9d machines and apparatus are described in the documents U.S. Pat. No. 3,278,359 and U.S. Pat. No. 4,626,314.
From an industrial point of view, the use of xe2x80x9cwet typexe2x80x9d apparatus to apply labels tends to be advantageous over the use of xe2x80x9cdry typexe2x80x9d apparatus in that xe2x80x9cwet typexe2x80x9d apparatus allows for the high speed application of labels with less costs associated therewith. The basic material of the labels is paper of various characteristics. The printing of such label is made on the side at view, (where as the glue is applied on the rear side) according to the conventional techniques for sheets or rolls and the employed ink and printing techniques are of the traditional type, The labels reservoir of the apparatus or machines of the xe2x80x9cwet typexe2x80x9d is, as aforesaid, normally made of pre-cut and pre-printed stacks of labels.
An available technique of the prior-art for the application of plastic labels to containers consists in adapting specific machines or apparatus of the xe2x80x9cdry typexe2x80x9d to apply labels that are of the self-adhesive type. For example, documents EP 0377384 and U.S. Pat. No. 4,601,771 describe the fundamental characteristics of said apparatus for the application of labels by means of a pressure on the container.
However, in comparison to wet type apparatus for the application of paper labels, conventional dry type, self-adhesive plastic label apparatus tends to suffer the drawbacks of having a lower speed of application and higher costs associated therewith. Additional costs associated with the dry type, self-adhesive methods arise, for example, due to: (a) the time and special machines needed to prearrange self-adhesive labels on rolled webs of paper covered by silicone and wound on a core of card board, plastic or metal (the labels used in apparatus of the wet type do not need any support and need not be wound), (b) the costs of the band with silicone and of the core themselves, (c) the costs associated with disposal of waste material produced in dry type machines, and (d) the increased technical difficulty of manufacturing the supporting material which must be sprayed with glue on one face.
Other known methods for the application of plastic labels involves winding label strips of a length greater than the diameter of the container onto which they are applied, whose end overlapping zones are glued by means of thermoplastic glues, as illustrated in FR 25003093 e U.S. Pat. No. 4,632,721. In such methods, the labels are printed by offset techniques, by flex or screen printing, or by typography in webs or sheets, whereas the cut of the labels is made by means of rotary or plane cutting machines. However, a drawback of the methods using winding strips glued at their ends by thermoplasticity is that such methods tend to be useful only in the application of labels to substrates of a regular form (parallelepiped or cylindrical).
Another conventional technique for the application of plastic labels to plastic containers is xe2x80x9cIn Mould Labellingxe2x80x9d (IML), which consists in positioning in advance the early printed plastic label in the moulds which give form to the containers; an example of such a process is disclosed in EP 0313400. In such methods,when a tube (parison) of melting plastic is pressed by the moulds to form a container, the label in contact with said tube, by means of heat and pressure, mixes within the plastic mass of the surface of the forming container, appearing eventually as a single item with the whole container.
Unfortunately, the production process of pre-labelled containers by means of the IML method has very high costs due to the fact that the moulds allow a low speed of manufacturing of container. Furthermore, the application of the label at the interior of the mould increases considerably the costs because of the consequent high rate of rejection. An additional drawback of the IML is that the labelling is physically incorporated within the external surface of the container and is therefore not removable: this renders the resulting containers unusable for different uses requiring relabelling.
Another conventional method of application of plastic labels on plastic, glass or metal containers is the one described in patent application WO 99/19412. Such method consists of applying to a plastic label a layer of hydrophilic material, for example, an acrylic layer. WO 99/19412 describes thirty-eight examples of application of labels. In each example, the material of which the label is made, the type of hydrophilic material, and the type of component that is used to activate the adhesion of the acrylic layer to the container are changed. Among thirty-eight examples, only four give good or excellent results, namely, examples 30, 33, 36 and 37. Example 30 is done with a white (non-clear) label of polyethylene. Example 33 is done with a white (non-clear) label of polypropylene, and examples 36 and 37 are done with clear labels of polypropylene. In examples 30 and 36, labels are applied on containers of polyethylene and in examples 33 and 37 labels are applied on glass containers. Examples 30 and 33 use water to activate adhesion of the hydrophilic layer on the container. Example 36 uses a starch and styrene maleic anhydride based adhesive to glue the polypropylene label to a polyethylene container. Example 37 uses a water resin based adhesive to glue the polypropylene label to a glass container.
The method described in WO 99/19412 presents difficulties in industrial application. Labels of a generic polypropylene are hardly machineable, labels with only a layer of acrilic material, on a unique face, loaded in well arranged piles, are not able to slip one on the other one. Adhesive to be applied must be chosen in function of the material of the container on which the label must be applied. Technicians are obliged to review plants for applying labels for every type of material of which is fabricated each container and each label. Results are uncertain. The method described in WO 99/19412 is not applicable to traditional apparatus for paper labels.
It will appear clearer in the following description how the present invention eliminates and overcomes the aforementioned drawbacks, making possible the application of plastic labels to hydrorepellent containers, the labels suitably conditioned and printed by means of apparatus normally designed for paper labels for water based glues.
The present invention allows for the use of machines and apparatus of the xe2x80x9cwet typexe2x80x9d, normally adopted for the application of paper labels with water based glues, to apply plastic labels to hydrorepellent of metal, plastic or glass containers. The invention is made possible by the combination of suitable treatment of the surface of the plastic label, in order to make them receptive either of inks containing oxidising additives for a quick drying either of water based glues.
The process of the invention provides also that the water based glue suitable to stick said labels to hydrorepellent containers have specific chemical-physical characteristics within well defined ranges. The same process allows, obviously, the application of plastic labels to any container, independently from the material of which it is made, as for example cardboard or waxed cardboard, and of any shape.
According to the invention, by substituting the paper labels reservoir, with the plastic labels treated in accordance with the following description and the reservoir of water based glue, with a reservoir of glue made of a solution of resinous substances, containing a terpolymer, having a viscosity of (70.000xc2x110.000) mPas and a pH of 5,5xc2x11,5, while the dry residual must be within the range of (46xc2x13)%, the apparatus or traditional machines for paper labels are made perfectly compatible with the plastic labels, which will be applied to the containers with the same process and at the same speed.
The advantages resulting by such a method, beyond the already aforementioned ones, are evident by the flexibility that said wet type apparatus and machines offer, said flexibility being the same as for plastic labels: it derives that with the same type of apparatus or machine operations which were before not compatible are made possible by means of the invention. As already said, the use of wet-type machines and apparatus for the application of plastic label to hydrorepellent containers allow to:
Obtain high speed of application vis-a-vis the apparatus for self-adhesive labels;
Obtain a readiness and a reduction of costs of production of the labels, either for the absence of adhesive on one of the face, either for the absence of supports with silicone winded on a core of cardboard or metal, strongly more expensive than the labels without glue and stored in ordered pile.
Furthermore, by means of the method of the present invention it is possible to print the plastic film constituting the label on the side susceptible to be glued, in case of transparent labels. This improves the quality of the characteristics of the label because the printed side does not come in contact with the user or with external agents and therefore it resists to possible scratches and abrasions or chemical agents. Such characteristic takes an important place for containers of substances of a particular danger or value, for the printed side not being in contact with the outside avoids that the printed information of danger or indicating the content of particular substances be easily damaged, sometimes till to make them unreadable.
The invention is made possible by means of combination of operations as described in the following:
The plastic label is covered on both sides by an acrylic aqueous solution purged from chlorine. Acrylic cover on both faces of label allow slipping of the labels put in piles, as well as gluing of them to hydrorepellent containers by means of water based glue; the basic film constituting the support of the label is made of polypropylene biaxially oriented. Said support of biaxially oriented Polypropylene guaranties dimensional stability, homogeneous optical qualities, high breaking strength, higher machineability.
The two opposite layers of acrylic solution, suitably dried and laminated, are ink receptive or water based adhesives receptive; in order to make the anchoring of ink on the acrylic layer it is necessary to use inks for non absorbing supports which are added with particular compounds of salts complex, which when in contact with the water base of the glue oxidise by freeing hydrogen. The label so formed can be printed either on the face external to the container, or in case of transparent labels, on the face to be glued.
When on the face to be glued to the container, the printing is performed using inks for non absorbing materials added with reactive dryers of the type known in commerce as xe2x80x9cGrafo Drier.xe2x80x9d
The printing by non absorbing inks added with salts complex, for example of the type known in commerce as Grafo Drier, which can be performed by various printing techniques on plastic by conventional or digital sort, is subsequently covered by a protective overprinting water based paint, made of a dispersion of an acrylic polymer. The overprinting paint tends to lessen the chance that the inks of the printed labels, when stacked in pile one over the other, are removed or damaged. Said paint improves, also, the anchoring of the printed ink to the water based glue of the type used for the application of the label to the hydrorepellent containers.

Method for gluing plastic labels on hydrorepellents containers by means of labelling apparatus for water based glues


Disclosed herein are compositions and methods of treating therapeutically, or metaphylactically infected mammals susceptible to, or infected mammals suffering from parasitic neurologic or abortigenic diseases such as Sarcocystis, Neosporosis or Toxoplasmosis or Isosporosis that are treatable with a praziquantel compound by administering thereto a composition containing a pharmaceutically effective amount of praziquantel or derivative thereof, including metaphylactic and single high dose treatment regimens.

Field of the Invention: The present invention relates to a praziquantel composition for treating animals infected with parasites that cause abortigenic or neurologic diseases. More specifically, the present invention relates a praziquantel composition that is useful in treating parasitic protozoa such as coccidia that cause abortigenic or neurologic diseases of mammals.
Brief Description of the Prior Art: In protecting and treating various mammals, insects and fish from diseases caused by protozoa suspected of causing neurologic and/or abortigenic diseases, the art has used a number of compounds, recent among which are triazineone compounds. Generally, protozoa that are sensitive to these compounds include parasites that infect the intestines of birds, mammals and insects causing diarrhea, wasting disease, nausea and vomiting. Recently it has been found that some parasites that pass through the blood brain barrier, as well as parasites that pass through the placental barrier can be treated with the triazineones. Illustrative of parasites that are now known to cross the blood brain barrier or the placental barrier are those causing coccidial diseases such as Toxoplasma gondii, Sarcocystis neurona, Neospora caninum, Neospora hugesii, and Isospora suis. Illustrative of the triazineone compounds are triazinediones such as diclazuril compounds, and triazinetriones such as toltrazuril compounds. See U.S. Pat Nos. 4,933,341; 4,935,423; 5,114,938; 5,141,938; 5,188,832; 5,196,562; 5,256,631 and 5,464,837.
While other art-related compounds pertinent among which is praziquantel (2-acyl-4-oxo-hexahydro-4H-pyrazino[2,1-a[isoquinoline derivatives) are disclosed for use in treating parasites, the disclosure lacks any teaching or suggestion relating to the compounds as being useful in treating parasites that cross the blood or placental barrier. Generally, praziquantel has been used by itself or in combination with other compounds to formulate anthelmintic compositions for treating infestation of cestodes and nematodes and the like. See U.S. Pat. No. 4,001,411, 4,447,414, and 5,824,653.
U.S. Pat. No. 5,663,155 discloses praziquantel for use in the prevention and treatment of parasitic infections, which cause diseases such as malaria, trypanosomiasis, leishmania, schistosomiasis and elephantitis. The patent also suggests that praziquantel could be used to treat parasitic infections limited to the blood, lymph and tissues. Toxoplasmosis and Sarcocystis are specifically mentioned in the context of their infection of muscle tissues or intestines. There is no mention of treatment or prevention of diseases wherein the Toxoplasma, Sarcocystis, Neospora or Isospora is embedded into the brain of adult mammals or passed through the placental barrier to infect central nervous tissues of the fetus, producing abortion or weak newborns.
Generally, the mode of action of the triazineones is to attack the intermediate parasite stages found in the gut and intestinal wall cells, causing the endoplasmic reticulum, the perinuclear space and the mitochondria of the parasite to swell. This purportedly disturbs the ability for nuclear divisions causing the schizonts and microgamonts to remain small, forming only a few merozoites and microgametes respectively. The end result is reported to be the loss of the ability of these latter stages of the parasites to penetrate new mammalian cells, effectively halting the replication of the parasite in the host.
The mode of action of paraziquantel, as disclosed by U.S. Pat. No. 5,663,155 (ibid.), is related to the disruption of enzymatic processes of the parasite that relate to the metabolism of purine derivatives and purine-like chemical structures. Parasites are acutely sensitive to interference of these processes, thus compositions that specifically target these processes can be used to selectively eliminate a parasitic infection. Praziquantel is administered so as to attack parasites that are related to muscle tissue, intestine or blood infection. There is no mention of treating parasites of the central nervous system (brain and spinal cord) or parasites that can pass the placental barrier.
While the art has been concerned with protozoa suspected of causing neurologic and/or abortigenic diseases of mammals since the 1970s, successful isolation and in vitro cultivation of some of these protozoa proved to be difficult. For example, successful isolation of parasites from the brain or cerebral spinal fluid was not accomplished until the late 1980s. However, once it was determined that neurologic diseases could be produced by protozoa infecting the brain, and abortigenic diseases could be produced by protozoa infecting the fetus, there was a need for effective anti-protozoa drugs which could cross the blood-brain barrier and the placental barrier without producing deleterious side effects. Very few drugs are able to pass the blood-brain barrier or the placental barrier of mammals. Unfortunately, many of the art-known drugs that do cross the blood-brain barrier and/or the placental barrier to effectively treat parasitic infections of the brain have detrimental side effects such that they cannot be used without great risk. Therefore, there have been no effective drugs approved to date which provide an effective treatment for such neurologic or abortigenic diseases.
It is noteworthy that based on the disclosed mode of action of praziquantel in U.S. Pat. No. 5,663,155, relative to its broad attack on enzymes which affect purine metabolism, one would have expected that this compound might also produce deleterious effects if used to treat mammals with parasitic brain infections.
The following is a brief description of the parasitic diseases of the immediate invention, which are treatable with praziquantel. Equine Protozoal Myeloencephalitis (EPM) is a neurologic disease of horses, with a predilection for young horses undergoing stress (e.g. thoroughbred racehorses and purebred performance horses), and is thus a disease with significant monetary impact for the horse industry. EPM, first recognized as a disease in the 1970s, was not cultured from a horse with EPM and given the name Sarcocystis neurona until 1991. In 1997, a Neospora spp., now named Neospora hugesi, was isolated from the brain of a horse with EPM. Accordingly, it is now proposed that EPM may be caused by this newly recognized organism alone, by Sarcocystis neurona alone or the combination of the two.
Another coccidial parasite, Toxoplasma gondii, has been known for some time and was first isolated from the intestines and muscle tissue of cats. The definitive host for this parasite is the cat that can harbor the organism for long periods of time spreading oocysts to other animals including bovines, ovines, porcines and humans. Infection of sheep, cattle and humans has been associated with abortion and congenitally acquired disorders, which primarily affect the central nervous system. It has also recently been associated with abortion and malformation in kittens born to infected queens that had been seronegative prior to infection during pregnancy. Non-feline hosts such as bovines, ovines, porcines and humans do not produce oocysts but develop and may suffer from invasion of muscle and brain by tachyzoites and bradyzoites which produce the clinical signs of diseasexe2x80x94neurological symptoms and abortion with fetal defects. It has been reported that 60% of cats are serologically positive to T. gondii. Once again, there is no approved treatment or prophylactic for toxoplasmosis.
Yet another coccidial parasite, Neospora caninum which was first isolated from dogs in 1988, produces both a neurologic and abortigenic disease in animals. It was previously confused with Toxoplasma gondii. The disease caused by this parasite occurs most severely in transplacentally infected puppies and is characterized by progressive ascending paralysis in the puppies, particularly of the hind limbs; polymyositis and hepatitis may also occur. This disease has more recently been recognized as a major cause of abortion and neurologically associated limb defects in newborn calves. Microscopic lesions of non-suppurative encephalitis and myocarditis in aborted fetuses may be seen in the brain, spinal cord and heart. A definitive host for Neospora caninum has recently been identified to be the dog. At this time there is no approved treatment or prophylaxis for either Neospora caninum of dogs or bovines or Neospora hugesi of horses.
As would be gathered from the foregoing, the prior art, including the above-cited references do not suggest or teach the use of praziquantel in treating animals infected with coccidia or, more specifically, of the family Sarcocystidae causing abortigenic or neurologic diseases without causing intolerable side effects. By the present invention, there is provided an improved and safe treatment for animals afflicted with parasitic diseases manifesting as neurologic or abortigenic diseases.
In accordance with the foregoing, the present invention encompasses a composition and a method of therapeutically treating a diseased animal suffering from a parasitic neurologic or abortigenic disease that is susceptible to being treated with a pharmaceutically effective amount of praziquantel. The method comprises administering to the animal a pharmaceutically effective amount of praziquantel.
The term xe2x80x9cpharmaceutically-effective amountxe2x80x9d as used herein means that the amount of praziquantel or a derivative thereof being administered is sufficient to inhibit the in vivo or in vitro growth of the parasitic protozoa, without causing adverse reactions in the mammal being treated. Typically the parasitic protozoa are coccidia that produce neurological disease and/or abortions. The pharmaceutically-effective amount controls the parasites in the infected tissues; consequently, the animal""s health improves. Moreover the pharmaceutically effective amount is neurologically-effective or placentally-effective in that the praziquantel or derivative thereof is in an amount that is able to cross the blood brain barrier to treat parasites infecting the central nervous system, or placental barrier without causing adverse reactions in the mammal being treated.
Further, the present invention encompasses a method of metaphylactically treating an animal infected with a parasite that can cause a neurologic or abortigenic disease that is susceptible to being treated with praziquantel. The metapylactic treatment comprises administering to the animal the praziquantel using a metaphylactically-effective regimen. By the term xe2x80x9cmetaphylactically-effective regimenxe2x80x9d is meant administering scheduled intermittent doses of a praziquantel compound or a derivative thereof for a prolonged period until said animal overcomes the invading parasites by, say, developing a protective immune response or otherwise clearing the parasite. Typically, the regimen is such as would effectively control the parasites and prevent clinical signs of disease. The metaphylactically-effective dose can also be administered for a prolonged period up to five years or the lifetime of the animal, especially in instance when the parasite is difficult to control.
Also, the present invention encompasses a single high dose treatment of the animals. This method comprises administering to the animals a single high dose of a pharmaceutically effective amount of praziquantel to a diseased animal suffering from a parasitic neurologic or abortigenic disease that is susceptible to being treated with a praziquantel compound or derivative thereof. By the term xe2x80x9csingle high dosexe2x80x9d is meant an amount that is administered only once to control the disease-causing parasites. This amount is significantly higher than the dose amount employed in the therapeutic or metapylactic treatment and is effective in controlling the disease-causing parasites, and as such would not result in detrimental effects such as toxicity. The single high dose of praziquantel is accordingly greater than 10 mg/Kg. This and other aspects of the invention are described more fully hereunder.
As set forth above, the present invention relates to a composition for, or method of treating an infected or diseased mammals suffering from a parasitic disease that manifests as neurologic or abortigenic disease that is susceptible to being treated with a praziquantel compound or derivative thereof. The method comprises administering to the mammal a composition containing a pharmaceutically effective amount of praziquantel. Illustrative but non-limiting examples of the animals can be equines, bovines, felines, canines, swine, ovines, birds, insects and humans. The parasites infecting or causing disease are coccidia of the Family Sarcocystidae that can manifest as neurologic or abortigenic diseases. Illustrative but non-limiting examples thereof can be selected from the group consisting of Sarcocystis spp., Neospora spp. and Toxoplasma spp. The Sarcocystidae are typically selected from the group consisting of S. neurona, N. hugesi, N. caninum and T. gondii. The protozoan infections or diseases include but are not limited to EPM, Neosporosis, and Toxoplasmosis.
In the practice of the invention, treatment of the parasitic infections or diseases caused by the protozoa described herein results in the alleviation of the symptoms of the neurologic and abortigenic diseases. Generally, the symptoms include lameness, ataxia, paralysis, abortion, weak newborns and other related disorders. For the therapeutic treatment, animals already suffering the above signs of disease are treated with the praziquantel compound. Typically the duration of treatment is from about 28 days to 90 days and preferably from about 28 to 60 days. It is understood that for therapeutic treatment, the treatment regimen can be administered once a day, two or more times a day, once every other day or even once per week, depending on factors such as the severity of the disease and the type of disease-producing parasite. In some cases, however, the treatment regimen can last indefinitely, sometimes for the remaining life of the animal. The latter treatment regimen would be required in the case of infection of an animal with a more resistant strain of parasite. However, the treatment can be extended for longer periods of time as necessary until the signs of disease are eliminated. The preferred treatment is once daily for about 28 days. The preferred dose for treatment ranges from 1 mg/Kg to 100 mg/Kg, preferably from 2.5 mg/Kg to 25 mg/Kg.
For the metaphylactic treatment, animals that are infected are treated to protect them against clinical manifestation of diseases. This treatment eventually results in the animals"" acquisition of the ability to control the parasite, say, by the establishing an effective immune response to impart protection against future infections, without a need for further administration of praziquantel. The metaphylactic activity, in accordance with the invention, refers to the use of the praziquantel compounds on a scheduled intermittent treatment regimen (metaphylactically-effective regimen) to control the protozoa, which may have infected the animal since the previous treatment. Accordingly, the metaphylactically-effective regimen is administered to reduce their ability to cause disease by, say, killing them or reducing them in number. In essence, the metaphylactically effective regimen can be administered about once per month, over the lifetime of the animal or until an inherent clearance mechanism, e.g., an effective immune response, develops within the animal to protect it from future infections. The latter can occur within 5 years or less. As would be realized, the metaphylactic treatment is based on the recognition that when animals are infected with the protozoa described herein, they do not demonstrate clinical signs such as neurological signs or abortion until a significant time has passed (e.g., 2-6 months post infection). In contrast, the enteric protozoan infections manifest themselves shortly after infection. In accordance with this invention, the metaphylactic treatment prevents the parasite from establishing itself and causing a clinical disease. The treatment regimen is on an intermittent schedule of about once per month, once per two months or once per two weeks at a dose equivalent to about between 1.0 and 100 mg/Kg, preferably about 1.0 to 25 mg/Kg and more preferably about 2.5 to 10 mg/Kg. The high range would be required in particularly resistant cases (e.g., when an animal is infected with a resistant strain). The required dose level and duration of treatment are within the purview of one of ordinary skill in the art. A preferred treatment regimen for horses with EPM or bovines and dogs with Neosporosis is about 1.0 to 25 mg/Kg, and a more preferred range is about 2.5 to 10 mg/Kg of praziquantel or derivatives thereof every 28 days.
For the single high dose treatment praziquantel is administered in pharmaceutically effective amounts that are greater than 10 mg/Kg and up to about 100 mg/Kg. It is a distinct feature of the invention that the compounds of this invention can be non-toxic, thus they can be administrated at high dose levels. The advantage of the high dose administration resides in the fact that repeated doses are not required.
Without being bound to any particular theory of the invention, it is believed that the unexpected success of the treatments described herein results from the ability of praziquantel to cross the blood-brain barrier or placental barrier. It is believed that the compounds of this invention easily cross the blood-brain barrier and, also, are able to penetrate the placenta and kill the protozoa in situ in the brain and cerebral spinal fluid/spinal cord. It has further been found that the compounds of this class are non-toxic and non-mutagenic even at the high doses necessary for the single high dose treatment regimen described herein.
Heretofore, no cost-effective, easily administered drugs have been available for effectively treating and protecting against these diseases without producing unacceptable side effects such as toxicity or mutagenicity in mammals.
In the practice of the invention, praziquantel can be formulated in any convenient manner for administration to animals. Formulations suitable for oral administration, which is preferred herein, can be suspensions, tablets, capsules, gels, pastes, boluses, or preparations in the form of powders, granules, or pellets. The more preferred orally administered formulation is in the form of a paste or a feed additive. Other modes of administration that can be employed including parenteral, topical, intramuscular, and intramucosal or by other routes known to those skilled in the art. Topical administration in the form of a pour-on is also preferred.
Typically, pharmaceutically acceptable carriers and auxiliaries are employed in the formulations. Examples thereof can be a thickening agents selected from the group consisting of Carbopol; inorganic thickeners such as silicates, bentonites or colloidal silica; organic thickeners such as fatty alcohols or fatty acid esters and wetting agents selected from the group consisting of polyethylene glycol and sodium lauryl sulfate with Carbopols. Preferred herein as thickening agents for paste formulations are Carbopol 974P and Carbopol 934P. Also employed herein can be preservatives selected from the group consisting of parabens, alcohols and aldehydes. These may be liquid, solid, or gaseous materials, which are otherwise inert or medically acceptable and are compatible with the active ingredients.
Surprisingly, the pastes, according to the invention, are effective when used in treating the parasites. More specifically, it is surprising that the pastes of the present invention are deliverable in a neurologically-effective dose. They are effective in delivering the praziquantel to cross the blood-brain or placenta barrier and attack the parasites that have already invaded the brain or infected the fetus of a pregnant animal. As a matter of convenience, there is provided herein a description of a specific embodiment of the pastes preferred herein and how it is prepared. A preferred paste, according to the present invention contains a micronized suspension of the praziquantel, propylene glycol, a thickening agent such as Carbopol, preservatives such as Methylparaben and Propylparaben, and water. The paste can be made by combining water, typically, purified water and Propylene Glycol, heating the combination to about 70xc2x0 C., and adding the preservatives, at this temperature. The resulting mixture is cooled to room temperature after which Carbopol, preferably in the form of Carbopol 974P or 934P, is added. Finally the praziquantel is added. After complete mixing, the pH is adjusted to approximately 6.0 with sodium hydroxide. The most preferable paste includes 15% w/w Praziquantel, 20% w/w Propylene Glycol, 0.5% w/w Carbopol 974P, 0.14% w/w Methylparaben, 0,02% w/w Propylparaben, 0.1% w/w sodium hydroxide with the remainder being purified water. Sweeteners including dextrose, sucrose, lactose, fructose, sorbitol, xylitol, artificial sweeteners and molasses may be added to improve palatability. Additionally, yeast or liver flavoring may be added for the same purpose.

Praziquantel compounds for treating diseases due to Sarcocystis Neospora Toxoplasma and Isospora


The primary operating system of a computer such as a notebook computer is stored on disk in a hard disk drive and a smaller, secondary operating system such as an email operating system, wireless phone operating system, DVD player operating system, etc. is stored on disk and is transferred to flash memory within the HDD upon power-down of the primary operating system. In this way, should the user subsequently elect to power up the computer only for a limited secondary purpose, the user can elect to boot the associated secondary operating system from flash memory of the HDD without having to spin up the disks, saving energy and reducing boot time.

When a computer is "booted", an operating system is loaded into memory from a hard disk drive. This means that the HDD must first be spun up and made operational, and then data transferred from disk to memory, lengthening the time to boot the computer.
In addition to the conventional functions of a personal computer (such as, e.g., word processing, spreadsheet generation, etc.) that are afforded by the primary operating system (such as, e.g., Windows 7), some computers are configured to execute functions that may otherwise be performed by special purpose devices. For example, some notebook computers are configured to be used as simple DVD players, or as wireless telephones, or as email devices. In each case, the present invention recognizes that a simpler secondary operating system with correspondingly limited device drivers may be stored on the HDD to be booted in lieu of the computer's primary operating system. In this way, if all a user wishes to do is to use the computer for a relatively simple function and then shut the computer down, booting time can be reduced because only the relatively smaller secondary operating system associated with the desired function need be booted into memory.
As recognized herein, however, booting under such circumstances still requires the HDD to be spun up. Although booting time is reduced, it still requires some period of time, and furthermore spinning up a HDD consumes energy, which is particularly undesirable for battery-powered computers. Nevertheless, because existing basic input-output systems (BIOS) of computers (the small programs that initiate operating system booting and that are not borne on the HDD but instead are stored in relatively small solid state memory) typically are configured to access a HDD to obtain the operating system, it remains desirable to boot from a HDD, since that is where BIOS expects the operating system to be. With these recognitions in mind, the invention herein is provided.

System and method for rapid boot of secondary operating system