The invention relates to a process for preparing reabsorbable polyesters by bulk polymerisation, wherein the reaction components are melted and homogenised in a stirred reactor, the reaction mixture is then transferred into a number of smaller-volume containers, the reaction mixture is polymerised in these containers and the polyester obtained is isolated by removing it from the containers, and the use of the reabsorbable polyesters thus produced for preparing reabsorbable implants.

The invention relates to a process for preparing reabsorbable polyesters by bulk polymerisation, wherein the reaction components are melted and homogenised in a stirred reactor, the reaction mixture is then transferred into a number of smaller-volume containers, the reaction mixture is polymerised in these containers and the polyester obtained is isolated by removing it from the containers.
Reabsorbable polyesters for the purposes of the present process are aliphatic polyesters based on lactide (L-lactide, D-lactide, DL-lactide, meso-lactide) or glycolide as well as copolymers with two or more different comonomer units of the abovementioned monomers with one another and copolymers of the monomers with trimethylene carbonate (TMC) and/or xcex5-caprolactone. This group of polyesters is preferably used to prepare reabsorbable implants for use in human or animal bodies, such as for example for fixation elements, films, membranes, suture thread or also for pharmaceutical release systems.
Polymerisation processes for preparing reabsorbable polyesters are known from the prior art. In addition to polycondensation processes which can only be used to produce relatively low-molecular polyesters, they are preferably prepared by ring-opening polymerisation of the corresponding cyclic monomers, namely L-lactide, D-lactide, DL-lactide, meso-lactide, glycolide, trimethylene carbonate, xcex5-caprolactone with the addition of metal catalysts. A plurality of catalysts are known from the prior art. Preferably, tin or zinc compounds are used. According to the prior art additives which make it possible to control the molecular weight in the polymer (chain length moderators) may be added to the reaction mixture. Aliphatic alcohols such as ethanol, dodecanol, hydroxycarboxylic acids, such as glycol or lactic acid or also oligomeric lactic acids or water have proved suitable, inter alia.
A number of techniques for the ring-opening polymerisation of lactides and related lactones are also known from the prior art. Fusion polymerisation, bulk polymerisation, solution polymerisation and suspension polymerisation are described, for example (e.g. J. Nieuwenhuis, Clinical Materials, 10, 59-67, 1992). Of these, fusion and bulk polymerisation are of the greatest technical importance. The difference between the two techniques is the reaction temperature. Whereas all the reaction components are in a molten state in fusion polymerisation, the bulk polymerisation is carried out at a temperature situated between the melting points of the particular monomer and polymer. Depending on the type of monomer/polymer the temperature during bulk polymerisation may be between about 50xc2x0 C. and 180xc2x0 C., whereas for fusion polymerisation temperatures in the range from about 190 to 230xc2x0 C. generally have to be selected.
The advantage of bulk polymerisation over fusion polymerisation is the lower reaction temperature: because of the more moderate temperature side reactions occur to a considerably lesser extent. Side reactions during polymerisation are detrimental on the one hand as they cause chain termination in the growth reaction and thereby reduce the molecular weight in the polymer. Reabsorbable polyesters with a very high molecular weight can therefore only be produced by bulk polymerisation and not in a melt. The high reaction temperatures of the fusion polymerisation also have the drawback that the resulting polymers may have some discoloration. These impurities produced at high temperatures are generally polymer-bound and cannot therefore be removed from the product in a subsequent purification step. With respect to the preferred use of the polyesters in the human body it is advantageous to avoid contamination of every kind.
Another advantage of a low reaction temperature may be the suppression of transesterifications during the polymerisation. In this way it is possible to prevent strong randomisation of the monomer sequences during copolymerisation. Because of the different reactivities of the individual monomers copolymers with a block-like sequence can be produced at low temperature.
It is known, particularly with regard to poly(L-lactide), e.g. from U.S. Pat. Nos. 4,539,981 and 4,550,449 as well as from J. Leenslag, A. Pennings, Makromol. Chem. 188, 1809-1814, 1987, that by a suitable choice of the reaction conditions such as the reaction time and temperature as well as the concentration of the catalyst and the chain length moderator, the bulk polymerisation can be controlled accordingly in terms of the molecular weight of the reaction product and the speed of the reaction.
Whereas fusion polymerisation can readily be carried out either continuously or discontinuously on a large scale in suitable polymerisation apparatus, bulk polymerisation presents major problems when performed on a large scale. As the reaction mass solidifies during the polymerisation, it is not possible to carry out the reaction in stirred reactors. The reaction product takes on the shape of the inner wall of the reactor and has to be removed from the reactor as a compact block. Thus, as the reaction mixtures are scaled up, ever larger blocks of material are produced. The handling and also subsequent grinding up into workable granules therefore becomes impossible upwards of a certain order of magnitude. A further difficulty is the removal of the heat of the reaction. As these polymerisation reactions are strongly exothermic, and moreover the polymer mass formed has very poor conductivity, in larger reactors temperature gradients may be formed which give rise to serious and unacceptable inhomogeneities in the product. These inhomogeneities may take the form of different molecular weights and, in the case of copolymers, in different molar compositions as well. According to reference (1) the temperature increase on the inside may be up to 80xc2x0 C.
Whereas the literature contains sufficient information on the choice of suitable reaction parameters for bulk polymerisation in a small-scale reaction, particularly for poly(L-lactides), the prior art contains no teaching as to how the reaction can be carried out on an industrial scale. The Examples in the literature are carried out on a small scale up to a maximum of a few hundred grams and are, moreover, carried out in test tubes in a laboratory.
The problem is therefore to provide a process which can be used on an industrial scale for preparing reabsorbable polyesters by bulk polymerisation at moderate temperatures by which high quality reabsorbable polyesters can be produced on a large scale.
When developing the process it was found, surprisingly, that the problems described above can be overcome by spatially and physically separating the polymerisation reaction into a larger reactor for melting and homogenising the reaction components and into a number of smaller subreactors, preferably made of plastics, for the actual reaction of polymerisation.
In this process the cyclic monomers are reacted, in a manner known per se, with the addition of metal catalysts and optionally chain length moderators to form the respective polymers at temperatures at which the monomer is present in molten form but the reaction product is solid or virtually solid.
The present invention thus relates to a process for preparing reabsorbable polyesters by bulk polymerisation, while the reaction components are melted and homogenised in a stirred reactor, then the reaction mixture is converted into a plurality of smaller-capacity containers, preferably plastic bottles, the reaction mixture is polymerised in these containers and the polyester obtained is isolated by removing it from the containers.
The invention also relates to the use of a reabsorbable polyester for preparing reabsorbable implants by the process according to the invention.
A preferred process comprises the following steps:
(a) melting the monomer(s) in a stirred reactor;
(a1) adding the catalyst;
(a2) optionally adding a chain length moderator;
(a3) homogenising the reaction mixture using a stirrer;
(b) transferring the reaction mixture into smaller plastic containers through a system of tubes;
(c) carrying out the polymerisation reaction in the plastic containers until the desired degree of reaction of the polymerisation is achieved;
(d) removing the polymer block formed from the plastic container.
Further processing can be carried out using methods known per se, such as e.g. grinding into granules and subsequently extracting to eliminate any unreacted monomers or by precipitation methods.
Preferred monomers are those which can be polymerised by ring-opening polymerisation of the corresponding cyclic monomers, for example L-lactide, D-lactide, DL-lactide, meso-lactide, glycolide, trimethylene carbonate and xcex5-caprolactone.
Homopolyesters selected from among the polyglycolides, particularly poly(L-lactide) or poly(DL-lactide), are preferred.
Also preferred are copolyesters selected from the following groups:
polylactides which may be obtained from various stercoisomeric lactides, particularly copolyesters of L-lactide and DL-lactide,
copolyesters of glycolide or lactide and trimethylene carbonate,
copolyesters of lactide, particularly DL-lactide or L-lactide and glycolide,
copolyesters of lactide and xcex5-caprolactone.
Also preferred are terpolymers which are obtained from three different cyclic monomers.
The catalyst may be added as it is or preferably as a solution in an inert and physiologically acceptable diluent. Aliphatic or aromatic hydrocarbons are preferred, particularly toluene or xylene.
The order of steps (a1) and (a2) may be reversed. Depending on the nature of the catalyst and chain length moderator the catalyst may also be dissolved in the chain length moderator.
Throughout the reaction the air space above the reaction mass is made inert by means of an inert anhydrous gas. Argon, helium and nitrogen are preferred, of which nitrogen is particularly preferred.
The reaction mass may be transferred from the melt container into the plastic containers using conventional pumps, by gravity or by applying pressure to the melt reactor using an inert gas, particularly nitrogen. To eliminate any particulate contaminants from the melt a melt filter made of plastics or stainless steel may be interposed.
The capacity of the plastic container may be in the range between 5 ml and 10 liters, preferably in the range between 100 ml and 5 liters, most preferably in the range between 0.5 and 5 liters, particularly about 1 liter.
The stirring reactor for melting and homogenising the reaction mixture may be a conventional reactor the inner wall of which consists of a material which is chemically inert to the reaction mixture, e.g. stainless steel, glass, enamel or Hastelloy. The preferred size of the reactor depends on the desired batch size and may be within the range between 5 and 10,000 liters.
As a rule the ratio of the internal volume of the stirring reactor to that of the internal volume of one of the smaller containers is between 1000:1 and 2:1, preferably 100:1 and 2,5:1, particularly between 75:1 and 3:1.
Containers made of plastics which are chemically and thermally stable at the reaction temperatures chosen may be used for the process. Containers made from plastics selected from among the polyolefins, polycarbonates or fluorinated and partly fluorinated plastics are preferred. Polypropylene and polytetrafluoroethane (Teflon(copyright)) are preferred.
The reactions are generally carried out at a temperature between 50xc2x0 C. and 170xc2x0 C., preferably between 60xc2x0 C. and 160xc2x0 C., particularly between 100xc2x0 C. and 150xc2x0 C. The preferred (and particularly preferred) reaction temperatures depend on the particular monomer or monomer mixture and are, for example, for:
The reactions are preferably carried out isothermically. In some cases, however, it is advantageous to start at lower temperatures in order to avoid strongly exothermic reactions, and to raise the temperature as the reaction proceeds in order to increase the speed of reaction of the monomers. This applies particularly to polymerisation involving monomers of comparatively low reactivity such as trimethylene carbonate or xcex5-caprolactone.
Preferred catalysts are tin or zinc compounds, while tin(II)halides such as tin(II)chloride and tin(II)alkoxides such as tin(II)octanoate or tin(II)ethylhexanoate are most particularly preferred. The additives used to regulate the chain length are compounds such as aliphatic alcohols, acids, hydroxycarboxylic acids and the esters thereof, water or oligomeric lactides. Water, lactic acid, oligomeric lactic acid, ethyl lactate or dodecanol are preferred.
In the process the catalysts are preferably used in low concentrations in order, on the one hand, to minimise the development of heat during the polymerisation by keeping the reaction speed low and, on the other hand, to prevent the reaction mass from polymerising to any appreciable extent while it is still in the melt reactor, which would make the transfer into the plastic containers more difficult because of the rise in viscosity. Moreover, the use of small amounts of catalyst is advantageous with respect to the use of the polyesters in the human body. In the case of tin compounds the preferred concentrations are 1 to 200 ppm, most preferably 5 to 100 ppm, particularly 10 to 50 ppm (calculated in each case as tin, based on the total reaction mass).
The preferred concentration of the chain length moderator depends on the structure of the moderator and the desired molecular weight of the polymer and is between 0 and 100,000 ppm, more preferably between 0 and 10,000 ppm, particularly 50 to 9,000 ppm, based on the total reaction mass.
The reaction times required depend on the reactivity of the monomer or monomers, the temperature selected and the concentration of catalyst and the required degree of conversion. Reaction times of between 0.5 and 25 days, more preferably between 1 and 10 days, particularly 2 to 9 days, are preferred.
As a rule the desired degree of polymerisation is reached when, of the monomers used, less than 10%, preferably 0 to 9%, most preferably 0.1 to 7%, particularly 0.2 to 5% are present in the polymer obtained by the process according to the invention.
The polyesters prepared by the process according to the invention generally have a mean inherent viscosity (Ubbelohde viscosimeter, chloroform, 0.1%, 25xc2x0 C.) of between 0.2 and 12 dl/g, preferably between 0.5 and 10 dl/g, most preferably between 1.0 and 9.0 dl/g.
In a particularly preferred embodiment of the process according to the invention a double-walled reactor is filled with 10 to 100 kg of a cyclic monomer under a nitrogen gas atmosphere. The double wall is heated to an external temperature of 100 to 160xc2x0 C. As soon as the monomer is totally melted, a chain length moderator, preferably an oligomeric lactic acid, a catalyst, preferably a solution of tin octanoate in toluene are added one after another. The quantity of catalyst is calculated so that the tin content based on the reaction mass as a whole is 5 to 100 ppm. The melt is homogenised for 5 to 60 minutes using a stirrer and then drained off through tubing, under a nitrogen gas atmosphere, into 8 to 90 plastic bottles made of polypropylene with a nominal capacity of 0.5 to 3 liters. The contents of the bottles are between 600 and 3500 g. The bottles are sealed and then placed in a warming cupboard preheated to 90 to 130xc2x0 C. and left there for a period of 2 to 10 days. During this time the warming cupboard is made inert with a gently current of nitrogen. After being taken out of the warming cupboard the bottles are cooled to ambient temperature. Then the polymer blocks formed are removed from the bottles. Samples of material from the individual blocks were analysed by GC both for their inherent viscosity and for their residual content of monomer, as follows.
The following Examples serve to illustrate some processes carried out by way of example for preparing the reabsorbable polyesters. They are intended solely as possible methods described by way of example without limiting the invention to their contents.

Process for preparing reabsorbable polyesters by mass polymerization

Boehringer Ingelheim Pharma GmbH and Co. KG


Process for the production of organic compounds in a membrane reactor. Inorganic membranes composed of an inorganic backing layer and an inorganic interlayer are used in the membrane reactor. The inorganic interlayer may be modified with organic groups.

This application is related to German Application DE 199 47 505.9, filed Oct. 1, 1999, which disclosure is incorporated herein by reference.
The present invention concerns a process for the catalytic production of organic compounds. In particular the process operates in membrane reactors equipped with inorganic membranes.
Catalytic processes are characterized in that the catalyst involved in the reaction is not consumed or is consumed only in small quantities. Even in a batch process a catalyst could, in ideal circumstances, be used for the reaction under consideration for an infinitely long period if losses during recycling or inactivation did not reduce the catalyst performance over time. Restricting the loss of catalyst can therefore contribute to minimizing process costs in catalytic synthesis performed on an industrial scale.
A continuous process, whereby the catalyst is immobilized in a reaction vessel while only the reactants can be added and only the products removed, is preferred to standard catalyst recycling, however. This processing mode can be put into practice in membrane reactors by the use of catalysts having increased molecular weight (Wandrey et al. in Jahrbuch 1998, Verfahrenstechnik und Chemieingenieurwesen, VDI p. 151ff.; Wandrey et al. in Applied Homogeneous Catalysis with Organometallic Compounds, Vol. 2, VCH 1996, p.832 ff.; Kragl et al., Angew. Chem. 1996, 6, 684f.).
Reports on catalysts having increased molecular weight or increased polymer have already appeared in the prior art on a number of occasions (Reetz et al., Angew. Chem. 1997, 109, 1559f.; Seebach et al., Helv. Chim Acta 1996, 79,1710 f.; Kragl et al., Angew. Chem. 1996, 108, 684f.; Schurig et al., Chem. Ber./Recueil 1997,130, 879f.; Bolm et al., Angew. Chem. 1997, 109, 773f.; Bolm et al. Eur. J. Org. Chem. 1998, 21f.; Baystone et al. in Speciality Chemicals 224f.; Salvadori et al., Tetrahedron: Asymmetry 1998, 9, 479; Wandrey et al., Tetrahedron: Asymmetry 1997, 8, 1529f.; ibid. 1997, 8, 975f.; Togni et al. J. Am. Chem. Soc. 1998, 120, 10274f., Salvadori et al., Tetrahedron Left. 1996, 37, 3375f.)
Until now exclusively polymeric membranes of organic origin have been used in processes in which homogeneously or colloidally soluble catalysts having increased molecular weight were used in membrane reactors.
The use of polymeric membranes is associated with a number of disadvantages, however, because of the organic solvents used in chemical synthesis.
The solvent resistance of the polymeric membranes that are commercially available at present applies in each case only to selected solvents. Different membranes therefore have to be used in production, depending on the reaction and solvent. In practice this means that the membranes have to be changed between different production batches. Moreover, when changing between polar and non-polar solvents, various membrane conditioning steps have to be interposed (Schmidt et al.; Chemie Ingenieur Technik (71), 3/1999).
Furthermore, the temperature resistance of the polymeric membranes that are commercially available at present is restricted to a maximum of 80xc2x0 C. Information available in the literature or supplied by the manufacturer fluctuates between 40xc2x0 and 80xc2x0 C. for solvent-stable polymeric membranes. In homogeneous catalysis in particular, however, it may also be necessary to operate at temperatures above 70xc2x0 C., since the degree of conversion can thereby be improved (xe2x80x9cMetal-cat. Cross-coupling Reactionsxe2x80x9d, Ed.: F. Diedrich, P. J. Stang, VCH-Wiley, 1998
xe2x80x9cTransition Metals for Org. Synthesisxe2x80x9d, Ed.: M. Beller, C. Bolm, VCH-Wiley, 1998).
The flow rates for the currently available polymeric membranes in the area of ultrafiltration and especially nanofiltration are very low for industrial use. The flow rates that can be achieved depend on the solvent and membrane used, but are generally well below 5 l/m2/h/bar (Schmidt et al.; Chemie IngenieurTechnik (71), 3/1999).
The polymeric membranes display poor mechanical stability in regard to pressure. The use of these membranes at elevated pressures is technically achievable only by incorporating them in specially made and hence expensive flat or filament-wound modules with appropriate module housings.
The object of the present invention was therefore to provide a process whereby the problems in terms of solvent dependence, sensitivity to pressure, poor flow rate or reduced temperature resistance of the membranes as referred to above do not arise, such that their use in the manufacture of organic compounds on an industrial scale appears to be possible without reservation and to be advantageous in economic terms.
This object is achieved both economically and effectively in a process for the production of organic compounds in a membrane reactor with the aid of homogeneously or colloidally soluble catalysts having increased molecular weight, by using as membrane an inorganic membrane that displays an inorganic backing layer and an inorganic interlayer, whereby the interlayer can be modified with organic groups.
In principle the use of inorganic membranes for the retention and separation of heterogeneous catalysts is documented by various processes (e.g. DE 197 27 715 A1), but such membranes have so far not been proposed for the separation of homogeneously or colloidally soluble catalysts having increased molecular weight.
One reason for this is that unlike heterogeneous catalysts, the retention ability of homogeneously or colloidally soluble catalysts having increased molecular weight is not linked in a straight-forward manner to the molecule size. Instead the retention ability is determined by what is known as the hydrodynamic molecule diameter, which is governed by various parameters (molecular structure, solvent, etc.). However, the importance of an extremely high retention ability in a catalyst behind a membrane relative to the loss of catalyst due to bleeding is illustrated in FIG. 1 by means of simple theoretical estimates. Only when the retention is well above  greater than 99.9% are the catalysts retained in the reactor to a sufficient degree and for residence times that are of any interest for industrial applications.
While polymeric membranes have enabled appropriate residence times to be achieved for some time now as a result of extremely favorable cut-offs, in the case of inorganic membranes this has only been technically feasible for a relatively short time.
Another effect likewise discouraged the use of inorganic membranes. The retention ability in the dead-end mode of operation is lower in comparison to that of polymeric membranes with a comparable cut-off.
Surprisingly it has been found that in the crossflow mode of operation, by contrast, a crossflow-dependent retention ability develops to such an extent that it can compensate for or even overcompensate for this disadvantage, even at relatively low crossflow speeds (see Table 2 and Example 1).
This was extremely surprising, yet no less advantageous as a consequence.
In principle all inorganic membranes familiar to the person skilled in the art that display an inorganic backing layer and an inorganic interlayer can be used as membranes. The interlayer forms the actual small pore diameter required for retention, whereby this can be modified using organic groups known to the person skilled in the art in order to modify its separation properties (e.g. hydrophobia and hydrophilia).
Examples of such components include silicon-organic compounds in general, particularly alkyl silanes (Noach et. al., Chemie lngenieur Technik (70) 8/98). Furthermore there are suitable organic compounds with which the interlayer can be modified, including (CH3)3SiCl, methyltriethoxysilane, ethyltriethoxysilane, octyltriethoxysilane, octadecyltriethoxysilane, mono- or polyfluoroalkylethoxysilane or also silanes with functionalized organic groups that permit a subsequent further modification by means of covalent linkage knotting by known means. Examples of these include trimethoxyvinylsilane, H2Cxe2x95x90C(CH3)CO2(CH2)3Si(OCH3)3, triethoxyvinylsilane and 3-glycidoxypropyl trimethoxysilane, as well as silanes with hydroxyl, carboxyl, epoxy and carboxylic acid ester groups carrying inorganic radicals. In a particular embodiment the filler is modified with silanes having the general formula RSi(OX)3, where R is an alkyl group with 1 to 18 C atoms and X is an alkyl group with 1 or 2 C atoms. Trimethyl chlorosilane is particularly used to increase stability and hydrophobicity, as described in Koyano, K. A.; Tatsumi, T.; Tanaka, Y.; Nakata, S. J. Phys. Chem. B 1997, 101, p. 9436 und Zhao, X. S.; Lu, G. Q., J. Phys. Chem. B 1998, 102, p. 1156.
The average pore diameter in the inorganic separation membrane should be dimensioned such that an economically meaningful product flow is ensured with as high a retention ability as possible. The pore diameter should preferably be greater than 0.1 nm, particularly preferably greater than 0.4 nm. The interlayer used should exhibit an upper average pore diameter of less than 200 nm, particularly preferably less than 10 nm, most particularly preferably less than 1 nm.
As has already been indicated, advantageous membranes are those exhibiting a structure wherein the backing layer of the membrane consists of one or more inorganic oxides, preferably aluminium oxide and/or SiO2. One or more interlayers consisting of one or more inorganic oxides, preferably titanium oxide, SiO2, Al2O3 and/or zirconium oxide, can moreover be applied to this backing layer. As indicated above, it can be advantageous to modify the interlayer additionally with organic components.
As has further been mentioned above, the membrane can be used in a dead-end filtration process. The embodiment whereby the membrane is used in crossflow mode as a mono- or multitubular module or in the form of a flat membrane as a plate module with tangential crossflow in a crossflow filtration module appears to be advantageous according to the invention. The crossflow speeds in this context should range within the industrial and economic limits. Linear crossflow speeds of 0.01-5 m/s are preferred, particularly preferably 0.05-2 m/s. The process can be performed in a temperature range from 10xc2x0 to 250xc2x0 C. and at a transmembrane pressure of max. 150 bar, preferably up to 10 bar, particularly preferably up to 50 bar.
Catalysts having increased molecular weight made from a dendritic, linear or variously branched homopolymer or copolymer consisting of butadiene and/or isoprene or a copolymer consisting of butadiene and/or isoprene optionally with propylene and/or styrene or a block copolymer consisting of polybutadiene and/or polyisoprene optionally with polypropylene and/or polystyrene as polymer framework or linear, branched and dendritic polymers consisting of polysiloxanes, polyacrylates, polyvinyl pyrrolidones and polystyrenes are advantageous.
The catalysts having increased molecular weight can preferably exhibit as active center a catalyst selected from the group of oxazaborolidines, TADDOLs, salens, quinidines, oxazolines, amino alcohols, diols, mono- and diphosphanes, -phosphites, -phosphonites, or phosphinites.
The process according to the invention can be used to produce non-chiral, racemic and enantiomer-enriched organic compounds.
In addition to the previously described advantages in the use of homogeneously or colloidally soluble catalysts having increased molecular weight in polymeric membranes, further advantages of this process include a pronounced expansion of the possible operating parameters in regard to pressure, temperature and solvent spectrum when a membrane is used. At the same time the specific filtrate flows of inorganic membranes are significantly higher in comparison to polymeric membranes with the same nominal cut-off and corresponding crossflow speed (Example 1).
It has been found that by making an optimum selection of operating conditions, matching the molecular weight and the type of polymer to the average pore diameter of the membrane, extreme retention capacities in the catalysts can be achieved that enable these catalysts to be used advantageously on an industrial basis.
In the context of the invention, the term membrane reactor refers to any type of reaction vessel whereby the catalyst is enclosed in a reactor while low-molecular substances are fed into the reactor or are able to leave it. The membrane can be integrated directly into the reaction chamber or incorporated into a separate filtration module outside, whereby the reaction solution flows continuously or intermittently through the filtration module and the retained matter is returned to the reactor. Suitable embodiments are described inter alia in WO98/22415 and in Wandrey et al. in Jahrbuch 1998, Verfahrenstechnik und Chemieingenieurwesen, VDI p. 151ff.; Wandrey et al. in Applied Homogeneous Catalysis with Organometallic Compounds, Vol. 2, VCH 1996, p.832 ff.; Kragl et al., Angew. Chem. 1996, 6, 684f.
Homogeneous or colloidal solubility refers to a solution in which phase separation does not occur under the influence of gravity or of a centrifugal force of equivalent strength to gravity.
In the context of the invention the term increased molecular weight refers to the increase in molecular weight of the catalyst under consideration by means of adsorptive or covalent bonding to appropriate organic or inorganic homogeneously or colloidally soluble support materials, e.g. nanoparticles (Zhao et al. Angew. Chem. 1999, 111, No.3).
The term enantiomer-enriched refers to the predominance of one optical antipode in a mixture of both optical antipodes.


The present invention relates to selectively electrically connecting an electrical interconnect line, such as a bit line of a memory cell, with an associated contact stud and electrically isolating the interconnect line from other partially underlying contact studs for other electrical features, such as capacitor bottom electrodes. The interconnect line can be formed as initially partially-connected to all contact studs, thereby allowing the electrical features to be formed in closer proximity to one another for higher levels of integration. In subsequent steps of fabrication, the contact studs associated with memory cell features other than the interconnect line can be isolated from the interconnect line by the removal of a silicide cap, or the selective etching of a portion of these contact studs, and the formation of an insulating sidewall between the non-selected contact stud and the interconnect line.

1. Field of the Invention
This invention relates to a semiconductor device and a method of manufacturing such a device, wherein signal lines (e.g., bit lines of a memory device, etc.) may be isolated from adjacent electrical conductors.
2. Discussion of the Related Art
Modern integrated circuit designers confront problems related to the need for increasingly smaller size and higher levels of integration. In the art of integrated circuit fabrication, and particularly when dealing with modern memory circuits, circuit manufacturers must design memory cells that are more densely constructed such that the basic elements making up the cell are closer together. This increasingly close proximity of the discrete electrical features within a memory cell, such as dynamic random access memory (DRAM) cells, becomes problematic in light of the increasing potential for shorting between adjacent electrical conductors. This shorting may cause a memory cell to function improperly or not at all.
An additional concern in the manufacture of integrated circuits is the increasing complexity and cost related to the necessity for diminishing size of the memory devices. The desire to utilize fewer stages of fabrication has led designers of memory cells to strive to simultaneously perform, at a given stage of fabrication, as many necessary steps as possible. An example of this may be seen in the standard technology of fabricating capacitor-over-bit-line (COB) type DRAM cells, which typically employs a process wherein all contacts to the memory cell active area are formed simultaneously. Thus, both bit line and capacitor contacts to the semiconductor substrate are formed using a single layering and etching step (utilizing material such as polysilicon), which creates contact studs over which the additional features of the memory cell are fabricated.
Specifically in a process such as described above, after the contact studs are formed in the memory cell, a dielectric layer is deposited and a bit line contact-hole pattern is lithographically delineated and subsequently etched down to the top of the stud corresponding to the bit line connection to the active area on the substrate below. A plug is next formed within each contact-hole, typically of doped polysilicon, and the conductive layers for the bit lines (typically silicide, polycide, or tungsten-based material) are deposited and subsequently delineated using lithographic-etching techniques. An interlayer dielectric is next deposited around the bit line and a capacitor contact-hole pattern is lithographically delineated and etched down between the formed bit lines to the tops of the studs corresponding to the capacitor bottom electrode connections to the active area on the substrate below. This fabrication step is completed when the capacitor contact-holes are then plugged with doped polysilicon or another conductor. Then the process of cell fabrication continues on to the formation of the capacitor features.
This standard method of fabricating memory cells utilizes the single-step forming of contact studs for both capacitors and bit lines, and the forming of bit line contacts and bit lines. Though this method is useful in reducing the steps required to form contacts to active areas of a substrate, it is desirable that the contacts, and subsequently the fully formed features, be located in a more densely packed array. It is also desirable to have the electrical features and interconnects, exemplified by bit line and capacitor features, arranged in such a more densely packed array without increasing the probability of shorting.
The present invention relates to integrated circuit fabrication and more particularly to selectively electrically connecting an electrical interconnect line with an associated contact to an active area and electrically isolating the interconnect line from other underlying contacts for other electrical features.
More specifically, in this invention a first interconnect line is formed over two underlying contact holes such that it is electrically connected to a first polysilicon stud but is electrically isolated from a second stud. The line is essentially formed over the first stud and partially over the second stud, and is thereafter electrically isolated from the second studs, thereby allowing the electrical features to be formed in closer proximity to one another for higher levels of integration.
The present invention also provides a method for efficiently connecting interconnect lines to a plurality of selected contact studs while maintaining electrical isolation from other non-selected plugs.
The above-described and other advantages and features of the invention will be more clearly understood from the following detailed description which is provided in connection with the accompanying drawings.

Interconnect line selectively isolated from an underlying contact plug


Dry bleach compositions particularly suitable for cleaning of hard surfaces or fabrics which, upon mixing with water, form a mixture that is easily removed from surfaces upon standing.

The present invention relates to dry bleach compositions, especially useful for cleaning hard surfaces or fabrics.
Dry bleach compositions for household use generally differ from typical laundry or hard surface cleaners in that they contain an increased level of bleach, and are typically used for stain removal from surfaces such as hard surfaces (e.g., in the kitchen or bathroom) or fabrics (e.g., laundry). The dry bleach compositions may employ a peroxy bleach. Particularly suitable, due to lower cost, is sodium perborate because it is stable within the composition. By contrast, percarbonate typically requires coating and, thus, can be more expensive and less stable.
U.S. Pat. No. 4,650,599 (Farnworth et al.) discloses free flowing laundry powder compositions containing 4-50% surfactant, 5-50% perborate and 5-80% carbonate. Chinese patent CN 1064885 discloses brushing powder and dry cleaning paste which may contain 2-30% surfactant, 0-4% perborate and either sodium carbonate or sodium sulfate in a range of 0-15%. Example 9 is a dry cleaning powder containing, among other ingredients, 90% starch and talc, 4.5% surfactant, 2% carbonate, 3% anhydrous sulfate and 0.4% perborate. WO 92/21744 discloses dry bleach composition, to be used as an additive in the laundry, with improved dispersability containing 5-50% perborate, 25-80% carbonate, optionally sulfate in an amount of 0-80%, preferably 10-50%, and optionally up to 5% surfactant.
Typically, the compositions are used as adjuncts in cleaning or laundry. A commercial bleaching multi-purpose stain remover product is xe2x80x9callxe2x80x9d Oxi-active(copyright), containing a mixture of perborate and carbonate. The consumers are directed to mix the xe2x80x9callxe2x80x9d Oxi-active(copyright) powder with some water and then apply the resulting solution or paste to a stain or a surface area in need of cleaning. Consumers do not necessarily wash off the applied paste right away, perhaps believing that cleaning/stain removal will be more effective if the paste is left on the surface for some time. It has been found, as part of the present invention, that, unfortunately, compositions which contain high levels of perborate and carbonate, cake-up and harden upon standing, forming a hard crust that is difficult to remove by mechanical means and/or which might not be readily dispersible in the laundry machine, particularly when cold water is employed.
The present invention includes a dry bleach composition comprising:
(a) from about 10% to about 80%, by weight of the composition, of sodium perborate;
(b) from about 10% to about 50%, by weight of the composition, of an anhydrous carbonate salt;
(c) from about 3% to about 40%, by weight of the composition, of an anhydrous sodium sulfate;
(d) from about 0% to about 3%, by weight of the composition, of a detergent surfactant.
Another aspect of the present invention is the paste which results from combining the inventive dry bleach composition with water.
Yet another aspect of the present invention are methods of cleaning surfaces with the inventive dry bleaching compositions.
Surprisingly, the inclusion of sulfate in certain ratios to carbonate prevents the hardening of the perborate/carbonate product when diluted with water.
Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word xe2x80x9cabout.xe2x80x9d All amounts are by weight of the final composition, unless otherwise specified.
It should be noted that in specifying any range of concentration, any particular upper concentration can be associated with any particular lower concentration.
For the avoidance of doubt the word xe2x80x9ccomprisingxe2x80x9d is intended to mean xe2x80x9cincludingxe2x80x9d but not necessarily xe2x80x9cconsisting ofxe2x80x9d or xe2x80x9ccomposed of.xe2x80x9d In other words, the listed steps or options need not be exhaustive.
xe2x80x9cDryxe2x80x9d means that that the composition is powdered or granular, dry-blended, as opposed to liquid.
xe2x80x9cAnhydrousxe2x80x9d means that water of hydration is always less than 0.5 molecule of water per molecule of salt.
xe2x80x9cPastexe2x80x9d means a mixture that results from combining the inventive compositions with from about 20% to about 80% water; it may be runny or somewhat hard.
Perborate
Sodium perborate suitable for use in the present invention may be in the form of tetrahydrate or monohydrate. Monohydrate is preferred, due to better stability and cost effectiveness. Sodium perborate is employed in an amount of from 10 to 80%, preferably, in order to attain improved cleaning/stain removal from 30 to 60%, most preferably from 35 to 45%, optimally to attain maximum cleaning at minimum cost, at about 50%.
Carbonate Salt
Suitable carbonate salt is preferably selected from alkali-metal carbonates, sesquicarbonates and bicarbonates. Preferred are sodium and/or potassium carbonates, most preferably sodium carbonate due to better cost effectiveness. The carbonate salt acts as the builder to remove divalent metal ions such as calcium, and additionally provides alkalinity and aids in soil removal.
Both the carbonate and the sulfate included in the present invention are anhydrous, in order to minimize excessive caking and improve the ease of dissolution in the laundry and/or removal from hard surfaces. Thus the sulfate and the carbonate, each contain less than 0.5 molecule of water per molecule of salt.
The carbonate salt is employed in an amount of from 10 to 50%, preferably, in order to attain improved cleaning/stain removal from 12.5 to 45%, most preferably from 15 to 45%.
Sulfate
Sodium sulfate is included in the inventive compositions in an amount of from 3 to 40%, in order to obtain a composition which does not harden extensively when mixed with water and let stand, and yet is not excessively crumbly or crystalline. Preferably, the sulfate is included in an amount of at least 5%, most preferably from 5 to 37.5%.
The preferred inventive compositions, in order to attain optimum cleaning and optimum paste properties include the carbonate and the sulfate in a ratio from 1:5 to 10:1, most preferably from 1:3 to 7:1.
The inventive compositions are bleach compositions, thius they are preferebly formulated to not include substantial amounts of ingredients other than perborate, the carbonate salt and the sulfate. Preferably, the total amount of perborate, alkaline builder, and sulfate in the inventive compositions is at least 90%, preferably at least 95%, and most preferably at least 98%.
Optional Detergent Surfactant
The inventive compositions preferably do not include a detergent surfactant, particularly when they are intended for hard surface cleaning include less than 3%, preferably less than 2%, most preferably less than 1%.
When included, surface active agents may be selected from the group consisting of anionic, nonionic, cationic, amphoteric and zwitterionic surfactants or mixtures thereof.
Anionic surface active agents which may be used in the present invention are those surface active compounds which contain a long chain hydrocarbon hydrophobic group in their molecular structure and a hydrophilic group, i.e. water solubilizing group such as carboxylate, sulfonate or sulfate group or their corresponding acid form. The anionic surface active agents include the alkali metal (e.g. sodium and potassium) water soluble higher alkyl aryl sulfonates, alkyl sulfonates, alkyl sulfates and the alkyl poly ether sulfates. They may also include fatty acid or fatty acid soaps. One of the preferred groups of anionic surface active agents are the alkali metal, ammonium or alkanolamine salts of higher alkyl aryl sulfonates and alkali metal, ammonium or alkanolamine salts of higher alkyl sulfates. Preferred higher alkyl sulfates are those in which the alkyl groups contain 8 to 26 carbon atoms, preferably 12 to 22 carbon atoms and more preferably 14 to 18 carbon atoms. The alkyl group in the alkyl aryl sulfonate preferably contains 8 to 16 carbon atoms and more preferably 10 to 15 carbon atoms. A particularly preferred alkyl aryl sulfonate is the sodium, potassium or ethanolamine C10 to C16 benzene sulfonate, e.g. sodium linear dodecyl benzene sulfonate. The primary and secondary alkyl sulfates can be made by reacting long chain alpha-olefins with sulfites or bisulfites, e.g. sodium bisulfite. The alkyl sulfonates can also be made by reacting long chain normal paraffin hydrocarbons with sulfur dioxide and oxygen as describe in U.S. Pat. Nos. 2,503,280, 2,507,088, 3,372,188 and 3,260,741 to obtain normal or secondary higher alkyl sulfates suitable for use as surfactant detergents.
Additional Optional Ingredients
In additional to the optional surfactant, the inventive compositions may include additional peroxy bleaches, such as percarbonate, bleach activators, and additional builders.
Certain zeolites or aluminosilicates can be used. One such aluminosilicate which is useful in the compositions of the invention is an amorphous water-insoluble hydrated compound of the formula Nax(AlO2)ySiO2, wherein x is a number from 1.0 to 1.2 and y is 1, said amorphous material being further characterized by a Mg++ exchange capacity of from about 50 mg eq. CaCO3/g. and a particle diameter of from about 0.01 micron to about 5 microns. This ion exchange builder is more fully described in British Pat. No. 1,470,250.
A second water-insoluble synthetic aluminosilicate ion exchange material useful herein is crystalline in nature and has the formula Naz[(AlO2)y.(SiO2)]xH2O, wherein z and y are integers of at least 6; the molar ratio of z to y is in the range from 1.0 to about 0.5, and x is an integer from about 15 to about 264; said aluminosilicate ion exchange material having a particle size diameter from about 0.1 micron to about 100 microns; a calcium ion exchange capacity on an anhydrous basis of at least about 200 milligrams equivalent of CaCO3 hardness per gram; and a calcium exchange rate on an anhydrous basis of at least about 2 grains/gallon/minute/gram. These synthetic aluminosilicates are more fully described in British Patent No. 1,429,143.
When intended as a laundry adjunct, the inventive composition may further include one or more well-known laundry ingredients, anti-redeposition agents, fluorescent dyes, perfumes, soil-release polymers, colorant, enzymes, bleaches, bleach precursors, buffering agents, antifoam agents, UV-absorbers, etc.
Optical brighteners for cotton, polyamide and polyester fabrics can be used. Suitable optical brighteners include Tinopal, stilbene, triazole and benzidine sulfone compositions, especially sulfonated substituted triazinyl stilbene, sulfonated naphthotriazole stilbene, benzidene sulfone, etc., most preferred are stilbene and triazole combinations. A preferred brightener is Stilbene Brightener N4 which is a dimorpholine dianilino stilbene sulfonate.
Also, soil release polymers and cationic softening agents may be used.
Examples of optional ingredients suitable for both laundry and hard surface inventive compositions include but are not limited to anti-foam agents (e.g. silicone compounds, such as Silicane L 7604), bactericides, e.g. tetrachlorosalicylanilide and hexachlorophene, fungicides, dyes, pigments (water dispersible), preservatives, e.g. formalin, ultraviolet absorbers, anti-yellowing agents, such as sodium carboxymethyl cellulose, pH modifiers and pH buffers, color safe bleaches, perfume and dyes and bluing agents such as Iragon Blue L2D, Detergent Blue 472/372 and ultramarine blue can be used.
The list of optional ingredients above is not intended to be exhaustive and other optional ingredients which may not be listed, but are well known in the art, may also be included in the composition.
Process of Making Composition
The inventive compositions are made by dry-mixing the ingredients.
Paste
The invention also includes a mixture (xe2x80x9cpastexe2x80x9d) that results from mixing the inventive dry bleach composition with 20-80%, preferably from 30 to 70%, most preferably from 40 to 60%, by weight of the paste, of water. Preferred paste compositions, in order to attain optimum paste-like consistency and to minimize hardening upon standing incorporate all the preferred embodiments, amounts and ratios for the bleach composition as described above.
Method of Use
The compositions are intended to be used as adjuncts, or independently, for cleaning of fabrics (e.g., laundry, carpets, draperies) or hard surfaces (e.g., in the bathroom or kithchen). Preferably the bleaching paste is prepared, as described hereinabove, applied to the surface, especially, a stain, and then allowed to remain on the surface for a reasonable amount of time (e.g. from about 5 minutes to about 1 hour), and then washed off the surface.
The following specific examples further illustrate the invention, but the invention is not limited thereto.

Unilever Home and Personal Care USA, division of Conopco, Inc.


A delivery device (20, 22) for and a method of delivering a substance to the nasal airway (1) of a subject, in particular the posterior region of the nasal airway, the delivery device comprising: a closure unit for causing the closure of the oropharyngeal velum of the subject; and a delivery unit for delivering a gas flow entraining a substance to one of the nostrils of the subject at such a driving pressure as to flow around the posterior margin of the nasal septum and out of the other nostril of the subject, wherein the delivery unit comprises a nosepiece (30, 40, 58, 82, 102, 132) which includes an outlet through which the gas flow is in use delivered to the one nostril and a sealing member for sealing the one nostril to the outlet such as in use to prevent the escape of the gas flow through the one nostril.

The present invention relates to a delivery device for and a method of delivering a substance, in particular one of a liquid, as a suspension or solution, or a powder containing a medicament, especially a topical pharmaceutical, a cleansing agent, or an irrigating agent, as a liquid, preferably combined with a cleansing agent, to the nasal airway of a subject. In particular, the present invention relates to the delivery of medicament to and the irrigation of the nasal mucosa, the anterior region of nasopharynx, the paranasal sinus ostia, the tubal ostia of the auditory tubes, the sinus tubes, the auditory tubes, the tympanic cavities and the paranasal sinuses.
Referring to FIG. 1, the nasal airway 1 comprises the two nasal cavities separated by the nasal septum, which airway 1 includes numerous ostia, such as the paranasal sinus ostia 3 and the tubal ostia 5, olfactory cells and is lined by the nasal mucosa. The nasal airway 1 can communicate with the nasopharynx 7, the oral cavity 9 and the lower airway 11, with the nasal airway 1 being in selective communication with the anterior region of the nasopharynx 7 and the oral cavity 9 by opening and closing of the oropharyngeal velum 13. The velum 13, which is often referred to as the soft palate, is illustrated in solid line in the closed position, as achieved by providing a certain positive pressure in the oral cavity 9, such as achieved on exhalation through the oral cavity 9, and in dashed line in the open position.
There are many nasal conditions which require treatment. One such condition is nasal inflammation, specifically rhinitis, which can be allergic or non-allergic and is often associated with infection and prevents normal nasal function. By way of example, allergic and non-allergic inflammation of the nasal airway can typically effect between 10 and 20% of the population, with nasal congestion of the erectile tissues of the nasal concha, lacrimation, secretion of watery mucus, sneezing and itching being the most common symptoms. As will be understood, nasal congestion impedes nasal breathing and promotes oral breathing, leading to snoring and sleep disturbance. Worryingly, the incidence of such allergic and non-allergic inflammatory diseases is increasing. Other nasal conditions include nasal polyps which arise from the paranasal sinuses, hypertrophic adenoids, secretory otitis media, sinus disease and reduced olfaction.
In the treatment of certain nasal conditions, the topical administration of medicaments is preferable, particularly where the nasal mucosa is the prime pathological pathway, such as in treating or relieving nasal congestion. Indeed, topical administration is advantageous in minimising the possible side effects of systemic administration. Medicaments that are commonly topically delivered include decongestants, antihistamines, cromoglycates, steroids and antibiotics.
There are now an increasing number of adults and children who rely on pharmaceuticals to relieve symptoms associated with nasal conditions. At present, among the known anti-inflammatory pharmaceuticals, topical steroids have been shown to have an effect on nasal congestion. Topical decongestants have also been suggested for use in relieving nasal congestion. The treatment of hypertrophic adenoids and chronic secretory otitis media using topical decongestants, steroids and anti-microbial agents, although somewhat controversial, has also been proposed. Further, the topical administration of pharmaceuticals has been used to treat or at least relieve symptoms of inflammation in the anterior region of the nasopharynx, the paranasal sinuses and the auditory tubes.
Aside from the delivery of medicaments, the irrigation of the nasal mucosa with liquids, in particular saline solutions, is commonly practised to remove particles and secretions, as well as to improve the mucociliary activity of the nasal mucosa. These solutions can be used in combination with active pharmaceuticals.
Furthermore, medicaments are now increasingly systemically delivered through the nasal pathway, the nasal pathway offering a good administration route for the systemic delivery of pharmaceuticals, such as hormones, for example oxytocin, and anti-migraine compositions, as the high blood flow and large surface area of the nasal mucosa advantageously provides for rapid systemic uptake.
A variety of delivery systems have been developed to deliver substances to the nasal airways of subjects.
Conventionally, spray bottles have been used to deliver a medicament-containing liquid or an irrigating liquid to the nasal airways of subjects. However, the distribution of the delivered substance, in particular to the posterior region of the nasal airway, is less than ideal, especially in the cases of moderate and severe nasal obstruction. This poor distribution is often further exacerbated by a subject inhaling through the nasal airway during delivery, as is often prescribed, in an attempt to deliver the substance to the posterior region of the nasal airway. Indeed, an amount of the substance can be drawn into the lungs or swallowed in each delivery, which could be problematic in paediatric subjects if the medicament is a potent pharmaceutical, such as a steroid, which has to be administered frequently. In addition, the spray is frequently directed against the nasal septum which can undesirably lead to localised deposition. Further, the mechanical action of the delivery mechanism of the spray bottles can cause irritation and bleeding.
GB-A-408856 discloses a delivery device, which, in one mode of use, allows for the inhalation of separate air flows entraining medicament into respective ones of the nasal cavities of a subject. This delivery device comprises a chamber containing a sponge saturated with medicament, a mouthpiece connected to the chamber and first and second nosepieces connected to the chamber. In one mode of use, the nosepieces are fitted into respective ones of the nostrils of a subject, and, on inhalation through the nosepieces, air flows entraining medicament are drawn into the lungs of the subject. In another mode of use, the mouthpiece is taken in the mouth of a subject, and, on inhalation through the mouthpiece, an air flow entraining medicament is drawn into the lungs of the subject.
WO-A-98/53869 discloses a delivery device for delivering a powder containing a medicament to the nasal mucosa in one of the nasal cavities of a subject. This device comprises a tubular section which contains a metered dose of powdered medicament. In use, the ends of the tubular section are respectively located in the nostril of one of the nasal cavities and the mouth of a subject, and on exhalation by the subject through his or her mouth the exhaled air entrains the powdered medicament and delivers the same into the one nasal cavity, with the exhaled air backflowing out of the one nostril around the tubular section. In one embodiment the tubular section includes a flexible portion upstream of the dose of powdered medicament. The provision of this flexible portion allows the subject to close the tubular section at a point upstream of the medicament, such that, on release of the closed flexible portion during exhalation, a short explosive air flow entraining medicament is delivered into the one nasal cavity. In another embodiment the end of the tubular section located in the nostril can be shaped to act to locate the tubular section in a position in the nostril which allows for the deposition of the powdered medicament on the nasal mucosa.
Whilst this delivery device is simple in construction, the operation of the device still does not provide for the effective delivery of substances, in particular one of a liquid or powder containing medicament, to the posterior region of the nasal airway, since medicament is delivered separately to each of the nasal cavities and the air flow into and out of each nasal cavity is through the same opening, namely the respective nostril, with the closed posterior region of the respective nasal cavity acting as a pressure reflecting surface which causes the exhaled air to backflow out of the one nostril before ever adequately reaching the posterior region of the respective nasal cavity. Further, in providing a short explosive burst of air flow into one of the nasal cavities, it is not possible to achieve a sustained and controlled bi-directional air flow through the nasal cavities which has been found necessary to deliver a substance effectively to the posterior region of the nasal airway.
For any substance to be delivered effectively to the nasal airway, it is highly desirable that the administration is efficient and simple. However, there can be problems in attempting to achieve this goal. In particular, the pathological changes observed with nasal inflammation make administration of substances, such as liquids or powders, tricky, particularly to the posterior region of the nasal airway and the posterior margins of the nasal structures. Indeed, as a consequence of the complex geometry of the narrow slit-like passages in the nasal airway, these passages become partially occluded when the nasal mucosa is inflamed and congested, making the distribution of topical pharmaceuticals to the nasal airway difficult.
It is thus an aim of the present invention to provide a delivery device for and a method of achieving a more optimally distributed deposition of a substance, especially topical pharmaceuticals, in the nasal airway, particularly the posterior region of the nasal airway, and in particular the anterior region of the nasopharynx where the adenoid and tubal ostia are located.
Accordingly, the present invention provides a nasal delivery device for delivering a substance to the nasal airway of a subject, comprising: a closure unit for causing the closure of the oropharyngeal velum of the subject; and a delivery unit for delivering a gas flow entraining a substance to one of the nostrils of the subject at a driving pressure which would be such as to cause the gas flow to flow around the posterior margin of the nasal septum and out of the other nostril of the subject, wherein the delivery unit comprises a nosepiece which includes an outlet through which the gas flow is in use delivered to the one nostril and a sealing member for providing a fluid tight seal between the outlet and the one nostril.
In one embodiment the substance comprises a dry powder.
In another embodiment the substance comprises liquid droplets.
Preferably, the particle size distribution of the substance is principally in the range of about 1 to 10 xcexcm.
In one embodiment the substance contains a medicament, particularly for the treatment of a nasal condition. In a preferred embodiment the particle size distribution of the substance can include a smaller fraction of larger particles, typically in the range of about 10 to 30 xcexcm, and preferably in the range of about 20 to 30 xcexcm.
In other embodiments the substance can be a cleansing agent, as a powder or liquid, for cleansing the nasal airway, or a liquid, which may preferably contain a cleansing agent, for irrigating the nasal airway. By way of example, the delivery device could be used to administer saline or other solutions to the nasal airway to remove particles and secretions, in particular from the posterior region of the nasal airway, which resulting solution could be analysed for diagnostic or research purposes. In a preferred embodiment the particle size distribution of the cleansing or irrigating agents can include a fraction of larger particles, particularly in relation to the mechanical action of the particles.
The present invention also provides a method of delivering a substance to the nasal airway of a subject, comprising the steps of: sealing one of the nostrils of a subject to an outlet of a delivery unit such as to prevent the escape of a gas flow through the one nostril; closing the oropharyngeal velum of the subject; and delivering a gas flow entraining a substance through the outlet at such a pressure as to flow around the posterior margin of the nasal septum and out of the other nostril of the subject.
In one embodiment the closure of the velum is achieved directly by the use of an instrument for pressing against the velum to close the same or a bung for temporarily closing the opening behind the velum between the nasal airway and the oral cavity.
In a preferred embodiment the closure of the velum is achieved indirectly by the creation of a positive pressure in the oral cavity, or more correctly a positive pressure differential between the oral cavity and the nasal airway, such as achieved on exhalation.
Preferably, the velum is closed simultaneously with the onset of the delivery of the substance to the nasal airway.
In a preferred embodiment closure of the velum is achieved automatically by the subject exhaling against a flow resistor, which flow resistor may be operably connected to a tubular section held between the lips of the subject. The flow resistor can be configured to provide the required intra-oral positive pressure.
It has been established that flow rates of about 1 to 20 litres per minute, and particularly about 3 to 15 litres per minute, can be easily achieved by a subject and that and a fairly constant air flow can be maintained for up to 20 seconds depending on the flow rate. For some treatment regimes, it is important that a stable flow of relatively high flow rate be maintained for a period of a few seconds, preferably 3 to 10 seconds, in order to enable the substance to penetrate to the more remote parts of the nasal airway.
In one embodiment the air flow of exhalation by a subject is used to power a mechanism which disperses the substance into a volume of air and delivers that dispersed substance into the nasal airway.
Preferably, the mechanism is so arranged that the substance is delivered into the nasal airway after the velum has been closed or simultaneously with velum closure. In this respect, it will be understood that bi-directional flow through the nasal cavities is possible only when the velum is closed and that any substance delivered prior to closure of the velum would undesirably be delivered to the lower airway or the gut.
Preferably, the release of the substance into the nasal airway is triggered by the air flow created on exhalation.
In a preferred embodiment a pressure-sensitive valve is utilised to trigger release of the substance when a predetermined flow rate has been developed. It should be understood that control of the flow rate of the gas in which the substance is delivered is important, as this flow rate, along with the particle size distribution of the substance, are the significant factors determining the particle deposition efficiency.
In a preferred embodiment the pressure-sensitive valve is not opened until the subject has maintained a predetermined flow rate, and can be closed when the flow rate drops below the predetermined flow rate so as to stop the delivery of the substance.
In a preferred embodiment, where medicament is delivered in a driving gas, one or both of the timing and duration of the opening of the pressure-sensitive valve and the dose released are carefully controlled to ensure a standardised dosage.
In one embodiment, where the substance is released into a chamber and a gas flow, in one embodiment the exhalation flow, is provided to induce the mixing of a metered dose of the substance, the delivery of the gas flow can be prolonged to flush the nasal airway as this prolonged flushing does not effect the delivered dose. A mechanical device powered by a hand-chargeable spring, pressurised air or similar, may be used to provide the driving gas.
Regardless of the system employed, the flow characteristics can be optimised to improve the deposition of the substance and the comfort factor, such as to avoid an abrupt onset which is likely to induce withdrawal reflexes.
Preferably, a metered dose of the substance is dispensed into a delivery chamber by a dosing mechanism. This dosing mechanism can be constructed in such a way as to allow for a gradual release of the substance. This gradual release will better enable the substance to be entrained by the gas flow and thereby improve delivery to all ventilated parts of the nasal airway, in particular in the contralateral nasal cavity.
In a preferred embodiment the exhalation air flow developed by the subject, which closes the velum, provides the gas flow for entraining the substance and providing the bi-directional flow. This configuration is advantageous in that a separate driving gas flow need not be developed.
Preferably, the nosepiece is configured to extend about 1 cm into the one nasal cavity so as to expand the valve region, a region located about 2 to 3 cm within a nasal cavity which is usually the flow limiting region, and reduce the resistance which may be high in the case of nasal inflammation.
The shape of the nosepiece can be tailored to suit specific needs. For example, the internal shape of the nosepiece may be optimised to promote turbulence and achieve a more optimal dispersion of the substance.
The nosepiece may include a tight fitting nasal olive, which can aid the creation of a suitable physiological gas flow. The olive may be detachable such as to allow for other olives of the same or different dimensions to be fitted. In the case of severe nasal obstruction, a nasal olive can be introduced into the other nostril to reduce resistance and facilitate flow therethrough.
As mentioned above, a gas flow of at least 20 litres per minute can easily be achieved by the delivery device. By providing a sufficiently high gas flow, all parts, or at least a larger part, of the complex nasal airway can be penetrated by the substance. In one embodiment the delivery device can include an indicator for indicating the magnitude of the gas flow.
The dimensions of the posterior passage and opening behind the nasal septum are almost always larger than the opening in the flow resistor. Thus, it is only in very rare cases of complete occlusion of the outlet nostril that the pressure in the posterior region of the nasal airway will approach the positive pressure in the oral cavity and jeopardise the velum closure. In the case of severe obstruction, insertion of the nosepiece in the occluded nostril may reduce the resistance and allow successful flushing.
After having flushed the nasal airway in one direction, the same procedure can be repeated from the other nostril. In this way both nasal cavities are irrigated in both directions. This is a unique feature of this device. This embodiment secures an improved distribution of the substance to all parts of the nasal mucosa, and in particular to the posterior region which is difficult to access using current techniques.
In a preferred embodiment, where the substance is in solid form, such as a powder, then a filter can be employed if high humidity represents a problem for administration of the solid.
The substance can be a single compound or a mixture of compounds, which compounds can be in any suitable form, such as a powder form, a solution, or a suspension.
The substance can be any suitable substance for delivery to a human or in some cases an animal. The substance may be for delivery for action in any part of the nasal airway, or in any of the surrounding tissues or organs. Also, the substance may be for delivery for action in a region remote from the nasal airway.
Preferably, the substance is for delivery for subsequent action in any part of the nasal airway, or in any of the surrounding tissues or organs.
The substance may have a beneficial medical effect, which can include a diagnostic effect, a therapeutic effect, a prophylactic effect, and a cleansing effect such as the removal of particles, crusts, secretions, debris, etc. Preferably, the substance has a therapeutic effect.
Preferably, the substance is a pharmaceutical. The pharmaceutical can be admixed with any suitable carrier, diluent, excipient or adjuvant.
Preferably, the pharmaceutical is for the treatment of any one or more of the above-mentioned conditions. By way of example, the pharmaceutical may be for the treatment of any allergic and non-allergic inflammatory disease.
Typical pharmaceuticals for administration include, but are not limited to, steroids, anti-histamines, cromoglycates, anti-allergic pharmaceuticals, anti-inflammatory pharmaceuticals, anti-leucotriens, lactation promoters such as oxytocin, and anti-migraine pharmaceuticals.
By achieving a more optimal delivery, the delivery device of the present invention improves the effect of topical pharmaceuticals in the treatment of upper airway pathologies, such as hypertrophic adenoids and chronic sectretory otitis media.
Aside from pharmaceuticals, the device can also be used to irrigate or cleanse the nasal airway with saline or other solutions, preferably containing oils or herbs.
The device of the present invention can be tailored to suit particular needs. For example, balloons or pop-up figures can easily be integrated to provide a semi-quantitaive indication of the flow rate and to improve the acceptability and ease of administration in small children.
Only in the rare circumstances when the nasal resistance is too high to achieve a gas flow through the nasal airway, even after attempting to expand the nasal cavities, would insufflation be jeopardised. In those cases, pre-treatment with decongestants may be necessary.
The delivery device may also be used as a nasal lavage means in the collection of mediators and cells that originate from the nasal mucosa for, for example, diagnostic analysis or research purposes. In this respect, the mediators and cells can be expelled into a suitable collecting vessel after the nasal airway has been exposed to a suitable solution, such as a saline solution, for a sufficient period of time to ensure sufficient transfer of the mediators and cells into the solution. This use of the device may require the use of a gas flow separate to the exhaled air flow as the flow used to flush the nasal airway. For this lavage purpose, use of the exhaled air may not be possible as the lower airways may contain mediators, secretions and cells originating from the lower airways which would contaminate the nasal sample. For this particular use, and as indicated, the fluid escaping from the outlet nostril may be collected in a vessel. Alternatively, the fluid escaping from the outlet nostril may be absorbed onto a filter for direct or delayed analysis. Indeed, such filters and the like may even yield an almost immediate detection result of certain organisms, such as bacteria, viruses or mediators.
The delivery device of the present invention is advantageous for a number of reasons.
Notably, the delivery device provides a very simple and efficient means of delivering substances, such as pharmaceuticals, saline solutions, etc, into the nasal airway. In this respect, the device utilises very simple technology with few movable parts, making the device relatively inexpensive to mass produce. In addition, the device of the present invention can be made in a disposable form, thus avoiding the need for the delivered substance to include any preservatives.
The present invention also eliminates the need for the subsequent flushing or spraying methods that are associated with some of the prior art devices. However, for some applications it may still be desirable to perform a subsequent flushing or spraying operation.
The delivery device of the present invention is advantageous as, in use, the tight seal between the nosepiece and the one nostril ensures a prolonged penetration of the complex nasal airway, a bi-directional gas flow through the nasal cavities and deposition of the substance in the contralateral nasal passage.
In accordance with the present invention, closure of the velum will normally be maintained. The delivered gas flow enters one nasal cavity, passes beyond the posterior margin of the nasal septum, making a 180 degree turn behind the posterior margin of the nasal septum, and passes out the other nasal cavity. This re-direction of the gas flow results in a better deposition of substance, notably pharmaceuticals, to the posterior regions of the nasal turbinates and the nasal mucosa.
In addition, the bi-directional deposition of substances, typically pharmaceuticals, and irrigation will also better reach all sinus ostia due to the anatomic locations and orientation of the sinus ostia, which can improve sinus ventilation and drainage which is essential to treat sinusitis and frequently accompanies inflammation of the nasal mucosa. In this respect, the ostia and tubes to the ethmoidal and sphenoidal sinuses are located in the posterior region of the nasal airway and the uncinate projections covering the infundibulum, housing the maxillary, frontal and anterior ethmoid ostia, are tilted backwards. Furthermore, the driving positive pressure used will increase the deposition of pharmaceuticals at the sinus ostia, the sinus tubes leading into the sinuses and even in the sinuses themselves.
In addition, the 180 degree re-direction of the flow behind the nasal septum particularly increases the deposition of substance on the roof of the nasopharynx where the adenoid is located and in proximity to the location of the tubal ostia to the auditory tubes connecting the nasopharynx and the middle ears. By way of example, steroids have been shown to reduce the size of hypertrophic adenoids which are commonly found in paediatric subjects and can have a positive effect on secretory otitis media. Deposition of topical decongestants closer to the tubal ostia may also more efficiently decongest the auditory tubes and relieve the negative pressure in the middle ears which accompanies rhinitis and predisposes paediatric subjects to secretory otitis media and the consequential reduced hearing. Surgery for enlarged adenoids is frequently performed in children and the improved medical therapy of the present invention should reduce the necessity for surgery.
A further advantage is that possible surplus substance, that is, substance which is not deposited, will be expelled out of the contralateral nostril, where it may be collected, if desired, and consequently not continue to the oral cavity and down into the gut as is the case with many other delivery techniques. In this way, the discomfort, and more importantly, the undesirable systemic exposure to the substance, where the substance is a medicament, will be reduced.
Also, with the present invention, irrigation by saline or other solutions can be performed more efficiently and with less spill and discomfort than the current techniques used for irrigation and flushing of the nasal airway.
Further, the present invention provides for simple and comfortable irrigation of the nasal mucosa with solutions, such as saline solutions, and other oils to remove secretions from the nasal mucosa and promote mucocilary function.
Still further, the present invention provides a simple and effective means for the lavage of the nasal mucosa, such as to collect and diagnose mucosal entities, such as bacteria, viruses, cell components and inflammatory mediators.
Still yet further, the exposure of the nasal mucosa to a positive pressure, particularly a dynamic positive pressure, will open the narrow, and sometimes occluded, parts of the nasal passages, rather than cause a dynamic collapse which may happen during sniffing and inhalation. The dynamic positive pressure is at least 5 cm H2O, preferably at least 50 cm H2O, more preferably at least 100 cm H2O, still more preferably at least 200 cm H2O, yet more preferably 400 cm H2O and still yet more preferably 500 cm H2O. The dynamic positive pressure achieved by the present invention can be contrasted with the static pressure provided by the Valsalva procedure where there is no flow through the nasal airway.
In addition, the use of warm and humid air as the gas flow is likely to be better tolerated and cause less irritation than room air or outdoor air, especially in cold climates.
Where the substance is a dry powder, then the humidity of the exhaled air may, in some instances, cause agglomeration of the powder. Naturally, this will depend on the properties of the powder and the construction of the device, in particular the dispersion chamber. In order to alleviate this specific problem, the surface properties of the powder could be modified, or the device could include a moisture-absorbing element, typically containing a desiccant such as silica, disposed upstream of the dispersion chamber. In a preferred embodiment the moisture-absorbing element could be provided as a filter which acts as the flow resistor.
In a preferred embodiment, in order to ensure that agglomeration of powder would not impede the use of direct insufflation of warm, humid exhaled air, the delivery device comprises transfer means which creates a gas flow of drier air, such as atmospheric air, as the delivery flow to the nasal airway. Such transfer means, which could be mechanical in nature, utilises the energy of the exhaled air to drive the atmospheric room air at the required flow rate, if necessary; to disperse the substance in the delivered air flow. In this embodiment agglomeration will be prevented or at least reduced to the same level as currently exhibited by dry powder inhalers.
If desired, the distribution of the substance delivered to the nasal airway could be studied using standard techniques. By way of example, use could be made of acoustic rhinometry or coloured fluids. The distribution of the delivered substance could even be determined by video endoscopy. In addition, or in the alternative, distribution studies could also be performed by using appropriate radioactive materials and following the passage in the nasal cavities. The results of these studies could be used to optimise the flow rate, the shape or dimension of the device, in particular the nosepiece geometry, and the particle size distribution of the substance. The results of these studies could even be used to optimise subject acceptance.
As already indicated, the delivery device may include a balloon or a similar pop-up device for indicating that the desired positive pressure has been attained, which balloon or pop-up device may improve the compliance in small children who are reluctant to use the device.
Alternatively, for particularly young children, the entraining gas flow can be provided by the exhalation air flow of another person, such as a parent, or even by the use of a pump or the like, while the child creates the required positive pressure in the oral cavity by inflating a balloon or pop-up device.


A method of continuously manufacturing tubular filter products includes rotating a mandrel in a first rotational direction, depositing nonwoven fibers on the mandrel to form a tube and continuously withdrawing the tube from the mandrel by engaging a peripheral surface of the tube with one or more detents extending radially from a surface of a roller. The roller rotates in a direction opposite the first rotational direction as the one or more detents engage the tube to a predetermined depth relative. For carrying out such a method, an apparatus includes a melt blowing die assembly for expelling melt blown fibers, a rotating mandrel arranged to receive the melt blown fibers from the melt blowing die assembly for allowing the melt blown fibers to accumulate in a body thereon and a rotating roll having a pattern of protruding detents. The roll is arranged so that at least some of the detents will come within a predetermined distance of the mandrel for contacting the melt blown fibers in a manner forcing the melt blown fibers accumulated on the mandrel to move in a direction parallel to the mandrel. A tubular filter product includes a plurality of melt blown fibers in a body defining an outer surface and an inner surface, the body defining a pattern of cavities between the outer surface and the inner surface.

The invention relates to nonwoven filter products and methods and apparatus for their manufacture. More particularly, the invention relates to methods and apparatus useful in manufacturing nonwoven filter products and nonwoven tubular filter products produced continuously thereby.
Various filter products are continuously manufactured and subsequently cut to desired sizes, shapes, and/or lengths for particular filter applications. One particular type of filter product is produced continuously in a tubular shape by depositing fibers onto a mandrel. A die is positioned adjacent the mandrel and fibers are fed through the die to contact the mandrel. Typically, the mandrel is rotated while initially deposited fibers contact the mandrel surface forming an inner diameter of the filter product. Subsequently deposited fibers form layers upon the initially deposited fibers, thereby building filter thickness radially outward to an exposed outer surface of predetermined diameter. Meanwhile, the filter product is either continuously or incrementally extracted from the mandrel to expose the mandrel surface for receiving additional fibers. In this manner, the tubular filter product is continuously produced.
Such tubular filter products have many uses. For example, in many chemical and beverage processing operations, tubular filter are used to remove particulate matter from liquids by passing the liquid around the outside of the tubular filter product while forcibly drawing the liquid from the inside of the tubular filter product. In this manner, the liquid is forced through the tubular filter, i.e., toward its inner diameter, the filter acting to trap the particulates while allowing the liquid to pass through to the open center. Of course, in other applications the process is reversed and the liquid/particulate solution is introduced in the open center of the tubular filter and forced outward through the filter to the outer diameter of the tube.
In one technique for manufacturing such filter products, the tubular body of the filter is contacted upon its outer surface by the smooth outer surface of a driven roll. The roll is driven in a direction opposite to the rotation of the mandrel such that friction between the roll outer surface and filter product causes the filter product to also rotate in a direction opposite rotation of the mandrel. In this manner, the filter product is continuously extracted from the mandrel.
In one aspect, the invention provides a method for manufacturing tubular filter products. The method includes rotating a mandrel in a first rotational direction, depositing nonwoven fibers onto the mandrel to form a tubular body, and continuously withdrawing the tubular body from the mandrel by engaging a peripheral surface of the tubular body with one or more detents extending radially from an opposed surface of a roller. The roller rotates in a direction substantially opposite the rotational direction of the mandrel as one or more detents engage the periphery of the tube to a predetermined depth.
Variations of this aspect of the invention may include one or more of the following features. The peripheral surface comprises the outer surface of a fully formed tubular body. The method further includes covering the peripheral surface with additional nonwoven fibers. The roller includes multiple detents. The multiple detents extend radially to equal distances from the surface of the roller. The multiple detents are uniformly distributed about the roller.
In another aspect, the invention provides a tubular filter product including a plurality of melt blown fibers interengaged to form a tubular body defining an outer surface and an inner surface, the tubular body further defining a pattern of cavities.
Variations of this aspect of the invention can include one or more of the following features. The cavities are enclosed between melt blown fibers of the outer surface and the inner surface. The cavities are exposed recesses extending into one of said inner and outer surfaces. Localized areas corresponding to the recesses are of greater melt blown fiber density per unit volume than an average melt blown fiber density per unit volume associated with the tubular filter product.
In another aspect, the invention-provides an apparatus for continuously producing a tubular filter product. The apparatus includes a melt blowing die assembly for expelling melt blown fibers, a rotating mandrel arranged to receive the melt blown fibers from the melt blowing die assembly for allowing the melt blown fibers to accumulate in a tubular body thereon, and a rotating roll having an outer surface with at least one detent protruding therefrom, the roll arranged so that said detent comes within a predetermined distance of the mandrel for contacting the tubular body of melt blown fibers in a manner forcing the melt blown fibers accumulated in the tubular body on the mandrel to move in a direction parallel to the mandrel.
Variations of this aspect of the invention may include one or more of the following features. The rotating mandrel extends adjacent the melt blowing die assembly to define a fiber receiving portion of the mandrel and the rotating roll is arranged to contact the tubular body at a location corresponding to the fiber receiving portion. The rotating roll has a plurality of detents protruding from its outer surface. The detents are uniformly distributed about the outer surface of the roller.
The method and apparatus provide many advantages over other techniques for manufacturing filter products. For example, great control over the filter-making process and great design flexibility for producing tubular filters having desirable characteristics because the many variables involved in the manufacturing process can be pre-selected and varied as desired. Such variables include, for example, the pre-set shortest distance between the tips of the detents and the mandrel; the outer diameter of the filter product at the point of contact with the detents, which, in turn, is dependent on the feed rate of fibers from the die, the rotational speed of the mandrel and the relative placement of the roll relative to the die; the rotational velocity and cant angle of the roll relative to the mandrel, and the rotational velocity of the mandrel. Thus, the method and apparatus provide for great control over the filter-making process and great design flexibility for producing tubular filters having desirable characteristics. Furthermore, the process of removing the filter product from the mandrel provides an easy and simple means of starting the filter making process without the need for additional equipment and starter pieces as are necessary in various known systems.
The filter products manufactured by the disclosed method and apparatus also offer many advantages over other filter products. For example, the cavities formed in the filter product provide for enhanced filtration characteristics. These cavities have been shown to provide bypass areas for fluid to pass further into the depth of the filter and provide areas for increased amounts of sediment to collect, thereby increasing the overall sediment (e.g., dirt) holding capacity of the filter proportionally by the number, size and shape of the cavities created during processing. Additionally, the penetration of detents into filter product locally compresses the affected fibers against one another. This compressing action increases the overall collapse strength of the filter product by interlocking the affected fibers of the various layers penetrated by the detents as well as closely adjacent fibers.


A high frequency, low loss, power, composite magnetic material includes alternating magnetic plates of low hysteresis loss material and electrically insulating films. The multi-layer structure allows for independently and simultaneously controlling and reducing hysteresis loss and eddy current loss, and maintaining a high resistivity, while operating at high frequencies and at high flux density levels, resulting in extremely low net loss density for the composite material. Methods of making this material include co-firing of the magnetic plates and thin insulating films, making the magnetic plates (of low hysteresis material, such as a ferrite) and insulating films separately, and using heat and/or pressure and/or adhesive or making a stack of magnetic plates with spacers in between them and dipping in a molten or liquid insulating material.

The present invention relates generally to magnetic materials, and more particularly, to high frequency magnetic materials used in power electronics applications.
High operating frequencies are desirable for power conditioning equipment (such as power supplies, power amplifies and lamp ballasts) in order to reduce the size of magnetic components. Unfortunately, however, it has been heretofore impossible to substantially reduce the size of magnetic components because the operating flux density has to be reduced too much to enable proper operation and still have acceptable losses at high frequencies. In particular, while at low frequencies (e.g. 100 kHz), the operating flux density can be in the 1000-3000 Gauss range using semi-conducting ferromagnetic materials (typically ferrites), the operating flux density to achieve acceptable losses in the megahertz range is from 20 to 300 Gauss, which is too low to give any significant size advantage.
In addition, there is considerable drive to push the operating frequencies of power conditioning equipment to frequencies even higher than 5.0 MHz. However, the losses of the current high frequency materials rise very sharply with increasing frequency in 1 to 10 MHz range, making these material unsuitable for use at such high frequencies. In particular, the losses of these high frequency materials increase as the 4th power of the frequency above one megahertz.
A variety of publications describe the state of the art in this field. These publications include a book by A. Goldman: Modern Ferrite Technology (Van Nostrand Reinhold, N. Y., 1990, p. 185-211). Detailed properties of soft ferrites are also described in a book by E. C. Snelling: Soft Ferries: Properties and Applications, 2nd edition (Butterworths, London, 1988) and 1st edition (Iliffe, London, 1969, chapters 2, 3).
The following are the four major reasons for the two problems described hereinabove and for making the current state-of-the-art materials unsuitable for use in high frequency and high flux density operation.
First, the people involved in the development of high frequency magnetic materials for use in power electronics have only tried to reduce eddy current losses. Unfortunately, the methods used to control eddy current losses (these methods include reducing the grain size to increase the grain boundary surface and increased addition of materials like SiO2 and CaO) have resulted in increased hysteresis loss. This increased hysteresis loss produces a very high dependence of the net high frequency losses on the flux density because hysteresis loss varies as the cube of the flux density. Thus, making these materials unsuitable for use at high flux densities and high frequencies.
Yet, another problem with the current approach for making low loss high frequency magnetic material is that the eddy current losses are not completely eliminated and they still make substantial contribution to the total loss in the 100 kHz to 1.0 MHz. This is evident from the measured net losses, which increase as the square of the frequency (hysteresis loss increase, generally, linearly with frequency). In addition, the eddy loss dominate the net losses at frequencies higher than 1 MHz. The main reason for this failure to control eddy current losses are very thin, non-uniform grain boundary layer, which is supposed to produce high resistivity. However, at high frequencies this layer begins to yield due to capacitive electrical shorting of boundary layer. The thinner that layer the more noticeable is this effect. The measured resistivity of the current state-of-the-art materials show a continuous decrease in the value of the resistivity in 100 kHz to 10 MHz range. All the previous attempts to reduce this effect have failed.
Yet, another problem with the current high frequency material is that very large electric fields are produced at the grain boundaries, which leads to a dielectric break down of the material at the grain boundaries and to a resistivity, which is a decreasing function of the flux density. This is because the thickness of the grain boundary layer is extremely small (for typical high frequency ferrite the thickness is in 10xe2x88x923 to 10xe2x88x922 micron range) and the fact that the resistivity of the crystallites is negligible compared to that of grain boundary layer. In particular, even for a very small core, the induced electric field at 1.0 MHz and at 500 Gauss exceeds 10 kV/cm. These values of electric field far exceed the dielectric strength (typically around 2 kV/cm) of the material at the grain boundary. This leads to resistivity, which decreases rapidly with increasing frequency and flux density. The end result is the increased dependence of high frequency loss on flux density, which further limits the flux density at which these materials can be operated.
The fourth major problem relate to the use of these materials for very high frequency applications and for very high power. This is because of large permeability and dielectric constant, which give a small electromagnetic wavelength at high frequencies. Due to this very small wavelength, dimensional resonance can be set up even in small cores and leads to additional losses. In particular, for typical high frequency ferrites, the wavelength is about 1 mm at 10 MHz and thus making these materials unsuitable even for very small cores. As power level of application such as power supply increases, the size of core increases making the problem worst and restricting the use of these materials to very low powers at such high frequencies.
Accordingly, it is desirable to provide high power magnetic material, which can be operated at high flux levels (e.g. greater than 500 Gauss) while maintaining high frequency operation (e.g. 1 to 10 MHz). Furthermore, such material should have a resistivity, which is independent of the frequency and flux density and should allow for independent control and reduction of hysteresis loss and eddy current loss. In addition, such magnetic material should have a structure, which allows for effective size of the core to be substantially smaller than the electromagnetic wavelength at high frequencies.
A composite, high frequency, low loss material consists of alternate magnetic plates and insulating films. The magnetic plates are designed to have very lax requirements on the resistivity of the magnetic material comprising the magnetic plates, so that the hysteresis loss can be reduced easily. The eddy current loss is controlled by the thin insulating films and by varying the thickness of the magnetic plates. The insulating films are designed to have high integrity (free of pin holes and other defects), high dielectric strength, high resistivity and, preferably, low dielectric constant. The insulating films perform the same functions as that of the grain-boundary layer in current state-of-the-art magnetic material (ferrites) but are able to maintain their functionality up to much high frequency and much higher flux densities resulting in very high resistivity of the composite material. The resistivity of the composite material is independent of the frequency and flux density to high values of frequencies (xcx9c100 MHz). The magnetic plates and the insulating films can be co-fired. One method of co-firing utilizes green tape technology.
Alternatively, the magnetic plates and the insulating films can be manufactured separately and then the composite ferrite be fabricated by using adhesive and/or heat and pressure treatment. Yet another method of fabricating these composite ferrites is by manufacturing the low hysteresis loss ferrite plates, depositing thin or thick films of the insulating material on both sides of the ferrite plates, stacking the ferrite plates and then applying heat and pressure to melt or soften the insulating films and to attach the ferrite plates to each other. A further method of fabricating these composite ferrite plates is by making a stack of low hysteresis loss ferrite plates with spacers, and dipping the stack in a liquid insulating material or pouring the insulating material over the stack.

Low loss, high frequency composite magnetic material and methods of making the same