An inhalable dry powder formulation containing SAE-CD and an active agent is provided. The formulation is adapted for administration by DPI. The SAE-CD serves as a carrier rather than as an absorption enhancer. The average particle size of the SAE-CD is large enough to preclude (for the most part) pulmonary deposition thereof. Following release from the DPI device, the SAE-CD-containing particles dissociate from the active agent-containing particles in the buccal cavity or throat, after which the active agent-containing particles continue deeper into the respiratory tract. The physicochemical and morphological properties of the SAE-CD are easily modified to permit optimization of active agent and carrier interactions. Drugs having a positive, neutral or negative electrostatic charge can be delivered by DPI when SAE-CD is used as a carrier.

The delivery of a drug by inhalation allows deposition of the drug in different sections of the respiratory tract, e.g., throat, trachea, bronchi and alveoli. Generally, the smaller the particle size, the longer the particle will remain suspended in air and the farther down the respiratory tract the drug can be delivered. Drugs are delivered by inhalation using a nebulizer, metered dose inhaler (MDI), or dry powder inhaler (DPI).
Dry powder inhalers provide powder pharmaceuticals in aerosol form to patients. In order to generate an aerosol, the powder in its static state must be fluidized and entrained into the patient's inspiratory airflow. The powder is subject to numerous cohesive and adhesive forces that must be overcome if it is to be dispersed. Fluidization and entrainment requires the input of energy to the static powder bed.
DPIs can be divided into two classes: passive and active devices. Passive devices rely solely upon the patients inspiratory flow through the DPI to provide the energy needed for dispersion. This method has the advantage that drug release is automatically coordinated with the patient's inhalation. The disadvantage is that dispersion is typically highly dependent on the patient's ability to inhale at an optimum flow rate for aerosol generation. Depending on the inhaler design, this requirement may be difficult for some patients if the device resistance to airflow is high. Active dispersion devices have been under development for the past ten years but none has yet been approved. Like propellant driven metered dose inhalers, active devices use a source external to the patient to provide the energy needed for powder dispersion. This has the advantage of potentially reducing the dependence of uniform dosing on the patient's capabilities. However, without a feedback mechanism for the energy source, it is still possible that different patients will receive different doses. In addition, the complexity of these devices has contributed to their inability to achieve regulatory approval and may increase the cost of the device.
Passive devices have progressed in their complexity and performance since the introduction of the Allen & Hanbury's Rotahaler and the Fison's Spinhaler in the 1970's. Passive dispersion relies on the airflow generated by the user to aerosolize the powdered drug. All passive devices disperse the drug by passing the airflow through the powder bed. Early devices dispersed very small quantities of respirable sized particles, often on the order of 10% of the nominal dose. In general, this poor performance can be attributed to the incomplete deaggregation of smaller drug particles from larger carrier particles used as a diluent and an aid to powder flow during dispersion. Modern devices utilize significant turbulence to aid in the deaggregation process. Turbulence can be provided by tortuous flow paths for the particle laden airflow as in the AstraZeneca Turbuhaler, the Schering-Plough Twisthaler and U.S. Pat. No. 5,469,843; changing dimensions of the airflow path (U.S. Pat. No. 5,437,271); or by impactor plates that also reduce the emission of large particles (U.S. Pat. No. 5,724,959). A device developed by Innovative Devices (U.S. Pat. Nos. 6,209,538 and 5,988,163) addresses the desirability of dispersing powder at optimal flow rates via channels whose operation is flow dependent. Initially, flow is diverted around the drug and is allowed to pass through the drug only when the optimal flow rate has been obtained. This device bridges the gap between passive and active devices by adding active features to a passive device.
Active devices use mechanisms such as springs or a battery to store energy that can be released to aid in powder dispersion. The best known active devices are the Inhale (Nektar) Deep Lung delivery system and the Dura Spiros. The Inhale device uses compressed air generated by the user through a spring loaded pump mechanism to disperse powder drug. There are a few other patents identified that utilize compressed air (U.S. Pat. Nos. 5,875,776 and 6,003,512) or a vacuum (U.S. Pat. No. 6,138,673) to provide energy for dispersion. The Dura Spiros DPI uses a battery driven impeller to disperse drug powder. The impeller operates only when the patient inhales through the DPI to ensure that dosing does not occur when not in use. U.S. Pat. Nos. 5,469,843 and 5,482,032 describe another mechanism of dispersion (use of a hammer or other means of impaction to dislodge drug from a powder bed typically contained on a blister strip). Little published data is available for the active devices since most of their development has occurred in a proprietary atmosphere. Some of the patented technology, both for active and passive devices, is only conceptual.
For lung deposition, drug particles are generally required to be smaller than 10 μm (microns) in aerodynamic diameter. They may be prepared by either size reduction methods, such as milling, or particle construction methods, such as condensation, evaporation or precipitation. Historically, respirable particles are produced by jet-milling, where there is little control over the particle size, shape or morphology. The resulting fractured particles are highly electrostatic, cohesive, and subjective to changes in crystallinity. Alternative methods of particle generation include spray-drying, solvent evaporation or extraction or supercritical fluid condensation. All of these methods produce structurally more uniform particles.
Particles smaller than 10 μm generally exhibit poor flow properties due to their high interparticle forces. Formulation strategies to improve the flowability of respirable particles include the controlled agglomeration of drug particles or adhesion onto excipient carrier particles in the form of interactive mixtures. The agglomerates or interactive mixtures are required to be strong enough to withstand processing, storage or transport processes, but weak enough to allow drug deaggregation and dispersion during actuation. Controlled agglomeration may be achieved by feeding micronized powders through a screw feeder, followed by spheronization in a rotating pan or drum. This method may be used for formulations containing drug alone or drug/lactose blends. Factors affecting the aerosol dispersion of carrier-based formulations include drug and carrier properties, such as size, shape, surface roughness (rugosity), chemical composition and crystalline state, the drug-carrier ratio and the presence of ternary components.
The drug particle size effects aerosol dispersion. Different sized spray-dried mannitol (2.7 to 7.3 μm) and disodium cromoglycate (2.3 to 5.2 μm) particles were examined. Higher aerosol dispersion, due to less cohesion, was observed in larger particles; however, lower fine particle fraction (FPF) was produced due to greater impaction on the throat and upper stages of the impinger and smaller proportion of fine particles. Conditioning or surface modification of drug particles may reduce aggregation and improve aerosol dispersion. The amorphous content of particles may be reduced by treatment with water vapor in controlled temperature and relative humidity conditions or treatment in a vacuum oven. Surface modification by adhesion of nanoparticles onto the drug particles may increase aerosol dispersion. Hydrophilic silicic acid and hydroxypropylmethylcellulose phthalate (HPMCP) nanoparticles increased device emission and respirable fractions of pranlukast hydrate in both drug alone and carrier-based formulations.
Conflicting reports exist on the influence of drug concentration in carrier-based DPI formulations. Increasing drug concentration may increase the respirable fraction or reduce the respirable fraction.
The particle size, shape, surface morphology and chemical composition of carrier particles can influence aerosol dispersion. Increased drug dispersion and deposition is generally observed with smaller carrier size and increased proportion of fine particles. However, the carrier size did not affect the FPF in some formulations. Higher FPF was produced with larger carrier sizes (within 63-90 μm). Poor dispersion of nedocromil was obtained using coarse carrier systems, whereas the use of fine carrier particles and high shear mixing techniques physically disrupted the drug-drug contacts and promoted deaggregation. Elongated carriers increased aerosol dispersibility and drug FPF, possibly due to increased duration in the airstream drag forces. Carriers with smooth surfaces produced higher respirable fractions. Low respirable fractions were obtained from carriers with macroscopic surface roughness or smooth surfaces, whereas high respirable fractions were obtained from carriers with microscopic surface roughness, where smaller contact area and reduced drug adhesion occurred at the tiny surface protrusions. A modification of carrier formulation involves the use of soft friable lactose pellets containing micronized lactose particles, which break down into primary particles during inhalation has also been described. The lactose pellet may be coated with drug. In another study, carrier particles with good powder flow characteristics exhibited reduced adhesion to a defined solid surface and produced higher drug deposition in an animal model. The influence of carrier particle size on the performance of a formulation in a DPI device is summarized in the following table.
PropertyImproved byUniformity and blendingIncreasing particle sizePowder flowIncreasing particle sizeEntrainment tendancyIncreasing particle size(typically, but depends onproperties of carrier)Dispersion and PotentialDecreasing particle sizefor Lung Delivery(function of drug-carrier andaggregate particle size)
Thus for dry powder inhaler formulations, the size of carrier particles should be selected on the basis of a balance between, these interrelated performance characteristics. Specifically, inter-particulate forces should be such that the drug particles adhere to the carrier (to aid in blending, uniformity, and allow the entrainment of drug into the inspiratory air-stream), yet also allow detachment of the fine drug particles from the surface of the coarser carrier particles so that delivery to the lung can be facilitated.
In vitro drug deposition has been examined using different grades of lactose carrier. The higher FPF of salbutamol (albuterol) sulphate obtained from anhydrous and medium lactose was attributed to a higher proportion of fine particles and smooth surface roughness. The higher FPF of nacystelyn obtained from anhydrous β-lactose was attributed to its intermediate surface roughness. Other sugars were investigated as fine and coarse carriers. Higher FPF was obtained using mannitol coarse carrier, possibly due to a higher fine particle content and more elongated shape. Mixtures with added fine particle carrier produced higher FPF with little difference observed between the fine carrier type.
The addition of fine ternary components has increased the FPF of various drug particles. Ternary components examined include magnesium stearate, lactose, L-leucine, PEG 6000 and lecithin. Many possible explanations exist for the mechanism of action of ternary components, including the saturation of active sites on the carrier, electrostatic interactions and drug redistribution on the ternary component.
Recent developments in the improvement of DPI formulation efficiency are focused on particle engineering techniques. Improved aerosol dispersion of particles may be achieved by the co-spray-drying with excipients, such as sodium chloride, or human serum albumin (HSA). Respirable-sized particles composed of hydrophobic drug and hydrophilic excipients were produced by simultaneous spray-drying of separate solutions through a co-axial nozzle. Therapeutically active peptide particles have been produced by spray-drying with good flow and dispersibility properties, including insulin, α-1-antitrypsin and β-interferon. The addition of stabilizing excipients, such as mannitol and human serum albumin (HSA) is generally required. Spray-dried microspheres composed of cellulose lower alkyl ethers, such as hydroxypropyl methyl cellulose, may be used for sustained drug release. These particles are adhesive following water adsorption from the lung mucosa. Stable dry powder formulations of polynucleotide complexes were produced by lyophilization with a cryoprotectant, such as mannitol, followed by sieving or milling.
Large porous particles (geometric diameters of 5-30 μm and tap density less than 0.4 g/mL) with aerodynamic diameters of 1-5 μm are prepared by spray-drying. These large particles are less cohesive, due, to reduced van der Waals forces, and have improved flow and aerosol dispersion properties. Increased rough surface texture may further minimize particle aggregation and improve flow. Particles deposited in the alveolar regions may avoid phagocytic engulfment by size exclusion. Controlled rate of drug release is achieved using biodegradable polymers, such as poly(lactic acid) (PLA) and poly(glycolic acid) (PGA). Surfactants, such as dipalmitoyl phosphatidylcholine (DPPC) may be incorporated to further improve powder flow, aerosol dispersion and lung deposition.
Drug or peptide encapsulated in hollow microcapsules are free flowing, easily deaggregated and produce high respirable fractions. Wall materials include human serum albumin (HSA) or PGA and PLA. Reduced dissolution may be obtained by coating with fatty acids, such as palmitic acid or lipid soluble surfactants, such as Span 85. The PulmoSphere™ small hollow particles (5 μm geometric diameter and bulk densities less than 0.1 g/mL) are spray-dried from emulsions of drug, phosphatidylcholine and perfluorocarbon.
Current commerical DPI formulations are based on drug agglomerates or carrier-based interactive mixtures. Excipients act as diluents and stablility enhancers and improve flowability and aerosol dispersibility. Since lactose is the only US-approved excipient for DPI formulations, there is a need for alternative safe excipients. Suggestions have included carbohydrates, such as fructose, glucose, galactose, sucrose, trehalose, raffinose, melezitose; alditols, such as mannitol and xylitol; maltodextrins, dextrans, cyclodextrins, amino acids, such as glycine, arginine, lysine, aspartic acid, glutamic acid and polypeptides, such as human serum albumin and gelatin. To mask the unpleasant taste of some inhaled drug compounds, flavoring particles containing maltodextrin and peppermint oil may be incorporated into dry powder formulations. Large sized particles increase mouth deposition and reduce lung deposition.
Commercial formulations predominantly deliver bronchodilators, anticholinergics and corticosteriods for the local treatment of asthma and chronic airways obstruction. New formulations contain multiple drug components, such as fluticasone and salmeterol. This brings about further complications in the particle interactions involved with powder systems. There has been much speculation on the potential delivery of locally and systemically acting drugs such as analgesics (fentanyl and morphine), antibiotics, peptides (insulin, vasopressin, growth hormone, calcitonin, parathyroid hormone), RNA/DNA fragments for gene therapy and vaccines. However, the only new therapy provided using DPI formulations is zanamivir (Relenza), which is mainly targeted at the upper respiratory tract for the treatment of influenza.
The use of formulation additives to enhance drug uptake has also been considered. The nature of these absorption promoters is based on a variety of mechanisms, not all of which are fully elucidated. The best known are the classical absorption enhancers such as bile salts and surfactants which are known to disrupt cell membranes and open tight junctions rendering epithelia more permeable. This has been followed by the use of small particulates containing drug, which may find their way across epithelia intact. Many of these particulate approaches have yet to be published with respect to lung delivery but some of the companies with relevant technology include Nanosystems, PDC and BioSante. An alternative approach involves the close association of a carrier molecule with peptides and proteins for transport across the epithelium. The mechanism of improved uptake is not fully characterized for these molecules with respect to the lung epithelium. The maximum doses that can be delivered to the lungs limit the systemic delivery of drugs. However, the potential advantage of all of the particulate or molecular transport promoters is that they may improve bioavailability of the drug, maximizing the proportion of the dose that reaches the site of action. This is particularly important for macromolecules which may not be delivered effectively by any other route of administration. The safety implications of using any agent that modifies the physiology of the lung must be fully considered if it is to be adopted for any commercially viable product.
The principle advantages of a DPI and MDI over a nebulizer are that very low volumes of a formulation can be used thereby making feasible the manufacture and use of small delivery devices. Moreover, DPI and MDI devices require very short administration times as compared to nebulizers. MDI devices, however, are becoming less acceptable due to the international restrictions on the use of chlorofluorocarbon propellants that are required for operation of an MDI.
The administration of these drugs in the form of micronized powder requires the use of suitable dry powder inhalers (DPIs).
DPIs in turn can be divided into two additional basic types:                single dose inhalers, for the administration of single subdivided doses of the active compound;        multidose dry powder inhalers (MDPIs), preloaded with quantities of active principles sufficient for longer treatment cycles.
Although micronization of the drug particles is essential for penetration to the deepest branchings of the pulmonary tree during inhalation, it is also known that the finer are the particles, the stronger are the cohesion forces. In multidose inhalers, said effects hamper the loading of the doses of powder from the reservoir system to the aerosolization chamber, since the cohesion forces reduce free flowing of the particles and promote their agglomeration and/or their adhesion to the walls. The aforementioned effects therefore impair the efficiency and reproducibility of the delivered dose and are detrimental to the respirable fraction.
Multidose inhalers work properly when so-called freeflowing powders are used, generally formulated by mixing the micronized drug with a carrier material (generally lactose, preferably α-lactose monohydrate) consisting of coarser particles, approximately equal or greater than 100 microns. In such mixtures, the micronized active particles mainly adhere to the surface of the carrier particles whilst in the inhaler device; on the contrary, during inhalation, a redispersion of the drug particles from the surface of the carrier particles occurs allowing the formers to reach the absorption site into the lungs.
Mixing with the carrier also facilitate the introduction and withdrawal of the inhalation preparation, in a regular dose, from the reservoir of a multidose inhaler or its dosage in single-dose containers. Mixing of the micronized drug with the coarse carrier therefore leads to the production of a mixture in which the micronized drug is distributed uniformly on the carrier particles as a result of the interactions, usually of an electrostatic nature, which establish between the drug particles and the carrier particles.
Said interactions lead to the production of a so-called ordered mixture. It is extremely important for the interactions to be weak and reversible, so that, since transport in the air stream and the respirability of the powder depend on the particle size, only the micronized drug particles will be able to be deposited in the lungs, whereas the coarser carrier particles will be deposited, because of their mass, in the upper airways. Due to the weak interactions between the two components of the mixture, breathing-in through the inhaler causes separation of the micronized drug particles from the coarse carrier particles and therefore inhalation of the smaller particles and deposition of the coarser particles in the oropharyngeal cavity. Accordingly, it is of great applicative interest to find new carriers for inhalers and new techniques for the production of drug-carrier mixtures that are easy to handle and able to generate a high respirable fraction.
The use of a carrier is indeed not free of drawbacks in that the strong interparticle forces between the two ingredients may prevent the separation of the micronized drug particles from the surface of the coarse carriers ones on inhalation, so compromising the availability of the drug to the respiratory tract.
In the prior art there are many examples of processes for modifying the surface conditions of the carrier with the aim of reducing the strength of the interactions between the particles during inhalation, without causing pre-separation of the drug particles in the inhaler.
Ganderton (GB 2 240 337) reports that the surface conditions of the particles, in particular their rugosity, are critical for the behavior of the carrier during inhalation and claims pharmaceutical carriers, such as lactose, consisting of particles whose rugosity is controlled by a crystallization process. The rugosity of the said particles is evaluated using measurements of surface area, based on gas permeametry. The surface area value measured by this technique, relative to the theoretical surface area value, provides a numerical index of rugosity called Ganderton scale.
Staniforth (WO 95/11666) claims a milling process preferably carried out in a ball mill, called corrasion (for analogy with the effect of wind on rocks), which alters the surface characteristics of the carrier by removing asperities in the form of small grains; these grains in turn can become attached to the clefts of the surface area of the particles, so saturating the high energy sites. As a result of this preliminary treatment of the carrier, the micronized drug particles are deposited preferentially on lower-energy sites and so are subject to weaker forces of interparticle adhesion.
On the other hand, the operation of some multidose inhalers requires the use of optimum carriers of high flowability, a characteristic that can only be imparted by using particles with a greater'granulometric distribution.
Disaggregation of the active principle from the carrier during inhalation can also be made more efficient by addition of a fraction of fine particles of the same carrier. The Boheringer patent EP 0 663 815 claims the use of carriers for controlling and optimizing the amount of drug released during the aerosolization phase, comprising suitable mixtures of coarse particles with size>20 microns and of fine particles with size<10 microns.
Finally, in the prior art, additives with lubricant, glidant or anti-adherent properties, dry-mixed with the carrier, have been employed with the aim of reducing the forces of attraction between drug and carrier. For example, mixing of magnesium stearate with crystalline lactose is able to reduce the forces of adhesion between drug and carrier, when this mixture is used as inhalation carrier. For explaining the effectiveness of magnesium stearate in the aerosolization of inhalation powders, investigations conducted on powder mixtures for tablets cap be taken into account (Staniforth et al., J. Pharm. Pharmacol. 1982, 34, 141-145). These investigations showed that the presence of lubricants causes a decrease in cohesion of the tablets because they form a lubricated layer on the powder particles that are to be pressed together, thereby interfering with the bond between them.
This mechanism is also regarded as responsible for the decrease in strength of adhesion of the micronized drug particles on the carrier particles (Kassem, thesis, London University, 1990).
In WO 96/23485, the particles are mixed with a substance with anti-adherent or antifriction properties, consisting of one or more compounds selected from amino acids (in particular leucine), phospholipids or surfactants; deposition of the additive on the carrier is preferably carried out in the dry form, and does not give rise to a complete coating of the carrier, but rather to a discontinuous covering in order to saturate the highenergy sites. Preferably, the carrier particles and the additive are submitted to the corrasion process in a ball mill as described in WO 95/11666.
It follows from examination of the prior art that in the case of an inhalation powder, consisting of a drug-carrier mixture, efficient disaggregation of the active principle from the carrier during inhalation is dependent upon the drug-carrier interparticle forces and so depends on the surface characteristics of the latter.
The current market for Dry Powder Inhalers (DPIs) is expanding for several reasons including: environmental and technical concerns with pressurized metered dose inhalers, improved performance and acceptance of newly marketed DPIs, and the potential utility of DPIs for novel and systemically acting drug compounds. However, despite market growth, current DPIs have several shortcomings. Commercially available dry powder inhalers are generally less efficient and reproducible in delivering drugs to the lower airways than pressurized metered dose inhalers. Thus, several opportunities exist for improving the performance of DPIs including:                increasing the fine particle fraction delivered (by inference, increasing lung deposition and reducing oropharyngeal deposition);        decreasing variability of emitted dose and fine particle fraction;        decreasing the dependence of dose delivered and region of delivery on inspiratory flow rate;        decreasing inhaler resistance and energy required to disperse drug aerosol;        increasing physical stability;        improving ease of manufacture of DPIs;        decreasing oropharyngeal deposition;        enhancing control over regional lung deposition; and        increasing pulmonary bioavailability.
There are other areas in which performance can be improved such as: increasing physical stability; and improving the ease of manufacture of DPIs and dry powder formulations. The most imminent needs of dry powder inhaler design are increasing the fine particle fraction and decreasing the variability between doses.
While DPI and MDI formulations of drug may be highly desirable, the number and type of suitable formulations that can be prepared is limited. This is due in large part to the limited compounds suitable as carriers in these dosage forms.
It is known in the art of inhalable powder formulations that the morphological and physicochemical properties of the drug and excipients (carrier) can affect the performance of a device used to administer the two. In particular, particle size of the drug and inert carrier has a great impact upon the ultimate site of delivery for each. A smaller particle size (less than about 10 microns) is accepted for lung delivery whereas larger particle sizes are preferred for tracheal, throat or buccal delivery with a DPI device. It is also known that the hygroscopicity of the drug and carrier can affect performance. Other factors known to affect the efficiency of delivery of a powdered solid with a DPI device include: electrostatic interactions between the drug and carrier particles, surface morphology of the particles, hydrophobicity/hydrophilicity of the drug and carrier particles, and others.
The desired properties of an inert carrier for use in a DPI include: 1) a particle diameter is within 50-1000 microns; 2) ability to associate with a drug sufficiently to aid in suspending it during a the period of administration balanced against an ability to dissociate from the drug in the buccal cavity or throat of a subject to permit pulmonary delivery of the drug but not of the carrier; 3) inertness toward degradation of the drug; 4) inertness in terms of not providing a therapeutic effect to a subject; 5) controllable and modifiable morphological properties; 6) suitability for preparation by a range of different processes; and/or 7) controllable and modifiable chemical properties.
Mono- or disaccharides, such as glucose, lactose, lactose monohydrate, sucrose or trehalose, sugar alcohols, such as mannitol or xylitol, polylactic acid, glucose, and trehalose are among the few compounds that are used as carriers in these devices. The properties of those compounds can be modified at least somewhat to optimize their performance. Even so, there are many drugs that cannot be suitably formulated with lactose for this type of administration. Therefore, identification of another material that is suitable as carrier and which properties can be modified in a controlled manner would be desired.
The current focus in DPI therapy is to administer higher concentrations of drug, use smaller unit dose volumes, develop new carriers having specific properties, identify and develop carriers suitable for use with specific DPI device formats.
In order to enhance drug absorption across the pulmonary lining, researchers have proposed the inclusion of permeation enhancers in DPI and PMDI devices. Cyclodextrins have been proposed for use in nebulizer liquid formulations as well as DPI and PMDI solid formulations. However, administration of some cyclodextrins into the lungs of a mammal might not be acceptable. Literature exists on the potential or observed toxicity of native cyclodextrins and cyclodextrin derivatives. The NTP Chemical Repository indicates that α-cyclodextrin may be harmful by inhalation. Nimbalkar et al. (Biotechnol. Appl. Biochem. (2001), 33, 123-125) cautions on the pulmonary use of an HP-β-CD/diacetyldapsone complex due to its initial effect of delaying cell growth of lung cells.
Even so, a number of studies regarding the use of cyclodextrins for inhalation have been reported although no ensuing formulations have been commercialized. The studies suggest that different drug-cyclodextrin combinations will be required for specific optimal or even useful inhaled or intra-nasal formulations. Attempts have been made to develop cyclodextrin-containing powders and solutions for buccal, pulmonary and/or nasal delivery.
A number of scientific publications and patent references disclose inhalable dry powder compositions comprising a cyclodextrin. For the most part, the cyclodextrin is included as an inclusion complex with the drug.
Rajewski et al. (J. Pharm. Sci. (1996), 85(11), 1142-1169) provide a review of the pharmaceutical applications of cyclodextrins. In that review, they cite studies evaluating the use of cyclodextrin complexes in dry powder inhalation systems.
U.S. Pregrant Patent Publication No. 2003-215512 and U.S. Pat. No. 6,309,671 to Billingsley et al. discloses a powdered inhalable composition wherein the drug is embedded within a glassy matrix formed of a cyclodextrin. As such, the drug is complexed with the drug and is not separable therefrom during administration with a DPI device.
Shao et al (Eur. J. Pharm. Biopharm. (1994), 40, 283-288) reported on the effectiveness of cyclodextrins as pulmonary absorption promoters. The relative effectiveness of cyclodextrins in enhancing pulmonary insulin absorption, as measured by pharmacodynamics, and relative efficiency was ranked as follows: dimethyl-β-cyclodextrin>α-cyclodextrin>β-cyclodextrin>γ-cyclodextrin>hydroxypropyl-β-cyclodextrin.
New Zealand Patent Application No. 510168 discloses a particulate composition for the delivery of a drug to the alveoli of the lung. The dry composition comprises the drug and at least 40% wt. of cyclodextrin. The particles are prepared by spray drying a liquid composition containing the cyclodextrin and drug, so the cyclodextrin is complexed with the drug and is not separable therefrom during administration of the composition with a DPI device.
Rodrigues et al. (Artificial Organs, (MAY 2003) Vol. 27, No. 5, pp. 492-497) disclose the preparation of particles containing a complex of insulin and cyclodextrin such that the two are delivered to the lung.
Nakate et al. (European Journal of Pharmaceutics and Biopharmaceutics (2003), 56(3), 319-325) disclose the administration of FK224 by DPI using β-CD particles in admixture with the drug. The formulation is made by simultaneous micronization of the FK224 and β-CD such that both are of a particle size suitable for delivery to the lungs.
Fukaya et al. (European Respiratory Journal (2003), 22(2), 213-219) disclose the results of an evaluation of a DPI dry powder formulation containing a complex of cyclosporin A and a cyclodextrin.
Kinnarinen et al. (Journal of Controlled Release (2003), 90(2), 197-205) disclose a DPI formulation comprising a complex of budesonide and γ-CD.
Vozone et al. (Journal of Inclusion Phenomena and Macrocyclic Chemistry (2002), Volume Date 2003, 44(1-4), 111-115) disclose the administration of budesonide and dimethyl-β-CD present as either a preformed complex or physical mixture in a composition for dry powder inhalation. They observed no statistically significant difference between the emitted dose means of both the complex and the physical mixture, but they observed a statistically significant higher fine particle fraction mean was for the complex. They suggest that using a spray-dried CD complex powder for pulmonary drug delivery may increase the drug's respirable fraction and consequently its therapeutic efficacy.
PCT International Publication No. WO 01/87278 to Kampinga discloses the preparation and use of particles containing 10-40% of drug and 90-60% of a saccharide, which can be cyclodextrin. If a cyclodextrin were present, it would be complexed with the drug due to the method of preparation employed.
Camoes et al. (Proceedings of the International Symposium on Controlled Release of Bioactive Materials (2000), 27th, 794-795) disclose β-CD complexes with salbutamol for dry powder inhalation.
Pinto et al. (S.T.P. Pharma Sciences (1999), 9(3), 253-256) disclose HP-β-CD complexes with beclomethasone and use thereof in a dry powder inhalable formulation.
U.S. Pat. No. 6,582,728 to Platz et al. discloses a dry powder inhalable formulation comprising a drug and a carrier, which can be cyclodextrin. The formulation is prepared by spray drying the drug and carrier together. If a cyclodextrin were the carrier, it would be complexed with the drug due to the method of preparation.
European Patent No. 1283035 discloses an inhalable dry powder formulation comprising parathyroid hormone, an absorption enhancer and a coarse particle carrier. The cyclodextrin can be an enhancer, but it is not suggested as being a suitable carrier. Since it is an absorption enhancer, it is delivered into the lungs with the drug.
U.S. Pregrant Patent Publication No. 2003-0138403 to Drustrup discloses formulations containing interferon and SAE-CD. The formulations are suggested as being suitable for administration by inhalation. The formulations contain the preformed complex of interferon and SAE-CD.
U.S. Pregrant Patent Publications No. 2003-064928 to Backstrom et al. and No. 2003-059376 to Libbey et al. and U.S. Pat. Nos. 6,436,902 and 5,952,008 to Backstrom et al. disclose inhalable formulations wherein cyclodextrin is incorporated into the matrix of particles to enhance the absorption of drug in the lung. The cyclodextrin is not separable from the drug during administration.
U.S. Pat. No. 6,599,535 to Guitard et al. discloses solid dispersion compositions comprising a macrolide drug and a carrier medium, which can be a cyclodextrin. A number of water soluble cyclodextrin derivatives are suggested, including SAE-CD; however, the process for preparing the composition results in complexation of the drug and cyclodextrin. So, the drug and cyclodextrin are both delivered to the lung.
U.S. Pregrant Patent Publications No. 2002-117170 to Platz et al. discloses a spray-dried composition containing FSH and a pharmaceutically acceptable carrier, which can be a cyclodextrin. It is likely that the FSA and cyclodextrin would be present as a complex due to the spray-drying process described in the application.
U.S. Pat. No. 6,495,120 to McCoy et al. discloses the pulmonary administration of a drug, HP-β-CD and a carrier solvent. The formulation comprises the drug, a cyclodextrin and a solvent, so the drug is complexed with the cyclodextrin.
U.S. Pat. No. 6,306,440 to Backstrom et al. discloses inhalable formulations comprising insulin and an absorption enhancer, such as a cyclodextrin. Both the cyclodextrin and insulin are intended to be delivered to the lung.
van der Kuy et al. (Eur. J. Clin. Pharmacol. (1999 November), 55(9), 677-80) report the results of the pharmacokinetic properties of two intranasal preparations of dihydroergotamine mesylate (DHEM)-containing formulation using a commercially available intranasal preparation. The formulations also contained randomly methylated β-cyclodextrin (RAMEB). No statistically significant differences were found in maximum plasma concentration (Cmax), time to reach Cmax (tmax), area under plasma concentration-time curve (AUC0-8 h), Frel(t=8 h) and Cmax/AUC(t=8 h) for the three intranasal preparations. The results indicate that the pharmacokinetic properties of the intranasal preparations are not significantly different from the commercially available nasal spray.
U.S. Pat. Nos. 5,942,251 and 5,756,483 to Merkus cover pharmaceutical compositions for the intranasal administration of dihydroergotamine, apomorphine and morphine comprising one of these pharmacologically active ingredients in combination with a cyclodextrin and/or a disaccharide and/or a polysaccharide and/or a sugar alcohol.
U.S. Pat. No. 5,955,454 discloses a pharmaceutical preparation suitable for nasal administration containing a progestogen and a methylated β-cyclodextrin having a degree of substitution of between 0.5 and 3.0.
U.S. Pat. No. 5,977,070 to Piazza et al. discloses a pharmaceutical composition for the nasal delivery of compounds useful for treating osteoporosis, comprising an effective amount of a physiologically active truncated analog of PTH or PTHrp, or salt thereof and an absorption enhancer selected from the group consisting of dimethyl-β-cyclodextrin.
PCT International Publication No. WO 00/015,262 to Clark et al. discloses inhalable powdered compositions comprising a hygroscopic growth inhibitor and a drug. The inhibitor can be a cyclodextrin among other things, and SBE-CD is exemplified as a suitable cyclodextrin. The cyclodextrin is complexed with the drug in the formulation due to the process of preparation employed.
PCT International Publication No. WO 00/066,206 to Thurston et al. discloses a multi-component inhalable composition, wherein a cyclodextrin can be included as a drug stabilizing agent. The cyclodextrin is complexed with the drug in the formulation due to the process of preparation employed.
Other references suggest the use, in general, of a cyclodextrin as a carrier in a DPI formulation. PCT International Publication No. WO 01/05429 to Caponetti et al. discloses the use of mixtures suitable for dry powder inhalation. The compositions comprise smooth carrier particles in admixture with a drug. Cyclodextrins, among other things, are suggested as being suitable for the carrier. There is no exemplification of such a use. The carrier particles are made by smoothing the surface of rough particles in a high speed mixer granulator alternately in the presence of a solvent or in dry form.
U.S. Pat. No. 6,645,466 to Keller et al. discloses a dry powder formulation for inhalation. The formulation contains a fine inhalable particle size drug, a coarser non-inhalable particle size carrier and magnesium stearate bound to the carrier. A cyclodextrin can apparently serve as the carrier. There is no disclosure regarding examples or preferred properties for the cyclodextrin as carrier, nor is there any disclosure of a method of preparing the CD to make it suitable as the carrier.
The parent cyclodextrins contain 6, 7, or 8 glucopyranose units and are referred to as α-, β-, and γ-cyclodextrin respectively. Each cyclodextrin subunit has secondary hydroxyl groups at the 2 and 3 positions and a primary hydroxyl group at the 6-position. The cyclodextrins may be pictured as hollow truncated cones with hydrophilic exterior surfaces and hydrophobic interior cavities.
The physical and chemical properties of the parent cyclodextrins can be modified by

This patent is subject to a terminal disclaimer.

DPI formulation containing sulfoalkyl ether cyclodextrin


Embodiments of the present disclosure relate to providing electronic survey content to a user in accordance with a particular layout. In particular, a survey system facilitates providing survey questions of an electronic survey to a user within a display area of a client device in accordance with a determined layout based on one or more features of the display area. For example, the survey system associates a plurality of layouts with one or more survey questions. Further, the survey system provides the survey questions and associated layout to a client device for presentation to a user. The client device identifies one or more features of a display area and determines a layout from the plurality of layouts to use in providing the survey question(s) to the user. Further, the client device provides one or more survey questions to a user within the display area in accordance with a determined layout.

1. Technical Field
One or more embodiments of the present disclosure relate generally to systems and methods for presenting electronic survey questions. More specifically, one or more disclosed embodiments relate to systems and methods for providing electronic survey questions in accordance with a display area on a client device.
2. Background and Relevant Art
Companies often rely on opinions and feedback from past customers to improve the experience of current and future customers. A common method of acquiring feedback is through customer surveys, including customer ratings and reviews (e.g., ratings and reviews for products, services, businesses, etc.). For example, a company may use feedback obtained from a survey administered to one or more past customers to improve future customer experience with the company.
Due to the development of electronic communication technologies, many surveys are administered to survey respondents via the Internet as electronic surveys. Additionally, as the number of different types of computing devices having Internet capabilities has increased, more and more electronic surveys are administered on computing devices that have various different features (e.g., monitor/screen sizes, input devices (touchscreen vs. mouse)). While the increased availability of computing devices has facilitated an increase in the use of electronic surveys, there currently exist a number of problems in administering electronic surveys on a variety of different computing devices.
As an initial problem, while computing devices have increased the convenience of administering electronic surveys, the presentation of an electronic survey designed for a computing device having a large display area often fails to translate effectively to a mobile device having a more limited display area. For example, where a multiple choice survey question fits on a monitor of a desktop computer, the same multiple choice survey question may fail to fit on a display screen of a mobile device. Often, in an attempt to fit the survey on a display screen of a mobile device, a user dramatically decreases the size of the text, but then, the readability of the survey question is also reduced for the user. As such, mobile devices and other electronic devices having a limited display area often fail to provide a user-friendly presentation of an electronic survey.
In addition to inadequacies in presenting the electronic survey on mobile devices (and other electronic devices having limited display areas), conventional electronic surveys often fail to account for differences in how a user interacts with a respective device. For example, where a desktop computer may include a keyboard, mouse, and/or other input device for interacting with an electronic survey, a mobile device may include a touch screen and/or keypad for interacting with the same electronic survey. As such, many electronic surveys are well-suited for administration with a particular type of input device, but ill-suited for administration using a different type of input device.
To account for administration of electronic surveys on different devices, many conventional systems administer different surveys for different respective devices. Nevertheless, administering different electronic surveys for different devices can become a burdensome process as individual surveys are created for different operating systems, different devices, and/or different applications. Furthermore, as the variety of mobile devices and other electronic devices continues to increase, creating different surveys to be administered for each different type of device can become time-consuming, expensive, and generally impractical.
Accordingly, these and other disadvantages exist with respect to conventional systems and methods for providing an electronic survey.

Providing a display based electronic survey


The disclosure provides a manufacturing method for TFT array substrate, a TFT array substrate and a display device. The manufacturing method includes following steps: in sequence, forming a gate pattern layer, a gate insulating layer, a patterned poly-silicon layer, a separation layer on s substrate, and adopting a mask to form a source pattern layer and a drain pattern layer on the separation layer by photolithography processes. The source pattern layer and the drain pattern layer are connected to the patterned poly-silicon layer. The mask blocks one side of the channel area, and the same mask is adopted to form a lightly doped area on the other side of the channel area not blocked by the mask. The disclosure may reduce production costs and has great design flexibility.

As the technology of low temperature poly-silicon (LTPS) in thin-film transistor (TFT) advances and the characteristic of ultra-high carrier mobility of the LTPS semiconductor, the corresponding peripheral integrated circuit of the panel has drawn much attention. Additionally, many people put effort in the research in relation to system on panel (SOP) and make it available. However, because of the ultra-high carrier mobility of the LTPS, it is much worse than A-Si in terms of electric leakage. Hence, it is crucial to solve the problem of electric leakage in the LTPS design.
As shown in FIGS. 1 and 2, FIG. 1 is a flow chart of a manufacturing method of a TFT array substrate of current technology and FIG. 2 is a process flow diagram of the manufacturing method of the TFT array substrate based on the current technology. In the current technology, the manufacturing method of LTPS-TFT having the bottom gate structure comprises the following steps:
S10, forming a gate pattern layer 41 on a substrate 40;
S11, forming a gate insulating layer 42 on the gate pattern layer 41;
S12, forming a patterned poly-silicon layer 43 on the gate insulating layer 42, the patterned poly-silicon layer 43 being connected to the gate insulating layer 42;
S13, forming a heavily doped source area 431 and a heavily doped drain area 432 on two sides of the patterned poly-silicon layer 43 respectively;
S14, adopting a mask to form a lightly doped source area 434 on the inner side of the heavily doped source area 431, and to form a lightly doped drain area 433 on the inner side of the heavily doped drain area 432, a channel area being between the lightly doped source area 434 and the lightly doped drain area 433;
S15, forming a separation layer 44 on the patterned poly-silicon layer 43; and
S16, forming source and drain pattern layers 45 on the separation layer 44 and making the source and drain pattern layers 45 be connected with the patterned poly-silicon layer 43.
In the manufacturing method, in step S14 where the lightly doped area is formed, it is required to specially design a mask to block the area outside the region for the lightly doped area. This therefore increases the cost of the method.

Manufacturing method for TFT array substrate, TFT array substrate and display device

Shenzhen China Star Optoelectronics Technology Co., Ltd.

Wuhan China Star Optoelectronics Technology Co., Ltd.


An upwardly open chest has a hinged lid, and oppositely movable roller blinds to close an upper compartment in which food can be cooked, or stored at normal refrigerator temperatures. A steam rod support structure slides parallel the lid's hinge line for selectively cooking food in this compartment, and front doors provide access to a frozen food storage compartment. Conventional steam cooking and refrigeration cycle components circulate cooling or heating fluid to coils or moist steam outlet pipes in certain compartments selectively.

This invention relates to cooling and cooking devices, and deals more particularly with a device which is suitable for both freezing and cooking by means of superheated system.
It has been known for some time that potatoes can be pressure-cooked to the required soft consistency by means of a potato steamer (German Patent No. PS 85 468); the loading compartment of this steamer, into which the potatoes are placed, is fitted with a horizontal pipe with lateral branchings which are connected to downward directed steam-jet pipes. On the one hand, this conventional potato steamer is only suitable for pressure-cooking potatoes; on the other hand, it would be neither suitable nor convenient enough to be utilized in households, snack bars, fast-food establishments and the like.
Another conventional process is to keep food frozen in freezers or the like and then, prior to their consumption, to quick-heat them by admitting dry steam (German Patent No. PS 1 271 338). The conventional device used for this purpose is utilized primarily in restaurants for the quick-cooking of frozen vegetables and the like. This device is hardly suitable for use in households or snack bars or fast-food establishments preparing an array of different foods (soups, sauces, vegetables and generally any pre-cooked dishes), because it is too unwieldy and ill equipped for the simultaneous heating of several different food items. Furthermore, it is bothersome to have to get the food items from a frozen food chest or deep freeze room in each instance and carry them to the location where they are to be heated and then, later on, to take those items back to the freezer or deep-freeze room which, perhaps, were not heated because there was no call for them.


A removable diode package for mounting beam-lead diodes in coaxial, stripline or waveguide microwave circuits is described. The diode package is capable of operation at frequencies above 40 GHz. A low-dielectric polyimide insulating washer is used to reduce parasitic elements normally associated with diode packages at microwave and millimeter frequencies.

The present invention relates to packaging and mounting beam-lead diodes in a stripline, coaxial or waveguide assembly.
Beam-lead technology is ideally suited to the production of diodes which must operate at high frequencies with low loss due to parasitic elements associated with the elements of the device. Beam-lead diodes also provide excellent mechanical reliability and can be protected by an appropriate encapsulant which adds negligibly to device parasitics without degrading RF performance. Beam-lead devices are easily adapted to mounting in microwave-integrated circuitry but difficult to adapt to other environments. This occurs because the diode is normally bonded in place and field replacement is difficult if not impossible.
Semiconductor chip diodes have been successfully packaged in various configurations. Usually these packages contain a spring-loaded pin or a fine gold wire to contact the enclosed semiconductor chip. The pin and the wire contribute a parasitic inductance in series with the semiconductor. Parasitic capacitance contributed by the cross-sectional area of the pin and end contacts of the package in conjunction with the parasitic inductance create spurious resonances that make satisfactory operation above 30 GHz nearly impossible. For more information concerning parasitic elements associated with conventional packaged and mounted diodes the article "The Packaged and Mounted Diode as a Microwave Circuit" by W. J. Getsinger, IEEE Transactions on Microwave Theory and Techniques, vol. MTT-14, No. 2, February, 1966, pp 58-69, which is incorporated herein by reference.
U.S. Pat. No. 3,974,518 discloses a package for microwave diodes wherein the semiconductor chip is mounted upon a diamond member embedded in a copper base member so that the diamond mounting surface and the copper base member surface are coplanar. A quartz insulator surrounds the chip and reduces parasitic capacitances to an extent. However, the diode is suitable for X-band (up to 8-12.5 GHz) operation only.
What is needed then is a packaging and mounting method apparatus and method for removably mounting a beam-lead diode in a coaxial, stripline or waveguide assembly that does not appreciably degrade device performance in the microwave and millimeter frequency ranges.


A rigid fiber glass air duct for conveying an airstream has an interior surface, adapted to be in contact with the airstream, which is coated with a polymeric coating with an organic biocide. The polymeric coating has a dry solids content of between 10 and 20 grams per square foot of duct board surface and retains its abrasion strength and puncture resistance whereby the interior surface of the duct can be cleaned by conventional industrial or commercial cleaning methods while in service without exposing glass fibers to the airstream.

The present invention relates to cleanable, fiber glass ducts for conveying air which are used in heating, ventilating and air conditioning systems.
It is common practice to use fiber glass duct liners in heating, ventilating and air conditioning systems. As discussed in Terry et al, U.S. Pat. No. 4,990,370, column 1, lines 33-50, the interior surfaces of these fiber glass duct liners, which are relatively low in density when compared to fiber glass ducts, are either coated with a rubberized or plastic material or a facing is applied to the surface to prevent portions of the duct liner from breaking away or flaking off due to erosion by the air stream within the duct liner. Without the coating, loose particles of dust and dirt, in the air stream being conveyed, strike the interior surface of the duct liner causing erosion so that portions of the duct liner break away or flake off. However, the coating is only sufficient to prevent the erosion of the interior surface of the duct liner and does not form the smooth, durable surface required to withstand the cleaning of the interior surface of the duct liner by maintenance personnel using conventional commercial cleaning methods.
Fiber glass air ducts are also used in heating, ventilating and air conditioning systems. These air ducts are formed from high density fiber glass duct boards having a density of at least 3.5 pounds per cubic foot as compared to a density of 1.5 pounds per cubic foot for low density duct liners. The duct boards are formed by compressing blankets of resin coated glass fibers to an appropriate thickness and density and curing the resin binder. Due to the high density and the heavy resin binder content on the interior surface of the duct boards forming the air duct, the high density fiber glass ducts formed from the duct boards do not require a coating or facing on their interior surfaces to prevent erosion by the air stream. However, like the duct liners discussed above, the prior art air ducts have not had an interior surface suitable for cleaning by conventional industrial or commercial cleaning methods.
With recent developments in air quality measurement devices and an overall increase in environmental awareness, there has been an increased interest in the air quality in all types of buildings employing heating, ventilating and air conditioning systems. While in service, especially when the air filtration system is not properly maintained, the interior air conveying surfaces of air ducts pick up dust and become increasingly dirty. The accumulation of dust on the interior surfaces of ducts uses been identified as a possible nutrient source for microbiological growth. The growth of microbes in an a heating, ventilating and air conditioning system may compromise the indoor air quality of the building or home served by the system. Accordingly, there has been a need to provide a cleanable interior surface for air ducts.
The interior surfaces of sheet metal air ducts are often cleaned with rotating brushes having plastic bristles six inches to a foot long. Another method of cleaning air ducts uses industrial type vacuum cleaners. In addition, it is common to clean the interior surfaces of sheet metal air ducts with liquid chemical disinfectants to remove microbiological growth from the interior surface of the duct.
Fiber glass air ducts not only effectively convey the air in a heating, ventilating and air conditioning system, they also, unlike sheet metal air ducts, provide an acoustical benefit by reducing the transmission of sound. While fiber glass does not support mold growth and the use of liquid chemical disinfectants on the interior surface of fiber glass ducts is not necessary, the cleaning of uncoated fiber glass air ducts to remove dust and dirt by the methods discussed above can result in damage to the interior surface of an uncoated fiber glass air duct by puncturing and/or wearing away the interior surface of the duct. Accordingly, there has been a need to provide a cleanable interior surface for fiber glass air ducts that can be subjected to normal commercial cleaning methods.

Fiber glass air duct with coated interior surface containing an organic biocide


A mounting bracket for curtains, which includes a first face of the bracket which would be positioned against the front face of a window molding; a mounting hook extending outwardly from the face of the bracket, for mounting a curtain rod thereupon; a first arm extending rearwardly from the top portion of the face, to a depth substantially the thickness of a window molding; a second arm extending along rearwardly from the side of the face also of a depth substantially the thickness of the window molding; a first downward depending tooth member extending downwardly from that arm extending rearwardly from the top portion of the bracket, and a second tooth member extending inwardly from that arm extending rearwardly from the side of the bracket, so that when the inwardly depending tooth is engaged into the side wall of the molding, and the downward depending tooth member is engaged into the upper wall of the molding, the bracket is secured onto the molding without the need for mounting screws or the like.

1. Field of the Invention
The apparatus of the present invention relates to curtain rods. More particularly, the present invention relates to an apparatus which is attachable to the corner of a window molding without the use of mounting nails or screws, which will accommodate a curtain rod thereupon after the bracket has been placed into position.
2. General Background
It is commonly known in the art of curtain hanging, that one of the more common types of rods are the type that are substantially flat and form an "L" bend at each end of the rod, so that once the curtain has been placed onto the rod, the rods are attached to a bracket along the corners of the opening, for example a window, and the curtain is therefore hanging from the window, yet moved apart from the frame of the window so as to allow free hanging of the curtains. Normally, these types of rods would include at their end portions an opening within the rod body, so that the end of the rod may slip around a bracket, with the upper point of the bracket engaging a port in the upper wall of the rod, so that the rod is attached to the bracket securely. These types of brackets are quite well known and have been used for many years.
One of the concerns of these types of brackets are the fact that these brackets normally have a rear face which would include a pair of ports in the face, for accommodating mounting tacks or screws through the ports, for allowing the bracket to be secured to the corner of the window molding, so that curtains may be hung thereupon. It is therefore necessary that normally a pair of holes be bored into the face of the window or door molding, and screws or nails be threadably engaged into the molding so that the bracket is held secure. This is often times quite unsightly, particularly when the brackets must be removed for any reason, and the molding facing the interior cf the room is flawed with holes in the corner that were once accommodating the curtain brackets. Therefore, there is a need for a new and improved type of bracket which may be mounted in a different fashion so as to allow the bracket to be easily secured onto the face of the molding without the molding being blemished.


A push-pull amplifier comprises first and second output circuits each comprising at least one transistor which circuits are mutually connected in push-pull configuration, first and second detection circuits for respectively detecting the differences between the input and output voltages of the first and second output circuits, and first and second variable bias circuits operating in response to the detection outputs of the first and second detection circuits, respectively, to apply constant bias voltages to the transistors of the first and second output circuits in the case where the absolute values of the output currents of the first and second output circuits are below a specific level and to apply, as bias voltages, voltages equal to the sums of the constant bias voltages and voltages corresponding to the detection outputs of the first and second detection circuits to the first and second output circuits in the case where the absolute values of the output currents are above a specific level. The transistors of the first and second output circuits continually operate in their active areas.

The present invention relates generally to push-pull amplifiers, and more particularly to a push-pull amplifier which operates with high efficiency, produces an output of low distortion factor, and carries out improved class "A" amplifier operation.
In general, amplifiers are classified as class "A", class "AB", class "B", etc., depending on the manner in which their operating points are selected. Of these amplifiers, a class "A" amplifier has an operating point which is set at substantially the middle of the linear part of the input voltage versus output current characteristic curve of the output-stage transistors. For this reason, a class "A" amplifier has the characteristic of a very low distortion but, on the other hand, has certain drawbacks such as the necessity of passing therethrough an idling current even when there is no signal, whereby the efficiency is poor, and a great quantity of heat is generated. In the case of an ordinary class "A" amplifier of 100 W output, for example, the power-source voltage is set at .+-.50 V, and the idling current is set at a value of the order of 4 A. Consequently, at the time when there is no signal, a power of 400 W is consumed. For this reason, a great quantity of heat is generated in a class "A" amplifier, which necessitates elaborate means for dissipating the heat, giving rise to problems such as high cost, increased weight, and difficulty in miniaturization.
Furthermore, the idling current of a class "A" amplifier is determined with consideration given to the estimated minimum value of the load impedance (for example, 4.OMEGA.). For this reason, in the case where the amplifier is used with a load impedance higher than this, there has been a disadvantage in efficiency as described hereinafter. Still another problem is that, when an output exceeding the rated value is produced by a conventional class "A" amplifier, its operation becomes one of class "AB", and switching distortion arises.
In the case of a class "AB" amplifier, the idling current is less than that of a class "A" amplifier, while in the case of a class "B" amplifier, the idling current is theoretically zero. In both of these amplifiers, the efficiency is higher than that in a class "A" amplifier, and less heat is generated. On the other hand, however, the output-stage transistors of the class "AB" and class "B" push-pull amplifiers are caused to undergo switching operation. For this reason, switching distortion is produced in their outputs, and the distortion factor is worse than that in a class "A" push-pull amplifier.


The novel current-mode switching regulator does not determine the load current by picking off a measurement voltage at a measuring resistor, as in the conventional prior art. Instead, the voltage drop across the inductor which is required in any case is picked off as the measurement voltage. A regulating signal derived from the load current is determined, by integration with respect to time, with a voltage-controlled current source. The regulating signal is fed back, as a regulated variable, into regulators of the inner control loop. In this way, it is possible to dispense with the measuring resistor. An additional compensation device makes it possible, moreover, to compensate for a regulation deviation in the desired potential of the outer control loop.

Field of the Invention
The invention lies in the electronics field. Specifically, the invention relates to a current-mode switching regulator for power supply, in particular for application in switched-mode power supplies.
Switched-mode power supplies are disclosed for example in Tietze and Schenk, "Electronic Circuits --Design and Application," Springer-Verlag 1991, p. 502. Switched-mode power supplies of this type usually comprise a rectifier, a power switch provided for the purpose of pulse width modulation, a filter, and also a regulator for controlling the power switch. An input voltage--for example a rectified power supply system voltage--is converted into a pulsed DC voltage with a variable duty ratio by the power switch acting as pulse width modulator. In this case, the pulse frequency may be set to be variable or fixed.
The task of the regulator is to keep the voltage at the output of the filter constant over a wide output current range. In other words, the regulator has to process the voltage at the output of the filter and the current at the output of the filter as input variables and form from them a control signal for the power switch. In this case, the timing ratio of the switch is influenced by the control signal.
Essentially three different control strategies exist for the regulation of such switching regulators: voltage-mode regulation, feedforward regulation and current-mode regulation. These control strategies are described for example in R. E. Tarter, Solid-State Power Conversion Handbook, Wiley Interscience, New York, 1993.
Current-mode regulation thereby constitutes a particularly elegant and effective type of regulation which, moreover, requires only comparatively small compensation capacitances. It is thus ideal for use in integrated circuits.
Current-mode switching regulators have two control loops. The inner control loop thereby serves to regulate the load current, while the outer control loop serves, together with the inner control loop, to regulate the output voltage. When the switching transistor is switched on, the voltage across a measuring resistor caused by the current rising in ramped fashion through the inductor coil of the switching regulator likewise has a ramped profile. When a desired voltage predetermined by the outer control loop is reached, the switching transistor switches off.
In current-mode switching regulators, it has been necessary heretofore, as described above, for the load circuit to have a measuring resistor in order to detect the current at the inductor. For the current detection, this measuring resistor is typically designed with a low resistance and, on account of its losses, is not suitable for use in integrated circuits. Such measuring resistors have to be connected externally to the integrated circuits in a cost-intensive manner, which requires considerable outlay in the course of fabrication.
However, the provision of a, typically, external measuring resistor turns out not only to be disadvantageous for cost reasons, but also reduces the efficiency of the switching regulator. Since the measuring resistor typically has to be connected externally to the integrated circuit, it is sometimes necessary, apart from a greater space requirement on the circuit board, to provide an additional output terminal on the integrated circuit.
Finally, the voltage drop measured across the measuring resistor has, for each switching period, an initial voltage spike produced by charge reversal of parasitic capacitances when the power switch is switched on. These undesirable voltage spikes have to be blanked out by additional measures--such as e.g. so-called "leading edge current blanking"--which are complicated in terms of circuitry, since the voltage spikes would otherwise impermissibly corrupt the actual measured value.

Current mode switching regulator configured such that a measuring resistor is not needed to measure the current at an inductor


A power sanding machine (10) has three circumferentially spaced cogged belts (40) that are under tension via bearings (36) to drive three discs (52). A grounded vacuum (16) with a metal canister (74) is mounted on the operating handle (14).

The field of this invention relates to wood floor sanding machines.
Hardwood floors have long been a desirable trait in a home. However, sanding and refurbishing a hardwood floor is one of the more difficult do-it yourself tasks for a homeowner.
The present sanding machines on the market commonly have a single belt drive all three sanding discs which creates a side torque that drives the machine to one side as it sands the floor. The operator then needs to always counter the torque which promotes an uneven surface finishing and fatigue on the operator for larger sanding jobs.
Many machines also have higher operating speeds which allow little error in operating the machines. The high operating speeds can quickly cause gouging and knicks in the wood floor without having time to control or eliminate these gouges. Furthermore, the high operating speeds produce significant amount of noise.
Attempts have been made to increase the sanding force of the discs by increasing the weight of the sander. These weights are obtrusive horseshoe shaped steel members that are mounted on top of the sander housing. The external weights require an extra fastening device and if not tightly mounting the weights, extra chatter and vibration may occur.
These sanding machines also have a housing edge which is widely spaced from the operating sanding discs. This prevents the machine to sand close to walls. Furthermore the housing may have a high periphery which prevents it from intruding under the toe recess under many kitchen cabinets. As a result, even after adding a shoe molding to the edge of the floor, an unsanded edge may be showing. Therefore, additional smaller edge sanders need to be extensively used to approach the edge of the floor which further make the sanding process difficult.
Furthermore, the sanding creates great amount of sawdust which needs to be controlled. The sawdust if not controlled can fill the room creating a mess and interfering with the visibility of the floor as it is being sanded. Secondly, uncontrolled sawdust, particularly when air born, may under certain circumstances be combustible from sparks or other ignition sources. If a vacuum is difficult to use on a floor sander, complacency is promoted in allowing loose sawdust to accumulate.
Furthermore, for do-it yourself applications, an operator often leases or rents a machine which therefore requires the operator to carry the machine from the rental outlet. If the machine is not easily disassembled to easily carried components, the weight of the machine may cause difficulty for the operator to transport the sander between the rental place and his home.
What is needed is a floor sander that can approach an edge of a floor within the distance of an ordinary shoe molding while reducing noise, that increases control and ease of use, reduces saw dust, and provides other conveniences for making a do it yourself operation feasible.
In accordance with one aspect of the invention, a power sander for a wood floor includes a housing, and a motor mounted to the housing and having a centrally positioned downwardly extending drive shaft. An inner bowl member is positioned within the housing and is rotatably mounted on the drive shaft to allow rotation of the inner bowl with respect to both the housing and drive shaft. A plurality of pulleys are circumferentially spaced about the drive shaft and are rotatably connected to the inner bowl member. The axis of rotation of each pulley is parallel to the axis of rotation of the drive shaft. Each pulley constructed to have sander discs mounted thereon. A plurality of belts, with each belt preferably having a cogged inside and mounted about one pulley and engageably driven by the drive shaft. The drive shaft and said pulleys having respective cogged peripheries for creating a positive engagement with said inner side of the respective belts. A plurality of pulley tensioners engage the outer side of a respective belt with the outer side preferably being flat and frictionally engaged by the pulley tensioners in the form of bearings.
The belts are vertically spaced with respect to the drive shaft at a vertical position adjacent from one another. Each respective pulley is respectively vertically positioned to engage its respective belt horizontally from the engaging vertical position on the drive shaft. Each tensioner also is vertically positioned to a proper height to operably engage its respective belt.
The housing is preferably bell shaped with a downwardly extending side wall and connectable to a vacuum motor for suction of saw dust up through the bell shaped housing. The housing has an aperture for connection to a vacuum hose for allowing vacuuming of sawdust up through the housing and through the aperture. A weighted metal plate is attached to an inner bowl member, said weighted metal plate having apertures for allowing said pulley to extend therethrough. The plate has an outer periphery spaced from said side wall of said housing to define a path for the vacuuming of said saw dust.
It is desirable that a weighted plate is mounted to the inner bowl and has notches at its outer periphery to create widened gaps with the housing to increase air flow therebetween. It is also preferred that the housing has its side walls spaced within xe2x85x9c inches from a sanding disc edge. The housing has handles mounted thereon near a front and rear portion thereof and extending upwardly therefrom. The housing also has a plurality of quick connect pins that removably connect the housing to the operating handle. In accordance with another embodiment of the invention, the center drive shaft has a gear section, these gears are circumferentially spaced about said drive shaft and are rotatably mounted on the inner bowl member in a coplanar fashion and operably engage said center gear section of the drive shaft. The gears having respective pulley sections affixed thereto with the pulley sections being coplanar with each other. The plurality of pulleys are coplanar with each other and with the pulley sections. The belts are also coplanar and engage a pulley section of the respective gear and the pulleys.
In accordance with another aspect of the invention, a vacuum cleaner is mounted to the operable handle. A vacuum hose operably extends from the vacuum cleaner and is resiliently flexible and stretchable from a rest length to an increased length. The distal end of the hose having a shaped nozzle that can receive a hose coupling on the housing allowing the hose to be directly connected to the hose coupling without removal of said shaped nozzle for vacuuming sawdust out of the housing, and with said hose being detachable from said hose coupling to allow said shaped nozzle to be operably used. The vacuum is grounded to ht power sanding machine and preferably has a metal canister.


An epoxy resin composition including an epoxy resin and a curing agent as essential components, in which the curing agent comprises a phenol resin which has each structural moiety of a phenolic hydroxyl group-containing aromatic hydrocarbon group (P), an alkoxy group-containing aromatic hydrocarbon group (B) and a divalent aralkyl group (X), and also has, in a molecular structure, a structure in which the phenolic hydroxyl group-containing aromatic hydrocarbon group (P) and the alkoxy group-containing aromatic hydrocarbon group (B) are bonded with the other phenolic hydroxyl group-containing aromatic hydrocarbon group (P) or alkoxy group-containing aromatic hydrocarbon group (B) via the divalent aralkyl group (X).

An epoxy resin composition comprising an epoxy resin and a curing agent as essential components is excellent in various physical properties such as high heat resistance, constitutional and low viscosity and is therefore widely used for electronic and electrical components such as semiconductor sealing material and printed circuit board, conductive adhesives such as conductive paste, adhesives, matrixes for composite material, coating materials, photoresist materials and color developing materials.
In various uses, particularly advanced materials, further improvement in performances such as high heat resistance and high moisture resistance has recently been required. In the field of semiconductor sealing materials, surface mounting packages such as BGA and CSP are developed and also a reflow treatment temperature increases due to the use of a lead-free solder, and thus electronic component sealing resin materials having excellent resistance to moisture and soldering have been required furthermore.
As a technique for producing the electronic component sealing resin material which meets these required characteristics, for example, there is known a technique in which a methoxy group-containing phenol resin obtained by methoxylating a phenolic hydroxyl group in a resol resin and converting the resulting methoxylated resol resin into a novolak resin in the presence of an acid catalyst is used as a curing agent for epoxy resin, thereby to improve fluidity and to impart moderate pliability to a cured article, and thus improving moisture resistance and impact resistance of the cured article itself (see, for example, Japanese Unexamined Patent Application, First Publication No. 2004-10700).
However, such a curing agent for epoxy resin is inferior in reactivity during the curing reaction because the number of functional groups per molecule decreases.
It is of urgent necessity for a high frequency device to enable high frequency operation in the field of electronic components, and therefore electronic component-related materials such as semiconductor sealing material have low dielectric constant and materials having low dielectric dissipation factor, which have never been obtained, have recently been required. Main factor for an increase in a dielectric constant and a dielectric dissipation factor in an epoxy resin cured article is a secondary hydroxyl group, which appears during the curing reaction, and therefore lower concentration of a functional group serving as a crosslinking point is more advantageous for dielectric characteristics. In this respect, although the hydroxyl group concentration of the curing agent for epoxy resin is decreased, there has never been realized recent required level of low dielectric constant and low dielectric dissipation factor.
As a technique for producing an epoxy resin which exhibits excellent heat resistance, for example, there has been known a technique in which an aromatic compound such as anthracene as an epoxy resin used for a composite material matrix is reacted with an excess crosslinking agent such as p-xylene glycol to obtain a reaction intermediate and the resulting reaction intermediate is reacted with a phenol compound to obtain a phenol resin in which an aralkyl structure and an aromatic compound are alternately arranged, and then the resulting phenol resin is epoxidated by reacting with epichlorohydrin and used (see, for example, Japanese Unexamined Patent Application, First Publication No. Hei 8-301980).
Such an epoxy resin certainly exhibits excellent heat resistance because of high content of an aromatic structure moiety in a polymer structure. However, when the epoxy resin is used as an electronic component sealing material, there has never been realized required level of low dielectric constant and low dielectric dissipation factor. It is considered to further decrease the concentration of a functional group by further introducing an aromatic structure into the polymer chain of the epoxy resin so as to decrease the dielectric constant and dielectric dissipation factor in the epoxy resin. However, it becomes impossible to avoid drastic deterioration of curability as a result of drastic decrease in concentration of the functional group.
As described above, in the field of the electronic component-related material, there has never been obtained an epoxy resin composition having dielectric characteristics capable of coping with recent high frequency operation without causing curing hindrance.

Epoxy resin composition,cured article thereof, semiconductor sealing material, novel phenol resin, novel epoxy resin,method for producing novel phenol resin, and method for producing novel epoxy resin


A thin film device, such as an intravascular stent, is disclosed. The device is formed of a seamless expanse of thin-film (i) formed of a sputtered nitinol shape memory alloy, defining, in an austenitic state, an open, interior volume, having a thickness between 0 5-50 microns, having an austenite finish temperature Af below 37° C.; and demonstrating a stress/strain recovery greater than 3% at 37° C. The expanse can be deformed into a substantially compacted configuration in a martensitic state, and assumes, in its austenitic state, a shape defining such open, interior volume. Also disclosed is a sputtering method for forming the device.

Medical implants are increasing in use in minimally invasive surgery because of the improved medical results attainable. In particular, intravascular stents are used to reinforce blood vessels to promote healing and to prevent stenosis (narrowing) of blood vessels following procedures such as angioplasty. Alloys of titanium nickel (TiNi or Nitinoi shape memory alloy) are gaining popularity over more traditional metals such as stainless steel for use in medical implants because the properties of shape memory and superelasticity enable improvements in design- and methods of deployment of these devices. Demonstrated biocompatibility and novel methods of fabrication have resulted in wide acceptance of orthodontic braces, catheter guidewires, surgical tools, and implantable coronary stents.
Fabrication of stents from drawn TiNi tubes is practical only for a limited range of sizes. In particular, it has not been feasible to make stents having the flexibility and size required for delivery intravascularly through small catheters via the carotid arteries.
There is a growing demand for smaller and thinner, more flexible stents that can be surgically implanted or delivered via catheter, into small diameter, highly tortuous blood vessels. Suitably flexible structures can be fabricated of thin film (2-10 micrometers thick) shape memory alloys that are sputter deposited on a substrate and heat treated. Composition and heat treatment affect the phase transition temperature of the alloy, which in turn determines whether it exhibits shape memory or superelastic properties.
For maximum effectiveness, an intracranial device should be installed through a small diameter catheter, then changed to a pre-determined shape so as to fill a space and apply continuous outward pressure against the blood vessel wall. To accomplish this, three-dimensional shapes such as cylinders, cones, and hemispheres are required, and a shape-changing capability is highly advantageous.

Thin-film shape memory alloy device and method


An apparatus, executing on a server or similar machine and a client machine, and a corresponding method, includes mechanisms for rendering a two-dimensional image of a three-dimensional object, and streaming the thus-rendered image to the client machine. The mechanisms include a rendering module that generates a first image, from a first point of view, having a plurality of pixels, as first image data for display on a client machine, and generates first depth information for one or more of the plurality of pixels, and a compression module that compresses the first image data and the first depth information, wherein the first image data and the first depth information are provided to the client machine. A user input coupled to the rendering module, provides a command to the rendering module to change a point of view from the first point of view to a second point of view, wherein the rendering module generates a second image, as second image data, from the second point of view, the second image including second depth information for one or more pixels comprising the second image. The second image data and the second depth information are then provided to the client machine. The client machine includes a decompression module that receives compressed image data, the compressed image data including depth information related to one or more pixels comprising the three-dimensional representation, and decompresses the compressed image data; a display module that displays the generated images, wherein a first image is displayed; and a warp module that generates an interim image for display based on the image data, including the depth information, and a second point of view.

In a conventional client-server architecture, a remote server may store a three dimensional (3D) model of an object and may deliver various views of the 3D model to connected clients. The delivered 3D model views may contain data necessary to render a two dimensional image of the 3D model at the client. The client then renders and displays the 2D image, and supports user interactions with the 3D model. Such user interaction may include rotating and translating the 3D model, for example, so that different 2D images of the 3D model are displayed. For complex models, a large amount of data may be needed to describe the model's geometric properties so that an image may be rendered at the client. Should the user desire to change views of the object (e.g., rotate the object 90 degrees to the right), the server must send a new set of model data to the client for rendering and display as a new image. Because of bandwidth limitations between the server and the client, and possibly processing limitations at the client, the rendering and display of the new image may be delayed considerably. As a result, the user's perception of an interactive graphics session is detrimentally affected.
One solution to this long-latency problem is proposed in U.S. Pat. No. 6,222,551 B1 to Schneider et al. Here, a server side apparatus renders a selected number of views of an object, and transmits the selected views to the client for display. The client maps the selected views onto facets of the object, and then displays the rendered object, one or more facets at a time. One limitation with this system is that the user is limited to viewing only those precise views that were transmitted to the client and mapped to the object. Thus, for example, the user may be restricted to viewing six sides of a cubical object, with the point of view of each facet of the cubical object at a center of the six facets. The user cannot subsequently rotate or translate the object to alter the view by, for example, 30 degrees left or right.
Another solution to 3D image rendering is described in U.S. Pat. No. 6,111,582 to Jenkins. Here, a technique of primitive reprojection is used in which convex graphics primitives are reprojected elements. Elements known to be visible in a previous frame are first determined by transformation and depth-comparison rasterization of the elements. Regions of the image that may contain newly visible elements are located by occlusion-exposure transitions in a depth (z) buffer and from incremental view volume motion. In these regions, a depth-prioritized data-access method of spatial ray casting is used to identify newly-identified primitives for rasterization. The server-client system uses visibility event encoding in which data representing newly visible and newly invisible primitives for each frame are transmitted to the client for display.

Streaming of images with depth for three-dimensional graphics

Hewlett-Packard Development Company, L.P.


A brake mechanism for a device for hauling up/down by rope, in particular one for the safe hauling up and down by rope of persons and loads. The device has a pulley which preferably has a back stop that prevents the pulley from turning during the roping down. The rope brake mechanism has a rope speed measuring device that cooperate with a rope brake, which acts upon the rope to exert a braking force onto the rope when the rope speed increases above a maximum predetermined speed.

The present invention relates to a brake mechanism for a device for hauling up/down by rope, in particular one for the safe hauling up and down by rope of persons and loads. The device has a pulley which preferably has a back stop that prevents the pulley from turning during the roping down.
In accordance with the European published patent EP-A-0 480 117 by the applicant, such devices for hauling up/down by rope are preferably used for hauling persons or loads up and down on a rope. The preferred area of application is for rescue services or in general as mobile equipment. The devices for hauling up/down by rope essentially function to reduce the retaining force during the roping down in connection with a safety to prevent an uncontrolled dropping of the person or load attached to the rope.
These known devices for hauling up/down by rope have a large-volume pulley equipped with a back stop. In most cases, a rope is placed with 2.5 windings around this pulley. The device is operated such that when pulling up, the pulley is running freely and represents only a low resistance. During the roping down, on the other hand, the pulley is blocked by the back stop and the rope slides over the surface of the pulley. The resulting friction takes over a large portion of the load attached to the rope.
As a safeguard during the roping down, the International Patent Application WO-A-9 717 107 suggests providing a self-activating rope stop on the pull side of the device for hauling up/down by rope. The advantage of this arrangement is that the rope stop only needs to take over a portion of the load since the device for roping up/down accepts the largest portion of the pull.
However, the disadvantage of this solution is that upon reaching the critical roping down speed, the roping down operation is stopped completely. In particular if a roping down speed near the permissible limit, e.g. 2 m/s, is required, a brief exceeding of this speed limit can trigger the stopping of the rope.

Brake mechanism for device for hauling up/down by rope


A new and distinct cultivar of Bougainvillea plant named ‘Kasumi’, characterized by its compact, upright and mounding plant habit; moderately vigorous growth habit; relatively small leaves; freely flowering habit; salmon pink-colored flower bracts; and good garden performance.

The present invention relates to a new and distinct cultivar of Bougainvillea plant, botanically known as Bougainvillea×hybrida and hereinafter referred to by the name 'Kasumi'.
The new Bougainvillea plant is a naturally-occurring branch mutation of a proprietary selection of Bougainvillea×hybrida known as 'Konatu', not patented. The new Bougainvillea plant was discovered and selected by the Inventor on a single flowering plant within a population of plants of 'Konatu' in a controlled greenhouse environment in Tsushima-shi, Aichi, Japan in July, 2004.
Asexual reproduction of the new Bougainvillea plant by cuttings in a controlled greenhouse environment in Tsushima-shi, Aichi, Japan since July, 2007, has shown that the unique features of this new Bougainvillea plant are stable and reproduced true to type in successive generations.


An engine oil solenoid control valve includes a molded one-piece valve nozzle and coil bobbin member that defines a valve nozzle and a solenoid coil bobbin and also defines an integral check valve receiving receptacle at an exhaust port and first and second valve seats for controlling valve stroke. A ball valve is disposed between the valve seats. A simple cylindrical armature rod can be used together with molded integral recesses that balance hydraulic pressure on the armature to prevent a hydraulic lock condition.

Internal combustion engines for motor vehicles are known which include a hydraulic system for performing work in addition to lubrication. This work can be used to activate/deactivate cylinders of an internal combustion engine to conserve fuel. Such a hydraulic valve lifter activation/deactivation system can include a hydraulic control valve in a valve housing mechanically connected to a separate solenoid. The solenoid includes a solenoid coil bobbin on which a wire coil is wound and an armature that moves the control valve in response to an input signal (coil electrical current signal) to the wire coil to control hydraulic pressure in the valve lifter oil control gallery. A separate check valve assembly is mounted in a fluid exhaust passage (vent-to-sump) in the engine block or cylinder head and functions to maintain oil pressure in the oil control gallery at a preselected minimum value. Such engine oil control solenoids comprise numerous components which must be assembled together and are known to suffer from hydraulic fluid (oil) leakage through various paths around the solenoid housing.
An object of the present invention is to provide an engine oil solenoid control valve that is simpler and less costly to make and less prone to hydraulic fluid leakage.