The invention provides for a method for the manufacture of multiwell plates and multiwell filter plates. The plates are the result of a two part construction in which individual filter discs are securely pinned between opposing plates, one of which is insert molded against the other.

The invention relates to a disposable multiwell filter apparatus for use in biological and biochemical assays that can be used and is compatible with existing equipment.
In pharmaceutical and biological research laboratories, plates with a multitude of wells have replaced traditional test tubes for assay and analysis. For many years, multi-well laboratory plates have been manufactured in configurations ranging from 1 well to 384 wells, and beyond. The wells of multi-well plates are typically used as reaction vessels in which various assays are performed. The types of analytical and diagnostic assays are numerous. The typical areas of use include cell culture, drug discovery research, immunology, and molecular biology, among others. Current industry standard multi-well plates are laid out with 96 wells in an 8xc3x9712 matrix (mutually perpendicular 8 and 12 well rows). In addition, the height, length and width of the 96-well plates are standardized. This standardization has resulted in the development of a large array of auxiliary equipment specifically developed for 96-well formats.
Many assays or tests require a mixture of particulate or cellular matter in a fluid medium. The mixture is then subjected to combination with reagents, separation steps and washing steps. The end product of such analysis is often a residue of solid matter which may be extracted for further analysis.
Separation of solids from fluid medium is often accomplished by filtration. The separation is accomplished in or on the filter material by passing the liquid through it. The liquid can be propelled through the membrane either by a pressure differential or by centrifugal force. Filter plates that conform to a 96 well standardized format are known as disclosed in U.S. Pat. Nos. 4,427,415 and 5,047,215. One significant problem that has been encountered with filter plates adapted for use with a 96 well plate is that cross contamination may occur between wells. When a unitary filter sheet is sandwiched between two pieces of plastic molded in a 96 well format, liquid from one well, upon wetting the filter material, may wick through the paper to neighboring wells thereby contaminating the sample contained within that well. One solution to this problem is offered in U.S. Pat. Nos. 4,948,442 and 5,047,215. In these patents, a 96 well filter plate is disclosed comprising a filter sheet placed between two plastic plates. One of the plates has a series of ridges that cut the filter sheet when the plates are ultrasonically welded together. By cutting the filter sheet around each well, the possibility of wicking between neighboring wells is effectively eliminated. A problem with this design is that it limits the product offering to membranes that can be cut by the process and to plate materials that can be ultrasonically welded. In fact, the potential for wicking and cross contamination still exists when the filter material is not completely severed in the welding process.
U.S. Pat. No. 4,427,415 discloses a filter plate of one piece construction having wells with drain holes in the bottom and capable of receiving filter discs into the wells. Wicking is obviously not a problem in this plate because individual filter discs are used as opposed to a unitary sheet of filter paper. The filter discs used in this plate are put into each well individually and are not secured to the bottom of the well. A danger exists with a filter disc that has not been secured down in that some liquid from the well could pass under the filter and thereby escape filtration, resulting in contamination of the filtrate.
Our invention solves several problems of prior art filter plate designs by providing a multiwell filter plate in which 1) filters are securely fastened to the plate without the use of glue or other potentially contaminant chemical adhesives, 2) an expansive variety of filter materials may be used, 3) a large number of thermoplastic components may be employed in its construction, and 4) no cross contamination through liquid wicking occurs between neighboring wells. The preferred embodiment of the present invention also offers a conical nozzle designed to cause exiting fluid to create droplets rather than lateral flow along the bottom of the plate. Further, a ring or skirt will preferably circumscribe the underside of each filter well. The skirt fits into a corresponding well of a receiver plate and is designed to prevent cross contamination that may otherwise occur by splashing of filtrate.
It is therefore an object of the present invention to provide a disposable filtration device for chemical and biological tests in which a large number of samples may be tested simultaneously. Further objects of the present invention are: to provide a filter plate that will be compatible with existing 96 well cluster plate formats as standardized by the industry; to provide a filter plate that can be handled by automated robotic assay equipment; to provide a filter plate having individual wells having a support grid on the bottom to help support the filter element, prevent tearing, and allow for an even distribution of filtered material on the filter; to provide a filter plate in which liquid from one well can not mix with liquid from a neighboring well (the filter plate of the present design prevents lateral flow or cross-talk of liquid through the membrane to other wells); to prevent cross contamination of filtrate after passing through the filter and passing to a receiver plate; to provide a filter plate of two part construction in which each individual well filter is securely pinned between opposing plates that are insert molded against each other; and to provide a unique method for the manufacture of filter plates.
Briefly, the present invention relates to an improved filter plate and its method of manufacture. The filter plate is a two part construction. It comprises a well plate preferably with 96 wells, each well being open on both ends, molded against a harvester plate insert preferably having 96 counter-bores, each containing a filter disc, whereby each counter-bore aligns with a corresponding and respective well from the well plate, and whereby the diameter of the counter-bore is greater than the diameter of the well, such that the well bonds with the outer rim of the counterbore thereby creating a lap joint. The lap joint also serves the purpose of fixing the filter disc securely to the insert without the need for glue or chemical adhesives. During the injection molding process, extremely high pressures in the mold ensure that the edges of the filter disc are pressed against the insert.
The assembled filter plate product has a plurality of interconnected wells of uniform diameter, each well being defined by a circular side wall, each of the side walls being interconnected to the side wall of at least two adjacent wells, each of the wells being open at one end. Further, the plate has a bottom wall at the bottom of each of the wells, which is connected to the side wall, each of the bottom walls having an opening therein. A conical drainage nozzle having an external surface and an internal passage communicating with the opening in the bottom wall, extends downwardly from the bottom wall from a point radially inward from the side wall. Finally, a filter disc is positioned on top of the bottom walls of the wells, the peripheries of each filter being sandwiched between a bottom portion of the side wall of each well and a top portion of the bottom wall of each well. The bottom walls have an opening therein, the opening preferably taking the form of a funnel shaped nozzle. A support grid preferably extends across the opening in order to provide support for the filter disc.
The method of manufacturing the plate comprises several steps, namely: forming an insert having a plurality of counter-bores; punching filter discs into the bottom surface of the counter-bore; and insert molding a well plate against the insert and filters such that wells from the well plate align with corresponding counter-bores from the insert thereby forming a lap joint that effectively secures the filter disc in place. The method can be extended for use in the manufacture of multiwell plates which do not have a filter, but require a well bottom of a different material than the side walls.

Method of manufacture for a multiwell plate and/or filter plate


A magnetic induction device having at least one secondary induction assembly including a secondary winding is mounted on a rotary element. A magnetic flux is induced the secondary induction assembly, causing an induced secondary alternating current in the secondary winding of the secondary induction assembly. The secondary alternating current is converting to direct current and is stored in an electrical storage device.

1. Field of the Invention
The present invention relates to an apparatus for controlling the transfer of power to a rotary element without the use of wires. It is useful in electroplating apparatus and more particularly, for recharging batteries which supply power to rotating elements in a rotary plater.
2. Description of the Background Art
There are many applications for devices with rotary elements which require some supply of electric current or charge to portions of the rotating elements. Electroplating is one of these applications. Electroplating has been used in the manufacture of thin film electronic components and magnetic read/write heads for disk drives. The quality of devices manufactured by this process is very sensitive to the uniformity of the metal films that are deposited. Uniformity of thickness is crucial as well as uniformity of composition of the deposit.
Using magnetic head manufacture as an example, the process is carried out by starting with a substrate, which has a conductive seed metal layer deposited on a planar surface (referred to as the xe2x80x9ctopxe2x80x9d even though in most plating steps, this surface will actually face downward into the plating solution), the deposition of the seed metal usually having been accomplished by a vacuum deposition or sputtering process. A photo-resist stencil is placed on top of this conductive metal layer. The substrate is then connected to an electrical power supply, with the substrate becoming the cathode (usually) with respect to the plating bath when voltage is applied. An anode (for most purposes) is created in the form of a plate connected to a positive terminal of the power supply, submerged in a plating bath. The substrate is also placed to be in contact with the plating bath, usually just barely interfacing with the surface of the bath so that the face surface (top) of the substrate engages the liquid but the edges and reverse surface of the substrate do not. Positively charged metal ions (cations) are drawn to the negatively charged substrate, and a layer of metal accumulates on the exposed seed metal surface, until the desired thickness has been achieved.
As mentioned above, a primary concern is the uniformity of thickness of the metal deposit. In an effort to obtain more uniformity, one kind of electroplating device spins the substrate to minimize the effects of localized variation in ion concentrations in the electroplating solution. Although this generally improves uniformity, there may still be problems of non-uniformity with radial displacement across the substrate. The biggest factor in this non-uniformity is generally the drop off in electric field strength found near an edge or corner of the plating target area of the substrate. A particular element from the central portion of the plating target area which is bounded on all sides by identical elements can be presumed to have a generally uniform electrical field applied over its extent. An element at an edge of the plating target area, however, which does not have identical neighboring elements on all sides, can be expected to have an electric field which differs in strength and configuration from that found in interior elements. This element attracts metal ions differently and thus can result in a non-uniform deposition layer in these regions.
In an effort to compensate for these xe2x80x9cedge effectsxe2x80x9d it has become common practice to include what is called a xe2x80x9cthieving ringxe2x80x9d around the perimeter of the substrate. This thieving ring is also negatively charged and serves to restore uniformity to the electric field at the edges of the substrate by providing similarly charged neighboring elements. The outer perimeter of the thieving ring has edge effects of its own, but is treated as a sacrificial element where the uniformity of metal deposition is unimportant.
Early thieving rings were constructed in one piece so that a uniform field was supplied around the entire perimeter of the substrate. However, it has been found that by segmenting the ring, and applying differing currents to the different segments, finer control of the electric field configuration could be achieved. This is especially useful when processing substrates and chip arrays on substrates which are not completely circular. For processing of substrates and arrays which are perhaps rectangular, or otherwise configured to have corners or protrusions, it is very beneficial to be able to adjust the charge on those specific thieving ring segments near those corners or protrusions in order to achieve more uniform field strength and thus achieve greater uniformity of deposition.
One problem in using a thieving ring having a number of segments is that power must be supplied to each segment independently from the others in order to optimize the electrical field. Therefore, at least one wire is required to be attached to each segment. In current practice, it is common to have sixteen segments, each with its own power supply wire. This number may increase to an even larger number of segments if finer control of the field configuration is desired. In addition, there are four wires required to supply power to the substrate itself. Thus, there may be a minimum of twenty wires involved. This number is increased when it may be necessary to sense the voltage and current on each supply wire in order to ensure that the proper fields are generated. In dealing with this great number of wires, the problem is compounded by the rotary nature of the cathode. Rotary connectors have an intrinsic problem relating to the difficulty of maintaining reliable electrical connections with a rotating element. Such connections are very prone to noise and friction effects. Any noise generated in the connection can be detrimental to the uniformity of the electric field and thus the uniformity of the deposition layer. When trying to maintain twenty to forty such rotary electrical connections, the odds of failure are thus greatly increased.
Power can be transferred to the cathode and the thieving ring segments through the shaft of the motor which drives the rotation of the cathode. A controller such as a microprocessor can then be mounted on the rotary substrate structure to control the current distribution to the thieving ring segments. Although it is theoretically possible to share part of the plating current from the plating power supply to power the microprocessor through the motor shaft as well, in practice, it has been found to be difficult to implement. Microprocessors and associated electronics are sensitive to plating supply fluctuations, which may stay at zero current for long periods of time. Thus an appropriate voltage divider storage and regulation circuit to supply power to the microprocessor is necessarily bulky, generates heat, and may interfere with the electroplater""s performance. Further, the power supply to the substrate is typically a very highly sensitive constant current supply and it is desirable to avoid introducing variables which might affect the field generated about the substrate.
To address these problems, a battery can be mounted on the rotary cathode structure to supply power to the microprocessor. However, the rotary cathode, which may run at speeds of 1-50 RPM during plating, can run at as much as 5,000 RPM, when the plate is spun to dry it. The forces generated during such high-speed rotation can make mechanical fastening of batteries too costly, too heavy or too unreliable. Consequently, batteries have typically been hand-soldered in place, which necessitates a lengthy replacement operation when the batteries become depleted. Batteries which are rechargeable in place are therefore preferred, but again, there is the problem of transferring power across a rotating interface to charge them.
Many prior patents have dealt with the problems of improving uniformity of plating by using a rotary cathode plater.
U.S. Pat. No. 5,785,826 to GREENS PAN describes an apparatus for electroforming in which the entire cathode head is mounted on a lead screw by which the distance between the cathode and anode can be adjusted, in order to control uniformity of deposition.
U.S. Pat. No. 5,628,892 to Kawashima describes an electroplating apparatus and method using an arcuate segmented anode. Electroplated metal foil is produced by depositing metal ions from an electroplating bath on the surface of a rotating cathode drum. This device produces metal foil with minimized thickness variations.
U.S. Pat. No. 5,472,592 to Lowery discloses an electroplating apparatus in which a cathode plate both rotates and revolves around the inner surface of an electroplating tank.
Electrical connections are made through an elaborate series of concentric contact bushings which form three electrically isolated conducting paths to evenly distribute current to a substrate.
U.S. Pat. No. 4,304,641 to Grandia describes an electroplating cell having a rotary cathode using a thieving ring. A flow-through jet plate is used to provide differential flow distribution for the plating solution. Variable resistors, to keep the current constant, control electrical current to the cathode and ring.
Each of these patented devices uses either a rotating or revolving cathode in an effort to produce improved uniformity of plating, but none of these address the problem of providing reliable and noise-free supply of power to a microprocessor and associated electronics without using wires.
It is, therefore, an object of the present invention to provide an improved method and apparatus for reliably supplying power to a rotary element such as a microprocessor mounted on the cathode structure of a rotary plater. Other objects and advantages will become apparent from the following disclosure.
The present invention relates to an apparatus and method for supplying power to rotary devices and particularly to a microprocessor mounted on a rotary cathode structure.
The method comprises: i) providing a magnetic induction device having at least one secondary induction assembly including a secondary winding on a rotary element; ii) inducing a magnetic flux in the secondary induction assembly, thereby causing an induced alternating current in the secondary winding of the secondary induction assembly; iii) converting the secondary alternating current to direct current; and iv) storing the current in an electrical storage device.
The apparatus used to effectuate the method comprises: i) a rotating assembly which includes a secondary induction assembly having a secondary core and a secondary winding; ii) a magnetic induction device which produces an alternating current in the secondary winding of the secondary induction assembly; iii) a converter for converting the induced alternating current to direct current; and iv) an electrical storage device which stores the electric power. One more specific application of this more general apparatus is used in a rotary cathode plater, as described in detail below.
A more through disclosure of the present invention is presented in the detailed description which follows and the accompanying figures.

Apparatus for wireless transfer of power to a rotating element

International Business Machines Corporation


A process for producing solid creatine-containing dosage forms, wherein

A process for producing solid creatine dosage forms and dosage forms obtainable thereby.
The invention relates to a process for producing solid creatine-containing dosage forms and to the dosage forms obtainable thereby.
The amino acid derivative creatine occurs in nature in particular as creatine phosphate in vertebrate muscle. Creatine phosphate acts in this case as energy carrier in the cell for muscular contraction energy. Creatine is absorbed from the food or synthesized endogenously in the pancreas and liver. It can be isolated from natural sources or be synthesized by guanylation of sarcosine. Creatine is used as food supplement in the therapy of neuromuscular disorders (e.g. muscular dystrophy) and endocrinopathies associated with insufficient creatine storage and increased excretion in the urine. Besides the use in culture media and as flavor enhancer in spices, creatine is increasingly being employed as food supplement in sport to increase physical capacity and, in particular, in body building.
Creatine occurs in the form of a monohydrate which is stable under ambient conditions. The known pharmaceutical preparations of creatine always contain this monohydrate form. Thus, WO 99/00122 describes the production of creatine granules by mixing creatine monohydrate with an aqueous polyvinylpyrrolidone solution and other excipients. The moist granules are dried at 45xc2x0 C. and compressed to tablets. The process has the disadvantage that several time-consuming and costly steps are necessary to obtain tablets. The resulting tablets contain 100 mg of creatine monohydrate in a tablet weighing 135 mg, equivalent to 5.0 mmol/g creatine tablet weight.
In addition, creatine dosage forms are commercially available in the form of two-piece gelatin capsules with a creatine monohydrate content of about 70%, equivalent to 4.7 mmol of creatine based on the weight of the capsule in g. The production and the filling of two-piece gelatin capsules are likewise time-consuming and costly.
The creatine content of these known dosage forms based on creatine monohydrate cannot be increased straightforwardly because the content of binder or the capsule shell as a proportion of the total weight cannot be reduced below a critical value without impairing the mechanical properties of the dosage form. Creatine monohydrate contains 12% by weight of water of crystallization. Since the water of crystallization has no physiological effect, it would be impossible to obtain solid dosage forms with a higher molar creatine content by use of a creatine hypohydrate or anhydrous creatine. However, these creatine forms are poorly defined and, moreover, hygroscopic. For this reason, they would lead to dosage forms which are unstable in the surrounding air.
A process which has been known for some time for producing solid pharmaceutical forms is the so-called melt calendering in which an active ingredient-containing, essentially solvent-free melt of a polymeric binder is extruded, and the extrudate is shaped to the desired drug form, for example in a calender with molding rolls, see EP-A-240 904, EP-A-240 906, EP-A-337 256 and EP-A-358 105. Polymers of N-vinylpyrrolidone or copolymers thereof, for example with vinyl acetate, in particular are employed as polymeric binder. The formation of the active ingredient-containing melt in this case is generally achieved at a temperature of about 150xc2x0 C.
The use of melt calendering for producing solid creatine dosage forms has not been described to date. It is unavoidable in melt calendering that the active pharmaceutical ingredient is exposed to relatively high temperatures. Since creatine starts to undergo thermal decomposition, in particular to creatine, at temperatures of about 80xc2x0 C., it was not obvious to use melt calendering for producing creatine-containing dosage forms.
Surprisingly, it has been found that solid creatine dosage forms can be produced in a process which can be used economically on the industrial scale, comprises few process steps and makes it possible to produce stable creatine dosage forms with a high molar content of creatine.
The invention relates to a process for producing solid creatine-containing dosage forms, wherein
a) a mixture which comprises at least one thermoplastic, physiologically tolerated, water-soluble or water-swellable polymeric binder and creatine, and contains 1 to 20 mol of water per mol of creatine is prepared,
b) the mixture is plasticated at or above the softening point of the polymeric binder, preferably with at least partial evaporation of the water,
c) the plasticated mixture is shaped to dosage forms and cooled.
The invention additionally relates to the dosage forms obtainable by the process. It further relates to a creatine-containing solid dosage form comprising at least 3.3 mmol of creatine, based on the weight of the dosage form in g, in fine dispersion or molecular dispersion in a matrix composed of a thermoplastic, physiologically tolerated, water-soluble or water-swellable polymeric binder.
The term xe2x80x9csolid dosage formxe2x80x9d is intended to refer to a presentation which is suitable in particular for oral or rectal administration and has any desired forms such as, for example, tablets, coated tablets, pastilles, pellets, granules and the like.
The mixture prepared in step a) contains 1 to 20 mol, preferably 1 to 15 mol, in particular 3 to 10 mol, of water per mol of creatine. The water content is composed of the content bound to creatine as water of crystallization and the xe2x80x9cfreexe2x80x9d water in the mixture. This water presumably on the one hand acts at elevated temperature as temporary plasticizer for the water-soluble or water-swellable polymeric binder, and on the other hand limits, through its enthalpy of vaporization, the thermal stress on the creatine.
The mixture can be prepared by starting from the dry, anhydrous components and mixing them with the required amount of water. However, it is more expedient to use creatine monohydrate, i.e. a creatine hydrate with 1 mol of water of crystallization per mol of creatine. Also suitable are creatine monohydrate forms which contain, beyond their content of water of crystallization, also unbound water which, for example, adheres as moisture to the surface of the crystallites or is trapped between the crystal system. Such forms are obtained when an aqueous suspension of creatine monohydrate, which is usually the initial result of chemical synthesis of creatine, is filtered or centrifuged. The filtration residue or centrifugation residue contains, for example, 5 to 50% by weight, usually 15 to 30% by weight, of adherent water which is not bound as water of crystallization. The use of the filtration residue or centrifugation residue with residual moisture has the additional advantage that drying to give creatine monohydrate is unnecessary.
Creatine is generally prepared industrially by guanylation of sarcosine, i.e. transfer of the guanyl radical (carbamimidoyl radical) to sarcosine or its salts. Suitable guanylating agents are O-alkylisourea salts, in particular O-methylisourea methyl sulfate (cf. JP 59000, DE 197 48 696 or DE-A 198 60 048.8) or cyanamide (cf. EP 0754 679).
The polymeric binder is usually employed in an essentially anhydrous form, i.e. preferably not as solution or dispersion. Many water-soluble or water-swellable polymeric binders absorb moisture on storage under ambient conditions. This results in an equilibrium moisture content of, for example, 1 to 5% by weight. These forms are regarded as xe2x80x9cessentially anhydrousxe2x80x9d for the present purposes.
In the process of the invention, creatine is embedded as a fine dispersion or molecular dispersion in a matrix of a water-soluble or water-swellable polymeric binder, preferably with formation of a solid solution. In this way there is stabilization of creatine hypohydrates (i.e. hydrates with less than 1 mol of water of crystallization per mol of creatine) or anhydrous creatine, so that dosage forms produced according to the invention are stable under ambient conditions even if they contain less than 1 mol of water per mol of creatine content.
Normally 15 to 70 g, preferably 40 to 70 g, of thermoplastic, physiologically tolerated, water-soluble or water-swellable polymeric binder are employed per mol of creatine. Preferably, the composition of the mixture is chosen so, and/or the amount of water evaporated in the plastication is such, that the plasticated mixture contains at least 3.3 mmol, preferably at least 4.2 mmol and, in particular, at least 5.1 mmol, e.g. 5.1 to 5.4 mmol, of creatine based on the weight of the plasticated mixture in g. The plasticated mixture preferably contains less than 1 mol of water per mol of creatine. The figures stated apply correspondingly to the resulting dosage forms.
Water-soluble or water-swellable polymeric binders contain units of hydrophilic monomers, where appropriate in conjunction with units of hydrophobic monomers. They can be assigned inter alia to the natural or modified polysaccharides; polyalkylene oxides which are solid at room temperature; homopolymers and copolymers of hydrophilic, ethylenically unsaturated monomers such as N-vinylamides, ethylenically unsaturated mono- and dicarboxylic acids, (meth)acrylamide, hydroxyalkyl (meth)acrylates and the like.
Examples of suitable binders are:
Polyvinylpyrrolidone (PVP), copolymers of N-vinylpyrrolidone (NVP) and vinyl esters, in particular vinyl acetate, copolymers of vinyl acetate and crotonic acid, partially hydrolyzed polyvinyl acetate, polyvinyl alcohol, poly(hydroxyalkyl acrylates), poly(hydroxyalkyl methacrylates), copolymers of methyl methacrylate and acrylic acid, polyacrylamides, polyethylene glycols, polyvinylformamide (where appropriate partially or completely hydrolyzed), cellulose esters, cellulose ethers, in particular methylcellulose and ethylcellulose, hydroxyalkylcelluloses, in particular hydroxypropylcellulose, hydroxyalkylalkylcelluloses, in particular hydroxypropylethylcellulose, cellulose phthalates, in particular cellulose acetate phthalate and hydroxypropylmethylcellulose phthalate, and mannans, in particular galactomannans. Of these, particular preference is given to polyvinylpyrrolidone, polyethylene glycol, copolymers of N-vinylpyrrolidone and vinyl esters, poly(hydroxyalkyl acrylates), poly(hydroxyalkyl methacrylates), alkylcelluloses and hydroxyalkylcelluloses, especially the polyvinylpyrrolidones and vinylpyrrolidone/vinyl acetate copolymers having the proprietary name Kollidon(copyright).
Binders which are advantageously used as polymeric binders are those having a K value (according to Fikentscher, Cellulose-Chemie 13 (1932), p. 58-64, 71-74) in the range between 10 and 100, preferably between 15 and 80, in particular of about 30.
The most preferred polyvinylpyrrolidones have a K value in the range between 20 and 60.
Dosage forms of the invention preferably contain at least one of the polymeric binders described above. They may additionally contain other binders. The properties of the solid creatine-containing dosage forms of the invention can be varied through the nature of the binder chosen or the mixture of different binders. In particular, it is possible in this way to control the creatine release.
It should be possible to convert the polymeric binder into a plastic state in the complete mixture of all the components in the range from 50 to 150xc2x0 C., preferably 60 to 130xc2x0 C. The softening point is reduced if necessary by conventional pharmacologically acceptable plasticizing excipients. However, the mixture preferably contains no plasticizer. Examples of such plasticizers are:
long-chain alcohols, ethylene glycol, propylene glycol, glycerol, trimethylolpropane, triethylene glycol, butanediols, pentanols, such as pentaerythritol, hexanols, polyethylene glycols, polypropylene glycols, polyethylene/propylene glycols, silicones, aromatic carboxylic esters (e.g. dialkyl phthalates, trimellitic esters, benzoic esters, terephthalic esters) or aliphatic dicarboxylic esters (e.g. dialkyl adipates, sebacic esters, azelaic esters, citric and tartaric esters), fatty acid esters such as glycerol mono-, di- or triacetate or sodium diethyl sulfosuccinate, of which polyethylene glycols and polyethylene/propylene glycols are preferred.
The use of a plasticizer results in a decrease in the softening point of the polymeric binder. The formation of the plastic mixture and the shaping can thus take place at lower temperatures, thereby limiting the polymer molecular weight reduction and the thermal decomposition of the creatine. If plasticizers are used, they are employed in an amount of less than 30% by weight, usually 1 to 15% by weight, based on the polymer component.
In preferred embodiments, the dosage forms produced according to the invention comprise at least one sugar alcohol such as, for example, mannitol, sorbitol, xylitol and, in particular, isomalt. The sugar alcohol is preferably employed in an amount of from 10 to 60 g, in particular from 15 to 45 g, per mol of creatine. The inclusion of a sugar alcohol allows the melt viscosity of the plasticated mixture to be set in a defined manner in the stated temperature range. The sugar alcohol also acts as solubilizer and leads to faster creatine release.
Dosage forms obtained according to the invention may comprise pharmaceutically acceptable excipients. Such excipients may facilitate the production of the dosage form and/or modulate the properties thereof. Examples of conventional pharmaceutical excipients, whose total amount can be up to 100% by weight based on the polymeric binder are
the abovementioned plasticizers;
extenders and bulking agents, such as silicates or diatomaceous earth, magnesium oxide, aluminum oxide, titanium oxide, methylcellulose, sodium carboxymethylcellulose, talc, sucrose, lactose, cereal or corn starch, potato flour, in particular in a concentration of from 0.02 to 50, preferably 0.20 to 20, % by weight, based on the total weight of the mixture;
lubricants, glidants and mold release agents such as magnesium, aluminum and calcium stearates, talc and silicones, and animal or vegetable fats, in particular in hydrogenated form and those which are solid at room temperature. These fats preferably have a melting point of 30xc2x0 C. or above. Triglycerides of C12, C14, C16 and C18 fatty acids are preferred. Waxes, such as carnauba wax, can also be used. These fats and waxes may advantageously be admixed alone or together with mono- and/or diglycerides or phosphatides, in particular lecithin. The mono- and diglycerides are preferably derived from the abovementioned fatty acid types. The total amount of lubricants and mold release agents is preferably 0.1 to 10% by weight;
flow regulators, for example diatomaceous earths, in particular the silicone dioxides of high purity which have the proprietary name Aerosil(copyright), in an amount of from 0.1 to 5% by weight based on the total weight of the mixture;
disintegrants, e.g. sodium starch glycolate;
dyes, such as azo dyes, organic or inorganic pigments or dyes of natural origin, preference being given to inorganic pigments in a concentration of from 0.001 to 10, preferably 0.5 to 3, % by weight, based on the total weight of the mixture;
stabilizers such as antioxidants, light stabilizers, hydroperoxide destroyers, radical scavengers, stabilizers against microbial attack;
it is also possible to add wetting agents, preservatives, adsorbents and mold release agents, and surfactants, preferably anionic and nonionic such as, for example, soaps and soap-like surfactants, alkyl sulfates and alkyl sulfonates, salts of bile acids, alkoxylated fatty alcohols, alkoxylated alkyl phenols, alkoxylated fatty acids and fatty acid glycerol esters, which may be alkoxylated, and solubilizers such as Cremophor (polyethoxylated castor oil), Gelucire, vitamin E TPGS and Tween (ethoxylated sorbitan fatty acid esters) (cf., for example, H. Sucker et al. Pharmazeutische Technologie, Thieme-Verlag, Stuttgart 1978).
The selection of suitable excipients is based on expert knowledge as described, for example, in Fiedler, H. B., Lexikon der Hilfsstoffe fxc3xcr Pharmazie, Kosmetik, und angrenzende Gebiete, 4th edition, Aulendorf: ECV-Editio-Cantor-Verlag (1996).
In the process of the invention for producing solid creatine-containing dosage forms, the components are usually first mixed together. The mixture is then preferably plasticated, i.e. converted to the plastic state, with at least partial evaporation of the water content. The sequence of the steps of mixing and plasticating is, however, not obligatory. The production and plastication of the mixture may also overlap to some extent or take place simultaneously in apparatuses suitable for this purpose.
The mixture is plasticated by heating, usually with additional input of mechanical energy, for example by kneading, mixing or homogenizing. The mixture is preferably plasticated at temperatures of from 50 to 150xc2x0 C., particularly preferably from 60 to 130xc2x0 C. The plastication takes place in an apparatus customary for this purpose. Extruders having, in a cylindrical housing, one or more rotatable axles equipped with kneading and/or conveying elements are particularly suitable. It is alternatively possible to employ heatable containers with agitator, for example kneaders. However, the plastic mixture is preferably formed by extrusion. The plastication process steps can be carried out in a known manner, for example as described in EP-A-0 240 904, EP-A-0 337 256, EP-A-0358 108, WO 97/15290 and WO 97/15291. The contents of these publications and, in particular, the statements contained therein about melt extrusion are incorporated herein by reference.
Extruders which can be employed in the process of the invention are single-screw machines, intermeshing screw machines or else multiscrew extruders, in particular twin-screw extruders, co-rotating or counter-rotating and, where appropriate, equipped with kneading disks. Since at least part of the water present in the mixture is evaporated during the extrusion, the extruders are generally equipped with an evaporation section. Particularly preferred extruders are those of the ZKS series from Werner und Pfleiderer.
The shaping to the dosage form before solidification can take place in a variety of ways, depending on the viscosity of the plastic mixture, for example by casting, injection molding, compression, nipping or calendering. This is done by conveying the plastic mixture described above to one or more shaping steps in the process of the invention. The conveying can take place by pressing, pumping, e.g. with gear pumps, or preferably with an extruder.
The first shaping step advantageously takes place when the extrudate emerges from the extruder through suitably shaped dies, draw plates or other orifices, e.g. through a breaker plate, a circular die or a slit die. This usually results in a continuous extrudate, preferably with a constant cross section, e.g. in the form of a ribbon or of a strand, preferably with a circular, oval, rounded or flat and broad cross section.
Suitable downstream shaping steps for extrudates are, for example, cold cut, i.e. the cutting or chopping of the extrudate after at least partial solidification, hot cut, i.e. the cutting or chopping of the extrudate while still in the plastic form, or pinching off the still plastic extrudate in a nip device. It is possible with hot or cold cut to obtain, for example, granules (hot or cold granulation) or pellets. Hot granulation usually leads to dosage forms (tablets or pellets) with a diameter of from 0.1 to 10 mm, while cold granulation normally leads to cylindrical products with a length to diameter ratio of from 1 to 10 and a diameter of from 0.5 to 10 mm.
It is possible in this way to produce monolayer but also, on use of coextrusion, open or closed multilayer drug forms, for example oblong tablets, coated tablets, pastilles and pellets.
The drug forms can be provided with a coating by conventional methods in a downstream process step. Suitable materials for film coatings are the polymers mentioned as polymeric binders, in particular polyacrylates, such as the Eudragit(copyright) types, cellulose esters such as the hydroxypropylcellulose phthalates, and cellulose ethers such as ethylcellulose, hydroxypropylmethylcellulose or hydroxypropylcellulose and gelatin. Further shaping steps may also follow, such as, for example, rounding off the pellets obtained by hot or cold cut using rounding-off devices as described in DE-A-196 29 753.
In a suitable embodiment, the plastic mixture is conveyed to a molding calender for the shaping. Suitable molding calenders normally have at least two molding rolls and/or belts, with at least one of the molding rolls and/or at least one of the belts having depressions to receive and shape the plastic mixture. It is preferred to use a molding calender with pairs of counter-rotating molding rolls, with at least one of the molding rolls having on its outer surface depressions for receiving and shaping the plasticated mixture. It is possible with the aid of these molding calenders to produce granules and tablets of any desired size and shape. Suitable molding calenders are disclosed, for example, in EP-A-0 240 904, EP-A-0 240 906 and WO 96/19962, and in EP-A-0 358 105, which are incorporated herein by reference.
The dosage forms of the invention are used, for example, as drugs for the therapy of diseases associated with deficient creatine storage or with increased creatine excretion. The creatine-containing dosage forms of the invention are additionally suitable as food supplements for enhancing performance in sport, especially in strength sport.

Process for producing solid creatine dosage forms and dosage forms obtainable thereby


A linear bushing attachable to a structural member is formed of a tubular body having a tail part and a lead part forward of said tail part, the tubular body defining a cylindrical wall about a central longitudinal axis and having inner and outer surfaces. First and second sets of resiliently bendable arms extend respectively from the lead part and from the tail part, the arms of each set being spaced apart circumferentially and extending generally forwardly and radially inwardly. The arms of each set have distal ends with inner surfaces which define a bore of first diameter, these arms of each set being deflectable radially outward to define between the inner surfaces of their distal ends a bore of greater diameter than the first diameter. Each of these arms when deflected radially outward applies a resilient opposite radially inward force. The bushing further includes attachment elements on the outer surface of the tubular body for attaching the tubular body to a structural member, with the first and second sets of arms being spaced apart axially forward and rearward respectively of the attachment means.

1. Field of the Invention
The invention is in the field of linear bushings which are mounted to a panel or other structural element, where each such linear bushing has a central bore in which a rod or bolt is situated and may be axially slidable.
2. Description of the Prior Art
A linear bushing is used to provide a slidable connection between two structural members, where, typically, the first member is a panel and the second member is a rod or bolt. For the discussion that follows the term xe2x80x9crodxe2x80x9d will be used to include a rod, bolt or other element that is positionable within the bore of the bushing. The bushing is to maintain such rod in proper relative position and orientation while it moves axially and/or while it is axially stationary. To insure such freedom of movement merely requires a sliding or clearance fit; however, for mass-produced bushings and rods inserted therein, it is quite possible for the fit to be too loose due to manufacturing tolerance stack-ups, namely the combined dimensional variations in the rod diameter, in the bore diameter of the bushing, and in the panel hole diameter in which the bushing is secured. Typically, a tolerance stack-up results in a fit so loose that the rod will rattle within the bushing, which might occur while the rod is moving axially or while it is axially still. Such rattling is worsened when the rod is subjected to lateral, tilting and/or vibration forces and when the dimensional stack-up increases due to wear.
Some prior art bushings or grommets include a set of flexible arms which extend from a wall of the bushing to engage and press radially inward on the rod situated within such arms. These arms sometimes are initially compressed radially inward when the bushing is inserted into the aperture of a panel, and subsequently they expand to define a diameter less than the outside diameter of the rod. Thus, these arms will bear inwardly against the rod at a specific axial location at one end or the other of the bushing; however, the portion of the loose-fitting rod not engaged by the flexible arms will still be able to tilt or rattle. A variety of prior art bushings and grommets may be seen in U.S. Pat. Nos. 2,424,757, 2,664,458, 5,733,046, 5,664,888, 5,476,350 and 4,874,276, none of which provides a structure as disclosed herein.
The present invention is a new linear bushing structure that greatly reduces or eliminates any excess looseness of the rod within the bushing bore by applying inward radial force via two sets of flexible arms located respectively both above and below the panel. These arms are in constant contact with the rod whether it is stationary or moving axially and whether it is aligned coaxially with the bushing or tilted, and even when the rod is urged and moved laterally. At all times at least one flexible arm above and one flexible arm below the panel is resiliently bearing against the rod and thus preventing it from rattling. In actual use of the new linear bushing the rod is usually engaged at all times by two or more of these flexible arms above the panel and by two or more of these arms below the panel.
Accordingly, even if there is a tolerance stack-up due to excess bore diameter of the bushing and/or excess bore diameter of the panel aperture and/or reduced outside diameter of the rod, the flexible arms will always contact and apply appropriate force above and below the panel to stabilize the rod within the bushing.
It is thus an object of this invention to provide a linear bushing that compensates for tolerance stack-up and assures a good sliding fit with a rod in all conditions normally encountered.
It is a further object to provide a linear bushing that is simple and economical to manufacture, and simple and reliable to use.
By utilizing this new structure to compensate for variations in critical dimensions of the respective components, it is now possible to have mass production of these bushings without highly expensive manufacturing equipment otherwise required to maintain very close tolerances. Thus, the new invention permits great economy of manufacture while still producing a simple and reliable product that is also better in use than known prior art linear bushings.
The new linear bearing has a tubular body having a lead end for insertion into an aperture in a panel or other structural element and an opposite tail end. This tubular body is formed by a cylindrical wall having an inner surface which defines a bore about a central axis and an outer surface. There is a first set of flexible arms extending from the lead end axially in the lead-end direction and radially inwardly, with the terminal ends of these arms defining a bore diameter that is smaller than the diameter of the rod to be inserted into the bushing. These arms are spaced apart circumferentially, but are otherwise similar in dimensions and shape. Non-uniform arms might be used in specific situations.
The new bearing further includes a second set of flexible arms extending from the bore surface of the bushing axially in the lead-end direction and radially inwardly. The terminal ends of these arms also define a bore diameter that is smaller than the outer diameter of the rod to be inserted therein. These upper and lower sets of arms are flexible, but strong and resilient so as to constantly apply a stabilizing force on the rod regardless of whether it is moving, stationery, tilted or urged laterally.
Finally, there are panel mounting elements for attaching the bushing to a panel or other structural member, these elements typically comprising one fixed element extending transversely outward from the tubular body, and axially spaced therefrom one or more movable resilient elements also extending transversely outward. In the first embodiment shown herein the fixed element is a radially outwardly extending disc or other form of lateral projection from the outer surface of the cylindrical body and situated axially between said upper and lower sets of flexible arms. Cooperating with such fixed element are projections or tabs which are either flexible and resilient or are attached to a flexile and resilient portion of the tubular body. The fixed element and flexible elements are axially spaced apart a distance generally corresponding to the thickness of the panel on which the bushing is to be mounted.
In use, this bushing is inserted lead-end first through the aperture in the panel. The tabs deflect inward to allow the lead part to pass through the aperture until the panel mounting element bars further axial motion of the bushing. The bushing then becomes locked onto the panel, barred by the tabs and the fixed element from further axial movement. The sets of flexible arms are situated above and below the panel, and a rod, when inserted or otherwise positioned within the bore of the bushing, is xe2x80x9ccapturedxe2x80x9d by the sets of flexible arms, which assure a snug sliding fit and significant reduction of tolerance stack-up, resultant rattling or other defective operation.
Numerous variations in the structure of the new linear bushing are possible as shown in the drawings appended hereto and as described in the detailed description of same as follows.


A sack trolley (1) comprises a support frame (2) presenting a lower pair of carrying wheels (4) and a hoist mechanism (6) for climbing steps, which comprises a lifting arm (10) equipped with support rollers at its free end and which can be swivelled about a swivelling axis (S) parallel to the carrying wheel axis (L) by means of a crank drive (8). In order to achieve step-climbing assistance which is simple, space-saving, easy to handle and functionally safe, the lifting arm (10) is comprised of a swing guide component (11) swivel-mounted about the swivel axis (S) and a support component (12) taking up the support rollers (13) and longitudinally displaceable compared to the swivel guide component (11), whereby the crank drive (8) is articulated on the support component (12) with its crank arm (9).

The present invention relates to a sack trolley having a support frame presenting a lower pair of carrying wheels and upper handles and a hoist mechanism for climbing steps, which comprises a lifting arm equipped with return rollers at its free end and which can be swivelled about a swivelling axis parallel to the carrying wheel axis by means of a crank drive.
A similar sack trolley is disclosed in EP 0 533 650 B and its hoist mechanism for climbing steps has thoroughly proven itself, whereby the lifting arm designated as support frame engages in a crank guide solid with the support frame by way of a guide member in its longitudinal central region, and its end averted from the free end with the return roller is articulated on the crank arm of the crank drive. Because of the cooperation of support frame, crank drive and crank guide the support wheels describe a stilt movement reaching forwards or backwards with switching on, off and reversing of the drive motor, by means of which the support frame, is lifted as it travels up over the steps with the carrying wheels over the support wheels now resting on the ground and the support frame is transferred to the next highest step, or as it travels backwards the support wheels grip downwards on the next lowest step and as a result lower the support frame with the carrying wheels. This hoist mechanism thus requires considerable structural expense and is also associated with a corresponding space requirement which impairs the handiness of the sack trolley and undesirably increases its tare weight. Further to this, because the centre of gravity is misplaced upwards due to the hoist mechanism there is less stable handling of the trolley as it climbs steps, and not least of all in tricky situations the result is unsafe climbing assistance adapted minimally to the step profiles of the step due to the stilt movements of the support wheels.
The object of the invention is therefore to create a sack trolley of the type mentioned at the outset, which is distinguished by its easily handled and functional hoist mechanism with a simple and compact structure.
The invention solves this task in that the lifting arm is comprised of a swing guide component swivel-mounted about the swivel axis and a support component taking up the support rollers and longitudinally displaceable compared to the swivel guide component, whereby the crank drive is articulated on the support component with its crank arm. The free end of the support component is moved on the one hand by the superposition of the swivel movement of the swivel guide component effective thereon and the rotary movement of the crank arm on the other hand along an approximately reinform curved path, resulting in trouble-free climbing assistance according to the direction of movement with the support component and its support rollers. When the sack trolley is in a position corresponding to the travel position the support rollers of the support component are set engagingly on the next highest step tread for travelling up a step, are supported there and raise the trolley from one step to the other. On the contrary, during descent the support rollers remain supported on the respective upper step and the trolley is lowered by way of the lifting arm to the next lowest step, giving rise to a simple and functionally safe raising and lowering movement for automatic step travel. The lifting arm with the crank drive can be accommodated without difficulty in narrow spaces, for example between the carrying wheels of the sack trolley, and thereby alters the centre of gravity position of the sack trolley only insignificantly, in addition to which the hoist mechanism does not weigh excessively because of its simple structure and barely increases the tare weight of the trolley noticeably. The path of motion of the support rollers is influenced by appropriate adaptation of the crank throw, axle position, lifting arm length, articulation point of the crank throw on the support component and the like and is adapted to different step profiles, whereby the passage speeds of the path of the support rollers are adapted to the respective functional areas and the empty run and vertex areas are passed through more quickly than the lifting or lowering areas required for climbing steps.
A path of motion for the support rollers best adapted to normal use with climbing steps occurs when the crank axis lies in the direction of the support frame above the swivel axis, whereby the crank axis preferably lies above and the swivel axis lies below the swivel carrying wheel axis, and whereby the distance of the crank axis from-the support frame is preferably greater than that of the swivel axis, and the distance of the carrying wheel axis from the support frame is greater than that of the crank axis.
To facilitate assembly of the hoist mechanism and also to be able to subsequently alter the curved path for the support rollers the hoist mechanism plus the crank drive and lifting arm are designed as assembly unit and attached displaceably to the support frame, such that the assembly unit can be mounted problem-free with few hand grips and can be adjusted in place, leading to change in position of the swivel and crank axes and thus to relative displacement of the curved path of the support rollers.
It is particularly advantageous if the support rollers of the support component are equipped with a combined free-wheel and brake device which releases rotating of the support rollers in terms of the trolley travelling backwards, but which brakes counter-rotation of the support rollers. Release of the rotary movement of the support rollers in one direction and their braking instead of blocking in the counter-rotation direction facilitates climbing steps with the assistance of the hoist mechanism, since the position of the support rollers on the steps can be corrected effortlessly by the driver of the trolley without losing the necessary support effect of the support rollers.


The present invention is directed to microemulsion techniques for rapidly preparing photochromic glass nanoparticles and to the photochromic glass nanoparticles so prepared. More particularly, the method of the invention comprises the combination of two microemulsions, one containing a water-soluble silver salt and a glass precursor and the other containing a halide salt and an initiator for glass formation, which process rapidly yields silver halide particles. This invention gives nanometer-sized silver halide particles embedded in glass, thus providing photochromic glass nanoparticles without further annealing, or at most mild annealing. These nanoparticles are valuable as added components to any macro-material that one might wish to have photochromic properties. The particles would impart photochromism while not affecting the physical properties of the material.

This invention is directed to a process for production of colloidal photochromic glass nanoparticles, that is, unagglomerated particles of ca. 100 nm or less in diameter.
Nanotechnology, defined broadly as the manufacturing and application of nanometer-sized materials (e.g. nanoparticles), is experiencing unprecedented research and development, largely due to the unique and valuable properties of such materials. In particular, the application of nanoparticles to macro-sized materials can add novel properties to the macro-sized material, without alteration of desired physical properties inherent to the macro-material. These synergies do not exist when two macro-materials are combined.
One method for the controlled syntheses of numerous types of nanoparticles is xe2x80x9cmicroemulsion-mediatedxe2x80x9d synthesis. This technique consists of combining differing amounts of two immiscible liquids and a surfactant or surfactant mixture. A surfactant is an ambiphilic molecule containing at least two segments, each of which is soluble in one of the two immiscible liquid phases. Surfactants act by decreasing the surface tension between the two phases, resulting in a dispersion of droplets called xe2x80x9cmicellesxe2x80x9d, between 2 and 50 nm in size, with the lesser volume of liquid (the disperse phase) within the other liquid (the continuous phase). Most commonly, the continuous phase is water and the dispersed phase is a hydrocarbon oil. A dispersion of water in oil is called a reverse micelle dispersion.
The reverse micelles function as xe2x80x9cnano-reactorsxe2x80x9d for reactions of molecules that dissolve exclusively in the aqueous phase. Brownian motion causes the micelles to continuously collide, coalesce, and break apart, resulting in constant exchange of the contents of the micelles. The addition of a reverse micelle dispersion or aqueous solution of reactant A to a reverse micelle dispersion of reactant B will cause reaction between A and B to afford product C as micelles containing the reactants collide and coalesce.
While highly controllable, the size of the nanoparticles produced is not directly related to micelle size and is not easily correlated to the concentration of reactants. An important factor governing particle size is the ratio R of the rate of nucleation (rn) to the rate of growth or agglomeration (rg), where R=rn/rg. A large ratio provides many, very small particles, whereas a smaller ratio results in fewer, larger particles. These competing factors can be empirically controlled by variation of reactant concentration and microemulsion compositional parameters (stirring speed, surfactant choice, amount of surfactant used, and temperature). Shah has reviewed the state of the art in this area. (Pillai et al., Adv. In Coll. and Interface Sci., 55,241 (1995)).
These techniques have been employed to produce mono-disperse inorganic nanoparticles, which can be purified on an industrial scale through cross-flow membrane filtration (U.S. Pat. No. 5,879,715). Mono-disperse glass nanoparticles have also been produced by addition of basic aqueous solutions to a reverse micelle emulsion containing silica sol and other inorganic glass components (U.S. Pat. No. 5,837,025). The basic solution causes precipitation of glass nanoparticles within the micelles. The resulting nanoparticles are isolated by temperature-induced phase separation, washing, and centrifugation.
Photochromic glass absorbs visible light (darkens) upon exposure to actinic radiation, e.g. ultraviolet light, and ceases absorption (fades) when the actinic radiation is removed. This reversible behavior is ascribed to nanocrystalline silver halide particles dispersed in the glass. Reversible ionization of the silver halide causes the photochromic effect. It is noteworthy that the silver halide particles must be isolated for reversibility; this is the function of the glass. In many embodiments, small amounts of copper(I) salts are also embedded in the glass; the copper sensitizes the silver halide particles to UV light.
In typical production, the silver halide is included in the glass melt and the melt is shaped into the desired form and cooled. Often, the shaped product is not photochromic and must be heated to a temperature between the annealing point and the softening point of the glass, typically between 500xc2x0 and 900xc2x0 C. This heating allows for a phase separation of the silver halide within the glass. The resulting nanocrystals need to be 5 nm or greater in size to exhibit photochromic behavior. It would be desirable to develop a process of forming nanoparticles of silver halide and embedding them in glass. Such a process would avoid the extra costs associated with the annealing process.
At present there are no methods described in the literature for preparing photochromic glass nanoparticles.
The present invention is directed to microemulsion techniques for rapidly preparing photochromic glass nanoparticles and to the photochromic glass nanoparticles so prepared.
More particularly, the method of the invention comprises the combination of two microemulsions, one microemulsion containing a water-soluble silver salt and glass precursors and the other microemulsion containing a halide salt and an initiator for glass formation, which process rapidly yields glass-encased silver halide particles. This invention gives nanometer-sized (preferably about 100 nm or less in diameter) unagglomerated silver halide particles embedded in glass, thus providing photochromic glass nanoparticles without further annealing, or at most mild annealing. Preparation of these nanoparticles can be at ambient or slightly elevated temperature. These nanoparticles would be valuable as added components to any macro-material that one might wish to have photochromic properties. The particles would impart photochromism while not affecting the physical properties of the material. In one embodiment of the invention, the photochromic glass nanoparticles comprise reactive sites on their surface to allow attachment of the nanoparticles to macro-materials.
This invention is further directed to fibers, yarns, fabrics (which may be woven, knitted, stitch-bonded or nonwoven), other textiles, or finished goods (encompassed collectively herein under the terms xe2x80x9ctextilesxe2x80x9d or xe2x80x9cwebsxe2x80x9d) treated with the photochromic glass nanoparticles. Such textiles and webs exhibit the property of reversible, light-induced darkening.
The method of the present invention comprises two parallel but non-interactive reactions, namely the formation of silver halide and the formation of glass. The reactions occur coincidentally in the same reverse micelle reactors. The reactions are initiated by combining two distinct precursor microemulsions. Each precursor microemulsion is chemically stable, as it contains only one or some of the components for each reaction. The components for formation of a silver halide nanoparticle are a water-soluble silver salt and a halide salt. The components for formation of glass are a glass composition comprising glass precursors and an initiator of glass formation. It is apparent that the precursor microemulsions must be constructed such that the reactive components are kept apart until mixing, but no other restriction on the microemulsion composition is implied. Thus, one preferred embodiment consists of a first precursor microemulsion containing a soluble silver salt and the glass-forming components, and a second precursor microemulsion containing a halide salt and an initiator of glass formation.
The precursor microemulsions are prepared by methods known in the art (see, for example, U.S. Pat. No. 5,837,025). The particulars of the preparation can be determined by one of skill in the art without undue experimentation.
Those skilled in the art will recognize that the rates of the two reactions are different. Insoluble silver halide particles form almost instantaneously when silver salts and halide salts are combined, whereas glass synthesis occurs at a slower rate. In the present invention, as the reactions occur in the combined reverse micelles, the resulting silver halide nanoparticles will remain dispersed within the micelles. Glass formation will then encase the suspended silver halide nanoparticles within a glass matrix. In a preferred embodiment, one precursor microemulsion contains silver nitrate and the other contains sodium chloride.
The glass precursor composition comprises glass-forming components. The composition generally comprises a source of silica, such as a silica sol (a colloidal dispersion of glass). Glass sols are commercially available in a variety of compositions. In addition, the glass composition may include, but is not limited to, silicon dioxide (SiO2), aluminum oxide (Al2O3), calcium oxide (CaO), disodium oxide (Na2O), zinc oxide (ZnO), diborate (B2O3), or mixtures thereof. These may be present in the precursor composition as salts, examples of which are: aluminum nitrate-nonhydrate, calcium nitrate-tetrahydrate, sodium acetate, boric acid, and zinc nitrate-hexahydrate.
The initiator for glass formation can be any material that precipitates or solidifies the glass precursor composition. Glass particles can be generated in the microdroplets of the emulsion via precipitation reactions that can occur by varying or changing the pH value. In one embodiment, the addition of base to a silica glass sol initiates the aggregation of the colloids into larger particles. The base may consist of any base capable of inducing sol aggregation. Presently preferred bases are alkali hydroxides and alkali earth hydroxides. Sodium hydroxide is particularly preferred.
Alternatively, dissolved glass in dispersed, alkaline aqueous droplets may be solidified/precipitated by acidification of the reverse microemulsion. In this embodiment, any acid capable of initiating solidification may be employed as the initiator for glass formation. Halide acids are particularly preferred in this embodiment as they can induce both silver halide nanoparticle formation and glass formation.
In one embodiment of the invention, capping agents are added to the combined microemulsion upon formation of the glass nanoparticles. These agents will perform up to three functions: they will form a coating around the glass, which will prevent agglomeration of the nanoparticles; they will provide reactive sites to allow attachment of the nanoparticles to macro-materials; and they may induce preferential dispersion of the nanoparticles into an aqueous phase. Preferred embodiments of the capping agents are combinations of alkylalkoxysilanes, epoxide-substituted alkoxysilanes, and quaternary ammonium-substituted alkoxysilanes, but any molecules that would react with the hydroxyl-terminated surface of the glass are considered to be capping agents within the scope of this invention. The capping agents, as well as any other species that mediates the capping reaction, may be added as a solution or a microemulsion.
The reactive sites or functional groups of the capping agents may be selected from those groups that will bind chemically with a particular structural element, macro-material, fiber, yarn, fabric, or finished good. For example, all cellulosic-based webs contain hydroxyl groups. Wool and other proteinaceous animal fibers, silk, and regenerated proteins contain hydroxyl, amine, carboxylate, and thiol groups (the latter as disulfides). It is desirable for the reactive sites to contain functional groups that are reactive to the fiber. For example, the capping agents may contain adjacent carboxyl groups that can form five- and six-membered cyclic anhydrides. The anhydrides form with the aid of a catalyst when the capping agent is heated and dried. These cyclic anhydrides react with fibers that contain hydroxyls or amines (e.g. cotton or wool). Alternatively, the reactive groups may contain epoxide groups or epoxide precursors, such as halohydrins. Epoxides can react with amines and hydroxyls. The capping agent may also comprise an N-methylolamide group, which reacts with hydroxyl groups at high temperatures and acidic pH. Anhydride groups are presently preferred.
Specific amine-reactive groups include isothiocyanates, isocyanates, acyl azides, N-hydroxysuccinimide esters, sulfonyl chlorides, aldehydes, glyoxals, epoxides, oxiranes, carbonates, arylating agents, imidoesters, carbodiimides, anhydrides, and halohydrins. Carboxylate-reactive groups include diazoalkanes and diazoacetyl compounds, carbonyl diimidazole, and carbodiimides. Hydroxyl-reactive functional groups include epoxides, oxiranes, carbonyl diimidazole, N,Nxe2x80x2-disuccinimidyl carbonate or N-hydroxysuccinimidyl chloroformate, alkyl halides, isocyanates, and halohydrins. Hydroxyl groups may also be oxidized enzymatically or with periodate. Thiol groups react with haloacetyl and alkyl halide derivatives, maleimides, aziridines, acryloyl derivatives, arylating agents, and thiol-disulfide exchange reagents such as pyridyl disulfides, disulfide reductants, and 5-thio-2-nitrobenzoic acid.
Surface coverage of the capping agents may in a later step be further enhanced by contacting these particles with linker molecules, such as a polymer or polymer precursor for example, containing functional groups that react with the particles. These polymers or polymer precursors can assist as anchors to attach the nanoparticles to macroscopic materials through entanglement or chemical reaction. Each linker molecule may have more than one type of functional group, but at least one of the types of functionality will belong to a group that is reactive with the macro-material to be treated. The linkers may be grafted onto the glass nanoparticles prior to treatment of the macro-material, or they may be an additional component applied to the macro-material along with the glass nanoparticles. In the latter case, the linkers will bind to both the nanoparticles and the macro-material during the curing process. In one embodiment of the invention, the photochromic glass nanoparticles are attached via the functional groups of the capping agents to N-methylol resin compounds. These N-methylol compounds are then covalently attached to a textile or web, for example. The N-methylol-containing compounds thus act as attachment bridges or linkers between the glass nanoparticles and the textile. In the practice of the invention, the N-methylol compound may react first with either the fabric or the glass nanoparticle. An additional advantage is that the N-methylol-containing compound, when present in an appropriate amount will provide a durable press finish to the final nanoparticle-treated textile or web. Alternatively, there may be two or more linker molecules that are employed to link the photochromic glass nanoparticle to the textile.
After formation of the glass nanoparticles containing encased silver halide kernels, the combined emulsion must be separated to recover the nanoparticles. Prior to this final recovery step, the microemulsion may be heated to promote completion of reactions and annealing of all glass. The small size of the nanoparticles and the isolated nature of the dispersed phase ensure expedient annealing.
A significant problem with the use of microemulsion production techniques in the past has been the separation of nanoparticles from the microemulsion on any scale larger than bench-top synthesis. The most common technique is centrifugation, which is not suited for large-scale production. Cross-flow membrane filtration with an ultra-fine ceramic membrane is better suited for large-scale production, but the filters are very expensive and may become clogged. In this invention, the capping procedure is designed so that the coated particles will preferentially disperse in one of the phases. For example, capping with quaternary ammonium-substituted alkoxysilanes will produce a charged surface with a bias towards dispersion in an aqueous phase. Alternatively, capping with alkylalkoxysilanes will produce low surface energy particles which will preferentially disperse in an oil phase. After capping, an extraction with the preferred dispersal phase is employed to generate a phase separation, effectively overwhelming the surfactant. The phases are separated and the colloidal phase may be used directly or concentrated to isolate the nanoparticles. Alternatively, the mixture may be sprayed into a heated column. While the liquid dispersants evaporate, the particles fall to the bottom of the column and are collected in an aqueous bath.
The capped particles may be chemically attached to macroscopic materials by reaction of either the capping agent or a polymer bonded to the capping agent with reactive groups on the macroscopic surface. Alternatively, an uncapped particle may be exposed to a reactive, polycationic polymer, which would electrostatically coordinate to the negatively charged silica surface; the reactive portion of the polycationic polymer could then be used for chemical attachment to macroscopic materials. The nanoparticles may also optionally be dispersed in a coating material which is then applied to a macroscopic material. The coating adheres to the macroscopic material and holds the nanoparticles in place through entanglement.
The photochromic nanoparticles and material treated therewith have the property of light-induced, reversible darkening. That is, when exposed to light, the particles and treated material will darken. Upon removal of the light source, the particles and material will revert to their original shade. This invention is therefore useful in any application where reversible darkening is a desired property. In the textile industry, such darkening may be of interest as a fashion item or as a useful feature of items such as sheer drapery.
This invention is further directed to fibers, yarns, fabrics, textiles, or finished goods (encompassed herein under the terms xe2x80x9ctextilesxe2x80x9d and xe2x80x9cwebsxe2x80x9d) treated with the photochromic glass nanoparticles. Such textiles or webs exhibit the property of reversible, light-induced darkening.
The novel webs of the present invention include fibers and/or filaments; woven, knitted, stitchbonded, and non-woven fabrics derived from natural, man made, and/or synthetic fibers and blends of such fibers; cellulose-based papers; and the like. They can comprise fibers in the form of continuous or discontinuous monofilaments, multifilaments, fibrids, fibrillated tapes or films, staple fibers, and yarns containing such filaments and/or fibers, and the like, which fibers can be of any desired composition. The fibers can be of natural, man made, or synthetic origin. Mixtures of natural fibers, man-made-fibers, and synthetic fibers can also be used. Included with the fibers can be non-fibrous elements, such as particulate fillers, flock, binders, sizes and the like. The textiles and webs of the invention are intended to include fabrics and textiles, and may be a sheet-like structure [woven (including jacquard woven for home furnishings fabrics) or non-woven, knitted (including weft inserted warp knits), tufted, or stitch bonded] and may be comprised of any of a variety of fibers or structural elements. The nonwovens may be stitch bonded, ultrasonic bonded, wet laid, dry laid, solvent extruded, air or gas blown, jet interlaced, hydroentangled, and the like, and may have a broad variety of properties including stretch, air permeability, or water vapor breathability. Examples of natural fibers include cotton, wool, silk, jute, linen, and the like. Examples of manmade fibers derived primarily from natural sources include regenerated cellulose rayon, Tencel(copyright) and Lyocell, cellulose esters such as cellulose acetate, cellulose triacetate, and regenerated proteins. Examples of synthetic fibers or structural elements include polyesters (including polyethyleneglycol terephthalate), wholly synthetic polyesters, polyesters derived from natural or biologic materials such as corn, polyamides (including nylon, such as nylon 6 and 6,6), acrylics, olefins such as polyethylene or polypropylene, aramids, azlons, modacrylics, novoloids, nytrils, aramids, spandex, vinyl polymers and copolymers, vinal, vinyon, and the like, and hybrids of such fibers and polymers.
To prepare webs having permanently attached photochromic glass nanoparticles, the fiber, the yarn, the fabric, or the finished good is exposed to a solution or dispersion/emulsion of the surface-capped photochromic glass nanoparticles (in one embodiment, preferably further surface-reacted with a polymer), by methods known in the art such as by soaking, spraying, dipping, fluid-flow, padding, and the like. If needed for the reaction, a catalyst is also present in the medium. The textile-reactive functional groups on the nanoparticle surface (either the surface capping agent or reacted polymer) react with the textile or web, by covalent bonding, to permanently attach to the textile. This curing can take place either before or after the treated textile is removed from the solution and dried, although it is generally preferred that the cure occur after the drying step.
In one embodiment, surface-capped photochromic glass nanoparticles reacted with a polymer containing excess hydroxyl groups are suspended in an aqueous solution that contains a compound having two or more N-methylol groups, such as DMDHEU or DMUG, and a Lewis acid catalyst, such as MgCl2. A surfactant may be used to help suspend the particles. The fiber, the yarn, the fabric, the nonwoven web, or the finished good to be treated is then exposed to the solution containing the nanoparticles and the N-methylol-containing compounds, by methods known in the art such as by soaking, spraying, dipping, fluid-flow, padding, and the like. The N-methylol groups react with the web, by covalent bonding, and the functional groups on the surface of the nanoparticles react with the N-methylol-containing compounds to permanently attach the particles to the web. The treated web is then removed from the solution and dried.
The concentration of the photochromic glass nanoparticles in solution can be from about 0.05% to about 95%, preferably from about 0.1% to about 75%, more preferably from about 0.75% to about 50%, or from about 0.1% to about 5%; depending, however, on the rheological characteristics of the particular polymer nanoparticle selected (such as size or material) and on the amount of silver halide-loading or photochromic activity desired.
In preparing the treated textiles and webs of the invention, the process temperature can vary widely, depending on the affinity of the textile-reactive functional groups for the substrate. However, the temperature should not be so high as to decompose the reactants or damage the web, or so low as to cause inhibition of the reaction or freezing of the solvent. Unless specified to the contrary, the processes described herein take place at atmospheric pressure over a temperature range from about 5xc2x0 C. to about 180xc2x0 C., more preferably from about 10xc2x0 C. to about 100xc2x0 C., and most preferably at xe2x80x9croomxe2x80x9d or xe2x80x9cambientxe2x80x9d temperature (xe2x80x9cRTxe2x80x9d), e.g. about 20xc2x0 C. The time required for the processes herein will depend to a large extent on the temperature being used and the relative reactivities of the starting materials. Therefore, the time of exposure of the web to the polymer in solution can vary greatly, for example from about one second to about two days. Normally, the exposure time will be from about 1 to 30 seconds. Following exposure, the treated web is dried at ambient temperature or at a temperature above ambient, up to about 200xc2x0 C. The pH of the solution will be dependent on the web being treated. For example, the pH should be kept at neutral to basic when treating cotton, because cotton will degrade in acid. Additionally, the deposition of nanoparticles with charged groups (e.g., amines, carboxylates, and the like) is expected to be dependent on solution pH. Salts (such as, for example, NaCl) may optionally be added to increase the rate of adsorption of anionic and cationic photochromic glass nanoparticles onto the web fibers. Unless otherwise specified, the process times and conditions are intended to be approximate.
The following examples are intended for illustrative purposes only and are in no way intended to be limiting.

Photochromic glass nanoparticles and methods of preparation


An object is to increase field effect mobility of a thin film transistor including an oxide semiconductor. Another object is to stabilize electrical characteristics of the thin film transistor. In a thin film transistor including an oxide semiconductor layer, a semiconductor layer or a conductive layer having higher electrical conductivity than the oxide semiconductor is formed over the oxide semiconductor layer, whereby field effect mobility of the thin film transistor can be increased. Further, by forming a semiconductor layer or a conductive layer having higher electrical conductivity than the oxide semiconductor between the oxide semiconductor layer and a protective insulating layer of the thin film transistor, change in composition or deterioration in film quality of the oxide semiconductor layer is prevented, so that electrical characteristics of the thin film transistor can be stabilized.

1. Field of the Invention
The present invention relates to a semiconductor device including an oxide semiconductor, a display device including the semiconductor device, and a manufacturing method thereof.
2. Description of the Related Art
In recent years, liquid crystal display devices typified by liquid crystal displays are becoming widespread. As liquid crystal displays, active matrix liquid crystal display devices where pixels are each provided with a thin film transistor (TFT) are often used. In thin film transistors included in an active matrix liquid crystal display device, amorphous silicon or polycrystalline silicon is used for an active layer. A thin film transistor including amorphous silicon has low field effect mobility, but can be easily formed over a large-sized substrate such as a large glass substrate. On the other hand, a thin film transistor using polycrystalline silicon has high field effect mobility, but needs a crystallization process such as laser annealing and takes an enormous amount of time to be formed over a large-sized substrate such as a large glass substrate.
In view of the foregoing, techniques in which a thin film transistor is manufactured using an oxide semiconductor instead of the above silicon material and applied to electronic devices or optical devices have attracted attention. For example, Patent Document 1 and Patent Document 2 disclose a technique in which a thin film transistor is manufactured using zinc oxide or an In—Ga—Zn—O-based oxide semiconductor as an oxide semiconductor film and such a transistor is used for a switching element or the like of an image display device.
[Reference]
    [Patent Document 1] Japanese Published Patent Application No. 2007-123861    [Patent Document 2] Japanese Published Patent Application No. 2007-096055

Semiconductor device and method for manufacturing the same

Semiconductor Energy Laboratory Co., Ltd.