The present invention provides a method of treating urinary incontinence in a mammal which comprises administering an effective amount of a competitive NMDA antagonist.

A variety of common clinical bladder disorders are characterized by spastic or hyperactive bladder smooth muscle, and the ability to store only small quantities of urine. These dysfunctions range from severe hyperactivity, seen following recovery from major spinal cord damage or spinal transection, to mild bladder detrusor hyperactivity, seen in large numbers of patients and due to a variety of causative factors. The causative factors for this latter group of patients include Parkinsonism, multiple sclerosis, cerebrovascular damage, cerebral arteriosclerosis, central nervous system lesions, and a recurrent bladder infection. The major symptoms of these patients are: frequency, nocturia, urgency, and urge incontinence. The treatment of these patients is generally directed to facilitating urine storage by inhibiting bladder contractility or increasing outlet resistance by enhancing sphincter activity.
Pharmacologic management is usually the first type of treatment attempted. A variety of pharmacologic agents have been used to treat these patients, including muscarinic anticholinergics, tricyclic antidepressants, calcium antagonists, .beta.-andrenergic agonists, and prostaglandin inhibitors. Anticholinergic agents, such as propantheline, oxybutynin, or dicyclomine, alone or in combination with a tricyclic antidepressant, such as imipramine, have proven useful in some patients with bladder hyperactivity. However, nearly 50% of these patients have little or no response to present pharmacological therapies. The consequences of therapeutic failure are costly, and often require serious surgical procedures, such as bladder over-distension, peripheral bladder denervation, or selective sacral rhizotomy. The need for novel pharmacologic approaches for management of these patients is generally agreed upon by urologists.
Incontinence is divided into two types, urge and stress. The urge incontinence type has been further divided into two subtypes in the classical literature, motor urge incontinence and sensory urge incontinence. Motor urge incontinence implies that there is excessive excitatory efferent input to the sacral spinal micturition center from supraspinal centers. Motor urge incontinence accompanies Parkinsonism, multiple sclerosis, cerebrovascular damage, cerebral arteriosclerosis, and central nervous system lesions. Sensory urge incontinence implies excessive sensory input to the sacral spinal micturition center from the bladder primary afferent fibers. Sensory urge incontinence typically accompanies spinal cord injury and bladder infection.
The excitatory amino acids are an important group of neurotransmitters that mediate excitatory neurotransmission in the central nervous system. Glutamic acid and aspartic acid are two endogenous ligands that activate excitatory amino acid (EAA) receptors. There are two types of EAA receptors, ionotropic and metabotropic, which differ in their mode of signal transduction. There are at least three distinct ionotropic EAA receptors characterized by the selective agonist that activate each type: the NMDA (N -methyl-D-aspartic acid), the AMPA (2-amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic acid), and the kainic acid receptors. The ionotropic EAA receptors are linked to ion channels that are permeable to sodium, and, in the case of NMDA receptors, calcium. Metabotropic receptors, linked to phosphoinositide-hydrolysis by a membrane associated G-protein, are activated by quisqualic acid, ibotenic acid, and (1S,3R)-1-aminocyclopentane 1,3-dicarboxylic acid.
The NMDA receptor is a macromolecular complex consisting of a number of distinct binding sites that gate an ion channel permeable to sodium and calcium ions. Hansen and Krogsgaard-Larsen, Med. Res. Rev., 10, 55-94 (1990). There are binding sites for glutamic acid, glycine, and polyamines, and a site inside the ion channel where compounds such as phencyclidine (PCP) and MK-801 exert their antagonist effects.
Competitive NMDA antagonists are compounds which block the NMDA receptor by interacting with the glutamate binding site. The ability of a particular compound to competitively bind to the NMDA glutamate receptor is determined using a radioligand binding assay. See Murphy et al., British J. Pharmacol., 95, 932-938 (1988). The antagonists are distinguished from the agonists using a rat cortical wedge assay. See Harrison and Simmonds, British J. Pharmacol., 84, 381-391 (1984). Examples of competitive NMDA antagonists include D-2 amino 5-phosphonopentanoic acid (D-AP5), D-2-amino-7-phosphonoheptanoic acid (D-AP7), CGS19775, CPPene, and CGP37849. Schoepp et al., J. Neur. Transm., 85, 131-143 (1991).
Antagonists of neurotransmission at NMDA receptors may prove to be useful therapeutic agents for the treatment of neurological disorders. U.S. Pat. No. 4,902,695 is directed to series of competitive NMDA antagonists useful for the treatment of neurological disorders, including epilepsy, stroke, anxiety, cerebral ischemia, muscular spasms, and neurodegenerative disorders such as Alzheimer's disease and Huntington s disease. U.S. Pat. No. 4,968,878 is directed to a second series of competitive NMDA receptor antagonists useful for the treatment of similar neurological disorders and neurodegenerative disorders.
Bladder activity is controlled by parasympathetic preganglionic neurons in the sacral spinal cord. DeGroat et al., J. Auton. Nerv. Sys., 3, 135-160 (1981). In humans, it has been shown that the highest density of NMDA receptors in the spinal cord are located at the sacral level, including those areas that putatively contain bladder parasympathetic preganglionic neurons. Shaw et al., Brain Res., 539, 164-168 (1991). Because NMDA receptors are excitatory in nature, pharmacological blockade of these receptors would suppress bladder activity. Recent studies have shown that MK-801, a non-competitive NMDA antagonist, increases the volume necessary to elicit micturition and decreases the amplitude of the micturition contraction. Maggie et al., Eur. J. Pharmacol, 181, 105-109 (1990); Yoshiyama et al., Neurosci. Lett., 126, 141-144 (1991). However, these studies have shown that the inhibitory effects of MK-801 are not stereospecific, suggesting that non-specific effects of MK-801 mediated the bladder inhibition. Also, these studies have shown that MK-801 produces endocrine effects that are dissociated from its NMDA antagonism. A separate study has shown that the administration of MK-801 to conscious, freely-moving rats produces an increase in the frequency of micturition. Vera and Nadelhaft, Neurosci. Lett., 134, 135-138 (1991).

Use of competitive NMDA receptor antagonists in the treatment of urinary incontinence


A blind having a blind operating mechanism and a blind control element and having an enclosure for the blind control element, with the element completely enclosed, a connector supporting the enclosure on the blind, and depending downwardly, and a drive device at the lower end of the enclosure for operating the element.

Blinds for building openings, eg windows, doors and the like, may be operated either simply down and up, in the case of eg. roller blinds, or in the case of eg. vertical shade panels, the vertical shade panels may be rotated open or closed.
The control elements for these blind operations are usually in the form of an endless cord or chain. The control element simply hangs down along one side of the building opening, in an endless loop.
Other forms of blinds and window coverings may also be operated by means of an endless control element hanging in a loop.
In the past this system has been widely used, and experience was believed to be mainly satisfactory. In some cases a pendant weight was located on the loop, to assist in controlling it.
U.S. Pat. No. 4,932,456, inventor G Buxbaum, shows the usual form of blind chain and drive sprocket gear on the blind roller such as being standard in the art.
However safety considerations for some time have been forcing Government agencies seek further ways to restrict unsafe or unwanted access to the endless loop type of control element. The intent of these considerations has been mainly to prevent any chance that the element, may possibly create a hazard to children, or handicapped persons, or even pets.
In addition, by guiding and controlling the loop of the element, its operation by anyone becomes somewhat easier. The element is prevented from becoming twisted, or entangled with any other blinds controls, curtains or the like.
A simple pulley, fixed to the building fabric, and holding the loop in tension, was proposed to achieve this result. However such a pulley may become dislodged or loosened from the building to which it was attached. The guide pulley will then hang loose on the loop of the element, leaving the element uncontrolled, as before.
This led to accidents and unsafe conditions.
In other cases the pulley might have been installed incorrectly.
In U.S. Pat. No. 8,539,645 Inventor Mario M Marocco, there is shown a form of lock for a blind cord loop control in which a spring operated lock is used.
One of the problems in simply attaching the lower end of the loop to a pulley, is that the pulley, in whatever form it took, was attached to the window frame.
This meant that the customer who wished to adjust the blind had to stand close to the window to reach the chain. This may have been an inconvenience to many.
To prevent unsafe conditions and accidents it is now proposed that the element will be enclosed, blocked or shielded. Also, while rendering the system safe, preferably, the entire control system should not be actually anchored at its lower end to the window frame. It should be at least be somewhat moveable so that a customer could reach for the control without having to actually stand alongside the window.
U.S. Pat. No. 9,038,696, Aaron Lava, issued May 2015, shows a form of a rigid wand, holding the chain in tension, but otherwise the chain is fully exposed outside of the elongate or wand.
Adjustment of the chain was performed manually by simply grasping the chain exposed on one side or the other of the wand. This proposal still does not meet the problem of safety. Children, or even pets, could easily reach the chain exposed on each side of the wand.
A generally similar proposal is shown in U.S. Pat. No. 8,967,226, W D Vesta, issued Mar. 3, 2015. This proposal describes a rigid wand with pulleys top and bottom. The chain is substantially exposed along each side of the wand. It would not satisfy the requirements for safety.
Other arrangements are shown in U.S. Pat. No. 3,022,819, U.S. Pat. No. 5,752,558, U.S. Pat. No. 4,865,109, U.S. Pat. No. 6,192,293, U.S. Pat. No. 5,797,441, U.S. Pat. No. 5,845,696 and U.S. Pat. No. 4,865,109


A monolithically integrated MOS-circuit with a substrate bias voltage generator is disclosed. A generator, a control loop, a threshold voltage detector, and a pump circuit are provided. An acceleration of the regulation of the substrate bias voltage is achieved wherein the output signal of an oscillator is connected to the Reset or Set input of a RS flip-flop. The two outputs of the flip-flop are applied in common to the substrate of the MOS-circuit via a respective pump circuit. A control loop with the threshold voltage detector serving for the regulation of the substrate bias voltage controls the flip onset via an additional input of the flip-flop and, thus, the substrate bias voltage.

The invention relates to a semiconductor circuit with at least two field effect transistors united in a semiconductor crystal with insulated control electrodes and coincident conductivity type of their source and sink zones which are surrounded in common by a semiconductor area of the opposite conductivity type. A generator exhibiting an oscillator and a control loop with a threshold voltage detector is provided for generating an auxiliary voltage V.sub.BB to be applied between the semiconductor area of the opposite conductivity type and ground. This auxiliary voltage is applied to the parts of the semiconductor circuit to be loaded via a pump circuit provided at the output of the generator.
Such a semiconductor circuit is discussed in "Electronics," Sept. 16, 1976, page 42 and in "1976 IEEE International Solid-State Circuit Conference, " pages 56/57, both incorporated herein by reference. In these semiconductor circuits, the substrate bias generator is integrated, is likewise realized in MOS technology, and pumps electric charges into the area of the opposite conductivity type surrounding the current-bearing zones of the field effect transistors generally designated as a substrate. A very narrow range of fluctuation of access time and power consumption from chip to chip results from the regulation of the pump process, since the effects of fluctuations of the process parameters, temperature and supply voltage are reduced.
In the known arrangements, the pump circuit is formed by means of a capacitance with a MOS-diode connected to the substrate and via which electric charge is pumped into the substrate during the operation of the generator. The capacitance is driven by means of an oscillator with an amplifier. However, as a result of the substrate leakage current, the bias voltage V.sub.BB to ground conditioned by the charging of the substrate again decreases until the occurrence of the respectively next falling edge of the oscillator pulse.

Semiconductor circuit with at least two field effect transistors united in a semiconductor crystal


A web publishing method using J2EE based controller. User submits an image from a workstation and chooses “Print to Website” option as the media type. The image is converted into an image format (e.g. JPEG) that can be display in a browser. These images can then be transmitted through a new output channel that would package them into a J2EE EAR file. The J2EE EAR file would abide by all J2EE conventions for specifying the URL and user interfaces via Struts MVC (Model View Controller). The EAR file can then be dropped in the JBoss deployment directory where it would be made available to the user. The user can receive a prompt at the driver or client tool interface letting them know that printing was successful, presenting them with the new URL, and optionally asking them to password the new web site if so desired.

In general a print job is a transitory task that provides limited feedback, has little memory of the actual print process, and has limited options in terms of security. Currently, sharing information electronically is becoming increasingly prevalent. Yet the process of sharing information, especially if web-based, is more ad hoc in nature. What is needed is a more robust electronic sharing media type where output is optimized for web-based viewing.
The J2EE platform simplifies enterprise applications by basing them on standardized, modular components, by providing a complete set of services to those components, and by handling many details of application behavior automatically, without complex programming. The J2EE platform adds full support for Enterprise Java Bean (EJB) components, Java Servlets Application programming interface (API), Java Server Pages (JSP) and Extensible Markup Language (XML) technology. The J2EE standard includes complete specifications and compliance tests to ensure portability of applications across a wide range of existing enterprise systems capable of supporting the J2EE platform. In addition, the J2EE specifications now ensure Web services interoperability through support for the Web Services-Interoperability (WS-I) Basic Profile.
The prior art provides an EJB based enterprise printing architecture for secured printing. Features of Enterprise Java Bean (EJB), Enterprise Printing Bean (EPB), JAVA, J2EE, and document authoring are combined to enable a robust enterprise printing architecture. A Java object encapsulates a print job specification and provides a framework enabling access control to print jobs as well as providing audit capabilities. Print control languages can be specified using methods provided by the Java object. Actual process implementation can be supplied via a server enabling another layer of security and control. A user wanting to securely print a job supplies appropriate credentials to the print job bean to gain access to the content and print server credentials allow printing of the print job. The EJB API is extendable to enable all of the J2EE capabilities found on standard EJBs to be applied to print Jobs. Further, a new Java API provides a more powerful page description language than that found in other printing languages.
Other methods provide a World Wide Web (WWW) formatting for program output through print functions. An application creates a source file that can be formatted for web viewing and transmits the source file to print driver program. The output of the program is formatted for viewing on the WWW in response to the selection for WWW format.
The prior methods can be complex and costly. As sharing information electronically is becoming increasingly prevalent, a need exists for a web publishing method with improved security and accessibility that is both simple and low cost. The present invention is described in the context of J2EE implementation and use of Enterprise Archive (EAR) file for packaging the web accessible content. The EAR format is portable, low cost, and extensible to provide basic Portable document format (PDF-like) functionality. This is an easy method of casual web publishing, simpler than converting content to a web friendly format and transferring the file to a repository that builds on the users' familiarity with the network print paradigm. It is anticipated that this functionality would be controlled via feature key, hence revenue generating.

Java 2 platform enterprise edition (J2EE) based web publishing


A new and distinct cultivar of Chrysanthemum plant named ‘Deliroma’, characterized by its daisy-type inflorescences with red and yellow bi-colored ray florets; freely flowering habit; early and uniform flowering response; good postproduction longevity; and resistance to White Rust.

The present invention relates to a new and distinct cultivar of Chrysanthemum plant, botanically known as Chrysanthemum×morifolium and referred to by the name 'Deliroma'.
The new Chrysanthemum is the product of a planned breeding program conducted by the Inventor in 's Gravenzande, The Netherlands. The objective of the breeding program is to create new vigorous cut Chrysanthemum cultivars with interesting inflorescence forms and attractive floret coloration.
The new Chrysanthemum originated from a cross-pollination on Mar. 24, 2000 in 's Gravenzande, The Netherlands, of a proprietary seedling selection of Chrysanthemum×morifolium identified as code number DB7661, not patented, as the female, or seed, parent with a proprietary seedling selection of Chrysanthemum×morifolium identified as code number DB8696, not patented, as the male, or pollen, parent. The new Chrysanthemum was discovered and selected by the Inventor as a single plant within the progeny of the stated cross-pollination in a controlled environment in 's Gravenzande, The Netherlands.
Asexual reproduction of the new Chrysanthemum by terminal cuttings in a controlled environment in 's Gravenzande, The Netherlands since May 22, 2001, has shown that the unique features of this new Chrysanthemum are stable and reproduced true to type in successive generations.


A method and kit for tendon repair and two variations thereof using double loop locking sutures in disclosed. A pair of loop locking sutures are formed in each tendon end. The needle of each loop locking suture extends through the tendon fiber out of the tendon end for securement to the corresponding loop locking sutures formed in the other tendon end. The loop locking sutures transfer tensile loading along the axis of the tendons into transverse compression loads through the loop locking sutures. In one variation, the double loop locking sutures connect tendons of different diameter together. In a second variation, the tendon is attached to bone.

Notwithstanding the advances in tendon surgery during the past half century, a significant number of patients with flexor tendon injuries do not regain satisfactory functions. Such injuries result in severe functional loss from adhesion of repaired tendons, stiffness and flexion contracture of the fingers.
The principal theory for base-of-tendon healing has been the extrinsic mechanism by synovial sheath, pari-sheath, and migration of fibroblasts, although a number of researchers have reported strong evidence supporting the intrinsic healing mechanism by tenocytes and tenoblasts. Other studies show that the healing of immobilized tendon repair begins with the extrinsic mechanism followed by the intrinsic mechanism.
There is ongoing controversy about whether the repaired tendon should be immobilized completely, partially, or not at all. A number of studies have shown that actively mobilized tendon repair can heal with less or no restraining adhesion followed by satisfactory functional recovery. However, a common drawback of currently popular techniques of tendon repair of which I am aware is that they do not provide enough tensile strength with safety margins for early active mobilization. When a tendon is repaired with any of these techniques, immediate active mobilization will likely separate the tendon juncture as a result of elongation of the suture frame, breakdown of the sutures or pull through of the sutures.
Accordingly, there exists an unfulfilled need in modern hand surgery for a tendon repair technique with sufficient tensile strength and safety margin to enable early active mobilization likely to discourage stiff joints, adhesion and flexion contracture while enhancing the intrinsic healing mechanism aided by synovial diffusion.

Surgical kit and method for tendon repair


A compression release mechanism for an internal combustion engine wherein a rotatable pin positioned axially parallel to the camshaft is rotatably received in the camshaft lobes, and has an auxiliary cam surface mounted at an axial end thereof. The auxiliary cam surface is adapted to extend above the outboard camshaft lobe to engage one of the valve lifters to thereby activate a compression release valve when the rotatable pin is rotated to a first position in response to low engine speed. The pin is rotated to a second position in response to high engine speed whereby the auxiliary cam surface is adapted so as not to engage the valve lifter. The pin is rotated by means of a centrifugally activated flyweight in response to engine speed.

This invention relates generally to internal combustion engines, and more particularly to an improved compression release mechanism for four-stroke cycle engines.
Compression release mechanisms for four-stroke cycle engines are well known in the art Generally, means are provided to hold one of the valves in the combustion chamber of the cylinder head slightly open during the compression stroke while cranking the engine. This action partially relieves the force of compression in the cylinder during starting, so that starting torque requirements of the engine are greatly reduced. When the engine starts and reaches running speeds, the compression release mechanism is rendered inoperable so that the engine may achieve full performance. It is normally advantageous for the compression release mechanism to be associated with the exhaust valve so that the normal flow of the fuel/air mixture into the chamber through the intake valve, and the elimination of spent gases through the exhaust valve is not interrupted, and the normal direction of flow through the chamber is not reversed.
Examples of compression release mechanisms for four-stroke engines are shown in U.S. Pat. Nos. 3,381,676; 3,496,922; and 3,897,768; all assigned to the assignee of the present application. Although prior art compression release mechanisms are generally effective for relieving compression in the cylinder during cranking the engine, these prior art mechanisms are typically designed to provide compression relief when the exhaust valve is located inboard on the camshaft relative to the cam gear. U.S. Pat. Nos. 3,496,922 and 3,381,676 are examples of such compression release mechanisms. U.S. Pat. No. 3,897,768 discloses a compression release mechanism that is operable to actuate the exhaust valve when said valve is located outboard of the cam gear. Although this prior art mechanism performs satisfactorily, it has more working parts than is desired, and also imparts more friction to the system than is desired.
Accordingly, it is desired to provide a compression release mechanism that is effective in operation and relatively simple in construction, and that may be utilized to actuate the exhaust valve in an internal combustion engine wherein the exhaust valve is located outboard of the cam gear.


The present invention provides a basic slag for use to protect molten steel in a tundish during continuous casting processes. The preferred slag of the present invention comprises a combination of CaO, MgO, Al.sub.2 O.sub.3, and TiO.sub.2. The resulting tundish covering has exceptional insulation, protective and Al.sub.2 O.sub.3 absorptive properties, while avoiding operational problems encountered with previous basic tundish slags, such as crusting and refractory erosion.

1. Field of the Invention
The present invention relates to compositions used to cover, protect and insulate molten steel in a tundish during continuous casting of steel and the methods of using such compositions.
2. Background of the Prior Art
In continuous casting of molten steel, a tundish acts as a reservoir of molten steel between a ladle and caster in order to provide a continuous supply of molten steel into a mold. In a sequence casting procedure, anywhere from four to fifteen ladles of steel are continuously cast in a sequence. Molten steel from the ladle is poured into the tundish through a shroud and steel from the tundish is poured into one or more molds with a SEN tube. Fluid flow through the tundish is directed using dams, weirs, and baffles in such a way as to float out inclusions to the top and collect clean steel to flow into the mold.
In the past, an insulating layer of burnt rice hull ash (carbon and SiO.sub.2) was used to insulate the molten steel. This is a cheap way to insulate the steel in the tundish, but produces less than fully satisfactory steel and is often environmentally disruptive. With increasing need for cleaner steel and a safer working environment, slag producing tundish powders have been introduced. These powders, such as Atlantic Metal Corporation's TUNDOLITE.RTM. TU920, comprise primarily carbon and aluminum silicate (Al.sub.2 O.sub.3 -SiO.sub.2) and are effective in preventing the re-oxidation of steel in the tundish and are environmentally clean. Unfortunately, these compositions do not have the ability to absorb large quantities of Al.sub.2 O.sub.3 and do not insulate well.
In order to meet continuously increasing demands for high quality steel, recent investigations have centered on use of basic tundish powders with high CaO+MgO/SiO.sub.2 ratios. Although these powders have the ability to absorb Al.sub.2 O.sub.3, they have other production problems, such as crust formation that prevents free operation of tundish during sequence casting, and severe erosion of Al.sub.2 O.sub.3 /graphite SEN tubes.
To attempt to solve some of these problems, applicant investigated using calcium aluminate (CaO-MgO-Al.sub.2 O.sub.3) slag chemistries. These slags provided a basic slag cover but could not absorb large quantities of Al.sub.2 O.sub.3 without forming a crust and causing operational problems during sequence casting. This reaction is believed to be a function of the amount of aluminum oxide absorbed in the slag causing a increase in the melting temperature of the slag.
Accordingly, it is a primary object of the present invention to provide a cover for use in continuous casting of molten steel which effectively provides insulation of molten steel in the tundish, absorbs inclusions floating on top of the steel, protects the steel from re-oxidation, contamination and crusting, and resists wear on continuous casting refractories.
It is a further object of the present invention to provide such a cover for molten steel which comprises a basic tundish powder having the ability to absorb Al.sub.2 O.sub.3 without forming a crust due to increased melting point.
It is an additional object of the present invention to provide such a cover for molten steel which improves the cleanliness of steel without adversely affecting continuous casting operation.
It is another object of the present invention to provide such a cover for molten steel which delivers the above benefits while being simple to apply in the continuous casting process and relatively inexpensive to produce.
These and other objects of the present invention will become evident from review of the following specification.

Process for insulating molten steel during continuous casting


Compounds having activity as inhibitors of ALK2 kinase and/or JAK2 kinase are disclosed. The compounds have the following structure (I):

Field of the Invention
The present invention is generally directed to novel compounds having activity as inhibitors of ALK2 and/or JAK2 kinases and use of the same for treatment of various cancers.
Description of the Related Art
The Janus kinases (JAKs) are a family of kinases of which there are four in mammals (JAK1, JAK2, JAK3 and TYK2) that are integral in signaling from extracellular cytokines, including the interleukins, interferons, as well as numerous hormones (Aringer, M., et al., Life Sci, 1999. 64(24): p. 2173-86; Briscoe, J., et al., Philos Trans R Soc Lond B Biol Sci, 1996. 351(1336): p. 167-71; Ihle, J. N., Semin Immunol, 1995. 7(4): p. 247-54; Ihle, J. N., Philos Trans R Soc Lond B Biol Sci, 1996. 351(1336): p. 159-66; Firmbach-Kraft, I., et al., Oncogene, 1990. 5(9): p. 1329-36; Harpur, A. G., et al., Oncogene, 1992. 7(7): p. 1347-53; Rane, S. G. and E. P. Reddy, Oncogene, 1994. 9(8): p. 2415-23; Wilks, A. F., Methods Enzymol, 1991. 200: p. 533-46). These non-receptor tyrosine kinases associate with various cytokine receptors and act to transduce the signal from extracellular ligand-receptor binding into the cytoplasm, by phosphorylating STAT (signal transducer and activator of transcription) molecules, which then enter the nucleus and direct transcription of various target genes involved in growth and proliferation (Briscoe, J., et al.; Ihle, J. N. (1995); Ihle, J. N. (1996); Rawlings, J. S., K. M. Rosier and D. A. Harrison, J Cell Sci, 2004. 117(Pt 8): p. 1281-3.). The four JAK isoforms transduce different signals by being associated specifically with certain cytokine receptors, and activating a subset of downstream genes. For example, JAK2 associates with cytokine receptors specific for interleukin-3 (Silvennoinen, O., et al., Proc Natl Acad Sci USA, 1993. 90(18): p. 8429-33), erythropoietin (Witthuhn, B. A., et al., Cell, 1993. 74(2): p. 227-36), granulocyte colony stimulating factor (Nicholson, S. E., et al., Proc Natl Acad Sci USA, 1994. 91(8): p. 2985-8), and growth hormone (Argetsinger, L. S., et al., Cell, 1993. 74(2): p. 237-44).
The JAK family of enzymes has become a set of targets for various hematological and immunological disorders. JAK2 is currently under study as a viable target for neoplastic disease, especially leukemias and lymphomas (Benekli, M., et al., Blood, 2003. 101(8): p. 2940-54; Peeters, P., et al., Blood, 1997. 90(7): p. 2535-40; Reiter, A., et al., Cancer Res, 2005. 65(7): p. 2662-7; Takemoto, S., et al., Proc Natl Acad Sci USA, 1997. 94(25): p. 13897-902) as well as solid tumors (Walz, C., et al., J Biol Chem, 2006. 281(26): p. 18177-83), and other myeloproliferative disorders such as polycythemia vera (Baxter, E. J., et al., Lancet, 2005. 365(9464): p. 1054-61; James, C., et al., Nature, 2005. 434(7037): p. 1144-8; Levine, R. L., et al., Cancer Cell, 2005. 7(4): p. 387-97; Shannon, K. and R. A. Van Etten, Cancer Cell, 2005. 7(4): p. 291-3), due to its activation of downstream effector genes involved in proliferation. Because of its association with, and deregulation in, neoplastic and myeloproliferative disorders, small molecule JAK2 inhibitors for the treatment of human malignancies are of significant interest.
Bone morphogenetic proteins (BMPs) are pleiotropic growth factors playing essential roles in coordinating tissue architecture throughout various organs in the body. BMP ligands interact with bone morphogenetic protein receptors (BMPRs), which belong to the transforming growth factor beta (TGF-b) superfamily of serine/threonine kinase receptors (Ikushima, H. and K. Miyazono, Biology of Transforming Growth Factor-beta Signalin. Curr Pharm Biotechnol, 2011). The ligands bind to type-II receptors, which then recruit type-I receptors forming a heteromeric complex. As a complex, the type-II receptor phosphorylates the type-I receptor, which allows the type-I receptor to become active and phosphorylate downstream signaling molecules. The downstream effects of activating these receptors are primarily carried out by the SMAD family of proteins. SMADs become phosporylated and transduce the signal from the cell membrane to the nucleus where they function as transcription factors to regulated gene expression (Massague, J., J. Seoane, and D. Wotton, Smad transcription factors. Genes Dev, 2005. 19(23): p. 2783-810).
In individuals with chronic diseases, such as cancer and inflammation, BMP signaling is constitutively activated leading to anemia. This condition is commonly referred to as anemia of chronic disease (ACD) and is a debilitating symptom associated with cancer patients (Cullis, J. O., Diagnosis and management of anaemia of chronic disease: current status. Br J Haematol, 2011. 154(3): p. 289-300). Chronic anemia in cancer patients leads to extreme weakness and fatigue, which leads to a poor quality of life for these individuals. In these patients, BMP signaling through two BMP type-I receptors, ALK2 (also known as ACVR1) and ALK3 induces the hepatic expression of the peptide hormone, called hepcidin (Steinbicker, A. U., et al., Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice. Blood, 2011. 118(15): p. 4224-30). Hepcidin reduces serum iron levels by promoting the degradation of the iron exporter, ferroportin, resulting in the increase of iron stored away in macrophages and other cell types and making the iron unavailable for hemoglobin and red blood cell (RBC) function. Supplementing a patient's intake of iron does not reverse ACD because the ingested iron simply is stored away due to the activated BMP pathway and high serum hepcidin levels. Currently, ACD in cancer is managed by limiting the physical activity of patients and blood transfusions are used in the most severe cases Inhibition of BMP signaling in these patients has the potential to provide a real difference in their quality of life and ultimately, may positively impact how they respond to therapy, radiation, or surgery (Steinbicker, A. U., et al., Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. Blood, 2011. 117(18): p. 4915-23; Coyne, D. W., Hepcidin: clinical utility as a diagnostic tool and therapeutic target. Kidney Int, 2011. 80(3): p. 240-4; Theurl, I., et al., Pharmacologic inhibition of hepcidin expression reverses anemia of chronic disease in rats. Blood, 2011).
In addition to its function in ACD, BMP signaling plays pivotal roles in the growth and metastasis of cancer cells, particularly in breast, prostate, and other cancers that frequently metastasize to the bone (Ye, L., M. D. Mason, and W. G. Jiang, Bone morphogenetic protein and bone metastasis, implication and therapeutic potential. Front Biosci, 2011. 16: p. 865-97). BMPs and BMPRs are more highly expressed in metastatic breast cancer cells compared to less metastatic ones and also in prostate cancer cells that generate osteosclerotic bone metastases (Bobinac, D., et al., Expression of bone morphogenetic proteins in human metastatic prostate and breast cancer. Croat Med J, 2005. 46(3): p. 389-96). In addition to effecting the invasiveness and metastasis of cancer cells, the BMP pathway has also been shown to influence the bone microenvironment. The cross-communication between cancer cells and the bone microenvironment via the BMP signaling pathway promotes the metastasis of the cancer cells to the bone. Studies have shown that the inhibition of BMP signaling significantly reduces bone tumor burden and osteolytic disease in a preclinical model of prostate cancer bone metastasis. These results suggest that a BMP inhibitor may have application in preventing bone metastases in addition to its activity against anemia induced by chronic disease.
Furthermore, a BMP inhibitor has the potential to treat multiple disease indications outside of cancer. ACD is a devastating condition that affects individuals suffering from other diseases, including rheumatoid arthritis, systemic lupus, chronic kidney disease, and many other inflammatory diseases. Additionally, a rare childhood genetic disease, called fibrodysplasia ossificans progressive (FOP) has been shown to be caused by activating mutations in the alk2 gene (Kaplan, F. S., et al., Investigations of activated ACVR1/ALK2, a bone morphogenetic protein type I receptor, that causes fibrodysplasia ossificans progressiva. Methods Enzymol, 2010. 484: p. 357-73). The mutation in ALK2 in this disease causes fibrous tissue (muscle, tendon, ligament, etc.) to be ossified when damaged. In other words, when patients with this condition experience injury to muscle or joint tissues, the repaired tissue is converted to bone causing joints to be permanently frozen in place. By the teenage years, these children have lost most of the function of their joints. Studies performed in animal models of FOP suggest that inhibiting ALK2 decreases the "flare-ups" associated with FOP and prevents the ossification of repaired tissue in the model. The medical and commercial benefits of a BMP inhibitor (i.e. ALK2) are quite broad and extend to multiple indications outside of cancer.
While progress has been made in this field, there is a need for the design of specific and selective inhibitors for the treatment of cancer and other conditions that are mediated and/or associated with ALK2 and/or JAK2 (including JAK2 V617F) protein kinases. The present invention fulfills these needs and offers other related advantages.

JAK2 and ALK2 inhibitors and methods for their use

Abstract: including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, z and A are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.


The present invention provides low hygroscopic forms of aripiprazole and processes for the preparation thereof which will not convert to a hydrate or lose their original solubility even when a medicinal preparation containing the anhydrous aripiprazole crystals is stored for an extended period.

Aripiprazole, 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]-butoxy}-3,4-dihydro carbostyril or 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]-butoxy}-3,4-dihydro-2(1H)-quinolinone, is an atypical antipsychotic agent useful for the treatment of schizophrenia (U.S. Pat. No. 4,734,416 and U.S. Pat. No. 5,006,528). Schizophrenia is a common type of psychosis characterized by delusions, hallucinations and extensive withdrawal from others. Onset of schizophrenia typically occurs between the age of 16 and 25 and affects 1 in 100 individuals worldwide. It is more prevalent than Alzheimer's disease, multiple sclerosis, insulin-dependent diabetes and muscular dystrophy. Early diagnosis and treatment can lead to significantly improved recovery and outcome. Moreover, early therapeutic intervention can avert costly hospitalization.
According to Example 1 of Japanese Unexamined Patent Publication No. 191256/1990, anhydrous aripiprazole crystals are manufactured for example by reacting 7-(4-bromobutoxy)-3,4-dihydrocarbostyril with 1-(2,3-dichlorophenylpiperadine and recrystallizing the resulting raw anhydrous aripiprazole with ethanol. Also, according to the Proceedings of the 4th Japanese-Korean Symposium on Separation Technology (Oct. 6-8, 1996), anhydrous aripiprazole crystals are manufactured by heating aripiprazole hydrate at 80° C. However, the anhydrous aripiprazole crystals obtained by the aforementioned methods have the disadvantage of being significantly hygroscopic.
The hygroscopicity of these crystals makes them difficult to handle since costly and burdensome measures must be taken in order ensure they are not exposed to moisture during process and formulation. Exposed to moisture, the anhydrous form can take on water and convert to a hydrous form. This presents several disadvantages. First, the hydrous forms of aripiprazole have the disadvantage of being less bioavailable and less dissoluble than the anhydrous forms of aripiprazole. Second, the variation in the amount of hydrous versus anhydrous aripiprazole drug substance from batch to batch could fail to meet specifications set by drug regulatory agencies. Third, the milling may cause the drug substance, Conventional Anhydrous Aripiprazole, to adhere to manufacturing equipment which may further result in processing delay, increased operator involvement, increased cost, increased maintenance and lower production yield. Fourth, in addition to problems caused by introduction of moisture during the processing of these hygroscopic crystals, the potential for absorbance of moisture during storage and handling would adversely affect the dissolubility of aripiprazole drug substance. Thus shelf-life of the product could be significantly decreased and/or packaging costs could be significantly increased. It would be highly desirable to discover a form of aripiprazole that possessed low hygroscopicity thereby facilitating pharmaceutical processing and formulation operations required for producing dosage units of an aripiprazole medicinal product having improved shelf-life, suitable dissolubility and suitable bioavailability.
Also, Proceedings of the 4th Japanese-Korean Symposium on Separation Technology (Oct. 6-8, 1996) state that, anhydrous aripiprazole crystals exist as type-I crystals and type-II crystals; the type-I crystals of anhydrous aripiprazole can be prepared by recrystallizing from an ethanol solution of aripiprazole, or by heating aripiprazole hydrate at 80° C.; and the type-II crystals of anhydrous aripiprazole can be prepared by heating the type-I crystals of anhydrous aripiprazole at 130 to 140° C. for 15 hours.
By the aforementioned methods, anhydrous aripiprazole type-II crystals having high purity can not be easily prepared in an industrial scale with good repeatability.

Low hygroscopic aripiprazole drug substance and processes for the preparation thereof


A diskette holder for rigid-case data diskettes is disclosed, comprising a platform having a plurality of lateral grooves in the upper surface thereof for receiving diskettes. Associated with each groove are diskette support means comprising a front support face angled upwardly and forwardly from the area of the groove and a rear support face angled upwardly and rearwardly from the area of the groove. At least one support face of a pair associated with a groove has the undercut portion disposed from the plane of the opposing support face by a distance not less than and substantially equal to the thickness of the diskette to be held, and preferably parallel to the opposing support face. In the preferred embodiment, the diskette support means are positioned at only one end of each groove and successively alternating grooves have the support means at alternating ends of the grooves. Stop means at opposite ends of the grooves position the diskettes laterally and preventing lateral movement. The stop means at the groove end remote from the end having the support means comprises the side of a support block comprising the support means associated with the adjacent grooves.

1. Field of the Invention
This invention relates to a holder for rigid-case data diskettes such as, for example, the 31/2 inch rigid-case diskettes now in use with the Apple Macintosh (trademark) computer.
2. Description of the Prior Art
In the prior art relating to data diskette storage, designs for diskette holders were restricted by the fact that the conventional diskettes were flexible, and thus could not be supported in cantilever fashion along an edge or from a corner without the possibility of damaging the recording medium. With the advent of rigid-case diskettes, existing designs for diskette holders were adapted, with apparently little thought being given to alternative methods of support of the diskettes within the holders. The present inventors have discovered that it is advantageous to resort to a new form of diskette holder which takes advantage of the rigid character of the protective cases of the new diskettes.


Embodiments provide an apparatus and method for dispensing a fluid, the apparatus including a container capable of retaining the fluid and having a top, bottom, front surface, and rear surface; a dip tube integrally formed with the rear surface of the container, the dip tube having a first end extending toward the top and a second end extending toward bottom; and a spout member mounted to the top of the container, the spout member including a pour spout adjacent the front surface for dispensing the retained fluid and an air vent adjacent the rear surface with a supply line in connection with the first end of the dip tube for directing air into the container.

The background description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure. Unless otherwise indicated herein, the approaches described in this section are not prior art to the claims in the present disclosure and are not admitted to be prior art by inclusion in this section.
A multitude of applications exist for a container that dispenses a fluid in a smooth and controlled stream. For example, it is often advantageous to pour bleach into a detergent reservoir of a conventional laundry machine without the bleach splashing or creating a mess. A user desiring to manually pour bleach from a container into the reservoir must do so carefully, in a manner that allows air to enter the container to compensate for the vacuum created as the bleach is poured out. If the user pours the bleach too quickly, thereby blocking the container opening, air entering the container as discrete bubbles causes periodic interruptions followed by sudden increases in flow as each bubble passes through the container opening. This creates an undesirable "glugging" effect that may result in missed application, spillage, wasted product, and/or inconvenience to the user. In other solutions, a separate funnel is used to catch uneven fluid flowing out of a container. However, employing a separate and typically small device to aid pouring requires the user to locate and store the device, as well as clean the device before and after use. Accordingly, it would be advantageous to provide an apparatus that conveniently and effectively delivers a steady and controlled stream of fluid without the use of a separate funnelling device.


The apparatus includes a powered bowl assembly having a tubular shaft journalled within a base of the apparatus. A pressurized air flow is discharged into slurry in the bowl assembly via a circular array of bubble generators. An impellor discharges the slurry outwardly against an upwardly inclined annular surface of the bowl assembly to cause the slurry to merge upwardly with the streams to promote flotation. Slurry within the bowl assembly forms a vortex with particle flotation forming a froth layer inwardly of a slurry vortex. The froth exits the bowl assembly upwardly past a barrier partially closing the bowl assembly. Heavier gangue particles exit via an outlet about the bowl assembly periphery. A collector shroud is partitioned to receive the froth and the heavier waste material. A modified form of the apparatus includes an independently powered bowl assembly and impellor.

The present invention pertains generally to equipment or devices utilized for the separation of mineral or metallic particles by the flotation process.
The scarcity of high grade ore has placed greater emphasis on the recovering of small particles, termed fines, during processing. In certain instances in the past, such efforts were not economically justified. Presently tailings from past and present mineral processing operations are believed to be a valuable resource assuming such tailings can be economically processed.
In the prior art are flotation systems wherein a slurry flow is fed into the flotation unit above an injected airflow. Briefly, the mineral particles adhere to airflow bubbles and result in a concentrate forming at the flotation units upper surface. To the extent known, such systems rely entirely on the effect of differential gravity in such a flotation process. The flotation process is widely used for processing material containing fine particles which, in many instances, are not recovered.
Further background information is in Chapter 35 "Fine Particle Flotation" in Vol. 1 of a publication entitled Fine Particles Processing by P. Somasundaran and E & MJ Second Operating Handbook of Mineral Processing by L. White.

Centrifugal flotation apparatus and method


In one embodiment, a processor includes multiple cores and a power control unit (PCU) coupled to the cores. The PCU has a stress detector to receive a voltage and a temperature at which the processor is operating and calculate lifetime statistical information including effective reliability stress, maintain the lifetime statistical information over multiple boot cycles of a computing system such as personal computer, server computer, tablet computer, smart phone or any other computing platform, control one or more operating parameters of the processor based on the lifetime statistical information, and communicate at least a portion of the lifetime statistical information to a user and/or a management entity via an interface of the processor. Other embodiments are described and claimed.

In modern processors and other semiconductor devices, it is known that as the product ages, certain degradations become manifest. Several different phenomena can cause degradation to a semiconductor device, for example, hot-carrier injection, bias temperature instability, oxide breakdown (also known as time dependent dielectric breakdown (TDDB)), electro-migration and more. Each of these degradation mechanisms occurs due to various factors like temperature, voltage, current and others, where temperature and voltage impact the degradation exponentially.
Accordingly, the probability of failure of a semiconductor device is a function of various run time parameters, its actual time and use and other utilization measures. It is difficult for consumers of such semiconductor devices, whether in the form of processors or other integrated circuits, to determine a product's probability of failure and take appropriate action, given that such information is generally not available whatsoever, and typically is in no way available to interested parties, such as end users, original equipment manufacturers (OEMs), information technology (IT) personnel and so forth.

This patent is subject to a terminal disclaimer.

Providing lifetime statistical information for a processor


A display system utilizing a non-linear raster generator is disclosed. As is conventional in raster scan displays, the scanning is controlled by two electrical signals arbitrarily designated the X and Y deflection signals. In the preferred embodiment, two memories are used to store signals which provide constants to control the amount of the non-linearity of the raster. These constants are processed to generate X and Y deflection signals which are generally hyperbolic in nature. This type of display is particularly useful for displaying mapping signals produced from airborne doppler radar.

1. Field of the Invention
The invention relates to display systems and in the preferred embodiment to a display system for displaying ground maps produced by utilizing doppler radar video signals.
2. Description of the Prior Art
The azimuth resolution of real beam radar systems is determined by the antenna beamwidth. To overcome this limitation the frequency shift (doppler effect) that occurs between the transmitter and the target due to their relative velocity is used to sort out targets inside the beam. Every point on the ground can be defined by an airborne ground map doppler radar system by its range and doppler frequency. Range is necessary because a given doppler frequency defines a locus of points that make up a hyperbola that is called "isodop" or a line of constant doppler frequency. The range dimension then defines a point along any isodop. Therefore, doppler radar systems that process all ranges of interest from the return for any given output pulse at a given doppler frequency can only map along a single isodop. To scan an area on the ground requires processing a number of returns at different doppler frequencies.
The usual ground map display system works on true azimuth and range outputs from a radar. If this approach is used to display video from the doppler radar system, severe distortion of the map occurs. The system which is the subject of this invention, overcomes this display problem by generating a non-linear raster which has the same basic geometrical form as the isodops.


A method of forming a thermodynamically stable transparent product by combining (i) water; (ii) a volatile cyclic methyl siloxane or volatile linear methyl siloxane; and (iii) a silicone polyether surfactant. The amounts of each component, the particular type of silicone polyether surfactant used, and the order of addition of the components, influence the type of product obtained, and these factors are such that the composition forms an optically clear gel. The gel is useful in personal care products such as cosmetics and antiperspirants.

This invention is directed to a transparent silicone, and more particularly to a ternary composition of water, a volatile cyclic or linear methyl siloxane (VMS), and a short-chain or low molecular weight silicone polyether, which when combined provide an optically clear gel.
It is well documented (i.e., U.S. Pat. No. 4,999,398) that emulsions, especially silicone emulsions, are opaque, cloudy, and tend to separate on standing. Thus, the desirability of microemulsions which contain micro-particles in the droplet phase providing a measure of clarity, or gels which are thermodynamically stable transparent structures.
As used herein, the term emulsion or macroemulsion means a dispersion of one immiscible liquid in another, in the form of droplets with diameters approximately in the range of 100-1,000 nanometers (0.1-1.0 microns/1,000-10,000 angstroms .ANG.).
In contrast, a microemulsion means a transparent dispersion of two or more immiscible liquids and a surfactant. Microemulsions are clear or transparent because they contain particles smaller than the wavelength of visible light, which is typically on order of about 10-100 nanometers.
Microemulsions may contain oil droplets dispersed in water (O/W), water droplets dispersed in oil (W/O), or they may be in the form of a bi-continuous structure. They are characterized by an ultra-low interfacial tension between the oil and water phases.
A microemulsion can be recognized by several of its inherent characteristics which are that (i) it contains oil, water, and a surfactant; (ii) there is a high concentration of surfactant relative to oil; (iii) the system is optically clear; (iv) the phases do not separate by centrifugation; and (v) the system forms spontaneously.
Thus, as used herein, an emulsion is considered as containing particles having an average diameter of more than 100 nanometers (0.1 microns/1,000 angstroms .ANG.), whereas a microemulsion is considered as containing particles having an average diameter of less than 100 nanometers (0.1 microns/1,000 angstroms .ANG.).
Clarity or transparency is controlled to a great extent by the particle size of the dispersed phase. The scattering of light is dependent on the particle size. Therefore, clear or transparent compositions appear to be a single phase without droplets or particles when viewed with the naked eye.
On the other hand, and in contrast to an emulsion or microemulsion, a gel is a semi-solid stabilized or set by a three-dimensional lattice system. Because a surfactant has a bipolar amphiphilic structure (i.e., a water-soluble polar head and a water-insoluble organic tail), surfactant molecules accumulate preferentially at the interface of two immiscible phases. If the concentration at the interface exceeds the critical micelle forming concentration (cmc), a colloidal surfactant solution is produced. With increasing concentration, or volume fraction of the internal phase, such a solution becomes a structured gel.
Bailey in U.S. Pat. No. 3,299,112 describes products formed from a ternary system of water, a silicone oil, and a silicone polyether. But in contrast to my invention, the products in Bailey are emulsions which are not clear; the ternary system in the '112 patent is not a gel; the silicone oil in Bailey is not a volatile cyclic VMS; and where Bailey does describe a linear silicone oil, it is not a volatile linear silicone oil.
Rather, the silicone oil in Bailey corresponds to R".sub.3 SiO(R".sub.2 SiO).sub.x SiR".sub.3 where x is 10-1,000. My corresponding volatile linear VMS have an "x" of 0-5, well below the range in Bailey. In fact, where "x" exceeds 5, products tend not to be clear.
Furthermore, emulsions as in Bailey are recognized as inherently unstable systems separating with time. In contrast, my gels are stable indefinitely. The order of addition of the components does influence their formation, and with mild mixing at room temperature (20.degree.-25.degree. C./68.degree.-77.degree. C.), that is sufficient to cause stable gels to form.
My clear gel has particular value in the personal care arena. Because of the unique volatility characteristics of the VMS component of my ternary system, it can be used alone, or blended with other cosmetic fluids to form a variety of over-the-counter personal care products.
Thus, it is useful as a carrier in antiperspirants and deodorants, since it leaves a dry feel, and does not cool the skin upon evaporation. It is lubricious and will improve the properties of skin creams, skin care lotions, moisturizers, facial treatments such as acne or wrinkle removers, personal and facial cleansers, liquid soaps, bath oils, perfumes, colognes, sachets, sunscreens, pre-shave and after-shave lotions, shaving soaps, and shaving lathers. It can be used in hair shampoos, hair conditioners, hair sprays, mousses, permanents, depilatories, and cuticle coats, to enhance gloss and drying time, and provide conditioning benefits.
In cosmetics, it will function as a leveling and spreading agent for pigments in make-ups, color cosmetics, foundations, blushes, lipsticks, lip balms, eyeliners, mascaras, oil removers, color cosmetic removers, and powders. It is also useful as a delivery system for oil and water soluble substances such as vitamins. When incorporated into sticks, other gels, lotions, aerosols, and roll-ons, my ternary composition imparts a dry, silky-smooth, pay-out.
Additionally, my clear gel exhibits a variety of advantageous and beneficial properties such as (i) clarity, (ii) the ability to combine properties of water and oil in a single homogeneous material, (iii) shelf stability, and (iv) ease of preparation; and consequently it has wide application but especially in cosmetics or antiperspirants.
A transparent gel for cosmetic or antiperspirant uses should be semi-solid materials at rest, but should thin sufficiently under moderately applied shear stress, to flow easily and smoothly when spread over the skin.
Beyond personal care, the gels have application in formulating consumer products such as ski waxes, insecticides, stain removal sticks, car waxes, tire treatments, and vinyl protectants.


A deer repellent device and method for warding off a deer from a shrub or plant. The device is an assembly of a deer repellent formulation and a support medium for the formulation. The support medium is a length of rope or a volume of clay granules, the rope, as treated, can be strung around shrubs or along plants. The clay medium, as treated, can be placed under and around a shrub or plant.

The prior art deer repellent formulation is described in U.S. Pat. No. 4,965,070, issued Oct. 23, 1990 to the same inventor as this application.
The prior art formulation consisted essentially of by volume:
84% water; PA1 8% thiram; PA1 1% chicken eggs; PA1 1% liquid hot sauce; PA1 5% adhesive.
One problem of the prior art deer repellent formulation is the difficulty of maintaining such formulation on a shrub, or plant, or the like, during snow or rain.


A two part plastic container for food products is provided having a main body and a base for being attached to the bottom of the body. The body has a frustoconical sidewall with a radial bottom rim and the base has a shorter frustoconical sidewall with a radial bottom rim. The rims are advantageous in that they allow stacks of the container bodies and bases to be processed with container feeding equipment presently in use as the rims provide distinct structure for being fed by the mechanical devices of the equipment. An energy director area is provided between the rims for ultrasonically attaching the container body and base. The container body has a smooth sidewall over substantially its entire extent without indentations or bumps for maximizing the printing area thereon. Both the container body and base minimize the size of their respective nest intervals when stacked to conserve space for shipping and processing purposes while still allowing for easy denesting with parts readily separated from the stack due to the provision of the rims. In a preferred form, the inner edges of the stacking shoulders of the bases are outwardly tapered for self-centering when stacked. The lip of the body defining the mouth of the container includes inner and outer annular portions, with the inner annular portion extending upwardly relative to the outer annular portion and terminating in a wedge shape for enhanced sealing.

One area where the use of plastic containers has become widespread is in the food packaging industry. Accordingly, it is common for these plastic food containers to serve as the end display package in which the product is presented for sale to the customer. Typical of these containers are those used for dairy products such as cottage cheese, sour cream, or the like where an integral body of the container is provided having a sidewall that tapers down to an integral transverse bottom wall with the top opening being closed by a plug fit lid. Normally, the lid has a depending peripheral skirt which locks onto the upper rim of the tapered wall of the container body. One difficulty encountered in the design of closure lids for the containers described above is ensuring that when they are nested in a stack such as for shipping, the stacked lids maintain a constant gap between adjacent skirts of respective stacked lids. Maintaining uniform gap spacing is important to allow them to be efficiently utilized with high-speed automated packaging equipment which position the containers for automatic filling and automatically caps the filled containers with lids taken from the stack by mechanical devices of the equipment. Various rib structures have been employed with lids to provide the requisite spacing, see e.g. U.S. Pat. Nos. 4,826,039 and 5,377,861.
Many of these food product plastic containers have their parts formed by a thermoforming process. In thermoforming, a thin plastic sheet is formed into the desired shape by heating and forcing the sheet against a mold to produce a container part having a uniform, very thin, cross-sectional thickness which can result in a part having very flexible walls. In the particular application of interest herein, currently there is a flavored yogurt thermoformed container that has a reverse tapered sidewall with a larger diameter bottom and being open at both the smaller diameter top and at the bottom thereof. A separate bottom closure member is also formed by thermoforming and is spinwelded to the sidewalls to close off the bottom for receiving yogurt therein. The bottom closure includes a base panel and depending skirt wall which is spinwelded to the interior surface of the body wall to permanently attach the pieces together. Thus, unlike the previously described top closure lids which are designed to be opened, the bottom closure for this particular yogurt container does not have a locking skirt which locks onto a rim of the sidewall and which can be opened to gain access to the food therein. Instead, after being filled with yogurt, the top is closed by a flexible foil seal as by an adhesive. To gain access to the yogurt, the seal is peeled open from over the opening at the top of the container sidewall.
The thermoformed and spinwelded yogurt containers described above suffer from numerous shortcomings. For spinwelding the bottom closure to the container body wall, both pieces are provided with integral gripping lugs which project relatively far radially inward relative to the body and skirt walls so that they can be grasped by the spinwelding equipment for rotating the two parts relative to each other to create frictional heating for welding the parts together. The bottom closure has the lugs formed on its skirt, and the body sidewall has lugs around the top thereof. The spinwelding technique requires specialized handling and filling equipment that results in a relatively slow production of containers for filling.
Since the parts of the above-described yogurt container are thermoformed parts having a constant wall thickness, the radially inward projecting lugs form corresponding indentations on their exterior wall surfaces. Because of the aforementioned display function of the exterior surface of the yogurt container, maximizing the amount of surface area available for printing information, such as product characteristics, e.g. ingredients, nutritional content, or other required information about the product, is an important consideration, especially where the containers are relatively small, such as for example with the preferred 6 oz. (170 g) yogurt containers herein. The lugs at the top of the wall restrict the height of the printing that can be received on the container sidewall. In addition, there are unsightly indentations on the sidewall due to the lugs that are readily visible to the purchaser, and because of the radial extent to which they project into the container interior, they can unduly interfere with removing the food product therefrom, e.g. spooning yogurt out from the container. Accordingly, there is a need for a plastic container for food products such as a yogurt container which is more aesthetically pleasing, and better maximizes the print receiving surface area thereon.
Another significant characteristic the containers should possess is the ability to stack with uniform spacing between the container parts and so that while stacked, adjacent parts do not become jammed and wedged together. In addition, the space taken up by a given number of stacked container parts should be minimized. The above described lugs of the prior yogurt container, in addition to their grasping function for spinwelding provide a stacking surface with their bottom flat surfaces. The indentations of the lugs extend relatively far down the sidewalls spaced from the top in both the container body and the bottom closure. This precludes stacking of these container parts in a compact fashion.
It is also important that the container be adapted to be used with conventional automated container feeding equipment that is currently employed in container filling assembly and printing operations. Both the upper container wall and the bottom closure lack an annular rim for feeding with mechanical mechanisms or devices such as mechanical fingers, feed screws or shuttles of the automated feeding equipment commonly used with the packaging of dairy products.
As previously mentioned, thermoformed plastic containers generally have very thin cross-sectional thickness so that their walls can be very flexible. This is especially true with the bottom closure of the above described yogurt container where the skirt sidewall is relatively thin in thickness and the base panel is quite wide in diameter which can cause the closure member to be very pliable.


An air intake vent (20) for the cowl opening (24) of an armored vehicle includes a front armor plate (26) extending upwardly from the cowl (22) forward of the opening and a holder (30) for mounting an air filter (32) over the cowl opening, and the vent also includes a flanged cover (34) that prevents projectiles from passing through the cowl opening while still permitting air to enter the vehicle. A front flange (36) of the cover extends downwardly in front of the front armor plate preferably with an inclined orientation so as to provide good deflection of projectiles away from the cowl opening. A pair of side armor plates (38) extend upwardly from the cowl on opposite lateral sides of the opening thereof and side flanges (44) on the cover extend downwardly outboard therefrom in a spaced relationship. The holder for the air filter includes an L-shaped rear mount (30) that positions the rear extremity (45) of a mounted filter such that the front and side extremities (46, 47) thereof are respectively positioned by the front and side armor plates on the cowl. Supports (48, 52) for the cover are mounted on the front and side armor plates and have a construction that permits removal and mounting of an air filter for servicing or replacement.

Passenger vehicles conventionally include an air intake vent located on the cowl between the front windshield and the rear end of the engine compartment hood. Such cowl vents normally include exposed openings through which air enters prior to passage into the passenger compartment to provide ventilation.
Armored vehicles are conventionally made from metal armor plate so as to be capable of stopping projectiles such as bullets or shrapnel. Air intake openings on armored vehicles conventionally utilize louvers or the like to define relatively small openings that are not big enough to allow a projectile of the normal size to pass into the vehicle. The cross-sectional area of air flow is thus smaller for any given size of such a vent as a result of the louvers located between the openings. Also, many armored vehicles are utilized for both on-road and off-road purposes and the air that is taken in by an intake vent on the cowl opening thereof thus quite often carries dust.


A numerical control device includes a program look-ahead unit for prereading and analyzing multiple blocks constituting a machining program, and a program execution unit for executing the blocks to control a machining operation and an auxiliary operation. The program execution unit sequentially executes the blocks in order from the initial block, and shifts an execution start time of the auxiliary operation block by an offset time corresponding to an auxiliary function code written in the auxiliary operation block.

Field of the Invention
The present invention relates to a numerical control device for controlling machining operations for machining workpieces to be machined with tools and auxiliary operations for assisting the machining operations, and also relates to a control method for the numerical control device.
Description of the Related Art
A numerical control device of a machine tool performs machining operations such as cutting, polishing, etc., of a workpiece while axially moving a tool and also performs subsidiary operations (auxiliary operations) for machining operations. Examples of auxiliary operations include tool changes, workpiece replacement and supply/suspension of cutting oil. By performing auxiliary operations of this kind in advance during machining operations as necessary, it is possible to shorten the processing time (cycle time) for the entire workpiece machining process.
For this reason, the numerical control device decides implementation of auxiliary operations by looking-ahead the machining program. For example, the numerical control device disclosed in Japanese Patent No. 5210070 includes a first machining program analyzer for analyzing the entire machining program and a second machining program analyzer for analyzing auxiliary operations alone in the machining program. Then, the auxiliary operations analyzed by the second program analyzer are performed in advance to thereby shorten the processing time.

Numerical control device and control method for numerical control device


This invention relates to an urethane group containing polyisocyanurate foam produced from a polyisocyanate and a polyhydroxy compound, wherein the polyhydroxy compound is the reaction mixture of a hydroxyl group containing amine which is at least difunctional and is selected from the group consisting of a secondary amine, a tertiary amine, and a mixture thereof, and a naphthenic acid, or a mixture of said reaction mixture and a conventional polyol, the reaction conditions are a temperature between 0.degree. C. and 150.degree. C. and an amino equivalent to carboxylic equivalent of 0.3:1 to 50:1.

1. Field of the Invention
This invention relates to a process of making an urethane group-containing polyisocyanurate foam from a polyisocyanate and a polyhydroxy compound wherein the polyhydroxy compound is an acid, neutral, or basic salt, or a mixture thereof of naphthenic acid and a hydroxyl group-containing amine selected from the group consisting of a secondary amine, a tertiary amine and a mixture thereof; or a mixture of the aforementioned salts and conventional polyols.
2. Description of the Prior Art
The manufacture of semi-rigid and rigid polyurethane foams from polyols, particularly polyfunctional polyether polyols, organic polyisocyanates, catalysts, blowing agents and auxiliaries and additives is described in detail in the appropriate literature (Plastics Handbook, Vol. VII, "Polyurethanes" by R. Vieweg and A. Hoechtlen, Carl Hanser Publishers, Munich, 1966).
Swiss Pat. No. 343,635 relates to the use of salts of secondary or tertiary amines which may contain hydroxyl groups in bonded form and monocarboxylic acid, polycarboxylic acids, sulfonic acids, or acid sulfuric ester as initiators for the manufacture of polyurethane foam in quantities of 1 weight percent to 10 weight percent relative to the polyhydroxy compound. When hydroxyl group-containing salts are used, the hydroxyl groups are masked prior to the urethane reaction by addition or condensation reaction.
Fatty acids, fatty acid esters, fatty acid amides or salts of fatty acids may also be used for making of polyurethane foam. German Patent Application No. 1,173,643 relates to the manufacture of flexible foams with the hand desired for textile processing and a velvet-like surface structure from toluene diisocyanate, a special polyester polyol, and a particular blowing agent mixture in the presence of 1 weight percent to 10 weight percent, relative to the polyester polyol, of tall oil. British Pat. No. 882,949 relates to making foams from natural water-containing salts of hydroxy fatty acids such as hydroxy stearic acid, resinoleic acid, and castor oils, and secondary and tertiary amines. British Pat. No. 1,248,919 relates to making foams from amides of fatty acids having 8 to 24 carbon atoms and dialkanol amines which also may contain salts of dialkanol amines and fatty acids as well as fatty acid esters. The salts themselves form extremely brittle foams which frequently collapsed. U.S. Pat. No. 3,178,300 relates to producing polyurethane foams with a skeletal structure of cell webs instead of cell walls from polyisocyanates and castor oil in the presence of monoalcohols having 1 carbon atom to 18 carbon atoms or of monocarboxylic acids having 2 carbon atoms to 18 carbon atoms.
A drawback of the above mentioned foams, particularly those based on tall oils, is that they usually have a very unpleasant odor. Furthermore, polyurethane foams containing high amounts of natural materials have somewhat less favorable compression strength characteristics than products containing synthetic polyols only.
The area of application of such foams is limited by their burning characteristics in relation to classification of construction materials. This drawback may be eliminated by adding fire protection agents in larger quantities. These include antimony oxide, chlorinated compounds such as the Diels-Alder adduct of hexahalogencyclopentadiene and maleic anhydride or of halogenated phosphorus compounds such as tris(2-chloroethyl)phosphate, tris(dichloropropyl)phosphate, or tris(2,3-dibromopropyl)phosphate.
However, the problem is only partially solved by these measures because the achieved flame resistance results in a considerable reduction of other physical properties such as compression strength and dimensional stability under influence of heat. Furthermore, this measure is expensive.
The manufacture of urethane group-containing polyisocyanurate foams is not new either.
Such polymer foams have a comparatively high dimensional stability under influence of heat and improved flame resistance. However, polyisocyanate foams are very brittle. The brittleness can be reduced by increasing the polyol content. A drawback of this, however, is that the flame-inhibiting properties are reduced thereby.

Urethane group-containing polyisocyanurate foam based on naphthenic acid-hydroxylamine adduct


A receiver with an integrated mixer/Sigma-Delta Modulator configuration for digitizing a relatively low-bandwidth signal modulated on a high-frequency carrier, for example in a radio receiver. The Sigma-Delta Modulator has an continuous-time loop filter (F1, F2) with anti-aliasing characteristics which eliminate the need for a separate lowpass filter between the mixer (MX) and the Sigma-Delta Modulator.

1. Field of the Invention
The invention relates to a receiver comprising: a mixer for mixing an oscillator signal with a carrier signal modulated by an information signal, and an analog-to-digital converter for converting the information signal to a digital signal.
2. Description of Related Art
FIG. 1 shows a block diagram of a conventional superheterodyne receiver. By way of example a receiver for a GSM (Global System for Mobile communication) telephone is shown. However, similar techniques are used in, for example paging or radio receivers. The radio frequency (RF) signal is first mixed to an intermediate frequency (IF) using a first local oscillator signal LO1. After that the information signals I and Q are separately mixed down to baseband signals using two mixers MX2A and MX2B and second local oscillator signals LO2A and LO2B which have a phase difference of 90 degrees. After passing an anti-aliasing lowpass filter LPF the information signals are converted to the digital domain by means of analog-to-digital (A/D) converters. In this conventional receiver the mixing-down to baseband signal and the conversion of the baseband signal to a digital signal requires a mixer, a lowpass filter and an A/D converter. Such a solution has a drawback that it is costly because of the relatively expensive passive filter used in the superheterodyne receivers.
It is an object of the invention to mitigate the drawbacks of the conventional receiver. To this end the receiver as specified in the opening paragraph is characterised in that the analog-to-digital converter is a sigma-delta converter comprising: an input stage for coupling the information signal to an input of a continuous-time loopfilter, a quantizer for quantizing an output signal of the loopfilter and for generating the digital signal, and a digital-to-analog converter for feeding back the digital signal to the input of the loopfilter, the input stage comprising the mixer and having a first input for receiving the carrier signal, a second input for receiving the oscillator signal and an output coupled to the input of the loopfilter for providing the information signal to the loopfilter.
The approach according to the invention uses a mixer and a Sigma-Delta Modulator for A/D conversion without anti-aliasing lowpass filter. The output of the mixer is directly supplied to the loop filter of the Sigma-Delta Modulator. The use of a Sigma-Delta Modulator for converting an analog signal to a digital signal is known from, for example, an article by E. J. van der Zwan and E. C. Dijkmans: xe2x80x9cA 0.2-mW CMOS Sigma-Delta Modulator for Speech Coding with 80 dB Dynamic Rangexe2x80x9d, IEEE Journal of Solid-State Circuits, Vol. 31, No. 12, December 1996. The principle of operation of the Sigma-Delta Modulator, as described in the referenced article, is that the information signal is fed to a feedback loop comprising a continuous-time analog filter, a sampler and a digital-to-analog converter (DAC). The output signal of the Sigma-Delta Modulator is a stream of bits at a highly oversampled rate. The oversampled bitstream is fed to subsequent digital processing which converts the bitstream to an accurate digitised representation of the information signal in a process known as decimation. The continuous-time analog loop filter used in the Sigma-Delta Modulator of the referenced article has good anti-aliasing characteristics. Therefore by employing the Sigma-Delta Modulator as an A/D converter in the aforementioned receiver, the lowpass filter between the mixer and the A/D converter can be omitted. This can lead to simple mixer/Sigma-Delta Modulator structures with less components, chip area and power consumption. Preferred and advantageous embodiments are defined in the dependent claims.

Receiver having integrated mixer and Sigma-Delta analog-to digital conversion


An anti-fouling coating utilizes capsaicin as an anti-fouling agent. In a preferred embodiment, finely divided capsaicin, an oleoresin capsaicin liquid solution, or crystalized capsaicin, is mixed with a suitable corrosion resistant epoxy resin which is then mixed with a hardening catalyst and applied to the surface to be treated. In some applications, finely divided inert particles may be added to impart additional desirable characteristic to the surface. The capsaicin constituent used in the coating preferably has a rating of from about 100,000 to about 1,500,000 Scoville Heat Units. The capsaicin may be mixed with a silicon dioxide and then solubilized into a free-flowing homogeneous liquid oleoresin composition by adding a solvent to increase solubility and facilitate mixing. The capsaicin may also be formed into crystals which are mixed with the coating material. The anti-fouling composition can be used in combination with conventional anti-fouling coatings and paints and binders and applied to wood, metal, and plastic surfaces. The anti-fouling composition may also be added to other materials in molding processes to form various articles of manufacture and molded products, such as boat hulls and water pipes, which resist fouling by organisms common in fresh water and sea water.

1. Field of the Invention
This invention relates generally to anti-fouling coatings, and more particularly to an anti-fouling coating containing capsaicin as an active ingredient.
2. Brief Description of the Prior Art
Various antifungal, algeacides, and antifouling agents have been used in coatings and paints for different environments to prevent mildew, fungus, and sea water flora and fauna.
The mildew or fungus which grows on house paints and the like, utilizes the paint medium, or in some cases, the underlying substrate, such as wood, as the nutrient. The micelia and fruiting bodies of the fungi contact or penetrate the paint film and thus, through intimate contact with any fungicides in the film (to a large extent regardless of whether the fungicides are highly soluble, slightly soluble, or insoluble in water), the fungi are destroyed.
In cooling towers and piping systems utilizing fresh water, slime and algea may develop if effective compounds for combating their growth are not present. In the area of anti-fouling paints, a relatively narrow group of compounds is useful for preventing the fouling of marine structures, such as boat or ship hulls, pilings, oil well drilling towers, and the like, by organisms common in sea water and brackish water. Such organisms include; algea, slime, hydroids, mollusks, barnacles, and the like.
A critical factor, particularly in fresh water and sea water marine applications is that the active ingredient in the coating or paint cannot be highly soluble or it will leach out of the anti-fouling coating or paint in a short period of time and drastically reduce its effectiveness. On the other hand, many anti-fouling coatings and paints provide an active ingredient which is allowed to leach over a period of time or which forms a film on the exterior of the coated or painted surface to combat the fouling organisms.
Conventional anti-fouling agents used in marine anti-fouling coatings and paints include inorganic heavy-metal compounds such as mercury and copper, and various types of organic and organo-metallic compounds. However, the inorganic metal compounds loose their effectiveness rapidly in sea water contaminated with hydrogen sulfide. Some of the organic anti-fouling agents are effective for preventing the attachment of only particular marine lives, but are not effective against others. Among the inorganic and organic compounds, there are many which may be effective for preventing the attachment of marine lives, but are not suited for practical use because of their toxicity to the human body or other marine life, or will pollute the environment.
Takagi et al, U.S. Pat. No. 3,912,519 discloses an anti-fouling ship bottom paint containing an active ingredient comprising 5-chloro-4-phenyl-1,2-dithiol-3-one or a mixture of that compound and 3,5-di-lower alkyl-4-hydroxy-benzylidene. These compounds have such a high rate of decomposition that they have no residual toxicity and cause no environmental pollution.
Davie, U.S. Pat. No. 3,997,461 discloses an anti-foulant coating composition composed of two components (A) and (B) which are mixed immediately before the composition is applied. The active ingredient of Component A is a base of coal-tar pitch or equivalent and epoxy resin. The active ingredients of component B are a curing agent for the epoxy resin and a solid organo tin toxicant, mainly a solid trialkylin carboxylate. The toxicant may either be a slurry of needle-like crystals or the toxicant may be dissolved in a solvent. The toxic activity is due to the tin content of the organatin toxicant.
Milne et al, U.S. Pat. No. 4,021,392 discloses an anti-fouling marine paint composition which releases organo tin ions into sea water. The composition comprises; a film-forming copolymer of at least one triorgano tin salt of an olefinically unsaturated carboxylic acid and the balance of the copolymer being units of at least one olefinically unsaturated comonomer, a substantially water insoluble metalliferous pigment capable of reacting with sea water to form the mater soluble metal compound, and a hydrophobic organic retarder for retarding the rate of ion exchange between sea water and the copolymer.
Dupont, U.S. Pat. No. 4,127,687 discloses an anti-fouling marine paint containing an organic binder and an effective amount of certain 3-isothaizolones.
Freeman et al, U.S. Pat. Nos. 4,789,567 and 4,968,538 disclose an abrasion resistant coating and method of application wherein a protective coating of resin containing finely divided abrasion resistant particles is diluted with a solvent and applied to a surface. The applied coating is cured to achieve either a single layer of inert material dispersed in the resin, or two layers including a dense layer of inert material in resin covered by a thin layer of resin, and to provide a glossy or matte appearance as desired.
"Capsaicin" is an incredibly powerful and stable alkaloid seemingly unaffected by heat or cold, which retains its original potency over time, cooking, or freezing. Capsaicin is the bitter compound and naturally occurring heat source for chile peppers of the genus Capsicum, as C. frutescens, and is concentrated mostly in the placental tissue of the pepper. For every hundred parts of capsaicin in the placental tissue, there are six parts in the rest of the fruit tissue, and four parts in the seeds. Two very pungent synthetic capsainoid compounds are capsaicin (C) and dihydrocapsaicin (DHC).
The technique for determining capsaicin pungency is by high-pressure liquid chromatography (HPLC). The standard industry measurement for capsaicin levels is given in Scoville Heat Units. Pure capsaicin equals 16 million Scoville Units. The following chart illustrates the range of Scoville Heat Units present in various chile pepper varieties utilizing HPLC.
______________________________________ Chile Pepper Variety Approx. Scoville Units ______________________________________ Habenaro, Bahamian 100,000-300,000 Santaka, Chiltepin, Thai 50,000-100,000 Aji, Rocoto, Piquin, Cayenne, Tabasco 30,000-50,000 de Arbol 15,000-30,000 Yellow Wax Hot, Serrano 5,000-15,000 Jalapeno, Mirasol 2,500-5,000 Sandia, Cascabel 1,500-2,500 Ancho, Pasilla, Espanola 1,000-1,500 NuMex Big Jim, NM 6-4 500-1,000 R-Naky, Mexi-Bell, Cherry 100-500 Mild Bells, Pimiento, Sweet Banana 0 ______________________________________
Various kinds of pepper derivatives have been known to be used to repel pests.
Yaralian, U.S. Pat. No. 4,455,304 discloses a composition for repelling birds wherein the active ingredients are finely divided dried cayenne pepper (30,000-50,000 Scoville Units), finely divided dried garlic diluted by inert, finely divided mineral material (dry application) or water (liquid application) for application to the earth surface or to growing plants. The garlic constituent is present in at least about one-fifth to about five times the pepper constituent.
Oleoresin Capsicum is an extract of natural spice and is commonly used in foods and medicinal applications whenever a warming or pungent sensation is desired.
Kalsec, Inc. of Kalamazoo, Mich. produces a commercially available oleoresin capsicum product which is commonly used as a food flavoring under the product name of "Oleoresin Capsicum, African type, 6% MC". This product is made from the dried fruit of Capsicum frutescens mixed with vegetable oils and contains 5.40% to 6.60% capsainoids.
Fischer, U.S. Pat. No. 5,226,380 discloses a marine coating containing cayenne pepper and method of applying the coating. Fischer teaches applying a layer of waterproof adhesive or paint to the surface to be protected, and then applying a deposit of cayenne pepper (30,000-50,000 Scoville Units), to the adhesive layer while it is in the uncured state. A layer of copper granules may also be applied to the adhesive layer after the cayenne pepper in sufficient density to cover the entire surface while leaving sufficient spacing between the copper granules to form a permeable layer through which the repellent properties of the pepper can diffuse and in cooperation with the copper granules provide additional protection for the surface. Alternatively, a copper wire screen, an unwoven mat of copper wires, or short chopped lengths of copper wire, may be used instead of the granules to provide a permeable layer of copper. Fischer also teaches that at least part of the anti-fouling materials may be mixed with the adhesive and applied simultaneously. As the paint leaches away, the anti-foulant is exposed to "release heat" to repel marine organisms in the vicinity of the surface.
In the Fischer process the anti-foulant properties of the pepper particles would be short lived whether it is applied as an outer layer or mixed with the paint prior to application, due to leaching either into the paint mixture or into the water surrounding the coating. Fischer also utilizes particles or an oleoresin capsicum derived from the cayenne pepper which would have a pungency rating of only 30,000-50,000 Scoville Units. It has also been found that merely mixing an oleoresin with an adhesive, ablative paint, or epoxy or polyurethane compounds, will often adversely affect the curing time and physical properties of the coating material.
The present invention is a significant improvement in that it utilizes an oleoresin capsicum, capaiscin particles, or capsaicin crystals which are derived from the Habenaro pepper which has a pungency rating of 100,000-300,000 Scoville Units in the natural state and which, as utilized in the preferred embodiment, is highly concentrated to produce a pungency rating of from 1,000,000-1,500,000 Scoville Units. To overcome the incompatibility problem with mixing oleoresin with marine coatings, the present process mixes the capsaicin (alkaloid) with a selected solvent and with silicon dioxide to form an improved additive which is more compatible with the coating material and with coloring agents, pigments, and dyes.
Compatibility of the present additive with the coating mixture is also improved by adding a binding agent to the coating material, prior to adding the previously described additive. The present invention also discloses a process for producing capsaicin crystals which prevents, to a large degree, the "bleedout" of the anti-foulant capsaicin into the coating mixture and permits greater loading of the coating with the capsaicin than the process using a liquid oleoresin capsaicin mixture. Mixing the crystalized capsaicin with various coating materials, such as marine paints, or epoxy or polyurethane compounds, reduces the adverse effects on the curing time and physical properties of the coating material which might otherwise occur when using a liquid oleoresin capsaicin.
A much longer lasting and durable anti-fouling coating is obtained by combining the present additive with finely divided abrasion resistant particles (ceramic). The improved compatibility of the present additive with other materials also makes it suitable for use in molding products and creating articles of manufacture having a surface with the capsaicin contained therein.
The present invention is distinguished over the prior art in general, and these patents in particular by an anti-fouling coating which utilizes capsaicin as an anti-fouling agent. In a preferred embodiment, finely divided capsaicin, an oleoresin capsaicin liquid solution, or crystalized capsaicin is mixed with a suitable corrosion resistant epoxy resin which is then mixed with a hardening catalyst and applied to the surface to be treated. In some applications, finely divided inert particles may be added to impart additional desirable characteristic to the surface. The capsaicin constituent used in the coating preferably has a rating of from about 100,000 to about 1,500,000 Scoville Heat Units. The capsaicin may be mixed with a silicon dioxide and then solubilized into a free-flowing homogeneous liquid oleoresin composition by adding a solvent to increase solubility and facilitate mixing. The capsaicin may also be formed into crystals which are mixed with the coating material. The anti-fouling composition can be used in combination with conventional anti-fouling coatings and paints and binders and applied to wood, metal, and plastic surfaces. The anti-fouling composition may also be added to other materials in molding processes to form various articles of manufacture and molded products, such as boat hulls and water pipes, which resist fouling by organisms common in fresh water and sea water.

Anti-fouling coating composition containing capsaicin