Disclosed herein are compositions comprising hyaluronic acid-nonsteroidal anti-inflammatory drug conjugates and methods for making the same. The compositions of the present disclosure can be used to prevent or treat subjects suffering from inflammation related conditions, such as, inflammation-mediated hearing loss.
Disclosed herein are compositions comprising hyaluronic acid-antioxidant conjugates, wherein a low molecular weight hyaluronic acid is used in said conjugates. These compositions can be used to prevent or treat subjects suffering from hearing loss, such as oxidative stress-mediated hearing loss.
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
A61K 47/50 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
3.
COMPUTER MODELING FOR DISCRETIONARY REST PREDICTIONS
Techniques for improving computer modeling for generating predictions are described herein. In one example, a computer model is generated to examine data representing time slots in a schedule. In particular, the computer model can be configured to calculate a homeostatic pressure at a first slot in the schedule and determine (1 ) whether the calculated value of homeostatic pressure at the first slot exceeds a preset threshold and (2) whether the first slot corresponds to a preset status. In response to positive determinations to both, the computer model can iteratively search for a second slot in a portion of the schedule that precedes the first slot such that discretionary operations at the second slot would reduce the homeostatic pressure at the first slot to not exceed the threshold. Thus, the computer model can predict the discretionary operations even without relying on historical records of such operations.
G06Q 10/04 - Forecasting or optimisation specially adapted for administrative or management purposes, e.g. linear programming or "cutting stock problem"
The present disclosure relates to an auto-expression broth and process of using the broth for the efficient expression of recombinant proteins of interest in a microbial host (e.g, a bacterial host). The broth and process produce high yields of recombinant proteins in a wide variety of expression systems. The disclosure also relates to auto-expression systems, methods and kits using the auto-expression broths of the present disclosure.
C12N 1/00 - Microorganisms, e.g. protozoaCompositions thereofProcesses of propagating, maintaining or preserving microorganisms or compositions thereofProcesses of preparing or isolating a composition containing a microorganismCulture media therefor
41 - Education, entertainment, sporting and cultural services
Goods & Services
Clothing, namely, sports jerseys, t-shirts, sweatshirts, sweaters, hats, beanies, shirts, pants, jackets, coats, socks, and gloves. Entertainment in the nature of competitions in the field of American football.
6.
COMPOSITIONS AND METHODS TARGETING FILAMENTOUS BACTERIOPHAGE
Multivalent conjugates and conjugate compositions of peptides derived from the CoaB coat protein of Pseudomonas aeruginosa filamentous (Pf) bacteriophage and conjugates adjuvanted with a TLR 4 and/or TLR 7/8 agonist induce and/or enhance an immune response toward Pseudomonas aeruginosa filamentous (Pf) bacteriophage. The conjugates, compositions, and vaccines have utility to reduce, prevent and/or ameliorate the adverse effect of Pseudomonas aeruginosa infection, such as biofilm formation.
C07H 13/08 - Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings
A61K 39/04 - Mycobacterium, e.g. Mycobacterium tuberculosis
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
41 - Education, entertainment, sporting and cultural services
Goods & Services
Clothing, namely, Rugby shirts, t-shirts, scrub tops not for medical purposes, scrub pants not for medical purposes, polo shirts, boxer shorts, lab coats, visors being headwear, caps being headwear, knit caps, flip flops for use as footwear, athletic pants, sweatshirts, wind resistant jackets Arranging and conducting athletic competitions
10.
APPARATUS AND METHOD FOR QUANTIFYING ENVIRONMENTAL DNA WITH NO SAMPLE PREPARATION
A fieldable processing and detection apparatus for automatically collecting, preparing, Identifying and quantifying environmental DNA in samples of a material of Interest. Environmental samples of materials of interest are combined with polymerase chain reaction (PGR) reagents that are selectively compatible with the material of Interest and mixed. Various processing methods may be employed at the discretion of the operator and include droplet concentration, thermoprofiling, particle separation and other techniques or methods that are compatible with and suitable for the specific material of interest and the testing environment The system will selectively lyse cells, breaking down the cell membrane via mechanical disruption, ultrasound, thermocycling, or other suitable techniques and thereafter quantify the preamplified concentration of target nucleic add sequences using digital quantification.
G01N 35/08 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
Lipidated oxoadenines of formula (I) are TLR7/8 receptor ligands useful for modulating immune responses. The compounds may have therapeutic application in the treatment of cancer, infectious diseases, allergy, or autoimmune disorders.
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
The present disclosure provides compounds of formula (I), (Ia), and (Ib), squaryl group- containing toll-like receptor ligands Also provided are pharmaceutical compositions and vaccine composition thereof and methods of treating a disease of disorder with the compounds and composition described herein.
The present disclosure provides compounds of formula (I), (Ia), and (Ib), squaryl group- containing toll-like receptor ligands Also provided are pharmaceutical compositions and vaccine composition thereof and methods of treating a disease of disorder with the compounds and composition described herein.
C07J 43/00 - Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta[a]hydrophenanthrene skeleton
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
13.
TLR7/8 AGONISTS TO ENHANCE IMMUNE RESPONSES IN OPIOID USING INDIVIDUALS
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/7028 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
A61K 31/4468 - Non-condensed piperidines, e.g. piperocaine having a nitrogen atom directly attached in position 4, e.g. clebopride, fentanyl
A61K 39/00 - Medicinal preparations containing antigens or antibodies
Clothing, namely, rugby shirts, t-shirts, scrub shirts not for medical purposes, scrub pants not for medical purposes, polo shirts, boxer shorts, lab coats, visors being headwear, caps being headwear, knit caps being headwear, flip flops, performance pants, sweatshirts, wind resistant jackets.
41 - Education, entertainment, sporting and cultural services
Goods & Services
Entertainment and educational services, namely, providing courses of instruction at the university level; arranging and conducting athletic competitions, college athletic events, athletic tournaments in the nature of football, basketball, cross country, track and field, golf, soccer, tennis, volleyball, and softball tournaments, and athletic exhibitions for entertainment purposes
16.
DEVICES COMPRISING HYALURONIC ACID AND SILK FIBROIN
The present disclosure provides biocompatible and bioresorbable devices for tissue repair and regeneration and delivery of an active agent across a biological barrier comprising silk fibroin and hyaluronic acid.
The present disclosure provides compositions comprising an isolated polysaccharide comprising β-1,4 linked galactosamine and glucosamine monomers, wherein the amino groups of each of the galactosamine and glucosamine are partially substituted with acetate. The disclosure further provides vaccine, methods of use, and methods of producing the isolated polysaccharide.
This disclosure relates to compounds that target microtubules, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases. More particularly, this disclosure relates to modified carbazole compounds and pharmaceutical compositions thereof, methods of targeting microtubules with these compounds, and methods of treating diseases affected by microtubule disruption.
The present disclosure provides compositions comprising a hydrolyzed tetraethyl orthosilicate (TEOS) and at least one macromolecule selected from the group consisting of hyaluronan and silk fibroin and methods of making thereof. The disclosure further provides methods of using the composition for delivery of an active agent and for treatment of diseases and disorders. Also provided are delivery devices and kits comprising the disclosed composition.
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
Lipidated oxoadenines of formula (I) are TLR7/8 receptor ligands useful for modulating immune responses. The compounds may have therapeutic application in the treatment of cancer, infectious diseases, allergy, or autoimmnune disorders.
Lipidated oxoadenines of formula (I) are TLR7/8 receptor ligands useful for modulating immune responses. The compounds may have therapeutic application in the treatment of cancer, infectious diseases, allergy, or autoimmnune disorders.
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
A fieldable processing and detection apparatus for automatically collecting, preparing, Identifying and quantifying environmental DNA in samples of a material of Interest. Environmental samples of materials of interest are combined with polymerase chain reaction (PGR) reagents that are selectively compatible with the material of Interest and mixed. Various processing methods may be employed at the discretion of the operator and include droplet concentration, thermoprofiling, particle separation and other techniques or methods that are compatible with and suitable for the specific material of interest and the testing environment The system will selectively lyse cells, breaking down the cell membrane via mechanical disruption, ultrasound, thermocycling, or other suitable techniques and thereafter quantify the preamplified concentration of target nucleic add sequences using digital quantification.
A fieldable processing and detection apparatus for automatically collecting, preparing, Identifying and quantifying environmental DNA in samples of a material of Interest. Environmental samples of materials of interest are combined with polymerase chain reaction (PGR) reagents that are selectively compatible with the material of Interest and mixed. Various processing methods may be employed at the discretion of the operator and include droplet concentration, thermoprofiling, particle separation and other techniques or methods that are compatible with and suitable for the specific material of interest and the testing environment The system will selectively lyse cells, breaking down the cell membrane via mechanical disruption, ultrasound, thermocycling, or other suitable techniques and thereafter quantify the preamplified concentration of target nucleic add sequences using digital quantification.
The present disclosure provides compounds of formula (I), (Ia), and (Ib), squaryl group- containing toll-like receptor ligands. Also provided are pharmaceutical compositions and vaccine composition thereof and methods of treating a disease of disorder with the compounds and composition described herein.
The present disclosure provides biocompatible and bioresorbable devices for tissue repair and regeneration and delivery of an active agent across a biological barrier comprising silk fibroin and hyaluronic acid.
The present disclosure provides biocompatible and bioresorbable devices for tissue repair and regeneration and delivery of an active agent across a biological barrier comprising silk fibroin and hyaluronic acid.
An autonomous bioaerosol sampling and detection system and method adapted to provide real-time detection and identification of bio-organisms in aerosols without human intervention.
The present disclosure provides compositions comprising an isolated polysaccharide comprising ?-1,4 linked galactosamine and glucosamine monomers, wherein the amino groups of each of the galactosamine and glucosamine are partially substituted with acetate. The disclosure further provides vaccine, methods of use, and methods of producing the isolated polysaccharide.
The present disclosure provides compositions comprising an isolated polysaccharide comprising β-1,4 linked galactosamine and glucosamine monomers, wherein the amino groups of each of the galactosamine and glucosamine are partially substituted with acetate. The disclosure further provides vaccine, methods of use, and methods of producing the isolated polysaccharide.
C07H 13/08 - Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings
This disclosure relates to compounds that target microtubules, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases. More particularly, this disclosure relates to modified carbazole compounds and pharmaceutical compositions thereof, methods of targeting microtubules with these compounds, and methods of treating diseases affected by microtubule disruption.
41 - Education, entertainment, sporting and cultural services
Goods & Services
Arranging and conducting athletic competitions; Basketball camps; Entertainment in the nature of competitions in the field of athletics; Organizing and conducting college athletic events; Recreational camps; Sport camps; Summer camps
The present disclosure provides compositions comprising a hydrolyzed tetraethyl orthosilicate (TEOS) and at least one macromolecule selected from the group consisting of hyaluronan and silk fibroin and methods of making thereof. The disclosure further provides methods of using the composition for delivery of an active agent and for treatment of diseases and disorders. Also provided are delivery devices and kits comprising the disclosed composition.
A61K 31/403 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61Q 1/04 - Preparations containing skin colorants, e.g. pigments for lips
The present disclosure provides compositions comprising a hydrolyzed tetraethyl orthosilicate (TEOS) and at least one macromolecule selected from the group consisting of hyaluronan and silk fibroin and methods of making thereof. The disclosure further provides methods of using the composition for delivery of an active agent and for treatment of diseases and disorders. Also provided are delivery devices and kits comprising the disclosed composition.
A61K 8/899 - Polysiloxanes containing atoms other than silicon, carbon, oxygen and hydrogen, e.g. dimethicone copolyol phosphate containing sulfur, e.g. sodium PG-propyldimethicone thiosulfate copolyol
21 - HouseHold or kitchen utensils, containers and materials; glassware; porcelain; earthenware
25 - Clothing; footwear; headgear
41 - Education, entertainment, sporting and cultural services
Goods & Services
All-purpose carrying bags; Backpacks; Duffle bags; Luggage Beverageware; Cups; Drinking glasses, namely, tumblers; Drinking
vessels; Insulated containers for food or beverages; Mugs Aprons; Bandanas; Baseball caps and hats; Pullovers; Shirts;
Sweatshirts; T-shirts; Education services, namely, training educators in the field of wildlife biology, management, and conservation and providing curricula in connection therewith; Educational and entertainment services, namely, providing motivational and educational speakers; Educational services, namely, providing online courses of instruction at the secondary, undergraduate, and graduate level and distribution of course material in connection therewith; Entertainment services in the nature of production of multimedia content
Lipidated oxoadenines of formula (I) are TLR7/8 receptor ligands useful for modulating immune responses. The compounds may have therapeutic application in the treatment of cancer, infectious diseases, allergy, or autoimmune disorders.
A61K 31/7056 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
Lipidated oxoadenines of formula (I) are TLR7/8 receptor ligands useful for modulating immune responses. The compounds may have therapeutic application in the treatment of cancer, infectious diseases, allergy, or autoimmune disorders.
An autonomous bioaerosol sampling and detection system and method adapted to provide real-time detection and identification of bio-organisms in aerosols without human intervention.
The methods and compositions described herein relate to methods of immunization or stimulating an immune response, e.g., using agonists of TLR7 and/or TLR8 as antigens. The methods and compositions described herein have particular relevance to use in infants.
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/685 - Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
16-membered macrolide compounds inhibit growth of various microbial species and have utility in the treatment of systemic or topical microbial infections, including methicillin-resistant strains (Formula I).
A61K 31/335 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
C07D 313/00 - Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 491/044 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
C07D 255/02 - Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups not condensed with other rings
This disclosure relates to compounds that target microtubules, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases. More particularly, this disclosure relates to modified carbazole compounds and pharmaceutical compositions thereof, methods of targeting microtubules with these compounds, and methods of treating diseases affected by microtubule disruption.
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 209/86 - CarbazolesHydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
A61K 31/403 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
The present invention provides minimally invasive methods of detecting, diagnosing, and assessing neuronal damage associated with traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE). Specific species of microRNAs (miRNA), small, noncoding RNA molecules that play gene regulatory functions, are correlated with cellular damage and oxidative stress following TBI or CTE, allowing for rapid, minimally-invasive diagnosis and assessment of brain injury. The early identification and longitudinal assessment of neuronal damage in subjects suffering from or at risk of suffering from a TBI (e.g., football players, boxers, military personnel, fall victims) will improve clinical outcomes by guiding critical medical and behavioral decision making.
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
52.
Fluorescent halogen bonding arylethynyl scaffolds for anion recognition
C07D 233/56 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
C07D 213/22 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing two or more pyridine rings directly linked together, e.g. bipyridyl
C07D 213/90 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having more than three double bonds between ring members or between ring members and non-ring members
A61K 31/7016 - Disaccharides, e.g. lactose, lactulose
A61K 31/7034 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
C07H 13/04 - Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
C07H 13/08 - Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings
A61K 31/7016 - Disaccharides, e.g. lactose, lactulose
A61K 31/7034 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
The present invention is directed to pharmaceutical compositions and methods of treating traumatic brain injury (TBI). The invention is also directed to pharmaceutical compositions and methods of treating a transient hypoxic and/or ischemic condition in the central nervous system. More specifically, the present invention is directed to pharmaceutical compositions and methods of reducing the occurrence of neuronal cell death in the central nervous system, such as, reducing the occurrence brain cell death in the hippocampus and/or the cortex.
16-membered macrolide compounds inhibit growth of various microbial species and have utility in the treatment of systemic or topical microbial infections, including methicillin-resistant strains (Formula I).
C07D 313/00 - Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
C07D 255/02 - Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups not condensed with other rings
The methods and compositions described herein relate to methods of immunization or stimulating an immune response, e.g., using agonists of TLR7 and/or TLR8 as antigens. The methods and compositions described herein have particular relevance to use in infants.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
The present invention provides minimally invasive methods of detecting, diagnosing, and assessing neuronal damage associated with traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE). Specific species of microRNAs (miRNA), small, noncoding RNA molecules that play gene regulatory functions, are correlated with cellular damage and oxidative stress following TBI or CTE, allowing for rapid, minimally-invasive diagnosis and assessment of brain injury. The early identification and longitudinal assessment of neuronal damage in subjects suffering from or at risk of suffering from a TBI (e.g., football players, boxers, military personnel, fall victims) will improve clinical outcomes by guiding critical medical and behavioral decision making.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
The present invention provides T-type calcium channel modulators and methods for producing and using the same. In some embodiments, compounds of the invention are of the formula:
m=0 to 1.
C07D 209/88 - CarbazolesHydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
The present invention provides minimally invasive methods of detecting, diagnosing, and assessing neuronal damage associated with traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE). Specific species of microRNAs (miRNA), small, noncoding RNA molecules that play gene regulatory functions, are correlated with cellular damage and oxidative stress following TBI or CTE, allowing for rapid, minimally-invasive diagnosis and assessment of brain injury. The early identification and longitudinal assessment of neuronal damage in subjects suffering from or at risk of suffering from a TBI (e.g., football players, boxers, military personnel, fall victims) will improve clinical outcomes by guiding critical medical and behavioral decision making.
The present invention provides minimally invasive methods of detecting, diagnosing, and assessing neuronal damage associated with traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE). Specific species of microRNAs (miRNA), small, noncoding RNA molecules that play gene regulatory functions, are correlated with cellular damage and oxidative stress following TBI or CTE, allowing for rapid, minimally-invasive diagnosis and assessment of brain injury. The early identification and longitudinal assessment of neuronal damage in subjects suffering from or at risk of suffering from a TBI (e.g., football players, boxers, military personnel, fall victims) will improve clinical outcomes by guiding critical medical and behavioral decision making.
A61M 1/00 - Suction or pumping devices for medical purposesDevices for carrying-off, for treatment of, or for carrying-over, body-liquidsDrainage systems
66.
Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
C07D 317/30 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07C 323/65 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton containing sulfur atoms of sulfone or sulfoxide groups bound to the carbon skeleton
C07C 69/616 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety polycyclic
C07C 69/73 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
C07D 339/06 - Five-membered rings having the hetero atoms in positions 1 and 3, e.g. cyclic dithiocarbonates
C07C 317/44 - SulfonesSulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
C07C 323/62 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
C07C 229/42 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
C07C 229/44 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by unsaturated carbon chains
C07C 57/50 - Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid containing condensed ring systems
C07C 59/54 - Unsaturated compounds containing hydroxy or O-metal groups containing six-membered aromatic rings and other rings
C07C 59/72 - Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings
C07C 59/86 - Unsaturated compounds containing keto groups containing six-membered aromatic rings and other rings
A real-time neural monitor and analyzer of neural activity and a method of using the real-time neural monitor as part of a treatment regime to reduce neurological injury in a subject in need thereof or a method of using the real-time neural monitor to identifying subjects in need of a treatment to prevent and/or reduce neuronal injury and/or onset of a seizure.
The present invention provides T-type calcium channel modulators and methods for producing and using the same. In some embodiments, compounds of the invention are of the formula (I): where R1 is selected from the group consisting of alkyl, alkenyl, polyether, alkoxy and cycloalkyl; X is selected from the group consisting of methylene, -C(=0)-[NR4]a-, -C(=S)-, and -S(=0)b; R2 is selected from the group consisting of heterocycloalkyl and heteroaryl; R3 is selected from the group consisting of alkyl, alkenyl, polyether, alkoxy, cycloalkyl, -NR5R6, -C(=0)NR5R6, -C(=0)ORa (where Ra is alkyl, typically C1-C8 alkyl, often C2-C6 alkyl, and in one particular embodiment Ra is tert-butyl), and -S02NR5R6; R4 is hydrogen, alkyl, or a nitrogen protecting group; each of R5 and R6 are independently selected from the group consisting of hydrogen and alkyl; a is 0 or 1; b is 1 or 2; n=l to 3; and m=0 to 1.
A01N 43/38 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings
The present invention provides minimally invasive methods of detecting, diagnosing, and assessing neuronal damage associated with traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE). Specific species of microRNAs (miRNA), small, noncoding RNA molecules that play gene regulatory functions, are correlated with cellular damage and oxidative stress following TBI or CTE, allowing for rapid, minimally-invasive diagnosis and assessment of brain injury. The early identification and longitudinal assessment of neuronal damage in subjects suffering from or at risk of suffering from a TBI (e.g., football players, boxers, military personnel, fall victims) will improve clinical outcomes by guiding critical medical and behavioral decision making.
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
70.
METHOD OF REDUCING NEURONAL CELL DEATH WITH HALOALKYLAMINES
The present invention is directed to pharmaceutical compositions and methods of treating traumatic brain injury (TBI). The invention is also directed to pharmaceutical compositions and methods of treating a transient hypoxic and/or ischemic condition in the central nervous system. More specifically, the present invention is directed to pharmaceutical compositions and methods of reducing the occurrence of nerounal cell death in the centeral nervous system, such as, reducing the occurrence brain cell death in the hippocampus and/or the cortex.
The present invention relates to a compound of Formula (I) or (II)
or a salt thereof, wherein R is described herein. The compounds are novel hydroxy-proline analog inhibitors of the ASCT1 and ASCT2 neutral amino acid transporters.
UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION (USA)
UNIVERSITY OF MONTANA (USA)
Inventor
Diaz, Philippe
Isoherranen, Nina
Abstract
The present disclosure is generally directed to compositions and methods for treating diseases that are ameliorated by the inhibition of CYP26 mediated retinoic acid metabolism. The compositions comprise compounds of formula (I). A repreid50000060307390 IB/345 nullsents aryl optionally substituted with one, two, three, or four groups that are each independently halogen, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, C1-C6 alkoxy, and C1-C6 haloalkoxy; X is a bond, −CH2-, -CHR5-, -C=CHR4-, -NR4-, -N=O-R4-, −O-, −S-, −SO-, −SO2-, −C(O)-, or −C(NR4)-, or X is of formula (a), (b) or (c), wherein each n is independently 1, 2, or 3; each R4 is independently hydrogen or C1-6 alkyl; R5 is independently hydrogen, C1-6 alkyl, or −OR6, where R6 is selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyL C3-12 cycloalkyl, heterocyclyl, aryl, arylC1-6 alkyl, heteroaryl, or heteroarylC1-6 alkyl; Y is C1-6 alkylene, C2-6 alkenylene, or C2-6 alkylylene moiety.
C07D 317/30 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07C 69/616 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety polycyclic
C07C 69/73 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
C07D 339/06 - Five-membered rings having the hetero atoms in positions 1 and 3, e.g. cyclic dithiocarbonates
C07C 317/44 - SulfonesSulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
C07C 317/46 - SulfonesSulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
C07C 323/62 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
C07C 229/42 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
C07C 229/44 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by unsaturated carbon chains
C07C 57/50 - Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid containing condensed ring systems
C07C 59/54 - Unsaturated compounds containing hydroxy or O-metal groups containing six-membered aromatic rings and other rings
C07C 59/72 - Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings
C07C 59/86 - Unsaturated compounds containing keto groups containing six-membered aromatic rings and other rings
A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
A61K 31/385 - Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
73.
Aspartylamide inhibitors of excitatory amino acid transporters
The compounds of the invention are inhibitors of excitatory amino acid transporters (EAAT) that penetrate the blood-brain barrier to access the central nervous system. The compounds of the invention follow the structural formula:
or a salt, ester or prodrug thereof, wherein X is a halogen, such as fluorine, or a radionuclide, such as fluorine-18. The compounds and methods described herein can be used for the treatment of, e.g., neurodegenerative disorders (e.g., amyotrophic lateral sclerosis), ischemia, spinal cord injury, and traumatic brain injury in a patient (e.g., a human). The invention further provides compounds and methods for the synthesis and use of radiographic tracers to diagnose and follow the progression of such disorders.
C07C 69/635 - Halogen-containing esters of saturated acids containing rings in the acid moiety
C07C 237/04 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
C07B 59/00 - Introduction of isotopes of elements into organic compounds
C07C 67/317 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groupsPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenolysis of functional groups
The invention provides methods for the detection of brain injury, such as traumatic brain injury (TBE) or chronic traumatic encephalopathy (CTE), in a patient (e.g., a human) that has suffered or is at risk of suffering one or more traumatic events. The methods of the invention measure, through non-invasive or invasive means, the expression of System xc- cystine/glutamate transporter expression in patient tissue (e.g., neuronal tissue). The loss of System xc- cystine/glutamate transporter expression is correlated with brain injury, severity, and disease progression.
The compounds of the invention are inhibitors of excitatory amino acid transporters (EAAT) that penetrate the blood-brain barrier to access the central nervous system. The compounds of the invention follow the structural formula: or a salt, ester or prodrug thereof, wherein X is a halogen, such as fluorine, or a radionuclide, such as fluorine-18. The compounds and methods described herein can be used for the treatment of, e.g., neurodegenerative disorders (e.g., amyotrophic lateral sclerosis), ischemia, spinal cord injury, and traumatic brain injury in a patient (e.g., a human). The invention further provides compounds and methods for the synthesis and use of radiographic tracers to diagnose and follow the progression of such disorders.
A process of growing a culture of cyanobacteria or algae using chitin or chitosan as a source of nitrogen for photosynthetic growth is described. This process can be used to remove pol lutants from nitrogen-deficient natural waters or wastewaters. Biomass that results from photosynthetic growth on chitin can be used, either as whole cells or the isolated components of the cells, for a large variety of commercial purposes.
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Educational services, namely, providing traditional classroom delivery, on-line delivery, and hybrid delivery, namely, a combination of traditional classroom delivery and on-line delivery, of courses of instruction at the college level including credit and non-credit instruction and programming
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Rugby shirts, t-shirts, scrub shirts not for medical purposes, scrub pants not for medical purposes, polo shirts, boxer shorts, lab coats, visors, caps, knit caps, flip flops, performance pants, sweatshirts, wind resistant jackets Entertainment and educational services, namely, providing courses of instruction at the university level; arranging and conducting athletic competitions, athletic events, athletic tournaments, and athletic exhibitions
83.
KNEE BRACE TO LIMIT ROTATION BETWEEN THE FEMUR AND TIBIA
An upper anchor attached to the thigh of a wearer and a lower anchor attached to the calf secure a strap across the knee to allow rotational orthosis control of the tibia and fibula to limit or decrease excessive rotation, and correct resting alignment. The anchors adhere to the skin allowing the strap to be tightened to correct the mal-rotation and to control the corrected position of these two bones thus preventing mal-ration and its associated pain.
A61F 13/06 - Bandages or dressingsAbsorbent pads specially adapted for feet or legsCorn-padsCorn-rings
A61F 5/01 - Orthopaedic devices, e.g. long-term immobilising or pressure directing devices for treating broken or deformed bones such as splints, casts or braces
A61F 5/05 - Devices for stretching or reducing fractured limbsDevices for distractionsSplints for immobilising
84.
Enantiomers of 2'-Fluoralky1-6-nitroquipazine as serotonin transporter positron emission tomography imaging agents and antidepressant therapeutics
Racemic mixtures and individual enantiomers of fluorine-18 or carbon-11 radiolabelled 2′-alkyl-6-nitroquipazine ligands are serotonin transporter (SERT) tracers for positron emission tomography (PET) imaging. The non-radioactive ligand forms possess therapeutic antidepressant in vitro and in vivo pharmacological binding profiles in rodent brain and cells expressing human serotonin transporter (hSERT). Twelve 2′-alkyl-6-nitroquipazine ligands potently bind in sub-nanomolar concentrations to the pre-synaptic SERT binding site where established antidepressant drugs bind and inhibit the re-uptake of the neurotransmitter serotonin (5-HT). In vivo tracer studies in rats as well as monkey PET scan trial have demonstrated the fluorine-18 and carbon-11 positron radionuclide labeled tracers perform as quantitative tracers of specific binding the SERT protein in live brain.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A Method of reducing the occurrence of brain cell damage or death caused by transient cerebral hypoxia/ischemia condition or a traumatic brain injury (TBI) event. The method typically comprises identifying a subject with a transient cerebral hypoxic and/or ischemic condition, or a TBI, and within 24 hours of onset of the condition, administering to the subject a continuous intravenous infusion dose of methamphetamine in an amount sufficient to reduce the occurrence of brain cell damage or death caused by the condition. Preferably, in addition to the continuous intravenous infusion dose, a bolus dose of methamphetamine is administered to the subject as soon as possible after onset of the condition or occurrence of the TBI event.
Therapeutic tools and methods useful in treating a subject having brain seizures. The methods comprise the step of increasing expression of excitatory amino acid transporter 3 (EAAT3) in GABAergic neurons located in the brain of the subject sufficiently to reduce the severity, frequency, and/or duration of the brain seizures. The therapeutic tools include recombinant adeno-associated viral vector (rAAV) comprises AAV 5' and 3' ITRs flanking a human excitatory amino acid transporter 3 (EAAT3) gene which is operatively linked to a promoter suitable for expression of the EAAT3 in GABAergic neurons of the hippocampus.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
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Hydroxypolyamides, hydroxypolyamide products, and post-hydroxypolyamides are disclosed as gel forming agents. Hydroxypolyamides and post-hydroxypolyamides are prepared from known methods. Hydroxypolyamide products are produced from a modified polymerization procedure which utilizes strong base for deprotonation of ammonium salts from the esterification of stoichiometrically equivalent polyacid:polyamine salts. The hydroxypolyamide products are capable of gel formation at lower concentrations than hydroxypolyamides and post-hydroxypolyamides from the known methods of preparation, and are therefore superior gel forming agents.
C08G 69/26 - Polyamides derived from amino carboxylic acids or from polyamines and polycarboxylic acids derived from polyamines and polycarboxylic acids
92.
1-[(2′-substituted)-piperazin-1′ -yl]-isoquinolines as norepinephrine transporter inhibitor therapeutics and positron emission tomography imaging agents
Racemic mixtures and enantiomerically pure forms of novel 1-[(2′-substituted)-piperazin-1′-yl]-isoquinolines are norepinephrine (NE) transporter (NET) inhibitor compounds. Compounds of the invention are considered therapeutic agents for central nervous system (CNS) diseases and disorders, without limitation, including neurodegeneration, anxiety, depression, attention deficit disorders, drug dependency, and post traumatic stress disorder. Examples of the chemical syntheses of the compounds of the invention are provided. The isoquinoline compounds of the invention competitively bind at NET at nanomolar concentrations. The isoquinoline agents of the invention bind selectively to NET over other competitive transporter targets and receptor binding sites, including those of serotonin and dopamine, amongst others. The chemical syntheses of the invention are suitable for labeling with radionuclide atoms. Radiolabeled forms of the novel 1-[(2′-substituted)-piperazin-1′-yl]-isoquinoline compounds are positron emission tomography and single photon emission tomography imaging tracers. Methods of in vivo imaging with the tracers within various subjects and tissues therein, including regions of the brain, are provided. Imaging methods with the tracers in combination other NET inhibitor agents are provided. The imaging methods within subjects allow quantitative detection of NET, determinations of NET distributions, and measures of tracer interactions at NET in the presence or absence of non-radioactive NET agents. The tracer imaging methods are suitable to locate, diagnose, identify, evaluate, detect or quantitate NET, or abnormalities of NET, or NE abnormalities; that are associated with various CNS diseases and disorders.
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
93.
1-[(2'-SUBSTITUTED)-PIPERAZIN-1'-YL]-ISOQUINOLINES AS NOREPINEPHRINE TRANSPORTER INHIBITOR THERAPEUTICS AND POSITRON EMISSION TOMOGRAPHY IMAGING AGENTS
Racemic mixtures and enantiomerically pure forms of novel 1-[(2'- substituted)-piperazin-1'-yl]-isoquinolines are norepinephrine (NE) transporter (NET) inhibitor compounds. Compounds of the invention are considered therapeutic agents for central nervous system (CNS) diseases and disorders, without limitation, including neurodegeneration, anxiety, depression, attention deficit disorders, drug dependency, and post traumatic stress disorder. Examples of the chemical syntheses of the compounds of the invention are provided. The isoquinoline compounds of the invention competitively bind at NET at nanomolar concentrations. The isoquinoline agents of the invention bind selectively to NET over other competitive transporter targets and receptor binding sites, including those of serotonin and dopamine, amongst others. The chemical syntheses of the invention are suitable for labeling with radionuclide atoms. Radiolabeled forms of the novel 1-[(2'-substituted)-piperazin-1'- yl]-isoquinoline comoundss are positron emission tomography and single photon emission tomography imaging tracers. Methods of in vivo imaging with the tracers within various subjects and tissues therein, including regions of the brain, are provided. Imaging methods with the tracers in combination other NET inhibitor agents are provided. The imaging methods within subjects allow quantitative detection of NET, determinations of NET distributions, and measures of tracer interactions at NET in the presence or absence of non-radioactive NET agents. The tracer imaging methods are suitable to locate, diagnose, identify, evaluate, detect or quantitate NET, or abnormalities of NET, or NE abnormalities; that are associated with various CNS diseases and disorders.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence
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95.
Enantiomers of 2′-fluoralkyl-6-nitroquipazine as serotonin transporter positron emission tomography imaging agents and antidepressant therapeutics
Racemic mixtures and individual enantiomers of fluorine-18 or carbon-11 radio-labelled 2′-alkyl-6-nitroquipazine ligands are serotonin transporter (SERT) tracers for positron emission tomography (PET) imaging. The non-radioactive ligand forms possess therapeutic antidepressant in vitro and in vivo pharmacological binding profiles in rodent brain and cells expressing human serotonin transporter (hSERT). Twelve 2′-alkyl-6-nitroquipazine ligands potently bind in sub-nanomolar concentrations to the pre-synaptic SERT binding site where established antidepressant drugs bind and inhibit the re-uptake of the neurotransmitter serotonin (5-HT). In vivo tracer studies in rats as well as monkey PET scan trial have demonstrated the fluorine-18 and carbon-11 positron radionuclide labeled tracers perform as quantitative tracers of specific binding the SERT protein in live brain.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
The present invention is directed to a method of reducing the occurrence of neuronal cell damage, including death, caused by transient cerebral hypoxia and/or ischemia. The method comprises the steps of: diagnosing a subject having a transient cerebral hypoxic and/or ischemic condition; and within 16 hours after onset of the condition, administering to the subject a neuroprotective amount of a pharmaceutical agent. The pharmaceutical agent is preferably selected from the group consisting of: a central nervous system stimulant (CNSS), monoamine neurotransmitter, monoamine oxidase inhibitor (MAOI), tricyclic antidepressant (TCA), or a combination thereof. Preferred agents include amphetamines, methamphetamine, methylphenidate, methylenedioxymethamphetamine, or a combination thereof.
A01N 43/42 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
A controlled nitric acid process employing oxygen and nitric acid as co-oxidants is used to oxidize organic compounds subject to nitric acid oxidation, to their corresponding carboxylic acids. Oxidation of some carbohydrates by this process can produce one or more of their corresponding acid forms. The process is carried out at moderate temperatures, typically in the range of 20°C to 45 °C in a closed reactor, with oxygen gas being introduced into the reaction chamber as needed in order to sustain the reaction. Computer controlled reactors allow for careful and reproducible control of reaction parameters. Nitric acid can be recovered by a distillation / evaporation process, or by diffusion dialysis, the aqueous solution made basic with inorganic hydroxide, and the residual inorganic nitrate removed using a filtration (nanofiltration) device. The method eliminates issues of thermal control of the oxidation, release of nitrogen into the atmosphere, and post-reaction difficulties in the removal of nitric acid and inorganic nitrates.
C07C 51/27 - Preparation of carboxylic acids or their salts, halides, or anhydrides by oxidation with oxides of nitrogen or nitrogen-containing mineral acids
C07C 59/285 - Polyhydroxy dicarboxylic acids having five or more carbon atoms, e.g. saccharic acids
98.
ENANTIOMERS OF 2'-FLUORALKYL-6-NITROQUIPAZINE AS SEROTONIN TRANSPORTER POSITRON EMISSION TOMOGRAPHY IMAGING AGENTS AND ANTIDEPRESSANT THERAPEUTICS
Racemic mixtures and individual enantiomers of fluorine-18 or carbon-11 radiolabeled 2'-alkyl-6-nitroquipazine ligands are serotonin transporter (SERT) tracers for positron emission tomography (PET) imaging. The non-radioactive ligand forms possess therapeutic antidepressant in vitro and in vivo pharmacological binding profiles in rodent brain and cells expressing human serotonin transporter (hSERT). Twelve 2'-alkyl-6-nitroquipazine ligands potently bind in sub-nanomolar concentrations to the pre-synaptic SERT binding site where established antidepressant drugs bind and inhibit the re-uptake of the neurotransmitter serotonin (5-HT). In vivo tracer studies in rats as well as monkey PET scan trial have demonstrated the fluorine-18 and carbon-11 positron radionuclide labeled tracers perform as quantitative tracers of specific binding the SERT protein in live brain.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A titration method uses a tracer in the titrant or titrand to quantify the amount of titrant added. The method does not require quantitative addition of titrant or sample. The tracer can be inert or can participate as an indicator of the titrant- analyte reaction. The tracer concentration is quantified by an appropriate method depending upon the type of tracer and analytical performance desired (e.g. precision, accuracy). The method simplifies titrations because it eliminates the need for a precision dispensing device and analytical balance.
G01N 31/16 - Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroupsApparatus specially adapted for such methods using titration
G01N 31/22 - Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroupsApparatus specially adapted for such methods using chemical indicators
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