52 results about "Intermittent dosing" patented technology

Methods and compositions for treating an infection or disease that results from (1) failure to elicit rapid T cell mediated responses, (2) induction of T cell exhaustion, T cell anergy or both, or (3) failure to activate monocytes, macrophages, dendritic cells and / or other APCs, for example, as required to kill intracellular pathogens. The method and compositions solve the problem of undesired T cell inhibition by simultaneously inhibiting the PD-1 ligands, PD-L1 and PD-L2. The immune response can be modulated by providing antagonists which bind with different affinity, by varying the dosage of agent which is administered, by intermittent dosing over a regime, and combinations thereof, that provides for dissociation of agent from the molecule to which it is bound prior to being administered again. In some cases it may be particularly desirable to stimulate the immune system, then remove the stimulation.

The invention provides compositions comprising, 16alpha-bromo-3beta-hydroxy-5alpha-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16alpha-bromo-3beta-hydroxy-5alpha-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

A device and method is disclosed for delivering NO to a patient. The device utilizes a single controller that controls two separate flow controllers to deliver an oxygen-containing gas and a NO-containing gas to the patient to provide NO-containing gas at a flow profile that is proportional or quasi-proportional to a flow profile of the oxygen-containing gas throughout patient inspiration. The controller further comprises logic for setting a nitric oxide delivery profile comprising at least two different concentrations of nitric oxide containing gas and for automatically switching between the at least two different concentrations of nitric oxide containing gas on a timed basis.

The invention provides compositions comprising formula 1 steroids, e.g., 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate and one or more excipients, including compositions that comprise a liquid formulation comprising less than about 3% v / v water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16α-bromo-3β-hydroxy-5α-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using the compounds. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

Methods and compositions for treating an infection or disease that results from (1) failure to elicit rapid T cell mediated responses, (2) induction of T cell exhaustion, T cell anergy or both, or (3) failure to activate monocytes, macrophages, dendritic cells and / or other APCs, for example, as required to kill intracellular pathogens. The method and compositions solve the problem of undesired T cell inhibition by binding to and blocking PD-1 to prevent or reduce inhibitory signal transduction, or by binding to ligands of PD-1 such as PD-L1, thereby preventing (in whole or in part) the ligand from binding to PD-1 to deliver an inhibitory signal. The immune response can be modulated by providing antagonists which bind with different affinity (i.e., more or less as required), by varying the dosage of agent which is administered, by intermittent dosing over a regime, and combinations thereof, that provides for dissociation of agent from the molecule to which it is bound prior to being administered again (similar to what occurs with antigen elicitation using priming and boosting). In some cases it may be particularly desirable to stimulate the immune system, then remove the stimulation.

A method and corresponding device are described for combating microbes and infections by delivering intermittent high doses of nitric oxide to a mammal for a period of time and which cycles between high and low concentration of nitric oxide gas. The high concentration of nitric oxide is preferably delivered intermittently for brief periods of time that are interspersed with periods of time with either no nitric oxide delivery or lower concentrations of nitric oxide. The method is advantageous because at higher concentration, nitric oxide gas overwhelms the defense mechanism of pathogens that use the mammalian body to replenish their thiol defense system. A lower dose or concentration of nitric oxide gas delivered in between the bursts of high concentration nitric oxide maintains nitrosative stress pressure on the pathogens and also reduces the risk of toxicity of nitric oxide gas.

The present invention provides a method of treating tumor in a patient comprising administering to said patient a CD40 agonist antibody according to an intermittent dosing schedule. The present invention also provides a method of treating tumor in a patient comprising administering a combination of a CD40 agonist antibody and a DNA replication inhibitor. Also provided is a formulation for use in the treatment.

A method and corresponding device are described for combating microbes and infections by delivering intermittent high doses of nitric oxide to a mammal for a period of time and which cycles between high and low concentration of nitric oxide gas. The high concentration of nitric oxide is preferably delivered intermittently for brief periods of time that are interspersed with periods of time with either no nitric oxide delivery or lower concentrations of nitric oxide. The method is advantageous because at higher concentration, nitric oxide gas overwhelms the defense mechanism of pathogens that use the mammalian body to replenish their thiol defense system. A lower dose or concentration of nitric oxide gas delivered in between the bursts of high concentration nitric oxide maintains nitrosative stress pressure on the pathogens and also reduces the risk of toxicity of nitric oxide gas.

The invention provides compositions comprising formula 1 steroids, e.g., 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate and one or more excipients, including compositions that comprise a liquid formulation comprising less than about 3% v / v water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16α-bromo-3β-hydroxy-5α-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using the compounds. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

The invention belongs to the fields of chemical industry and water treatment and in particular relates to a composite bacteria and algae inhibitor and application thereof. The composite bacteria and algae inhibitor contains the following components in percentage by mass: 1-40 percent of isothiazolinone, 5-40 percent of 2,2-dibromo-3-nitrilo-propanamide, 20-60 percent of solvent and 10-70 percent of water. The composite bacteria and algae inhibitor is a non-oxide biocide, and when the bacteria and algae inhibitor is applied to a water treatment system, an impact type intermittent dosing mode is adopted, and the addition amount of the bacteria and algae inhibitor in each liter of water is 1mg-100mg. The components in the formula have an obvious synergistic effect and are high in compatibility with a scale inhibitor and a corrosion inhibitor, and the bacteria and algae inhibitor is low in biotoxicity and high in biodegradation rate, has the effects of killing and inhibiting bacterioplankton and algae in water and has effects of stripping and inhibiting bacteria and algae attachments settling and growing on equipment surfaces. During actual application, the composite bacteria and algae inhibitor has the advantages of small addition amount, low using cost, convenience in operation, pollution-free discharge and the like.

The invention provides a continuous diazotization production process of aromatic amine. The process is as follows: by utilizing a multistage serially connected diazotization reaction kettle, throwing a powdery aromatic amine raw material into a stock bin of a feeding system, integrally weighing the feeding system and the solid raw material through a weighing device, continuously and stably adding the aromatic amine into the diazotization reaction kettle through an automatic feeder, calculating the feeding dosage of the aromatic amine raw material within a unit time through a difference method, continuously and stably adding nitrosyl sulfuric acid and sulfuric acid into the diazotization reaction kettle according to a feeding molar ratio of the aromatic amine, the sulfuric acid and the nitrosyl sulfuric acid of 1:(1-5): (1.01-1.10) through a liquid metering and adjusting device, stirring and controlling the temperature to 0-40 DEG C to carry out a diazotization reaction. By adopting the continuous diazotization production process disclosed by the invention, industrial large-scale production becomes possible, the traditional intermittent dosing method of raw materials is improved, the reaction raw material proportion, the reaction temperature and the reaction time are accurately controlled to improve the diazonium salt yield, stabilize the diazonium salt quality and reduce the color differences between lots.

The invention provides compositions comprising formula 1 steroids, e.g., 16alpha-bromo-3beta-hydroxy-5alpha-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16alpha-bromo-3beta-hydroxy-5alpha-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

The present invention relates to the treatment of dopamine-related dysfunction using full D1 dopamine receptor agonists in an intermittent dosing protocol with a short, but essential, “off-period.” The D1 agonist concentration is reduced during the “off-period” to obtain a plasma concentration of agonist that suboptimally activates D1 dopamine receptors for a period of time to prevent induction of tolerance. Specifically, the method comprises the steps of periodically administering to a patient a full D1 agonist with a half-life of up to about 6 hours at a dose resulting in a first plasma concentration of agonist capable of activating D1 dopamine receptors to produce a therapeutic effect. The dose is reduced at least once every 24 hours to obtain a second lower plasma concentration of agonist that results in suboptimal activation of D1 dopamine receptors for a period of time sufficient to prevent induction of tolerance.

A method is provided for administering to a mammal suffering from, or at risk for, multiple sclerosis, an initial dosing of a therapeutically effective amount of an anti-LFA-1 antibody, followed by a subsequent intermittent dosing of a therapeutically effective amount of the anti-LFA-1 antibody wherein the antibody is administered to the mammal no more than once per week in the intermittent dosing.

The present invention is directed to a novel trifluoromethylsulfonamide derivative which inhibits the processing of APP by the putative γ-secretase and thus is useful in the treatment or prevention of Alzheimer's disease. This compound possesses favorable pharmacokinetic properties in higher species (rhesus) and thus can be dosed on an intermittent dosing regiment (e.g., once weekly). When dosed on such a regiment the compound exhibits significant and continuous Aβ lowering without the manifestation of Notch associated gastrointestinal toxicity for extended periods, e.g., 7 days. Pharmaceutical compositions and methods of use are also included.

Methods for promoting immunologic control of human immunodeficiency virus (HIV) in an HIV-infected subject are provided. The methods comprise administering to the subject highly active antiretroviral therapy (HAART) for at least one cycle of an intermittent dosing regimen in combination with administration of a pharmaceutical composition comprising a therapeutically effective amount of interleukin-2 (IL-2) or variant thereof. The combination of daily or intermittent administration of IL-2 (or variant thereof) and intermittent HAART promotes immunologic control of viral replication in the absence of HAART, thereby prolonging the length of time a patient may discontinue HAART before viral rebound necessitates further administration of HAART. Administration of IL-2 therapy in combination with an intermittent HAART dosing regimen provides an effective method for treating a subject infected with HIV.

The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to the patient a therapeutically effective amount of an EGFR kinase inhibitor and docetaxel combination, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy, wherein the EGFR kinase inhibitor is administered intermittently after administration of a dose of docetaxel. Multiple cycles of this treatment can be administered until an effective result is obtained. Other anti-cancer agents that, like docetaxel, induce M-phase arrest, can be also used in the practice of this invention, e.g. vinblastine, paclitaxel. A preferred example of an EGFR kinase inhibitor that can be used in practicing this invention is the compound erlotinib HCl (also known as TARCEVA™).

The present invention relates to the treatment of dopamine-related dysfunction using full D1 dopamine receptor agonists in an intermittent dosing protocol with a short, but essential, “off-period.” The D1 agonist concentration is reduced during the “off-period” to obtain a plasma concentration of agonist that suboptimally activates D1 dopamine receptors for a period of time to prevent induction of tolerance. Specifically, the method comprises the steps of periodically administering to a patient a full D1 agonist with a half-life of up to about 6 hours at a dose resulting in a first plasma concentration of agonist capable of activating D1 dopamine receptors to produce a therapeutic effect. The dose is reduced at least once every 24 hours to obtain a second lower plasma concentration of agonist that results in suboptimal activation of D1 dopamine receptors for a period of time sufficient to prevent induction of tolerance.

Compositions and methods for treating peripheral artery disease in a patient are provided. Compositions comprise recombinant fibroblast growth factor-2. Fibroblast growth factor, such as FGF-2, is administered in therapeutically effective amounts to treat or prevent peripheral artery disease including claudication and critical limb ischemia. Pharmaceutical compositions comprising a therapeutically effective amount of FGF-2 and a pharmaceutically acceptable carrier are also provided. The methods of the invention to treat peripheral artery disease and claudication comprise administering at least a single dose of a pharmaceutical composition comprising the FGF, such as FGF-2, via intra-arterial, intravenous, or intramuscular infusion to the patient. It is recognized that increased benefits may result from multiple dosing, including intermittent dosing.

A method for promoting a sustained increased level of T-cell production in immunocompromised subjects in which method enkephalin peptides are administered according to an intermittent dose schedule. In particular, the method involves treatment of immunocompromised patients which includes the administration of enkephalin, either alone or in conjunction with other therapies, in an initial dosage regimen, with periodic booster dosages of enkephalin as necessary to maintain sustained immune system response.

The present disclosure relates to mdm2 inhibitors for use in specific dosing schedules. It was found that if sufficiently potent or, in alternative, sufficiently high dose of a Mdm2 inhibitor is used, it can cause antineoplastic effect by triggering much longer lasting antiproliferative mechanism in cells. The long lasting effect can sustain for several weeks after a single dose, which eliminates the need for daily treatment and allows administering the Mdm2i intermittently. A treatment with the intermittent dosing schedule of a Mdm2 inhibitor can be combined with a daily treatment of the Mdm2i or with another pharmaceutically acceptable ingredient.

The invention discloses a dosing device for awake tracheal intubation. The dosing device comprises an automatic dosing device, a fiberoptic bronchoscope and an oral cavity supporting device, wherein the automatic dosing device comprises a medicine inlet, a medicine outlet and an automatic dosing mechanism, the medicine inlet is connected with a flexible medicine bag, the medicine outlet is connected with a dosing tube, the interiors of the medicine inlet and the medicine outlet communicate with each other through the automatic dosing mechanism, the fiberoptic bronchoscope comprises a display screen, an optical fiber cable and a lens which are connected in sequence, the dosing tube and the optical fiber cable are connected with an insertion tube through a fixed tongue piece, the insertion tube communicates with the dosing tube, a dosing spray head is arranged at the front end of the insertion tube, the optical fiber cable is arranged in the insertion tube and penetrates out of the front end of the insertion tube in a sealed mode, and the lens is arranged at the front end of the dosing spray head. According to the above scheme, automatic intermittent dosing can be achieved through the automatic dosing device, accurate dosing in the trachea of a patient is achieved through the fiberoptic bronchoscope, the dosing spray head can be automatically closed, a liquid medicine can be prevented from spilling and leaking, and in addition, the comfort of the patient can be improved through an oral cavity supporting device.

A system comprising a highly concentrated micro component source, an accumulator, a micro component valve and a controller. The accumulator may be configured to keep the highly concentrated micro component under a first pressure. The micro component valve may be configured to dose the highly concentrated micro component at the first pressure for a first period of time. The controller may be configured to control the dosing of the highly concentrated micro component by the micro component valve. The system may further comprise a source of a diluent configured to provide a flow of the diluent during a second period of time at a second pressure. The highly concentrated micro component along with the diluent may be dosed using different time periods and under different pressures.

The invention relates to a pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof for the treatment of cancer and a process for its preparation. The invention also relates to administering the pharmaceutical composition to a patient according to an intermittent dosing regimen.

A medicament delivery device (10) for the administration of one or more drug agents is described. The device (10) has a priming mode (920, 945) and a drug delivery mode (947) for administering delivery of the drug agents. The device includes a controller (700) operative for controlling the device (10) to perform a priming operation, and a user interface (74) for activation of the priming operation. The controller (700) is operative to perform the priming operation by way of a plurality of intermittent doses of medicament, the number of intermittent doses being dependent on the activation of the user interface (74).

The invention relates to dosing equipment, in particular to automatic dosing equipment for a flocculation basin. The invention provides the automatic dosing equipment for the flocculation basin, wherein theequipment can be used for automatically blanking, realizing automatic stirring and reducing the labor intensity. The automatic dosing equipment for the flocculation basin comprises a supporting connecting frame, wherein the two sides of the supporting connecting frame are respectively provided with a precipitation, dosing and stirring mechanism; medicine discharging mechanisms arranged on the left portion and the right portion of the rear side of the supporting connecting frame; and automatic intermittent dosing opening mechanisms arranged on the precipitation, dosing and stirring mechanisms. The stirring rod is driven to rotate through the output shaft of the motor, so that wastewater and medicine powder in the water discharging frame are stirred, impurities in the wastewater are precipitated, and the precipitation, dosing and stirring effects are achieved.

The invention relates to a pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof for the treatment of cancer and a process for its preparation. The invention also relates to administering the pharmaceutical composition to a patient according to an intermittent dosing regimen.