1098 results about "Pharmacodynamics" patented technology

Fc fusion proteins of human EPO with increased biological activities relative to rHuEPO on a molar basis are disclosed. The HuEPO-L-vFc fusion protein comprises HuEPO, a flexible peptide linker of about 20 or fewer amino acids, and a human IgG Fc variant. The Fc variant is of a non-lytic nature and shows minimal undesirable Fc-mediated side effects. A method is also disclosed to make or produce such fusion proteins at high expression levels. Such HuEPO-L-vFc fusion proteins exhibit extended serum half-life and increased biological activities, leading to improved pharmacokinetics and pharmacodynamics, thus fewer injections will be needed within a period of time.

The system described herein enables clinicians and researchers to use aggregated genetic and phenotypic data from clinical trials and medical records to make the safest, most effective treatment decisions for each patient. This involves (i) the creation of a standardized ontology for genetic, phenotypic, clinical, pharmacokinetic, pharmacodynamic and other data sets, (ii) the creation of a translation engine to integrate heterogeneous data sets into a database using the standardized ontology, and (iii) the development of statistical methods to perform data validation and outcome prediction with the integrated data. The system is designed to interface with patient electronic medical records (EMRs) in hospitals and laboratories to extract a particular patient's relevant data. The system may also be used in the context of generating phenotypic predictions and enhanced medical laboratory reports for treating clinicians. The system may also be used in the context of leveraging the huge amount of data created in medical and pharmaceutical clinical trials. The ontology and validation rules are designed to be flexible so as to accommodate a disparate set of clients. The system is also designed to be flexible so that it can change to accommodate scientific progress and remain optimally configured.

Fc fusion proteins of human EPO with increased biological activities relative to rHuEPO on a molar basis are disclosed. The HuEPO-L-vFc fusion protein comprises HuEPO, a flexible peptide linker of about 20 or fewer amino acids, and a human IgG Fc variant. The Fc variant is of a non-lytic nature and shows minimal undesirable Fc-mediated side effects. A method is also disclosed to make or produce such fusion proteins at high expression levels. Such HuEPO-L-vFc fusion proteins exhibit extended serum half-life and increased biological activities, leading to improved pharmacokinetics and pharmacodynamics, thus fewer injections will be needed within a period of time.

Compositions and methods for modulating the activity of RNA and DNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. Reactive portions which act, alternatively, through phosphorodiester bond cleavage, through backbone sugar bond cleavage or through base modification are preferrably employed. Groups which improve the pharmacodynamic and pharmacokinetic properties of the oligonucleotides are also useful in accordance with certain embodiments of this invention. Delivery of the reactive or non-reactive functionalities into the minor groove formed by the hybridization of the composition with the target RNA is also preferrably accomplished. Therapeutics, diagnostics and research methods and also disclosed. Synthetic nucleosides and nucleoside fragments are also provided useful for elaboration of oligonucleotides and oligonucleotide analogs for such purposes.

A pharmacodynamic (PD), pharmacokinetic (PK), or both and PK guided infusion device, system and method optimizes the safety and efficacy of various forms of treatment or therapy (e.g., drug and / or fluid) in a variety of health-care and other settings.

The present invention provides modified oligomeric compounds that modulate gene expression via an RNA interference pathway. The oligomeric compounds of the invention include one or more conjugate moieties that can modify or enhance the pharmacokinetic and phamacodynamic properties of the attached oligomeric compound.

A method for maintaining consistent unit relationships during graphical pharmacological computational model construction is disclosed. A graphical user interface is presented through which a user may place and connect objects representing pharmacokinetic and pharmacodynamic elements. The user may specify units definitions for variables and constants using unit expressions. As the objects are converted into an internal format representing the statements of the corresponding computational model, the unit expressions are included in this internal format as multidimensional data type information. This multidimensional data type information is regularly and automatically propagated for each statement in the internal format to identify inconsistent units. When such inconsistent units are identified, a warning message is generated to notify the user, substantially immediately after the inconsistent units are created.

This invention provides modified rapamycins that have specific monosaccharide(s), oligosaccharide(s), pseudosugar(s) or derivatives thereof attached through a linker to create rapamycin carbohydrate derivatives having enhanced pharmacokinetic and / or pharmacodynamic profiles. For example, administration of the rapamycin carbohydrate derivative results in altered pharmacokinetic profiles and reduced toxicities. Thus, the present invention provides compounds with characteristics that are distinct from other drugs in its class such as rapamycin.

The invention belongs to the field of medicine, and in particular relates to a medical application of 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl 4-((3-chloro-4-methylphenyl) amino)-4-oxobutanoate in a selective histone lysine-specific demethylase 1 (LSD1) inhibitor, especially the application in anti-tumor medicaments. Pharmacodynamic tests indicate that the 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl 4-((3-chloro-4-methylphenyl) amino)-4-oxobutanoate has a remarkable LSD1 inhibiting effect, and has selectivity to homologous proteins MAO-A (monoamine oxidase-A) and MAO-B.

Fluidic multiwell bioreactors are provided as a microphysiological platform for in vitro investigation of multi-organ crosstalks for an extended period of time of at least weeks and months. The disclosed platform is featured with one or more improvements over existing bioreactors, including on-board pumping for pneumatically driven fluid flow, a redesigned spillway for self-leveling from source to sink, a non-contact built-in fluid level sensing device, precise control on fluid flow profile and partitioning, and facile reconfigurations such as daisy chaining and multilayer stacking. The platform supports the culture of multiple organs in a microphysiological, interacted systems, suitable for a wide range of biomedical applications including systemic toxicity studies and physiology-based pharmacokinetic and pharmacodynamic predictions. A process to fabricate the disclosed bioreactors is also provided.

The invention belongs to the field of drug synthesis and in particular relates to a series of novel peptide boric acids as well as an ester compound or pharmaceutical salt thereof, and a preparation method and application of the peptide boric acids as well as the ester compound or pharmaceutical salt thereof in pharmacodynamics. A structure of the peptide boric acid and the ester compound or pharmaceutical salt thereof is shown in a formula I (described in the specification). The compound provided by the invention can be used for preparing a proteasome inhibitor and can further be used for treating solid tumours and blood tumours, wherein the solid tumours are selected from non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous carcinoma, pancreatic cancer, breast cancer, prostate cancer, liver cancer, skin cancer, epithelial cell cancer, gastrointestinal stromal tumor, nasopharynx cancer and leukemia; and the blood tumours are selected from multiple myeloma, mantle cell lymphoma and histiocytic lymphoma.

Methods for treating Hepatitis infections are provided. In one embodiment, an initial dosage of interferon is administered to a patient, and interferon serum levels and viral load data is collected over time. This data can be used to determine patient-specific pharmacokinetic and pharmacodynamic parameters and then construct patient-specific interferon delivery profiles. Patient-specific delivery profiles can then be used to design patient-specific therapeutic regimens.

An orally taken medicine of hyproval-PA in the form of tablet, capsule, soft capsule, instant particles, etc for treating breast cancer and functional metrorrhagia is disclosed. its advantages are high biologic utilization rate and high curative effect.

Provided are immediate or prolonged administration of certain salts of KATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving KATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.

Insulin conjugates comprising an insulin molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and / or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

The invention relates to application of substituted isosilybin in preparing a medicament for treating virus hepatitis B, in particular to application of E-ring substituted isosilybin or medicinal salt thereof in preparing a medicament for clearing hepatitis B e antigen, inhibiting HBV DNA replication and treating hepatitis B virus infected diseases. The E-ring substituted isosilybin has strong effect of inhibiting HBeAg activity, and the strength of the E-ring substituted isosilybin at the concentration of 100 micrograms per milliliter for clearing the HBeAg is 3.5 times that of a positive control front-line medicament (10,000 units per milliliter of alpha-interferon); and moreover, the compound at the concentration of 100 micrograms per milliliter has strong inhibiting rate (97.7 percent) on the HBV DNA. Pharmacodynamical results show that the E-ring substituted isosilybin or the medicinal salt thereof can be expected to be used for preparing the medicament for treating the hepatitis B virus infected diseases.

Materials and methods are provided for producing aptamer therapeutics having improved pharmacokinetic and pharmacodymanic properties, as well as increased target valency. The aptamers produced by the methods of the invention are useful as therapeutics for treating disease.

The invention relates to application of an angle flavonoids lignan to preparation of medicaments for treating viral hepatitis B, in particular to application of the angle flavonoids lignan or medicinal salts thereof to preparation of medicaments for inhibiting hepatisis B virus (HBV) DNA replication and treating HBV infection diseases. The flavonoids lignan can exactly inhibit HBV DNA activity; the inhibition activity of the flavonoids lignan with high dosage (20 microgram / ml) to the HBV DNA replication is 189 percent higher than that of alpha-interferon with the maximum concentration of 10,000 unit / ml; and the flavonoids lignan belongs to a strong-effect non-nucleosides inhibition HBV natural product. The pharmacological results show that the angle flavonoids lignan or the medicinal salts thereof can be expected to be used for preparing the medicaments for inhibiting hepatisis B virus (HBV) DNA replication and treating the HBV infection diseases.

The invention relates to application of ring A dioxane flavonolignan in preparing medicaments for resisting hepatitis B viruses (HBV), in particular to application of ring A dioxane coupling type flavone lignan or a pharmaceutically acceptable salt thereof in preparing medicaments for clearing away hepatitis B e antigen (HBeAg), suppressing the HBV DNA replication and treating HBV infection diseases. The flavonolignan has certain activity on resisting the HBeAg, and the intensity of the flavonolignan for clearing away the HBeAg is higher than that of Lamivudine which is a positive control and close to that of 10,000 units / milliliter of alpha-interferon. Meanwhile, the suppression ratio of the compound to the HBV DNA replication is higher than 80 percent in the presence of a concentration of 100 micrograms / milliliter. The pharmacodynamical results indicate that the flavonolignan or the pharmaceutically acceptable salt thereof can be expected to be used for preparing the medicaments for clearing away the HBeAg, suppressing the HBV DNA replication and treating the HBV infection diseases.

The invention relates to application of ring A substituted silybin ester in preparing medicaments for treating viral hepatitis B, in particular to application of silybin ester flavonolignan substituted by ethoxycarbonyl methyl on the ring A or a pharmaceutically acceptable salt thereof for preparing medicaments for reducing the hepatitis B virus surface antigen (HBsAg), suppressing the HBV (Hepatitis B Virus) DNA replication and treating HBV infection diseases. The flavonolignan has quite obvious activity on suppressing the HBsAg, and in the presence of a concentration of 100 micrograms / milliliter, the intensity of the flavonolignan for clearing away the HBsAG exceeds that of alpha-interferon which is a positive control medicament by 3.3 times. Meanwhile, in the presence of a concentration of 20 micrograms / milliliter, suppression ratio of the compound to the HBV DNA is close to 60 percent. The pharmacodynamical results indicate that the flavonolignan or the pharmaceutically acceptable salt thereof can be expected to be used for preparing the medicaments for treating the HBV infection diseases.

A unit dosage form, such as a capsule or the like for delivering drugs into the body in a circadian release fashion, is comprising of one or more populations of propranolol-containing particles (beads, pellets, granules, etc.). Each bead population exhibits a pre-designed rapid or sustained release profile with or without a predetermined lag time of 3 to 5 hours. Such a circadian rhythm release cardiovascular drug delivery system is designed to provide a plasma concentration-time profile, which varies according to physiological need during the day, i.e., mimicking the circadian rhythm and severity / manifestation of a cardiovascular disease, predicted based on pharmaco-kinetic and pharmaco-dynamic considerations and in vitro / in vivo correlations.

A pharmacodynamic (PD), pharmacokinetic (PK), or both and PK guided infusion device, system and method optimizes the safety and efficacy of various forms of treatment or therapy (e.g., drug and / or fluid) in a variety of health-care and other settings.

The invention belongs to the field of medicines, relates to anti-tumor medicines, and in particular relates to anti-tumor medicines in double-aryl urea structures based on indazole, indole, azaindazole or azaindole. The structural formulae of the anti-tumor medicines are shown in formula (Ia) and formula (Ib), wherein Z is N atom or C atom; W is O; M is O, S, N or CH; n is 1 or 2; Y and R are halogen atoms, H, R1, CF3, OCF3, OH, OR2, OCOR3, NH2, NHR4, NR52, NHCOR6, carboxyl group, ester group, cyano group, mercapto group, alkyl sulphanyl, sulfuryl, sulfoxide, sulfonic group, sulfamate, sulfonamide, ketonic group, aldehyde group, nitro group or nitroso group. Pharmacodynamic experiments prove that the medicines have good anti-tumor effects on human lung cancer, human kidney cancer, human colon cancer, human liver cancer, human gastric cancer, human breast cancer, melanoma and the like.

The invention discloses a xiluomosi liposome freeze dried and making technique, which comprises the following steps: selecting liposome component, buffer, organic solvent, antioxidant and freeze-drying protective as raw material; adopting film diffusion method to make the liposome turbid liquor with xiluomosi through high-pressure or hypersonic dispersing method evenly; drying the liposome to improve the storage stability obviously; dispersing the freeze dried at random proportion in the water evenly without any sediment and impurity; making the packing rate of liposome at 96% with the grain size at 50-250nm; improving the drug effect greatly in comparison with oral agent; lengthening the circulating time in the blood; elevating the biological utility of drug.

The invention belongs to the fields of polymer chemistry and medicinal preparations, and particularly relates to a method for synthesizing an active targeted hyaluronic acid-polylactic acid carrier, a method for preparing an anti-tumor medicinal micelle of the active targeted hyaluronic acid-polylactic acid carrier and an application thereof. By adopting a novel self-assembly technology, amphipathic PEG (polyethylene glycol) block polyester copolymer and tumor targeted ligand hyaluronic acid-polylactic acid copolymer are self-assembled by means of the electrostatic interaction to form a multifunctional composite micelle; the solubility of insoluble tumor medicaments and the drug loading capacity and encapsulation efficiency of water-soluble anti-tumor medicines can be remarkably improved by virtue of the anti-cancer drug-loaded micelle and composite micelle composition, the medicines can be biodegraded in a body, phagocytosis of a reticuloendothelial system (RES) and excretion of a kidney can be avoided. The active targeted hyaluronic acid-polylactic acid carrier has a long-circulating effect, the multifunctional composition has a prominent advantage of tumor active targeting effect, and parameters of pharmacodynamics in vitro and in vivo of the micelle are remarkably superior to those of common anti-tumor injections. Clinically acceptable administration means of the micelle includes injection administration or mucosal administration, and preparations of the micelle can be injection, transfusion, injection lyophilized powder injections or dry powder inhalation.

In this invention, first It is set that an object of study of a compound traditional Chinese medicine with its chemical compositions being clear about. The molecules of chemical constitutions of each ingredient of the Chinese medicine prescription are collected and reorganized, and setting a data base for chemical constitutions molecules of said Chinese medicine prescription. For the aim of pharmacodynamics effects of main therapeutical functions of the traditional Chinese medicine prescription with their clear therapeutical effects, clear mechanism and definited target spots, we search or set up the corresponding molecular target spots. Three procedures (without odor of priority) are: poisonousness sieving, analogous medicine properties estimation and molecular abutment decision to these molecular data base of the set pharmacodynamics models respectively. Finally we estimating all the molecules in the molecular data base, selecting-out the molecules with higher grading, to obtain the pharmacodynamics effect P(i) molecular pre-prescription, and then producing novel prescriptions.

The present invention relates to inhibitors of ROCK1 and ROCK2 and methods of modulating the pharmacokinetic and / or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCK1 and or ROCK2 that are useful for the treatment of disease.