126 results about "Potency" patented technology

The invention relates to the technical field of biological pharmacy, and discloses a QS-21 saponin adjuvant as well as a preparation method and application thereof, the adjuvant is a composite liposome and comprises a liposome skeleton composed of distearoyl phosphatidylcholine and cholesterol, and QS-21 saponin, monophosphoryl lipid A and a local anesthetic are jointly entrapped in the liposome skeleton. The problem that high reactogenicity and immunogenicity of potent adjuvants are difficult to consider at the same time is solved, the immunostimulation component and the pain inhibition component are jointly entrapped in the same nano-carrier, collaborative delivery in injection local is achieved, and therefore pain and swelling caused by the adjuvants are accurately inhibited. The co-entrapment structure avoids the potential inhibition effect of the free anesthetic on the immune system, the potent body fluid and cellular immune enhancement activity of the adjuvant is completely reserved, and a new technical scheme is provided for developing vaccines with high safety and strong immune efficacy.

The invention discloses a multi-target joint optimized antibiotic molecule design system and method applied to the field of biological medicine, and the method comprises the steps: obtaining FabI enzyme and AcrAB-TolC efflux pump structure data, extracting double-target space and physicochemical characteristics, and constructing a joint pharmacophore model containing a FabI inhibition domain and an efflux pump blocking domain; screening candidate molecules meeting a double-domain space matching threshold, screening high-affinity double-target molecules through conformation sampling and free energy calculation, and forming a lead compound library through multi-layer filtration of metabolic stability, membrane penetrability, quantum chemical properties and synthesis feasibility; carrying out electron effect, chain length or heteroatom fine tuning on dominant molecules through in-vitro bacteriostasis and efflux inhibition experiment feedback, and carrying out iterative optimization until MIClt is met; 2 [mu] g / mL and the efflux inhibition rate is gt; according to the present invention, the antibacterial effect and the drug resistance inhibition ability are significantly improved, the molecular synthesizability and the biological safety are ensured, and the engineering design new path is provided for the Gram-negative bacterium drug resistance crisis.

Provided herein is an antibody-drug conjugate (ADC) especially a PEGylated mono- or bispecific antibody hydroxyl-bearing drug conjugate prepared with site-specific conjugation to provide homogeneous conjugate with high potency and low toxicity. The disclosure also relates to a method for the preparation of the antibody hydroxyl-bearing drug conjugate, a composition comprising the antibody hydroxyl-bearing drug conjugate, and the use thereof in treating diseases.

Embodiments provide for methods of predicting glycation percentage of an amino acid in a therapeutic biomolecule. In one example, a method of predicting a glycation percentage of an amino acid in a biomolecule includes determining a first set of rates for a de-glycation reaction for a first set of temperatures, inferring a second set of one or more rate(s) for the de-glycation reaction for a second set of temperatures, and using the second set of one or more rate(s) to predict the glycation percentage at any temperature corresponding to the second set of temperatures and over any time duration. Also provided are methods for maintaining a glycation percentage of an amino acid within a predetermined glycation percentage range over a shelf-life of a therapeutic biomolecule, and methods for either reducing or increasing a potency of a therapeutic biomolecule in a subject at a time of administration.

The invention discloses a living body screening method of a high-throughput addiction inhibitor, which comprises the following steps: acquiring addictive nematodes with a plurality of addiction behavioral phenotypes; applying different addiction inhibitors to the addictive nematodes; the screening of the addiction inhibitors is realized according to the inhibition efficacy of the addiction inhibitors on the addiction behavioral phenotypes of the addiction nematodes, and based on the steps, the drug screening of the addiction inhibitors can be realized through the inhibition efficacy of the addiction inhibitors on the addiction behavioral phenotypes of the addiction nematodes in a high-throughput manner. Compared with the prior art, the medicine screening method of a traditional cell function system is abandoned, and medicine screening is carried out on the living animal behavioristics level in a brand new mode. Meanwhile, the advantages of easiness in large-scale culture, abundant behavioral modes and the like of the nematodes are utilized, and compared with expensive mammal feeding and experimental operation for drug screening, the method has higher cost performance, practical operability and high throughput.

Respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) are commonly treated with β2-adrenergic receptor agonists that activate intracellular signaling pathways to induce airway relaxation. However, current therapies are limited by progressive receptor desensitization, or tachyphylaxis, largely attributed to β-arrestin recruitment. This desensitization reduces therapeutic efficacy over time and complicates long-term disease management, resulting in suboptimal outcomes for patients who rely on bronchodilators for daily symptom control. Disclosed herein are pharmaceutical compositions comprising biased agonists and their methods of use, which minimally activate recruitment of beta-arrestin2.

The present application relates to azapeptide compounds of formula (I) derived from melanocyte-stimulating hormone release-inhibiting factor-1. A method to obtain compounds of formula (I) is also described herein. The compounds of formula (I) have been shown to be suitable for the treatment of dopamine-related disorders of the central nervous system. These compounds showed enhanced potency as positive allosteric modulators of the dopamine D2 receptors in comparison with the melanocyte-stimulating hormone release- inhibiting factor-1 and, in general, do not exhibit meaningful cytotoxicity.

Methods and materials for treating mammals having cardiovascular and / or metabolic disease are provided herein. For example, methods and materials for treating mammals having cardiovascular and / or metabolic disease by administering (a) an analog of a natriuretic peptide (NP), such as atrial natriuretic peptide (ANP) or dendroaspis natriuretic peptide (DNP), and (b) a glucagon-like peptide-1 (GLP-1) receptor / glucose-dependent insulinotropic polypeptide (GIP) receptor agonist are provided herein. The NP analogs used in the methods provided herein can be less than 20 amino acids in length and, in some cases, can have one or more variations in their ring portion (as compared to wild type ANP or DNP) that affect the potency of the analog in activating the particulate guanylyl cyclase (GC-A) receptor.

The invention provides novel compounds which are peptide hormone analogues, and which are useful in treating disorders such as diabetes and obesity. The compounds of the general sequence recited in the specification possess a tailored profile with regards5 to potency properties at the GIP receptor. With regard to in vivo properties, administration of example peptides of the invention have been shown, in animal models, to result in increased weight loss. Preferred compounds achieve this without reducing food intake significantly.

Described herein are compositions, kits, and methods for potent delivery to a cell of a subject. The cell can be of a particular cell type, such as a basal cell. In some cases, the cell can be a lung cell of a particular cell type. Also described herein are pharmaceutical compositions comprising a therapeutic or prophylactic agent assembled to a lipid composition. The lipid composition can comprise an ionizable cationic lipid, and a selective organ targeting lipid. The lipid composition can further comprise a phospholipid. Further described herein are high-potency intravenous dosage forms of a therapeutic or prophylactic agent formulated with a lipid composition.

The application provides an aniline skeleton compound with antitumor activity and a preparation method and application thereof, and belongs to the technical field of small molecule inhibitor preparation. The aniline skeleton compound with antitumor activity has a structural formula as shown in formula I. The aniline skeleton compound has good antitumor activity in vivo and in vitro, and effectively solves the problems of target drug resistance and insufficient efficacy in the prior art.

The invention discloses a halogen modified hapten for enhancing antibody titer and affinity as well as a preparation method and application of the halogen modified hapten, and belongs to the technical field of biochemical engineering. According to the method, an amantadine structure is innovatively and chemically modified, various halogens such as fluorine, chlorine and bromine are introduced, the AMA halogen modified hapten shown in the formula (I) is formed, and the traditional'most similar 'design principle is broken through. Compared with an unmodified hapten, the hapten modified by halogen in the invention has the advantages that the titer of the polyclonal antibody on amantadine can be obviously improved by 3.4-14 times; wherein the haptens A5 and A6 can obviously improve the titer of the monoclonal antibody to amantadine by 3-18 times, and the affinity is improved by 10.8-16.1 times. The invention provides a new thought and a new method for the rational design of the hapten of the small molecule compound and the preparation of the high-affinity antibody, and the related halogen modification type and quantity strategy can also provide valuable reference for the design of the hapten of other small molecule compounds.

The application provides a method for detecting the titer of vitamin B12 in a fermentation liquor. The method comprises the following steps: preparing a potassium dichromate solution, a hydrochloric acid solution and a potassium dihydrogen phosphate solution, mixing the three solutions with the vitamin B12 fermentation liquor under certain conditions to generate cyanocobalamin, and then testing the titer of the cyanocobalamin by using a high performance liquid chromatography. The titer of the vitamin B12 detected by using the method is consistent with the titer detected by using a sodium cyanide method. The operation method greatly reduces the safety risk of an analyst caused by using the sodium cyanide, and the operation method is simple, easy to manage in a laboratory and can save the testing cost.

The present disclosure discloses an alkanolamine multi-tailed lipid, a preparation method therefor, and a use thereof. The structural formulas of the lipid such as compound of Formula I, compound of Formula II or their stereoisomers, their tautomers, or their pharmaceutically acceptable salts:The ionizable lipid compound of the present disclosure maintains nanoparticle stability and delivery efficiency while simplifying LNP composition, offering advantages of high efficacy and low toxicity. Even under neutral conditions, the ionizable lipid compound can still adsorb mRNA through hydrogen bonding and van der Waals interactions. The synthesis method for the diethanolamine multi-tailed ionizable lipid of the present disclosure is straightforward. The ionizable lipid can be prepared on a large scale via a few addition reaction steps, which is convenient for high-throughput material screening.

The present disclosure relates to methods for determining potency of multivalent RNA vaccines.

The invention discloses a parameterized constraint system and method for efflux pump avoidance and off-target risk inhibition, which are applied to the field of biological medicines, and aims to solve the dual problem that toxic risks are caused by efflux pump mediated drug resistance enhancement and off-target combination of existing antibacterial drugs. The method comprises the following steps: constructing an efflux pump identification avoidance five-dimensional feature space and a target spot specificity geometric-electrical constraint boundary, performing structure mapping and deviation degree evaluation on candidate molecules, and triggering directional modification; the target matching is verified through molecular docking, and if the target does not reach the standard, the pharmacophore is locally adjusted; virtual screening is carried out based on an off-target protein database, a secondary structure disturbance mechanism is started for high-risk molecules, and a stereoisomerism or electrical reversal group is introduced to destroy non-target binding; according to the method, collaborative optimization of antibacterial efficacy, drug resistance avoidance and safety risk is achieved, and the research and development efficiency and druggability of candidate molecules are remarkably improved.

Methods for determining the function and / or activity and / or potency of isohydrolase proteins are provided.

This invention relates to compositions, and uses and methods thereof, with therapeutic deciparticles. Described herein are deciparticle (nanoparticle) compositions composed of an amphiphilic compound complexed with an auxiliary compound such as a biologically active molecule. Deciparticles of this invention are active drugs having potency for anti-tumor effects and for immunosuppression. This invention is also directed to amphiphilic compounds useful for making deciparticle complexes.

Bioassay Laboratory Device for Quantitative Measurement of Drug Potency and Dose Response Relationships

The invention discloses an AKR1C3 selectively activated small molecule drug conjugate and application of the AKR1C3 selectively activated small molecule drug conjugate. The invention discloses a series of compounds with a structure as shown in a general formula I, and also discloses application of the compounds in cancer treatment. The inventor evaluates the efficacy of the compound represented by the general formula I in treatment of various cancers by taking an in-vitro anti-tumor cell experiment as a carrier, and finds that the compound has good in-vitro activity and extremely high selectivity and can be used as a precursor substance for further development of a cancer treatment effect through selective activation of aldoketoreductase 1C3.

To provide hepcidin analogs with improved in vivo half-lives, and related pharmaceutical compositions and methods of use thereof.SOLUTION: The present invention relates generally to hepcidin analog peptides and methods of making and using the same. In certain embodiments, hepcidin analogs exhibit one or more hepcidin activities. In certain embodiments, the present invention is directed to hepcidin peptide analogs comprising one or more peptide subunits, wherein the peptide subunits form a cyclized structure via an intramolecular bond, e.g., an intramolecular disulfide bond. In certain embodiments, cyclized structures have increased potency and selectivity compared to non-cyclized hepcidin peptides and analogs thereof. In certain embodiments, the hepcidin analog peptides of the present invention exhibit an extended half-life compared to hepcidin or conventional hepcidin analogs when delivered orally.SELECTED DRAWING: None

The present invention relates to cell-based methods for determining the biological activity of defibrotide. In particular, the invention provides a method for assessing the potency of defibrotide by assessing the viability of mammalian cells in the presence of at least one cytotoxic agent and one or more concentrations of defibrotide. Such methods are particularly useful for standardizing pharmaceutical compositions comprising defibrotide.

The application belongs to the technical field of biological medicine, and proposes a use of a pterostilbene derivative and a preparation of a medicine for treating and / or preventing diseases caused by oxidative stress. The chemical structure of the pterostilbene derivative is shown as formula (I)-(III). The scavenging effect of the obtained derivative on DPPH·, O2 ‑ · and ABTS + · free radicals and its total reducing capacity are detected respectively. In terms of DPPH· and total reducing capacity, it is found that the scavenging capacity of some derivatives is equivalent to that of pterostilbene or vitamin C. Derivatives 2a, 4a, 4c, 4e, 4h, 4i and 4m-4p have the same scavenging effect on O2 ‑ · free radicals as pterostilbene or vitamin C; the scavenging effect of derivative 2b on ABTS + · is equivalent to that of vitamin C and is superior to that of pterostilbene. The pterostilbene derivative has potential application prospects in the preparation of antioxidants.

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain H-APPAMP compounds (referred to herein as “H-APPAMP compounds”) that, inter alia, inhibit cyclin-dependent protein kinases (CDKs), especially CDK12 and / or CDK13, and are selective, for example, for CDK12 and / or CDK13 as compared to CDK7. In addition to selectively inhibiting CDK12 and / or CDK13, the compounds also act as selective Cyclin K degraders thereby removing the key signaling mechanism required for CDK12 and / or CDK13 activation; this confers additional cellular potency and selectivity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK, especially CDK12 and / or CDK13; and to treat disorders including: disorders that are associated with CDK, especially CDK12 and / or CDK13; disorders that result from an inappropriate activity of a CDK, especially CDK12 and / or CDK13; disorders that are associated with CDK mutation, especially CDK12 and / or CDK13 mutation; disorders that are associated with CDK overexpression, especially CDK12 and / or CDK13 overexpression; disorders that are associated with upstream pathway activation of CDK, especially CDK12 and / or CDK13; disorders that are ameliorated by the inhibition of CDK, especially CDK12 and / or CDK13; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; cardiovascular disorders (including atherosclerosis); autoimmune disorders (including rheumatoid arthritis); and disorders caused by dysfunction of translation in cells (including muscular dystrophy). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti estrogen, an anti-androgen, a Her2 blocker, a cytotoxic chemotherapeutic agent, an agent stimulating the immune system, a checkpoint inhibitor, a DNA repair inhibitor, etc.

The present invention provides isolated Clostridium difficile binary toxin antibodies that are capable of neutralizing binary toxin with high potency, polypeptides and nucleic acids encoding the same, and methods of use thereof.

The present invention provides novel compounds that are peptide hormone analogs and are useful for treating disorders such as diabetes and obesity.The compounds of the general sequence listed herein have tailored profiles of potency at the GIP receptor.Regarding in vivo properties, administration of exemplary peptides of the present invention has been shown to result in improved weight loss in animal models.Preferred compounds achieve this without significantly reducing food intake.

The present disclosure provides a method for the treatment of Parkinson's disease comprising simultaneously or sequentially administering to a patient in need of treatment of Parkinson's disease a dosage form comprising(i) levodopa in an amount ranging from 50 mg to 300 mg,(ii) carbidopa in an amount ranging from 25 mg to 150 mg or a therapeutically equivalent amount of another aromatic amino acid decarboxylase inhibitor, and(iii) entacapone in an amount ranging from 50 mg to 300 mg, wherein the proportion of entacapone to carbidopa in said dosage form ranges from 0.3:1.0 to 3.2:1.0 by weight, a moderately potent COMT inhibitor in an amount ranging from 25 mg to 200 mg, wherein the proportion of said COMT inhibitor to carbidopa in said dosage form ranges from 0.16:1.0 to 3.08:1.0 by weight, or a highly potent COMT inhibitor in an amount ranging from 1 mg to 100 mg, wherein the proportion of said COMT inhibitor to carbidopa in said dosage form ranges from 0.006:1.0 to 1.54:1.0 by weight. Pharmaceutical dosage form used in said method are also disclosed.

The invention discloses a preparation method and application of pleuromutilin and derivatives thereof. The preparation of C7-site substituted, C8-site axial substituted and C8-site exocyclic double bond substituted derivatives of pleuromutilin is realized. The pleuromutilin derivative shows activity which is obviously superior to that of a parent compound pleuromutilin in the aspect of inhibiting proliferation of human cancer cells (such as breast cancer MDA-MB-231 cells and liver cancer HepG2 cells) with high expression of TrxR. Wherein the C8-position axially substituted derivative has particularly outstanding advantages in the aspect of inhibiting TrxR enzyme activity, and compared with a parent compound pleuromutilin and a positive control drug Jinnofen, the TrxR inhibiting efficacy of the C8-position axially substituted derivative is improved to 9 times and 16.7 times respectively.

Providing a method for testing the efficacy of andexanet. [Solution] This disclosure relates to a kit and method for measuring the potency of an andexanet sample in neutralizing a factor Xa inhibitor and restoring the activity of wild-type factor Xa. This disclosure provides a method for determining the activity of an andexanet sample, comprising: mixing a test sample containing an andexanet with a mixture containing human factor Xa (HFXa) and a direct factor Xa (fXa) inhibitor, wherein the molar ratio of FXa to Xa inhibitor is 0.2:1 to 0.3:1; adding a chromogenic fXa substrate to the mixture, wherein the chromogenic fXa substrate can release a chromophore upon reaction with HFXa; detecting the amount of chromophore released; and calculating the activity of the andexanet sample in releasing HFXa from a direct fXa inhibitor from the amount of chromophore released.