28 results about "Hydroxycarbamide" patented technology

The present invention provides a liquid composition comprising effective amount of Hydroxyurea for oral administration. The invention further discloses liquid formulation in form of ready to use oral suspension which remains stable at room temperature at the time of dispensing, storage and even after reopening of the container comprising the suspension. Also provided is a method of preparing the formulation and treating sickle cell anemia in pediatric patients.

The invention discloses a preparation method of an N-hydroxyurea compound, which specifically comprises the following steps: step 1, sequentially carrying out Lossen rearrangement and nucleophilic reaction under the action of alkali by taking Boc NHOH as shown in a formula 1 as an initial reactant, SO2F2 gas as an acylating agent and an amine compound RR 'NH as a nucleophilic reagent to obtain a tert-butoxyurea compound as shown in a formula 2; and 2, removing the tert-butoxy group from the tert-butoxyurea compound to obtain the N-hydroxyurea compound as shown in a formula 3. The innovation point of the invention is that commercialized easily available gas sulfonyl fluoride promotes Lossen rearrangement of tert-butylhydroxylamine to generate a key intermediate tert-butoxy isocyanate, the key intermediate tert-butoxy isocyanate and a substrate amine compound are subjected to a one-pot reaction to obtain the N-hydroxyurea compound, the reaction conditions are simple, the operation is convenient, the compatibility of substrate functional groups is strong, and the application prospect is good.

The lyophilized formulations comprise steepstercetin, including hydroxyurea methyl acyl fulvene and pharmaceutically acceptable salts thereof, in combination with a cyclodextrin. These formulations are designed to enhance the solubility, stability and therapeutic efficacy of steep steep cephalosporin, which has been illustrated due to its potent anti-cancer properties. Methods for producing these lyophilized formulations are provided, including a lyophilization process.

The invention discloses a cGAS-STING activated micro-needle system and a preparation method and application thereof.The cGAS-STING activated micro-needle system comprises a needle tip and a backing which are connected, the needle tip is loaded with a mesoporous photosensitive nano-composite drug, the mesoporous photosensitive nano-composite drug takes hollow Prussian blue nanoparticles as a carrier, the interior of the mesoporous photosensitive nano-composite drug is loaded with a small molecule drug, and the surface of the mesoporous photosensitive nano-composite drug is coated with a coating. The outer layer is coated with natural CD44 ligand polysaccharide; the small molecular medicine is a mixture of hydroxyurea and carotene. The mesoporous photosensitive nano-composite drug can induce death of immunogenic cells through mild photothermal induction, and release an injury-related molecular mode; meanwhile, a cGAS-STING signal channel is activated, secretion of type I interferon is promoted, and dendritic cells are induced to be activated and mature, so that T cell mediated anti-tumor immune response is enhanced. The invention provides an innovative tumor immunotherapy strategy and has important clinical application value.

The application provides a strong adsorption type temperature-resistant-45 DEG C drilling fluid wetting agent for polar drilling and a preparation method and application thereof, and belongs to the technical field of polar drilling. The wetting agent is prepared from the following raw materials: alkyl amine polyoxyethylene ether, amine-based compound and dimethylacetamide; wherein the alkyl amine polyoxyethylene ether is one of octadecylamine polyoxyethylene ether or dodecylamine polyoxyethylene ether; and the amine-based compound is one of hydroxyurea or 5-hydroxytryptamine. The wetting agent has simple raw material composition and preparation method, is safe and environmentally friendly, and has no irritating odor; the wetting agent is applied to the drilling fluid for polar drilling, can improve the ultralow-temperature dispersion performance and colloid performance of the drilling fluid, effectively solves the problem of poor dispersion performance of organic soil in the drilling fluid under the ultralow-temperature condition, and further improves the polar drilling efficiency.

The application belongs to the technical field of biological medicine, and particularly relates to application of hydroxyurea in preparation of a drug for preventing or treating retinoblastoma, which can achieve the effect of effectively treating RB by specifically targeting ecDNA in retinoblastoma tumor cells, and has high effectiveness and high specificity. The hydroxyurea provided by the application can inhibit the expression of SUZ12 in retinoblastoma cell lines WERI-RB1 or Y79 cells, reduce the modification level of H3K27 trimethylation, and can inhibit the proliferation and tumorigenicity of retinoblastoma cell lines WERI-RB1 or Y79 cells.

Methods of using one or more fumaric acid esters or pharmacologically active salts, derivatives, analogues, or prodrugs thereof to increase expression of fetal hemoglobin (HbF) are disclosed. The methods typically include administering to a subject an effective amount of one or more fumaric acid esters optionally in combination or alternation with hydroxyurea to induce HbF expression in the subject in an effective amount to reduce one or more symptoms of a sickle cell disorder, a hemoglobinopathy, or a beta-thalassemia, or to compensate for a genetic mutation is the human beta-globin gene (HBB) or an expression control sequence thereof. Pharmaceutical dosage units and dosage regimes for use in the disclosed methods are also provided.

The present invention provides a liquid composition for oral administration comprising an effective amount of hydroxyurea. The present invention also discloses a liquid formulation in the form of a ready-to-use oral suspension which remains stable at room temperature when dispensed, stored, even after the container containing the suspension is reopened. Also provided is a method of preparing the formulation and treating sickle cell anemia in a child patient.

The present invention relates to a pharmaceutical composition for preventing or treating cancer, comprising vaccinia virus and hydroxyurea as active ingredients. The pharmaceutical composition for treating cancer, comprising vaccinia virus and hydroxyurea as active ingredients according to the present invention, exhibits a higher anti-cancer effect and safety than conventional vaccinia virus alone administration. Therefore, the pharmaceutical composition comprising vaccinia virus and hydroxyurea as active ingredients according to the present invention can be advantageously used for treating cancer.

An oral pharmaceutical solution comprising hydroxycarbamide as active ingredient and an aqueous carrier comprising a pharmaceutically acceptable buffer and 0.5 mg / ml to 2.4 mg / ml xanthan gum, wherein the pH of the solution is from 3.0 to 6.0.

The invention relates to the technical field of organic synthesis, and particularly discloses a method for synthesizing a 2-hydroxyl diaryl urea derivative. According to the method, benzoxazole compounds and aryl iso (thio) cyanate are used as raw materials and react in a methanol solvent at 60 DEG C under the synergistic catalysis of PIFA and protonated aluminum oxide, and an o-hydroxyl-ureido structure is constructed in one step. According to the method, highly toxic phosgene / isocyanate and noble metal catalysts are thoroughly avoided, the problems of low yield and more byproducts of a traditional route are solved, and the highest yield of 87% is achieved under normal-pressure mild conditions. 100% regioselectivity is achieved through a ring opening / coupling mechanism, derivatives containing 24 substituent groups such as halogen, trifluoromethoxy and naphthyl are successfully synthesized, and the bottleneck of asymmetric urea selective synthesis is broken through.

A companion diagnostic method, kit, and integrated system for quantifying expression of Prostaglandin Reductase 1 (PTGR1) in a patient sample are disclosed. When the measured expression equals or exceeds a predetermined threshold, the patient is selected to receive hydroxyurea methylacylfulvene (LP-184) or a related acylfulvene. The invention enables personalized cancer therapy, improves objective response rates, and minimizes unnecessary exposure to ineffective treatment. Also provided are pharmaceutical combinations, uses, and claims for treating PTGR1 -positive solid tumors and hematological malignancies.

The present invention relates to oral pharmaceutical compositions comprising:(i) hydroxyurea at a concentration of about 10 mg / mL to about 100 mg / mL;(ii) at least one pharmaceutically acceptable liquid vehicle;(iii) one or more amino acids at a concentration of about 0.1 mg / mL to 10.0 mg / mL, and(iv) 0.001% to 10% of one or more pharmaceutically acceptable excipients,wherein the composition is in the form of a ready-to-use and safe-to-administer solution suitable for oral administration,wherein the hydroxyurea is dissolved in the liquid vehicle and the solution is homogeneous, andwherein the solution is stable, such that the level of carbamoyloxyurea in the solution is less than 0.5% w / w as measured by HPLC upon storage at 25° C. / 60% RH for at least 3 months, or at 2-8° C. for at least 12 months.

Disclosed are methods, compositions, and kits for treating pediatric cancers using hydroxyureamethyl acylfulvene (LP-184) or pharmaceutically acceptable salts / solvates thereof. The methods include monotherapy and combination regimens for pediatric sarcoma, medulloblastoma, glioma (including DIPG), hepatoblastoma, Wilms tumor, and related malignancies. Combination therapies include LP-184 with vincristine, topoisomerase I poisons (topotecan or irinotecan), PARP inhibitors (e.g., rucaparib), or spironolactone, yielding additive or greater-than-additive reductions in tumor growth or cell viability.

The present invention relates to the preparation of protected piperidine carboxylates suitable as intermediates for preparing the beta-lactamase inhibitor (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfato)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide via a series of further process steps including the sulfation of a hydroxyurea compound.

A method for treating liver cancer, particularly in subjects exhibiting homologous recombination deficiency (HRD) positivity, includes using hydroxyureamethyl acylfulvene. The compound can be administered as a monotherapy or in combination with other chemotherapeutic agents and / or radiotherapy.

The present invention provides a stable aqueous hydroxycarbamide solution comprising: hydroxycarbamide; a pH adjuster being sodium hydroxide, potassium hydroxide, sodium bicarbonate, and sodium carbonate, or a mixture of one or more of these substances; and optionally a preservative being a base of methyl hydroxybenzoate and / or ethyl hydroxybenzoate; wherein: the solution is controlled to have a pH of between 6.1 and 7.1. The solution of the present invention is beneficial as compared to solutions according to the prior art in that it can be safely stored at ambient temperatures for prolonged periods of time without significant degradation.

A method of detecting an hydroxycarbamide in a solution including contacting an electrochemical sensor with the solution, where the electrochemical sensor includes gold coated copper oxide circular nanoplates and a substrate. The gold coated copper oxide circular nanoplates are coated on the substrate. The method further includes applying a potential and irradiating the electrochemical sensor in the solution, and measuring a Raman signal of the electrochemical sensor in the solution. The intensity of the Raman signal correlates with the amount of hydroxycarbamide in the solution.

The present disclosure relates to methods of treating a subject having sickle cell disease, comprising administering to the subject a therapeutically effective amount of an inhibitor of polycomb repressive complex 2 (PRC2). In certain embodiments of the disclosed methods, prior to the administration to the subject of the inhibitor of polycomb repressive complex 2 (PRC2) the subject has (a) been administered hydroxyurea; and / or (b) been administered a stable dose of one or more of voxelotor, crizanlizumab, and L-glutamine.

An electrochemical sensor comprising an array of working electrodes made of noble metals, wherein the array includes: one or more bare working electrode(s); and a first set of working electrodes coated with a first transition metal dichalcogenide, the first set comprises at least subset A and subset B, wherein working electrodes of subset B show the presence of hydroxide form(s) and / or high oxidation state oxide forms(s) of the noble metal, whereas working electrodes of subset A are free of such forms; and / or working electrodes of subset B show higher capacitive currents and lower charge transfer resistance compared to working electrodes of subset A, as determined by electrochemical impedance spectroscopy.

Provided herein are methods for increasing the therapeutic efficiency of oncolytic bacterial therapeutics. Bacterial oncolytic therapies, especially the ones targeting tumor hypoxia such as C. novyi-NT, often encounter incomplete tumor clearance in less hypoxic tumoral areas and severe inflammatory reactions. In this study, we explored immune-modulating preconditioning to suppress the host neutrophils and significantly enhanced the antitumor efficacy of C. novyi-NT in animal models, including an orthotopic brain tumor model in rabbits. The optimized preconditioning agent, hydroxyurea, is clinically approved and C. novyi-NT has demonstrated manageable safety and promising antitumor responses in clinical trials. Thus, the proposed preconditioning of neutrophil suppression is readily translatable to patients undergoing C. novyi-NT trials or other oncolytic biologic therapies and could improve outcome.

The disclosure provides combination regimens and compositions for the treatment of triple-negative breast cancer (TNBC). A subject in need thereof is administered a therapeutically effective amount of hydroxyureamethyl acylfulvene and a therapeutically effective amount of an immunotherapy such as a PD-1 or PD-L1 checkpoint inhibitor. Also disclosed are pharmaceutical compositions and kits containing the acylfulvene, the immunotherapy component, or both in admixture with pharmaceutically acceptable carriers.

The invention relates to the method of use of a pharmaceutical composition containing hydroxyurea, for the treatment of severe chronic anemia in a patient suffering from sickle cell anemia not already undergoing treatment with hydroxyurea and not suffering a vaso-occlusive crisis.

This method involves treating individuals diagnosed with renal cell carcinoma using a therapeutically effective amount of hydroxyureamethyl acylfulvene. The treatment is applicable to various types of renal cell carcinoma, including clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma, and medullary carcinoma.

The present invention provides a stable aqueous hydroxycarbamide solution comprising: hydroxycarbamide; a pH adjuster being sodium hydroxide, potassium hydroxide, sodium bicarbonate, and sodium carbonate, or a mixture of one or more of these substances; and optionally a preservative being a base of methyl hydroxybenzoate and / or ethyl hydroxybenzoate; wherein: the solution is controlled to have a pH of between 6.1 and 7.1. The solution of the present invention is beneficial as compared to solutions according to the prior art in that it can be safely stored at ambient temperatures for prolonged periods of time without significant degradation.

The invention discloses a pharmaceutical composition for treating drug-resistant brain glioma, and belongs to the technical field of biological medicines.The pharmaceutical composition comprises at least one blood-brain barrier opener and at least one drug-resistant brain glioma chemotherapy drug, the blood-brain barrier opener is arginine or hydroxyurea, and the drug-resistant brain glioma chemotherapy drug is a drug-resistant brain glioma chemotherapy drug. The drug-resistant brain glioma chemotherapeutic drug comprises doxorubicin hydrochloride, mitoxantrone or methotrexate. The blood-brain barrier opener and the drug-resistant brain glioma chemotherapeutic drug are combined for treatment of drug-resistant brain glioma, the blood-brain barrier opener arginine or hydroxyurea can obviously increase the accumulation amount of the chemotherapeutic drug in the brain, and the pharmaceutical composition can effectively inhibit the growth of the drug-resistant brain glioma and prolong the lifetime of a model animal. According to the technical scheme, a new solution is provided for overcoming the blood-brain barrier and treating the drug-resistant brain glioma.

The invention belongs to the technical field of organic synthesis, and mainly relates to a synthesis method of pyroxasulfone intermediate 5, 5-dimethyl-4, 5-dihydroisoxazole-3-thioformamidine hydrochloride, which comprises the following steps: reacting a compound IV with hydroxyurea under alkaline conditions to obtain a compound III; directly reacting the compound III with a chlorination reagent under an acidic condition without purification to obtain a compound II; reacting the compound II with thiourea in the presence of inorganic acid to obtain a compound I; according to the method provided by the invention, 3, 3-methyl dimethacrylate is used as a raw material, so that compared with 3, 3-ethyl dimethacrylate used in similar methods, the cost is lower, and the cyclization yield is higher; meanwhile, phosphoric acid is added as a catalyst, so that the generation of by-products is greatly reduced; finally, the compound I is prepared by directly reacting with thiourea in the presence of inorganic acid, the yield of a finished product is up to 86% or above, the purity can reach 98%, most of used solvents can be recycled and reused, and the method is suitable for industrial production.

The invention provides a strong adsorption type drilling fluid wetting agent capable of resisting the temperature of-45 DEG C for polar region drilling as well as a preparation method and application thereof, and belongs to the technical field of polar region drilling. The wetting agent is prepared from the following raw materials: alkylamine polyoxyethylene ether, an amino compound and dimethylacetamide. Wherein the alkylamine polyoxyethylene ether is one of octadecylamine polyoxyethylene ether or dodecylamine polyoxyethylene ether; the amino compound is one of hydroxyurea or 5-hydroxytryptamine. The wetting agent is simple in raw material composition and preparation method, and the obtained wetting agent is safe, environmentally friendly and free of pungent smell; the wetting agent is applied to the drilling fluid for polar region drilling, can improve the ultralow-temperature dispersion performance and colloid performance of the drilling fluid, effectively solves the problem that the dispersion performance of organic soil in the drilling fluid is poor under the ultralow-temperature condition, and further improves the polar region drilling efficiency.