- Preparation method of labetalol hydrochloride
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The invention provides a preparation method of labetalol hydrochloride, and belongs to the technical field of medicines. The invention provides a preparation method. The method comprises the following steps: carrying out nucleophilic substitution reaction on 5-halogenated acetyl salicylamide serving as an initial raw material and benzylamine, and then carrying out nucleophilic substitution reaction on the obtained product and 3-halogenated butylbenzene (or carrying out amine-ester exchange reaction on the obtained product and an esterification reaction product of 3-hydroxybutylbenzene and p-toluenesulfonyl chloride); and carrying out catalytic hydrogenation reaction and salifying to obtain the labeolol hydrochloride. According to the preparation method provided by the invention, benzylamine is adopted to replace dibenzylamine, so that the raw materials are high in atom utilization rate and environment-friendly, and atom economy of green chemistry is embodied; wherein the amine-ester exchange reaction is high in selectivity, and the obtained product is directly used for the next-step reaction. The one-step method is adopted to remove the protective agent and reduce carbonyl, so that the process route is shortened; meanwhile, the preparation method is simple and convenient to operate, high in stability and controllability, high in production cost, high in yield and suitable for industrial production.
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Paragraph 0062; 0068; 0073-0074; 0078-0083; 0084; 0089
(2021/11/27)
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- Preparation and evaluation of a triazole-bridged bis(β-cyclodextrin)–bonded chiral stationary phase for HPLC
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A triazole-bridged bis(β-cyclodextrin) was synthesized via a high-yield Click Chemistry reaction between 6-azido-β-cyclodextrin and 6-propynylamino-β-cyclodextrin, and then it was bonded onto ordered silica gel SBA-15 to obtain a novel triazole-bridged bis (β-cyclodextrin)–bonded chiral stationary phase (TBCDP). The structures of the bridged cyclodextrin and TBCDP were characterized by the infrared spectroscopy, mass spectrometry, elemental analysis, and thermogravimetric analysis. The chiral performance of TBCDP was evaluated by using chiral pesticides and drugs as probes including triazoles, flavanones, dansyl amino acids and β-blockers. Some effects of the composition in mobile phase and pH value on the enantioseparations were investigated in different modes. The nine triazoles, eight flavanones, and eight dansyl amino acids were successfully resolved on TBCDP under the reversed phase with the resolutions of hexaconazole, 2′-hydroxyflavanone, and dansyl-DL-tyrosine, which were 2.49, 5.40, and 3.25 within 30 minutes, respectively. The ten β-blockers were also separated under the polar organic mode with the resolution of arotinolol reached 1.71. Some related separation mechanisms were discussed preliminary. Compared with the native cyclodextrin stationary phase (CDSP), TBCDP has higher enantioselectivity to separate more analytes, which benefited from the synergistic inclusion ability of the two adjacent cavities and bridging linker of TBCDP, thereby enabling it a promising prospect in chiral drugs and food analysis.
- Shuang, Yazhou,Liao, Yuqin,Wang, Hui,Wang, Yuanxing,Li, Laisheng
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p. 168 - 184
(2019/11/25)
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- COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SALT SENSITIVITY OF BLOOD PRESSURE
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To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating. See those miRNAs with asterisks in FIG. 1 and below. The present invention encompasses the use of one or more of these markers for identifying and diagnosing SR, SS, and ISS subjects.
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- THERAPY FOR COMPLICATIONS OF DIABETES
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A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.
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- ANTIHYPERTENSIVE THERAPY
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A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.
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- FLUORESCENCE BASED DETECTION OF SUBSTANCES
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A method for the fluorescent detection of a substance, the method comprising providing particles comprising a metal or a metal oxide core, wherein one or more optionally fluorescently tagged antibodies or human specific peptide nucleic acid (PNA) oligomers for binding to a substance is/are bound, directly or indirectly, to the surface of the metal or metal oxide; contacting a substrate, which may or may not have the substance on its surface, with the particles for a time sufficient to allow the antibody/PNA oligomer to bind with the substance; removing those particles which have not bound to the substrate; if the antibodies or PNA oligomers are not fluorescently tagged, contacting the substrate with one or more fluorophores that selectively bind with the antibody and/or substance, then optionally washing the substrate to remove unbound fluorophores; and illuminating the substrate with appropriate radiation to show the fluorophores on the substrate.
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- Pharmaceutical formula
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The present invention concerns a pharmacological vehicle or carrier system, which makes possible administration of the active ingredient with a high absorption thereof in the blood circulation of the patient treated therewith, in particular also in the case of oral administration. The pharmacological vehicle system according to the invention comprises ultrafine particles of a reaction product of a reactive derivative of an at least dibasic inorganic acid or an alkane-carboxylic acid having 2 or 3 carboxyl groups and optionally one or two hydroxy groups, wherein one bond of the dibasic inorganic acid or one carboxy group of the alkane-carboxylic acid is bonded to a pharmacological active ingredient containing a hydroxy group, SH group and/or a primary or secondary amino group having a ractive hydrogen atom on this group, and the other bond is bonded to the free hydroxy group of a glycerolipid having at least one free hydroxy group on the glycerol. The invention further concerns these reaction products and a process for the preparation of ultrafine particles of these reaction products.
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- Diastereoisomers of 5-(1-hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl)salicylamide
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Disclosed is an improved process for separating 5-[1-hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl]salicylamide into its two diastereoisomeric racemates; a process for converting either diastereoisomer into the other; and the use of one specified diastereoisomer as a superior antiarrhythmic agent.
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- 5-[1-HYDROXY-2-(1-METHYL-3-PHENYL-PROPYL)AMINOETHYL] SALICYLAMIDE AND PHYSIOLOGICALLY ACCEPTABLE ACID ADDITION SALTS THEROF
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Compounds of the formula: STR1 and physiologically acceptable acid addition salts thereof, in which R 1 isA. AN ARYLALKYL GROUP, THE ALKYL PORTION OF WHICH CONTAINS FROM 1 TO 6 CARBON ATOMS AND THE ARYL PORTION OF WHICH MAY BE SUBSTITUTED BY ONE OR MORE ALKOXY GROUPS OR HYDROXY GROUPS; ORB. AN ARYLOXYALKYL GROUP, THE ALKYL PORTION OF WHICH CONTAINS FROM 1 TO 6 CARBON ATOMS, AND THE ARYLOXY PORTION OF WHICH IS SUBSTITUTED WITH ONE OR MORE ALKOXY OR HYDROXY GROUPS.These compounds have a blocking action on both α-and β-adrenergic receptors. Processes for the production of these compounds and pharmaceutical compositions containing them are also provided.
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