356 results about "Antihypertensive drug" patented technology

The invention discloses a preparation method of one of components of a novel antihypertensive drug LCZ696, namely, sacubitril (sacubitril, AHU-377, I). The method comprises the following preparation steps: carrying out cyclization, addition, debenzylation, ring opening, esterification, amidation and the like on a chiral induciton reagent (S)-1-(alpha-aminobenzyl)-2-naphthol (S-betti Base) and 2R-methyl-4-oxo-butyric acid to prepare the sacubitril (I). The preparation method is available in raw materials, concise in process, economic and environmentally friendly, and is suitable for industrial production.

Compounds are disclosed having the formulae: wherein R' is hydrogen, lower alkyl or lower alkoxy; r is 0 or 1 and p is zero to four; and wherein R1 is selected from the group, consisting of radicals represented by the general formulae: wherein Y is selected from the group consisting of lower alkyl, lower alkoxy, and halogen; Z is oxygen, sulfur or -NH, Q is -CH or nitrogen; a is zero or an integer of from one to three; and wherein, R2 is selected from the group consisting of hydrogen and straight chain, branched and cyclic hydrocarbyl radicals having from one to four carbon atoms, and optionally substituted with a hydroxyl radical; and wherein X is two hydrogen atoms or oxygen and B is selected from oxygen and nitrogen, and pharmaceutically acceptable salts thereof, with the proviso that when X is two hydrogen atoms, B is oxygen, and with the further proviso that when B is oxygen then R1 cannot be a phenyl or a substituted phenyl radical. Pharmaceutical preparations using these compounds and a method for inducing an adenosine response mediated by the adenosine A2 receptor by administering these compounds are also disclosed.

A pharmaceutical composition comprising at least one of components (a) and at least one of components (b) shown in below: (a) a compound represented by the general formula (I) (wherein R1 represents a hydrogen atom or a hydroxyl group) or an acid addition salt or hydrate thereof; and (b) an ameliorant of cerebral circulation, a vasodilator, a cerebral protecting drug, an brain metabolic stimulants, an anticoagulant, an antiplatelet drug, a thrombolytic drug, an amelirant of psychiatric symptom, a antihypertensive drug, an antianginal drug, a diuretic, a cardiotonic, an antiarrhythmic drug, an antihyperlipidemic drug, an immunosuppressant, or a pharmaceutically acceptable salt (except the components shown in (a)). It is useful as a preventive or remedy for cerebrovascular disorders and cardiac diseases.

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.

The invention belongs to the technical field of medicine detection, and particularly relates to a method for detecting 43 types of medicines in blood by liquid chromatogram tandem mass spectrum. Aiming at the problem of lack of a method capable of simultaneously detecting seven types of common poisons, eleven types of antihypertensive drugs, eleven types of hypoglycemic agents and fourteen types of psychiatric drugs in the prior art, the invention provides the method. The method comprises the following steps of (a) performing protein precipitation on a to-be-detected sample with acetonitrile;and (b) detecting a selected drug by a multi-reaction monitoring (MRM) mode of high performance liquid chromatography-tandem mass spectrometry, and mass spectrum screening analysis is performed in a segmented way according to compound retention time and by two or three pairs of parent ions / daughter ions. By the method, the screening analysis of 43 types of drugs such as common antihypertensive drugs, common hypoglycemic agents, psychiatric drugs and poisons can be rapidly and accurately completed within 25 minutes in one time, the detection efficiency is high, and the method is good in sensitivity and is suitable for promotion and application.

A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, 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.

The present invention generally concerns the management of age-related diseases in domestic animals. Specifically, the present invention is directed to combination therapies for the treatment of progressive renal diseases (e.g., Chronic Renal Failure) and their accompanying secondary disease states. In a composition aspect, the present invention provides a composition comprising a phosphate binder and another pharmaceutically active ingredient. The other pharmaceutically active ingredient is selected from a group consisting of antihypertensives, calcitrol, vitamin D analogues, lipid restriction products, potassium salts, treatments for anemia and alkalization compounds.

An application of a high-intensity focused ultrasound system to treatment of essential hypertension. A treatment process includes: conducting ultrasonic positioning measurement on both sides of perirenal fat tissue of a patient, setting a therapeutic window and parameters of the system, and setting corresponding power parameter of the system, so as to make local temperature of the tissue during treatment reach 40-70° C., wherein treatment portions are both sides, and treatment scope is one third to all of the whole tissue; starting the system to treat one side of the tissue according to the set parameters and then the other. By treating a secondary center for regulating the activity of a whole-body sympathetic system, the activity of the whole-body sympathetic system can be reduced, so that the blood pressure level of the patient can be reduced, and fewer kinds and smaller dosage of antihypertensive drugs can be taken or ceased.

The invention provides an albumin angiotensin converting enzyme inhibition peptide and a preparation method thereof, belonging to the biotechnology field. A new active peptide with angiotensin converting enzyme inhibition function is separated and purified from albumin zymolyte and has a sequence of RVPSL. The preparation method comprises the steps of: carrying out the enzymolysis on albumin to prepare the zymolyte, purifying the albumin angiotensin converting enzyme inhibition peptide, identifying the structure of the albumin angiotensin converting enzyme inhibition peptide, synthesizing the albumin angiotensin converting enzyme inhibition peptide and checking the activity of the albumin angiotensin converting enzyme inhibition peptide. The invention can be used for preparing antihypertensive drugs and functional foods assisting blood pressure reduction.

The invention belongs to the fields of food biotechnologies and function healthcare and discloses an antihypertensive peptide derived from a sardine as well as a preparation method and application of the antihypertensive peptide. The method comprises the following main technical steps of after pretreating the sardine to obtain homogenate, adding papain to carry out enzymolysis firstly, and then, adding an alkaline protease to carry out enzymolysis; deactivating the enzyme after enzymolysis is finished, and centrifuging the enzyme-deactivated enzymatic hydrolysate; taking the centrifuged supernatant, and separating and purifying a crude product by using an ultrafiltration and gel chromatography method; carrying out freeze-drying on the separated and purified efficient component to obtain the antihypertensive peptide derived from the sardine. The sardine is high in yield and low in price, so that the comprehensive utilization value of the sardine can be sufficiently increased when the sardine is used as the raw material to prepare the antihypertensive peptide; in addition, the antihypertensive peptide derived from the sardine and obtained through enzymolysis is free of safety problems and side effects of chemical antihypertensive drugs and ideal in antihypertensive effect.

A concomitant agent to be used simultaneously or separately, comprising a combination of (a) 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine, a salt of the compound with an organic or inorganic and mono- or di-basic acid or a solvate thereof, and(b) at least one kind of active ingredient selected from the group consisting of an active ingredient of a pharmaceutical agent selected from (i) an antidiabetic drug, (ii) a lipid lowering drug, (iii) an antihypertensive drug, (iv) a therapeutic drug for diabetic complications, (v) an antiobesity drug, (vi) an antiplatelet drug and (vii) an anticoagulant, a pharmaceutically acceptable salt thereof and a solvate thereof.

The invention discloses a compound apigenin nanoemulsion antihypertensive drug which comprises the following raw materials in mass percent: 1-15% of apigenin, 5-35% of surfactant, 1-20% of cosurfactant, 1-20% of oil, 0.5-10% of motherwort fruit aqueous extract, 0.5-10% of semen cassiae water extract and the balance of distilled water; and the sum of mass percents of the above raw materials is 100%. The nanoemulsion is small in emulsion droplet, uniform in distribution, low in viscosity and good in liquidity. After apigenin is prepared into a nanoemulsion, blood brain barrier transmission capacity is obviously increased, the bioavailability of a technical material is obviously improved, the half-life period of the drug can be prolonged; and the drug administration times can be reduced; with adoption of the nanoemulsion, the dissolution and infiltration capacity of atenolol can be improved and the stability of apigenin is increased; and the nanoemulsion has obvious synergistic effect compounded with the motherwort fruit and the semen cassiae; and the medicinal cure effect can be more fully played.

The present invention relates to pharmaceutical compositions for reducing essential hypertension and systemic inflammation. While many drugs have been found to treat hypertension, the currently available drugs often do not maintain reduced blood pressure at the preferred norm of 115 / 75 mm Hg or less throughout a 24 hour period. The current invention provides compositions comprising at least one hypertensive drug combined with the natural product Coenzyme Q10 (ubiquinone or CoQ10), which synergizes with the antihypertensive drugs to maintain low blood pressure throughout the day and night while generating other positive effects on the risks of cardiovascular disease, renal failure, and stroke. CoQ10 also counteracts some of the side effects of some hypertensive drugs such as tiredness, weakness, and / or liver toxicity. The invention further describes therapeutically effective methods for reducing systemic inflammation in hypertensive mammals comprising treatment with an antihypertensive composition that includes at least one angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and CoQ10 (ubiquinone). The invention metrics for reducing systemic inflammation comprise the reduction of serum levels of high sensitivity C-reactive protein (CRP), Interleukin 6 (IL-6), and / or tumor necrosis factor-alpha (TNF-alpha). These antihypertensive-CoQ10 combinations will synergistically reduce both hypertension and systemic inflammation.

The invention provides a medical composite for treating hypertension and a preparation thereof. The medical composite comprises antihypertensive drug, HMGCoA reductase inhibitor and insulin sensitizer. The medical composite of the invention not only can effectively reduce blood pressure, but also has good effect on the treatment and prevention of hypertension complications. The long term survival of patients can be improved obviously.

The present invention relates to a combination, such as a combined preparation or pharmaceutical composition comprising: (a) compound of formula (I), and / or (II) or a pharmaceutically acceptable salt thereof; (b) at least one therapeutic agent selected from the group consisting of: an antihypertensive agent; an antidiabetics agent; a hypolipidemic agent; an antiplatelet agent; an antiobesity agent; an antithrombotic agent; an agent for diabetic vascular complications; and an agent for treatment of heart failure; or a pharmaceutically acceptable salts thereof, optionally in presence of a pharmaceutically acceptable carrier for separate, simultaneous or sequential use. The present invention also relates to a use of such combination for the treatment of mammal including human being. R1, R2, R3, R1, R2, R3, R4, R5, X, Y, A and B and m are as defined in the specification.

The present invention relates to cholesteryl ester transfer protein (CETP) inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors optionally in combination with certain therapeutic agents, such as antihypertensive agents, in the treatment of certain diseases / disorders Applications.

The invention relates to a pharmaceutical composition containing one of angiotensin converting enzyme inhibitors (ACEI) and active metabolites or medical salt thereof in medicine dosage, one or more of B vitamins in medicine dosage, ginkgo biloba extracts (GbE) in medicine dosage and a medical carrier, and relates to application of the pharmaceutical composition in preparing medicines for treating, preventing or retarding stroke. The medicines prepared by the pharmaceutical composition provided by the invention are superior to the simple antihypertensive drugs in the aspect of treating, preventing or retarding stroke and facilitate the patients to take. The invention belongs to the pharmaceutical field.

The invention provides a drug recommendation method, device and server based on literature data. The method includes the steps that abstract data of all articles in a biomedicine literature database is obtained; an abstract database of articles related to a certain special people group with hypertension is set up by limiting medical subject headings; data indexes for evaluating quality of the articles related to the certain special people group with hypertension are set up; the article, author, periodical and print type in all the articles related to the certain special people group with hypertension and information of various kinds of antihypertensive drugs are extracted according to the abstract database; weighted isomerism graphs are constructed according to the extracted information and the data indexes; the weighted isomerism graphs are sorted, and ranking information of the antihypertensive drugs suitable for the certain special people group with hypertension is obtained. The method can recommend ranking information of the antihypertensive drugs suitable for the various special people groups to improve the cognition degree to use conditions of the antihypertensive drugs of grass-roots doctors, increase blood pressure rate of reaching the standard and improve the current situation of poor control over hypertension.

The invention relates to a method for preparing a sartan antihypertensive drug side-chain. The method comprises the following steps of: dissolving (4'-methylbiphenyl-2-nitrile, 4'-methylbiphenyl-2-carboxylic methyl, 5-[2-(4'-methylbiphenyl)]-2-H-imidazole and 5-[2-(4'-methylbiphenyl)]-2-triphenylmethyl-imidazole) into an aprotic organic solvent, adding 0.5-0.8 of brominated agent with equivalent weight, and then adding a small quantity of initiators; raising temperature until backflow reaction is performed for 3-6 hours, and then dropping temperature by 5-10 DEG C; and refilling the brominated agent and a small quantity of initiators for several times, adding 0.02-0.2 of brominated agent with equivalent weight in every time, and refilling every 3-5 hours. The temperature is dropped to the room temperature after raw materials are basically reacted, water washing and layering are carried out, a reaction solvent is recovered, a fining solvent is added into exhaust liquor for agitated crystallization, cooling and filtering, and the sartan antihypertensive drug side-chain is obtained. The yield is 90 percent, the purity is more than 96 percent, and the dibromo products are less than 2 percent.

The invention discloses a preparation method of methyl 2-(2,3-dichlorobenzylidine)acetoacetate which is a synthetic intermediate of antihypertensive drug felodipine. The method is characterized by allowing a condensation reaction between 2, 3-dichlorobenzaldehyde and methyl acetoacetate in alcohol solution under the catalytic action of a novel combined catalyst consisting of secondary amine and quinoline carboxylic acid. Reaction liquid is cooled at room temperature for crystallization, filtered, washed and dried after the condensation reaction to obtain primary eluent of the intermediate methyl 2-(2,3-dichlorobenzylidine)acetoacetate with purity not less than 98%. Mother liquor is subject to vacuum condensation, cooling crystallization, filtering and recrystallization to obtain secondary eluent product of the intermediate methyl 2-(2,3-dichlorobenzylidine)acetoacetate with purity not less than 98%. Compared with the prior art, the new method helps enhance synthetic yield of the felodipine intermediate, and provide ideal intermediate purity. The method is also applicable to preparing other 4-sustituted-1,4-dihydropyridine antihypertensive drug intermediates with chemical structure and pharmaceutical and clinical actions similar to those of felodipine.

The invention relates to the technical field of drug residue detection and aims at providing a method for detecting residue of 18 illegally-added blood-glucose-reducing and antihypertensive drugs in ahealth product, which has the characteristics of rapidness, accuracy, simplicity and low cost. According to the technical scheme, the method for detecting the residue of the 18 illegally-added blood-glucose-reducing and antihypertensive drugs in the health product comprises the following steps: (1) preparing homemade extract, namely refluxing a mixture of methyl alcohol, ethyl acetate and decyl alcohol polyoxyethylene ether for 30 minutes at the temperature of 60-65 DEG C, and cooling for later use; (2) taking health product tablets, capsules or granules, breaking, accurately weighing 3-10g of sample, putting into a centrifugal tube provided with a plug, then adding 20-60mL of homemade extract, mixing, carrying out ultrasonic extraction for 2-10 minutes, carrying out centrifugal separation, then taking 1mL of supernatant, carrying out blow drying with nitrogen, and redissolving with 1mL of 50% acetonitrile aqueous solution; and (3) filtering the redissolved solution by virtue of a 0.22 microns microporous membrane, and carrying out HPLC-MS / MS (high performance liquid chromatography+mass spectroscopy+secondary mass spectroscopy detection) determination on filtrate.

Methods and therapeutic combinations are provided for lowering blood pressure in a subject exhibiting resistance to a baseline antihypertensive therapy with one or more drugs, or a subject having diabetes and / or chronic kidney disease. A method of the invention comprises administering, in some embodiments adjunctively with a modified baseline therapy, a compound of formula (I) as defined herein. A therapeutic combination of the invention comprises a compound of formula (I); 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; wherein the at least one diuretic and / or the at least one antihypertensive drug are present at substantially less than a full dose.

Compounds of the formulaare disclosed, wherein R1, represents secondary alkyl; aralkyl; cycloalkyl; heteroaryl substituted alkyl; norbornyl; and substituted secondary alkyl, aralkyl, cycloalkyl, heteroaryl substituted alkyl, norbornyl; and para-substituted phenyl groups; and R2 and R3 are hydrogen or pharmacologically acceptable acyl groups. The compounds of the invention are useful as cardiovascular vasodilator or anti-hypertensive agents. The therapeutically useful compounds of the invention as well as similar 5-N and N-6 substituted adenosine 5-uronamides are prepared, in accordance with a novel process, from isopropylidene (or otherwise suitably blocked) inosine-5'-uronic acid. Isopropylideneinosine-5'-uronic acid is reacted with a suitable inorganic acid halide, such as thionyl chloride, to yield 6-halogeno-9-[2',3'-O-isopropylidene-beta-D-ribofuranosyl-5-uronic acid halide]-9H-purine. This intermediate is reacted with an amine of the general formula R4R5NH to give a 6-halogeno substituted, substituted uronic acid amide of the formulawherein X is halogen. Reaction of the latter intermediate with an amine of the formula R1-NH2, and removal of the isopropylidene (or other) blocking groups yields the compounds of the invention.

The invention discloses a preparation method of combination of wild chrysanthemum effective parts and combination of wild chrysanthemum effective parts obtained by the said method. The preparation method comprises: taking 100 portions of wild chrysanthemum and performing supercritical fluid extraction of 1-100 portions of wild chrysanthemum and collecting the extract to obtain effective part 1; mixing the remained wild chrysanthemum, or dregs mixture after supercritical fluid extraction with water to decoct and then concentrating the decoction liquid and adding 90-95% ethanol(volumetric ratio) into the concentrated decoction liquid, standing and depositing, leaching the supernatant, concentrating the supernatant to be clear paste, adding adjuvant into the clear paste, drying, or directly drying the clear paste, thereby obtaining effective part 2; mixing the effective part 1 with the effective part 2. The invention also discloses a pharmaceutical preparation obtained by the combination of the wild chrysanthemum effective parts and use thereof in preparing antihypertensive drug. The combination of the wild chrysanthemum effective parts has overall drug-efficacy parts and gradual and long antihypertensive effect and good blood-pressure stabilization effect. The preparation method has features of quick speed, high extraction ratio, high product purity, simple flow, low energy consumption and no residual organic solvent.

The invention relates to a metal palladium catalyst, and a preparation method and an application thereof. The catalyst is polymer immobilized metal palladium containing nitrogen and phosphine, wherein the mass load capacity (measured through ICP) of metal palladium in a polymer is 0.2-2%; and micro-molecules containing nitrogen and phosphine undergo carbon-phosphine and carbon-nitrogen coupling under the action of palladium to generate the metal palladium coated macromolecular polymer catalyst. The activity and the stability of the palladium catalyst are improved under the combined action of immobilized phosphine-containing ligand and polyaniline. The catalyst can catalyze a Suzuki reaction in an alcohol and water mixed solution in an ultrahigh efficiency manner under an extremely low dosage; and the catalyst is easy to recover, is convenient to apply, can be used in amplification experiments for synthesizing sartanbipheny(2-cyan-4'-methylbiphenyl) and 4-chloro-2'-nitrobiphenyl (drug intermediates for synthesizing boscalid) drug intermediates of novel losartan antihypertensive drugs, and has very large application values.

Methods of using a genetic polymorphic variation in the human beta-1 adrenergic receptor gene as a drug response marker are presented. Determining the presence or absence of the A145G genetic variation in the human beta-1 adrenergic receptor gene is useful in predicting an individual's relative response to different antihypertensive drugs; optimizing antihypertensive treatment for an individual; selecting candidate human subjects for participation in clinical trials involving antihypertensive drugs; and, predicting the relative responses among a plurality of individuals to an antihypertensive drug.

The invention discloses a gracilaria lemaneiformis antihypertensive peptide and application thereof to preparing antihypertensive drugs and healthcare products. Gracilaria lemaneiformis antihypertensive peptide extract is obtained through enzymolysis and then further separated and purified to obtain the gracilaria lemaneiformis antihypertensive peptide with a specific sequence; the amino acid sequence of the gracilaria lemaneiformis antihypertensive peptide is Phe Gln-Ile-Asn-[Met(O)]-Cys-Ile-Leu-Arg(FQIN[M(O)]CILR), and the molecular weight of the gracilaria lemaneiformis antihypertensive peptide acquired through mass spectrum identification is 1153.43Da. The selected gracilaria lemaneiformis antihypertensive peptide is significant in activity on angiotensin converting enzyme inhibition and can in vitro express temperature, pH, gestro-intestinal digestion and angiotensin converting enzyme (ACE) degradation stability. enzyme kinetics survey shows that the gracilaria lemaneiformis antihypertensive peptide is an ACE non-competitive inhibitor and can achieve good antihypertensive effects in vitro and in vivo of spontaneously hypertensive rats (SHRs), thereby being applicable to hypertensive treatment-related healthcare products and drugs.

The invention relates to a method for preparing drugs for treating hypertension employing dendrobium officinale and semen raphani as main materials. The method comprises the steps of grinding fried semen raphani, radix ophiopogonis and a white peony root into powder, mixing evenly, heating the mixture, extracting and concentrating to obtain a water extract concentrate; grinding dendrobium officinale into powder, adding the powder to the water extract concentrate; and adding auxiliary materials for molding; or grinding the four medicinal materials into powder and then carrying out alcohol extraction: adding 5fold 75% ethanol for extracting at 60 DEG C for 24h, carrying out extraction twice in all and recovering the ethanol; after alcohol extraction, carrying out water extracting treatment on residues, concentrating and merging the alcohol extraction solution and the water extraction solution; and adding the auxiliary materials for molding. The prepared drugs all are suitable for treatment of patients with hypertension, caused by a yin-deficiency syndrome or a yin-deficiency and yang-predominance syndrome, accompanied by restlessness and insomnia, or all are combined with antihypertensive drugs of the Western medicine for treatment to reduce the dosage of the antihypertensive drugs of the Western medicine. Meanwhile, the drugs are suitable for health use of patients with mild hypertension or normal hypertension.

The invention discloses certain antihypertensive peptides and antihypertensive proteins and applications thereof. Amino acid sequences of the antihypertensive peptides are TTW, VHW and KAKW respectively; amino acid sequences of the antihypertensive proteins contain one or more of TTW, VHW and KAKW. The antihypertensive peptides and the antihypertensive proteins can restrain the activities of angiotensin converting enzymes so as to play roles in lowering blood pressure, and can be prepared into various antihypertensive drugs or healthcare products.