32 results about "Sarpogrelate" patented technology

Preferred embodiments of the present invention are related to novel therapeutic drug combinations and methods for treating and / or preventing pulmonary arterial hypertension and / or stable angina. More particularly, aspects of the present invention are related to therapeutic combinations comprising a Rho-kinase inhibitor, such as fasudil, and one or more additional compounds selected from the group consisting of prostacyclins, such as iloprost, endothelin receptor antagonists, PDE inhibitors, calcium channel blockers, 5-HT2A antagonists, such as sarpogrelate, selective serotonin reuptake inhibitors, such as fluoxetine, statins, and vascular remodeling modulators, such as Gleevec.

The invention relates to a novel oral enteric preparation which is composed of 0.1-1000mg of Grel drugs, or medically acceptable salts, ester or derivatives, 37.5-325mg of aspirin and at least one medically acceptable load, wherein the Grel drugs, or medically acceptable salts, esters or derivatives are clopidogrel, prasugrel, brilinta, sarpogrelate, ozagrel, anagrelide, pamicogrel, or medically acceptable salts, ester or derivatives, preferably, clopidogrel sulfate. The oral enteric preparation is used for curing acute coronary syndrome (ACS), angor pectoris, stroke, myocardial infarction or cardia cerebrovascular diseases of patients. According to the oral enteric preparation, adverse reactions such as functional gastrointestinal disorders, nausea, vomit, gastritis, concealed hemorrhage, ulcer exacerbation and gastrointestinal bleeding caused by strong stimulus of aspirin to stomach can be avoided.

Provided is an orally administrable preparation of hydrochloride sarpogrelate facilitating the administration by miniaturization. The miniaturized orally administrable preparation of the hydrochloride sarpogrelate has a high content of >=40% of the hydrochloride sarpogrelate per preparation, and exhibits good manufacturability by suppressing tablet trouble. The preparation also has a rapid elution rate from the preparation in the alimentary tract, and exhibits good preservation stability.

The invention relates to the field of medicine, in particular to a medical application of a compound medicine composition of 5-HT2R (5-hydroxytryptamine 2 receptor) antagonist sarpogrelate and a 5-HT synthesis inhibitor, that is, the compound medicine composition can be used for treating dyslipidemia and preventing and treating AS (artherosclerosis). The compound medicine composition has the function of synergic improvement of dyslipidemia and can be used for treating diseases related with dyslipidemia, especially AS.

The invention provides a sarpogrelate intermediate and a preparation method thereof. The sarpogrelate intermediate is a compound shown as formula VI. The preparation method of the intermediate comprises a Grignard reaction of salicylic aldehyde with phenolic groups protected and a Grignard reagent. The method is mild in reaction conditions, low in energy consumption and small in pollutions, and has relatively high conversion rate and low cost of the raw materials. The obtained sarpogrelate hydrochloride has high purity with the detection purity of HPLC higher than 99%. The method is suitable for large-scale production conversion.

The invention relates to the field of medicine, in particular to a compound medicine composition for treating II type diabetes or metabolic syndrome and particularly discloses a compound medicine composition formed by combining 5-hydroxytryptamine 2 receptor antagonist sarpogrelate with a 5-hydroxytryptamine synthesis inhibitor. The compound medicine composition can be used for improving insulin resistance so that II type diabetes or metabolic syndrome can be treated.

The invention provides a preparation method of sarpogrelate hydrochloride. The sarpogrelate hydrochloride is shown as Formula I. The method comprises the following steps of 1) performing the following dehydration reaction on sarpogrelate intermediate shown as formula VI in the presence of an acid dehydrating agent to obtain a compound shown as formula VII; and 2) further preparing the sarpogrelate hydrochloride from the compound shown as the formula VII. The method is mild in reaction conditions, low in energy consumption and small in pollution, and has relatively high conversion rate and low raw material cost. The obtained sarpogrelate hydrochloride has high purity with detection purity of HPLC over 99%, and is suitable for large-scale production conversion.

The invention belongs to the technical field of pharmaceuticals, discloses application of a sarpogrelate containing pharmaceutical composition in treatment of diabetic nephropathy, and specifically discloses the application of a compound pharmaceutical composition taking sarpogrelate and 5-hydroxytryptamine synthesizing inhibitor as pharmaceutical active components in preparation of drugs for treating diabetic nephropathy. The test shows that gene silencing 5-HT synthetase and a 5-HT 2 receptor show good effect on inhibiting in-vitro culture and high glucose-induced oxidative stress of human renal mesangial cell strain, proinflammatory factor and chemotactic factor, and meanwhile, the gene silencing 5-HT synthetase system (Tph1 or AADC) and a 5HT 2 receptor are capable of greatly inhibiting high glucose-inducing effect and performing synergistic effect. With the adoption of the pharmaceutical composition, the diabetic nephropathy caused by high-fat feed feeding and streptozotocin induced diabetic nephropathy can be obviously treated; compared with simple prescription, the compound prescription is high in attenuation, and the lethal amount of mice orally taking the drug is obviouslyhalved.

The invention aims to provide a preparation method of Sarpogrelate intermediate 2-((3-methoxy) phenethyl) phenol (I), which comprises the following steps of: 1) carrying out perkin reaction on 3-methoxyphenylacetic acid (II), salicylic aldehyde (III), organic base and acetic anhydride; 2) further obtaining 2-(3-methoxyphenyl)-3-(2-acetoxy-phenyl) acrylic acid (IV); 3) decarboxylating a compound IV under the existence of quinoline and metal copper to obtain 3-methoxy-2'-acetoxy stilbene (V); 4) hydrolyzing the compound IV to obtain 2-((3-methoxy) styryl) phenol (VI); and 5) carrying out catalytic hydrogenation on the compound IV to obtain a compound I. The technical scheme disclosed by the invention has the characteristics of simplicity in operation, mild reaction condition, no hydroxyl protection or deprotection required, easiness for product purification, short synthetic route, easiness for material obtaining, high yield, low cost and the like and has a wide industrial application prospect.

The invention belongs to the technical field of medicines, and discloses application of medicine compositions with sarpogrelate to treating or preventing fatty livers, liver fibrosis and / or liver injury. As proved from experiments, the application has the advantages that the fatty livers due to high fat and high cholesterol can be obviously reversed by the aid of the medicine compositions, and the liver fibrosis and the liver injury due to combination effects of the high fat, the high cholesterol and streptozotocin irritation can be obviously reversed.

The invention relates to the field of medicine, in particular to a medical application of a compound medicine composition of 5-HT2R (5-hydroxytryptamine 2 receptor) antagonist sarpogrelate and a 5-HT synthesis inhibitor, that is, the compound medicine composition can be used for treating dyslipidemia and preventing and treating AS (artherosclerosis). The compound medicine composition has the function of synergic improvement of dyslipidemia and can be used for treating diseases related with dyslipidemia, especially AS.

The invention discloses a one-pot method for preparing sarpogrelate hydrochloride photodegradation impurities I, II, III and IV. The method comprises the steps as follows: S1, photodegradation: 2-4 mg / mL of a solution is prepared by dissolving sarpogrelate hydrochloride in water, is treated at the high temperature of 80-90 DEG C for 1-2 h and then sequentially irradiated by a 1200,000-lux cold white fluorescent lamp for 4-6 h and a 200 Wh / m<2> ultraviolet fluorescent lamp for 3-5 h, finally, the degraded solution is concentrated and frozen to dryness, and a degraded mixture is obtained; S2, high-speed countercurrent chromatography: the degraded mixture is dissolved with a fixed phase and a mobile phase with the same volume to serve as a sample solution, ethyl acetate-ethanol-water-formic acid (4:1:5:0.025, v / v / v / v) serves as a two-phase solvent system, the upper phase is the fixed phase, the lower phase is the mobile phase, and the impurities I, II, III and IV are prepared through one-time separation under the conditions that the main engine rotational speed is 800 r / min, the flow velocity is 2.0 mL / min and the detection wavelength is 272 nm. The method adopts few steps and has high efficiency.

The invention belongs to the technical field of medicines, and discloses application of medicine compositions with sarpogrelate to treating or preventing fatty livers, liver fibrosis and / or liver injury. As proved from experiments, the application has the advantages that the fatty livers due to high fat and high cholesterol can be obviously reversed by the aid of the medicine compositions, and the liver fibrosis and the liver injury due to combination effects of the high fat, the high cholesterol and streptozotocin irritation can be obviously reversed.

The present invention relates to the use of serotonergic compounds for the treatment of virus-induced thrombocytopenia. More particularly, the invention relates to methods of treating thrombocytopenia by blocking serotonin activity. For example, inhibitors of receptor 5HT2A and / or receptor 5HT1A and / or inhibitors of mast cell degranulation and / or inhibitors of serotonin uptake may be used. Preferably, the thrombocytopenia is induced by dengue or Japanese Encephalitis virus, and the inhibitors are preferably ketanserin, WAY-100135, sarpogrelate, or fluoxetine.

Preferred embodiments of the present invention are related to novel therapeutic drug combinations and methods for treating and / or preventing pulmonary arterial hypertension and / or stable angina. More particularly, aspects of the present invention are related to therapeutic combinations comprising a Rho-kinase inhibitor, such as fasudil, and one or more additional compounds selected from the group consisting of prostacyclins, such as iloprost, endothelin receptor antagonists, PDE inhibitors, calcium channel blockers, 5-HT2A antagonists, such as sarpogrelate, selective serotonin reuptake inhibitors, such as fluoxetine, statins, and vascular remodeling modulators, such as Gleevec.

The invention aims to disclose sarpogrelate hydrochloride prepared by a convenient and environment-friendly method, relates to a solvent, in particular to a solvent which is prepared by free condensation of 2-[2-(3-methoxyphenyl) ethyl] phenol and epoxy chloropropane (2-[2-(3-metoxypherol) ethyl] pherol withepoxychloropropane). Under atmospheric pressure, dimethylamine is used for ring opening ofethylene oxide of the obtained intermediate, and then the intermediate reacts with succinic anhydride to obtain sarpogrelate. The obtained free alkali is treated by using isopropanol IPA.HCl to obtainthe sarpogrelate hydrochloride. Crystals of hydrochloride are formed in acetone, and a pure product is obtained. According to the preparation method, solvent-free reaction is adopted in the first step, atmospheric pressure reaction is adopted in the second step, and thus the preparation method is suitable for industrial production.

The invention discloses a synthetic method of a sarpogrelate intermediate 2-[2-(3-methoxyphenyl)ethyl]phenol and relates to the technical field of organic synthesis. In the method, with m-methoxyl chlorobenzene, which is easy to obtain and is low in cost, as a raw material, the method includes the steps of: 1) performing condensation to the raw material with triethyl phosphite; and 2) performing condensation with o-phenylmethoxyl benzaldehyde (which is prepared from salicylic acid and chlorobenzene), performing hydrogenation to alkylate a double bond, and crystallizing a product with petroleum ether to prepare a white crystal target product. The method simplifies process steps, reduces loss ratio and is 99.5% in product purity. The 2-[2-(3-methoxyphenyl)ethyl]phenol is used for preparing sarpogrelate hydrochloride, wherein single impurity is less than 0.1% in content and the product purity reaches more than 99.8%.

The invention discloses a one-pot method for preparing sarpogrelate hydrochloride photodegradation impurities I, II, III and IV. The method comprises the steps as follows: S1, photodegradation: 2-4 mg / mL of a solution is prepared by dissolving sarpogrelate hydrochloride in water, is treated at the high temperature of 80-90 DEG C for 1-2 h and then sequentially irradiated by a 1200,000-lux cold white fluorescent lamp for 4-6 h and a 200 Wh / m<2> ultraviolet fluorescent lamp for 3-5 h, finally, the degraded solution is concentrated and frozen to dryness, and a degraded mixture is obtained; S2, high-speed countercurrent chromatography: the degraded mixture is dissolved with a fixed phase and a mobile phase with the same volume to serve as a sample solution, ethyl acetate-ethanol-water-formic acid (4:1:5:0.025, v / v / v / v) serves as a two-phase solvent system, the upper phase is the fixed phase, the lower phase is the mobile phase, and the impurities I, II, III and IV are prepared through one-time separation under the conditions that the main engine rotational speed is 800 r / min, the flow velocity is 2.0 mL / min and the detection wavelength is 272 nm. The method adopts few steps and has high efficiency.

The invention discloses the application of a compound pharmaceutical composition in the preparation of medicines for treating acute kidney injury. The compound pharmaceutical composition in the invention uses sarcogrelate and a 5-serotonin synthesis inhibitor as active ingredients, and the 5-serotonin synthesis inhibitor Carbidopa or benserazide. Sagrelate and carbidopa or benserazide can inhibit the synthesis of 5-HT 2 receptors and 5-HT in kidney cells, and have an obvious synergistic effect on the treatment of acute kidney injury, and have a significant effect on the treatment of acute kidney injury. Effect.

One solution of the present invention provides (±)-2-[2-(3-carboxypropionyloxy)-3-dimethylaminopropoxy]-3'-methoxybibenzyl hydrochloride ( (±)‑2‑[2‑(3‑carboxypropionyloxy)‑3‑dimethylaminopropoxy]‑3'‑methoxybibenzylhydrochloride) is a pharmaceutical composition as an active ingredient.

The present invention relates to the use of a serotoninergic receptor antagonist, such as sarpogrelate or compositions thereof, for the treatment and / or prevention of heart damages in mammals.

The invention relates to a medicinal composition for treating atherosclerosis, and application of the medicinal composition. The medicinal composition comprises L-arginine, a platelet aggregation inhibitor and a pharmaceutically acceptable salt or ester thereof, and one or more pharmaceutically acceptable carriers, wherein the platelet aggregation inhibitor comprises aspirin, clopidogrel, sarpogrelate and pharmaceutically acceptable salts or esters thereof. The medicinal composition can be used for preventing and / or treating atherosclerosis, and is capable of reducing morbidity and mortality rates of atherosclerosis.

The present invention relates to a pharmaceutical composition, containing sarpogrelate or a pharmaceutically acceptable salt thereof as an active ingredient, for preventing, alleviating, or treating sensorineural hearing loss. The sarporgrelate according to the present invention protects against hearing loss caused by noise through the suppression of auditory cell apoptosis and the expression increase of antioxidant enzyme in auditory cells, and thus can be advantageously used in the prevention and alleviation of sensorineural hearing loss.

The invention discloses an application of a compound medicine composition taking sarpogrelate and carbidopa as active ingredients in preparation of a medicine for treating interstitial pneumonia, the compound medicine composition can inhibit 5-hydroxytryptamine (5-HT) synthetase and 5-HT2A receptor (5-HT2AR) activity of lung tissue cells (including macrophages), and can inhibit the activity of sarpogrelate and carbidopa. Specifically, the 5-HT2AR antagonist sarpogrelate and the 5-HT synthetic inhibitor carbidopa form a compound within a certain weight ratio range, and the composition has an obvious synergistic effect on treatment of interstitial pneumonia and has an obvious treatment effect.

The present invention relates to a pharmaceutical composition, containing sarpogrelate or a pharmaceutically acceptable salt thereof as an active ingredient, for preventing, alleviating, or treating sensorineural hearing loss. The sarporgrelate according to the present invention protects against hearing loss caused by noise through the suppression of auditory cell apoptosis and the expression increase of antioxidant enzyme in auditory cells, and thus can be advantageously used in the prevention and alleviation of sensorineural hearing loss.

The invention relates to the field of medicine, in particular to a compound medicine composition for treating II type diabetes or metabolic syndrome and particularly discloses a compound medicine composition formed by combining 5-hydroxytryptamine 2 receptor antagonist sarpogrelate with a 5-hydroxytryptamine synthesis inhibitor. The compound medicine composition can be used for improving insulin resistance so that II type diabetes or metabolic syndrome can be treated.

The invention belongs to the field of pharmaceutical preparations and discloses a sarpogrelate hydrochloride sustained release preparation. The sustained release preparation consists of sarpogrelate hydrochloride, a polyvinyl acetate povidone mixture and other auxiliary materials.

The invention provides a preparation method of sarpogrelate hydrochloride. The sarpogrelate hydrochloride is shown as Formula I. The method comprises the following steps of 1) performing the following dehydration reaction on sarpogrelate intermediate shown as formula VI in the presence of an acid dehydrating agent to obtain a compound shown as formula VII; and 2) further preparing the sarpogrelate hydrochloride from the compound shown as the formula VII. The method is mild in reaction conditions, low in energy consumption and small in pollution, and has relatively high conversion rate and low raw material cost. The obtained sarpogrelate hydrochloride has high purity with detection purity of HPLC over 99%, and is suitable for large-scale production conversion.