40 results about "Gemfibrozil" patented technology

Provided are methods of increasing metabolic maturation of an immature hepatocyte, by contacting an immature hepatocyte which expresses alpha-fetoprotein (AFP) and albumin with an effective amount of a fatty acid or a small molecule selected from the group consisting of: an amphipathic carboxylic acid, Thiazolidinedione (TZD), WY-14643 (Pirinixic Acid), GW409544, GW6471, Leukotriene B4, GW 7647, Perfluorooctanesulfonic Acid, Perfluorooctanoic Acid, CP-775146, CP-865520, UNII-999KY5ZIGB, and Gemfibrozil. Also provided are isolated hepatocytes and uses thereof.

The present invention is process of preparing gemfibrozil medicine powder, and belongs to the field of insoluble medicine micronizing technology. Through dissolving gemfibrozil medicine in water solution of sodium hydroxide, neutralizing and replacing with added water solution of hydrochloric acid containing surfactant to obtain suspension of gemfibrozil medicine, filtering, washing and drying, spheroid gemfibrozil medicine powder in submicron size is produced. The process is simple, low in cost and easy in industrial application, and the obtained gemfibrozil medicine powder has regular shape, narrow size distribution and high dispersivity. The present invention lays foundation for the industrial production and the new preparation form development of gemfibrozil medicine.

The invention relates to a choline salt of a hypolipidemic drug and a preparation method and a pharmaceutical use thereof. The invention provides a choline salt of a class of hypolipidemic drugs, and the hypolipidemic drugs include but not limited to clofibrate, libet, fenofibrate, ciprofibrate, gemfibrozil, acipimox, niacin, lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin, pitavastatin, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and other unsaturated fatty acids. The choline salt of the hypolipidemic drug can be used for treating hyperlipidemia and other cardiovascular diseases. The invention also provides a preparation method of the choline salt of the hypolipidemic drug.

The invention relates to a Gemfibrozil crystal form II and a preparation method thereof. Gemfibrozil is dissolved through with certain amount of toluene and is crystallized, filtered and dried to form a new Gemfibrozil crystal form. The X-ray diffraction pattern of the crystal form shows character diffraction peaks at 2theta(degree,+ / -0.2)5.85 degrees, 8.06 degrees, 8.51 degrees, 11.49 degrees, 11.79 degrees, 12.66 degrees, 12.86 degrees, 13.43 degrees, 13.78 degrees, 16.24 degrees, 16.59 degrees, 17.12 degrees, 19.00 degrees, 20.86 degrees, 21.88 degrees, 23.23 degrees, and 24.14 degrees and has the advantages that the crystal form has good stability and no static electricity, is convenient to produce, transport and store, and can meet all requirements as a preparation material and the like. The Gemfibrozil crystal form II can be kept unchanged for two years under the condition of normal temperature, does not reduce the content of medicine and fully meets the requirement of the medicine.

The invention provides a gemfibrozil hapten and an artificial antigen. Molecular structural formulas of the gemfibrozil hapten and the artificial antigen are correspondingly as shown in the description. The invention further discloses preparation methods for the gemfibrozil hapten, the artificial antigen and an antibody prepared from the gemfibrozil hapten and the artificial antigen and purposes of the gemfibrozil hapten and the antibody. The antibody which is finally prepared by the preparation method provided by the invention has the advantages of high detection sensitivity and high specificity.

The invention discloses a method for screening acid drugs in liquid medicines by coupling solid phase extraction-liquid chromatography. The method comprises the following steps: preparing a standard sample, and preparing the single and mixed standard sample of meloxicam, ketoprofen, indomethacin, diclofenac and gemfibrozil; preprocessing a test sample, adding anhydrous calcium chloride and acetonitrile / phosphoric acid solution into the sample for extraction, and carrying out separation to obtain supernate; carrying out solid phase extraction column purification, processing the supernate by the solid phase extraction column of aluminium oxide and kieselguhr mixed filler to obtain the test sample; carrying out efficient liquid phase chromatography detection, and detecting the single and mixed standard sample and a test sample. The method is suitable for emulsion samples, various ingredients are simultaneously detected, and the method has the advantages of high degree of separation, high appearance time and high recovery rate.

The invention discloses a high-purity low-chroma gemfibrozil preparation method. The method comprises 1, preparing a gemfibrozil isobutyl ester crude product and can also comprises 2, adding an alkali liquor II in the gemfibrozil isobutyl ester crude product until the system pH is in a range of 10.0-12 and carrying out reduced pressure rectification to obtain gemfibrozil isobutyl ester, 3, carrying out reflux alkaline hydrolysis on the gemfibrozil isobutyl ester and carrying out acid adjustment to obtain a gemfibrozil crude product, and 4, refining the gemfibrozil crude product through adding an alcohol-water solution into the gemfibrozil crude product, carrying out heating reflux, carrying out heat preservation for 0.5-1h, carrying out cooling to a temperature of 0-5 DEG C, carrying out thermal insulation stirring for 1.5-2.5h, carrying out filtration to obtain filter cake and drying the filter cake to obtain high-purity low-chroma gemfibrozil.

The invention discloses a Gemfibrozil composite method. 2, 5-dimethyl phenol and 5-halogenate-2,2-dimethyl valerate are subjected to condensation polymerization in the presence of alkali under the action of phase transfer catalyst; alkali is added for hydrolysis reaction to obtain the product of Gemfibrozil. The invention simultaneously carries out condensation and hydrolysis in the same kettle and has simple operation; in the technical process, no organic solvent is added, so that the invention has small pollution to environment and low cost.

The invention relates to Gemfibrozil polymorphism and a preparation method thereof. The preparation method comprises the following steps: the Gemfibrozil is dissolved in a certain amount of a solvent with alcohol, ketone, ester and ether, and crystallized, filtered and dried to form a Gemfibrozil crystal form I, and an X-ray diffraction pattern of the crystal form I shows characteristic diffraction peaks at 2 theta (degrees, + / -0.2) 6.32 degrees, 11.52 degrees, 11.89 degrees, 12.69 degrees, 13.45 degrees, 13.83 degrees, 15.02 degrees, 16.65 degrees, 17.14 degrees, 17.39 degrees, 17.99 degrees, 17.27 degrees, 18.78 degrees, 19.13 degrees, 19.79 degrees, 21.95 degrees, 23.27 degrees, 24.23 degrees, 25.12 degrees, 26.92 degrees and 34.94 degrees. The Gemfibrozil polymorphism has the advantages of simple process, good stability of the crystal forms, and convenient production, transport and storage, being capable of being stored at normal temperature for more than 2 years without change, no decrease of drug content and completely meeting drug requirements.

The invention provides a preparation method of gemfibrozil. The preparation method is characterized by comprising the following steps: carrying out a salt-forming reaction between starting materials, namely 2,5-dimethylphenol and diethyl malonate, under the action of alkali; carrying out a nucleophilic substitution between the reaction product and 1,3-dibromopropane; hydrolyzing in an aqueous solution of alkali and carrying out a decarboxylation reaction to generate 5-(2,5-dimethylphenoxyl)pentanoic acid; and carrying out a methylation reaction between the reaction product and dimethyl sulphate (V) under the action of alkali so as to generate gemfibrozil. The preparation method has simple processing steps, reaction conditions are not harsh, synthesis route has no special requirements on equipment, investment cost of production equipment is greatly reduced, and it is easy to realize industrial production. The raw materials are easily available in the market, and cost is relatively low. Thus, industrial cost reduction is realized.

The invention discloses a high-purity low-chroma gemfibrozil preparation method. The method comprises 1, preparing a gemfibrozil isobutyl ester crude product and can also comprises 2, adding an alkali liquor II in the gemfibrozil isobutyl ester crude product until the system pH is in a range of 10.0-12 and carrying out reduced pressure rectification to obtain gemfibrozil isobutyl ester, 3, carrying out reflux alkaline hydrolysis on the gemfibrozil isobutyl ester and carrying out acid adjustment to obtain a gemfibrozil crude product, and 4, refining the gemfibrozil crude product through adding an alcohol-water solution into the gemfibrozil crude product, carrying out heating reflux, carrying out heat preservation for 0.5-1h, carrying out cooling to a temperature of 0-5 DEG C, carrying out thermal insulation stirring for 1.5-2.5h, carrying out filtration to obtain filter cake and drying the filter cake to obtain high-purity low-chroma gemfibrozil.

The invention relates to a gemfibrozil-xenopus glucagon-like peptide-1 derivative. The gemfibrozil modified XenGLP-1 (xenopus glucagon-like peptide-1) derivative is prepared by structurally modifyinga side chain of XenGLP-1, and introducing a micromolecular gemfibrozil derivative with a high serum protein binding rate and a high lipid-lowering effect. The invention provides an application of thederivative in preparation of a medicine and a composition containing the derivative. The XenGLP-1 derivative has high lipid-lowering activity which other GLP-1 medicines do not have, and at the same time, also has high stability, high blood sugar reduction activity and long blood sugar reduction action time.

Methods of delaying the onset or treating the progression of Type 2 diabetes in subjects that have increased blood levels of an inflammation marker protein. In one embodiment, the method includes administering an inhibitor OF α1-antitrypsin (AT) to the subject, and optionally co-administering an anti-diabetic medicament or anti-inflammatory agent to the subject. Treatment regimens provided by the invention may be used to delay the onset of or to control Type 2 diabetes. The invention provides for the use of an inhibitor of α1-antitrypsin, such as gemfibrozil (GF), for the manufacture of a medicament for the uses described herein. The invention further provides combinations of agents for treating or delaying the progression or onset of diabetes, comprising an inhibitor of α1-antitrypsin and an anti-inflammatory agent and / or an anti-diabetic medicament.

The present invention relates to pharmaceutical compositions comprising a fibrate (e.g. ciprofibrate, gemfibrozil, benzafibrate, and fenofibrate) and a polychitosamine (e.g. chitosan) having molecular weights of less than 650 Kda and degrees of deacetylation of from 70% to 100%. Uses of said compositions for the treatment of hyperlipidemia and associated conditions (e.g. hypercholesterolemia, atherosclerosis, coronary heart disease and cardiovascular disease) or as functional foods are also disclosed.

This invention relates to an absorbent including trimethylsilylated mesoporous silica SBA-15, and more particularly to an absorbent including trimethylsilylated mesoporous silica SBA-15, which can effectively remove 90% or more of the seven pharmaceuticals of carbamazepine, diclofenac, estrone, gemfibrozil, ibuprofen, ketoprofen, and trimethoprim which are present in high concentration.

The invention relates to gemfibrozil eutectic crystals prepared by a solvent-assisted ball milling method, belonging to the field of drug development. The method comprises the following steps: putting gemfibrozil and a corresponding eutectic crystal synthon in a mole ratio of 1:0.5-1:2 into a ball mill, adding 0.1-0.3 mL of different secondary solvents and a stainless steel milling ball with the diameter of 12mm, and carrying out ball milling under the vibration condition of 1300-1800 r / min for 20-30 minutes; and after finishing the ball milling, naturally drying the test sample in the air, thereby obtaining the gemfibrozil eutectic crystals. The structure of the gemfibrozil eutectic crystals is characterized by powder X-ray diffraction (PXRD), infrared spectrometry (IR), 1H nuclear magnetic resonance (1H NMR), differential scanning calorimetry (DSC), thermogravimetry (TG) and other means. The in-vitro dissolution rate experiment indicates that the solubility of the gemfibrozil eutectic crystals is obviously enhanced by 10.7 times and 132.48 times as compared with the original drug.

The invention relates to a gemfibrozil oxime derivative and its use as an FXR antagonist. The invention provides a compound shown in the formula (I) or its pharmaceutically acceptable salt and a preparation method thereof. In the formula, R1 represents hydrogen, hydroxyl, methyl, methoxyl, halogen, or a nitro group, R2 represents hydrogen, hydroxyl, methyl, trifluoromethyl or halogen, R3 represents hydrogen, hydroxyl, methyl, methoxyl, halogen or a nitro group, R4 represents hydrogen or methyl, R5 represents hydrogen or methyl, R6 represents hydrogen or methyl, and X represents NH, O or S. In addition, the compound shown in the formula (I) or its pharmaceutically acceptable salt has pharmacological effects of reducing blood fat and is a FXR antagonist.

The present invention is process of preparing gemfibrozil medicine powder, and belongs to the field of insoluble medicine micronizing technology. Through dissolving gemfibrozil medicine in water solution of sodium hydroxide, neutralizing and replacing with added water solution of hydrochloric acid containing surfactant to obtain suspension of gemfibrozil medicine, filtering, washing and drying, spheroid gemfibrozil medicine powder in submicron size is produced. The process is simple, low in cost and easy in industrial application, and the obtained gemfibrozil medicine powder has regular shape, narrow size distribution and high dispersivity. The present invention lays foundation for the industrial production and the new preparation form development of gemfibrozil medicine.

The invention provides gemfibrozil for use in adjusting the effect of a CYP2C8 and / or OATP substrate drug, wherein gemfibrozil is administered in an amount of less than 1200 mg / day. The invention also provided a pharmaceutical composition comprising gemfibrozil providing a significant improvement to the plasma profiles of a CYP2C8 and / or OATP substrate drug in a mammal.

The new use of gemfibrozil relates to the field of glioma treatment. Application of the gemfibrozil of the present invention in improving the therapeutic effect of temozolomide on glioma. The application of the gemfibrozil of the present invention in enhancing the killing effect of temozolomide on glioma cells. A pharmaceutical composition for preventing and / or treating glioma of the present invention, the pharmaceutical composition contains gemfibrozil and temozolomide. It has been proved by experiments that gemfibrozil can improve the therapeutic effect of temozolomide on glioma, has synergistic effect of temozolomide on killing glioma cells, and can enhance the killing effect of temozolomide on glioma cells. The preparation of gemfibrozil and temozolomide into a drug for preventing and / or treating glioma can improve the therapeutic effect of temozolomide on glioma. The application of gemfibrozil in the preparation of drugs for the prevention and / or treatment of glioma opens up a new application of gemfibrozil, and provides a new therapy and treatment plan for the treatment of the chronic disease of glioma.

The invention discloses a medicinal composition of gemfibrozil and medicinal application of the medicinal composition. The medicinal composition of gemfibrozil, which is disclosed by the invention, comprises gemfibrozil and a natural product component (I) of a novel structure. When being used independently, gemfibrozil and the compound (I) have protection functions on acute gastric ulcer damage; when being used cooperatively, the protection functions of gemfibrozil and the compound (I) on acute gastric ulcer damage are further enhanced, so that a medicine for treating acute gastric ulcer damage can be developed, and compared with the prior art, the medicinal composition has outstanding substantial characteristics and remarkable improvement.

The invention discloses an aryl gemfibrozil derivative hypervalent iodine compound and a preparation method thereof. The structural formula of the aryl gemfibrozil derivative hypervalent iodine compound is formula (I). The aryl gemfibrozil derivative hypervalent iodine compound is an efficient electrophilic reagent. The aryl gemfibrozil derivative hypervalent iodine compound can realize nucleophilic substitution reaction of specific sites on aryl of gemfibrozil molecules, and achieves the purposes of modifying the gemfibrozil drug molecules and expanding the types of the gemfibrozil drug molecules. Meanwhile, the invention provides a preparation method of the compound. The method is direct, simple, efficient and suitable for large-scale preparation of the aryl gemfibrozil derivative hypervalent iodine compound.

The invention relates to a composition capable of comprehensively improving blood lipid and insulin resistance state of a body at the same time, and belongs to the field of pharmacy. The composition comprises pharmaceutically acceptable doses of phenoxyaromatic acid drugs (including fenofibrate, bezafibrate, gemfibrozil, etc.) or pharmaceutically acceptable salts thereof, pharmaceutically acceptable doses of taurine and pharmaceutically acceptable carriers or excipients. The present invention also relates to that the composition is used to comprehensively control blood lipids of patients, including reducing total cholesterol (TC), low-density lipoprotein (LDL) and triglyceride (TG), and increasing high-density lipoprotein (HDL); simultaneously the present invention The composition involved can be used to treat metabolic syndrome, synergistically improve the insulin resistance state of the body, and improve the insulin sensitivity index, and its effect is obviously better than that of a single medicine. The present invention also relates to the application of the composition in the preparation of medicines for the treatment of living bodies with dyslipidemia or metabolic syndrome.

The invention provides application of gemfibrozil and pharmaceutically acceptable salt, ester or stereoisomer thereof in preparation of medicines for treating and / or preventing neurodegenerative diseases. The neurodegenerative disease are selected from Alzheimer's disease, Parkinson's disease, Huntington's disease or amyotrophic lateral sclerosis. The invention also provides a pharmaceutical composition for treating and / or preventing the neurodegenerative diseases, wherein the pharmaceutical composition comprises the gemfibrozil, and the pharmaceutically acceptable salt, ester or stereoisomerthereof; and preferably, the pharmaceutical composition further comprises one or more pharmaceutical carriers. The invention also provides application of the pharmaceutical composition containing thegemfibrozil and the pharmaceutically acceptable salt, ester or stereoisomer thereof in preparation of medicines for treating and / or preventing the neurodegenerative diseases.

The invention provides a gemfibrozil pharmaceutical composition and a preparation method thereof. The pharmaceutical composition is characterized in that the prescription of the pharmaceutical composition consists of the following components in percentage by weight: 8-69% of gemfibrozil and 31-92% of pharmaceutical adjuvants. The preparation (gemfibrozil pharmaceutical composition) is obtained through the prescription of reasonable compatibility by mixing raw materials and adjuvant materials so as to obtain a soft material, drying, straightening granules and totally blending. The preparation method is simple and easy to operate; production demands can be satisfied by conventional equipment; the obtained gemfibrozil pharmaceutical composition is good in dissolving and release; and the gemfibrozil pharmaceutical composition has a market prospect.

The invention relates to a gemfibrozil oxime derivative and its use as an FXR antagonist. The invention provides a compound shown in the formula (I) or its pharmaceutically acceptable salt and a preparation method thereof. In the formula, R1 represents hydrogen, hydroxyl, methyl, methoxyl, halogen, or a nitro group, R2 represents hydrogen, hydroxyl, methyl, trifluoromethyl or halogen, R3 represents hydrogen, hydroxyl, methyl, methoxyl, halogen or a nitro group, R4 represents hydrogen or methyl, R5 represents hydrogen or methyl, R6 represents hydrogen or methyl, and X represents NH, O or S. In addition, the compound shown in the formula (I) or its pharmaceutically acceptable salt has pharmacological effects of reducing blood fat and is a FXR antagonist.

The invention relates to gemfibrozil eutectic crystals prepared by a solvent-assisted ball milling method, belonging to the field of drug development. The method comprises the following steps: putting gemfibrozil and a corresponding eutectic crystal synthon in a mole ratio of 1:0.5-1:2 into a ball mill, adding 0.1-0.3 mL of different secondary solvents and a stainless steel milling ball with the diameter of 12mm, and carrying out ball milling under the vibration condition of 1300-1800 r / min for 20-30 minutes; and after finishing the ball milling, naturally drying the test sample in the air, thereby obtaining the gemfibrozil eutectic crystals. The structure of the gemfibrozil eutectic crystals is characterized by powder X-ray diffraction (PXRD), infrared spectrometry (IR), 1H nuclear magnetic resonance (1H NMR), differential scanning calorimetry (DSC), thermogravimetry (TG) and other means. The in-vitro dissolution rate experiment indicates that the solubility of the gemfibrozil eutectic crystals is obviously enhanced by 10.7 times and 132.48 times as compared with the original drug.

Provided herein are methods for treatment of a neurodegenerative disease, such as Late Infantile Neuronal Ceroid Lipofuscinosis, including administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of an agent comprising a fibrate.

The invention discloses a preparation method of gemfibrozil crystal form I, which comprises the following steps: 1), adding 10 g of gemfibrozil into 20-50 ml of ethanol, stirring until gemfibrozil dissolves; 2), crystallizing, selecting Either of the following methods: method 1, add 20±5ml of water dropwise to the gemfibrozil ethanol solution obtained in step 1), after the dropwise addition, cool down to 10±2°C, stir for 1.5 to 2.5 hours, and filter; method 2 . Add dropwise the gemfibrozil ethanol solution obtained in step 1) into a mixed solvent consisting of 12-15ml of water and 6ml of ethanol. After the dropwise addition, cool down to 10-20°C, stir for 1-2 hours, and filter ; 3), the filter cake obtained by filtering in step 2) was vacuum-dried at 40±5° C. for 7-8 hours to obtain Gefibrozil crystal form I. The preparation of the gemfibrozil crystal form I by the method has a high yield and can significantly reduce the environmental protection pressure of enterprises.

The invention discloses a preparation method of gemfibrozil crystal I, comprising the steps of 1), adding 10 g of gemfibrozil into 20-50 ml of ethanol, and mixing until gemfibrozil dissolves; 2) crystallizing in any one of the manners: I, dropwise adding 20+ / -5 ml of water into the gemfibrozil ethanol solution of step 1), cooling to 10+ / -2 DEG C after dropwise adding, mixing for 1.5-2.5 h, and filtering; II, dropwise adding the gemfibrozil ethanol solution of step 1) to a mixed solvent composed of 12-15 ml of water and 6 ml of ethanol, cooling to 10-20 DEG C after dropwise adding, mixing for 1-2 h, and filtering; 3) drying filter cake, obtained by filtering in step 2), in vacuum at 40+ / -5 DEG C for 7-8 h to obtain gemfibrozil crystal I. The gemfibrozil crystal I prepared via the preparation method has high yield and enables environmental protection burden to be significantly relieved for enterprises.