30 results about "Hydroxychloroquine sulphate" patented technology

The invention discloses a new use of chloroquine in prevention and control of root-knot nematodes, and belongs to the technical field of the prevention and control of root-knot nematodes. The invention relates to a use of chloroquine in prevention and control of root-knot nematodes and a use of chloroquine in inhibition of infection, development and/or oviposition of root-knot nematodes, wherein the chloroquine is chloroquine phosphate, hydroxychloroquine sulfate or quinine sulfate. The invention also relates to a use of chloroquine in preparation of a root-knot nematode pesticide or a root-knot nematode infection, development and/or oviposition inhibitor, wherein the active component of the root-knot nematode pesticide or the root-knot nematode infection, development and/or oviposition inhibitor is chloroquine phosphate, hydroxychloroquine sulfate or quinine sulfate; and the root-knot nematode pesticide or the root-knot nematode infection, development and/or oviposition inhibitor is an aqueous solution of chloroquine phosphate, hydroxychloroquine sulfate or quinine sulfate. According to the present invention, the prevention and control of root-knot nematodes with the aqueous solution of chloroquine are safe, non-toxic and effective.

Two crystals of (S)-(+)-hydroxychloroquine sulfate. One crystal features diffraction peaks at 12.3 +/- 0.1 degrees, 13.1 +/- 0.1 degrees, 17.9 +/- 0.1 degrees, 22.8 + 0.1 degrees, 23.4 + 0.1 degrees, 25.1 +/- 0.1 degrees, and 26.3 +/- 0.1 degrees as 2theta angles in a powder X-ray diffraction pattern. The other crystal features diffraction peaks at 12.8 +/- 0.1 degrees, 14.5 +/- 0.1 degrees, 16.7 + 0.1 degrees, 17.6 + 0.1 degrees, 20.2 +/- 0.1 degrees, 21.4 +/- 0.1 degrees, 23.8 +/- 0.1 degrees, 25.7 +/- 0.1 degrees, and 26.0 +/- 0.1 degrees as 2theta angles in a powder X-ray diffraction pattern. Also disclosed are methods of preparing crystals of (S)-(+)-hydroxychloroquine sulfate.

The invention discloses a method for analyzing a composition of a hydroxychloroquine sulfate preparation by high performance liquid chromatography. The method comprises the following steps: a. selecting 50mg of hydroxychloroquine sulfate reference substance, and precisely weighing; b, precisely weighing 1.0 ml, 2.0 ml, 3.0 ml, 4.0 ml, 5.0 ml, 6.0 ml and 7.0 ml of the mixed solutions obtained in the step a, and putting the mixed solutions into a 10ml volumetric flask for later use; c, performing chromatographic analysis by using a chromatographic column to obtain a regression equation of a concentration C and a peak area A; and d, removing a proper amount of a mixture obtained in the step a, precisely weighing, adding a diluent to dissolve, and quantitatively diluting to prepare a solutioncontaining 0.5 mg per 1ml to obtain a test solution; and precisely measuring the test solution, adding a mobile phase, diluting to prepare a solution containing 0.05 g per 1ml as a control solution, precisely measuring 0.2 ml of the control solution, injecting the control solution into a liquid chromatograph, and adjusting sensitivity of an instrument for testing. The method for analyzing the composition of the hydroxychloroquine sulfate preparation by the high performance liquid chromatography is simple and convenient to operate, sensitive, high in accuracy, suitable for clinical hydroxychloroquine serum drug concentration monitoring and high in specificity.

The invention discloses a method for detecting hydroxychloroquine sulfate related substances. The method comprises the following step: carrying out separation and detection by adopting reverse liquidchromatography, wherein chromatographic conditions are as follows: a mobile phase is a mixed solvent consisting of a water-soluble organic solvent and a buffer solution; wherein the buffer solution isan ammonium acetate solution or an ammonium formate solution; wherein the pH value of the buffer solution is 9.0 to 10.5. The detection method disclosed by the invention can be used for simultaneously detecting seven impurities recorded in quality standards of hydroxychloroquine sulfate raw materials in European Pharmacopoeia 9.8 versions in hydroxychloroquine sulfate raw materials and preparations, and has the advantages of good separation effect, high sensitivity, no blank interference, low detection cost, high analysis speed and the like.

The invention discloses hydroxychloroquine sulfate and a preparation method thereof, and relates to the technical field of medicinal chemistry. The preparation method comprises the steps of mixing 4, 7-dichloroquinoline with a hydroxychloroquine side chain, carrying out heating condensation in the presence of an organic base catalyst, adding water and liquid, and carrying out cooling crystallization to obtain hydroxychloroquine; and dissolving hydroxychloroquine in an ethyl acetate and ethanol aqueous solution, heating, dissolving and clarifying, dropwise adding concentrated sulfuric acid, cooling, crystallizing, filtering and drying to obtain hydroxychloroquine sulfate. The method has the beneficial effects that a solvent-free reaction is used, and a catalyst is added, so that high pollution is avoided, the reaction process is accelerated, and the operation is simple; and meanwhile, the HPLC purity of the obtained hydroxychloroquine refined product is not less than 96.50%, the maximum single impurity content is less than 0.10%, the yield can reach 85%, the HPLC purity of hydroxychloroquine sulfate is not less than 98.00%, the maximum single impurity content is less than 0.10%, and the yield can reach 90%.

The invention relates to hydroxychloroquine sulfate as well as a crystal form and a preparation method of an enantiomer of hydroxychloroquine sulfate. The invention provides a crystal form A hydroxychloroquine sulfate. An X-ray powder diffraction pattern of the crystal form A hydroxychloroquine sulfate has characteristic peaks at 10.8 degrees, 13.0 degrees, 13.3 degrees, 16.9 degrees, 17.2 degrees, 17.5 degrees, 19.9 degrees, 21.3 degrees, 23.5 degrees, 24.0 degrees and 26.7 degrees +/-0.2 degrees, and does not contain hydroxychloroquine nitrogen oxide; the invention provides a hydroxychloroquine crystal, the X-ray powder diffraction pattern has characteristic peaks at 7.5 degrees, 14.9 degrees, 16.5 degrees, 19.2 degrees, 19.6 degrees, 22.8 degrees, 23.6 degrees and 26.7 degrees+/-0.2 degree; the invention provides an S-hydroxychloroquine sulfate monohydrate, the X-ray powder diffraction pattern has characteristic peaks at 12.2 degrees, 13.0 degrees, 14.9 degrees, 17.8 degrees, 22.7 degrees, 23.3 degrees, 25.0 degrees and 26.2 degrees +/-0.2 degrees; the invention also provides R-hydroxychloroquine sulfate, the X-ray powder diffraction pattern has characteristic peaks at 12.2 degrees, 13.0 degrees, 14.9 degrees, 17.8 degrees, 22.7 degrees, 23.3 degrees, 25.0 degrees and 26.2 degrees +/-0.2 degrees.

The invention discloses a hydroxychloroquine sulfate sustained-release microsphere for articular cavity injection and a preparation method thereof. The preparation method comprises the following steps: dissolving a surfactant in an organic solvent to form an oil phase; adding hydroxychloroquine sulfate and gelatin into water to obtain a water phase; dropwise adding the water phase into the oil phase, stirring and emulsifying to form a W/O type emulsion; transferring the W/O emulsion into an ice bath, and adding a curing agent for cross-linking curing; and then adding isopropanol for dehydration, suction filtration, washing and drying to obtain the hydroxychloroquine sulfate sustained-release microspheres for articular cavity injection. The prepared hydroxychloroquine microspheres can stably and continuously release drugs for more than 48 hours, a sustained-release preparation is obtained, the administration frequency can be reduced, the total dosage can be reduced, the compliance of patients can be improved, and the clinical application potential is good.

The invention discloses a preparation method of hydroxychloroquine sulfate, and belongs to the technical field of medicine synthesis. The method comprises the following steps: (1) mixing 4, 7-dichloroquinoline, an auxiliary agent and phenol, heating, adding a side chain, and reacting to obtain a hydroxychloroquine crude product; (2) purifying the hydroxychloroquine crude product obtained in the step (1) to obtain hydroxychloroquine; and (3) dissolving the hydroxychloroquine obtained in the step (2), and adding sulfuric acid to obtain hydroxychloroquine sulfate. The preparation method can shorten the reaction time, reduce the reaction temperature, reduce the generation of impurities, greatly reduce the production cost and reduce the environmental pollution, and is simple to operate and suitable for industrial production.

The invention relates to a preparation method of hydroxychloroquine, which comprises the following steps: protecting hydroxyl of 5-(N-ethyl-N-ethoxyl)-2-aminopentane through a silanization reagent, removing amino protons from tetrahydrofuran or toluene by using a bis(trimethylsilyl lithium amide) solution to form amino anions, and carrying out a substitution reaction with 4.7 dichloroquinoline to generate hydroxychloroquine. The hydroxychloroquine and sulfuric acid are salified in an alcoholic solution to generate hydroxychloroquine sulfate, and the hydroxychloroquine sulfate preparation method provided by the invention has the characteristics of low toxicity, low pollution, high purity, low reaction temperature, short reaction time, high yield and the like, and is suitable for industrialization.

The invention discloses a preparation method of a hydroxychloroquine sulfate impurity, and belongs to the field of drug synthesis, the preparation method provided by the invention is reasonable in process design, strong in operability, high in yield and capable of realizing mass production. 5-chloro-2-pentanone is taken as a raw material, synthesis of the hydroxychloroquine sulfate impurity is realized through electrophilic reaction, reductive amination, hydrogenation deprotection and nucleophilic substitution reaction, the target impurity prepared by the method provides an important basis for scientific evaluation of quality and safety of hydroxychloroquine sulfate, and the method is suitable for industrial production. The method is of great significance to reasonable medication of hydroxychloroquine sulfate.

The invention discloses a method for detecting mixing uniformity of hydroxychloroquine sulfate particles. The method comprises the following steps of: acquiring a near infrared spectrum of a mixture in a mixing process, wherein the mixture comprises hydroxychloroquine sulfate particles and magnesium stearate; and calculating a standard deviation value of a collected near infrared spectrum peak area by adopting a moving window standard deviation method. The method for detecting the mixing uniformity of the hydroxychloroquine sulfate particles, disclosed by the invention, is relatively high in accuracy and safety coefficient; and when the detection method is applied to industrial production, the mixing uniformity of the hydroxychloroquine sulfate particles can be rapidly and accurately detected, and the end point of the mixing time can be efficiently and conveniently monitored.

The invention relates to a method for detecting the content of hydroxychloroquine nitrogen oxide impurities in hydroxychloroquine sulfate. The method comprises the following steps: performing detecting by using liquid chromatography under the following detection conditions: a chromatographic column is a phenyl chromatographic column, the mobile phase is composed of 0.05 mol/L of potassium dihydrogen phosphate solution and methanol, the 0.05 mol/L of potassium dihydrogen phosphate solution is used as a mobile phase A, and the methanol is used as a mobile phase B, and the volume ratio of the mobile phase A to the mobile phase B is 80: 20. The method has a high degree of separation for hydroxychloroquine nitrogen oxide.

The invention discloses a method for determining organic impurities in hydroxychloroquine sulfate. According to the method, a chromatographic column taking octadecylsilane chemically bonded silica asa filler is adopted, a diode array detector or an ultraviolet detector is used as a detector, the mobile phase is subjected to gradient elution by a mobile phase A (NH3-NH4 < + > buffer solution) anda mobile phase B (ammonia water-acetonitrile mixed solution), the elution procedure (the volume ratio of A to B at different times) is as follows: 0 min (65: 35), 15 min (65: 35), 16 min (35: 65), 30min (35: 65), 30.01 min (65: 35) and 40 min (65: 35). The method is high in specificity and can be used for rapidly detecting the organic impurities in the hydroxychloroquine sulfate.

The invention provides a hydroxychloroquine sulfate pharmaceutical composition and a preparation method thereof. The hydroxychloroquine sulfate pharmaceutical composition comprises the following components in percentage by weight: 60-70% of a pharmaceutical active component, 20-30% of a filler, 2-10% of an adhesive, 2-10% of a disintegrating agent, 0.5-2% of a lubricant and 2-6% of a coating material. The pharmaceutical composition and the preparation method have the advantages that the hygroscopicity is low, the compressibility and the reproducibility are good, the problem of tablet sticking caused by moisture absorption of hydroxychloroquine sulfate particles can be solved, and the production convenience and the stability are greatly improved.

The invention provides a preparation method of hydroxychloroquine sulfate, specifically a preparation method of hydroxychloroquine sulfate. The method comprises the following steps: (1) preparation of hydroxychloroquine: (1.1) in a first solvent, in the presence of KI and an antioxidant, reacting 4, 7-dichloroquinoline (formula I) with an amino side chain as shown in a formula II to obtain a reaction mixture containing hydroxychloroquine (formula III); and (1.2) separating the hydroxychloroquine from the reaction mixture containing the hydroxychloroquine; and (2) preparation of hydroxychloroquine sulfate: (2.1) in a second inert solvent, reacting the hydroxychloroquine obtained in the step (1) with sulfuric acid to form a salt so as to obtain the hydroxychloroquine sulfate (formula IV).

The invention relates to a method for detecting the content of hydroxychloroquine sulphate impurities in hydroxychloroquine sulfate. The method comprises the following steps: performing detecting by using a liquid chromatography under the following detection conditions: a chromatographic column is a phenyl chromatographic column, the mobile phase is composed of 0.05 mol/L of potassium dihydrogen phosphate solution and methanol, the 0.05 mol/L of potassium dihydrogen phosphate solution is used as a mobile phase A, and the methanol is used as a mobile phase B, and the volume ratio of the mobilephase A to the mobile phase B is 80: 20. The method has a high degree of separation for hydroxychloroquine sulphate.

The invention relates to the technical field of drug analysis and detection, and provides a method for detecting the content of hydroxychloroquine sulfate in hydroxychloroquine sulfate tablets, and the method comprises the following steps: preparing a sample analysis solution from the hydroxychloroquine sulfate tablets; and analyzing the sample analysis solution by using a high performance liquid chromatography to determine the content of hydroxychloroquine sulfate in the hydroxychloroquine sulfate tablet. Wherein in the step of liquid chromatography, a used mobile phase is a mixed solvent composed of a buffer solution and an organic solvent, the buffer solution is an ammonium formate solution, the organic solvent is acetonitrile, and the volume ratio range of ammonium formate to acetonitrile in the mixed solvent is (80-87): (13-20). The invention provides a method for efficiently detecting the content of hydroxychloroquine sulfate in hydroxychloroquine sulfate tablets without solvent poison prevention labor protection.