Disclosed in the present invention is a preparation method for a low-viscosity sertaconazole nitrate cream, comprising the following steps: (1) preparing an oil phase: mixing light liquid paraffin, glyceryl monostearate, glyceryl distearate, octadecanol, and ethylparaben according to prescription dosages, heating, and performing heat preservation for later use; (2) preparing a water phase: mixing polysorbate 80 of a prescription dosage, and purified water of a prescription dosage, and part of propylene glycol of a prescription dosage, heating, and performing heat preservation for later use; (3) preparing a main drug dispersion liquid: dispersing sertaconazole nitrate by using the remaining propylene glycol and grinding to obtain the main drug dispersion liquid; and (4) emulsifying: mixing the oil phase prepared in the step (1), the water phase prepared in the step (2), and the main drug dispersion liquid prepared in the step (3), and stirring and emulsifying to obtain the low-viscosity sertaconazole nitrate cream. Tests show that the viscosity of the sertaconazole nitrate cream provided by the present invention is less than 20,000 mPa.s, and compared with a known prescription, the viscosity is obviously reduced.
A61K 31/4178 - 1,3-Diazoles non condensés et contenant d'autres hétérocycles, p. ex. pilocarpine, nitrofurantoïne
A61K 47/14 - Esters d’acides carboxyliques, p. ex. acides gras monoglycérides, triglycérides à chaine moyenne, parabènes ou esters d’acide gras de PEG
A61K 47/06 - Composés organiques, p. ex. hydrocarbures naturels ou synthétiques, polyoléfines, huile minérale, gelée de pétrole ou ozocérite
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
A purification method for sertaconazole nitrate, which is used for preparing a sertaconazole nitrate crystal form with a melting point of 156-161°C. The purification method comprises: (1) mixing a crude product of sertaconazole nitrate with 95% ethanol, then raising the temperature to reflux; (2) adding activated carbon, then continuing to reflux; (3) after reflux finishes, filtering to remove the activated carbon so as to obtain a filtrate; (4) adding water dropwise to the obtained filtrate while stirring to precipitate a crystal; and (5) after dropwise addition is complete, filtering the crystal and then drying. After using 95% ethanol to heat and dissolve the crude product of sertaconazole nitrate, water is added dropwise to dissolve and crystallize same; it was unexpectedly found that a crystal form of sertaconazole nitrate with a melting point of 156-161°C can be obtained. The melting point of the crystal form meets requirements of the European Pharmacopoeia or the British Pharmacopoeia, which provides technical support for exporting the drug to these countries and regions.
C07D 409/12 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes de soufre comme uniques hétéro-atomes du cycle contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
3.
PREPARATION METHOD FOR SERTACONAZOLE NITRATE CRYSTAL FORM
A preparation method for a sertaconazole nitrate crystal form, which is used for preparing a sertaconazole nitrate crystal form having a melting point of 156-161°C and which comprises the following steps: A. mixing a crude product of sertaconazole nitrate with an ethanol aqueous solution having a concentration of 45-55 mass%, then raising the temperature to reflux; B. adding activated carbon and continuing to reflux; C. after the activated carbon is removed by filtering, cooling down and letting stand for crystallization; and D. filtering to obtain a crystal, and then drying. A sertaconazole nitrate crystal form having a melting point of 156-161°C can be obtained by using the preparation method provided in the present application, which meets requirements for exporting to countries and regions such as the United Kingdom and the European Union.
C07D 409/12 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes de soufre comme uniques hétéro-atomes du cycle contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
Disclosed in the present invention is a method for synthesizing 3-bromomethyl-7-chlorobenzo[b]thiophene, the method comprising the following steps: adding a substrate of 3-methyl-7-chlorobenzo[b]thiophene into a C6-C8 straight-chain alkane, which acts as a solvent, irradiating same with a bulb, adding an initiator of benzoyl peroxide while stirring, heating same until boiling, adding a brominating agent of N-bromosuccinimide in batches, and after the addition is finished, continuing to stir same for reaction under boiling. In the present invention, the 3-bromomethyl-7-chlorobenzo[b]thiophene is prepared by means of a bromination reaction by taking the C6-C8 straight-chain alkane as a reaction solvent. Compared with carbon tetrachloride, the C6-C8 straight-chain alkane is less toxic and will not destroy the ozone layer of the atmosphere. Furthermore, the use thereof is not limited, and the method is more suitable for industrial production.
C07D 333/54 - Benzo [b] thiophènesBenzo [b] thiophènes hydrogénés avec uniquement des atomes d'hydrogène, des radicaux hydrocarbonés ou des radicaux hydrocarbonés substitués, liés directement aux atomes de carbone de l'hétérocycle
5.
METHOD FOR PREPARING SERTACONAZOLE NITRATE INTERMEDIATE
A method for preparing a sertaconazole nitrate intermediate. Cyclohexane is used as a solvent, and in the presence of benzoyl peroxide, 3-methyl-7-chlorobenzo[b]thiophene reacts with a bromination reagent to generate 3-bromomethyl-7-chlorobenzo[b]thiophene. Compared with carbon tetrachloride, cyclohexane is less toxic and will not react with ozone, damaging the atmosphere.
C07D 333/54 - Benzo [b] thiophènesBenzo [b] thiophènes hydrogénés avec uniquement des atomes d'hydrogène, des radicaux hydrocarbonés ou des radicaux hydrocarbonés substitués, liés directement aux atomes de carbone de l'hétérocycle
6.
METHOD FOR DETECTING SMALL POLAR IMPURITIES IN PAZUFLOXACIN MESYLATE BULK DRUG
Provided is a method for detecting small polar impurities in a pazufloxacin mesylate bulk drug, wherein detection is performed using a high-performance liquid chromatography method; and a mobile phase comprises acetonitrile, a 10% triethylamine mesylate solution, a 1.0 mol/L dipotassium hydrogen phosphate, and water at a volume ratio of 45 : 10 : 7 : 138. The method comprises the following steps: respectively injecting a test sample solution and a control solution into a high-performance liquid chromatograph, and recording a chromatogram until 7 times the retention time of a pazufloxacin mesylate characteristic peak. According to the method, a pazufloxacin mesylate bulk drug is subjected to detection by using HPLC, and small polar impurities with a retention time longer than that of a pazufloxacin mesylate characteristic peak can be effectively detected within 7 times the retention time of pazufloxacin mesylate by means of a mobile phase with a specific ratio. Therefore, the quality control of a pazufloxacin mesylate bulk drug can be more accurately and scientifically realized.
Disclosed in the present invention is an ofloxacin vaginal suppository. The ofloxacin vaginal suppository is prepared by means of a hot melting method and according to a prescription, and has a melting time limit of less than 30 minutes; and the prescription consists of the following components in parts by weight: 10 parts of an ofloxacin bulk drug, 60-70 parts of polyethylene glycol 4000, 30-32 parts of polyethylene glycol 400, 16-20 parts of glycerol and 2-2.5 parts of polysorbate 80. For the ofloxacin vaginal suppository provided in the present invention, by means of using a specific matrix prescription, the melting time limit of the suppository is within 30 minutes, and preferably may be within 18 minutes. Compared with the 60-minute melting time limit required for the water-soluble matrix specified in the Chinese Pharmacopoeia, the time limit is shortened by 2 times or more. Thus, the ofloxacin vaginal suppository provided in the present invention can exert the therapeutic effect thereof more quickly.
A61K 9/02 - SuppositoiresBougiesExcipients pour suppositoires ou bougies
A61K 31/5383 - 1,4-Oxazines, p. ex. morpholine condensées en ortho ou en péri avec des systèmes hétérocycliques
A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
The present application provides a method for detecting impurities in sertaconazole nitrate, comprising the following steps: S1, preparing a test sample solution: weighing sertaconazole nitrate, adding methanol to dissolve same, and diluting to obtain a test sample solution in which the concentration of sertaconazole nitrate is 15-25 mg/mL; and S2, detecting impurities in the sample by means of thin layer chromatography: using a thin layer chromatography test, suctioning 15-30 μL of the test sample solution, applying same on a silica gel GF254 thin layer plate, placing same in an environment at a temperature of 22-33°C and relative humidity of 75-90% for development by using a potassium tartrate-n-hexane-methanol-concentrated ammonia solution as a developer, drying for 12-20 min after development, spraying an n-butanol solution of ninhydrin having a mass fraction of 0.1-1%, and placing same under an ultraviolet lamp for inspection, to determine impurities. In the present application, the thin layer chromatography analysis and detection method is used, the separation of main spots is obvious during thin layer chromatography, impurity spots are very easy to diffuse, regular stripes are formed, and impurities existing in sertaconazole nitrate can be effectively and accurately detected.
A content measurement method for a clindamycin phosphate vaginal tablet. The method allows for measurement using high performance liquid chromatography, and comprises: selecting components of a mobile phase, using an appropriate ratio, and setting elution conditions by means of gradient elution, such that the clindamycin phosphate content in the clindamycin phosphate vaginal tablet can be quickly and accurately measured.
A clindamycin phosphate vaginal tablet, which is prepared from the following raw materials in parts by weight: 125 parts of clindamycin phosphate, 140-160 parts of lactose, 90-95 parts of microcrystalline cellulose, 7-8 parts of sodium starch glycolate, 1.5-2.0 parts of magnesium stearate, and 10-20 parts of a 1.8-2.2 wt% hypromellose aqueous solution. Further disclosed is a preparation method for a clindamycin phosphate vaginal tablet.
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
A61K 47/36 - PolysaccharidesLeurs dérivés, p. ex. gommes, amidon, alginate, dextrine, acide hyaluronique, chitosane, inuline, agar-agar ou pectine
A61K 47/12 - Acides carboxyliquesLeurs sels ou anhydrides
A61K 31/7056 - Composés ayant des radicaux saccharide et des hétérocycles ayant l'azote comme hétéro-atome d'un cycle, p. ex. nucléosides, nucléotides contenant des cycles à cinq chaînons avec l'azote comme hétéro-atome d'un cycle
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