17 results about "Rocuronium Bromide" patented technology

The invention relates to a deuterated diaryl glycoluril tetramer compound and application thereof. Specifically, the invention discloses a deuterated glycoluril tetramer compound with aryl incorporated at two ends as shown in a formula (1), and a pharmaceutical composition containing the compound. The deuterated compound disclosed by the invention can be used for antagonizing a clinically used non-depolarized muscle relaxant, the antagonistic activity on rocuronium bromide and vecuronium bromide is obviously superior to that of sugammadex sodium under the same dosage, and the antagonistic activity on cisatracurium besilate and rocuronium bromide is obviously superior to that of a non-deuterated control molecule. # imgabs0 #

The invention relates to an industrial preparation method of an intermediate 5alpha-androstane-2-ene-17 ketone, the intermediate is a rocuronium bromide intermediate, and the method comprises the following steps: taking epiandrosterone as a starting material, and reacting with paratoluensulfonyl chloride to obtain a compound I; and carrying out elimination reaction on the compound I in organic alkali or a DBU catalyst to obtain the compound 5 alpha-androstane-2-ene-17 ketone. The method is good in elimination reaction selectivity, high in yield, good in quality, low in cost, mild in reaction condition, short in production period, recyclable in reaction solvent and green and environment-friendly in production process, and a single impurity of the product is less than 0.3%.

According to an embodiment of the present disclosure, the room-temperature stable, unbuffered rocuronium injection formulation for intravenous administration comprises of 1% w / v of rocuronium bromide, a pH adjusting agent comprising hydrochloric acid at a concentration between 125 mMol and 20 mMol for the adjustment of pH between 3.5 to 4.5 and a quantity sufficient of water to make the formulation to 1 mL. The proposed formulation of the present disclosure is stabilized through optimization of pH of the formulation using only hydrochloric acid and / or sodium hydroxide as the pH adjusting agents without use of any buffering agents is suitable for moist heat sterilization. Further, the rocuronium injection formulation of the present disclosure contains lower than 3% of rocuronium related compound C, more preferably less than 2% over the stability period at room temperature conditions.

This invention provides a method for preparing rocuronium bromide injection. By optimizing the conventional moist heat sterilization process, specifically by increasing the initial temperature of the heating process and decreasing the initial temperature of the cooling process, the overall exposure time of the injection to high temperatures is significantly shortened while maintaining the sterilization time at 121°C, thus significantly improving the quality stability of rocuronium bromide injection. Multiple batches of samples from this invention have met the related substance limits for rocuronium bromide injection as specified in the Chinese Pharmacopoeia, after accelerated stability and long-term stability studies.

A method is used to manufacture a prefilled glass syringe containing a sterile pharmaceutical composition of rocuronium bromide. The prefilled syringe containing the sterile pharmaceutical composition of rocuronium bromide can be part of a kit. The sterile pharmaceutical composition of rocuronium bromide can include at least one stabilizer, a buffer system, a tonicity agent, and water. Prefilled syringes containing the sterile pharmaceutical composition of rocuronium bromide can be storage-stable for extended periods of time at room temperature.

According to an embodiment of the present disclosure, the room-temperature stable, unbuffered rocuronium injection formulation for intravenous administration comprises of 1% w / v of rocuronium bromide, a pH adjusting agent comprising hydrochloric acid at a concentration between 12.5 mMol and 20 mMol for the adjustment of pH between 3.5 to 4.5 and a quantity sufficient of water to make the formulation to 1 mL. The proposed formulation of the present disclosure is stabilized through optimization of pH of the formulation using only hydrochloric acid and / or sodium hydroxide as the pH adjusting agents without use of any buffering agents is suitable for moist heat sterilization. Further, the rocuronium injection formulation of the present disclosure contains lower than 3% of rocuronium related compound C, more preferably less than 2% over the stability period at room temperature conditions.

The invention relates to application of two diaryl glycoluril tetramer derivatives. Specifically, the invention discloses two diaryl glycoluril tetramer derivatives as shown in a formula A-1 and a formula A-2 and application of a pharmaceutical composition containing any one of the diaryl glycoluril tetramer derivatives and the pharmaceutical composition containing any one of the diaryl glycoluril tetramer derivatives. The compound can be used for antagonizing clinically used non-depolarized muscle relaxants (such as cis-atracurium besylate and rocuronium bromide), and under the same dosage, the antagonistic activity of the diaryl glycoluril tetramer on rocuronium bromide is obviously superior to that of sugammadex sodium, and the antagonistic activity is far higher than that of neostigmine. # imgabs0 #

The invention relates to the technical field of drug detection and analysis, in particular to a method for rapidly and accurately detecting rocuronium bromide intermediates and impurities, which comprises the following steps: carrying out gradient elution by using octadecylsilane chemically bonded silica as a chromatographic column of a filler, a dipotassium phosphate aqueous solution as a mobile phase A and acetonitrile as a mobile phase B; according to the present invention, with the method, the balance time during the rocuronium bromide intermediate detection can be significantly reduced, the two impurities in the rocuronium bromide synthesis process can be separated and detected, and the verification results show that the method has advantages of good specificity, repeatability meeting the requirement, and high sensitivity.

The present invention discloses a cyclopropylmethyl steroid quaternary ammonium salt compound represented by formula (I) and a preparation method thereof. Such compounds can be used to prepare non-depolarizing short-acting muscle relaxants. Compared with rocuronium bromide widely used clinically at present, the onset and duration of action of this short-acting muscle relaxant are similar, but the drug metabolism is significantly faster, the muscle relaxation time is significantly shortened, and it has better safety, and is expected to greatly reduce the high incidence of postoperative residual muscle relaxation effect that seriously affects the safety of postoperative patients.

The invention relates to the technical field of pharmaceutical preparations, and discloses a rocuronium bromide injection preparation method, which comprises: preparing injection water, a rocuronium bromide raw material, sodium acetate, glacial acetic acid, an osmotic pressure additive, propylene glycol and butylated hydroxytoluene; uniformly mixing the water for injection with sodium acetate, and adding glacial acetic acid to adjust the pH value; adding a rocuronium bromide raw material, propylene glycol and butylated hydroxytoluene into the solution, uniformly mixing, and adding glacial acetic acid to adjust the pH value; adding an osmotic pressure additive into the solution, stirring and dissolving; filtering the solution through a filter membrane, and then filling and sealing; and carrying out hot-pressing sterilization on the filled and sealed solution to obtain a finished product. According to the preparation method of the rocuronium bromide injection, the stability of the prepared rocuronium bromide injection can be guaranteed, impurities generated in the rocuronium bromide injection in the long-term storage process are effectively reduced, the safety and stability of the rocuronium bromide injection are guaranteed, and meanwhile the preparation process is convenient to operate, environmentally friendly, economical and beneficial to commercialized production.

The invention discloses a method for purifying rocuronium bromide. The method comprises the following steps: reacting a rocuronium bromide crude product with alkali metal bromine in dichloromethane, filtering, mixing the filtrate with methyl tert-butyl ether, and separating out a solid. The method can effectively control the chloride ion residues in rocuronium bromide, and has a good application prospect in industrial production of rocuronium bromide.

The invention discloses a deuterated glycoluril tetramer compound with aryl groups incorporated at two ends as shown in a formula (1), and a pharmaceutical composition containing the compound. The deuterated compound can be used for antagonizing a clinically used non-depolarized muscle relaxant, the antagonistic activity on rocuronium bromide and vecuronium bromide is remarkably superior to that of sugammadex sodium under the same dosage, and the antagonistic activity on cisatracurium besilate and rocuronium bromide is remarkably superior to that of a non-deuterated control molecule. # imgabs0 #

The invention discloses a preparation method of a rocuronium bromide key intermediate, and the preparation method comprises the following steps: taking 5alpha-androstane-2-ene-17-ketone as a raw material, and carrying out bromination, nucleophilic substitution and oxidation to obtain 2alpha, 3alpha-epoxy-16beta-(1-pyrrolyl)-5alpha-androstane-17-ketone; the preparation method has the advantages of cheap and easily available raw materials, simple operation, short preparation period, high purity and high yield, and can be used for industrial production of rocuronium bromide.

The invention provides a rocuronium bromide preparation method, which comprises: dissolving a rocuronium bromide crude product in an acetic acid aqueous solution to obtain a crude product solution, drying the crude product solution through a spray dryer, and collecting through a cyclone separator to obtain rocuronium bromide. The method provided by the invention is simple and convenient in operation procedure, the problem that the residual solvent in the prior art exceeds the standard is solved, the impurity content does not exceed the standard, meanwhile, the generation of residue on ignition is avoided without using sodium acetate, and the prepared rocuronium bromide is high in purity and good in stability.

Disclosed are deuterated glycoluril tetramer compounds having aryl groups incorporated at both ends represented by formula (1), pharmaceutical compositions containing the compounds. The deuterated compounds are useful for antagonizing clinically used non-depolarizing muscle relaxants, and have significantly superior antagonistic activity against rocuronium and vecuronium to sugammadex at the same dose, and significantly superior antagonistic activity against cisatracurium and rocuronium to a non-deuterated control molecule.

The invention relates to a sugammadex sodium / tetraphenyl vinyl pyridinium salt inclusion compound as well as a preparation method and application thereof. Comprising the following steps: synthesizing a tetraphenyl vinyl pyridinium derivative, assembling the tetraphenyl vinyl pyridinium derivative and sugammadex sodium in water or a phosphoric acid buffer solution through hydrophobic interaction and electrostatic interaction to form an inclusion compound with a bonding ratio of 2: 1, and performing red shift on fluorescence emission from 555 nm to 600 nm. The preparation method is simple and pollution-free. The clathrate compound has remarkable ratio fluorescence change on nerve blocking agents such as rocuronium bromide, vecuronium bromide and pantocuronium bromide, fluorescence emission is blue-shifted from 600 nm to 555 nm, the clathrate compound is suitable for high-sensitivity detection of positive charge nerve blocking agents, and the sensitivity of the clathrate compound reaches the nanomole level. The supramolecular host-guest clathrate compound provides an efficient way for high-sensitivity detection of a nerve blocking agent.

The present invention relates to an injectable formulation based on Rocuronium bromide and the relative preparation and sterilization process.