193 results about "Nitrosamine" patented technology

The present invention relates to a stable pharmaceutical composition of therapeutically active agent, wherein the amount of nitrosamine impurity is below the FDA acceptable intake limit for shelf life of the pharmaceutical composition and a process for preparing the same.

The present invention provides a method for removing a nitrosamine with high selectivity and high efficiency.　More specifically, the present invention provides a method for removing a nitrosamine, the method including a step in which a substance to be irradiated, which contains the nitrosamine, is irradiated with light in the presence of an aromatic polyamine and a photocatalyst.

The invention provides a betahistine hydrochloride pharmaceutical preparation and a preparation method thereof. The betahistine hydrochloride pharmaceutical preparation comprises conjugated linoleic acid, betahistine hydrochloride and auxiliary materials. Conjugated linoleic acid and betahistine hydrochloride are combined together for the first time, and conjugated double bonds of conjugated linoleic acid can be specifically combined with nitrite to block the generation of nitrosamine, so that the content of N-nitrosobetahistine can be remarkably reduced. Based on the chemical characteristics of conjugated linoleic acid, conjugated linoleic acid is used as a functional additive, targeted removal of nitrosamine impurities is achieved, and meanwhile the situation that exogenous toxic substances are introduced to affect the drug effect of betahistine hydrochloride is avoided. In the experiment process, it is also accidentally found that after the conjugated linoleic acid is added, the positive effect on cerebrovascular diseases is also achieved.

This invention relates to N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide drug substance substantially free of a nitrosamine impurity, e.g. the nitrosamine impurity N-(3-(6-amino-5-(2(methyl)(nitroso)amino)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide and novel processes of preparation thereof. The invention further relates to pharmaceutical composition comprising N-(3-(6-Amino-5-(2-(N- methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide, wherein the composition is substantially free of a nitrosamine impurity, e.g. the nitrosamine impurity N-(3-(6-amino-5-(2(methyl)(nitroso)amino)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide. Pharmaceutical products containing said drug substance and compositions are also disclosed, as well as methods for preparing said drug substance, pharmaceutical compositions and products.

To provide a sitagliptin preparation in which the production of nitrosamines is suppressed, and to provide a method of storage of a sitagliptin preparation to suppress the production of nitrosamines.SOLUTION: According to an embodiment of the present invention, a sitagliptin preparation is provided, comprising a sitagliptin-containing tablet, and a case or a packing sealing the sitagliptin-containing tablet, wherein the equilibrium relative humidity of the sitagliptin-containing tablet, as converted to 24°C, is 50.3% or less when the sitagliptin preparation is stored for one month under conditions of 25°C and 60% relative humidity.SELECTED DRAWING: Figure 1A

The invention relates to the technical field of medicines, relates to a preparation method and application of a genotoxic impurity standard substance in acarbose, and in particular relates to a preparation method and application of a genotoxic impurity N-nitrosyl acarbose in an acarbose tablet. According to the method, the nitrosamine new structure compound NNA is prepared for the first time, the genotoxic impurity NNA with high purity can be effectively prepared through the method, the blank of an impurity preparation method at present is filled, the preparation process is simple, and a large number of high-purity NAA impurity standard substances can be prepared. The invention provides a UHPLC-Orbitrap-HRMS (Ultra High Performance Liquid Chromatography-Orbitrap-High Resolution Mass Spectrometry) combined technology, so that the quality control of the NNA in the acarbose tablet is effectively realized, the side reaction of medication is reduced, and the medication safety is ensured to a certain extent. Meanwhile, reference is provided for quality evaluation of other starting materials or intermediates capable of generating NNA.

The invention provides a method for quantitatively detecting a nitrosamine impurity in a macassavir raw material medicine and an intermediate TG9, and relates to the technical field of medicine detection, the method comprises the step of detecting the nitrosamine impurity in the macassavir raw material medicine or the intermediate TG9 sample by adopting a high performance liquid chromatography and mass spectrometry combined method, the mobile phase A is a formic acid solution, and the mobile phase B is a formic acid methanol solution; gradients, such as segmented gradients of the raw material medicines, are respectively designed for the intermediate and the raw material medicines through a dynamic gradient elution program, so that TG801, TG901 and TG1001 realize baseline separation; an acidic mobile phase is adopted, formic acid acetonitrile is added into the solution, protonation competition of nitrosamine impurities is inhibited, the ionization efficiency and stability are improved, the sensitivity is high, and the LOQ of the method is 0.033 ng / g. The technical problem that in the prior art, a method for quantitatively detecting three nitrosamine impurities in a macassavir raw material medicine and an intermediate TG9 does not exist is solved.

The invention provides a preparation method of dehydronandrolone acetate, and relates to the technical field of medicine synthesis. The dehydronandrolone acetate is prepared by carrying out oxidation reaction on etherates; wherein the preparation of the etherate comprises the following steps: step 1, carrying out esterification reaction on nandrolone to obtain an ester; and 2, carrying out an etherification reaction on the esterified product obtained in the step 1 to obtain an etherified product. According to the method for preparing the dehydronandrolone acetate, the dehydrogenation reaction can be completed at normal temperature, and compared with the prior art, the energy consumption and the operation complexity are remarkably reduced. The method disclosed by the invention is safe and environment-friendly, is convenient for recycling, reduces the recycling cost, avoids the problem of generating high-risk nitrosamine genotoxic impurities, and meanwhile, the chloranil is used as the dehydrogenating agent, and the reduction product is easy to recycle and reuse, so that the production cost is further reduced, and the generation of wastes is reduced.

The invention relates to methods for the preparation of protein hydrolysates having low concentrations of undesired nitrosamines as well as the thus obtained protein hydrolysates, compositions containing them and uses thereof. The methods comprise the steps of (a) contacting at least one protein with at least one oxidant, preferably a peroxide, at a concentration of 10 to <500 ppm relative to the weight of the at least one protein, at a pH in the range of 2.0 to <7.0; and (b) subjecting the at least one protein of step (a) to a hydrolysis reaction to obtain a protein hydrolysate.

The present invention relates to a stable pharmaceutical formulation comprising linagliptin or pharmaceutically acceptable forms or derivatives thereof and at least one pharmaceutically acceptable excipient is obtained wherein the manufacturing method is direct compression method, wherein the composition is free of any nitrosamine impurity.

The invention provides a UPLC-MS / MS (Ultra Performance Liquid Chromatography-Mass Spectrometry / Mass Spectrometry) detection method for N-nitroso landiolol in a landiolol hydrochloride bulk drug. The method comprises the step of carrying out qualitative detection or quantitative analysis on a potential nitrosamine impurity-N-nitroso landiolol in a landiolol hydrochloride bulk drug by adopting an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS / MS), wherein the structural formula of the N-nitroso landiolol is shown as a formula I in the specification. The detection method disclosed by the invention is high in sensitivity, strong in specificity and good in repeatability, can be used for rapidly and effectively detecting N-nitroso landiolol in the landiolol hydrochloride bulk drug, and has important significance on quality control of the landiolol hydrochloride bulk drug. ; formula I.

The invention belongs to the technical field of barbecue meat product processing, and particularly relates to a method for inhibiting cancerogen content in a fresh meat roasting process, which comprises the following steps: (1) adding liquorice into water, and boiling to obtain a liquorice extracting solution; (2) adding the fresh meat into the licorice root extracting solution, and pickling to obtain the pickled fresh meat; and (3) baking the pickled fresh meat. Polyphenols substances rich in the licorice extract are utilized to inhibit decomposition of protein, fat and the like in the baking process of the fresh meat, reduce generation of free radicals and inhibit conversion of precursor substances of polycyclic aromatic hydrocarbons, N-nitrosamines and heterocyclic amines, so that generation of the polycyclic aromatic hydrocarbons, the N-nitrosamines and the heterocyclic amines is inhibited. The method is easy and convenient to operate, raw and auxiliary materials are easy to obtain, the production cost is low, the content of polycyclic aromatic hydrocarbon, N-nitrosamine and heterocyclic amine in the baked fresh meat can be greatly reduced, and the baked meat product is safer to eat.

The invention discloses a method for determining nitrosamine impurity N-nitrosociprofloxacin in ciprofloxacin lactate, and relates to the field of substance detection methods, the method adopts a liquid chromatography-mass spectrometry technology, and the liquid chromatography condition comprises that a mobile phase is a mixture of a formic acid solution with the concentration of 0.08%-0.12% and acetonitrile, and the volume ratio of the formic acid solution to the acetonitrile is (45-55): (45-55). According to the present invention, the liquid chromatography (LC) technology and the mass spectrometry (MS) technology are combined, such that the efficient separation ability of the liquid chromatography and the high sensitivity detection ability of the mass spectrometry are combined, the detection sensitivity and the detection accuracy are significantly improved, and the strict requirements of drug quality control and safety are met.

The present invention relates to a method for preparing nitrosamine impurities in vonoprazan fumarate, belonging to the technical field of chemical synthesis. By mixing vonoprazan with an organic solvent and reacting the mixture with a nitrosating agent at room temperature, the nitrosamine impurities prepared by this method have a purity exceeding 85%. This method solves the problem of preparing nitrosamine impurities and also provides a reference substance for the study of impurities in vonoprazan fumarate.

The present invention relates to the use of ascorbic acid fatty acid esters for reducing nitrosamine formation in compositions comprising methylphenidate.

Provided are compositions comprising certain miglustat-related nitrosamine compounds, such as pharmaceutical compositions comprising miglustat and such miglustat-related nitrosamine compounds. Also provided are pharmaceutical compositions comprising miglustat and less than certain levels of such miglustat-related nitrosamine compounds. Also provided are methods of analyzing such miglustat-related nitrosamine compounds.

The invention discloses application of acid-producing bacteroides in treatment of hepatic fibrosis and hepatocellular carcinoma. In-vitro cell experiments verify that the Bacteroides acidogenes and the culture medium thereof can inhibit LX2 cell fibrosis induced by TGF-beta, can inhibit the activity of LX2, Huh7 and 97H cells and can inhibit the cell proliferation capacity at the same time, and further, in a hepatocellular carcinoma spontaneous animal model induced by diethylnitrosamine and carbon tetrachloride, the application of the Bacteroides acidogenes and the culture medium of the Bacteroides acidogenes and the culture medium of the Bacteroides acidogenes and the culture medium of the Bacteroides acidogenes in the hepatocellular carcinoma spontaneous animal model has the advantages of being capable of inhibiting the fibrosis of the LX2 cells induced by the TGF-beta and inhibiting the proliferation capacity of the cells. The inhibition effect of the acid-producing bacteroides on hepatic fibrosis and liver cancer progression is verified; the acid-producing bacteroides is recognized as probiotics and has low side effect risk, so that the acid-producing bacteroides has a good clinical application prospect.

A synthetic polyisoprene latex emulsion has pre-vulcanization composition and post vulcanization composition. The pre-vulcanization composition comprises insoluble amorphous sulfur extracted with zinc dithiocarbamate catalyst at 20° C. to form sulfur chain and transported to interior of synthetic polyisoprene particle forming physical attachment of sulfur to active sites. The degree of pre-vulcanization is verified by expansion of cast and dried film of latex in toluene in 20 minutes by means of a swelling index test. The latex emulsion is vulcanized at 90° C. to 120° C. for 3 to 5 minutes. Post-vulcanization composition with accelerators crosslink between synthetic polyisoprene particles, uniformly curing both in the inter-particle and intra-particle regions to produce high cross link density, uniform distribution of double bonds with zinc segregation at the boundaries of original particles. The condom exhibits high tensile strength, tensile modulus, elongation with excellent tear strength releasing below 10 ppb of nitrosamines.

This invention discloses a strain of *Lactobacillus rhamnosus* H7 and its applications, belonging to the field of food microbiology technology. This invention provides a *Lactobacillus rhamnosus* H7 isolated from fermented meat, deposited at the Guangdong Provincial Microbial Culture Collection Center. This strain has the function of degrading nitrite. When inoculated into dried sausage, the residual nitrite and nitrosamine levels in the dried sausage are reduced, and the color of the meat product is significantly improved. When inoculated into fermented mandarin fish, the residual nitrite and nitrosamine levels in the fermented mandarin fish are also reduced. Therefore, inoculating fermented meat products with *Lactobacillus rhamnosus* H7 not only helps improve the safety of fermented meat products but also enhances their quality. This strain has good application prospects as a starter culture for fermented meat products.

The invention relates to the technical field of chemical synthesis, and particularly discloses a procaterol hydrochloride nitrosamine synthesis method and application, and the procaterol hydrochloride nitrosamine impurity synthesis method comprises the following process steps: procaterol hydrochloride, sodium nitrite and acid are subjected to a reaction in a first solvent to generate a procaterol hydrochloride nitrosamine impurity, the procaterol hydrochloride nitrosamine impurity obtained in the invention can be used as a standard substance for detecting the content of the nitrosamine impurity in procaterol hydrochloride granules, and has a high application value.

The invention relates to a nitrosamine-free balloon and a preparation method thereof, and belongs to the technical field of balloon products. In order to solve the problem that nitrosamine is easily generated by using a vulcanization accelerator in the traditional latex balloon, the balloon disclosed by the invention adopts a double-layer composite structure, the inner layer is a natural latex / waterborne polyurethane composite film containing a coupling agent and an acrylic acid hydroxyl compound, and the outer layer is a waterborne polyurethane protective layer film; according to the technology, active groups decomposed by a silane coupling agent are used for promoting cross-linking of sulfur and rubber, and chemical bond cross-linking is formed through surface hydroxyl groups, latex protein and polyurethane groups; the balloon product prepared by utilizing a cross-linking mechanism of reaction of a hydroxyl acrylic acid compound with carboxyl in latex and carbamate of polyurethane and matching with an impregnation process is free of nitrosamine. According to the technology, amine-containing vulcanization accelerators such as thiazoles and thiurams are completely abandoned, and nitrosamine generation is completely eradicated from the source.

Provided herein is a pharmaceutical composition comprising cytisine and a nitrite scavenger, wherein, upon storage of the composition at about 60 ºC, the amount of N-nitrosocytisine relative to a total weight of cytisine is 4.2 ng / mg or less after about 30 days. A method of manufacturing a cytisine tablet is also provided.

A process for preparing rifampicin substantially free of 1-methyl-4-nitrosopiperazine (MeNP) may include: providing a mixture of crude rifampicin in an organic solvent, wherein the mixture is obtained by dissolving a solid crude rifampicin in the organic solvent; washing the mixture with an aqueous solution, having a pH greater than or equal to 2 and less than or equal to 7, so as to obtain an organic layer and an aqueous layer which are then separated; adding at least one antioxidant to the separated organic layer; distilling the organic solvent under inert atmosphere; crystallizing under the inert atmosphere; and isolating the rifampicin thus obtained under the inert atmosphere.

The invention relates to a method for determining the content of nitrosamine impurities in a pramipexole dihydrochloride sustained-release tablet, which comprises the following steps: grinding the pramipexole dihydrochloride sustained-release tablet into fine powder as a sample to be detected, and extracting with a diluent to obtain a test solution; and carrying out liquid chromatography-mass spectrometry detection on the test solution, and calculating according to the detection result to obtain the content of the nitrosamine impurity N-nitroso-pramipexole in the pramipexole dihydrochloride sustained release tablet. According to the method, the nitrosamine impurity N-nitroso-pramipexole can be effectively extracted from the pramipexole dihydrochloride sustained release tablet, and the nitrosamine impurity is quantitatively detected by liquid chromatography-mass spectrometry, so that the problems that the nitrosamine impurity N-nitroso-pramipexole is low in content, difficult to detect and easy to interfere are successfully solved. The method is high in accuracy, precision and sensitivity and good in linearity, specificity and system adaptability.

This invention discloses a method for the deamination functionalization of aliphatic nitrosamines, comprising: reacting an aliphatic nitrosamine as shown in formula (II) with a nucleophile in the presence of an acid and a solvent to generate a deamination functionalized product as shown in formula (III); wherein, R 1 R 2 R 3 Each group is independently selected from hydrogen, hydroxyl, alkyl, alkoxy, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, aryl, heteroaryl, phenylalkyl, or R 1 R 2 R 3 Two or three of the functional groups form a non-aromatic ring, cage-like compound; FG is a functional group in which a nucleophile participates in the reaction. The method of this invention has the advantages of inexpensive and readily available raw materials, simple reaction conditions, and wide substrate applicability.

The application belongs to the technical field of substance analysis and detection, and provides an extraction method and a detection method for N-nitrosamine compounds in aquatic products. The N-nitrosamine compounds in the aquatic products to be measured are extracted by steam distillation, and the extraction rate of the N-nitrosamine compounds is high. The obtained distillate is purified and enriched by using an acid-modified coconut shell activated carbon column, the acid-modified coconut shell activated carbon column can effectively adsorb N-dimethyl-nitrosamine and N-diethyl-nitrosamine in the distillate, the acid-modified coconut shell activated carbon column is first eluted with n-hexane to remove part of the fat-soluble impurities, then N-dimethyl-nitrosamine and N-diethyl-nitrosamine are eluted with dichloromethane, due to the strong adsorption of the acid-modified coconut shell activated carbon column to the impurities, the impurities are not easily eluted by dichloromethane, so that the impurities, N-dimethyl-nitrosamine and N-diethyl-nitrosamine are effectively separated, and the purpose of purification is achieved.

Provided are compositions comprising certain miglustat-related nitrosamine compounds, such as pharmaceutical compositions comprising miglustat and such miglustat-related nitrosamine compounds. Also provided are pharmaceutical compositions comprising miglustat and less than certain levels of such miglustat-related nitrosamine compounds. Also provided are methods of analyzing such miglustat-related nitrosamine compounds.

This invention discloses a sophoridine tricyclic derivative or its pharmaceutical salt, with the following general structural formula: R1 is selected from hydrogen, C1-C20 straight-chain alkyl, and C1-C20 branched alkyl. In vitro experiments have verified that the sophoridine tricyclic derivative can inhibit TGF-β-induced activation of hepatic stellate cells, improve CCl4- and bile duct ligation-induced liver injury and liver fibrosis in mice, inhibit TGF-β / Smads signaling pathway activation, and also inhibit diethylnitrosamine-induced primary liver cancer in mice. Therefore, this invention provides new evidence for the treatment, alleviation, or improvement of liver fibrosis or primary liver cancer using sophoridine tricyclic derivatives.

The invention discloses a preparation method of cefoperazone sodium, which comprises the following steps: S1, adding cefoperazone acid into a first solvent system, and dropwise adding a sodium salt-forming agent aqueous solution for reaction to obtain a first reaction solution; s2, adding the first reaction solution into a second solvent system, and filtering to obtain an amorphous cefoperazone sodium wet product; s3, the amorphous cefoperazone sodium wet product is added into a third solvent system for suspension pulping, the crystal transformation temperature is controlled, and crystalline cefoperazone sodium is obtained; the high-purity cefoperazone sodium is obtained by salifying and crystallizing cefoperazone acid and then carrying out suspension crystal transformation, so that the molecular space structure of the cefoperazone sodium can be changed, and N-nitrosamine genotoxic impurities such as NDMA embedded into the crystal can be effectively separated.

The application relates to the technical field of chemical analysis, and discloses a method for extracting, separating and detecting N-nitrosamine, which comprises the following steps: a sample obtaining step; a sample purification step; a preparation and extraction solution step; an extraction solution separation step; an extraction solution concentration step; a chromatographic detection and quantitative analysis step; the sample to be detected is crushed to a size of 0.01g of powder, and the powder is mixed with sodium chloride, barium hydroxide and water. In the application, the sample to be detected is subjected to a step-by-step sample treatment process before detection, so that the interference factors of the sample to be detected can be effectively reduced, the influence on the detection instrument is reduced, the detection result and detection data are more accurate, and when the application is detected, a large amount of sample does not need to be weighed like in the traditional detection mode, the overall operation is more convenient, and the detection demand of N-nitrosamine in smoked food is met.