75 results about "Methoxamine" patented technology

This invention generally relates to novel compositions and methods for the treatment of certain cancers. Additionally, this invention relates to novel compositions and methods to screen drugs for the treatment of certain cancers. Specifically, the invention contemplates that temozolomide and methoxyamine, in combination or in sequence, shall be used as a treatment for certain tumors that are resistant to treatment by temozolomide alone.

Disclosed is an anti solid tumor medicine composition, which comprises medicinal adjuvant and DNA restoring enzyme inhibitor and / or Nitrosoureas anti-cancer drugs, wherein the DAN restoring enzyme inhibitor is selected from methoxamine, hydroxylamine and their analogues, which can effectively destroy the DNA restoring function in the tumor cells, and lower the survivability of tumor cell to Semustine anti-cancer drugs and their analogues, the medicinal adjuvant is biological compactable, degradable and absorbing macromolecular polymer, which can slowly release the DNA restoring enzyme inhibitor onto tumor partially during the degradation and absorption process, thus the whole body toxicity reaction is reduced appreciably , and the effective medicinal concentration can be sustained to the tumor partially. By dispensing the composition to the tumor partially, the whole body toxicity reaction of Nitrosoureas anti-cancer drugs and / or DNA restoring enzyme inhibitor can be lowered, selectively increase the tumor local medicinal concentration, and the treatment effect of the non-operative treatment methods such as chemotherapy, medicament and radiation can be improved.

The invention provides a method for synthesizing methoxyamine hydrochloride and includes the following steps: ethyl acetate and hydroxylamine hydrochloride are added into a reaction vessel and 10 to 30 percent of sodium hydroxide solution is instilled for oximation reaction; then dimethyl sulfate is instilled, and at the same time sodium hydroxide solution with the mass fractions of 10 to 30 percent is instilled for methylation reaction; cold water is added after the temperature is decreased and a halohydrocarbon solvent is adopted for extraction; pressure is reduced under the temperature of 30 to 50 DEG C to recover the halohydrocarbon solvent and the product obtained is added into inorganic acid solution for hydrolysis reaction; after the hydrolysis is over, hydrochloride is used to obtain the product methoxyamine hydrochloride. The synthetic method which is simple improves the operation environment and increases the yield ratio.

The invention relates to a method for synthesizing (z)-2-(alpha-methoxy imine) furan ammonium acetate, comprising the following method: 2-oxo-2-furyl acetate and water are added into a vessel, the PH is adjusted by inorganic acid, and then methoxamine solution or the hydrochloride solution thereof are added; insulating reaction is carried out, inorganic base and inorganic acid are used for controlling in the reaction process, the PH of the reaction solution is adjusted by the inorganic acid, and organic layers are extracted and combined by an organic solvent; alkaline air or liquid ammonia is pumped into the organic layers, and crude product is obtained after filtration and centrifugation; the crude product is added into refining solvent, active carbon is added to decolorize, heating reflux is carried out, the active carbon is filtered and removed before getting cold, then mother solution is concentrated, cooled and crystallized, thus obtaining the product. The synthesizing method reduces cost and operation steps and improves the yield rate.

The invention discloses a preparation method for methoxylamine hydrochloride, comprising the following preparation steps of: 1) preparing acetyl hydroxylamine; 2) preparing acetyl methoxyamine; and 3) preparing methoxylamine hydrochloride. The preparation method is moderate in reaction conditions, and is capable of avoiding the toxic substances such as sulfur dioxide and sodium nitrite which are used in the existing production process for methoxylamine hydrochloride, reducing the emission of waste gases such as nitric oxide, and lightening a pressure of environment.

The invention provides continuous reactive distillation equipment for synthesising methoxylamine hydrochloride by taking oxime methyl ether and hydrochloric acid as raw materials, and a process thereof, wherein a vertical clapboard is arranged in a reactive distillation dividing-wall column in the continuous reactive distillation equipment provided by the invention, and used for dividing the column into four areas, namely, a common distillation section, a reaction section, a stripping section and a lateral stripping section; and oxime methyl ether and hydrochloric acid solution enter from the upper part and the lower part of the reactive distillation section respectively, hydrolysis reaction for oxime methyl ether is performed in the reaction section, the generated methoxylamine hydrochloride is discharged from the bottom of the reactive distillation section, the generated by-product, namely, the mixture of acetone and oxime methyl ether, enters in the common distillation section in the form of a gaseous phase to be separated, more than 95% acetone is obtained on the top of the column, and the separated oxime methyl ether is recycled. According to the continuous reactive distillation equipment and the process provided by the invention, the dividing-wall column is combined with reactive distillation, and hydrolysis reaction and product separation are intensively performed in one column, thus effectively reducing energy consumption and equipment investment cost.

Compositions and methods useful in the treatment of certain cancers. The methods include administering, to a patient receiving an antifolate anticancer agent, methoxyamine administered in an amount sufficient to enhance or increase the effect of the antifolate anticancer agent. In part, this application is based on the recognition that certain molecules that target abasic lesions or AP sites in DNA improve, augment, or potentiate the chemotherapeutic efficacy of certain anticancer agents.

The invention provides a chemical derivatization-ultra-high performance liquid chromatography-tandem mass spectrometry method for simultaneously detecting 18 steroid hormones in serum, which is characterized in that a novel derivatization reagent 3-pyridylmethoxylamine is adopted for derivatization and then ultra-high performance liquid chromatography-tandem mass spectrometry is used for detection. According to the method, only 10 minutes are needed for detecting 18 steroid hormones at the same time, the hydrophobicity index logP is greatly improved after derivatization, the peak shape and theseparation degree in a high performance liquid phase reversed phase chromatographic column are improved, and the ionization efficiency is better, so that the mass spectrum detection sensitivity is improved. The method has the characteristics of simplicity and convenience in operation, good accuracy, strong specificity, wide detection range and the like.

The invention discloses a method for separating methoxamine from distillation liquid by using electrodialysis. The method comprises the following specific processes: filtering methoxamine distillation liquid by using micro-pores; pumping a solution into one of a salt chamber or a salt / fresh water chamber of a bipolar membrane electrodialysis device; injecting an electrolyte solution with a certain concentration into other compartment chambers; respectively connecting a cathode and an anode of the device with the negative electrode and the positive electrode of a direct-current power supply; starting the bipolar membrane electrodialysis device; controlling the current density of the direct-current electric field of the membrane electrodialysis device to be 10 to 150 A / m<2>, and the temperature to be 5 to 30 DEG C, thereby obtaining the methoxamine solution in an acid chamber, wherein the recovery rate reaches over 95 percent, and the current efficiency reaches about 70 percent. The method has the advantages of high yield, low energy consumption and no pollution, and has a good application prospect.

The invention provides a method for preparing methoxamine hydrochloride. 4'-methoxypropiophenone is taken as a raw material, is subjected to bromination, condensation, hydrogenation and salt forming reaction to obtain the methoxamine hydrochloride; and the 4'-methoxypropiophenone is utilized to prepare 2-bromine-1-(2, 5-dimethoxybenzene) acetone at first, the 2-bromine-1-(2, 5-dimethoxybenzene) acetone is then reacted with 2-di-tert-butyl carbonylamine to obtain 2-di-tert-butyl carbonylamine-1-(2, 5-dimethoxybenzene) acetone, the 2-di-tert-butyl carbonylamine-1-(2, 5-dimethoxybenzene) acetone is subjected to hydrogenation reduction to obtain 2-di-tert-butyl carbonylamine-1-(2, 5-dimethoxybenzene) propyl alcohol, and finally, the 2-di-tert-butyl carbonylamine-1-(2, 5-dimethoxybenzene) propyl alcohol is reacted with hydrochloric acid to obtain the methoxamine hydrochloride. The method has the advantages of short reaction steps, moderate operation conditions, convenience and suitability for industrial production.

The invention discloses a novel synthesis method for methoxamine hydrochloride, which comprises the following steps: under the protection of nitrogen, liquid methyl p-toluenesulfonate is added into certain amount of acetonitrile solution of potassium carbonate, the temperature is controlled to between 12 and 18 DEG C, and proper amount of acetonitrile mixed liquid of hydroquinone is slowly dripped. Then the stirring is performed for 5 minutes, the temperature is increased to 83 DEG C for violent reflux reaction, the nitrogen is turned off when the reflux appears, and the complete reaction can be finished 22 hours later. Then a Friedel-Crafts acylation reaction, an oximation reaction, a hydroximino reduction reaction and a ketoamine hydrogenation reaction are orderly performed, and finally a target product is synthesized by an economical and environment-friendly route. The yields of 5-step operations are 94 percent, 72 percent, 80 percent, 79 percent and 88 percent respectively. The method has the advantages that the method has mild reactions and simple conditions, is steady and easy for scale-up production, and improves the yield compared with the prior synthesis of the methoxamine hydrochloride.

The invention relates to a method of preparing furfural oxime acid. The method comprises the steps of (1) mixing acetyl furan, sodium nitrite and hydrochloric acid to carry out oximation to generate ketoxime, carrying out Beckmann rearrangement reaction on the ketoxime in the presence of a Br phi nsted acid ionic liquid catalyst to generate amid, and carrying out hydrolysis, separation and purification on the amid under the acidic condition to obtain 2-oxo-2-furyl acetic acid; (2) carrying out silicate reaction on the 2-oxo-2-furyl acetic acid and a methoxamine salt in a solvent under the acidic condition (wherein a pH value is2.0-6.0), and carrying out separation and purification to obtain the furfural oxime acid. By virtue of adopting the method, the product yield is high, the reaction steps are less, and three-waste pollution is not generated.

The invention discloses a synthetic method of methoxamine hydrochloride, and the synthetic method comprises the following steps of: adopting DL-alpha-alanine as a raw material and adopting methanol as a solvent, and obtaining N-trifluoroacetyl-DL-alpha-alanine under the action of triethylamine; reacting the N-trifluoroacetyl-DL-alpha-alanine with hydroquinone dimethyl; obtaining 2-trifluoroacetyl-1-(2,5-dimethoxyphenyl)-1-acetone by adopting methylene dichloride as a solvent and adopting oxalyl chloride as an acylating agent; obtaining 2-amino-1-(2,5-dimethoxyphenyl)-1-acetone hydrochloride after the removal of a protective group by adopting alcohol as a solvent under the action of hydrochloric acid; and finally, obtaining a course product of the methoxamine hydrochloride after a reduction reaction under the action of potassium borohydride and obtaining a refined product of the methoxamine hydrochloride by adopting alcohol as a refined solvent, wherein the purity of the refined product of the methoxamine hydrochloride is 99.9%, the content of an individual impurity of the refined product of the methoxamine hydrochloride is less than 0.05%, and the content of the total impurities of the refined product of the methoxamine hydrochloride is less than 0.1%. The preparation method disclosed by the invention has the advantages of easiness for the acquisition of raw materials and convenience for operation; and the prepared product has the advantages of high purity, high yield and lower cost and is very suitable for large-scale production.

The invention provides a method for synthesizing methoxyamine hydrochloride and includes the following steps: ethyl acetate and hydroxylamine hydrochloride are added into a reaction vessel and 10 to 30 percent of sodium hydroxide solution is instilled for oximation reaction; then dimethyl sulfate is instilled, and at the same time sodium hydroxide solution with the mass fractions of 10 to 30 percent is instilled for methylation reaction; cold water is added after the temperature is decreased and a halohydrocarbon solvent is adopted for extraction; pressure is reduced under the temperature of 30 to 50 DEG C to recover the halohydrocarbon solvent and the product obtained is added into inorganic acid solution for hydrolysis reaction; after the hydrolysis is over, hydrochloride is used to obtain the product methoxyamine hydrochloride. The synthetic method which is simple improves the operation environment and increases the yield ratio.

The invention provides a preparation method of methoxylamine hydrochloride. The method comprises the following steps of adding diacetylmonoxime (C4H9NO), dimethyl sulfoxide (DMSO, C2H6OS), triethylamine (C6H15N) and a methylation reagent into a reaction vessel, and reacting at 15-75 DEG C to generate O-methyl-2-diacetylmonoxime ether. Compared with the prior art. The method has the advantages thatthe operation is simple, wastes are few, furthermore, reaction raw materials can be completely converted, a generated intermediate by-product can be decomposed into diacetylmonoxime (C4H9NO) and triethylamine (C6H15N), equivalently, no side reaction exists, the yield of synthesized methoxylamine hydrochloride is improved, the use of toxic substances such as sulfur dioxide and sodium nitrite is avoided, the emission of toxic gases such as nitric oxide is reduced, and the sustainable development of enterprises is facilitated.

The invention discloses a methoxylamine preparation method which at least comprises the following steps of enabling feed gas containing methyl nitrite and a reducing agent to be in contact with a reduction reaction catalyst in a reactor, and performing reduction reaction to obtain methoxylamine. According to the method, the important intermediate methyl nitrite in the technical process of preparing ethylene glycol from coal can be fully utilized, and the conversion rate of methyl nitrite is high. The invention also provides a method for preparing methoxylamine hydrochloride by taking methoxylamine obtained by the method as a raw material.

The invention is directed to anti-cancer compositions comprising methenamine or its derivatives or conjugates, and to use of such methenamine containing compositions to treat cancer.

The invention belongs to the technical field of preparation of medical intermediates, particularly relates to a method for preparing furan ammonium salt with high selectivity, and solves the problems of low conversion rate of a raw material 2-acetylfuran, low yield of furan ammonium salt, harsh reaction conditions of a furan ammonium salt preparation process and the like in the prior art. The method comprises the following steps: adding water, an acidic solution and 2-acetylfuran into an oxidation kettle, heating, dropwise adding an oxidant, and reacting to obtain 2-oxo-2-furanacetic acid; cooling 2-oxo-2-furanacetic acid, and then adding methoxyamine to react, so as to obtain 2-methoxyamine-2-furanacetic acid; adding methanol an ammoniation salifying kettle, adding 2-methoxyamine-2-furanacetic acid, introducing ammonia gas for a reaction, and obtaining the furan ammonium salt. The synthesis raw materials are low in price and easy to obtain, the preparation process is mild in reaction condition, safe and environmentally friendly, the yield and purity of the furan ammonium salt product are improved, and the production cost is reduced.

The invention discloses a vitamin D oxime derivative and a synthetic method and an application thereof. The method comprises the following steps: carrying out an oximation reaction between a compound I and hydroxylamine hydrochloride, thereby obtaining two A cyclic oxime derivatives such as (Z)-3-oxime vitamin D2 and (E)-3-oxime vitamin D2 of the vitamin D2 of different configurations; and enabling a compound 1.2 to react with methoxylamine hydrochloride, thereby obtaining two A cyclic oxime ether derivatives such as (Z)-3-methyl oxime ester vitamin D2 and (E)-3-methyl oxime ester vitamin D2 of the vitamin D2 of different configurations. The four vitamin D oxime derivatives have good effects of inhibiting human hepatoma cells Hep G2 and human breast cancer cells MCF-7 and have potential medicinal values.

A disclosed preparation method for erythro-structure methoxamine hydrochloride comprises the following steps: (1) dissolving an initial raw material 2,5-dimethylpropiophenone in an organic solvent, under the condition of introducing dry hydrogen chloride gas, dropwise adding a 1-butyl nitrite solution to perform an oximation reaction, so as to obtain an intermediate I; (2) under the acidic condition, taking a methanol solution as a solvent, take palladium on activated carbon as a catalyst, employing hydrogen to reduce the oximido group in the intermediate I, so as to obtain an intermediate II; and (3) performing hydrogenation reduction reaction on the intermediate II to obtain the erythro-structure methoxamine hydrochloride. The method provided by the invention is simple in operation, economic, environment-friendly, mild in reaction conditions, excellent in product quality and high in yield, and can help to obtain the single erythro-structure methoxamine hydrochloride.

The invention generally relates to the compositions and methods related to the use of adrenergic receptor agonists solutions for the treatment of skin and mucosal superficial wounds. Some of the preferred adrenergic receptor agonists include epinephrine, phenylephrine, norepinephrine, methoxamine, and mixtures thereof. The invention also relates to devices suitable for applying these solutions to the skin or the mucosal area. Methods according to the invention are especially effective to control superficial skin and mucosal bleeding and accelerate healing time.

The invention relates to the field of medicines and provides a composite injection for treating or preventing anesthesia hypotension. 1000 mL of the composite injection comprises 0.1-2g of atropine sulfate, 2-5g of methoxamine hydrochloride, 10-15g of medicinal auxiliary materials and the balance of injection water, and the pH value of the composite injection is adjusted to 4.5+ / -0.3. According tothe composite injection provided by the invention, the atropine sulfate and the methoxamine hydrochloride are adopted as active components, the methoxamine hydrochloride and the atropine sulfate arecompounded, and by virtue of the property that an alpha1-adrenergic receptor stimulant can be antagonized by atropine, reflective decreased heart rates caused by methoxamine hydrochloride can be antagonized. After the two components are compounded, a blood pressure boosting effect which is not inferior to that of independently used methoxamine hydrochloride can be achieved, the probability of reflective decreased heart rates can be reduced, and thus the composite injection provided by the invention is relatively safe and effective when being used for treating or preventing anesthesia hypotension.

The invention provides an aldehyde removing gypsum board and a preparation method thereof, wherein the aldehyde removing gypsum board comprises a mixture of modified zeolite, methoxyamine hydrochloride, polymer amine, guar gum and phosphate. According to the present invention, the aldehyde removing gypsum board can quickly capture indoor formaldehyde and decompose, such that the indoor formaldehyde concentration can be effectively reduced, and the aldehyde removing effect can be maintained for a long time; and the aldehyde removing gypsum board has excellent mechanical property.

The invention relates to the technical field of compound synthesis methods, particularly a method for coproducing vasoxine hydrochloride and N,O-dimethylhydroxylamine hydrochloride. The method comprises the following steps: carrying out methylation reaction on hydroxylamine salt under alkaline conditions by using a methylating agent to obtain a reaction solution containing vasoxine and N,O-dimethylhydroxylamine, rectifying to separate a vasoxine bottom solution and an N,O-dimethylhydroxylamine crude distillate, respectively adding hydrochloric acid for salification, concentrating and crystallizing under reduced pressure, cooling, carrying out vacuum filtration, recrystallizing with water or methanol, and drying to obtain the vasoxine hydrochloride product and N,O-dimethylhydroxylamine hydrochloride product. The method has the advantages of simple and reliable technique, high product quality, high total yield and low comprehensive cost, and is more friendly to the environment and suitable for industrial production.

The invention relates to the technical field of compound synthesis methods, particularly a method for coproducing vasoxine hydrochloride and N,O-dimethylhydroxylamine hydrochloride. The method comprises the following steps: carrying out methylation reaction on hydroxylamine salt under alkaline conditions by using a methylating agent to obtain a reaction solution containing vasoxine and N,O-dimethylhydroxylamine, rectifying to separate a vasoxine bottom solution and an N,O-dimethylhydroxylamine crude distillate, respectively adding hydrochloric acid for salification, concentrating and crystallizing under reduced pressure, cooling, carrying out vacuum filtration, recrystallizing with water or methanol, and drying to obtain the vasoxine hydrochloride product and N,O-dimethylhydroxylamine hydrochloride product. The method has the advantages of simple and reliable technique, high product quality, high total yield and low comprehensive cost, and is more friendly to the environment and suitable for industrial production.

The invention relates to a double-effect evaporation device and a double-effect evaporation method for methoxylamine mother liquor in furan ammonium salt production. The double-effect evaporation device is characterized by (1) preheating the methoxylamine mother liquor at 0.9-1.2 m <3> / h and 0.6-0.8 m <3> / h respectively and then pumping into a first-effect evaporator and a second-effect evaporator, (2) controlling the pressure in the first-effect evaporator and the pressure in the second-effect evaporator to be 0.07-0.09 Mpa, controlling the temperature of the first-effect evaporator to be 78-85 DEG C, and enabling a gas phase of the first-effect evaporator to enter the second-effect evaporator to be heated and evaporated, (3) condensing a gas phase from the second-effect evaporator, extracting, evaporating for 3040 minutes, and respectively extracting materials at the bottoms of the first-effect evaporator and the second-effect evaporator into a first-effect crystallization kettle anda second-effect crystallization kettle, and (4) crystallizing at 45-50 DEG C for 30-40 minutes, centrifuging to obtain white solid anhydrous sodium sulfate, and returning the centrifuged mother liquor to a double-effect evaporator for evaporation or discharging to a sewage system. The device has the advantages that the device is simple in structure and easy to operate, continuous production can be achieved, and production efficiency is improved, the utilization rate of a heat source is improved, the steam consumption is reduced from 0.9-1.1 to 0.4-0.55, the recovery efficiency of the methoxylamine mother liquor is improved from original 45%-55% to 75%-80%, and the purity of sodium sulfate is improved from original 97%-98% to 98.5%-99.5%.

The present invention contemplates a high dose finished pharmaceutical dosage form comprising a methenamine salt, such as methenamine mandelate, as an active pharmaceutical ingredient wherein the methenamine salt API has a moisture content that is less than the upper limit specified in the USP. A preferred embodiment of the present invention has a moisture content that is half of the limit set forth in the USP for each particular methenamine salt. An even more preferred embodiment has a moisture content of less than or equal to one-tenth of a percent (0.1%), regardless of the methenamine salt. The present invention may include one or more pharmaceutically acceptable ingredients. The present invention also contemplates a moisture content of the high dose finished pharmaceutical dosage form that is less than one percent.

The invention belongs to the field of synthesis of fine chemical intermediates, and discloses a method for preparing methoxyamine hydrochloride by adopting a microreactor. The method specifically comprises the steps of preparation of acetohydroxylamine, preparation of acetomethoxylamine and preparation of methoxylamine hydrochloride, wherein the preparation processes of acetohydroxylamine and acetomethoxylamine are carried out in a microreactor. Specifically, a hydroxylamine hydrochloride solution, ethyl acetate and alkali liquor are pumped into a micro-channel reaction module A and mixed in a micro-channel, then the mixture, dimethyl sulfate and alkali liquor are pumped into a micro-channel reaction module B again, collection is conducted after mixed reaction, and then the methoxylamine hydrochloride is obtained through the processes of hydrolysis, distillation, neutralization, salification, concentration and the like. Compared with the prior art, the method has the advantages that the yield of methoxyamine hydrochloride is effectively improved by utilizing the microreactor, the generation of three wastes is reduced, the reaction time is shortened, and the production cost is reduced.

The invention relates to the technical field of compound synthesis methods, and discloses a method for synthesizing methoxyamine hydrochloride. The method comprises the following steps: adding water, sodium hydroxide, diacetylmonoxime and a phase transfer catalyst into a reaction kettle; after cooling, adding a methylation reagent; conducting standing for layering to obtain an organic layer, a water layer and a distilled water layer, collecting distillate, combining an oil layer and the distillate, and adding hydrochloric acid for mixing to obtain a mixed solution; feeding and rectifying the mixed solution from the middle of a rectifying column, recovering butanone and methanol at the top of the column, recovering a methoxyamine hydrochloride solution at the bottom of the column, and carrying out evaporating and dehydrating to obtain a concentrated solution; and cleaning a reaction kettle, wherein a stirring mechanism and a cleaning mechanism are arranged in the reaction kettle, the cleaning mechanism comprises a scraping plate, a spraying pipe, a lifting assembly and a rotating assembly, a water inlet pipe and a cleaning nozzle are connected to the spraying pipe, the reaction kettle comprises a kettle body and a kettle cover, the water outlet end of the cleaning nozzle faces the side wall of the kettle body, and the scraping plate is attached to the side wall of the kettle body. The method has the effect of conveniently cleaning residues on the side wall of the kettle body.