33 results about "ITOPRIDE HYDROCHLORIDE" patented technology

The invention relates to a preparation method of gastrointestinal crude drug itopride hydrochloride, and belongs to the field of medicines. The invention discloses a method for preparing itopride hydrochloride, which comprises the following steps of: taking cheap N,N-dimethylaminoethanol as an initial raw material; implementing an etherification reaction to obtain an intermediate product (VII) and implementing one-step reduction ammoniation to obtain a benzylamine product (IX); and reacting with 3,4-dimethoxy benzoyl chloride to generate hydrochloride. The preparation method of the itopride hydrochloride is cheap in raw material, moderate in reacting condition, and low in preparation cost of the itopride hydrochloride.

The invention discloses an itopride hydrochloride oral preparation. The oral preparation comprises 15-20 percent by weight of itopride hydrochloride and 10-30 percent by weight of a disintegrating agent, wherein the disintegrating agent is povidone. The oral preparation is used for overcoming the problems that a tablet is rough in appearance and easy to fracture, the tablet which is rough in appearance easily absorbs moisture and the color is changed in regions at low air temperature in winter and the like, is short in disintegrating time, good in dispersion uniformity, rapid in medicine dissolution, rapid in absorption, high in bioavailability, convenient and flexible to take and also good in taste and has the advantage that the compliance of patients for taking the medicine is improved.

The invention discloses a preparation method of medicine of itopride hydrochloride for promoting gastrointestinal motility. The method comprises the following steps that p-hydroxy methylbenzene is used as a raw material to take a reaction with dimethylaminoethyl chloride hydrochloride; then, 4-(2-dimethylamino oxethyl) benzyl bromide is synthesized through bromination; next, the 4-(2-dimethylamino oxethyl) benzyl bromide and 3,4-dimethoxybenzonitrile take a reaction to obtain a product of itopride under the solvent-free condition through copper trifluoromethanesulfonate catalysis. The preparation method has the advantages a bran-new synthesis route is provided; the itopride is synthesized through Ritter reaction under the solvent-free condition; the advantage of green and environment-friendly effects is realized; meanwhile, the used raw material resources are wide and sufficient; the price is low; the reaction conditions are mild.

The invention provides a preparation method of itopride hydrochloride. The method comprises a step that N,N-dimethylamino ethoxy aniline and 3,4-dimethoxy benzoyl chloride are subjected to an amidation reaction in dichloromethane. The method provided by the invention also comprises a step that a hydrogen chloride isopropyl alcohol solution and an itopride prototype material are subjected to a reaction, such that a salt is produced. According to the itopride hydrochloride preparation method provided by the invention, dichloromethane is used for replacing toluene, such that the harm brought by toluene is avoided. Also, no water is introduced during the salt formation process, such that loss can be reduced, product yield can be improved, and impurities are further removed. Therefore, the quality of a finished product is improved.

The invention relates to a preparation method of itopride hydrochloride. The preparation method includes: using 2-dimethylaminoethyl chloride hydrochloride and phenol as starting materials for reaction; subjecting the starting materials to etherification, chloromethylation, amino substitution, amidation and salifying to obtain itopride hydrochloride. Chloromethylation promoted by C / CHO is adopted, so that a step of imine reduction is omitted, solid residue generated by a reductant is eliminated, and reaction safety is improved; raw materials used in the method are low in price, sufficient in market supply and easy to purchase; reaction in each step is classic, and the preparation method is safe, easy to control and suitable for industrial production.

The invention provides an improved method for detecting related substances in an itopride hydrochloride preparation, which is characterized in that a monopotassium phosphate solution is used as a mobile phase A, a 90% acetonitrile solution is used as a mobile phase B to carry out gradient elution, the detection wavelength is 223 nm, the volume ratio of the monopotassium phosphate solution to the acetonitrile solution in a blank solution is 85:15, the separation degree of the itopride, the impurity VA, the impurity IHD and the impurity PH peak is more than 1.2, the abnormal phenomenon of no peak appearance during the continuous test of a plurality of samples does not exist, the method verification results show that the method meets the related requirements, the method meets the detection requirements, and the related substances in the itopride hydrochloride preparation can be effectively detected.

The present invention relates to a novel method for preparing an itopride-hydrochloride mediate of the formula 1, which is useful for digestive tract activator, and more particularly, the present invention provides with a method for preparing 4-[2-(dimethylamino)ethoxy]benzylamine of the formula 1, an itopride-hydrochloride mediate, whereby being capable of manufacturing in a high yield and lowering cost through a simple purification and a selective reaction, and the method is harmless and safe to human and environment due to not generating toxic gas. And specially, a super-high pressure hydrogenation and a reduction reaction using a metal catalyst are not carried out, therefore, it is very safe method, and also special manufacturing equipments are not needed.

The invention discloses a itopride hydrochloride sustained release preparation which is prepared from the following components in parts by weight: 50 to 100 parts of itopride hydrochloride, 40 to 50 parts of hydroxypropyl methylcellulose K100, 20 to 40 parts of hydroxypropyl methylcellulose E5, 20 to 30 parts of microcrystalline cellulose, 20 to 30 parts of lactose and 1 to 2 parts of magnesium stearate. The invention further discloses a preparation method thereof. The preparation method has the beneficial effects that the preparation is convenient, and the effective components of prepared tablets are slowly released.

The invention discloses an itopride hydrochloride micro-tablet, a preparation method thereof and application thereof in consistency evaluation of generic drugs. According to the itopride hydrochloridemicro-tablet, the preparation method thereof and the application thereof in the consistency evaluation of the generic drugs, itopride hydrochloride and various ingredients are mixed, pelletized and dried, and then evenly mixed with an extra disintegrant and a lubricant, and the mixture is pressed into the micro-tablet of which the diameter is no more than 3MM. A capsule can be filled with the micro-tablet, multiple dissolution curves of a prepared itopride hydrochloride capsule in vitro are consistent with an original product (product name: itopride hydrochloride tablet; trade name: Weilisu;specification: 0.05g; certificate holding merchant: ABBOTT LABORATORIES (M) SDN. BHD), in the process of accelerated test and long-term test stability investigation, related substances have no significant change, and the micro-tablet has a bioequivalence trend with the original product after the meal.

The invention discloses a synthesis method of itopride hydrochloride, and relates to the technical field of organic synthesis. Hydroxybenzylamine is taken as starting material, in non-polar solvent, in the presence of an acid-binding agent, the Hydroxybenzylamine and 3,4-dimethoxybenzoyl chloride are subjected to amidation to obtain an intermediate N-(4-hydroxyl) benzyl-3,4-dimenthoxybenzamide, and in polar solvent, in the presence of a catalyst, the intermediate N-(4-hydroxyl) benzyl-3,4-dimenthoxybenzamide and 2-chlorine-N,N-dimethylethylamine are subjected to etherification to obtain the itopride hydrochloride. According to the method, the raw materials are easy to obtain, the route is short, only two steps of synthetic reactions are needed, the high yield of 85-97% can be achieved in each step, by means of amidation and etherification with high product purity, a dangerous process of high-pressure hydrogenation is avoided successfully, and meanwhile, the production and raw materialcosts are greatly reduced.

The invention relates to an itopride hydrochloride sustained-release tablet composition. The technical scheme comprises that the cores of per 1000 tablets of itopride hydrochloride composition comprises 75 g of itopride hydrochloride, 45 g of Hydroxypropyl methyl cellulose, 15 g of sodium alginate, 40 g of microcrystalline cellulose, 8 g of aerosi, 7 g of polyvinylpyrrolidone K30, and 3 g of magnesium stearate. The beneficial effects comprise that the itopride hydrochloride sustained-release tablet according with clinic requirements is obtained through reasonable prescription adjusting, and the problem that the table release degree difference of the itopride hydrochloride sustained-release tablets is large is solved.

The invention relates to the technical field of pharmaceutical preparations, in particular to an orally disintegrating itopride hydrochloride tablet and a preparation method thereof: 50 parts by weight of itopride hydrochloride, 90-110 parts by weight of mannitol, and 10-30 parts by weight of lemon Acid, 30-40 parts by weight of polyvinylpyrrolidone and an appropriate amount of 50% ethanol solution are mixed evenly and added to the above-mentioned mixed material powder, 10-30 parts by weight of citric acid and stevioside are mixed in an appropriate amount to make a uniform soft material, and passed through 30 mesh Wet granules are prepared by nylon sieve, dried at 50-60°C for about 30 minutes, sieved with 30 meshes for granulation, the granules and 2-3 parts by weight of magnesium stearate and 1-2 parts by weight of micro-powdered silica gel are mixed evenly, and pressed into tablets. It can disintegrate quickly in the oral cavity under anhydrous conditions (or only a small amount of water exists), enter the digestive tract with swallowing action, and have no mucosal absorption in the oral cavity. The absorption and metabolism process in the body are consistent with ordinary tablets. Compared with common preparations, it has the advantages of convenient administration, fast absorption, high bioavailability, and less irritation to the mucous membrane of the digestive tract.

The invention discloses an itopride hydrochloride oral preparation. The oral preparation comprises 15-20 percent by weight of itopride hydrochloride and 10-30 percent by weight of disintegrating agent, wherein the disintegrating agent is povidone. According to the oral preparation, the problems that the appearance of tablets is rough, the tablets are easily broken, the tablets with rough appearance are easily moisturized and the colors of the tablets are easily changed in areas where the temperature is relatively low in winter are overcome. The oral preparation is short in disintegration time, high in dispersion uniformity, high in medicine dissolution speed, high in absorption and high in bioavailability, is convenient and flexible to orally take and has good taste; moreover, the medication compliance of patients is improved.

The invention discloses an itopride hydrochloride tablet, a preparation method of the tablet, and application in consistency evaluation of generic drugs. The raw material medicine of itopride hydrochloride has the characteristics of easily absorbing moisture, becoming sticky in water and crystallization, so that the materials become sticky and has poor granulation. Therefore, wet granulation is not suitable for preparing itopride hydrochloride tablets. In the present invention, itopride hydrochloride and various auxiliary materials are mixed uniformly, and then tablets with a diameter of about7 mm, a thickness of about 3 mm and a weight of about 130 mg, are obtained by directly pressing the above mixture. According to the itopride tablets produced by directly pressing powder, not only thedifficulty of granulation can be solved, but also the production process is simple, and the manufacturing cost is low. The multiple dissolution curves of the tablets in vitro are consistent with thedissolution curves of the original research product, related substances have no obvious change in the process of an accelerated test and long-term test stability investigation, and the tablets are bioequivalent with the original research product after meal.

The invention relates to a method for detecting related substances in itopride hydrochloride tablets by HPLC (High Performance Liquid Chromatography), and the related substances comprise an impurity A, an impurity B and an impurity C. The method comprises the following steps: step 1, respectively preparing a blank solvent, a blank auxiliary material, a reference solution, a test solution and a system applicability solution; 2, detecting the blank solvent, the blank auxiliary material, the reference substance solution, the test solution and the system applicability solution in the step 1 by adopting HPLC (High Performance Liquid Chromatography), and recording a chromatogram; the quality of the main degraded impurities in the tablet is controlled by the method, and the method has the advantages of high sensitivity, strong specificity, good separation degree, high precision, good reproducibility and good accuracy, and can more conveniently and effectively control the quality of the product.

The invention relates to an itopride hydrochloride fast-release preparation and a preparation method thereof. The itopride hydrochloride fast-release preparation comprises the following components inparts by weight: 50-100 parts of itopride hydrochloride, 10-50 parts of croscarmellose sodium, 20-150 parts of starch and 1-2 parts of magnesium stearate. The invention achieves the following beneficial effects: in order to release an effective drug component, namely the itopride hydrochloride, as soon as possible, the types of other auxiliary materials are few, a small amount of croscarmellose sodium is used as a swelling agent, a small amount of thickening agent is used, and the only auxiliary material with a higher content is the starch, which is beneficial to human digestion, so that the release speed of the whole tablet is very high.

The invention aims to provide a method for detecting 3, 4-dimethoxybenzoyl chloride in itopride hydrochloride. The method comprises the following steps: adding aniline into itopride hydrochloride to carrt out pre-column derivatization on 3, 4-dimethoxybenzoyl chloride; then, using octadecylsilane chemically bonded silica as a stationary phase to separate 3, 4-dimethoxybenzoyl chloride from itopride hydrochloride so as to confirm the residual amount of 3, 4-dimethoxybenzoyl chloride in itopride hydrochloride. The system applicability, specificity, precision, detection limit, quantification limit, linearity and range, accuracy, durability and the like are verified to confirm the feasibility and effectiveness of the method. The method for detecting 3, 4-dimethoxybenzoyl chloride in itopride hydrochloride is provided for the first time, has the characteristics of high accuracy, high precision, good reproducibility, good stability, strong specificity and the like, and has the advantages ofshort time consumption, simple operation, low cost and the like.

The invention relates to the technical field of pharmaceutical preparations, in particular to an itopride hydrochloride chewable tablet and a preparation method thereof: 50 parts by weight of itopride hydrochloride, 100-170 parts by weight of a filler, 20-40 parts by weight of citric acid, 3-8 parts by weight of polyvinylpyrrolidone and an appropriate amount of 50% ethanol solution are mixed and added to the above-mentioned mixed material powder, mixed to make a uniform soft material, passed through a 30-mesh nylon sieve to make wet granules, and dried at 50-60 ° C for about 30 minutes. The 30-mesh sieve is sized, and the granules are mixed with 2 to 3 parts by weight of magnesium stearate evenly and pressed into tablets. The filler is one or more of pregelatinized starch, lactose, dextrin, microcrystalline cellulose, mannitol, sorbitol and xylitol. It has the characteristics of simple preparation, convenient administration, fast absorption and high bioavailability.

The invention relates to a preparation method of gastrointestinal crude drug itopride hydrochloride, and belongs to the field of medicines. The invention discloses a method for preparing itopride hydrochloride, which comprises the following steps of: taking cheap N,N-dimethylaminoethanol as an initial raw material; implementing an etherification reaction to obtain an intermediate product (VII) and implementing one-step reduction ammoniation to obtain a benzylamine product (IX); and reacting with 3,4-dimethoxy benzoyl chloride to generate hydrochloride. The preparation method of the itopride hydrochloride is cheap in raw material, moderate in reacting condition, and low in preparation cost of the itopride hydrochloride.

The invention provides a detection method of an impurity demethylated itopride nitrosamine in itopride hydrochloride, wherein the method comprises the steps: selecting octadecylsilane chemically bonded silica as a filler, and an ammonium acetate aqueous solution and acetonitrile as mobile phases to carry out liquid chromatography separation, and detecting target molecules by using combination of mass spectrometry. According to the method, the system applicability, specificity, precision, quantitation limit, detection limit, linearity and range all meet the requirements, the separation effect is good, operation is easy and convenient, and the method sensitivity is high.

The invention discloses an itopride hydrochloride micro-tablet, a preparation method thereof and application thereof in consistency evaluation of generic drugs. According to the itopride hydrochloridemicro-tablet, the preparation method thereof and the application thereof in the consistency evaluation of the generic drugs, itopride hydrochloride and various ingredients are mixed, pelletized and dried, and then evenly mixed with an extra disintegrant and a lubricant, and the mixture is pressed into the micro-tablet of which the diameter is no more than 3MM. A capsule can be filled with the micro-tablet, multiple dissolution curves of a prepared itopride hydrochloride capsule in vitro are consistent with an original product (product name: itopride hydrochloride tablet; trade name: Weilisu;specification: 0.05g; certificate holding merchant: ABBOTT LABORATORIES (M) SDN. BHD), in the process of accelerated test and long-term test stability investigation, related substances have no significant change, and the micro-tablet has a bioequivalence trend with the original product after the meal.

The invention relates to an itopride hydrochloride controlled-release tablet combination. The technical scheme includes that an itopride hydrochloride controlled-release tablet comprises a tablet core and a coating layer; the itopride hydrochloride controlled-release tablet is characterized in that the tablet core contains itopride hydrochloride, polyethylene glycol 1000, lactose, mannitol, aerosil and povidone K30, and the coating layer contains ethyl cellulose and hydroxypropyl methyl cellulose. By the technical scheme, the problem that release rate of single-chamber itopride controlled-release tablets can reach about 70% only is solved, and a pharmaceutical which is safe, effective and high in utilization rate is provided for clinical medication.

The present invention relates to an itopride hydrochloride pharmaceutical composition, belonging to the technical field of pharmaceutical preparations. The technical solution of the present invention is: an itopride hydrochloride pharmaceutical composition, each tablet containing 50 mg of itopride hydrochloride, 25-45 mg of polyoxyl 40 stearate, 20-30 mg of alginate, 10 mg of low-substituted hydroxypropyl cellulose, 20 mg of microcrystalline cellulose, 30 mg of mannitol, 6 mg of cross-linked polyvinylpyrrolidone, and 1 mg of magnesium stearate. The present invention provides an itopride hydrochloride pharmaceutical composition having a good mouthfeel, rapid dispersion, and a dissolution profile similar to that of the original formulation, and a preparation method.

A method for measuring the content of itopride hydrochloride in itopride hydrochloride tablets through HPLC comprises the steps that a blank solvent is prepared, and the blank solvent is an acetonitrile-0. 01mol / L ammonium dihydrogen phosphate solution; taking a proper amount of an itopride hydrochloride reference substance, precisely weighing the itopride hydrochloride reference substance, and diluting the itopride hydrochloride reference substance with a mobile phase to obtain a reference substance solution; taking a proper amount of itopride hydrochloride tablets, placing the itopride hydrochloride tablets in a measuring flask, adding a hydrochloric acid solution, carrying out ultrasonic treatment, cooling, diluting with the hydrochloric acid solution to a scale, uniformly shaking, filtering, precisely measuring 2ml of a continuous filtrate, placing the itopride hydrochloride tablets in the measuring flask, diluting with a mobile phase to a scale, and uniformly shaking to obtain the itopride hydrochloride tablet. Using liquid chromatography to obtain chromatograms of the test solution and the reference solution under qualified chromatographic separation conditions, and determining the content of itopride hydrochloride by an external standard method; through the steps, the content of itopride hydrochloride can be detected, the method has the advantages of being high in specificity, sensitivity, precision and accuracy, the quality of itopride hydrochloride tablets is guaranteed, and the safety of clinical medication is improved.

The invention relates to an itopride hydrochloride sustained-release tablet composition. The technical scheme comprises that the cores of per 1000 tablets of itopride hydrochloride composition comprises 75 g of itopride hydrochloride, 45 g of Hydroxypropyl methyl cellulose, 15 g of sodium alginate, 40 g of microcrystalline cellulose, 8 g of aerosi, 7 g of polyvinylpyrrolidone K30, and 3 g of magnesium stearate. The beneficial effects comprise that the itopride hydrochloride sustained-release tablet according with clinic requirements is obtained through reasonable prescription adjusting, and the problem that the table release degree difference of the itopride hydrochloride sustained-release tablets is large is solved.

A kind of preparation method of itopride hydrochloride The present invention relates to the preparation method of itopride hydrochloride, the reaction takes 2-dimethylaminochloroethane hydrochloride and phenol as starting materials, through etherification, chloromethylation , amino substitution, amidation, and salt-forming 5-step reaction to obtain itopride hydrochloride. In the present invention, the chloromethylation promoted by HCl / CHO avoids the imine reduction step, eliminates the solid waste generated by the reducing agent, and improves the safety of the reaction; the raw materials used are cheap, the market supply is sufficient, and they are easy to purchase; The one-step reaction is more classic, safe and easy to control, and suitable for industrial production.

The invention provides a preparation method of itopride hydrochloride. The method comprises a step that N,N-dimethylamino ethoxy aniline and 3,4-dimethoxy benzoyl chloride are subjected to an amidation reaction in dichloromethane. The method provided by the invention also comprises a step that a hydrogen chloride isopropyl alcohol solution and an itopride prototype material are subjected to a reaction, such that a salt is produced. According to the itopride hydrochloride preparation method provided by the invention, dichloromethane is used for replacing toluene, such that the harm brought by toluene is avoided. Also, no water is introduced during the salt formation process, such that loss can be reduced, product yield can be improved, and impurities are further removed. Therefore, the quality of a finished product is improved.

The invention relates to an itopride hydrochloride controlled-release tablet combination. The technical scheme includes that an itopride hydrochloride controlled-release tablet comprises a tablet core and a coating layer; the itopride hydrochloride controlled-release tablet is characterized in that the tablet core contains itopride hydrochloride, polyethylene glycol 1000, lactose, mannitol, aerosil and povidone K30, and the coating layer contains ethyl cellulose and hydroxypropyl methyl cellulose. By the technical scheme, the problem that release rate of single-chamber itopride controlled-release tablets can reach about 70% only is solved, and a pharmaceutical which is safe, effective and high in utilization rate is provided for clinical medication.

The invention discloses an itopride preparation method, the method comprises the steps of 1, 2-(dimethylamino) chloroethane hydrochloride and hydroxybenzaldehyde synthesizing into 4-(2- dimethylamino ethoxy) benzaldehyde, then synthesizing into 4-(2- dimethylamino ethoxy) benzyl alcohol in alcohol solvent by revivification; 2, in alcohol solvent 3, 4-dimethoxy benzaldehyde and hydroxylamine hydrochloride creating reaction, then in nonpolar solvent synthesizing into 3, 4- dimethoxybenzonitrile by dehydration using the dehydrant; 3, the 4-(2-dimethylamino ethoxy) benzyl alcohol and the 3, 4- dimethoxybenzonitrile synthesizing into itopride in one step; 4, obtaining hydrochloric acid itopride by dissolving itopride in hydrogen chloride alcohol solution and salifying. The adopted raw material in the method is wide in sourcing scope, simple in preparation processing, and is suitable for large scale industrialization production; the preparation process involves no danger process, the production equipment is simple, the synthesized circuit is shorter than the existed circuits, the preparation time is short and the use effect is good.