19 results about "Azilsartan" patented technology

The application relates to a preparation method of an azilsartan solid dispersion and a medicinal composition thereof, and belongs to the technical field of pharmaceutical preparations. A unit dose of the azilsartan solid dispersion comprises azilsartan 20 mg, povidone K30 50-105 mg, sodium acetate trihydrate 4.9-5.7 mg, microcrystalline cellulose 210-270 mg, mannitol 65.6-83.2 mg, and sodium croscarmellose 8-24 mg which is added internally, and the preparation method is wet granulation; a unit dose of the azilsartan medicinal composition comprises the solid dispersion 429.5 mg, sodium croscarmellose 16 mg which is added externally, magnesium stearate 4.5 mg, and film coating premix 18 mg. The preparation process of the azilsartan solid dispersion is simple, almost all pharmaceutical factories have the hardware conditions, and no first and second class organic solvents are used, so that the safety and bioavailability of the azilsartan preparation are effectively improved; the stability of the azilsartan solid dispersion is good, and the dissolution rate and related substances do not obviously decrease after long-time storage.

The invention belongs to the field of organic chemistry, and particularly relates to a low-concentration hydroxylamine composition and a method for preparing an azilsartan intermediate by using the same. The invention provides the hydroxylamine composition with low concentration, high stability and high reaction performance, the hydroxylamine composition has been applied to synthesis of azilsartan, and the azilsartan intermediate synthesized by using the hydroxylamine composition has the advantages of few impurities, high yield, low reaction cost and strong stability, and is suitable for industrial large-scale production.

The invention belongs to the technical field of antigen-antibody detection, and relates to a monoclonal antibody of a non-biphenyl tetrazolsartan drug, a nucleic acid molecule, a detection kit and application thereof. The monoclonal antibody of the non-biphenyl tetrazolsartan medicine comprises a heavy chain variable region (VH) and a light chain variable region (VL), the heavy chain variable region comprises a VH-CDR1, a VH-CDR2 and a VH-CDR3, the light chain variable region comprises a VL-CDR1, a VL-CDR2 and a VL-CDR3, the sequence of the VH-CDR1 is as shown in SEQ ID NO.1, and the sequence of the VH-CDR2 is as shown in SEQ ID NO.2. The monoclonal antibody of the non-biphenyl tetrazolsartan medicine has the advantages that the monoclonal antibody of the non-biphenyl tetrazolsartan medicine can be used for preparing the non-biphenyl tetrazolsartan medicine; the monoclonal antibody capable of simultaneously recognizing azilsartan and telmisartan is successfully prepared by taking candesartan as an immunogen and azilsartan as a coating antigen, the azilsartan and telmisartan are specifically detected, and the problem that the two drugs cannot be covered by the existing immunodetection technology is solved.

The present application relates to the technical field of pharmaceutical preparations, and specifically discloses a kind of azilsartan tablet and its preparation method. A kind of azilsartan tablet, the raw material of the tablet includes the following components in parts by weight: 35-45 parts of azilsartan, 72-76 parts of silicified microcrystalline cellulose, 10-12 parts of low-substituted hydroxypropyl cellulose, 3-7 parts of talc, 0.39-1.04 parts of carnauba wax; The particle size D90 of the azilsartan is 50-80um. In this application, azilsartan, silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and talc having a particle size D90 of 50-80um are first used to press into tablets, and then carnauba wax is used to form a coating on the tablet surface, which not only improves the dissolution rate and dissolution uniformity of the tablet, but also greatly improves the stability of the tablet.

The invention belongs to the technical field of medicine preparation, and particularly relates to a preparation method of Milsartan potassium. Comprising the following steps: (1) mixing azilsartan, alkali, ethyl acetate and N, N '-carbonyldiimidazole, heating, adding 4-hydroxymethyl-5-methyl-1, 3-dioxole-2-ketone, and reacting to obtain a product 1; and (2) cooling the product 1, mixing with potassium isooctanoate, stirring, crystallizing, carrying out suction filtration, and washing to obtain the product 1. The method provided by the invention has the advantages of few steps, easily available raw materials, simple post-treatment and less generation of three wastes, and is suitable for industrial production.

The invention provides a synthesis method of azilsartan medoxomil, which comprises the following steps: reacting azilsartan with thionyl chloride to obtain an intermediate reaction solution, and then adding 4-hydroxymethyl-5-methyl-1, 3-dioxole-2-ketone into the intermediate reaction solution to react to obtain the azilsartan medoxomil. According to the synthesis method provided by the invention, the target product is synthesized through the sulfite intermediate, the yield is higher, the purity is better, the subsequent purification pressure is reduced, in addition, the synthesis method provided by the invention does not need to use a high-toxicity and corrosive reagent, the process safety is improved, the reaction condition is mild and easy to control, and the synthesis method is environment-friendly and high in industrial practicability.

The present invention relates to a nanosuspension composition comprising i) Azilsartan medoxomil and / or pharmaceutically acceptable salts, ii) copovidone iii) at least one surfactant and iv) at least one pharmaceutically acceptable excipient. The said nanosuspension composition has a desirable pharmacokinetic characteristic properties and stability. The invention further relates to a process for the preparation of said nanocomposition and use thereof for the preparation of medicament, which is useful in the treatment of hypertension.

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an aqueous phase preparation process for improving the stability of an azilsartan crystal form. The aqueous phase preparation process for improving the crystal form stability of azilsartan comprises the following steps: mixing an alkaline compound and azilsartan medoxomil to react by taking water as a solvent, cooling and filtering after the reaction is ended, adjusting the pH value of filtrate to 4-6 by taking acetic acid as a pH regulator, crystallizing, filtering and drying to obtain azilsartan. The structural formula of the azilsartan medoxomil is shown in the specification, and R is CH3 or CH2CH3. According to the aqueous phase preparation process for improving the stability of the azilsartan crystal form, provided by the invention, the high-purity and high-stability azilsartan target crystal form is directly obtained by a one-step method, and any organic solvent is not needed for subsequent refining.

The present invention relates to compositions, systems, and methods for treating a subject with an eye condition (e.g., topically) using a composition comprising an ACE-2 receptor antagonist (also known as Angiotensin II Receptor Blocker or “ARB”) (e.g., losartan, telmisartan, valsartan, olmesartan, candesartan, irbesartan, eprosartan, azilsartan, or losartan metabolite EXP3174). In certain embodiments, the eye condition is selected from: i) a corneal scarring fibrosis, ii) a transforming growth factor beta-induced (TGFBI) corneal dystrophy, iii) a conjunctival fibrotic disease, iv) an intraocular fibrotic disease, and v) a conjunctival bleb scarring and / or shunt encapsulation (e.g., following glaucoma surgery).

The invention provides a method for detecting illegal antihypertensive drug components in antihypertensive functional food, which comprises the following steps: firstly, qualitatively screening three compounds, namely rutin, torasemide and azilsartan, in the functional food by adopting high performance liquid chromatography-ultraviolet spectrum, and then further detecting and analyzing by adopting high performance liquid chromatography-mass spectrometry. The method disclosed by the invention has the characteristics of exclusiveness, sensitivity and rapidness, and provides a reliable means for screening, confirming and supervising rutin, torasemide and azilsartan in antihypertensive functional food through methodology verification; the method is mainly suitable for determining the content of rutin, torasemide and azilsartan in foods such as substitutional tea drinks, tablet candies and the like and functional foods such as capsules, tablets and the like.

The invention belongs to the technical field of pesticide preparation and insect prevention and control, and particularly relates to application of Azilsartan as an insect epidermis lipid synthesis inhibitor and in the aspect of pest prevention and control. The invention finds that a small molecule compound Azisartan is an inhibitor of targeted trans-enoyl coenzyme A reductase (TE) for the first time, and results of an in-vitro enzyme activity inhibition test and an insecticidal test prove that the Azisartan can significantly inhibit the activity of a key membrane protein (TE) in an epidermal lipid synthesis pathway of insects, and can be used for preparing a drug for preventing and treating the epidermal lipid synthesis pathway of the insects, so that the drug can be used for preparing a drug for preventing and treating the epidermal lipid synthesis pathway of the insects, and the drug can be used for preventing and treating the epidermal lipid synthesis pathway of the insects and preventing and treating the epidermal lipid synthesis pathway of the insects. And the insecticidal composition has obvious insecticidal activity on Asiatic corn borer, plutella xylostella, tenebrio molitor and tribolium cavaleriei. Meanwhile, the small molecule compound Azilsartan provides a research basis for research and development of insecticides, and is beneficial to research and development of green pesticides.

The application belongs to the field of medicine synthesis, and particularly relates to a preparation process of high-purity azilsartan. Compound I and compound II are added into a solvent, a base and a catalyst are added, compound III is obtained after reaction; compound III and compound IV are added into a solvent, a catalyst and a base are added, compound V is obtained after reaction; compound V is subjected to an oximation reaction with hydroxylamine hydrochloride to obtain VI; VI is subjected to ring closure under the action of CDI, and azilsartan is finally obtained; a reaction equation is as follows: the application can shorten a synthesis route, simplify process steps, select cheap and green and environmental protection raw materials, avoid the use of toxic raw materials, is convenient to operate, has less impurities generated in a synthesis process, improves the purity and yield of product azilsartan, and is convenient for industrialized production.

The invention relates to a preparation method of high-purity azilsartan medoxomil. The preparation method at least comprises the following steps: (1) chlorination; (2) esterification; the method has the advantages of simple operation, high yield, high purity and good stability, and is suitable for industrial production.

The present disclosure relates to co-crystals of sacubitril (or a salt of sacubitril, in particular an alkaline earth metal salt or alkali metal salt) and azilsartan (or a salt of azilsartan, in particular an alkaline earth metal salt or alkali metal salt) and methods of preparation thereof, pharmaceutical compositions containing the co-crystals and uses of the co-crystals, in particular for the treatment of cardiovascular system diseases.

The invention discloses a synthesis method of azilsartan isomer impurities, and relates to the technical field of medicine and medical intermediate preparation. The synthesis method of the azilsartan isomer impurity comprises the following steps: carrying out cyclization reaction on 2, 3-diaminobenzoic acid methyl ester and tetraethyl orthocarbonate to obtain a compound A; and carrying out N-alkylation reaction on the compound A and 4-(bromomethyl)-2 '-cyanobiphenyl under the catalytic action of bis (trimethylsilyl) amino alkali metal salt to obtain the azilsartan isomer impurity. The target product with high purity and high chiral purity is prepared and can be used as a standard substance for azilsartan quality research; the synthetic route of the method has the advantages of mild reaction conditions, simple post-treatment, low price and easily available starting materials, low process cost, and suitableness for industrial production.

The invention relates to the technical field of medicine impurities, in particular to an azilsartan impurity M as well as a preparation method and application thereof. The structural formula of the impurity M is as follows: the impurity M takes methyl 2-((2 '-cyanobiphenyl-4-yl) methylamino)-3-nitrobenzoate A1 as a raw material, and an intermediate A2 is prepared through iron powder reduction under the condition of organic acid; in an organic solvent, the intermediate A2 is subjected to ring closing under the action of acetic acid and triethyl orthoacetate, and an intermediate A3 is prepared; carrying out oximation reaction on the A3 and hydroxylamine in an organic solvent under an alkaline condition to prepare an intermediate A4; carrying out ring closing through a carbonylation reagent to prepare an intermediate A5; and finally hydrolyzing under an alkaline condition to obtain the azilsartan impurity M. The preparation method has the characteristics of simple process, short process period and high purity, and the purity meets the quality research requirement.

The present application discloses a compound tablet for treating hypertension, comprising: an azilsartan layer and an amlodipine layer. The raw materials and auxiliary materials for preparing the azilsartan layer include azilsartan, a binder 1, a disintegrant 1, a diluent 1, and a lubricant 1; the binder 1 is a compound of polyethylene glycol, hypromellose, and pregelatinized starch; and based on 100% by weight of the azilsartan layer, the content of azilsartan is 10-20%, the content of the binder 1 is 1-15%, the content of the disintegrant 1 is 5-10%, the content of the diluent 1 is 60-70%, and the content of the lubricant 1 is 0.1-1%; the raw materials and auxiliary materials for preparing the amlodipine layer include amlodipine besylate, a binder 2, a disintegrant 2, a diluent 2, and a lubricant 2. The compound tablet for treating hypertension obtained by the present invention has good dissolution and stability.

To provide a method for industrially producing azilsartan fine crystals which are stable and easy to formulate.SOLUTION: Provided is a method for producing stable azilsartan having a particle size distribution in terms of an average particle diameter of 3-18 μm. The production method comprises a step of stirring technical azilsartan product powder and a solvent of 1 to 40 times the volume of the technical azilsartan product powder at a stirring temperature between 0°C and a solvent reflux temperature for a stirring time of 5 minutes to 100 hours and does not comprise a step of recrystallization.SELECTED DRAWING: Figure 2

Hydroxylamine, dimethyl sulfoxide (DMSO) and a decomposition product dimethyl sulfide thereof exist in an ethanol recovery product obtained by simply and roughly steaming a centrifugal mother solution of an azilsartan ethyl ester adduct crude product, and the impurities enable the ethanol recovery product to have an unpleasant odor, harm human health and pollute the environment at the same time. In order to solve the problem, the invention provides a method for recovering impurities in ethanol by removing azilsartan ethyl ester, which comprises the following steps of: adding acid to acidify to remove hydroxylamine impurities, desalting and separating out, oxidizing by using sodium hypochlorite to remove thioether substances, and rectifying to remove high-boiling-point dimethyl sulfoxide (DMSO) to obtain clean ethanol with high purity and no peculiar smell. Optimized resource reutilization is achieved, the production cost is reduced, and the sustainable development road is met.