40 results about "Atorvastatin calcium" patented technology

The invention relates to the technical field of medicines, in particular to a compound amlodipine atorvastatin calcium tablet and a production mixing device. The compound amlodipine atorvastatin calcium tablet is a core-coated tablet and comprises an inner-layer tablet core containing atorvastatin calcium and an outer-layer tablet layer containing amlodipine besylate, the inner-layer tablet core further comprises meglumine and sodium lauryl sulfate, the mass ratio of meglumine to sodium lauryl sulfate is (0.5-5): 1, the mass ratio of meglumine to sodium lauryl sulfate is (0.5-5): 1, and the mass ratio of meglumine to sodium lauryl sulfate is (0.5-5): 1. And the mass of the meglumine accounts for 1-3% of the total mass of the inner-layer tablet core. The amlodipine and atorvastatin calcium are prepared into the coated tablet, so that two active ingredients in the same tablet are effectively isolated, and the compatibility of the atorvastatin calcium and the amlodipine besylate is remarkably improved; meanwhile, the inner layer and the outer layer of the core-coated sheet are separately granulated before tabletting, so that the problem that the mixing uniformity of total mixed particles is relatively poor when conventional tablets are prepared is effectively solved.

The invention discloses a method for qualitatively identifying oxidation stability of an atorvastatin calcium bulk drug by adopting a multispectral fusion technology, and belongs to the technical field of detection analysis, and the method comprises the following steps: S1, preparing amorphous atorvastatin calcium; s2, grinding, screening, mixing and tabletting the atorvastatin calcium raw material medicine with the crystal form I and the amorphous atorvastatin calcium; s3, detecting the tabletting sample to obtain near infrared spectrum data and Raman spectrum data; s4, performing feature extraction on the near infrared spectrum data and the Raman spectrum data, fusing near infrared spectrum features and Raman spectrum features, and establishing a mathematical model of the fused features after standardization treatment and amorphous atorvastatin calcium content data in the mixed sample; and S5, establishing classification boundaries of oxidability and oxidation stability by using a plurality of atorvastatin calcium samples with known oxidation stability, and identifying the oxidation stability of the unknown atorvastatin calcium sample to be detected according to the classification boundaries by using the mathematical model established in S4.

The invention provides a platycodon grandiflorum extract for preventing or / and treating non-alcoholic fatty liver disease, which is prepared by the following steps: extracting a platycodon grandiflorum medicinal material with absolute ethyl alcohol to obtain a platycodon grandiflorum extract PG-1; and extracting platycodon grandiflorum dregs with water to obtain the platycodon grandiflorum extract PG-2. The invention also provides a preparation method and application of the platycodon grandiflorum extract. The platycodon grandiflorum extract disclosed by the invention has an obvious effect of treating the non-alcoholic fatty liver disease, and compared with an atorvastatin calcium tablet, the medicinal effect of the platycodon grandiflorum extract is equivalent to that of the atorvastatin calcium tablet in two groups of extracts PG-1 and PG-2-1; according to the present invention, the pharmacological effects of the extracts PG-2 and PG-2-2 groups are significantly superior to the pharmacological effects of atorvastatin calcium tablets, and particularly, the separated and purified extracts PG-2-2-1, PG-2-2-2 and PG-2-2-3 can provide significant effects under the milligram-level use amount, and provide the pharmacological effects better than the pharmacological effects of the single platycodin D so as to provide the synergistic effect. In the preparation process of the PG-2-2-3, only ethanol with different concentrations needs to be used for separation and purification, so that the production cost is greatly reduced, and meanwhile, the pollution of chemical reagents is reduced.

The invention discloses application of a polyketone natural product enterocin in preparation of a lipid-lowering medicine, and relates to the technical field of medicine preparation. Research finds that the compound enterocin can regulate a cell ASGR1 target spot and promote cholesterol to flow out of cells, and is different from the action mechanism of statins; the polyketone enterocin can reduce the levels of lipid, TC, TG, LDL-C and the like in an animal body, improve the HDL-C content and promote excretion of TC and TG, part of indexes are equivalent to that of a clinical medicine atorvastatin calcium, part of indexes have remarkable advantages, and the polyketone enterocin has a good application prospect in preparation of the lipid-lowering medicine, and the application proposes that the polyketone natural product enterocin is applied to the lipid-lowering medicine for the first time, so that the application prospect of the polyketone enterocin is wide. A new development direction is provided for the source of the lipid-lowering medicine.

The invention relates to the technical field of mixing equipment, and particularly discloses a high-shear mixing device for preparing atorvastatin calcium, the high-shear mixing device comprises an outer silo, an inner silo, a mixing mechanism and a sliding mechanism, the outer silo comprises an outer silo body and a discharge valve communicated with a cavity, the inner silo is provided with a mixing cavity, the inner silo is coaxially arranged in the outer silo body, and the mixing mechanism is arranged in the outer silo body. The top cover covers the top surface of the inner silo, and a protective cover is arranged on the side wall, close to the mixing cavity, of the top cover in an inverted mode. The mixing mechanism comprises a driving motor arranged on the outer surface of the top cover, a rotating shaft arranged in the axis direction of the mixing chamber, and one end of the rotating shaft sequentially penetrates through the protective cover and the top cover to be in transmission connection with the driving motor, impellers are arranged on the rotating shaft at intervals, a plurality of vertical rods are distributed around the rotating shaft, and the two ends of each vertical rod extend to be connected with the inner wall of the top cover and the bottom wall of the inner silo correspondingly; the two ends of the backflow pipeline are connected with the mixing cavity and the bottom of the outer silo respectively, materials are fully mixed, and meanwhile the mixing efficiency of the materials is improved.

The invention discloses a method for quantitatively detecting the content of an amorphous state in an atorvastatin calcium raw material medicine, and belongs to the technical field of detection and analysis, and the method comprises the following steps: S1, preparing amorphous atorvastatin calcium; s2, grinding, screening and mixing the atorvastatin calcium raw material medicine with the crystal form I and the amorphous atorvastatin calcium; s3, respectively obtaining standardized peak area data and near infrared spectrum data of the melting peak by using a differential scanning calorimetry method and a near infrared spectrum detection technology; s4, preprocessing the near infrared spectrum data, and performing feature extraction to obtain near infrared spectrum features; s5, fusing the near infrared spectrum characteristics and the standardized peak area data of the melting peak, and establishing a mathematical model based on the standardized fusion data and the amorphous atorvastatin calcium content; and S6, calculating by using the mathematical model obtained in S5 to obtain the amorphous state content in the atorvastatin calcium sample to be detected. The method is rapid and accurate, multi-dimensional data are fully utilized, and the quality of the raw material medicine can be effectively controlled.

The utility model discloses a solvent evaporation and recovery device for producing atorvastatin calcium intermediates M4, which comprises a plurality of exhaust pipelines on production equipment, each exhaust pipeline is provided with a fire-retardant single exhalation valve, the exhalation end of each fire-retardant single exhalation valve is connected with one end of an air inlet pipe through a flange, and the other end of the air inlet pipe is connected with the other end of the fire-retardant single exhalation valve. The other end of each air inlet pipe is correspondingly inserted into the bottom of a cooling area of a water cooler, a circulating cooling water pipe is arranged in the water cooler, a plurality of baffle plates are arranged in the cooling area in a crossed mode, the bottom of the water cooler is connected with a liquid inlet of a collecting tank through a flow guide pipe, and air outlet pipes are arranged at the tops of the cooling areas of the water cooler. The top of each gas outlet pipe is connected with a waste gas pipeline, and the waste gas pipeline flows to the gas inlet end of the burn-back furnace. According to the technical scheme, different solvent steam discharged by multiple pieces of production equipment can be collected and uniformly cooled and separated through the cooler, so that the solvent steam discharged by the breather valve is effectively recycled, the use waste of the solvent is avoided, and the cost is saved.

[Problem] To provide an atorvastatin calcium anhydride crystal having higher solubility than that of a conventional hydrate crystal and being more stable than an amorphous form. [Solution] The present invention pertains to an atorvastatin calcium anhydride crystal that exhibits an X-ray diffraction pattern, which has peaks at 2θ = 8.7°, 10.4°, 18.1°, 19.5°, 20.9°, 22.5°, 24.1°, and 25.6°, by X-ray powder diffraction measurement (XRPD) using CuKα radiation.

The present invention discloses the application of atorvastatin calcium in the preparation of an anti-tumor preparation for enhancing dendritic cell vaccines, belonging to the technical field of immune adjuvants. The application of atorvastatin calcium disclosed by the present invention in the preparation of an anti-tumor preparation for enhancing dendritic cell vaccines. Atorvastatin calcium can be used in the preparation of dendritic cell vaccines, significantly up-regulating the expression of pro-inflammatory factors Tnfa, Il6, Il12p40, and Il12p35 and the expression of surface co-stimulatory molecules CD80 and CD86 in dendritic cells, promoting the ability of dendritic cells to mediate the activation of CD4+ T cells and CD8+ T cells and their differentiation into IFNγ-secreting effector cells, and effectively enhancing the anti-tumor effect of dendritic cell vaccines. The present invention provides a method for using atorvastatin calcium in the preparation of dendritic cell vaccines to promote the efficacy of dendritic cell vaccines, providing a new direction for tumor prevention and treatment.

The present invention relates to the technical field of drug preparation, and in particular to a compound amlodipine atorvastatin calcium tablet and a tablet press for its production. The tablet comprises: a mixture of 1-4% amlodipine and 3-12% atorvastatin calcium as active ingredients and pharmaceutically acceptable excipients based on the total weight of the tablet core; the pharmaceutically acceptable excipients are, based on the total weight of the tablet core, 13%-35% alkaline stabilizer, 40%-80% filler, appropriate amount of wetting agent, 3%-10% disintegrant, 0.4%-2% cosolvent, 0.2%-1.2% glidant and 0.2%-1.2% lubricant. The present invention maintains the stability of the drug after dissolution and reduces the surface tension of the drug particles through the cosolvent, so that the drug molecules are more easily dispersed in the solvent. The present invention not only makes the drug have excellent stability, but also can achieve rapid disintegration and fast dissolution rate.

The invention relates to a preparation method of an atorvastatin calcium intermediate. The preparation method comprises the following steps: mixing 3-6 parts of acetonitrile, 0.14-0.16 part of concentrated hydrochloric acid and 1.5-1.8 parts of water for later use; mixing 0.13-0.15 part of sodium bicarbonate and 3-5 parts of water for later use; mixing 4.0-5.5 parts of acetonitrile and 1 part of the atorvastatin calcium intermediate I, heating to dissolve the solid, cooling, adding an acetonitrile hydrochloric acid aqueous solution, and reacting for 2-3 hours to obtain a first mixed solution; adding a sodium bicarbonate aqueous solution into the first mixed solution, and then adding 2.5-5 parts of water to obtain a second mixed solution; cooling the second mixed solution to 0-10 DEG C, stirring for 6-10 hours, and then carrying out suction filtration to obtain a crude product of an atorvastatin calcium intermediate II; and adding 6-9 parts of water into the crude product of the atorvastatin calcium intermediate II, stirring for 2-4 hours, then carrying out suction filtration, washing with water, and carrying out vacuum drying to obtain the atorvastatin calcium intermediate II. According to the method, the atorvastatin calcium intermediate can be more sufficiently separated out, and the molar yield reaches 90% or above, so that the production cost is reduced.

The invention relates to the technical field of pharmaceutical analysis, in particular to a method for detecting a residual solvent in an atorvastatin calcium intermediate by headspace gas chromatography, which comprises the following steps: respectively preparing a reference solution and a sample solution, respectively injecting into a headspace gas chromatograph, recording chromatograms, and calculating by peak area according to an external standard method; the residual solvent comprises methanol, ethanol, dichloromethane, benzene and methyl isopropyl ketone. The method for determining the residual solvents in the atorvastatin calcium intermediate M4, provided by the invention, is quick and simple to operate, high in sensitivity, good in repeatability and accurate in result, and can qualitatively or quantitatively detect the contents of the residual solvents including methanol, ethanol, dichloromethane, benzene and methyl isopropyl ketone in the atorvastatin calcium intermediate M4 at the same time; a good reference is provided for controlling organic solvent residues from raw material introduction, intermediate by-products and a production process of the atorvastatin calcium intermediate M4, and the quality of the atorvastatin calcium intermediate M4 is ensured, so that the safety of clinical medication is improved.

The invention belongs to the field of pharmaceutical preparations, and discloses an atorvastatin tablet preparation for treating hyperlipidemia and a preparation process of the atorvastatin tablet preparation. The preparation process comprises the following steps: (1) pretreating raw materials; (2) pretreating auxiliary materials; (3) preparing quick-release layer particles: stabilizing atorvastatin calcium nanocrystals by adopting an anti-solvent precipitation method and combining with a surfactant; (4) preparing sustained-release layer particles: preparing amorphous sustained-release layer particles of atorvastatin calcium by adopting a hot-melt extrusion method, and realizing targeted sustained release of intestinal tracts in combination with a pH-dependent polymer Eudragit L100-55; (5) performing double-layer tabletting: performing filling twice to obtain a high-hardness double-layer tablet; and (6) coating. According to the invention, the hot melt extrusion is creatively combined with the nanocrystal technology, the problems of low solubility and photothermal sensitivity are solved, the process continuity is realized, the effective content time of the blood fat reducing medicine in the body is prolonged, the balance blood concentration of the medicine in the body is favorably kept, and the medicine taking compliance of a patient is improved.

The invention provides an ezetimibe and atorvastatin calcium compound coated tablet and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The ezetimibe and atorvastatin calcium compound coated tablet provided by the invention comprises an atorvastatin calcium tablet core, an isolating layer coated on the surface of the atorvastatin calcium tablet core, an ezetimibe medicine applying layer coated on the surface of the isolating layer and a coating layer coated on the surface of the ezetimibe medicine applying layer, the components of the isolating layer comprise a film-forming material and a first plasticizer, and the weight gain of the isolating layer is 4-6%. The ezetimibe and atorvastatin calcium compound coated tablet provided by the invention is good in stability, is convenient to prepare by adopting conventional coating equipment (such as a high-efficiency coating machine), does not need special production equipment such as a double-layer tablet press and a core-spun tablet press, and is low in production cost and simple in production process.

The invention relates to the technical field of medicines, in particular to a sustained-release pharmaceutical composition for treating hypertension and a tablet press for preparing the sustained-release pharmaceutical composition. The double-layer tablet consists of a quick release part and a slow release part, and every 1000 tablets comprise the following components: the slow release part: 20.0 g of atorvastatin calcium; 100.0 g of ethyl cellulose; 2.0 g of sodium bicarbonate; 5.0 g of calcium hydrogen phosphate; 2.0 g of talcum powder and the like; a quick release part: 6.9 g of amlodipine besylate; 40.0 g of microcrystalline cellulose; 20.0 g of lactose; and 3.0 g of calcium hydrophosphate and the like. The atorvastatin calcium with a short half-life period is prepared into a sustained-release part, so that one-time administration every day is realized, and the contradiction of administration frequency caused by half-life period difference of a compound preparation is solved; the atorvastatin calcium sustained-release design reduces the fluctuation of blood concentration and reduces the risk of gastrointestinal tract stimulation; the amlodipine quick-release part avoids delayed effect and maintains the blood pressure to be stable.

The invention discloses a preparation method of ezetimibe atorvastatin calcium tablets. The ezetimibe atorvastatin calcium tablets are prepared from atorvastatin calcium, ezetimibe, microcrystalline cellulose, lactose, polyvinylpolypyrrolidone, hydroxypropyl cellulose, magnesium stearate and colloidal silicon dioxide through a specific process. Comprising the following steps: sieving micronized atorvastatin calcium, ezetimibe, a filler, a disintegrating agent and other auxiliary materials, and carrying out first-step mixing in an environment in which the temperature and humidity are strictly controlled to prepare total mixed powder; then adding a lubricant and carrying out second-step short-time low-speed mixing to obtain final mixed particles; and finally, carrying out high-speed tabletting under the condition of controlling the temperature of a punch of a tabletting machine, and optionally carrying out film coating. The core technical problems that the content uniformity of low-dose ezetimibe in a compound preparation is poor and the stability of atorvastatin calcium is poor are effectively solved, and the prepared tablet is high in content uniformity, good in dissolution behavior, excellent in stability and suitable for industrial production.

The application belongs to the technical field of synthesis of medical intermediates, and particularly relates to a synthesis method of a chiral intermediate of atorvastatin calcium. 1,3-propanediol is used as raw material, a silicon-based protection reaction is carried out, and then oxidation is carried out, a ring addition reaction occurs under the catalysis of a chiral catalyst and a lithium salt, and a first chiral center is introduced; then, t-butyl acetate is added to carry out a ring opening reaction, a Narasaka-Prasad reduction reaction is carried out to induce a second chiral center; 2,2-dimethoxypropane is added to protect cis diol, finally, tetrabutylammonium fluoride is added to remove the silicon-based reaction, and a Fukuyama amine synthesis method is used to replace the hydroxyl group with the amino group to obtain the chiral intermediate of atorvastatin calcium. The application uses 1,3-propanediol which is cheap and easy to obtain as raw material, and various dangerous, toxic and expensive drugs are not used in the synthesis route process, the method has a simple route, high yield and good repeatability, and can be used for industrial production.

An atorvastatin calcium albumin nanoparticle, and a preparation method therefor and the use thereof. The atorvastatin calcium albumin nanoparticle consists of atorvastatin calcium and serum albumin in a mass ratio of 1:3-1:10. The preparation method comprises: adding absolute ethanol to atorvastatin calcium to obtain an organic phase, adding deionized water to serum albumin and adjusting the pH to obtain an aqueous phase, adding the organic phase in a dropwise manner to the aqueous phase, adding a glutaraldehyde solution for cross-linking, removing anhydrous ethanol, performing centrifugation, and collecting the lower precipitate layer to obtain the atorvastatin calcium albumin nanoparticle.

The invention discloses a semen cassiae naphthopyrone extraction enriched product as well as a preparation method and application thereof. The preparation method comprises the following steps: crushing semen cassiae, sieving, carrying out ball milling, carrying out ultrasonic extraction, carrying out vacuum concentration on an extract, and freeze-drying to obtain crude extract powder, carrying out gradient elution by virtue of AB-8 macroporous resin, and freeze-drying to obtain a naphthopyrone extraction enriched product; pharmacological experiments show that the enriched product can significantly reduce the levels of triglyceride, total cholesterol and low-density lipoprotein of mice induced by high-fat diet, and also can regulate the blood sugar level, and the lipid and blood sugar reducing level of the enriched product is close to that of a positive drug atorvastatin calcium group; according to network pharmacological mechanism research, it is speculated that the enrichment is mainly used for improving the metabolic syndrome through a phenotypic pathway with lipid and atherosclerosis as the core, and the metabolic syndrome is possibly activated by a PPAR signal pathway (especially PPAR gamma).

The invention discloses a preparation method of an atorvastatin calcium oral suspension, and belongs to the technical field of pharmaceutical preparations. The preparation method provided by the invention comprises the following steps: adding part of water into a liquid preparation container, heating and carrying out nitrogen filling treatment, then adding a preservative and part of a suspending aid, and stirring to obtain first liquid; the suspending aid comprises Arabic gum; adding a part of water into another container, carrying out nitrogen charging treatment, then adding the remaining suspending aid and atorvastatin calcium, carrying out shearing dispersion, then mixing with the second liquid, then adding a flavoring agent and the remaining water, carrying out volume metering and nitrogen charging, and controlling the dissolved oxygen content to be less than 3mg / L; and filling into a bottle purged by nitrogen, carrying out headspace nitrogen charging after the filling is finished, so that the residual oxygen content in the bottle is below 5%, and sealing a cover. According to the invention, the physical stability and chemical stability of the atorvastatin calcium oral suspension are remarkably improved, and meanwhile, compared with the existing dosage form, the dosage form of the obtained oral suspension has better patient compliance and flexibility.

1. The name of the product of this design: packaging box (Alectin Atorvastatin Calcium Tablets). 2. Purpose of this design product: used as outer packaging for medicines. 3. The design key points of this appearance design product are: the combination of shape, pattern and color. 4. The picture or photo that best illustrates the key points of the design: main view. 5. The design for which protection is sought includes color.

The invention belongs to the field of biological medicine, and discloses a synthesis process of atorvastatin calcium, which comprises the following steps: by taking a compound 1 and a compound 2 as raw materials and acid as a catalyst, carrying out Paal-Knorr reaction on the compound 1 and the compound 2 under the condition of heating reflux, and separating water generated by the reaction by using a water segregator in the reaction process; after the reaction is finished, sequentially crystallizing and recrystallizing to obtain a compound 3; the method comprises the following steps: by taking methanol as a reaction solvent, carrying out deprotection reaction on a compound 3 under an acidic condition to obtain a compound 4, carrying out salt forming reaction on the compound 4 under an alkaline condition to obtain a compound 5, carrying out salt forming reaction on the compound 5 and hydrated calcium acetate to obtain atorvastatin calcium, and refining to obtain an atorvastatin calcium product. In the synthesis process of the compound 3, the reaction process is propelled by adopting the water segregator, so that the reaction completion time is shortened by more than 10 hours; the crystallization process of the compound 3 is optimized by changing the solvent proportion. # imgabs0 #

The invention discloses a method for determining a dissolution curve of atorvastatin calcium in an acidic medium, and belongs to the technical field of pharmaceutical analysis. The determination method provided by the invention comprises the following steps: dissolving an atorvastatin calcium drug to be determined in an acidic dissolution medium under a stirring condition, taking out a dissolution solution at different dissolution times, centrifuging, taking a supernatant, adding the supernatant into a stabilizer, and uniformly mixing to obtain a test solution; detecting the content of atorvastatin calcium in the test solution by adopting high performance liquid chromatography to obtain dissolution rates at different time; establishing a dissolution curve according to the dissolution rate and the dissolution time; wherein the stabilizer is a mixed solution of an organic solvent and an alkali metal hydroxide water solution. According to the method, through the solubilizing effect of the organic solvent and the dual synergistic mechanism of the alkaline environment, the degradation reaction and drug precipitation process continuously occurring after the sample is taken out is effectively inhibited, and the accuracy of the dissolution rate detection result is remarkably improved.

The invention relates to a preparation method of atorvastatin calcium tablets, and belongs to the technical field of pharmaceutical preparations. The invention provides a preparation method of an atorvastatin calcium tablet, which comprises the following steps: continuously mixing a nanoscale atorvastatin calcium raw material with bovine serum albumin sustained-release microspheres through a microchannel reactor to form a drug-loaded compound; uniformly mixing the obtained drug-loaded compound with a filling agent microcrystalline cellulose and lactose blend, a disintegrating agent cross-linked sodium carboxymethyl cellulose and a lubricating agent magnesium stearate, preparing particles by adopting a dry granulation process under the rolling pressure of 5-15MPa, and directly tabletting the particles to obtain a plain tablet, namely the tablet. The surface of the tablet is coated with a hydroxypropyl methyl cellulose nanocrystalline layer through an electrostatic spray coating method to form a quick release-slow release double-layer structure, the particle size of the nanoscale atorvastatin calcium raw material is 1-100 nm, and the particle size of the bovine serum albumin sustained release microspheres is 425 nm; the invention has the advantages of good component release effect, high dissolution rate, good stability, good compound compatibility and the like.

The invention discloses a blood fat reducing composition containing supramolecular group composite peptide, which is composed of raw materials and basic energy substrates, the raw materials comprise supramolecular group composite peptide, natto freeze-dried powder, black pepper extract and bamboo leaf flavone, and the basic energy substrates comprise proteins, dietary fibers, fatty acids and / or lipids; the composite peptide is composed of soybean peptide and bitter gourd peptide. The composition prepared by compounding the components of specific types and dosages has the effects of remarkably reducing the triglyceride level, reducing the content of low-density lipoprotein cholesterol and increasing the content of high-density lipoprotein cholesterol, and part of the composition can also cooperate with statin western medicines (such as atorvastatin calcium) to achieve the effects of enhancing the effect of reducing blood fat and improving the blood fat content. The effect of assisting in improving or preventing and reducing blood fat is achieved. Therefore, the method can be used for developing functional foods and medicines and has a considerable market prospect.

The invention relates to the technical field of medicines, and discloses a method for detecting related substances of an ezetimibe atorvastatin calcium composition, a sample solution is detected by adopting a liquid chromatography, octadecylsilane / pentafluorophenyl bonded silica gel is used as a filler, and a gradient elution method is adopted. One method can detect more than 20 related substances in ezetimibe and atorvastatin calcium at the same time, the separation and detection efficiency is improved, and the method is high in specificity, high in separation degree, high in sensitivity and good in accuracy and has positive effects and practical application value.

The invention belongs to the technical field of medical chemistry, and particularly relates to a preparation method of an atorvastatin calcium intermediate, which realizes continuous preparation through a fixed bed reactor.

The invention discloses a novel synthesis process of an atorvastatin intermediate. A compound III is prepared from a compound I and a compound II; dissolving the compound III in an organic solvent, adding a reducing agent, carrying out a heating reaction for 4-6 h, adding diluted hydrochloric acid after the reaction is finished, carrying out a neutralization reaction until the product is neutral, and separating the product to obtain a compound IV. The method has the beneficial effects that the process steps are few, the used chemical reagent raw materials are easy to obtain, the price is low, the process is environment-friendly, the operation is simple and convenient, the risk is low, and the method is a green synthesis process suitable for industrial production. According to the process provided by the invention, the synthesis steps of ATS-8 and ATS-9 are effectively shortened, the total yield of synthesis of atorvastatin calcium is improved, and the production cost is effectively reduced; the method is good in product selectivity, high in yield, less in waste, convenient in product post-treatment and suitable for industrial expanded-scale production.

The invention relates to a pharmaceutical composition for treating cardiovascular diseases and a preparation method thereof, in particular to a pharmaceutical composition containing levamlodipine besylate and atorvastatin calcium, and the pharmaceutical composition is used for treating mixed hypertension and hyperlipidemia, has a synergistic effect and can effectively reduce blood pressure and blood fat levels. By controlling the granularity and crystal form of levamlodipine besylate and atorvastatin calcium, the dissolution rate and stability of the medicine are optimized. The preparation method adopts a direct powder tabletting process, so that the production process is simplified, the production efficiency is improved, and meanwhile, the uniformity and the stability of the medicine are ensured. In-vitro dissolution experiments show that the dissolution rate of the composition reaches 90% or above within 15 minutes, and the composition has good bioavailability.

The invention provides a synthesis method of atorvastatin calcium. The preparation method comprises the following steps: by taking A8 as a starting raw material, carrying out reduction reaction under a sodium borohydride / zinc chloride system to generate an intermediate 1; carrying out ring closing reaction on the intermediate 1 and M4 at high temperature to generate an intermediate 2; and carrying out hydrolysis reaction on the intermediate 2 in sulfuric acid to directly generate an intermediate 3, and salifying the intermediate 3 with calcium chloride to generate atorvastatin calcium. The synthesis method is safe and environment-friendly, simple in chemical reaction and post-treatment steps, relatively high in yield and suitable for industrial large-scale production.