44 results about "Ganciclovirum" patented technology

Stereochemically defined dipeptide esters of nucleoside-analogous antiviral agents including acyclovir and ganciclovir are provided. Certain of these stereochemically defined dipeptide esters are found to have unexpectedly enhanced delivery to and uptake by ocular tissues, crossing the blood-ocular barrier more effectively than other stereochemically defined dipeptide esters. For example, (L-Val)-(D-Val)-acyclovir was found to be taken up more effectively into corneal tissue than were underivatized acyclovir, monoesters (L-Val)-acyclovir or (D-Val)-acyclovir, or diester (L-Val)-(L-Val)-acyclovir.

A process for the preparation of valganciclovir with triacetyl ganciclovir (V) as a starting material, comprising the following steps: selective hydrolysis, reacting with a coupling agent and a solvent, followed by hydrolysis under basic conditions and hydrogenolysis in the presence of a catalyst.

The invention discloses a method for determining content of guanine in ganciclovir, which belongs to the technical field of drug analysis and detection, and adopts a high-performance liquid chromatography as the detection method. The invention provides a normal phase detection method, which enables the guanine to have good peak shapes in a liquid chromatographic column and being able to be completely separated from ganciclovir for facilitating quantitative analysis. The method is characterized by comprising the steps of: taking n-hexane-isopropanol as a mobile phase; adopting cellulose-tris (4-methylphenyl formate) silica gel as a filler; taking the n-hexane- isopropanol (80:20) as the mobile phase, wherein the flow rate is 0.8-1.5 ml / min, the column temperature is 25-35 DEG C, the detection wavelength is 252 nm and a sample injection quantity is 10 mu L; and waiting for elution. The method of the invention is simple, reliable and high in sensitivity, has good resolution and reproducibility, is precise and reliable in result, and can be used for controlling the content of guanine in ganciclovir.

The invention discloses a novel valganciclovir hydrochloride synthesis method. The method includes: taking ganciclovir as a raw material, adopting ortho-ester for protecting a hydroxyl radical, then subjecting to condensation with N-carbobenzoxy-L-valine, and performing hydrolysis reaction to obtain N-carbobenzoxy valganciclovir; performing hydrogenation reduction reaction to obtain valganciclovir hydrochloride. The product purity reaches 99.0% or above and accords with United States Pharmacopeia standards.

The invention discloses a method for synthesizing valganciclovir hydrochloride, which comprises the following steps: with 1,3-dichloro-2-acetoxymethoxypropane as an initial raw material, preparing monochlorinated ganciclovir, and carrying out esterification, hydrolysis and deprotection salification to finally obtain the valganciclovir hydrochloride. The invention provides a synthesis method of siganciclovir hydrochloride, which avoids the problem of separation and conversion of N-7 and N-9 isomers in the diacetyl guanine condensation process. The method directly synthesizes monochlorinated ganciclovir without using ganciclovir, instead of the synthesis of monoacetyl ganciclovir in the prior art, so that the method avoids the problem of diester compound separation caused by ganciclovir residues, has the advantages of short process steps, simple operation, convenient purification and low cost, is beneficial to industrial production, and is suitable for synthesis of valganciclovir hydrochloride.

The invention discloses an energy-saving grinding device before impurity removal of a ganciclovir crude product, belongs to the technical field of ganciclovir grinding, and aims to solve the problems of high energy consumption and long time during grinding of the ganciclovir crude product. The device comprises a shell and an inner cylinder arranged in the shell, and further comprises a grinding roller arranged in the inner cylinder, the inner cylinder is composed of a third grinding cylinder, a second grinding cylinder, a first grinding cylinder and a collecting disc, the diameters of the third grinding cylinder, the second grinding cylinder and the first grinding cylinder are gradually decreased, and the inner cylinder is matched with the grinding roller which is fixedly connected and provided with inclined grinding teeth on the outer edge to form a multi-layer progressive grinding space; the grinding teeth incline and rotate to generate an inclined downward extrusion force, so that the material crushing is more efficient, the grinding degree can be accurately controlled, and the material is sequentially subjected to coarse grinding and accurate grinding, the motor drives the grinding roller to rotate forwards and backwards, and the material transfer and circulation are realized through the cooperation of the linkage mechanism and the discharging control mechanism, the anticlockwise rotation grinding of the motor and the clockwise rotation of the motor; the overall grinding efficiency is greatly improved, the grinding period is effectively shortened, and the efficiency is improved compared with traditional grinding equipment.

The invention belongs to the technical field of medicine preparation, and particularly relates to a ganciclovir injection and a preparation process thereof. The ganciclovir injection comprises ganciclovir and a pH modifier. According to the ganciclovir injection, water for injection is adopted as a solvent, and a plastic ampoule is adopted as an inner packaging container in direct contact with the ganciclovir injection. The mechanism that the ganciclovir injection is prone to generate muddy sediment is deeply analyzed and studied, and the essence reason for easily generated unqualified visible foreign matter and increase of insoluble particles is found. Compared with the prior art, when the ganciclovir injection is prepared, a plastic container packaging material is selected, medicine liquid and the packaging material both have good compatibility, and therefore the visible foreign matter and the insoluble particles are remarkably reduced.

The invention relates to a novel ganciclovir compatible impurity as shown in a formula (I). Repeated tests show that the impurity is very easy to generate in the compatibility process of ganciclovir and a 5% glucose solution. The structure of the impurity is determined by characterizing the impurity shown in the formula (I), and the impurity can be used as a reference substance for quality research of ganciclovir preparations (such as ganciclovir preparations for injection), has important significance, and can avoid reduction of the clinical curative effect of ganciclovir due to too high impurity content. The invention further relates to a preparation method of the ganciclovir compatible impurity shown in the formula (I), the method is simple to operate, and the purity of the obtained product can reach 95% or above. # imgabs0 #

The energy-saving grinding device before the impurity removal of ganciclovir crude product belongs to the technical field of ganciclovir grinding, and aims to solve the problems of high energy consumption and long time during the grinding of ganciclovir crude product. The device comprises a shell, an inner cylinder arranged in the shell, a grinding roller arranged in the inner cylinder, and a collecting disc. The inner cylinder is composed of a third grinding cylinder, a second grinding cylinder, a first grinding cylinder and the collecting disc. The grinding roller is fixedly connected and has inclined grinding teeth on the outer edge. The grinding teeth form a multi-level progressive grinding space in cooperation with the grinding roller. The inclined grinding teeth generate a downward extrusion force, the material crushing is more efficient, the grinding degree can be accurately controlled, the material can be sequentially coarsely ground and finely ground, the grinding roller is driven by a motor to rotate in the forward and reverse directions, the motor is connected with a linkage mechanism and a discharging control mechanism, the motor rotates counterclockwise to grind, and clockwise rotation realizes material transfer and circulation, thereby greatly improving the overall grinding efficiency, effectively shortening the grinding period, and improving the efficiency compared with the traditional grinding equipment.

The invention discloses a preparation method of ganciclovir, and belongs to the technical field of organic synthesis. The process comprises the following four steps of: 1, reacting glycerol and phenylboronic acid in an organic solvent to generate an intermediate 1; 2, reacting the intermediate 1, paraformaldehyde and anhydrous magnesium sulfate in an organic solvent under the action of hydrogen chloride to generate an intermediate 2; 3, reacting the intermediate 2 with N-acetylguanine under the action of alkali to generate an intermediate 3; and 4, reacting the intermediate 3 in an organic solvent under the action of alkali and hydrogen peroxide to generate ganciclovir. According to the technical scheme, operation is easy, convenient and stable, products in all steps are easy to separate, the yield is high, environment friendliness is achieved, and a new synthesis way is provided for the compound.

The invention relates to a method for preparing high-purity triacetylganciclovir, comprising the steps of mixing diacetylguanine, triacetylganciclovir N7 isomer, ganciclovir side chain and solvent I, adding a catalyst, heating to carry out a condensation reaction; vacuum concentrating the obtained product to concentrate solvent I to dryness; adding solvent II, heating and refluxing to dissolve, then slowly cooling to a predetermined temperature and keeping the temperature, so that triacetylganciclovir N7 isomer slowly precipitates, and centrifuging to obtain triacetylganciclovir N7 isomer and mother liquor I; concentrating mother liquor I to dry solvent II, and concentrating at normal pressure during the concentration process, and then concentrating under reduced pressure until no solvent II is distilled out; adding mixed solvent III to the obtained product, heating and refluxing, cooling and crystallizing, centrifuging to obtain triacetylganciclovir, and drying to obtain the finished product. The beneficial effects are as follows: the separation method is simple to operate, has a high safety factor, and a high separation efficiency, and triacetylganciclovir and its N7 isomer have high purity, both of which are ≥99%, and are suitable for industrial production.

The invention relates to the field of biological medicine, in particular to application of a reagent for up-regulating PEX5 expression level or improving PEX5 protein activity in preparation of a medicine for treating demyelination diseases. A lentivirus infection experiment and lysolecithin are utilized to induce a mouse demyelination model, it is found that PEX5 can promote differentiation and maturation of oligodendroglia cells and remyelination and repair of demyelination mice, and ganciclovir can promote differentiation of the oligodendroglia cells and effectively relieve demyelination diseases by promoting expression of PEX5. PEX5 can be used as a drug intervention target, and a drug for promoting expression or function of PEX5 can be used as a potential therapeutic drug for demyelination diseases.

The invention discloses a method for detecting an impurity K in ganciclovir and a method for separating the impurity. The method comprises the following steps: detecting a test solution containing ganciclovir by adopting high performance liquid chromatography, wherein a chromatographic column adopted by the high performance liquid chromatography is a cation exchange chromatographic column, mobile phases comprise a mobile phase A and a mobile phase B, and the mobile phase A is a phosphoric acid aqueous solution containing 0.012 M ammonium dihydrogen phosphate, in the phosphoric acid aqueous solution, the volume percent of phosphoric acid is 0.12%, the mobile phase B is acetonitrile. In combination with a specific elution mode, the method not only can realize effective separation and detection of the impurity K, but also can completely elute other known impurities, and is beneficial to the service life of a chromatographic column.

A process for the preparation of valganciclovir with triacetyl ganciclovir (V) as a starting material, comprising the following steps: selective hydrolysis, reacting with a coupling agent and CBZ valine and a solvent, followed by hydrolysis under basic conditions and hydrogenolysis in the presence of a catalyst.

The invention provides ganciclovir sodium monohydrate, which is radiated by Cu-K alpha, and an X-ray powder diffraction pattern of the ganciclovir sodium monohydrate comprises the following diffraction peaks expressed by angle 2 theta: 4.2 degrees + / -0.1 degrees, 18.1 degrees + / -0.1 degrees, 23.2 degrees + / -0.1 degrees, 8.44 degrees + / -0.1 degrees, 15.28 degrees + / -0.1 degrees, 20.381 degrees + / -0.1 degrees, 21.24 degrees + / -0.1 degrees, 24.441 degrees + / -0.1 degrees, 30.98 degrees + / -0.1 degrees and 31.96 degrees + / -0.1 degrees. The X-ray powder diffraction pattern of the ganciclovir sodium monohydrate is basically as shown in Figure 1. According to the preparation method provided by the invention, water and ganciclovir react, 95% ethanol is added for crystallization after the reaction is finished, and the monohydrate crystal form of ganciclovir sodium is prepared; operation is simple, and reaction conditions are mild and easy to control.

The invention discloses a preparation method of ganciclovir powder injection and a filter press used therefor, belonging to the technical field of pharmaceutical production. The sodium chloride aqueous solution is mixed evenly, and finally ganciclovir powder injection is obtained by freeze-drying; the filter press includes a bracket, a thrust plate, a pressure plate, a filter plate, a filter cloth and a driving part, and the filter cloth and the filter plate are separated and installed in the On the frame body, the material of the frame body is polypropylene, and the upper and lower edges of the frame body are provided with deep clamping grooves and shallow clamping grooves corresponding to the upper and lower guide rods, which can be easily installed and disassembled on the upper and lower guide rods. The filter plates are respectively provided with the first sealing components, and the opposite surfaces of the two adjacent filter plates are respectively provided with the second sealing components. The impurity content of the ganciclovir powder injection prepared by the method provided by the present invention is relatively small, and the effect of the ganciclovir powder injection can be improved; Clean and replace.

Human cytomegalovirus vectors comprising heterologous antigens are disclosed. The vector derived from the TR strain is ganciclovir-sensitive, contains active US2, US3, US6, US7, and UL131A genes, and has a deleterious or inactivating mutation in the UL82 gene that prevents expression of pp71.

The invention belongs to the field of medicine synthesis, and discloses a preparation method and application of ganciclovir. According to the preparation method, N-(6-carbonyl-6, 9-dihydro-1H-purine-2-yl) acetamide and 2-hydroxy-1, 3-propylene diacetate are subjected to condensation with chloroformyl chloride at the same time, an obtained intermediate is subjected to hydrolysis, and ganciclovir is obtained. The preparation method of ganciclovir can effectively improve the utilization rate of raw materials, reduce the use cost of the raw materials in the production process, shorten the process flow, and reduce the occurrence of side reactions and the use amount of solvents. The preparation method is suitable for preparing ganciclovir, and the prepared ganciclovir is used for preparing ganciclovir for injection.

The invention belongs to the field of medicines, and relates to a method for detecting a main component (ganciclovir) and / or related substances in ganciclovir ophthalmic gel. Specifically, the method comprises a step of removing carbomer in ganciclovir ophthalmic gel and a step of performing HPLC (High Performance Liquid Chromatography) analysis, and the detection method disclosed by the invention is high in specificity and stable in retention time of a chromatographic peak; according to the method for removing the carbomer from the sample, ganciclovir is good in solubility, the solution is stable, the carbomer can be effectively removed, a chromatographic column is not damaged, and the ganciclovir has a good application prospect.

Stereochemically defined dipeptide esters of nucleoside-analogous antiviral agents including acyclovir and ganciclovir are provided. Certain of these stereochemically defined dipeptide esters are found to have unexpectedly enhanced delivery to and uptake by ocular tissues, crossing the blood-ocular barrier more effectively than other stereochemically defined dipeptide esters. For example, (L-Val)-(D-Val)-acyclovir was found to be taken up more effectively into corneal tissue than were underivatized acyclovir, monoesters (L-Val)-acyclovir or (D-Val)-acyclovir, or diester (L-Val)-(L-Val)-acyclovir.

The invention discloses ganciclovir for injection and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. According to the preparation, through innovative auxiliary material combination and process optimization, the problems that in the prior art, high pH value irritation is high, a freeze-drying structure is prone to collapse, and redissolution performance is poor are solved. The ganciclovir freeze-drying preparation comprises ganciclovir, trehalose, poloxamer 188 and sodium hydroxide, and through auxiliary material innovation and freeze-drying process improvement, the stability of the drug is improved.

The invention provides a Gancilorvir dispersable tablet and its preparation, wherein the dispersion tablet comprises 62.5 wt% of Ganciclovir, 10-25% of crystalline cellulose, or calcium hydrogen phosphate and / or starch, 1-10% of sodium carboxymethylstarch, or low substituted methylcellulose propylene glycol ether and / or cross bonding polyvinylpyrrolidone or crosslinked sodium carboxymethylcellulose, 0.1-1.4% of polyvinylpyrrolidone, or methyl hydroxypropylcellulose, 5-15% of lactose, 0.5-1.4% of magnesium stearate. The preparing process comprises sieving, mixing, granulating, drying, and tabletting.

The invention discloses a ganciclovir composition for injection and a freeze drying process of the ganciclovir composition. The ganciclovir composition for injection comprises ganciclovir and sodium hydroxide, and is prepared by freeze drying of a liquid medicine containing 150-180 mg / mL of ganciclovir. The freeze drying process comprises the following steps: sequentially pre-freezing, sublimationdrying and desorption drying of the ganciclovir liquid medicine to obtain a ganciclovir powder injection. The prescription is simple and reasonable, the process is simple and easy to operate, the obtained product has excellent stability and redissolution performance, the problems that moisture is not easy to remove in the freeze drying process and the freeze-dried product structure is easy to collapse and shrink due to high solid content are solved on the premise of not greatly prolonging the freeze drying period, and the quality stability of the product and the safety of clinical medicationare fundamentally ensured.

The invention discloses a chemical detection method for oculent.The chemical detection method relates to the technical field of chemical analysis, the oculentcomprises ganciclovir, yellow vaseline, lanolin, liquid paraffin, white vaseline, glycerin, ethylparaben and vitamin E. The method comprises the following steps that (a) the content of ganciclovir in the oculent.The content of ganciclovir in the oculent.The content of ganciclovir in the oculentis is measured through a high performance liquid chromatography; (b) carrying out quality control on the lanolin raw material, namely measuring an acid value, a saponification value and a peroxide value; (c) carrying out wool fat related quality monitoring on the oculentum finished product, wherein the wool fat related quality monitoring comprises determination of a peroxide value; according to the method, chromatographic conditions are optimized, an exclusive impurity detection method is established, and raw materials are associated with finished product detection, so that the quality control problem of ganciclovir oculentum is solved.

The invention discloses a ganciclovir related substance detection method, and relates to the field of pharmaceutical analysis. According to the ganciclovir related substance detection method, an octadecyl silane bonded silica gel chromatographic column is used, 0.012 mol / L ammonium dihydrogen phosphate solution-methanol (98-95: 2-5, V / V) is used as a mobile phase A, methanol is used as a mobile phase B, gradient elution is carried out, and the related substances in ganciclovir are detected. The pH value of the ammonium dihydrogen phosphate solution is adjusted to 2.5-3.5 by using a phosphoric acid solution. The method can be used for rapidly and effectively separating various potential trace related substances in ganciclovir raw material medicines, has the advantages of stable base line, attractive peak shape, good separation degree between a main peak and adjacent impurities and between the adjacent impurities, high durability and the like, and can be used for efficiently realizing qualitative and quantitative treatment of various related substances in ganciclovir. The method is suitable for rapid quality monitoring of ganciclovir in industrial mass production, and has important significance for product quality control.

The invention discloses a novel valganciclovir hydrochloride synthesis method. The method includes: taking ganciclovir as a raw material, adopting ortho-ester for protecting a hydroxyl radical, then subjecting to condensation with N-carbobenzoxy-L-valine, and performing hydrolysis reaction to obtain N-carbobenzoxy valganciclovir; performing hydrogenation reduction reaction to obtain valganciclovir hydrochloride. The product purity reaches 99.0% or above and accords with United States Pharmacopeia standards.

The invention relates to an external preparation of ganciclovir and application thereof. The external preparation is prepared from the following raw materials: ganciclovir, a polymer matrix and a pH regulator. Compared with acyclovir gel, the external preparation of ganciclovir disclosed by the invention has a better antiviral effect.