37 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 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 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 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 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.

The invention belongs to the technical field of vacuum freeze drying, and particularly relates to a vacuum freeze drying method of 0.25 g ganciclovir for injection, which comprises the following steps: sequentially carrying out pre-freezing, staged temperature-controlled sublimation drying, temperature-controlled desorption drying, nitrogen charging and plug pressing on ganciclovir injection to obtain a ganciclovir freeze-dried preparation. According to the invention, an optimal freeze-drying one-time drying path is designed, a technical route of staged temperature control sublimation drying is adopted under vacuum, efficient freeze-drying of a low-collapse-temperature product is realized, the whole average total freeze-drying time is shortened to be less than 48 hours on the basis of ensuring the product quality, and the prepared freeze-drying preparation can be quickly redissolved and is free of toxic and side effects. The water content of the freeze-dried product is controlled to be less than 3.0%, and the appearance of the freeze-dried product shows complete white loose blocks.

The invention discloses a method for synthesizing valganciclovir hydrochloride. Using 1,3-dichloro-2-acetoxymethoxypropane as a starting material, monochloroganciclovir is prepared by esterification. , hydrolysis, deprotection into salt and finally obtain valganciclovir hydrochloride. The invention provides a method for synthesizing cganciclovir hydrochloride, which avoids the problem of separation and conversion of N-7 and N-9 isomers in the condensation process of diacetylguanine, and directly synthesizes monochlorovir without ganciclovir. Genanciclovir replaces the synthesis of monoacetyl ganciclovir in the prior art, and avoids the difficult problem of separation of diesters caused by residual ganciclovir. The method has short process steps, simple operation, easy purification and low cost. , conducive to industrial production, suitable for the synthesis of valganciclovir hydrochloride.

The present application provides a new use of ganciclovir for treating, alleviating and / or relieving non-allergic rhinitis characterized by eosinophilia. The present application research shows that the use of ganciclovir in the treatment of nasal allergic symptoms in NARES patients is obviously relieved, and the originally poor efficacy of anti-allergic drugs can be re-exerted, effectively and durably improving the nasal symptoms of refractory NARES patients, effectively improving the symptoms of rhinitis.

The application discloses tumor-related fibroblasts which can be targeted to die, the tumor-related fibroblasts carry polynucleotide fragments of sequences such as SEQ ID No:1 in chromosomes, and the tumor-related fibroblasts have morphology and in-vitro growth rate comparable to other tumor-related fibroblasts.The tumor-related fibroblasts can be specifically induced to die by drugs when co-cultured with other tumor-related fibroblasts, and the drugs are ganciclovir, and the ganciclovir drug concentration ranges from 1 to 100 μM.The application provides a novel and convenient cell construction method for studying the functions of different subtypes of CAFs and application thereof, and the novel CAFs can be targeted to die under the treatment of ganciclovir, weaken the effect of the CAFs of the type on co-cultured tumor cells, and help effectively distinguish the roles of different subtypes of CAFs in tumor occurrence and development.

The technical field of the invention relates to pharmaceutical compositions of 9-(1,3-dihydroxy-2-propoxymethyl) guanine (ganciclovir) that are stable and contain more than 1% water content. One pharmaceutical composition includes ganciclovir having more than about 1% water content, and one or more pharmaceutically acceptable excipients. The ganciclovir retains at least about 97% of its initial purity after one month, at least about 96% of its initial purity after two months, and at least about 95% of its initial purity after three months when stored at 40° C. and 75% RH. In particular, the water content may be between about 2% and about 6%.