CN115504977B - Preparation method of ganciclovir and preparation method of ganciclovir for injection - Google Patents
Preparation method of ganciclovir and preparation method of ganciclovir for injection Download PDFInfo
- Publication number
- CN115504977B CN115504977B CN202211162515.2A CN202211162515A CN115504977B CN 115504977 B CN115504977 B CN 115504977B CN 202211162515 A CN202211162515 A CN 202211162515A CN 115504977 B CN115504977 B CN 115504977B
- Authority
- CN
- China
- Prior art keywords
- ganciclovir
- preparation
- injection
- dissolution
- crude product
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a preparation method of ganciclovir and a preparation method of ganciclovir for injection, belonging to the technical field of medicine preparation, wherein the ganciclovir is prepared by adding 68-70wt% of isopropanol water solution into sodium hydroxide for dissolution, then adding ganciclovir crude product, heating to 50-55 ℃ for dissolution, maintaining the temperature of 50-55 ℃ for decolorization, dropwise adding acid water solution for regulating the pH value, and slowly cooling for crystallization; the ganciclovir for injection is sodium hydroxide aqueous solution, and is prepared by adding ganciclovir for dissolution, then supplementing water to full dose, decoloring, filtering and freeze-drying. According to the invention, the difference between the solubility of ganciclovir and 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine in a specific solvent system is utilized, and the ganciclovir crude product is refined by selecting the specific solvent system and utilizing an alkali dissolution and acid precipitation mode under specific conditions, so that impurities in the ganciclovir crude product can be effectively removed, and the purity of ganciclovir is improved.
Description
Technical Field
The invention relates to a medicine preparation technology, in particular to a preparation method of ganciclovir and a preparation method of ganciclovir for injection.
Background
The impurities of the medicine refer to substances which exist in the medicine and have no therapeutic effect or influence on the curative effect and stability of the medicine and even are harmful to the health of human bodies. The purity of the medicine must be ensured in the aspects of researching, producing, storing, clinically applying and the like, and the impurity of the medicine is reduced, thereby ensuring the curative effect and the safety of the medicine. The purity of the drug is usually evaluated by combining the aspects of structure, physical and chemical constants, appearance properties, content measurement, impurity inspection and the like of the drug. The main factors influencing the purity of the medicine are impurities contained in the medicine, and if the impurities contained in the medicine exceed a limit, the impurities are very likely to change physical and chemical constants, change appearance characteristics and influence the stability of the medicine; the increase of impurities also inevitably reduces the content or activity of the medicine, and simultaneously obviously increases toxic and side effects.
9- [ (2, 3-dihydroxypropoxy) methyl ] guanine (also known as isoganciclovir) is gradually introduced into side chain raw materials for synthesizing ganciclovir as one related substance in the antiviral drug, and is difficult to remove in the actual production process because the structure of the compound is similar to that of ganciclovir, and the compound can be completely removed by adopting a column chromatography mode.
Disclosure of Invention
The invention provides a preparation method of ganciclovir and a preparation method of ganciclovir for injection.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
the preparation method comprises the steps of adding sodium hydroxide into an aqueous solution of isopropyl alcohol with the concentration of 68-70 wt% for dissolution, adding a ganciclovir crude product, heating to 50-55 ℃ for dissolution, maintaining the temperature of 50-55 ℃ for decolorization, dropwise adding an aqueous acid solution for regulating the pH value, slowly cooling and crystallizing, and drying the obtained crystal to obtain the ganciclovir.
Further, the pH value is adjusted to 4.5-5.0.
Further, the crystallization temperature is 10-12 ℃.
Further, the time required for slow cooling is 1.5-2 hours.
Further, the weight ratio of the sodium hydroxide to the ganciclovir crude product is 0.157-0.167: 1.
further, the weight-volume ratio of the ganciclovir crude product to the isopropanol water solution is 1g: 15-18 mL.
Further, the aqueous acid solution is hydrochloric acid.
Further, the concentration of the aqueous acid solution is 15 to 20wt%.
The preparation method of the ganciclovir for injection comprises the steps of taking sodium hydroxide aqueous solution, adding the ganciclovir for dissolution, then supplementing water to a full amount, decoloring, filtering and freeze-drying to obtain the ganciclovir for injection.
The preparation method of ganciclovir and the preparation method of ganciclovir for injection have the beneficial effects that:
according to the invention, the difference between the solubility of ganciclovir and 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine in a specific solvent system is utilized, a specific solvent system is selected, and a ganciclovir crude product is refined by an alkali dissolution and acid precipitation mode under specific conditions, so that impurities in the ganciclovir crude product, especially 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine, can be effectively removed, the purity of ganciclovir is improved, and column chromatography is not required;
because of slight difference of solubility of ganciclovir and 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine under different pH values, the invention can prevent 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine from precipitating at neutral in a specific solvent system by maintaining the pH value at high temperature, and 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine is more difficult to precipitate from the solvent system of the invention relative to ganciclovir precipitation when the pH value is regulated to be slightly acidic, and at the moment, 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine can not be precipitated in the ganciclovir precipitation process by controlling proper cooling rate and crystallization temperature, and meanwhile, ganciclovir can be completely precipitated.
Detailed Description
The following description of the technical solution in the embodiments of the present invention is clear and complete. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways other than those described herein, and persons skilled in the art will readily appreciate that the present invention is not limited to the specific embodiments disclosed below.
Example 1 preparation method of ganciclovir
The embodiment is a preparation method of ganciclovir, comprising the following specific steps:
1. preparation of ganciclovir crude product
1, 3-dichloro-2-propanol is used as a starting material, and is treated by acetic anhydride after paraformaldehyde reaction to obtain 1, 3-dichloro-2-acetoxyMethoxypropane, and N 2 Condensing 9-diacetylguanine to obtain intermediate 2-alkanoyl-2 (1, 3-dichloro-2-propoxymethyl) guanine, reacting the intermediate with carboxylate to obtain ganciclovir derivative, hydrolyzing, recrystallizing with water to obtain ganciclovir crude product with purity of 95.67%, wherein 9- [ (2, 3-dihydroxypropoxy) methyl is contained]Guanine 1.23%, guanine 2.74%, and the detection method uses ganciclovir in European pharmacopoeia 7.0 (EP 7.0) for high performance liquid chromatography detection.
2. Preparation of ganciclovir
Adding 15.7G of sodium hydroxide into 1.6L of 69wt% isopropyl alcohol aqueous solution, stirring and dissolving, adding 100G of ganciclovir crude product, heating to 50 ℃ while stirring, maintaining 50 ℃ until the ganciclovir crude product is completely dissolved, continuously maintaining 50 ℃ and adding 2G of active carbon, stirring and decoloring for 30min, filtering while the hot state, continuously maintaining 50 ℃ while stirring, dropwise adding 16wt% hydrochloric acid aqueous solution to the filtrate while stirring, regulating the pH value to 4.6, slowly cooling to 10 ℃ while stirring, cooling to 10 ℃ from 50 ℃ for 2h, maintaining 10 ℃ for 5h, and drying the obtained crystal to obtain 94.32G of ganciclovir, marked G1, wherein the purity is 99.60%, the recovery rate is 94.32% (actual recovery rate is 98.19%), and 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine is 0.13% and guanine is 0.26%.
Actual recovery = ganciclovir Wei purity of ganciclovir/(crude ganciclovir x purity of crude ganciclovir) x 100%.
Examples 2 to 5 preparation of ganciclovir
Examples 2 to 5 are a preparation method of ganciclovir, respectively, and the steps are basically the same as example 1, except that the process parameters are different, and the details are shown in table 1:
table 1 list of process parameters in examples 2 to 5
The process parameters and steps of the other parts of examples 2 to 5 are the same as those of example 1.
Example 6 preparation method of Ganciclovir for injection
In this example, ganciclovir G1 prepared in example 1 was used to prepare ganciclovir for injection, and the specific preparation process includes the following steps in sequence:
weighing 50G of ganciclovir G1 and 7.84G of sodium hydroxide for later use;
firstly, 200mL of water for injection is used for dissolving 7.84g of sodium hydroxide to obtain sodium hydroxide aqueous solution for standby;
adding 600mL of water for injection into the whole sodium hydroxide aqueous solution, stirring, adding 50G of ganciclovir G1 while stirring, continuously stirring to completely dissolve, measuring the pH value of the dissolved liquid medicine to be 11.0-12.0, adjusting the pH value to be 11.5 in the embodiment (with dilute hydrochloric acid or sodium hydroxide solution if necessary), supplementing the water for injection to 1000mL, adding 1G of active carbon, circularly stirring for 30 minutes at room temperature, circularly decarbonizing and filtering through a 3 mu m titanium filter rod, measuring the content of an intermediate, performing primary sterilization and filtering through a 0.22 mu m filter element after detection is qualified, and transferring the obtained rough filtration liquid medicine to a filling machine hundred-level laminar flow hood for secondary terminal sterilization and filtering through the 0.22 mu m filter element to a liquid medicine barrel to obtain the liquid medicine.
2) Filling
Filling the liquid medicine into an injection bottle, half-tamponading, self-checking the filling quantity and the quality condition of the half-tamponade once every 30min, adjusting the filling quantity in time, and performing secondary sterilization and filtration on all sample for spot check; and (3) filling and placing qualified products in the freeze-drying machine box on a shelf in the freeze-drying machine box while filling.
3) Freeze drying
The filling and qualified products are put into a material tray and put on a baffle plate in a freeze-drying box in time for freeze-drying, and the specific freeze-drying process is as follows:
pre-freezing: the shelf is lowered to below-50 ℃, and after the product temperature reaches the eutectic point, the temperature is kept for 3-7 h, and the temperature is kept for 6h in the embodiment; the temperature of the cold trap is reduced to-50+/-5 ℃, and the vacuum is pumped to 10+/-5 Pa;
sublimation drying (primary drying): slowly heating the shelf to enable the temperature of the product to be lower than the eutectic point of the product (the temperature of the embodiment is-30+/-1 ℃) to carry out low-temperature sublimation until the ice crystal of the product completely disappears, and then keeping for 5-8 hours, wherein the embodiment keeps for 6 hours;
analytical drying (secondary drying): the shelf is firstly raised to 40+/-5 ℃ for heat preservation for 4-6 hours, the temperature is kept for 5 hours in the embodiment, then is lowered to 30+/-5 ℃ for heat preservation for 2-3 hours, the embodiment is kept for 2 hours, freeze-drying is finished, a full plug is pressed, and the ganciclovir for injection (the specification of medicines is 0.05 g) is obtained after being taken out of the box, and the ganciclovir is marked as ZG1.
Examples 7 to 10 preparation method of ganciclovir for injection
Examples 7 to 10 ganciclovir for injection was prepared using ganciclovir M2 to M5 prepared in examples 2 to 5, respectively, and the procedure was substantially the same as example 1, except that the process parameters were different, and specific details are shown in table 2:
table 2 list of process parameters in examples 7 to 10
The other parts of examples 7 to 10 are the same as in example 6.
Experimental example 1
Comparative examples 1-8 are comparative experiments for the preparation of ganciclovir in example 1, using the same batch of crude ganciclovir as in example 1, except that:
in comparative example 1, a 60wt% aqueous isopropanol solution was used as a solvent system to give 88.27g of ganciclovir, labeled DG1, at 99.11% purity, 88.27% (actual recovery 91.44%) containing 0.59% 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine and 0.27% guanine.
In comparative example 2, a 75wt% aqueous isopropanol solution was used as a solvent system to give 94.74g of ganciclovir, labeled DG2, at a purity of 98.82%, at a recovery of 94.74% (actual recovery of 97.86%), containing 0.12% 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine and 1.04% guanine.
After cooling to room temperature in comparative example 3, an aqueous solution of hydrochloric acid was added dropwise to adjust the pH to 4.6, 91.27g of ganciclovir, labeled DG3, was 98.58% pure and 95.34% recovered (actual recovery: 98.24%), which contained 0.93% 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine and 0.42% guanine.
The aqueous hydrochloric acid solution in comparative example 4 was adjusted to pH 7.0 to give 96.84g of ganciclovir, labeled DG4, at a purity of 97.01% and a recovery of 96.84% (actual recovery 98.42%) containing 1.17% 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine and 1.60% guanine.
The aqueous hydrochloric acid solution in comparative example 5 was adjusted to pH 3.0 to give 89.32g of ganciclovir, labeled DG5, at 99.59% purity and 96.84% recovery (actual recovery 92.98%), which contained 0.13% 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine and 0.27% guanine.
The crystallization temperature in comparative example 6 was 5℃to give 95.42g of ganciclovir, labeled DG6, at a purity of 98.48% and a recovery of 95.42% (actual recovery 98.22%), which contained 0.79% 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine and 0.66% guanine.
The crystallization temperature in comparative example 7 was 20℃to give 84.21g of ganciclovir, labeled DG7, at a purity of 99.62% and a recovery of 84.21% (actual recovery 87.69%), which contained 0.12% 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine and 0.25% guanine.
In comparative example 8, 84.21g of ganciclovir, labeled DG8, was obtained at a purity of 99.21% and a recovery of 94.27% (actual recovery of 97.76%) and 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine was 0.52% and guanine was 0.42% by cooling from 50℃to 10℃for only 30 min.
As can be seen from comparative examples 1 to 8, the preparation process of the present invention is more useful for purifying ganciclovir.
Experimental example 2 stability detection
Ganciclovir for injection ZG 1-ZG 5 prepared in examples 6-10 were taken and placed under conditions of 40+ -2deg.C and 75+ -5% RH for 5 months, respectively, during which time samples were taken at 1, 2,3 and 6 months, tested according to the stability test item, and compared with the data of day 0.
The ganciclovir for injection was tested for its appearance, clarity and color according to the method in chinese pharmacopoeia 2020 edition (where the content is different from the previous content, and the indicated amounts are calculated here), and for 9- [ (2, 3-dihydroxypropoxy) methyl ] guanine and guanine according to the method in EP7.0, as shown in the following table:
TABLE 3 list of test results
As can be seen from Table 3, the ganciclovir for injection prepared in examples 6 to 10 of the present invention has good stability.
It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Claims (6)
1. The preparation method of ganciclovir is characterized by comprising the steps of adding sodium hydroxide into an aqueous solution of isopropanol with the concentration of 68-70wt% for dissolution, adding a ganciclovir crude product, heating to 50-55 ℃ for dissolution, maintaining the temperature of 50-55 ℃ for decolorization, dropwise adding an aqueous acid solution for regulating the pH value to 4.5-5.0, slowly cooling and crystallizing, and drying the obtained crystal to obtain ganciclovir;
the crystallization temperature is 10-12 ℃;
the time required for slowly cooling is 1.5-2 hours.
2. The preparation method of ganciclovir according to claim 1, wherein the weight ratio of sodium hydroxide to ganciclovir crude product is 0.157-0.167: 1.
3. the preparation method of ganciclovir according to claim 1, wherein the weight-to-volume ratio of the ganciclovir crude product to the isopropanol aqueous solution is 1g: 15-18 mL.
4. The method for preparing ganciclovir according to claim 1, wherein the aqueous acid solution is hydrochloric acid.
5. The method for preparing ganciclovir according to claim 4, wherein the concentration of the aqueous acid solution is 15-20wt%.
6. The preparation method of ganciclovir for injection is characterized in that ganciclovir for injection is prepared by firstly utilizing the preparation method of ganciclovir according to any one of claims 1-5, then taking sodium hydroxide aqueous solution, adding ganciclovir for dissolution, then supplementing water to full quantity, and then decoloring, filtering and freeze-drying to obtain ganciclovir for injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211162515.2A CN115504977B (en) | 2022-09-23 | 2022-09-23 | Preparation method of ganciclovir and preparation method of ganciclovir for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211162515.2A CN115504977B (en) | 2022-09-23 | 2022-09-23 | Preparation method of ganciclovir and preparation method of ganciclovir for injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115504977A CN115504977A (en) | 2022-12-23 |
| CN115504977B true CN115504977B (en) | 2024-02-09 |
Family
ID=84505323
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211162515.2A Active CN115504977B (en) | 2022-09-23 | 2022-09-23 | Preparation method of ganciclovir and preparation method of ganciclovir for injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115504977B (en) |
Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4642346A (en) * | 1985-06-24 | 1987-02-10 | Syntex (U.S.A.) Inc. | Anhydrous crystalline 9-(1,3-dihydroxy-2-propoxymethyl)guanine |
| US5223619A (en) * | 1989-03-20 | 1993-06-29 | A/S Gea Farmaceutisk Fabrik | Process for the preparation of 9-substituted guanine derivatives |
| CN101851240A (en) * | 2009-04-03 | 2010-10-06 | 上海益威实业有限公司 | Ganciclovir purification process |
| CN102627643A (en) * | 2012-04-10 | 2012-08-08 | 常州康丽制药有限公司 | Refining method for ganciclovir |
| CN102643277A (en) * | 2012-04-10 | 2012-08-22 | 常州康丽制药有限公司 | Refining method of ganciclovir |
| CN103044426A (en) * | 2012-12-27 | 2013-04-17 | 海南锦瑞制药股份有限公司 | Ganciclovir crystal compound, new composition thereof and preparation method thereof |
| CN103524505A (en) * | 2013-10-30 | 2014-01-22 | 湖北华世通潜龙药业有限公司 | Crystal type ganciclovir sodium hydrate and preparing method thereof |
| CN107141291A (en) * | 2017-07-10 | 2017-09-08 | 湖北天义药业有限公司 | A kind of preparation method of GCV |
| CN108467396A (en) * | 2018-04-25 | 2018-08-31 | 安徽海康药业有限责任公司 | A kind of preparation method of Ganciclovir |
| CN108912122A (en) * | 2018-08-31 | 2018-11-30 | 信阳师范学院 | A method of acyclovir and Ganciclovir are synthesized using carbon-hydrogen bond activation |
| CN112661757A (en) * | 2020-12-23 | 2021-04-16 | 河北合佳医药科技集团股份有限公司 | Method for synthesizing valganciclovir hydrochloride |
| CN113149988A (en) * | 2021-04-23 | 2021-07-23 | 海南锦瑞制药有限公司 | Ganciclovir preparation method and application |
| CN113149987A (en) * | 2021-04-22 | 2021-07-23 | 南京杏药原医药科技开发有限公司 | Preparation method of injection-grade ganciclovir |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0405798B8 (en) * | 2003-11-28 | 2021-05-25 | Halex Istar Ind Farmaceutica L | process for eliminating alkaline residues present in 9-((1,3-dihydroxypropan-2-yloxy)methyl)-2-amino-1h-purin-6(9h)-one and pharmaceutical presentation |
-
2022
- 2022-09-23 CN CN202211162515.2A patent/CN115504977B/en active Active
Patent Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4642346A (en) * | 1985-06-24 | 1987-02-10 | Syntex (U.S.A.) Inc. | Anhydrous crystalline 9-(1,3-dihydroxy-2-propoxymethyl)guanine |
| US5223619A (en) * | 1989-03-20 | 1993-06-29 | A/S Gea Farmaceutisk Fabrik | Process for the preparation of 9-substituted guanine derivatives |
| CN101851240A (en) * | 2009-04-03 | 2010-10-06 | 上海益威实业有限公司 | Ganciclovir purification process |
| CN102627643A (en) * | 2012-04-10 | 2012-08-08 | 常州康丽制药有限公司 | Refining method for ganciclovir |
| CN102643277A (en) * | 2012-04-10 | 2012-08-22 | 常州康丽制药有限公司 | Refining method of ganciclovir |
| CN103044426A (en) * | 2012-12-27 | 2013-04-17 | 海南锦瑞制药股份有限公司 | Ganciclovir crystal compound, new composition thereof and preparation method thereof |
| CN103524505A (en) * | 2013-10-30 | 2014-01-22 | 湖北华世通潜龙药业有限公司 | Crystal type ganciclovir sodium hydrate and preparing method thereof |
| CN107141291A (en) * | 2017-07-10 | 2017-09-08 | 湖北天义药业有限公司 | A kind of preparation method of GCV |
| CN108467396A (en) * | 2018-04-25 | 2018-08-31 | 安徽海康药业有限责任公司 | A kind of preparation method of Ganciclovir |
| CN108912122A (en) * | 2018-08-31 | 2018-11-30 | 信阳师范学院 | A method of acyclovir and Ganciclovir are synthesized using carbon-hydrogen bond activation |
| CN112661757A (en) * | 2020-12-23 | 2021-04-16 | 河北合佳医药科技集团股份有限公司 | Method for synthesizing valganciclovir hydrochloride |
| CN113149987A (en) * | 2021-04-22 | 2021-07-23 | 南京杏药原医药科技开发有限公司 | Preparation method of injection-grade ganciclovir |
| CN113149988A (en) * | 2021-04-23 | 2021-07-23 | 海南锦瑞制药有限公司 | Ganciclovir preparation method and application |
Non-Patent Citations (1)
| Title |
|---|
| 盐酸缬更昔洛韦的合成;赵士魁，等;中国医药工业杂志;第46卷(第02期);第120-122页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115504977A (en) | 2022-12-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2013386219B2 (en) | Beta-hydroxy-beta-methylbutyric acid purification method | |
| US20010047089A1 (en) | Preparation method of azithromycin dihydrate | |
| CN113214259B (en) | Synthesis method of pentoxifylline | |
| US20150038740A1 (en) | Alanyl glutamine compound and preparation method thereof | |
| CN113350276A (en) | Preparation method and packaging method of octreotide acetate injection | |
| CN115504977B (en) | Preparation method of ganciclovir and preparation method of ganciclovir for injection | |
| CN110627792A (en) | Pentoxifylline compound | |
| CN114874237B (en) | Refining method of cefotaxime sodium | |
| CN111548310A (en) | Levosimendan sodium crystal form and preparation method thereof | |
| HRP20020231A2 (en) | ISOSTRUCTURAL PSEUDOPOLYMORPHS OF 9-DEOXO-9a-AZA-9a-METHYL-9a-HOMOERYTHROMYCIN A | |
| EP2658840B1 (en) | Process for making fingolimod hydrochloride crystals | |
| CN112028862A (en) | Preparation method of ranitidine hydrochloride with low NDMA content | |
| CN111718299A (en) | Levosimendan sodium crystal form B and preparation method thereof | |
| CN1328281C (en) | Ceftazidime pentahydrate purifying method | |
| CN113171347B (en) | Preparation method of vidarabine monophosphate freeze-dried powder injection for injection | |
| CN113577033B (en) | Preparation process of azithromycin for injection | |
| KR20200039750A (en) | Method for preparing a pharmaceutical composition | |
| CN115448966B (en) | Preparation method of fludarabine phosphate and preparation method of fludarabine phosphate for injection | |
| CN113143855A (en) | Bromhexine hydrochloride oral liquid and preparation method thereof | |
| CN111961066B (en) | Preparation method of antibacterial drug | |
| CN111253456B (en) | Preparation method of denufosol sodium | |
| CN115073368B (en) | Milrinone-5-sulfosalicylic acid crystal form | |
| EP3992173B1 (en) | Treprostinil monohydrate crystals and methods for preparation thereof | |
| CN114685581B (en) | Troxerutin for injection and preparation process thereof | |
| CN116687848A (en) | Citicoline sodium injection and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |