CN105342993A - Preparation technology of dexamethasone sodium phosphate injection - Google Patents
Preparation technology of dexamethasone sodium phosphate injection Download PDFInfo
- Publication number
- CN105342993A CN105342993A CN201510758973.6A CN201510758973A CN105342993A CN 105342993 A CN105342993 A CN 105342993A CN 201510758973 A CN201510758973 A CN 201510758973A CN 105342993 A CN105342993 A CN 105342993A
- Authority
- CN
- China
- Prior art keywords
- dexamethasone
- sodium phosphate
- dexamethasone sodium
- injection
- recrystallization
- 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.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparation technology of dexamethasone sodium phosphate injection. The preparation technology comprises the following steps: synthetizing dexamethasone sodium phosphate; sequentially carrying out ring-opening reaction, recrystallization, base-catalyzed hydrolysis, pyrophosphoryl chloride esterification and salt-formation from neutralization to obtain a dexamethasone sodium phosphate solution, and carrying out further recrystallization on the dexamethasone sodium phosphate solution to obtain a dexamethasone sodium phosphate crystal by taking dexamethasone acetate epoxide as a starting material; drying the dexamethasone sodium phosphate crystal, and ball-milling the dried crystal into powder; and dissolving the dexamethasone sodium phosphate powder by water for injection for dilution, adding medicinal propylene glycol, and phosphate buffered solution with the pH being 8.0 to prepare the dexamethasone sodium phosphate injection. With the adoption of the method, the problems that in the existing preparation methods, the yield is low, and the active ingredients of the prepared dexamethasone sodium phosphate injection are rapid in efficacy-decreasing speed are solved.
Description
Technical field
The present invention relates to medical art, particularly, relate to a kind of preparation technology of dexamethasone sodium phosphate injection.
Background technology
Dexamethasone sodium phosphate, chemistry 16 Alpha-Methyl-11 β, 17 α by name, 21 trihydroxy-9 α-fuprednate-Isosorbide-5-Nitrae-diene-3,20-diketone-21-organic phosphate disodium salt, be a kind of Aeroseb-Dex, there is antiinflammatory, antiallergic, rheumatism, immunosuppressive action.The mechanism of action is: (1) antiinflammatory action: can alleviate and prevent tissue to the reaction of inflammation, thus the performance reduced inflammation.Can inflammation-inhibiting cell, comprise macrophage and leukocyte gathering at inflammation part, and suppress phagocytosis, the synthesis of lysosomal release and inflammation chemistry mediator and release.(2) immunosuppressive action: comprise prevent or T suppression cell mediation immunoreation, the anaphylaxis of retardance, reduce the number of T lymphocyte, mononuclear cell, oxyphil cell, reduce the binding ability of immunoglobulin and cell surface receptor, and suppress synthesis and the release of interleukin, thus reduce T lymphocyte to lymphocyte transformation, and alleviate and formerly send out expansion immunoreactive.Also can reduce immunity and check thing by basement membrane, and the concentration of complement component and immunoglobulin can be reduced.
Dexamethasone sodium phosphate is mainly used in anaphylaxis and auto-immune inflammatory disease, be used for connective tissue disease, activeness rheumatism, rheumatoid arthritis, lupus erythematosus, serious bronchial asthma, serious dermatitis, ulcerative colitis, acute leukemia etc., also for some severe infections and poisoning.The Comprehensive Treatment of malignant lymphoma.Within 1 hour after intramuscular injection, blood peak concentration of drug can be reached, and its plasma protein binding rate is low compared with other corticosteroids medicine, therefore clinical its injection inhibitor conventional.
Preparation technology's yield of existing dexamethasone sodium phosphate injection is low, and the drug effect of the effective ingredient of the dexamethasone sodium phosphate injection made underspeeds comparatively fast.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of preparation technology of dexamethasone sodium phosphate injection, to underspeed problem faster to overcome the yield that existing preparation method the causes drug effect of the effective ingredient of dexamethasone sodium phosphate injection that is low, that make.
The present invention's adopted technical scheme that solves the problem is: a kind of preparation technology of dexamethasone sodium phosphate injection, comprises the following steps:
1), the synthesis of dexamethasone sodium phosphate: with dexamethasone acetate epoxy material for initiation material, successively through ring-opening reaction, recrystallization, alkali catalyzed hydrolysis, pyrophosphoryl chloride esterification, be neutralized into reactant salt and obtain dexamethasone sodium phosphate solution, dexamethasone sodium phosphate solution again recrystallization obtains dexamethasone sodium phosphate crystalline solid;
Described ring-opening reaction: with dexamethasone acetate epoxy material for initiation material, add HF, DMF, reaction temperature is-10 DEG C ~ 0 DEG C, and response time 3h carries out ring-opening reaction and obtains dexamethasone acetate solution;
Described recrystallization: add acetone or ether and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
Described alkali catalyzed hydrolysis: the dexamethasone acetate obtained is joined Na
2cO
3with in methanol, reaction temperature 20 DEG C ~ 30 DEG C, obtains dexamethasone after response time 10min;
Described pyrophosphoryl chloride esterification: the dexamethasone obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate;
Describedly be neutralized into reactant salt: the dexamethasone phosphate obtained and NaOH, methanol are reacted, reaction temperature 20 DEG C ~ 30 DEG C, the response time, 1h obtained dexamethasone sodium phosphate;
2) ball milling powdered after the dexamethasone sodium phosphate crystalline solid drying, step 1) obtained;
3), by step 2) the dexamethasone sodium phosphate powder water for injection dissolved dilution prepared, add the Proplyleng Glycol of 4 ~ 6%, the phosphate buffered solution of the pH8.0 of 0.4 ~ 0.5% makes dexamethasone sodium phosphate injection.
Reagent used in the present invention is available reagent, wherein HF is Fluohydric acid., and DMF is dimethyl formamide, and the step that the present invention prepares dexamethasone sodium phosphate is simple, raw material is easy to get, reaction condition is gentle, is suitable for suitability for industrialized production, and with low cost, and, the present invention adopts acetone to be used for the recrystallization of dexamethasone acetate, can effectively improve dexamethasone acetate recrystallization ratio, and then improves the yield of final products dexamethasone sodium phosphate; The present invention, by adding phosphate buffered solution in dexamethasone sodium phosphate injection, effectively can avoid the problem that the effective ingredient drug effect of dexamethasone sodium phosphate injection reduces.
Further, in step 1), the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 1 ~ 2:92 ~ 95:44 ~ 50.
Further, dexamethasone acetate, Na in step 3)
2cO
3, methanol mol ratio be 1 ~ 2:4 ~ 8:214 ~ 220.
Further, in step 4), the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 1 ~ 3:5 ~ 8:19 ~ 25.
Further, in step 5), the mol ratio of dexamethasone phosphate, NaOH, methanol is 1 ~ 2:2 ~ 5:169 ~ 175.
To sum up, the invention has the beneficial effects as follows:
1, to prepare the step of dexamethasone sodium phosphate simple in the present invention, raw material is easy to get, reaction condition is gentle, be suitable for suitability for industrialized production, and with low cost, and the present invention adopts acetone to be used for the recrystallization of dexamethasone acetate, can effectively improve dexamethasone acetate recrystallization ratio, and then improve the yield of final products dexamethasone sodium phosphate.
2, the present invention by adding phosphate buffered solution in dexamethasone sodium phosphate injection, effectively can avoid the problem that the effective ingredient drug effect of dexamethasone sodium phosphate injection reduces.
Detailed description of the invention
Below in conjunction with embodiment, to the detailed description further of invention do, but embodiments of the present invention are not limited thereto.
Embodiment 1:
A preparation technology for dexamethasone sodium phosphate injection, comprises the following steps:
1), the synthesis of dexamethasone sodium phosphate: with dexamethasone acetate epoxy material for initiation material, successively through ring-opening reaction, recrystallization, alkali catalyzed hydrolysis, pyrophosphoryl chloride esterification, be neutralized into reactant salt and obtain dexamethasone sodium phosphate solution, dexamethasone sodium phosphate solution again recrystallization obtains dexamethasone sodium phosphate crystalline solid;
Ring-opening reaction: with dexamethasone acetate epoxy material for initiation material, add HF, DMF, reaction temperature is-10 DEG C, and response time 3h carries out ring-opening reaction and obtains dexamethasone acetate solution, and the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 1:92:44;
Recrystallization: add acetone or ether and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
Alkali catalyzed hydrolysis: the dexamethasone acetate obtained is joined Na
2cO
3with in methanol, reaction temperature 20 DEG C, obtains dexamethasone after response time 10min, dexamethasone acetate, Na
2cO
3, methanol mol ratio be 1:4:214;
Described pyrophosphoryl chloride esterification: the dexamethasone obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate, the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 1:5:19;
Describedly be neutralized into reactant salt: the dexamethasone phosphate obtained and NaOH, methanol are reacted, reaction temperature 20 DEG C, the response time, 1h obtained dexamethasone sodium phosphate, and the mol ratio of dexamethasone phosphate, NaOH, methanol is 1:2:169;
2) ball milling powdered after the dexamethasone sodium phosphate crystalline solid drying, step 1) obtained;
3), by step 2) the dexamethasone sodium phosphate powder water for injection dissolved dilution prepared, add the Proplyleng Glycol of 4%, the phosphate buffered solution of the pH8.0 of 0.4% makes dexamethasone sodium phosphate injection.
Embodiment 2:
A preparation technology for dexamethasone sodium phosphate injection, comprises the following steps:
1), the synthesis of dexamethasone sodium phosphate: with dexamethasone acetate epoxy material for initiation material, successively through ring-opening reaction, recrystallization, alkali catalyzed hydrolysis, pyrophosphoryl chloride esterification, be neutralized into reactant salt and obtain dexamethasone sodium phosphate solution, dexamethasone sodium phosphate solution again recrystallization obtains dexamethasone sodium phosphate crystalline solid;
Described ring-opening reaction: with dexamethasone acetate epoxy material for initiation material, add HF, DMF, reaction temperature is-5 DEG C, and response time 3h carries out ring-opening reaction and obtains dexamethasone acetate solution, and the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 1.5:94:48;
Described recrystallization: add acetone or ether and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
Described alkali catalyzed hydrolysis: the dexamethasone acetate obtained is joined Na
2cO
3with in methanol, reaction temperature 25 DEG C, obtains dexamethasone after response time 10min, dexamethasone acetate, Na
2cO
3, methanol mol ratio be 1.5:6:216; Described pyrophosphoryl chloride esterification:
The dexamethasone obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate, and the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 2:6:22;
Describedly be neutralized into reactant salt: the dexamethasone phosphate obtained and NaOH, methanol are reacted, reaction temperature 25 DEG C, the response time, 1h obtained dexamethasone sodium phosphate, and the mol ratio of dexamethasone phosphate, NaOH, methanol is 1.5:4:173;
2) ball milling powdered after the dexamethasone sodium phosphate crystalline solid drying, step 1) obtained;
3), by step 2) the dexamethasone sodium phosphate powder water for injection dissolved dilution prepared, add the Proplyleng Glycol of 5%, the phosphate buffered solution of the pH8.0 of 0.5% makes dexamethasone sodium phosphate injection.
Embodiment 3:
A preparation technology for dexamethasone sodium phosphate injection, comprises the following steps:
1), the synthesis of dexamethasone sodium phosphate: with dexamethasone acetate epoxy material for initiation material, successively through ring-opening reaction, recrystallization, alkali catalyzed hydrolysis, pyrophosphoryl chloride esterification, be neutralized into reactant salt and obtain dexamethasone sodium phosphate solution, dexamethasone sodium phosphate solution again recrystallization obtains dexamethasone sodium phosphate crystalline solid;
Described ring-opening reaction: with dexamethasone acetate epoxy material for initiation material, add HF, DMF, reaction temperature is 0 DEG C, and response time 3h carries out ring-opening reaction and obtains dexamethasone acetate solution, and the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 2:95:50;
Described recrystallization: add acetone or ether and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
Described alkali catalyzed hydrolysis: the dexamethasone acetate obtained is joined Na
2cO
3with in methanol, reaction temperature 30 DEG C, obtains dexamethasone after response time 10min, dexamethasone acetate, Na
2cO
3, methanol mol ratio be 2:8:220;
Described pyrophosphoryl chloride esterification: the dexamethasone obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate, the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 3:8:25;
Describedly be neutralized into reactant salt: the dexamethasone phosphate obtained and NaOH, methanol are reacted, reaction temperature 30 DEG C, the response time, 1h obtained dexamethasone sodium phosphate, and the mol ratio of dexamethasone phosphate, NaOH, methanol is 2:5:175;
2) ball milling powdered after the dexamethasone sodium phosphate crystalline solid drying, step 1) obtained;
3), by step 2) the dexamethasone sodium phosphate powder water for injection dissolved dilution prepared, add the Proplyleng Glycol of 4%, the phosphate buffered solution of the pH8.0 of 0.4% makes dexamethasone sodium phosphate injection.
As mentioned above, the present invention can be realized preferably.
Claims (5)
1. a preparation technology for dexamethasone sodium phosphate injection, is characterized in that, comprises the following steps:
1), the synthesis of dexamethasone sodium phosphate: with dexamethasone acetate epoxy material for initiation material, successively through ring-opening reaction, recrystallization, alkali catalyzed hydrolysis, pyrophosphoryl chloride esterification, be neutralized into reactant salt and obtain dexamethasone sodium phosphate solution, dexamethasone sodium phosphate solution again recrystallization obtains dexamethasone sodium phosphate crystalline solid;
Described ring-opening reaction: with dexamethasone acetate epoxy material for initiation material, add HF, DMF, reaction temperature is-10 DEG C ~ 0 DEG C, and response time 3h carries out ring-opening reaction and obtains dexamethasone acetate solution;
Recrystallization: add acetone or ether and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
Described alkali catalyzed hydrolysis: the dexamethasone acetate obtained is joined Na
2cO
3with in methanol, reaction temperature 20 DEG C ~ 30 DEG C, obtains dexamethasone after response time 10min;
Described pyrophosphoryl chloride esterification: the dexamethasone obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate;
Describedly be neutralized into reactant salt: the dexamethasone phosphate obtained and NaOH, methanol are reacted, reaction temperature 20 DEG C ~ 30 DEG C, the response time, 1h obtained dexamethasone sodium phosphate;
2) ball milling powdered after the dexamethasone sodium phosphate crystalline solid drying, step 1) obtained;
3), by step 2) the dexamethasone sodium phosphate powder water for injection dissolved dilution prepared, add the Proplyleng Glycol of 4 ~ 6%, the phosphate buffered solution of the pH8.0 of 0.4 ~ 0.5% makes dexamethasone sodium phosphate injection.
2. the preparation technology of a kind of dexamethasone sodium phosphate injection according to claim 1, is characterized in that, in step 1), the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 1 ~ 2:92 ~ 95:44 ~ 50.
3. the preparation technology of a kind of dexamethasone sodium phosphate injection according to claim 1, is characterized in that, dexamethasone acetate, Na in step 3)
2cO
3, methanol mol ratio be 1 ~ 2:4 ~ 8:214 ~ 220.
4. the preparation technology of a kind of dexamethasone sodium phosphate injection according to claim 1, is characterized in that, in step 4), the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 1 ~ 3:5 ~ 8:19 ~ 25.
5. the preparation technology of a kind of dexamethasone sodium phosphate injection according to claim 1, is characterized in that, in step 5), the mol ratio of dexamethasone phosphate, NaOH, methanol is 1 ~ 2:2 ~ 5:169 ~ 175.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510758973.6A CN105342993A (en) | 2015-11-10 | 2015-11-10 | Preparation technology of dexamethasone sodium phosphate injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510758973.6A CN105342993A (en) | 2015-11-10 | 2015-11-10 | Preparation technology of dexamethasone sodium phosphate injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105342993A true CN105342993A (en) | 2016-02-24 |
Family
ID=55319161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510758973.6A Pending CN105342993A (en) | 2015-11-10 | 2015-11-10 | Preparation technology of dexamethasone sodium phosphate injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105342993A (en) |
-
2015
- 2015-11-10 CN CN201510758973.6A patent/CN105342993A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Neish | THE BIOSYNTHESIS OF CELL WALL CARBOHYDRATES: II. FORMATION OF CELLULOSE AND XYLAN FROM LABELED MONOSACCHARIDES IN WHEAT PLANTS | |
| CN104003894B (en) | The preparation method of N-acetyl-β-chloro-ALANINE methyl esters | |
| CN105734109A (en) | Producing and refining method for high-purity cycloastragenol | |
| CN102153567B (en) | Method for preparing cefoxitin acid | |
| CN102399253A (en) | Preparation method for trenbolone acetic ester | |
| CN105342992A (en) | Preparation method of dexamethasone sodium phosphate injection | |
| CN105342993A (en) | Preparation technology of dexamethasone sodium phosphate injection | |
| CN105342991A (en) | Preparation technology of dexamethasone sodium phosphate injection for quality improvement | |
| CN105326787A (en) | Technology for preparing dexamethasone sodium phosphate injection | |
| CN105326788A (en) | Preparation method of dexamethasone sodium phosphate for injection | |
| CN105646580A (en) | Method for producing pentahydrate s-ornidazole disodium phosphate | |
| CN105348359A (en) | Preparation technology for dexamethasone sodium phosphate | |
| CN103709209B (en) | The preparation method of isopropyl-β-D-thiogalactoside | |
| CN116393170B (en) | Preparation method of trifluoro methanesulfonic anhydride | |
| CN105348358A (en) | Preparation method for dexamethasone sodium phosphate | |
| CN105348360A (en) | Preparation technology for dexamethasone sodium phosphate based on raising recrystalline particle size | |
| CN103665063B (en) | A kind of method preparing isopropyl-β-D-thiogalactoside(IPTG) | |
| CN102584726B (en) | Method for preparing penconazole serving as bacteriacide | |
| CN103923143B (en) | Method for synthesizing dinucleoside tetraphosphate and P2,P3-(dihalo) methylene dinucleoside tetraphosphate | |
| CN103665064B (en) | One prepares the method for 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose | |
| Wang et al. | Gold (i)-promoted α-selective sialylation of glycosyl ortho-hexynylbenzoates for the latent-active synthesis of oligosialic acids | |
| CN109517019B (en) | Recycling method of 3 beta-acetoxyandrostane-5-alkene-17-ketone addition reaction byproduct | |
| CN102351729A (en) | Method for preparing N-hydroxymethyl acrylamide | |
| CN102329286A (en) | Novel method for synthesizing 3-oxetanone | |
| CN103709212B (en) | A kind of technique preparing 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160224 |