[Overview]
Dexamethasone sodium phosphate is also called flumethasone sodium phosphate, its Chinese name is 1,4-pregnadiene-9α-fluoro-16α-methyl-11β, 17α-diol-3,20-dione-21 -Phosphate disodium salt is an adrenal glucocorticoid and a steroid hormone substance. It plays a very important role in clinical practice with high curative effect, small side effects, and wide range of uses. It is mainly used to treat allergic and autoimmune inflammatory diseases, such as connective tissue diseases, active rheumatism, lupus erythematosus, severe bronchial asthma, and surgical procedures. After vomiting, eye diseases, joint disorders, etc., it is also used for the comprehensive treatment of some serious infections and poisonings, and malignant lymphoma. It was once known as the “King of Corticosteroid Drugs”.
[Physical and chemical properties]
From the perspective of properties, pure dexamethasone sodium phosphate product is white or slightly yellow powder; odorless and slightly bitter; it has strong hygroscopicity in the air. This product is soluble in water or methanol and almost insoluble in acetone or ether.
[Identification]
1. In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
2. The infrared light absorption spectrum of this product should be consistent with the control spectrum (Figure 141 of “Drug Infrared Spectrum Collection”).
3. This product shows the identification reaction of organic fluoride (2010 edition of Pharmacopoeia, Part II, Appendix III).
4. Take about 40mg of this product, add 2ml of sulfuric acid, slowly heat until white smoke appears, add 0.5ml of nitric acid dropwise, continue to heat until the nitrogen oxide vapor is removed, let it cool, add 2ml of water dropwise, and then slowly heat until White smoke occurs and the solution is slightly yellow. Let it cool. Add 10 ml of water dropwise. Neutralize with ammonia test solution until the solution shows a neutral reaction when it meets litmus paper. Add a little activated carbon to decolorize and filter. The filtrate shows sodium salt and phosphate. Identification of sodium salt and phosphate Reaction (2010 edition of Pharmacopoeia, Part II, Appendix III).
[Pharmacology and Toxicology]
1. Inhibit the accumulation of inflammatory cells, including macrophages and leukocytes, at inflammatory sites, and inhibit phagocytosis, the release of lysosomal enzymes, and the synthesis and release of inflammatory chemical mediators, thereby exerting an anti-inflammatory effect.
2. Immunosuppressive effect, preventing or inhibiting cell-mediated immune reactions, delayed allergic reactions to epoxy paint curing agents, reducing the number of T lymphocytes, monocytes, and eosophages, and reducing immunoglobulins The ability to bind to cell surface receptors and inhibit the synthesis and release of interleukins, thereby reducing the transformation of T lymphocytes into lymphoblasts and reducing the expansion of the primary immune response. This product also reduces the passage of immune review substances through the basement membrane, and can reduce the concentration of complement components and immunoglobulins.
[Preparation method]
1. Preparation of dexamethasone phosphate. Add dexamethasone to a three-necked flask, add redistilled tetrahydrofuran, cool down, slowly add pyrophosphoryl chloride to it, keep the temperature unchanged, react for 1 hour after the addition is completed, and then use water Dilute, raise the temperature to about 60°C, add a certain amount of Na2CO3 to it until no bubbles are released, stir the reaction at a certain temperature, filter, separate layers, and spin-evaporate the lower aqueous solution at 50°C until there are no obvious bubbles. Add hydrochloric acid dropwise to it to precipitate a white precipitate, wash it three times with hydrochloric acid and dry it.
2. Preparation of dexamethasone sodium phosphate. Add dexamethasone phosphate and methanol to the reaction bottle and stir until completely dissolved. Add 1 mol/L NaOH-methanol solution dropwise, adjust to pH about 9, continue stirring the reaction for 1 hour, after completion, add dropwise until the pH is 9.3, distill under reduced pressure until almost dry, add acetone, stir for 1 hour, let stand in the refrigerator for 8 hours, and take out Wash with acetone, filter and dry the solid in an oven at 70°C for 10 hours to obtain the product dexamethasone sodium phosphate.
Figure 1 is the production process flow chart of dexamethasone sodium phosphate
【Clinical Use】
Adrenocortical hormone drugs have anti-inflammatory, anti-allergic, anti-toxic and other effects, and can be used for severe infectious adrenal insufficiency, connective tissue disease, severe bronchitis, asthma and other allergies.
【Indications】
Mainly used for allergic and autoimmune inflammatory diseases. It is mostly used for connective tissue diseases, active rheumatism, rheumatoid arthritis, lupus erythematosus, severe bronchial asthma, severe dermatitis, ulcerative colitis, acute leukemia, etc. It is also used for certain serious infections and poisonings, and malignant lymphoma. Comprehensive Treatment.
【Usage and Dosage】
The general dose is intravenous injection of 2-20mg each time; during intravenous drip, it should be diluted with 5% glucose injection, and can be repeated for 2-6 hours until the condition is stable, but continuous administration of large doses generally does not exceed 72 hours. . It can also be used to relieve cerebral edema caused by malignant tumors. The first dose is intravenous bolus injection of 10 mg, followed by intramuscular injection of 4 mg every 6 hours. Generally, the patient will improve in 12-24 hours, and gradually reduce the dose after 2-4 days, 5-7 Stop taking medication for days. For brain tumors that are not suitable for surgery, the first dose can be given as an intravenous bolus injection of 50 mg, followed by repeated doses of 8 mg every 2 hours, and then reduced to 2 mg per day after a few days, divided into 2-3 divided intravenous doses. For intrathecal injection, 5 mg each time, with an interval of 1-3 weeks; intra-articular injection is generally 0.8-4 mg each time, depending on the size of the joint cavity.
[Notes]
Mild external eye infections do not require the addition of corticosteroids. For severe bacterial keratitis, high-efficiency antibacterial drugs should be used with appropriate combination�Use. Contraindicated for fungal eye infections. It is contraindicated for viral infections, superficial and ulcerated types, and should be used in appropriate amounts for substantial herpes simplex keratitis and combined with effective antiviral drugs.
[Main reference materials]
[1] Deng Huiyin. Research on polycrystalline potassium hydroxide form of dexamethasone sodium phosphate [D]. Tianjin University, 2007.
[2]Zhou Sui. Research on the synthesis process of dexamethasone sodium phosphate[D]. Nanjing University of Science and Technology, 2012.
[3]Dang Shaochun. Process research on dexamethasone sodium phosphate sterile powder[D]. Tianjin University, 2014.
