Preparation
CN201310539987.X provides a production process for Prednisolone phosphate sodium. The production process for Prednisolone phosphate sodium provided by this invention includes using prednisolone phosphate as raw material and comprising the following steps: (a) Dissolving prednisolone phosphate in methanol, adding purified water after dissolution, and adding sodium hydroxide solution dropwise to a tank for reaction. The temperature during the dropwise addition process is controlled at 15-30℃. The pH value is slowly adjusted to 9.2-10, stirred, and filtered after confirming that the pH value remains unchanged. (b) Adding ethanol to a dilution tank, adding the filtrate from step (a), stirring to precipitate a large amount of crystals, allowing it to stand for at least 8 hours, then discharging the material. The material is washed with ethanol and dried to obtain Prednisolone phosphate sodium. The volume of methanol used in step (a) is 4-5 times the weight of prednisolone phosphate, and the volume of purified water added is 4-6 times the weight of prednisolone phosphate. In step (a), the pH is slowly adjusted to 9.5. In step (b), the amount of ethanol added to the dilution vessel is 15-30 times the amount of prednisolone phosphate in grams.
Description
Prednisolone is a synthetic analog of the natural glucocorticoid corticosterone that has anti-
inflammatory and immunsuppressive actions. It avidly binds both glucocorticoid and mineralocorticoid receptors (K
is = 2.4 and 37 nM). Prednisolone Phosphate, prepared as the sodium salt, is a water-
soluble ester of the poorly soluble parent molecule, prednisolone. It is rapidly hydrolyzed
in vivo to the parent molecule when administered intravenously. In addition, when given orally, prednisolone phosphate is more readily absorbed than prednisolone, resulting in a higher effective blood concentration of prednisolone.
Chemical Properties
White or almost white, hygroscopic, crystalline powder.
Originator
Hydeltrasol, MSD ,US ,1957
Uses
Prednisolone Sodium is a synthetic corticosteroid; metabolically interconvertible with prednisone.
Definition
ChEBI: Prednisolone sodium phosphate is an organic sodium salt of prednisolone phosphate. It is an ophthalmology drug used for the treatment of short-term inflammatory eye conditions and helps relieve inflammation, redness and irritation of the eyes. It has a role as an ophthalmology drug, an anti-inflammatory agent, a glucocorticoid receptor agonist, a prodrug and an anti-allergic agent. It is an organic sodium salt and a glucocorticoid. It contains a prednisolone phosphate(2-).
Manufacturing Process
Preparation of Prednisolone 21-Methanesulfonate: Seventy liters of dry pyridine and 7.5 kg of prednisolone are charged to a 30-gallon jacketed glasslined still. The mixture is agitated until complete solution is obtained. About 40 liters of pyridine are distilled at high vacuum while maintaining the batch temperature below 40°C. The solution is cooled to 0°C, and 2.2 liters of methanesulfonyl chloride are charged. The batch temperature is maintained between 0°C and +3°C during charging of the methanesulfonyl chloride. An atmosphere of flowing nitrogen is maintained in the still, and the mixture isagitated during the last stages of the addition. The mixture is then aged for one hour, and 15 gallons of ice water are added cautiously to the still while maintaining the temperature between 0° and 5°C.
The still contents are then transferred to a jacketed kettle equipped with an agitator, and 62 kg of cracked ice in 15 gallons of deionized water are added. The batch is aged one hour and a solution of 2 liters of concentrated (37%) hydrochloric acid in 4 gallons of deionized water is added. The batch is centrifuged and the centrifuge cake washed free of pyridine with deionized water. The centrifuge cake is then vacuum-dried at 50°C to a moisture content of about 1%, which requires about 3 days of drying. Yield about 7.77 kg (92%), according to US Patent 2,932,657.
Preparation of Prednisolone 21-Iodide: To a 30-gallon jacketed glass-lined still 64.5 lb (31.0 liters) of dimethylformamide are charged by vacuum. The still contents are agitated as 7.74 kg of dry (less than 1% moisture) prednisolone 21-methanesulfonate are charged. Then 4.02 kg of sodium iodide are charged. The still contents are heated to 57° to 60°C by means of a steam jacket and held at this temperature for 30 minutes. The batch is cooled to 35°C and 12 gallons of deionized water are added at the rate of about 1 gallon per minute. In the event the solution becomes cloudy, addition of water is interrupted and the mixture agitated for five minutes before resumption of water addition. After all of the water is added, the batch is transferred to a 50 gallon kettle equipped with agitator and an additional 16.7 gallons of deionized water are added. The batch is cooled to 0° to 5°C and aged for one hour. The batch is filtered and the filter cake washed and vacuum dried at 30° to 35°C to a moisture content of less than 1%. Yield about 7.95 kg (96%), according to US Patent 2,932,657.
Preparation of Prednisolone 21-Disodium Phosphate: Acetonitrile (50.0 ml) containing phosphoric acid (90%; 1.0 ml) was treated with triethylamine (3.0 ml) and the solution added to 11β,17α-dihydroxy-21-iodopregna-1,4-diene-3,20dione (1.0 gram; powdered). The mixture was refluxed for 2.75 hours and the solvent was then evaporated under reduced pressure to give a yellow oil. The oil was taken up in methanol (25 ml) and titrated to pH 10.9 with sodium hydroxide in methanol (N) using a pH meter. The precipitate was filtered off and the filtrate evaporated to a gum under reduced pressure. The gum was taken up in methanol (5 ml), filtered through filter paper and acetone (100 ml) was added to the filtrate. The precipitate was filtered off, washed with acetone and dried at 100°C/1 mm for 0.75 hour giving a pale yellow solid, prednisolone disodium phosphate (0.74 gram), which was completely soluble in water, according to US Patent 2,936,313.
brand name
Hydeltrasol (Merck); Inflamase (Novartis); Metreton (Schering); Orapred
(BioMarin); Pediapred (UCB); Predair (Pharmafair).
Therapeutic Function
Glucocorticoid
References
[1] W. HOFKENS . Liposomal targeting of glucocorticoids to the inflamed synovium inhibits cartilage matrix destruction during murine antigen-induced arthritis[J]. International Journal of Pharmaceutics, 2011, 416 2: Pages 486-492. DOI:
10.1016/j.ijpharm.2011.02.060[2] RAYMOND M. SCHIFFELERS . Liposome-Encapsulated Prednisolone Phosphate Inhibits Growth of Established Tumors in Mice[J]. Neoplasia, 2005, 7 2: Pages 118-127. DOI:
10.1593/neo.04340
