Description
Cortisone acetate(50-04-4) is a synthetic glucocorticoid with anti-inflammatory properties. It decreases the size of Bacillus Calmette-Guérin (BCG) vaccine-induced dermal lesions and tuberculin reactions in rabbits when administered at 2 mg/kg on alternate days over the course of 46 days. It also reduces the number and percentage of activated lesion-infiltrating mononuclear cells and decreases the amount of caseous necrosis and ulceration. Cortisone acetate (2.5 mg/kg per day, s.c.) slows tissue regeneration in a rabbit model of wound healing. It also decreases the number of dexamethasone binding sites on isolated human lymphocytes by 30%. Formulations containing cortisone acetate have been used to relieve inflammation, pruritic manifestations of corticosteroid-responsive dermatoses, and in the treatment of immune and allergic disorders.
Chemical Properties
White needle crystal or crystalline powder (acetone), odorless. Stable in the air. Mp239- 241°C, specific rotation [α]20D+164°(0.5%, acetone), [α]23D+169°(chloroform), [α]25D+208°-+217°(dioxane), The ethanol solution of this product has a maximum absorption at a wavelength of 240nm. Soluble in chloroform (1:4), soluble in acetone (1:75), slightly soluble in ethanol and ether, and hardly soluble in water. This product dissolves in sulfuric acid and turns yellow without fluorescence (different from hydrocortisone acetate).
Originator
Cortone Acetate,MSD,US,1950
Uses
Cortisone Acetate is a glucocorticoid. Cortisone Acetate is an antiinflammatory agent. Cortisone Acetate is bioavailable and readily converted to the therapeutically active form, Hydrocotisone (H71461
5).
Definition
ChEBI: Cortisone acetate is a corticosteroid hormone.
Preparation
Cortisone acetate is prepared from dehydropregnenolone by epoxidation, Wolff's oxidation, mycoxidation, chromic acid oxidation, hydrogen bromide ring-opening, Raney's nickel-catalyzed debromination, iodination, and acetyloxy substitution.
Manufacturing Process
The following technique is described in US Patent 2,541,104. A solution of 2.0
g of 3(α)-hydroxy-21-acetoxy-11,20-diketo-pregnane, which can be prepared
as described in Helv. Chim. Acta 27, 1287 (1944), is treated in a mixture of
25 cc of alcohol and 6.4 cc of acetic acid at 0°C with 6.0 g of potassium
cyanide. The solution is allowed to warm to room temperature and after 3
hours is diluted with water. The addition of a large volume of water to the
alcohol-hydrogen cyanide mixture precipitates a gum which is extracted with
chloroform or ethyl acetate. The extract is washed with water, and evaporated
to small volume under reduced pressure. The crystalline precipitate (1.3 g)
consists of 3(α),20-dihydroxy-20-cyano-21-acetoxy-11-keto-pregnane; dec.
175° to 185°C.
A solution of 0.60 g of chromic acid in 1.2 cc of water and 11 cc of acetic acid
is added to a solution containing about 1.2 g of 3(α),20-dihydroxy-20-cyano-
21-acetoxy-11-ketopregnane at room temperature. After 1 hour, water is
added and the product, which precipitates, is filtered and recrystallized from
ethyl acetate to produce 3,11-diketo-20-hydroxy-20-cyano-21-acetoxypregnane; dec. 214° to 217°C.
0.40 cc of phosphorus oxychloride is added to a solution containing about 950
mg of 3,11-diketo-20-hydroxy-20-cyano-21-acetoxy-pregnane dissolved in 3
cc of pyridine. After standing at room temperature for 24 hours, the solution
is poured into water and dilute hydrochloric acid, extracted with benzene and
concentrated to dryness. The crude product, after chromatography gives one
main constituent, namely δ17-3,11-diketo-20-cyano-21-acetoxy-pregnene; MP
189° to 190°C.
A solution of 1.0 g of δ17-3,11-diketo-20-cyano-21-acetoxy-pregnene in 10 cc
of benzene is treated with 1.0 g of osmium tetroxide and 0.43 g of pyridine.
After standing at room temperature for 18 hours, the resulting solution is
treated successively with 50 cc of alcohol, and with 50 cc of water containing
2.5 g of sodium sulfite. The mixture is stirred for 30 hours, filtered, and the
filtrate acidified with 0.5 cc of acetic acid and concentrated to small volume in
vacuo. The aqueous suspension is then extracted four times with chloroform,
the chloroform extracts are combined, washed with water and concentrated to
dryness in vacuo. Recrystallization of the residue from acetone gives 9°C. This
compound is then treated with acetic anhydride and pyridine for 15 minutes at
room temperature to produce 3,11,20-triketo-17(α)-hydroxy-21-acetoxypregnane or cortisone acetate.
Therapeutic Function
Glucocorticoid
General Description
Cortisone acetate, 21-(acetyloxy)-17-hydroxypregn-4-ene-3,11,20-trione, is the 21-acetate of naturally occurring cortisone with good systemicanti-inflammatory activity and low-to-moderate salt-retentionactivity after its in vivo conversion to hydrocortisoneacetate. This conversion is mediated by 11β-hydroxysteroiddehydrogenase. It is used for the entire spectrum of uses discussedpreviously under the heading, “Therapeutic Uses ofAdrenal Cortex Hormones”—collagen diseases, Addisondisease, severe shock, allergic conditions, chronic lymphocyticleukemia, and many other indications. Cortisone acetateis relatively ineffective topically, mainly because itmust be reduced in vivo to hydrocortisone. Its plasma halflifeis only about 30 minutes, compared with 90 minutes to3 hours for hydrocortisone.
Purification Methods
Crystallise -1cortisone-21-acetate from acetone or CHCl3. The UV has 15,800 M-1cm at 238nm in dioxane. [Sarett J Biol Chem 162 601 1946, Beilstein 8 III 4058, 5 IV 3481.]
References
1. Cortisone acetate in skin disease; local effect in the skin from topical application and local injection. DOI:
10.1001/ARCHDERM.1952.015302100560072. McCue, R.E., Dannenberg, A.M., Jr., Huguchi, S., et al. The effect of cortisone on the accumulation, activation, and necrosis of macrophages in tuberculous lesions. Inflammation 3(2), 159-176 (1978). DOI:
10.1007/BF009107373. Joseph, J., and Tydd, M. The effects of cortisone acetate on tissue regeneration in the rabbit’s ear. J. Anat. 115(Pt. 3), 445-460 (1973).
4. Schlechte, J.A., Ginsberg, B.H., and Sherman, B.M. Regulation of the glucocorticoid receptor in human lymphocytes. J. Steroid Biochem. 16(1), 69-74 (1982). DOI:
10.1016/0022-4731(82)90145-55. Sittig's Pharmaceutical Manufacturing Encyclopedia
6. Textbook of organic medicinal and pharmaceutical chemistry. DOI:
10.1002/jps.30304511207. Purification of Laboratory Chemicals DOI:
10.5860/choice.50-6768
