Conventional anti-inflammatory steroids, such as cortisone, hydrocortisone, prednisone, prednisolone, etc., are high molecular weight steroidal compounds containing a number of hydrophilic functions, e.g., hydroxyl and keto functions. These compounds are characterised as having (1) extremely low water solubility, (2) extensive intermolecular hydrogen bonding due to the combination of hydrophilic functions, such as --OH and .dbd.O [as evidenced by their high melting point], and (3) high molecular weight.
All three points enumerated above contribute to the inefficient and slow penetrability of these conventional steroidal compounds through biological barriers, among which the most important are (i) the skin and (ii) the gastrointestinal wall.
It is recognized that in the case of the skin, the higher molecular weight anti-inflammatory steroids are absorbed primarily through the appendages and the hair follicles as opposed to the more efficient molecular intercellular absorption. See, M. Katz and B. J. Poulsen, "Absorption of Drugs through the Skin", [Handbook of Experimental Pharmacology, Vol. XXVII/I, Chapter 7, page 104, Springer Verlag, Berlin-Heidelberg-New York (1971).
It too is art recognized that (4) a serious side effect of certain of the known anti-inflammatory steroids is the decrease in thickness, or atrophy, of the skin at the site of application; (5) another adverse effect is a deleterious, systemic side effect on the thymus gland; and (6) in certain instances, with certain of the, e.g., hydrocortisone derivatives, the reduction of inflammation is inadequate.
In view of the foregoing, it is apparent that a serious need exists for a class of novel anti-inflammatory steroidal compounds which will overcome the aforementioned inefficiencies such that penetration of the same through biological barriers will be enhanced, such that less atrophy results, such that less effect on the thymus gland is evidenced, and such that inflammation is reduced to the comparable extent of the highly potent triamcinolone acetonide.
USPTO Backgrounds
USPTO Backgrounds