Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1997-07-02
2000-12-05
Spear, James M.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424465, 424474, 514970, A61K 920, A61K 928
Patent
active
061563412
DESCRIPTION:
BRIEF SUMMARY
The invention relates to pharmaceutical agents that contain gallic acid ester as an antioxidant in combination with a steroidal active ingredient, their production and their use.
This invention involves the production of pharmaceutical formulations that contain low-dosed steroid hormones as active ingredients and are stabilized against oxidative degradation reactions by the addition of gallic acid ester. The active ingredient concentrations in the respective form of administration, for example a tablet or coated tablet, are usually 0.1-200 .mu.g.
Low-dosed hormones are oxidatively degraded (e.g., to the corresponding 6-hydroxy, 6-keto and delta-6 or delta-9 compounds) in pharmaceutical preparations according to what is probably a radical reaction mechanism. To prevent or delay the oxidation process in pharmaceutical preparations or to be able to guarantee the declared amount of active ingredient continuously over the storage period, antioxidants are often added. The increased stability of the steroid-containing pharmaceutical preparations that is thus achieved offers the advantage of a longer shelf life without having to use special primary packing means such as, e.g., oxyblock bags.
Antioxidants are adjuvants that are used at low concentrations to protect oxidation-sensitive substances in pharmaceutical preparations over a prolonged period or to delay their oxidation. Quite generally, they are stabilizers or oxidation inhibitors, which are used not only in pharmaceutics but also in the food, plastic, and rubber sectors. (H. Sucker, P. Fuchs, P. Speiser in Pharmazeutische Technologie [Pharmaceutical Technology], Thieme Verlag, Stuttgart, 1991; Patent WO 93/17567). In aqueous preparations the mechanism of action is known.
The mode of action of antioxidants in non-aqueous systems is presumed to involve multi-stage radical chain mechanisms in which antioxidants intervene at specific stages depending on type and as a result interrupt or inhibit the chain mechanisms (K. H. Bauer, K. H. Fromming, C. Fuhrer in Pharmazeutische Technologie, Thieme Verlag, Stuttgart, 1986). In non-aqueous systems, antioxidants are used mainly in semi-solid preparations such as ointments, emulsions, and suspensions (Rote Liste 1994 [Red List 1994], Editio Cantor Aulendorf). Thus, for example, contained phosphatide is protected against discoloration by adding butylhydroxytoluene and/or butylhydroxyanisole to a corticoid-containing skin preparation. Its shelf life has been extended considerably (U.S. Pat. No. 4,427,670). The use of antioxidants in different combinations increases the chemical and physical stability of an antibiotic-containing eye ointment and the corresponding eye drop (Drug. Dev. and Industrial Pharmacy 19 (1993) pp. 2595-2609).
By comparison, there are only a few solid, oral dosage forms that contain antioxidants (Stoffliste [List of Substances], 8th Edition, Werbe- u. Vertriebsgesellschaft [Advertising and Marketing Company], Eschborn). For example, i.a., DL.alpha.-tocopherol is used as an adjuvant in lynesternol- and desogestrel-containing tablet preparations. (Rote Liste 1994, Editio Cantor, Aulendorf).
In such dispersed systems, however, in addition to the selection of the suitable antioxidant, how the antioxidant is incorporated into the pharmaceutical preparation is of decisive importance for the desired improvement in stability (Walter Lund in The Pharmaceutical Codex, 12th Edition, The Pharmaceutical Press, 1994, pp. 289-292).
The object was to prevent or delay, by using antioxidants, the massive oxidative degradation of the steroidal active ingredient in the solid oral form of administration by using the lowest possible concentrations of the antioxidant, so that storage times of up to 5 years can be achieved.
Just as when the active ingredient is incorporated into the production of low-dosed tablets in the dose range of 0.1 .mu.g to 200 .mu.g, dilution steps at a ratio of 1:1000 to 1:100,000 are also to be implemented in incorporating the antioxidant. To ensure the required dosage accuracy per single-dosed d
Backensfeld Thomas
Keitel Susanne
Lipp Ralph
Schering Aktiensgesellschaft
Spear James M.
LandOfFree
Low-dosed steroid tablets that contain gallic acid ester as an a does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Low-dosed steroid tablets that contain gallic acid ester as an a, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Low-dosed steroid tablets that contain gallic acid ester as an a will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-959110