Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Cosmetic – antiperspirant – dentifrice
Reexamination Certificate
2000-08-21
2003-03-18
Hartley, Michael G. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Cosmetic, antiperspirant, dentifrice
C424S400000, C424S486000, C424S487000, C424S078020, C424S078050, C514S557000, C514S574000, C514S859000
Reexamination Certificate
active
06534070
ABSTRACT:
PRIOR ART
EP 0 336 880 A2, which was applied for on Mar. 29, 1998, describes a pharmaceutical composition that consists of (i) azelaic acid at a concentration of 20% by weight, (iii) triacylglycerides and diacylglycerides, (iv) propylene glycol, (v) polysorbate, for example polyethylene (20) sorbitan monooleate, and (vii) water and salts. This composition that is to be administered topically is used for the treatment of various age-related changes in the facial skin. The composition exists as a cream. In addition, it is known to use the azelaic acid for inflammatory and infectious dermatoses, such as, for example, acne and rosacea.
Under the number 32 282, the 1996 Red List (ISBN 3-87193-167-5) describes a pharmaceutical composition with the name Skinoren that consists of (i) azelaic acid at a concentration of 20% by weight, (iii) triacylglycerides and diacylglycerides, (iv) propylene glycol, (v) polysorbate, for example macrogol stearate 1000 and (vii) water and salts. This composition that is to be administered topically is used for the treatment of acne. The composition exists as a cream. This document is regarded as the closest prior art.
International Application WO 96/11700, which was filed on Oct. 29, 1993, describes a pharmaceutical composition that is used as an adjuvant for a vaccine. This composition is to replace the Freund adjuvant. It is injected. As a (i) pharmaceutical active ingredient, for example, hepatitis B surface protein is used. In addition, (ii) polyacrylic acid, (iii) triacylglycerides and/or diacylglycerides, such as MIGLYOL, (iv) propylene glycol, and (v) polysorbates are used in the form of TWEEN, EMULROR and SIMULSOL M-53. (vi) Soybean lecithin is also to be added. The composition is an (vii) aqueous phase with salts. The composition is not administered topically. The emulsion has particles measuring 0.03 to 0.5 &mgr;m, preferably 0.05 to 0.2 &mgr;m.
International application WO 95/05163, which was filed on Aug. 5, 1994, describes a pharmaceutical composition that exists as an emulsion for the administration of biologically active substances on the skin surface. This composition contains particles measuring 30 to 500 nm, preferably 70 to 200 nm. As (i) pharmaceutical active ingredients, for example, anti-inflammatory medications are used. In addition, (ii) polyacrylic acid, (iii) triacylglycerides and/or diacylglycerides, (iv) propylene glycol, and (v) polysorbates are used in the form of TWEEN, EMULROR, TRITON X and SIMULSOL M-53. (iv) Soybean lecithin is also to be added. The composition is an (vii) aqueous phase with salts. The composition is administered topically.
European Patent Application EP 0 696 452, which was filed on Jul. 26, 1995, describes a nanoemulsion that is used for medication for treating the eyes, whereby the nanoemulsion is administered as eye drops that are to be applied topically. This composition contains particles of a mean size of 520 nm. As (i) pharmaceutical active ingredients, for example, anti-inflammatory medications are used. In addition, (ii) polyacrylic acid, (iii) triacylglycerides and/or diacylglycerides, (iv) propylene glycol, and (v) polysorbates are used in the form of polyoxyethylene polyoxypropylene copolymers. The composition is an (vii) aqueous phase with salts. The composition is administered topically.
Object and Achievement
The object is to offer a pharmaceutical composition with azelaic acid as a therapeutic active ingredient, whereby the bioavailability of the azelaic acid is to be increased.
In a composition according to the prior art that comprises the following features:
(i) azelaic acid as a therapeutic active ingredient,
(iii) triacylglycerides,
(iv) propylene glycol, and
(v) polysorbates
(vii) in an aqueous phase that comprises water and salts, the object is achieved in that the composition comprises
(ii) polyacrylic acid, and
(vi) lecithin
as other additives, and that in this case the composition is a hydrogel.
Advantages
The composition according to the invention has the advantage that it allows a larger amount of pharmaceutical active ingredient to penetrate into living skin layers and/or cutaneous organs. In this connection, the availability of the azelaic acid in the composition according to the invention is higher by a factor of three to five than in the azelaic acid-cream according to the prior art. This availability was demonstrated in a FRANZ-flow-diffusion cell test, which is depicted in detail in the examples. Specifically the living skin layers and/or cutaneous organs are the desired target sites for azelaic acid. It is especially common to use the composition in azelaic acid at high concentrations.
Another Embodiment of the Composition
A composition that is to be administered topically is advantageous.
Preferred is a composition according to the invention in which the azelaic acid is present at a concentration of 5 to 20% by weight, more preferably at a concentration of 10 to 18% by weight, and most preferably at a concentration of 14 to 16% by weight.
The presence of polyacrylic acid is essential. It is decisive for the production of the hydrogel. In the gel, the soybean lecithin is preferred as lecithin. The lecithin or soybean lecithin is advantageous at a concentration of up to 3% by weight. More preferred is a concentration of up to 1.5% by weight and most preferred a concentration of up to 1% by weight. The last concentration has the effect that the hydrogel is no longer present as a nanoemulsion.
Advantages
It has unexpectedly proven that the composition according to the invention in the case of concentrations in lecithin of 1% by weight and less does not form any standard nanoemulsion according to the prior art. Rather, a gel is present that comprises a homogenous mass with virtually no vesicles, but does have membrane fragments. The fact that azelaic acid and the remainder of the solution do not form any nanoemulsion was not expected. Only with the aid of scanning electron microscope recordings was it possible to provide clarity. It turned out that no nanoemulsion could be identified in microscopic examination. Advantageously, the composition according to the invention has a high penetration in living skin layers and/or cutaneous organs, which cannot be observed in creams.
Preferred Embodiments
Preferred is a composition in which the individual parameters, independently of one another, can have the following concentrations:
(ii) Polyacrylic acid at a concentration of 0.5 to 2% by weight,
(iii) triacylglycerides at a concentration of 0.5 to 5% by weight,
(iv) propylene glycol at a concentration of 5 to 15% by weight, and
(v) polysorbates at a concentration of 0.5 to 3% by weight.
The components are to be adapted to one another, of course, so that a sum of 100% is achieved.
Most preferred is a composition in which the individual parameters, independently of one another, can have the following concentrations:
(ii) Polyacrylic acid at a concentration of 1±0.25% by weight,
(iii) triacylglycerides at a concentration of 2±1% by weight,
(iv) propylene glycol at a concentration of 10±2% by weight, and
(v) polysorbates at a concentration of 2±0.5% by weight.
The components are to be adapted to one another, of course, so that a sum of 100% is achieved.
Definitions
Azelaic acid and its production is described in German Patent DE 28 17 133.7. Cf. Römpp, Chemie Lexikon [Lexicon of Chemistry], issued by Jürgen FALBE and Manfred REGNITZ, 1989, 9th Edition, page 323, Thieme Verlag Stuttgart, ISBN 3-13-734609-6.
Polyacrylic acid represents an anion-active polymerizate of acrylic acid, which is only partially water-soluble. The one-percent aqueous suspension has a pH of 3 and approximately the same viscosity as water. It is only during neutralization with inorganic or organic bases that gel formation and the production of highly viscous products take place. Rudolf VOIGT and Manfred BORNSCHEIN, 1979, Lehrbuch der pharmazeutischen Technologie [Textbook of Pharmaceutical Technology], page 314, VEB Verlag Volk und Gesundheit Berlin. Cf. Römpp, Ch
Franke Patrick
Günther Clemens
Riedl Jutta
Gollamudi Sharmila S
Hartley Michael G.
Millen White Zelano & Branigan P.C.
Schering Aktiengesellschaft
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