WO1994007509A1

WO1994007509A1 - Topical treatment agent or medicament containing finely divided transparent zinc oxide

Info

Publication number: WO1994007509A1
Application number: PCT/EP1993/002606
Authority: WO
Inventors: Claus E. Lange
Original assignee: Lange Claus E
Priority date: 1992-09-25
Filing date: 1993-09-24
Publication date: 1994-04-14
Also published as: AU5122393A; DE4232143A1

Abstract

The object of the invention consists of topical treatment agents or medicaments, especially for the treatment of eczemas and pustulous forms of acne, which, in addition to cosmetic or pharmaceutical auxiliaries and carriers, contain finely divided transparent zinc oxide with a primary particle size in the region of 5 to 30 nm, and especially 5 to 15 nm. Said agents, with increased microbiological activity, are distinguished by a relatively low concentration of finely divided zinc oxide which does not put a white coating on the skin and does not soil clothing. In addition, by contrast with ordinary commercial zinc oxide, it gives no unpleasantly dull, dry skin feeling.

Description

Topical care products or pharmaceuticals containing fine-particle transparent zinc oxide

The invention relates to topical care products or medicinal products, in particular for the treatment of eczema and pustular forms of acne.

Coarsely disperse zinc oxide has been used for decades, particularly in the local treatment of skin diseases. It has an astringent effect and is considered to have an antimicrobial effect. Due to its weakly alkaline reaction, zinc oxide is able to bind unpleasant smelling acids (K. Thoma: Dermatika, Munich, 1983, p. 310; Schneider and H. Ruther: general therapy, II. Old-style local therapy, in: HA Gottron &. Schönfeld: Dermatology and Venereology Volume 1 / Part 2, p. 973; G. Thie e, Stuttgart, 1962.

Coarse disperse zinc oxide is used in particular in shake mixes, pastes and powders. These are used, among other things, to treat eczema and dermatitis, ie superficial inflammatory skin diseases that are accompanied by redness, swelling and / or blistering and which cause itching. used. The use of zinc oxide in pustular forms of acne is also proposed.

However, the therapeutic applicability in outpatient treatment is limited by a number of negative side effects: Coarse disperse zinc oxide acts like a white pigment in the concentrations necessary for local treatment, for example in the range from 5 to 25% by weight. It covers the skin white and soils the clothing. It also causes an uncomfortably dull, dry feeling on the skin.

Fine-particle transparent zinc oxide is commercially available and is known in particular as a product for UVA and UVB protection in light protection formulations. According to EP-0 435 086 Al, finely divided zinc oxide with a particle size of less than 50 nm is used in sunscreens. In GB-2 184 356 B zinc oxide with an average particle size of 30 to 70 nm is used for the same purposes.

From DE 37 04 214 C2 it is known to use cosmetic dyes based on pulverized iron oxide to match different skin tones, in particular with acne ointments. This is to ensure that the ointment containing zinc oxide is well tolerated and easy to apply and, moreover, is as little as possible.

With the help of the dyes mentioned, it is possible to adapt the ointment to different skin tones, but the soiling of the clothing and the uncomfortably dull, dry feeling on the skin are not eliminated during use. In addition, the pharmaceutical effect, especially in the treatment of eczema and pustular forms of acne, is not sufficient.

FR-PS 1066 describes a medicament which, in addition to pharmaceutical auxiliaries and carriers, contains a red zinc oxide. While the introduction describes that o a powder with a particle size of about 200 A (20 nm) im

In contrast to white zinc oxide, it simply penetrates the folds of the epidermis, the text goes on to say that X-ray diffraction according to Debye-Scherrer measures crystallites with a size of 40 nm for red zinc oxide and 100 to 500 nm for white zinc oxide according to the pharmacopoeia has been.

The important pharmacopoeias of the world prescribe, however, that only white zinc oxide may be used in medicinal products, since red zinc oxide contains at least traces of impurities (dopants) which are responsible for the color change. This red zinc oxide cannot therefore be used as an active pharmaceutical ingredient.

In contrast, the object of the present invention is to provide topical care products or pharmaceuticals, in particular for the treatment of eczema, dermatitis and pustular forms of acne, which overcomes the aforementioned disadvantages of the prior art and, in contrast, has an improved effectiveness, in particular in the treatment of Have eczema and pustular forms of acne.

The solution to the aforementioned problem consists in topical care products or medicaments, in particular for the treatment of eczema and pustular forms of acne, containing, in addition to pharmaceutical auxiliaries and carriers, finely divided, transparent zinc oxide with a primary particle size in the range from 5 to 30 nm.

Surprisingly, it was found that finely divided zinc oxide in the sense of this invention has a significantly increased effectiveness in the treatment of eczema, dermatitis and pustular forms of acne compared to zinc oxide of conventional particle size.

Compared to conventional zinc oxide, finely divided zinc oxide has an increased microbiological activity. Similarly, a stabilizing effect on the ointment and emulsion bases was also observed. The presence of the finely divided zinc oxide caused an inhibition of the germ growth. The inhibition of germ growth in the ointment and cream bases also serves as a preservation. This achieves a stabilizing effect of the ointment and emulsion bases.

The preferred primary particle size is 5 to 15 nm, since there is complete transparency in this particle size range. It has surprisingly been found that finely divided, transparent zinc oxide can be incorporated in a particularly good manner into formulations known per se for the production of zinc oxide pastes. It was found that the usually uncomfortably dull, dry feeling on the skin did not occur when using finely divided transparent zinc oxide. This cosmetic effect also allows zinc oxide to be used in skin care products in which it has so far been of no importance because of this disadvantageous effect. In addition, it is possible to produce topical medicaments for the above-mentioned indications in a transparent form, which allow the treatment of patients to be carried out far more frequently, so that the exposure times can be increased overall. Here, too, the cosmetic effect is of particular importance, since the pleasant feeling on the skin in conjunction with the transparency enables it to be used more frequently, even on exposed parts of the body.

The zinc oxide to be used according to the invention differs from the conventional zinc oxide pigment by its very small primary particle size (5 to 30 nm, in particular 5 to 15 nm compared to approximately 200 nm of the conventional zinc oxide), in particular with a very high specific surface area (BET 90 to 140 m ² / g). The particle size was determined by X-ray diffractometry. However, the properties of light scattering in the visible range which are characteristic of a pigment are no longer present in the zinc oxide to be used according to the invention. Thin films are therefore completely transparent. While the previous applications for finely divided, transparent zinc oxide can be seen in physical sun protection in light protection formulations, the essence of the present invention is to use particularly fine-particle zinc oxide in the treatment of inflammatory skin diseases and as a skin care component. The use of conventional coarse-particle zinc oxide for these purposes has long been known in the pharmaceutical sector.

According to Römpps Chemie-Lexikon, 9th edition, p. 5143, zinc preparations usually contain 10 to 30% by weight zinc oxide in addition to other components. Corresponding concentrations of finely divided zinc oxide can also be used in the context of the present invention.

However, it has been found that finely divided transparent zinc oxide according to the present invention can be used in much lower concentrations. It was found that, despite the reduced concentration of zinc oxide, the properties known per se from coarsely dispersed zinc oxide were in some cases greatly improved or even effects were observed which could not be observed at all with coarsely dispersed zinc oxide. Accordingly, there is a further embodiment of the present ¬ invention in that the agents contain only 0.5 to 15, in particular 1 to 10, preferably 2 to 8 wt .-% of finely divided zinc oxide.

Zinc preparations based on coarsely dispersed zinc oxide for skin and wound treatment are known per se and are differentiated into zinc oil, zinc glue, zinc paste, soft zinc paste and zinc ointment. All of the aforementioned preparations can also be produced with the finely divided zinc oxide in the sense of the present invention. According to Römpps Chemie Lexikon, 9th edition, p. 3969, it is known to refer to the ointment base materials required for the production of ointments, pastes and creams as the ointment base. As carriers or vehicles, these are intended to promote the penetration or absorption of the active substances. For the purposes of the present invention, it is therefore preferred to use the gels used as the ointment base, hydrocarbon gels, for example petroleum jelly, piastibase; Lipogels, for example waxes, in particular beeswax, walrus, wool wax, oils, fats, for example ethoxylated or acetylated fats and oils; hardened peanut oil, semi-synthetic fats; Hydrogels, in particular Aerosil, bentonites, organic hydrogels, in particular starch, tragacanth; Polyethylene glycol gels and / or silicone oils, in particular silicone oils, solidified with Aerosil or calcium stearate, contain.

In a further embodiment of the present invention, the topical agents may further contain emulsifiers, antioxidants, preservatives and / or humectants.

The advantages of the finely divided, transparent zinc oxide in the treatment of eczema, in particular seborrheic eczema, and pustular forms of acne have been found to be particularly advantageous. Pustular forms of acne that can be treated particularly well with the agents according to the invention are understood to mean in particular acne vulgaris, rosacea and perioral dermatitis.

In particular, it was found that, in patients with atopic dermatitis, fine-particle transparent zinc oxide in a low concentration, applied within a few days, led to a clear regression of the reddening of the skin and the wetting of the skin. In a number of patients who had extensive skin symptoms, in particular in the face, neck, arms and legs, it was found that that the reddening of the skin subsided within a few days and the skin wetting was significantly reduced. The itching was also greatly reduced. No habituation effect was demonstrated for weeks.

Examples

A 25-year-old patient, who since early childhood ausge¬ stretched skin conditions, relating in particular to the face, neck, arms and legs, suffered, was treated with finely divided transparent zinc ^'oxide. The symptoms consisted of reddening, oozing, thickening (lichenification) and scaling of the skin. In addition, there were scratched skin areas. The patient suffered from severe itching. In the past, the patient was treated with cortisone-containing externals, with UV light and with skin-care creams and ointments.

An ointment was produced which contained 5% by weight of finely divided transparent zinc oxide (primary particle size 5 to 15 nm, BET surface area 90 to 140 m ² / g) with 47.5% by weight of Eucerin ^R (wool wax alcohol ointment for pharmaceutical and cosmetic use, Beiersdorf) and mixed homogeneously with 50% by weight of water.

The ointment was applied to the patient twice a day.

Within 3 days there was a clear regression of reddening of the skin and wetting of the skin. This was associated with a significant decrease in the itch.

Medical treatment with a conventional zinc paste (20% by weight) did not lead to a comparable result over the course of weeks.

Comparative Example 1

A 38-year-old patient who suffered from skin appearances of the same type as in Example 1 was treated analogously to Example 1 with a conventional soft zinc paste, which was applied only once a day. No significant regression of reddening and oozing of the skin was found become. There was also no decrease in the itch.

Claims

PATENT CLAIMS

1. Topical care products or pharmaceuticals, in particular for the treatment of eczema and pustular forms of acne, containing, in addition to cosmetic or pharmaceutical auxiliaries and carriers, finely divided transparent zinc oxide with a primary particle size in the range from 5 to 30 nm.

2. Composition according to claim 1, characterized in that the primary particle size of the finely divided transparent zinc oxide is in the range of 5 to 15 nm.

3. Composition according to claim 1 or 2, characterized in that the specific surface of the finely divided transparent zinc oxide is 90 to 140 m ² / g, determined according to BET.

4. Composition according to one or more of claims 1 to 3, containing 0.5 to 15, in particular 1 to 10, preferably 2 to 8% by weight of zinc oxide.

5. Composition according to one or more of claims 1 to 4, comprising zinc oil, zinc glue, zinc paste, soft zinc paste and zinc ointment.

6. Composition according to one or more of claims 1 to 5, containing hydrocarbon gels, lipogels, oils, fats, hydrogels, polyethylene glycol gels and / or silicone gels.

7. Composition according to one or more of claims 1 to 6, containing emulsifiers, antioxidants, preservatives and / or humectants. 8. Use of the medicament as defined in one or more of claims 1 to 7, for the treatment of eczema and pustular forms of acne.

9. Use according to claim 8 for the treatment of atopic dermatitis, seborrheic eczema and acne vulgaris, rosacea and perioral dermatitis.

CHANGED REQUIREMENTS

[Received at the International Office on February 17, 1994 (February 17, 1994), original claims 8 and 9 replaced by amended claims 8 and 9; added new claim 10; al le further claims unchanged (1 page)]

8. Use of the topical care products or pharmaceuticals as defined in one or more of claims 1 to 7, for the treatment of eczema and pustular forms of acne.

9. Use of f-part zinc oxide with a primary particle size in the range from 5 to 30 nm for the production of topical care products or medicaments as defined in one or more of claims 1 to 7, for the treatment of eczema and pustular forms of acne.

10. Use according to claim 8 or 9 for the treatment of atopic dermatitis, seborrheic eczema and acne vulgaris, rosacea and perioral dermatitis.