WO1997027837A1

WO1997027837A1 - New chemical mixtures with excellent microbicide, fungicide, and virucide effects; preparation methods, and use

Info

Publication number: WO1997027837A1
Application number: PCT/SI1996/000001
Authority: WO
Inventors: Slavko Dokmann
Original assignee: Slavko Dokmann
Priority date: 1996-02-02
Filing date: 1996-02-02
Publication date: 1997-08-07
Also published as: AU4500196A

Abstract

The invention relates to the new chemical mixtures with excellent microbicide, fungicide and virucide effects that are characterised by their containing alums or the mixture of various alums, zinc sulphate and glycerine. The invention refers particularly to the procedures for obtaining the new chemical mixtures that are used as a cosmetic or healing agent. The invention refers particularly to the use of described chemical mixtures as the effective agents for elimination of skin damages and skin manifestations that arise after the action of the herpes simplex virus.

Description

NEW CHEMICAL MIXTURES WITH EXCELLENT MICROBICIDE, FUNGICIDE, AND VIRUCIDE EFFECTS; PREPARATION

METHODS, AND USE

Relevant field of technology:

Int. class: A 61K 7/38 A 61K 7/40 A 61K 33/30 A 6 IK 45/06 A 61K 33/38

The invention refers to a new products which contain the alums or the mixtures of various alums and zinc sulphate; to the methods for theirs preparation and theirs use.

The invention refers particularly to the new chemical mixtures that are characterised by their containing aluminium ammonium sulphate, ferric ammonium sulphate, aluminium potassium sulphate, zinc sulphate and glycerine; or aluminium ammonium sulphate, aluminium potassium sulphate, zinc sulphate, and glycerine; or aluminium ammonium sulphate, ferric ammonium sulphate, zinc sulphate, and glycerine; or aluminium ammonium sulphate, zinc sulphate, and glycerine; or aluminium potassium sulphate, zinc sulphate, and glycerine; or ferric ammomum sulphate, zinc sulphate, and glycerine; or aluminium potassium sulphate, ferric ammonium sulphate, and glycerine; or aluminium ammonium sulphate, ferric ammonium sulphate, and glycerine; or aluminium ammonium sulphate, aluminium potassium sulphate, and glycerine; or aluminium ammonium sulphate in glycerine; or aluminium potassium sulphate in glycerine. The chemical mixtures described in the invention have a clear-cut microbicide, fungicide, and virucide effects and are used for elimination of skin damages. The subject of this invention also refers on the use of described chemical mixtures as effective preparations of all kinds of skin disturbances; it specially prevents and eliminates skin manifestations caused by the virus of herpes simplex.

The advantage of the chemical mixtures described in this invention is that their use prevents and eliminates the consequences of microbide, fungicide and virucide skin infections or rather consequences of all kinds of skin disturbances.

A special advantage ofthe chemical mixtures described in the invention is that they eliminate consequences of damages whose instances of intolerability are particularly manifested in restricted parts of skin. The top advantage of the described products are that they eliminate superbly very different skin manifestations caused by the virus of herpes simplex.

In the technical literature there have not been so far descriptions of preparation and use of the chemical mixtures that serve to treat skin disturbances, and which contain alumnus or the mixture of various alumnus with zinc sulphate, and a corresponding humectant acceptable for the skin. In the literature there have not been so far descriptions of preparation of chemical mixtures which contain two salts dissolved in glycerine.

It is well known that various alums and sulphate salts are, owing to their specific features, used for skin care, for elimination of skin disturbances, and for elimination of infectious skin manifestations.

It is known that aluminium salts have extraordinary deodorant, astringent and markedly bactericide features. In the literature there are descriptions of numerous preparations serving for skin care, body and foot deodorising, and treatment of cystic acne and seborrhoea, which contain aluminium salts or aluminium ammonium sulphate. So the literature offers a descriptions of an extraordinary astringent and deodorant cream that contains about 10 % aluminium ammonium sulphate and 3-5 % boric acid (Japanese patent 83, 83.612 of 19 May 1983, quoted from "Chem. Abstr." 99 (1983) 58747 j ). Also in the more recent literature there is a description of an antiperspirant product containing 40-60 % of aluminium ammonium sulphate and 40-60 % boric acid (American patent 4.954.334 of 4 September 1990, quoted from "Chem. Abstr." ϋ4 (1991) 29947 x). For treatment of cystic acne, seborrhoea and other skin anomalies there are descriptions of lotions and creams that contain 13 % aluminium salt (American patent 4.331.653. of 25 May 1982, quoted from "Chem. Abstr." 97 (1982) 78904 v).

Ferric salts, along with their mildly astringent and deodorant features, have also distinct fungicide effect, and especially the ferric ammonium sulphate. In the literature there is a description of a product for revitalisation of skin and prevention of wrinkles, which contains 0.5-20 % ferric alum (French patent 2.238.473 of 21 February 1975, quoted from "Chem. Abstr." 83 (1975) 136730 j). The ferric ammonium sulphate is used as a deodorant, preservative, astringent, and an anti-inflammatory agent with an outstanding fungicide effect ("Chem. Abstr "115 (1991) 113274 d).

Aluminium potassium sulphate is traditional and most often used deodorant, astringent and antiseptic with excellent microbicide features. Known are numerous cosmetic preparations that contain, as an active component, aluminium potassium sulphate, and are more frequently used as deodorants (Japanese patent 87.101.201 of 11 May 1987, quoted from "Chem. Abstr." 107 (1987) 140915 e). More recent literature data describe an anti- inflammatory cosmetic preparation for treatment of acne, folliculitis, eczema and other skin disturbances, which contains aluminium potassium sulphate and salts (Japanese patent 90.111.714. of 24 April 1990, quoted from "Chem Abstr " 113 (1990) 84830 h).

Zinc salts are used with roughly equal success in cosmetic and pharmaceutics preparations. Due to their astringent and anti-inflammatory features, zinc compounds are used in compositions that serve for acne treatment (European patent application 281812 of 14 September 1988, quoted from "Chem. Abstr." £& 1988) 237059 h). In the literature there is a description of a cosmetic gel, which contains, as active components, aluminium chloride, alum, and zinc sulphate, and is used as astringent, deodorant, and agent for stimulation of peripheral circulation (Ger. Offen. 2.423.637 of 27 November 1975, quoted from "Chem. Abstr " 84 (1976) 65190 r).

The efficiency of zinc sulphate is well known, especially with treatment herpes simplex lesions. So it is described in the literature that 0.25 % zinc sulphate in a camphor water solution eliminates very successfully all skin damages that arise as consequences of the activity of the herpes simplex virus. A patient with acute herpes simplex lesions on the lips and cheeks applies 0.25 zinc sulphate in a camphor water solution: itching ceases, lip and cheek lesions get dry, and scabs come off very quickly (American patent 4.661.354 of 28 April 1987, quoted from "Chem. Abstr." 107 (1987) 161701 x). The mechanism of antiviral action of the zinc sulphate is described in the literature, where it is stated that unspecified depositing of zinc on the "virion" membrane components has been proved by means of electronic micrography ("Chem. Abstr." 1J4 (1991) 55348 x). In the literature there is also a description of a synergistic pharmaceutics mixture with pronounced virucide andbactericide actions, which contains, as active components, lithium succinate, zinc sulphate, ascorbic acid, and salicylic acid (European patent application 287210 of 19 October 1988, quoted from "Chem. Abstr." I l l (1989) 70953 x).

The invention refers to the new chemical mixtures with excellent microbicide and virucide actions, which contain, as active substances, alums or the mixture of various alums, zinc sulphate, and a hydrophylic emollient. The alums in glycerine described in the invention act very effectively, so aluminum ammonium sulphate in glycerine has bactericide action, and aluminum potassium sulphate has effective microbicide action. The chemical mixtures described in the inventions act in a synergistic way, or rather that they have greater efficiency than individual active components used in the mixture. The described synergistic mixtures are more active and they extend the boundaries of microbicide, fungicide and virucide actions.

The next advantage of the chemical mixtures desribed in this invention is that they present a non-ionic system, and non-ionizations have a smaller tendency to irritate skin, and they make the products stable and homogeneous.

The chemical mixtures described in the invention are characterised by the fact that the active substances dissolved in tbe glycerine, that is in the agents which, in itself, make the skin elastic and smooth, and which maintain a normal natural factor of moistening the skin.

The saturated glycerine solutions described in the invention contain maximum concentration of alum or mixture of various alums, and optimal concentration of zinc sulphate; they do not contain a preservative, and they are, in themselves, protected. With regard to what has been said, its use does not lead to irritation and sensitisation during its application on the skin. The advantage of the chemical mixtures described in the invention are that with their use all skin manifestations are eliminated successfully, or rather consequences of exogenous and endogenous skin damages such as acne, folliculitis, seborrhoea, eczema, pimples and other local inflammations.

A special advantage ofthe chemical mixtures described in the invention are that they eliminate efficiently consequences of sudden erosions on the skin surface that arise through the action ofthe herpes simplex virus.

In a healthy and unchanged skin, moistness, elasticity and smoothness of the skin are regulated by emulgated fats of the corneous part of the skin. Healthy and undamaged skin is protected from bacteria and fungi by a normal regeneration, small humidity of the keratinous matter. An increased production of sebaceous glands and a deranged process of skin keratinization are manifested as folliculitis and seborrhoea.

Biochemical changes in the epidermis and dermis are causes of various eczema and itchings in the skin. Hormonal derangements and a derangement in sebacious glands are manifested as cystic acne, purulent pimples and various edema. Lack of vitamins and minerals also causes changes in the keratinous part ofthe skin.

Skin damages may also arise after sudden eruptions of a smaller or greater number of grouped, hemispherical or polygonal limpid vesicles, size from millet to lens, on the unchaged or somewhat hyperemic skin. These skin damages are consequences of the herpes simplex virus. Such superficially located sharply restricted erosions create all the greater defects and cause itching, tension and burning of the skin. With cracking of watery vesicles a favoravle medium is created for actions of various microorganisms.

The chemical mixtures described in the invention have very efficient impact on the demaged and changed skin. After the described chemical products have been used, the skin is humid, elastic, and smooth; it is not too much degreased and is not irritated. The next effect of the described chemical mixtures are their efficacious elimination of the effects of sudden skin eruptions or rather their elimination of action of the herpes simplex virus; they prevent expansion of larger defects on the skin.

The subject-matter of this invention are the new products that have an efficient impact on the changed skin, that remove efficiently consequences of all kinds of skin damages and that meet the following basic requirements:

- they act in a keratinotropic manner, or rather they penetrate into the keratinous layer of the skin, and thus they speed up regeneration of the skin.

- they act in a sebotropic manner, or rather they have effects on manner functions of the sebacious glands, on the sebum created, and on the accompanying microflora; in this way, they prevent larger skin defects.

- they act in a dermatotropic manner, or rather they penetrate into deeper layers of the skin, hair follicles, sebacious glands; in this way, they accelerate indirectly elimination of ail kinds of skin damages.

- they act in a virucide manner, and in this way they eliminate the consequences ofthe action ofthe hermes simplex virus.

The new chemical mixtures of the invention contain:

- aluminium ammonium sulphate dodecahydrate which acts in a bactericide and mildly astringent manner, and/or

- ferric ammonium sulphate dodecahydrate which acts in a fungicide and mildly astringent manner and/or

- aluminium potassium sulphate dodecahydrate which acts in a microbicide and mildly astringent manner, and/or

- zinc sulphate which acts in a markedly virucide and mildly astringent manner, and/or

- appropriate humectant that makes the skin soft and elastic and/or

- double salts dissolved in glycerine.

They do not contain any preservatives that might act in an irritating manner. The described invention refers particularly to the new chemical mixtures that are characterised by their containing aluminium ammonium sulphate, ferric ammonium sulphate, aluminium potassium sulphate, zinc sulphate and glycerine; or aluminium ammonium sulphate, aluminium potassium sulphate, zinc sulphate, and glycerine; or aluminium ammonium sulphate, ferric ammonium sulphate, zinc sulphate, and glycerine; or aluminium ammonium sulphate, zinc sulphate, and glycerine; or aluminium potassium sulphate, zinc sulphate, and glycerine; or ferric ammonium sulphate, zinc sulphate, and glycerine; or aluminium potassium sulphate, ferric ammonium sulphate, and glycerine; or aluminium ammonium sulphate, ferric ammonium sulphate, and glycerine; or aluminium ammonium sulphate, aluminium potassium sulphate, and glycerine; or aluminium ammonium sulphate in glycerine; or aluminium potassium sulphate in glycerine.

The chemical mixtures of the invention can be of the following composition:

aluminium ammonium sulphate dodecahydrate 20.0 - 30.0% ferric ammonium sulphate dodecahydrate 0.1 - 0.5% aluminium potassium sulphate dodecahydrate 1.0 - 5.0% zinc sulphate 0.5 - 5.0% and glycerine up to 100%,

or aluminium ammonium sulphate dodecahydrate 5.0 - 20.0% aluminium potassium sulphate dodecahydrate 5.0 - 15% zinc sulphate 1.0 - 5.0% and glycerine up to 100%,

or aluminium ammonium sulphate dodecahydrate 5.0 - 30.0% ferric ammonium sulphate dodecahydrate 1.0 - 5.0% zinc sulphate 1.0 - 5.0% and glycerine up to 100%.

or aluminium ammonium sulphate dodecahydrate 10.0 - 35.0% zinc sulphate 1.0 - 5.0% and glycerine up to 100%, or aluminium potassium sulphate dodecahydrate 10.0 -35.0% zinc sulphate 1.0 - 5.0% and glycerine up to 100%.

or ferric ammonium sulphate dodecahydrate 10.0 - 35.0% zinc sul phate 1.0 - 5.0% and glycerine up to 100%,

or ferric ammonium sulphate dodecahydrate 1.0 - 5.0% aluminium potassium sulphate dodecahydrate 10.0 - 35.0% and glycerine up to 100%,

or aluminium ammonium sulphate dodecahydrate 5.0 - 35% ferric ammonium sulphate dodecahydrate 1.0 - 5.0% and glycerine up to 100%,

aluminium ammonium sulphate dodecahydrate 5.0 - 20.0% aluminium potassium sulphate dodecahydrate 5.0 - 20.0% and glycerine up to 100%,

or aluminium ammonium sulphate dodecahydrate 40.0% and gylcerine up to 100%,

or aluminium potassium sulphate dodecahydrate 40.0% and glycerine up to 100%.

Chemical mixtures of the invention can be in the form of a saturated gylcerine solu¬ tion. The chemical mixtures described in this invention present the new products with excellent microbicide, fungicide and virucide impacts.

The invention refers to the application of the previously defined products as microbicide, fungicide and virucide agents, and to the procedure for local medicamentosus medical treatment characterized by the fact that the agent is applied to the damaged skin.

The invention refers to the procedure of preparation of the new chemical mixture with excellent microbicide, fungicide and virucide effects and is illustrated by the following examples:

Example 1:

The procedure consists of mixing and slow heating to 35-45 °C of the following substances:

20.0 - 30.0 g aluminium ammonium sulphate dodecahydrate 0.1 - 0.5 g ferric ammonium sulphate dodecahydrate 1.0 - 5.0 g aluminium potassium sulphate dodecahydrate 0.5 - 5.0 g zinc sulphate

60.0 - 80.0 g glycerine

A cooled solution is toned with one of the approved synthetic organic colours. The preparation is filled into appropriate polyethylene or glass small contairnes with or without a special piece.

Example 2:

5.0 - 20.0 g aluminium ammonium sulphate dodecahydrate 5.0 - 15.0 g aluminium potassium sulphate dodecahydrate 1.0 - 5.0 g zinc sulphate 60.0 - 90.0 g glycerine

A cooled solution is toned with one ofthe approved synthetic organic colours. The preparation is filled into appropriate polyethylene or glass small contairnes with or without a special piece.

Example 3:

5.0 - 30.0 g aluminium ammonium sulphate dodecahydrate

1.0 - 5.0 g ferric ammonium sulphate dodecahydrate

1.0 - 5.0 g zinc sulphate

60.0 - 90.0 g glycerine A cooled solution is toned with one of the approved synthetic organic colours. The preparation is filled into appropriate polyethylene or glass small contairnes with or without a special piece.

Example 4.

10.0 - 35.0 g aluminium ammonium sulphate dodecahydrate

1.0 - 5.0 g zinc sulphate

60.0 - 90.0 g glycerine

Example 5_*

10.0 - 35.0 g aluminium potassium sulphate dodecahydrate

1.0 - 5.0 g zinc sulphate

60.0 - 90.0 g glycerine

A cooled solution is toned with one of the approved synthetic organic colours. The preparation is filled into appropriate polyethylene or glass small contairnes with or without a special piece. Example 6.

10.0 - 35.0 g ferric ammonium sulphate dodecahydrate

1.0 - 5.0 g zinc sulphate

60.0 - 90.0 g glycerine

Example 7.

1.0 - 5.0 g ferric ammonium sulphate dodecahydrate

10.0 - 35.0 g aluminium potassium sulphate dodecahydrate

60.0 - 90.0 g glycerine

Example 8.

5.0 - 35.0 g aluminium ammonium sulphate dodecahydrate.

1.0 - 5.0 g ferric ammonium sulphate dodecahydrate

60.0 - 95.0 g glycerine

A cooled solution is toned with one of the approved synthetic organic colours. The preparation is filled into appropriate polyethylene or glass small contairnes with or without a special piece. Example 9.

5.0 - 20.0 g aluminium ammonium sulphate dodecahydrate

5.0 - 20.0 g aluminium potassium sulphate dodecahydrate

60.0 - 90.0 g glycerine

Example 10.

40.0 g aluminium ammonium sulphate dodecahydrate

60.0 g glycerine

Example 11.

40.0 g aluminium potassium sulphate dodecahydrate

60.0 g glycerine

A cooled solution is toned with one of the approved synthetic organic colours. The preparation is filled into appropriate polyethylene or glass small contrariness with or without a special piece. Results of clinical tests:

Chemical mixtures - preparations of the invention were clinically tested with regard to their activity and acceptability. The mixture tested was the microbicide/virucide gel prepared according to example 1.

The preparation was administered as an agent for skin treatment and soothing of symptoms caused by the herpes simplex virus. The test was p rformed in 30 volun¬ teers aged from 18 to 63 years. All persons tested had a clinically confirmed diagnosis of herpes simplex - 24 in the vesicular stage and 6 in the crust stage of the disease.

For the majority of patients, 29 of them, the disease was a recurrent one and only one had the disease for the first time. 27 patients had felt prodromal symptoms before changes in skin occured. The most frequent location of changes were the lips, the upper lip in 16 patients, the lower lip in 8 patients and both lips in 1 patient. Other locations were the cheek in 2 patients, the nose in 1 patient and the gluteus region in 2 patients. The skin changes were of the dimensions from 3x4 mm to 15x30 mm.

By clinical examination a classification of the skin changes was performed by the fol¬ lowing scale: vesicles, reddening, moistening, crusts, itching, burning, pains were evaluated in grades from 0 - 3 (i.e. 0-none, 1-weak, 2-medium, 3-strong). The patients were administered the gel on skin changes several times a day. After 7 days an evaluation of the effect was performed in 28 patients, whereas 2 patients ceased the therapy due to side effects before the end of the test. The remaining patients did not have any side effects.

intensity of changes developed as represented in the following table:

Intensity of changes Number of persons tested day (30) day 7 (28)

Vesicles strong - 3 19 0 medium - 2 5 0 weak - 1 0 0 none - 0 6 28

Reddening strong - 3 14 0 medium - 2 13 0 weak - 1 2 4 none - 0 1 24

Moistening strong - 3 11 0 medium - 2 14 0 weak - 1 2 0 none - 0 3 28

Crusts strong - 3 7 0 medium - 2 1 2 weak - 1 1 2 none - 0 21 24

(Crusts were mostly formed between days 1 and 3, and fell off between days 3 and 6.)

i ching strong - 3 12 0 medium - 2 9 0 weak - 1 4 0 none - 0 4 28 Burning strong - 3 12 0 medium - 2 9 0 weak - 1 4 0 none - 0 4 28

Pains strong - 3 3 0 medium - 2 6 0 weak - 1 9 0 none - 0 12 28

After day 7 an evaluation of the tested gel was performed on the basis of clinical find¬ ings and the rate of regression of skin changes. 15 (50%) persons tested evaluated the microbicide/virucide gel as very effective for the treatment of the skin with herpes simplex, 11 (36.7%) persons evaluated it as effective and 4 (13.3%) persons tested evaluated it as non-effective. Side effects of local nature (itching, burning, ten¬ sion, pains) occured in 2 (6.7%) patients who ceased the treatment. Cosmetic accept¬ ability ofthe preparation was fair.

As it is evident from the above efficiancy and acceptability data, the preparation of the invention, e.g. in the form of a microbicide/virucide gel, can be used as an effec¬ tive agent for the treatment and soothing of herpes simplex symptoms.

Claims

1. Chemical mixture characterized in that it contains aluminium ammonium sulphate dodecahydrate 20.0 - 30.0 % ferric ammonium sulphate dodecahydrate 0.1 - 0.5 % aluminium potassium sulphate dodecahydrate 1.0 - 5.0 % zinc sulphate 0.5 - 5.0 % and glycerine up to 100 %.

2. Chemical mixture characterized in that it contains aluminium ammonium sulphatedodcahydrate 5.0 - 20.0 % aluminium potassium sulphate dodecahydrate 5.0 - 15.0 % zinc sulphate 1.0 - 5.0 % and glycerine up to 100 %.

3. Chemical mixture characterized in that it contains aluminium ammonium sulphate dodecahydrate 5.0 - 30.0 % ferric ammomum sulphate dodecahydrate 1.0 - 5.0 % zinc sulphate 1.0 - 5.0 % and glycerine up to 100 %.

4. Chemical mixture characterized in that it contains aluminium ammonium sulphate dodecahydrate 10.0 - 35.0 % zinc sulphate 1.0 - 5.0 % and glycerine up to 100 %.

5. Chemical mixture characterized in that it contains aluminium potassium sulphate dodecahydrate 10.0 - 35.0 % zinc sulphate 1.0 - 5.0 % and glycerine up to 100 %.

6. Chemical mixture characterized in that it contains ferric ammonium sulphate dodecahydrate 10.0 - 35.0 % zinc sulphate 1.0 - 5.0 % and glycerine up to 100 %.

7. Chemical mixture characterized in that it contains ferric ammonium sulphate dodecahydrate 1.0 - 5.0 % aluminium potassium sulphate dodecahydrate 10.0 - 35.0 % and glycerine up to 100 %.

8. Chemical mixture characterized in that it contains aluminium ammonium sulphate dodecahydrate 5.0 - 35,0 % ferric ammonium sulphate dodecahydrate 1.0 - 5.0 % and glycerine up to 100 %.

9. Chemical mixture characterized in that it contains aluminium ammonium sulphate dodecahydrate 5.0 - 20.0 % aluminium potassium sulphate dodecahydrate 5.0 - 20.0 % and gh/cerine up to 100 %.

10. Chemical mixture characterized in that it contains aluminium ammonium sulphate dodecahydrate 40.0 % and gylcerine up to 100 %.

11. Chemical mixture characterized in that it contains aluminium potassium sulphate dodecahydrate 40.0 % and glycerine up to 100 %.

12. Chemical mixture according to claims 1-11, characterized in that it is in the form of saturated glycerine solution.

13. Process for the preparation of the chemical mixture according to claims 1-12 characterized in that the active ingredients, glycerine and a suitable synthetic organic colour are mixed together and slowly heated to 35-40°C.

14. Chemical mixture accoding to claims 1-12 for use as a cosmetic agent.

15. Chemical mixture according to claims 1-12 for use as a medicament.

16. Chemical mixture according to claims 1-12, for use as a microbicide, fungicide and/or virucide agent in the treatment of skin.

17. Chemical mixture according to claims 1-12 for use in the treatment of skin by ap¬ plying an appropriate quantity thereof to the skin.

18. Chemical mixture according to claims 1-13 for use as an agent for the elimination of skin damage consequences.

19. Use of the chemical mixture according to claims 1-13 for prevention and elimination of skin manifestations caused by herpes simplex virus.