EP1732651A1

EP1732651A1 - Topical preparation for use on the skin containing natural evening primrose oil (oenothera biennis) (=oleum oenotherae) and osmolytes originating from extremophilic micro-organisms

Info

Publication number: EP1732651A1
Application number: EP05716456A
Authority: EP
Inventors: Thomas Schwarz
Original assignee: Bitop AG
Current assignee: Bitop AG
Priority date: 2004-03-30
Filing date: 2005-03-30
Publication date: 2006-12-20
Also published as: JP2007530624A; US20080014153A1; WO2005094771A1; DE102004049062A1

Abstract

The invention relates to formulations comprising fats and natural oils that contain an osmolyte originating from extremophilic micro-organisms and unsaturated fatty acids. According to the invention, the osmolyte is present in a concentration of between 0.01 and 50 wt. % of the total weight of the composition. The invention also relates to the use of osmolytes originating from extremophilic micro-organisms for stabilising unsaturated fatty acids. A preferred combination consists of the osmolyte and evening primrose oil (Oleum Oenotherae).

Description

Topical preparation for use on the skin containing natural evening primrose oil (Oenothera biennis) (= Oleum Oenotherae) and osmolytes from extremophilic microorganisms

The invention relates to a formulation which contains an osmolyte from extremophilic microorganisms and unsaturated fatty acids containing natural oils and fats. The formulation contains at least one osmolyte in an amount of 0.01 to 50 wt .-%, based on the total weight of the formulation.

In particular, the invention relates to the use of an osmolyte formed by extremophilic bacteria (e.g. ectoin, hydroxyectoin, Firoin, Firoin-A, diglycerol phosphate, cyclic diphosphoglycerate, di-inositol phosphate; hereinafter referred to as Osmolyte X) in combination with natural evening primrose oil (Oleum Oenotherae) for the production of drugs, medical devices or cosmetics for external treatment, prophylaxis or care of the skin.

Certain fatty acids are essential for the human organism, i.e. they must be ingested with the food if there are no symptoms of deficiency. These include polyunsaturated fatty acids (PUFAs) from the Omega 6 and Omega 3 series, such as linoleic acid and alpha-linolenic acid, which, as precursors to eicosanoids, influence a wide range of physiological functions.

The stability of the fats is also heavily dependent on the percentage of PUFAs. The influence of oxygen, light and heat can lead to the formation of

BESTÄTSGUNGSECOPIE Hydroperoxides cause. These reactive molecules can then form polymers (resinification, drying out) and low-molecular fragments, which cause a rancid odor. Vitamin E, for example, increases resistance to oxidative changes. Therefore only relatively stable oils such as olive or peanut oil should be used for cooking and roasting.

A distinction is made between unsaturated fatty acids and polyunsaturated fatty acids (PUFAs). Naturally occurring unsaturated fatty acids usually have the cis configuration on the double bonds. So-called. Trans fats result from the "hardening" of fat, whereby the double bonds of the unsaturated fatty acids are hydrogenated with hydrogen and vegetable fats are formed which are solid even at room temperature. In animal fat and rumen from ruminants, hydrogenation produces linoleic acid derivatives of linoleic acid, which contain two conjugated double bonds in the ice and / or trans configuration and are referred to as conjugated linoleic acid (CLA = conjugated linoleic aeid).

All monounsaturated and polyunsaturated fatty acids are more or less unstable against the effects of oxidation and need if they are not are intended for immediate use, stabilization through low temperatures or suitable substances. The same naturally applies to compositions and formulations which contain unsaturated fatty acids, in particular also to natural oils and fats.

Osmolytes or compatible solutes (see above) from extremophilic microorganisms form a well-known group of low-molecular protective substances. Extremophiles are very unusual microorganisms, because they optimally e.g. grow at high salt concentrations (up to 200 g NaCI / l) and high temperatures (60-110 ° C), which would lead to massive damage to cellular structures in mesophilic ("normal") organisms. A large amount of research has therefore been carried out in recent years in order to identify the biochemical components that lead to the remarkable thermal, chemical and physical stabilization of cell structures.Although many enzymes from hyperthermophilic microorganisms are stable even at high temperatures, this does not generally apply to the cellular structures of thermo- and hyperthermophilic organisms The high temperature stability of cell structures makes a significant contribution to low molecular weight organic substances (compatible solutes, osmolytes) in the intracellular milieu, and various novel osmolytes have been identified in extremophilic microorganisms for the first time in recent years bonds to protect cellular structures - especially enzymes - against heat and drought have already been shown (Lippert, K., Galinski, E.A. (1994), Appl. Microbiol. Biotech. 37, 61-65; Louis, P., Trüper, H.G., Galinski, E.A. (1994), Appl. Microbiol. Biotech. 41, 684-688; Ramos, Raven, Sharp, Bartolucci, Rossi, Cannio, Lebbink, v.d. Oost, de Vos, Santos (1997), Appl. Environm. Microbiol. 63, 4020-4025; Da Costa, Santos, Galinski (1998), Adv. In Biochemical Engineering Biotechnology, 61, 117-153).

The osmolytes (compatible solutes) found in the extremophilic microorganisms are not produced by human or animal cells.

Through processes developed by the company bitop AG (processes for the in vivo production of ingredients from cells; EP 94 903 874.9; processes for the production of valuable materials from organisms by influencing / Impairment of the cell's own transport systems for these valuable materials; EP 98 121 243.4; Process for separation u. high purity isolation of low molecular weight, structurally similar compounds, in particular tetrahydropyrimidine derivatives; DE10047444.6) it is possible to purify osmolytes from extremophilic microorganisms in sufficient quantities in the highest quality. In principle, the use of these substances as medicinal products, cosmetics or medical products is conceivable.

The osmolyt ectoin was previously used as a moisturizer and active ingredient in cosmetic products with the aim of protecting healthy, clinically unremarkable human skin against the damaging effects of ultraviolet solar radiation (e.g. Use of ectoine or ectoine derivatives in cosmetic formulations, EP19990941; Use of ectoine or ectoine derivatives for the prophylaxis and / or treatment of UV induced immunosuppression). In vitro and in vivo studies have shown that this cosmetic effect of ectoin is based, among other things, on the fact that this molecule influences the function of epidermal Langerhans cells as well as epidermal keratinocytes and dermal fibroblasts in such a way that these cells counteract the pro-inflammatory effects of UV Radiation, for example would lead to the formation of a sunburn, are better protected.

The production of a medicament for the treatment of skin diseases using ectoin or hydroxyectoin is generally described by the European patent EP 98 113 132.9 from bitop AG.

The evening primrose (Oenothera biennis; Onagraceae plant family), also known as the "Queen of the Night", is a plant and bears its name because it opens its bright yellow flowers in the evening or in cloudy weather. In North America, the original homeland of evening primrose, the Algonkin Indians treated various skin conditions with a slurry of crushed evening primrose oil seeds (Oleum Oenotherae) over 500 years ago.

The oil obtained from the evening primrose's flower seeds (Oleum Oenotherae) has a high proportion of polyunsaturated fatty acids such as linoleic acid and gamma-linolenic acid. The seeds used for oil production come from plants grown without chemical pesticides. Evening primrose oil is a natural and biologically active source of essential fatty acids, including cis-gammalinolenic acid (GLA) with a share of approx. 10%. The acidity is active thanks to the unique triglizeryd structure, which is unique to evening primrose oil. These fatty acids play an important role in metabolism, especially in cell renewal.

Cold-extracted evening primrose oil (Oleum Oenotherae) contains important amino acids, minerals and vitamins, including vitamin E, which plays the natural role of an antioxidant. The oil is not only used in high-quality cosmetic products, but is also used as a valuable nutritional supplement. Numerous cosmetic products describe the care effects of evening primrose oil on very dry, irritated, flaky and problematic skin. Evening primrose oil can also be used internally as a nutritional supplement.

The storage and use of evening primrose oil (Oleum Oenotherae) in topical preparations is severely limited due to its short shelf life. Since it is perishable, evening primrose oil is usually preserved with vitamin E. In addition, evening primrose oil is always mixed with another base oil to increase stability. This significantly improves the durability. Heating evening primrose oil e.g. for conservation purposes is not possible due to instability.

The same applies to a number of other natural oils that have more or less found their way into the food, cosmetics and pharmaceutical industries than there would be fish oil (e.g. mackerel, tuna, salmon, herring), coconut oil, palm oil, Cocoa oil, olive oil, peanut oil, cottonseed oil, sesame oil, corn oil, safflower oil, soybean oil, wheat oil, borage oil, linseed oil, rapeseed oil, black nettle oil, castor oil, black cumin oil, rose hip seed oil, hemp oil and the like.

Surprisingly, it has now been found that the addition of osmolytes X extremophilic microorganisms to natural oils of the Oenothera biennis (= Oleum Oenotherae) in formulations for topical (surface) use on the skin lead to a significant stabilization of evening primrose oil in the topical preparation for use on the skin. The addition of Osmolyten X significantly improves the stability and thus preservation of evening primrose oil without limiting the possible uses in cosmetic and dermatological products. The addition of osmolytes also significantly increases the temperature stability of evening primrose oil (Oleum Oenotherae), so that evening primrose oil can be preserved thermally without losing its natural properties.

Surprisingly, it could also be shown that in comparison with a post-primrose oil-based care product, an evening primrose-oil based care product of the same composition with the addition of 0.5% (weight percent) of the osmolyte ectoin has a significantly better care effect with very dry, irritated, flaky and problematic Skin showed. Surprisingly, the care effect of the combination product of evening primrose oil and osmolyte was significantly better than that of a care product that only contained the osmolyte in a 0.5% concentration.

A topical preparation containing a combination of evening primrose oil (Oleum Oenotherae) and Osmolyte X for cosmetic and dermatological applications thus surprisingly had the significant advantage of a significantly improved preservation and longer shelf life with a synergistically increased care effect for very dry, irritated, flaky and problematic skin , This means that a preparation made from osmolyte and evening primrose oil is also ideal for the care of inflamed areas of the skin, such as those e.g. in people suffering from atopic dermatitis.

The cosmetic and dermatological formulations are produced by one or more compounds from the group of the osmolytes, the physiologically tolerable salts of the compounds of the osmolyte in

Combination with the evening primrose oil (Oleum Oenotherae) (Oenothera biennis) if necessary with auxiliaries and / or carriers in a suitable formulation.

The auxiliaries and carriers come from the group of carriers, preservatives and other customary auxiliaries. The osmolytes contained in cosmetic and dermatological formulations and the evening primrose oil are used externally. As an application form e.g. called: solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleaning preparations, oils and sprays. In addition, any customary carriers, auxiliaries and, if appropriate, further active compounds can be added to the formulations. Preferred additives come from the group of preservatives, antioxidants, stabilizers, solubilizers, vitamins, colorants and

Odor.

In addition to one or more compounds selected from the group of osmolytes plus oil of evening primrose, ointments, pastes, creams and gels can contain the usual carriers, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.

Powder and sprays can, in addition to one or more compounds from the group of osmolytes plus evening primrose oil, in addition to the usual carriers, the usual blowing agents, e.g. Chlorofluorocarbons, propane / butane or dimethyl ether.

In addition to one or more compounds from the Osmolyte X plus evening primrose oil (Oleum Oenotherae) group, solutions and emulsions may contain the usual carriers such as solvents, solubilizers and emulsifiers.

Suspensions can be selected in addition to one or more compounds from the group of Osmolyte X plus evening primrose oil (Oleum Oenotherae) such as. B. contain water or ethanol. Other application forms are e.g. B. soaps, surfactant-containing cleaning agents, facial and body oils, lipsticks, lip care sticks, mascara, eyeliner, eye shadow, blush, powder, emulsion and wax make-up as well as sunscreen, pre-sun and after-sun preparations.

The proportion of the compounds of the Osmolyte X group in cosmetic and dermatological formulations is preferably 0.0001 to 50% by weight, particularly preferably 0.001 to 10% by weight, based on the preparation as a whole.

The proportion of evening primrose oil (Oleum Oenotherae) in cosmetic and dermatological formulations is preferably 0.0001 to 50% by weight, particularly preferably 0.001 to 10% by weight, based on the preparation as a whole.

The following examples are intended to illustrate the present invention without restricting it.

Example 1 O / W lotion

A lotion (O / W) according to the invention containing Osmolyte X and evening primrose oil (Oleum Oenotherae) is produced from the following components:

Example 2 O / W cream

A cream (O / W) according to the invention containing Osmolyt X is produced from the following components:

Example 3:

O W cream with cyclic diphosphoglycerate (cDPG)

A cream (O / W) according to the invention containing osmolyte cyclic diphosphoglycerate (cDPG) is produced from the following components:

Example 4:

Stabilization of a solution of γ-linolenic acid from evening primrose plants using the osmolyte diglycerol phosphate (DGP)

The stability of evening primrose oil at higher temperatures (room temperature, 25 ° C) strongly depends on the proportion of γ-linolenic acid and the purity of the evening primrose oil. After adding 0.1% (percent by weight) of diglycerol phosphate to a preparation of evening primrose oil, an increased storage stability of evening primrose oil of five days was found compared to the control without diglycerol phosphate. The stability of the preparation was assessed based on the first appearance of a rancid smell of evening primrose oil.

Example 5:

Increased temperature stability of evening primrose oil after adding an osmolyte mixture of mannosylglycerate (Firoin) and mannosylglyceramide (Firoin-A).

If the temperature rises sharply to 70 ° C within an hour, rapid destabilization / denaturation of Evening primrose oil. Hydroperoxides are formed. These reactive molecules can then form polymers (resinification, drying out) and low-molecular fragments, which cause a rancid odor. A 50:50 mixture of the osmolytes mannosylglycerate and mannosylglyceramide in a concentration of 5% (weight percent) increases the resistance of evening primrose oil to oxidative changes at temperatures of 70 ° C by 24 hours. Only after 24 hours of incubation at 70 ° C is a rancid odor noticeable in the presence of 50% mannosylglycerate-mannosylglyceramide mixture. The use of mannosylglycerate-mannosylglyceramide mixture can thus, for example, significantly improve the processing and storage of evening primrose oil and products containing evening primrose oil.

Example 6:

Gel containing evening primrose oil and the osmolyte di-inositol phosphate

A gel (O / W) according to the invention containing diinositol phosphate and evening primrose oil is produced from the following components:

0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative

Example 7:

Sun protection emulsion containing evening primrose oil and the osmolyte hydroxyectoin

A sun protection emulsion according to the invention containing evening primrose oil and hydroxyectoin is produced from the following components:

- claims

Claims

claims

1. Formulation comprising an osmolyte from extremophilic microorganisms and natural oils and fats containing unsaturated fatty acids, so that it contains 0.01 to 50% by weight of at least one osmolyte, based on the total weight of the formulation.

2. Formulation according to claim 1, characterized in that it contains 0.05 to 10% by weight, in particular 0.1 to 5% by weight, of the osmolyte (s).

3. Formulation according to claim 1 or 2, characterized in that it contains 0.01 to 50 wt .-% natural oils and fats.

4. Formulation according to claim 3, characterized in that it contains 0.05 to 10 wt .-%, in particular 0.1 to 50 wt .-%, natural oils and fats.

5. Formulation according to one of the preceding claims, characterized in that it contains the oil of the evening primrose (Oleum Oenotherae).

6. Formulation according to one of the preceding claims, characterized in that as osmolyte ectoin, hydroxyectoin, cDPG, DGP, firoin,

Firoin A and / or diinositol phosphate is used.

7. Formulation according to one of claims 1 to 6 for cosmetic use on the skin.

8. Cosmetic formulation according to claim 7, characterized in that it is in the form of a solution, a suspension, an emulsion, a paste, an ointment, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleaning preparation, one Oil, a lipstick, a lip care stick, a mascara, an eyeliner, eyeshadow, rouge, a powder, emulsion or wax make-up, a sunscreen, pre-sun and after-sun preparation, a hair tonic, a plaster, bandage or spray.

9. Use of an osmolyte from extremophilic microorganisms to stabilize and / or preserve unsaturated fatty acids.

10. Use according to claim 9, characterized in that the osmolyte is used in an amount of 0.01 to 50 wt .-%, based on the entire formulation.

11. Use according to claim 9 or 10, characterized in that it contains 0.05 to 10% by weight, in particular 0.1 to 5% by weight, of the osmolyte (s).

12. Use according to one of claims 9 to 11, characterized in that as osmolyte ectoin, hydroxyectoin, cDPG, DGP, Firoin,

Firoin A and / or diinositol phosphate is used.

13. Use according to one of claims 9 to 12 for stabilizing the oil of the evening primrose (Oleum Oenotherae).

14. Use of an osmolyte from extremophilic microorganisms for the production of formulations for topical use in cosmetics and dermatology.

15. Use according to claim 14 for the production of cosmetics for the care of very dry, irritated, scaly and problematic skin, for the care of inflamed skin in atopic dermatitis, psoriasis and other inflammatory skin diseases, for the protection and stabilization of human skin cells against physical, chemical and biological influences , especially against UV and IR radiation and denaturing substances, to protect the microflora of the skin, to stabilize the natural skin barrier and as a radical scavenger and / or antioxidant.

16. Use according to claim 14 for the manufacture of medical devices and / or medications for care, prophylaxis or

Treatment of atopic dermatitis, psoriasis, other inflammatory skin diseases and eczema.

17. Use according to one of claims 14 to 16, characterized in that the osmolyte is ectoin or hydroxyectoin.

18. Use according to any one of claims 14 to 17 in the form of a

Solution, a suspension, an emulsion, a paste, an ointment, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleaning product, an oil, a lipstick, a lip balm, a mascara, an eyeliner, and eyeshadow , from blush, a powder, emulsion or wax make-up, a sunscreen, pre-sun and after-sun preparation, a hair tonic, a plaster, a bandage or a spray.

19. Use according to claim 18, characterized in that the formulation further contains at least one UV filter, enzymes, vitamins, vitamin derivatives and / or proteins.

- Summary -