WO2013023641A2

WO2013023641A2 - Method for producing a composition for application to the skin

Info

Publication number: WO2013023641A2
Application number: PCT/DE2012/000822
Authority: WO
Inventors: Gabriele Blume
Original assignee: Gabriele Blume
Priority date: 2011-08-16
Filing date: 2012-08-13
Publication date: 2013-02-21
Also published as: DE102011110749A1; WO2013023641A3

Abstract

The invention relates to a composition for application to the skin, wherein at least one sugar fatty acid ester is mixed with water and at least one further lipophilic and/or at least one further hydrophilic substance and is heated above 30° C.

Description

Process for the preparation of a composition for application to the skin

The present invention relates to a process for the preparation of a composition for application to the skin, that is to say a formulation to be applied topically.

Conventional cosmetic or pharmaceutical formulations used to care for and / or treat the skin are usually oil-in-water (O / W) or water-in-oil (W / O) formulations. These are oil droplets in water or water droplets in oil.

It has been found, however, that formulations containing lamellar structures that correspond to skin physiology are much more effective, for example, in skin care. Especially the upper layer of the skin, the stratum corneum, protects the skin against the ingress of external substances. The stratum corneum consists of corneocytes - keratinized cells - which slough off on the surface. The corneocytes are embedded in a lipid layer, which is formed, among others, from ceramides, cholesterol and its derivatives as well as fatty acids. These lipids are arranged into a multi- lamellar layer. There are aqueous regions and lipophilic areas here.

Lamellar structures, as they also occur in the stratum corneum, are formed by substances that have both a polar (head group) and non-polar part (hydrocarbon group) in their molecule (amphiphilic substances). In the water, both the polar parts to each other and the apolar parts arrange, with superimposed double membrane layers can be formed. However, not every amphiphilic substance can form lamellar structures or membranes. The formation of lamellar structures depends, among other things, on the geometric population factors of the amphiphilic substances, as well as on the volume of the hydrocarbon chains of the critical chain length and on the area occupied by the head group. Topical formulations having amellar structures are known in the art. Most of these formulations are based on phosphatidylcholine (PC), which is usually present in hydrogenated form. PC is also part of human cell membranes. It can be found in a high concentration (> 75%) in the purified lecithin, which can be of plant origin (usually soya alecithin), but also of animal origin (egg lecithin).

DE 198 57 492 describes the use of such a formulation as skin protection. EP 1 259 21 8 describes this formulation for the treatment of aging and / or stressed skin. In DE 10 2006 01 5 544 such a formulation for use in infants and toddlers is described.

Further, PC-based formulations are known which are used as universal base creams for skin care, skin protection and as dermatics. The previously known preparation of both W / O formulations and the above-described PC-based formulations is carried out by a lipophilic phase and a hydrophilic water phase separated from each other usually heated to about 70 ° C and then the water phase carefully and slowly added to the oil phase. In some of the known processes, after the two phases have been mixed, the mixture is homogenized and then subjected to a very complicated high-pressure homogenization at almost 800 bar, in order then to re-homogenize. In the prior art, therefore, always hydrophilic phase and lipophilic phase are prepared separately from each other, to then be combined.

The methods known from the prior art are very complicated and often do not lead to optimal lamellar structures.

The present invention has for its object to develop a method which overcomes the disadvantages of the prior art. The invention is in particular the object of developing a skin-friendly formulation with lamellar structures, which can be produced on a simple and inexpensive production route. This object is achieved by a method for producing a composition for application to the skin, wherein at least one sugar fatty acid ester is mixed with water and at least one further lipophilic and / or at least one further hydrophilic substance and heated above 30 ° C. It has been found that the use of sugar fatty acid esters in conjunction with water and at least one other lipophilic and / or hydrophilic substance can produce optimal lamellar structures (see Figure 1). In contrast to the processes of the prior art, both hydrophilic and lipophilic substances are in contact with each other from the beginning. introduced. In the method according to the invention z. B. no costly and costly Hochdruckhomogenisation of needs.

The sugar component of the at least one sugar fatty acid ester is preferably selected from the group of sucrose, glucose, fructose, sugar alcohols (eg sorbitol) and the fatty acid component is preferably derived from a fatty acid having a chain length of at least 14 C atoms, in particular stearic acid or Palmitic acid.

In a particularly preferred embodiment of the method according to the invention, the at least one sugar fatty acid ester is a sugar fatty acid triester, in particular sucrose tristearate. When using sucrose tristearate, it has been found that particularly advantageous lamellar structures are formed. It has also been found that sucrose tristearate has an enormously high water binding capacity due to the hydrophilic sugar head group, resulting in a significant

Increases skin moisture and reduces skin roughness. Sucrosetristearat is an extremely skin-friendly and mild emulsifier.

The at least one further lipophilic substance is preferably selected from the group of skin-related substances of plant origin, such as triglycerides (for example olive oil), vegetable phytosteroules, shea butter, ceramide III and squalans.

The at least one further hydrophilic substance is preferably a polyhydric alcohol, in particular glycerol and / or pentylene glycol. For example, virgin olive oil, which has a similar fatty acid composition to human sebum, has a high affinity to the skin surface. Medium chain triglycerides also have the ability to partially substitute for sebum. Skin-friendly lipids which correspond to the lipid matrix of the stratum corneum are preferably used as the basis for the topical preparation (inter alia the abovementioned plant phytosterols, ceramide III and squalane). The above said polyhydric alcohols, such as. Pentylene glycol or glycerol also increase skin moisture.

As further components may be present in the lamellar formulation cosmetic and / or pharmaceutical agents, which may be both lipophilic and hydrophilic nature. Such substances are all active ingredients that can be incorporated into the lamellar formulation and exert cosmetic and / or pharmaceutical effects in or on the skin.

In a preferred variant of the method or in a preferred composition according to the invention, further vesicles are added containing at least the following constituents: an aqueous core which may comprise at least one cosmetic and / or at least one pharmaceutical active substance, and - a continuous membrane surrounding the core from at least one emulsifier selected from the group of food additives E472a to f, and at least one membrane-stabilizing single-chain lipid and / or one or more lipophilic cosmetic and / or pharmaceutical agents.

Such vesicles are also described in WO 201 1/1 16738 A2 by the Applicant. The content of this document is expressly also part of the present application.

The vesicles mentioned promote the transport of active substances from the lamellar structures into the deeper skin layers (epidermis and dermis). In contrast to the conventional flexible liposomes, the vesicles mentioned form stable, drug-carrying vesicles. For example, a vitamin A integrated in the vesicle membrane can be effectively protected against external influences. Likewise, an im

Vesicle interior encapsulated antioxidant (eg green tea extract) by means of said vesicles are transported from the formulation in significantly higher concentration in the skin and is there increasingly bioavailable. Neither stabilization of encapsulated drugs nor their effective transport into the skin can be achieved with the help of commercially available liposomes. This combination of the lamellar formulation and the vesicles protected herein enables targeted treatment on and in the skin by the incorporation of drugs into the formulation or into the vesicles.

Due to the particularly pronounced lamellar structure in the formulation described here, which is modeled on the intracellular "lipid putty" of the stratum corneum, the formulation according to the invention is particularly suitable for reducing barrier damage This may be compensated / repaired after application of the dermal formulation The TEWL value decreases and is accompanied by a more homogeneous smooth surface profile of the skin (see Example 7).

In a preferred process variant, two phases (mixtures) are first prepared separately, both phases containing at least one sugar fatty acid ester, especially sucrose tristearate and water, and at least one of the two phases containing at least one further lipophilic and / or hydrophilic substance, both Phases are heated to above 30 ° C, preferably 50 ° C to 60 ° C until in each case a homogeneous dispersion is formed and then combined with each other (see Example 1). By doing so, particularly advantageous lamellar structures result in the resulting composition.

Preferably, the homogenous dispersions are homogenized prior to combining, in particular for about 2 minutes at about 8000 rpm, preferably homogenized with an Ultra Turrax. Before combining, the two dispersions are preferably cooled, in particular to room temperature. The present invention further relates to a composition for application to the skin, in particular produced by the process according to the invention, comprising at least one sugar fatty acid ester, water and at least one further lipophilic and / or hydrophilic substance.

The sugar fatty acid ester in the composition of the invention is preferably sucrose tristearate.

Examples

Example 1 :

Formulation with dermal structures

Phase 1

Sucrosetristearate 5.0%

Pentylene glycol 5.0%

Glycerol 3, 0%

Water 35.9%

Phase 2

Sucrosetristearate 1, 0%

Triglycerides 6.0%

Shea butter 3, 0%

Squalane 1, 0%

Ceramide III 0, 1%

Water 40.0%

Phase 1 and Phase 2 are slowly heated separately with stirring to 50-60 ° C until all solids are melted and then briefly homogenized (about 2 minutes 8,000 rev / min). This results in a highly viscous phase 1 and a liquid phase 2 after cooling, wherein the liquid phase is stirred under the creamy phase.

Preparation according to the conventional method of the prior art: heat the lipophilic phase separately from the hydrophilic phase and then carefully add the aqueous phase to the lipid phase at 70 ° C. This results in a liquid, very sticky emulsion.

Evidence of the formation of dermal structures was obtained after a freeze-fracture preparation followed by an electron microscopic observation (see Fig. 1).

Example 2:

Concentrated formulation

Sucrosetristearate 6.0 g

Pentylene glycol 10.0 g

Glycerol 6.0 g

Triglycerides 12.0 g

Shea butter 6.0 g

Squalane 2.0 g

Ceramide III 0.2 g

Water 32.8 g

The whole mixture is slowly warmed to 50-60 ° C until all solids are melted and then briefly homogenized (2 minutes 8,000 rpm).

The formulation is then slowly cooled. It creates a semi-solid cream after 6 hours.

Formulation is used as the basis for further active substances tende preparations used.

Example 3:

Formulation with hydrophilic active ingredient

Phase 1

Sucrosetristearate 5.0 g

Pentylene glycol 5.0 g

Glycerol 3, 0 g

Ethyl ascorbate 5.0 g

Water 32.0 g

Phase 2

Concentrate from Example 2

The entire composition of Phase 1 is slowly heated to 50-60 ° C until all solids are melted and then briefly homogenized (2 minutes 8,000 rpm).

The result is a high-viscosity formulation.

Add 50 g of the concentrated formulation of Example 2 to give a well spreadable white cream with a pleasant feel on the skin.

Example 4:

Formulation with lipophilic active ingredient (UV filter)

Phase 1

Octocrylene (UV-B) 10.0 g Avobenzone (UV-A) 9.0 g

C i ₂ -C i 5 alkyl benzoate 20.0 g

Water 30.0 g

Sucrosetristearates 6.0 g

Phase 2

Concentrate from Example 2

The two UV filters are dissolved under heat in the solvent (C i ₂ -Ci ₅ alkyl benzoate) until a clear yellow solution is formed. After cooling to 40 ° C, the water is added to further cool the solution. At 30 ° C, the emulsifier is sprinkled into the solution and the mixture is heated slowly to 50-60 ° C until all solids are melted and then briefly homogenized (2 minutes 8,000 rev / min). The result is a hochvsikose formulation.

Addition of 25 g of the concentrated formulation from example 2 gives a readily dispersible whitish-yellow cream with a pleasant feel on the skin, which enables a good, homogeneous distribution of the filters on the skin surface.

Example 5:

Stability of retinyl propionate (0.2%) in the dermal formulation with lamellar structures (see Fig. 2). The content of Retinylpropionate was determined by HPLC.

Example 6:

Penetration of a green tea extract (0.2%) into the deeper skin layers from the dermal formulation with lamellar structures by means of carrier systems (see Fig. 3). The detailed measurement method is described in the following (K Jung et al., Antiaging Status of Skin Characterized by the Skin Antioxidant Protection (SAP) - efficacy of topically applied antioxidants) SÖFW journal 9 (2006))

Example 7:

Use of the dermal formulation with lamellar structures in subjects with dry skin. The reduction in transepidermal water loss (TEWL) was determined using Tewameter ™ 300 from Courage and Khazaka Elektronic GmbH (see FIG. 4).

Claims

claims

A process for the preparation of a composition for application to the skin, wherein at least one sugar fatty acid ester is mixed with water and at least one further lipophilic and / or at least one further hydrophilic substance and heated above 30 ° C.

Method according to claim 1,

characterized,

that the sugar component of the at least one sugar fatty acid ester is selected from the group of sucrose, glucose, fructose, sugar alcohols (for example sorbitol) and the fatty acid component preferably consists of a fatty acid having a chain length of at least 14 C atoms, in particular stearic acid or Palmitic acid emerges.

Method according to one of claims 1 or 2,

characterized,

the at least one sugar fatty acid ester is a sugar fatty acid triester, preferably sucrose tristearate.

Method according to one of the preceding claims,

characterized,

the at least one further lipophilic substance is selected from the group of skin-related substances of plant origin, such as triglycerides (for example olive oil), vegetable phytosteroules, shea butter, ceramide III and squalans.

Method according to one of the preceding claims,

characterized,

the at least one further hydrophilic substance is a polyhydric alcohol, in particular glycerol and / or pentylene glycol. Method according to one of the preceding claims,

characterized,

in that further vesicles are admixed containing at least the following constituents:

an aqueous core which may comprise at least one cosmetic and / or at least one pharmaceutical active substance, and

- A continuous membrane surrounding the core, formed from at least one emulsifier selected from the group of food additives E472a to f, and at least one membrane stabilizing single-chain lipid and / or one or more lipophilic len cosmetic and / or pharmaceutical agents.

Method according to one of the preceding claims,

characterized,

that two phases are prepared separately, both phases containing at least one sugar fatty acid ester, in particular sucrose tristearate and water, and wherein at least one of the two phases contains at least one further lipophilic and / or hydrophilic substance, both phases to above 30 ° C, preferably Be heated to 50 ° C to 60 ° C until in each case a homogeneous dispersion is formed and then combined with each other.

Method according to claim 7,

characterized,

that the homogeneous dispersions are homogenized before combining, in particular for about 2 minutes at 8000 U / min, preferably homogenized with an Ultra Turrax and preferably cooled.

Composition for application to the skin, in particular produced according to one of claims 1 to 8 with a lamellar structure, comprising at least one sugar fatty acid ester, water and at least one further lipophilic and / or hydrophilic substance. O.A composition according to claim 9,

characterized,

the at least one sugar fatty acid ester is sucrose tristearate.