CH713023A2 - Process for the preparation of dermatological and cosmetic preparations with pronounced lamellar structures using phosphatidylcholine and biological cell materials, which are disrupted by the action of ultrasonic waves and at the same time embedded between the lamellar structures. - Google Patents

Abstract

The invention relates to a method for the preparation of dermatological or cosmetic preparations, using biological cell materials and active ingredients which are disrupted by the action of ultrasonic waves and at the same time enclosed in a multilamellar lipid structure which is very similar to human skin fat.

Description

description

PRIOR ART As early as 1995, the inventor and applicant developed and sold products with the designation DMS (Derma Membrane Structure) which were produced on the basis of hydrogenated phosphatidylcholine, medium-chain triglycerides, cosmetic active ingredients and by means of high-pressure homogenization. These cosmetic products could do without conventional emulsifiers. The lipophilic and hydrophilic components of the cream also had lamellar structures for the first time, similar to those of the lipid matrix of the stratum corneum. The lamellar structures correspond to the skin physiology and serve to protect the skin against the penetration of external substances and regulate the transepidermal water loss through the skin.

The formation of the lamellar structures is dependent on the geometric packing factors, such as the volume of the fatty acid chains, the critical chain length and the area occupied by the head group (Israelachviii, JN In Intermolecular and Surface Forces 2nd Ed .; Jovanovich, HB; Académie Press Ltd., London 1994). This means that not every amphiphilic substance can form lamellar structures or membranes. The best-known lipid that is capable of forming such lamellar structures is phosphatidylcholine (PC), which is also part of the human cell membrane. A high concentration of phosphatidylcholine can be found in soy lecithin.

DE 19 857 492, EP 1 259 218 and DE 10 2006 015 544 from Kuhs GmbH describe formulations based on hydrogenated phosphatidylcholine, medium-chain triglycerides, mixed with different active ingredients. However, these formulations cannot be prepared using customary emulsification processes. A special high-pressure homogenization is required for the production, the process also having to be carried out repeatedly and at a temperature of 70-80 ° C. (Hans Lautenschläger, Österreichische Apothekerzeitung, 56 (14), 679 (2002). DE 10 2011 110 749 by Gabriele Blume describes a manufacturing process according to which preparations with a lamellar structure can be produced using a simple emulsion technique, but the phosphatidylcholine, which is so valuable for the skin, is replaced by sucrose tristearates.

However, phosphatidylcholine, especially the hydrogenated one, shows a pronounced barrier-stabilizing effect. The skin barrier is stabilized by PC-H-containing preparations with a lamellar structure in such a way that after the application of the transepidermal water loss (TEWL) changes only slightly if external substances act on the skin. The protection obtained in this way is also characterized by high water resistance and sweat resistance. For this reason, the use of hydrogenated phosphatidylcholine is extremely desirable for cosmetic or dermatological preparations.

It is also particularly desirable to store biological cell materials between the lamellar structures, which, however, often have to be removed from the cells or have to be disrupted and which are very sensitive to oxidation and temperature. This means that the biological components should preferably be stored in the lamellar structures immediately after cell disruption, and this at room temperature (18-25 ° C).

However, this is with the o.b. Procedure not possible.

Object of this invention The object of this invention was to develop a method by which it is possible, using the ingredients for membrane structure creams that have been known since 1995, in particular using hydrogenated phosphatidylcholine, to produce stable cream bases for topical application, which have a qualitatively and quantitatively pronounced lamellar structure and in which active ingredients and biological materials can be disrupted at room temperature in one operation (ie detached from their cells and cleaved agglomerates) and stored directly between the lamellar structures that form.

Description of the invention It has now surprisingly been found that ultrasound devices, such as are also used for the digestion of biological material in the laboratory, in the presence of suitable membrane lipids, not only unlock the cells contained, but also spontaneously quantitatively very pronounced lamellar Create structures. This takes place at room temperature (18-25 ° C) in an astonishingly good, homogeneous quality, whereby the active substances and intracellular materials present are very stably enclosed in the lamellar layer structures. This protects sensitive substances particularly well against oxidation and decomposition. A so-called cryofixation and subsequent microscopic examination in the SEM showed that the multilamellar layers are much more pronounced than is the case with conventional high-pressure homogenization.

Another important advantage of the manufacturing process according to the invention is the possibility of producing very small units of 20-50 ml with individual formulations tailored to the skin type.

Galenical preparations for cosmetic or dermatological products mainly consist of a water and a fat phase. Both phases are usually mixed or emulsified with the aid of appropriate emulsifiers and with the use of high-speed stirrers, mixers or the like.

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It is important that the inner phase is distributed as finely as possible in the outer phase so that sufficient stability and storage time are achieved. A sufficient amount of emulsifiers and preservatives is also necessary to ensure a practical storage period for the products.

However, emulsifiers and preservatives are substances that strain the skin and are often triggers of allergies.

It is therefore desirable to prepare preparations, especially for dermatological applications, which contain very little or no emulsifiers and preservatives.

Pharmacists and beauticians are therefore making fresh preparations more and more frequently, but this is an enormous effort. The ingredients must be weighed and heated according to a recipe in a container before they can then be emulsified and filled with a homogenizer. The vessels and stirrers must then be cleaned. A lot of time and material is lost.

The inventive introduction of ultrasonic waves (this can also happen from the outside, for example, through the vessel wall), a cosmetic or dermatological preparation can be produced in less than a minute, without chemical emulsifiers and this at room temperature, even using temperature-sensitive , biological materials.

Definition of terms The terms used in this document are defined in more detail below.

Ultrasound devices There are different versions and performances of ultrasound devices. For the ultrasound application according to the invention, devices are required which supply sufficient energy which is required to disperse a liquid phase (fat phase) in small drops in a second phase (stable phase). In this sound field, imploding cavitation bubbles cause intense shock waves in the liquid and, as a consequence, generate liquid jets of very high speed. The newly formed drops of the dispersed phase align themselves immediately with the help of the membrane lipids and form lamellar structures with a thickness of a few nanometers, with the lipophilic phases and the hydrophilic phase then layering alternately. The vibration amplitudes of the introduced ultrasound preferably range from approximately 1 to 200 micrometers, while the high-pressure and low-pressure cycles between 15,000-30,000 cycles / sec., Preferably at 20,000 cycles / sec. be.

Cell and tissue disruption If liquids are sonicated with high intensity, the sound waves in the liquid medium produce alternating high pressure cycles (compression) and low pressure cycles (rare refraction), the oscillation rate of which depends on the frequency. During a low pressure cycle, the high-energy ultrasonic waves form small vacuum bubbles or voids in the liquid. If these bubbles reach a volume at which they cannot absorb any more energy, they burst during a high pressure cycle. This phenomenon is called cavitation. During the implosion, very high temperatures (approx. 5000 K) and pressures (approx. 2000 atm) are reached locally. In addition, the implosion of the cavitation bubbles creates liquid jets at speeds of up to 280 m / s. The shear forces mechanically unlock the cell envelope and thereby increase the exchange of materials. At the same time, the membrane lipids (hydrogenated phosphatidylcholine) form the lamellar layers in which the intracellular material is stored spontaneously.

Biological cell material In this patent specification, biological cell material is understood to mean materials which have been removed from biological cells. These can be of vegetable origin, e.g. Algae and / or animal or human origin. They can come from tissues and / or from body fluids such as blood and / or from microorganisms such as yeast or bacteria.

Example recipes

Example 1 Production of a membrane structure cream by means of ultrasound:

2% Phosphatidylcholine hydrogenated 25% almond oil 3% shea butter 5% Pentylene glycol

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65% water

Example 2 Production of a membrane structure cream using a lamellar preconcentrate and introduction of intracellular material from yeast cells:

10% MS concentrate (made with hydrogenated phosphatidylcholine, neutral oil and homogenized using a high-pressure homogenizer)

24% neutral oil (medium chain triglycerides)

4% pentylene glycol 2% yeast cell sponge

60% water Manufacturing process

The components are placed in a glass container which is closed and placed in the ultrasound device, which introduces the ultrasound from the outside through the wall. The formation of a homogeneous cream mass is evident after just one minute.

Example 3 Production of a day cream by means of ultrasound and storage of intracellular materials from algae:

2% hydrogenated phosphatidylcholine 35% Almond oil raf. 5% Pentylene glycol nat. 0.2% Na hyaluronate 10% Algae neckling 0.3% perfume oil 47.5% Water the.

Manufacturing process

The components are placed in a glass container which is closed and placed in the ultrasound device, which introduces the ultrasound from the outside through the wall. The formation of a homogeneous cream mass is evident after just one minute.

This example recipe shows a very nice consistency and a very good storage stability of more than 30 months. It also has a complete lamellar structure, which means that it is optimally absorbed by the skin and strengthens its protective barrier.

Claims (10)

claims 1. Process for the preparation of dermatological or cosmetic preparations with multilamellar structure, using hydrogenated phosphatidylcholine and exposure to ultrasound waves. 2. The method according to claim 1, characterized in that the proportion of hydrogenated phosphatidylcholine is 0.5-10% of the total formulation. Most preferably 1-3%. 3. The method according to claim 1-2, characterized in that the formulation vegetable oils or fats are added in a proportion of 1-60%, preferably 10-30% 4. The method according to claim 1-3, characterized in that the formulation hydrocolloids, such as xanthan gum, sodium cabomer, hyaluronic acid, cellulose derivatives, starch derivatives, alginates, pectins are added in a proportion of 0.1-2%. 5. The method according to claim 1-4, characterized in that the formulation pentylene glycol is added in a proportion of 2-6% and / or ethyl alcohol in a proportion of 5-20%. CH 713 023 A2 6. The method according to claim 1-5, characterized in that the formulation vegetable cell material is added in a proportion of 1-95%. 7. The method according to claim 1-6, characterized in that the formulation animal and / or human material in the form of tissue and / or blood components is added, with a proportion of 1-50%. 8. The method according to claim 1-7, characterized in that the formulation is treated with ultrasonic waves, with a frequency of 15-25 KHz and thereby form multilamellar lipid structures. 9. The method according to claim 1-8, characterized in that the formulation dermatological, medicinally active substances such as vitamins, provitamins, surface anesthetics, antihistamines, antifungals, anti-inflammatory drugs, antiseptics, astringents, proteins, peptides, urea with a proportion of 0.1 -10% can be added. 10. The method according to claim 1-9, characterized in that the ultrasonic waves are optionally introduced from the outside through the closed vessel wall or by at least one sonotrode, which is brought into direct contact with the formulation components.