DE1792353A1 - Cosmetic preparations - Google Patents

Description

The invention "relates to new uses of fat-soluble Malic acid derivatives, especially malic acid esters, in the Cosmetics. It relates in particular to preparations that contain certain malic acid esters. According to a further feature, can the preparations according to the invention also contain esters of acids which in a manner analogous to malic acid a Role "play in the post-cancer tricarboxylic acid cycle.

The invention is based on the following considerations:

The beauty of a skin, i.e. its suppleness and its freshness, depends on a very fine film of molecular fat Thickness attributed to the surface of the body like a shell against external attack, namely excessive moisture protects against absorption, dehydration and infection. Under the Protection of this film will be through physiological activity of the cells of the skin maintain the necessary balance. When you give your skin its beauty and youthful freshness want to preserve, it is essential to ensure the integrity of this moisture-containing fat film, which is caused by water, that is loaded with electrolytes, and by nitrogen-containing products in which a fat complex is emulsified, is formed. It provides a buffer medium with an acidic p ^ value and plays an extremely important role in protecting the skin and the "Phaneres". This functional surface

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emulsion is very different both chemically and physically from the fat deposits that are stored in the subcutaneous tissues as reserve substances. When the skin covering is damaged, if the coat, which represents the moisture-containing film of fat, no longer playing its protective role in other words, skin disorders occur: faded, lackluster or dried skin, premature L _a chfalten, dehydration, greasy and shiny face and all little aesthetic appearances. If they are not the result of an organic disease that requires medical treatment, these disorders are mostly due to a lack of care of the skin or, above all, errors that are "committed in constant skin care. For example, contrary to popular belief, that a dry skin is dehydrated, a so-called dry skin is simply a skin whose peeling and moisture-containing fatty film are abnormal, such skin is generally richer in water than normal skin.

Accordingly, there are two broad principles within the scope of the invention applied to make products available that ensure proper skin care.

In the first place is contrary to the most common It has been recognized that everything in the constitution and physiology of the skin is subject to absorption opposed to the skin, which would presuppose the passage of a substance through the epidermis. Under normal concentration conditions It is known that the electrolytes do not exceed the "electrophysiological" barrier. This means, that water does not penetrate the skin and consequently water-soluble substances, whether active or not, penetrate even less. So it is completely illusory to want to incorporate such substances into the aqueous phase of a product, that is intended for the treatment of the skin.

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Only, the fatty substances penetrate the inside of the skin, though not in their entirety, taking them points from Take advantage of the lower resistance that consists of the hair follicles. This penetration occurs through the bottom of the follicle dissolving the sebum »

In the second place it is therefore not a question of the Rehydrate skin or not by applying a product to the surface. Just through the normal physiological activity of the cells will be the necessary Equilibria ensured. Any skin that is in bad condition is skin, its physiological Activity is disturbed. Any such enzymatic activity normally sets a permanent one for its sequence Energy source, which is represented by the tricarboxylic acid cycle described by Krebs, and which is the true one is the biochemical center of the intermediate metabolism, i.e. the totality of the reactions that make up the specific metabolism in common are: the carbohydrate metabolism, the Protein metabolism and fat metabolism.

The chain of substrates of this intermediate metabolism has no beginning and no end, but rather forms a circle i.e. to the various reactions of catabolic degradation Condensation reactions join in such a way that the Synthesis of each of the substrates is always possible at the expense of its degradation products.

The - "- malic acid ion is one of the essential keys of the Krebs cycle, for which it is an important source of energy and the real engine of the cell's life.

Malic acid, which has the formula COOH-CHg-CHOH-COOH, is a very important link in the tricarboxylic acid cycle according to Krebs and thereby plays a first-order physiological role in the intermediate metabolism, i.e. in the entirety of the Reactions that affect the specific metabolism (carbohydrate metabolism, Protein metabolism, fat metabolism) together

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are. The chain of substrates of intermediate metabolism has no beginning and no end, but represents a circle, i.e. it joins the various catabolic reactions condensation reactions of such a nature that the synthesis of each substrate always takes place at the expense of its degradation products is possible. The energy of the ATP and DNP system (adenosine triphosphoric acid and diphosphonucleotide), and malic acid is an excellent source of energy for the synthesis of ATP enables. Their presence in the cells guarantees effective activity and enables it to be carried out physiological metabolism in the epidermis and normal renewal of the basal layer. She causes a particular delicacy and transparency of the skin that justify its use in cosmetics.

It was therefore justified to use the malic acid in cosmetics as a cell activator, so that the cell in normal Wise in the organism draws the substances necessary for its activity are necessary.

Malic acid is an organic acid that is widespread in nature. Along with citric acid and tartaric acid, it is one of the main acids in fruits W and is contained in particularly high concentrations in apples. However, there remained a problem of ensuring the penetration of the malic acid ion, which is soluble in water and insoluble in oils, into the cells. The desired result is obtained according to the invention by using a fat-soluble ester of malic acid.

After all, it was necessary to choose a carrier for this active substance that not only ensures its penetration, but also can complement and complete its effect by smoothing and improving the skin. The vegetable oils, in particular Avogado oil, through its content of physiological products, e.g. vitamins, can play this role alone

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take over perfectly. Thanks to these vegetable oils, skin milks and creams could be produced that are quickly absorbed by the skin and thus do not leave the impression of "fat" and with complete certainty fulfill their task as carriers and distributors of the active ingredients and thereby create a pleasant impression of freshness.

According to the invention, the malic acid is in the form of an ester incorporated into a carrier or auxiliary material, which is used to Formation of a face cream that has been tested on animals and then on humans is suitable. '

The carrier, which is of great importance, consists of a combination of different vegetable oils, of which the avogado oil is in the foreground «, it gets very quickly from absorbed by the skin, creates an impression of freshness and does not leave any greasy appearance on the face. He carries and distributes the active ingredient that penetrates with him, and that The water contained in the cream evaporates quickly from the arms of the face. The p-rr value of the cream is in the acidic range, whereby the classic "acid mantle" is preserved, which is necessary for the skin.

The esters according to the invention can be prepared with an alcohol at a temperature between about 110 and 200 ⁰ C by a process of direct esterification of malic acid. The water is removed by evaporation in proportion to its formation. The ester is then purified by customary methods, e.g. vacuum distillation, extraction with a solvent and evaporation of the solvent, treatment with activated charcoal, etc.

As alcohols are used for the esterification process for production the ester according to the invention preferably uses lipophilic and hydrophobic alcohols in order to obtain derivatives that are insoluble in water and soluble in lipids, which are the best carriers for skin care products

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are, ■ Examples of suitable alcohols are: 1-phenyl-1-propanol C, -H ₁ - -CHO H-CpH ₁ -

2-phenyl-2-propanol

CH ₅ .. OH

^ TC ^ ° 6 ^H 5

2-phenyl-1-ethanol C ₅ H ₅ - CH ₂ - CH ₂ OH 3-phenyl-1-butyne-3-o1

HC = C OH

C - C _C H _C / 6 5

OH *.

The products are generally in the form of a light yellow to dark yellow oil which is insoluble in water and in oils and is soluble in practically all organic solvents with the exception of petroleum ether.

It is also possible to add other fat-soluble esters, in particular, to the cosmetic preparations according to the invention Esters of acids, which, like malic acid, play a role as factors in the Krebs cycle, as already mentioned. In in this context are in particular the esters of the above named alcohols with acetic acid, citric acid, a-ketoglutaric acid, To mention pyruvic acid and oxaloacetic acid.

Embodiments of the process for the preparation of esters of malic acid according to the invention are shown in the following Examples described.

Example 1 Diester of malic acid and 2-phenyl-1-ethanol

In a 1 1-ßeaktor 268 g of malic acid (2 mol) and 600 g of 2-phenyl-1-ethanol (molar excess) are given. Man heated with agitation for 7 hours at 130 ° C and allowed to do so evaporate the formed water. You then steam

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The excess of the unreacted 2-phenyl-1-ethanol is removed under reduced pressure, allowed to cool, taken up in 2 l of acetone, decolorized with 20 g of charcoal, filtered and evaporated under reduced pressure to remove the acetone. 620 g of the diester of the gross formula ^G 20 ^H 22 ° 5 ^{with a molecular} weight of 94-2.396 are obtained. Composition:

G% Wo 0% 70.16 6.4-7 23.37 Malic acid 35%

2-phenyl-ethanol 64.6%

100.0%

Structural formula:

IJ 22 rjj

The product is a viscous yellow oil that has the characteristic Has smell of rose oil in fatty substances, methanol, ethanol, isopropanol, propylene glycol, acetone, ether, benzene, dimethylformamide, Oxyethylene glycols, acetonitrile, etc. is soluble and insoluble in water and petroleum ether.

In the ultraviolet spectrum the ester has a maximum around £ 2590.

Characteristic reactions

After hydrolysis with NaOH with boiling in a dilute medium and centrifugation two phases are obtained: an upper phase, consisting of phenyl-2-ethanol, and one lower phase, consisting of sodium malate in aqueous solution.

Example 2 Diesters of malic acid and 1-phenyl-1-propanol

In a 1 1 reactor, 268 g of malic acid (2 mol) and g 1-Phenylä * S.yi «S.« e * part (4 mol) given. One heats under

Movement for 12 hours at 110 ° C, with the water of reaction evaporated, allowed to cool, taken up in 2 liters of ether, washed with water, dried over anhydrous NapSO ^ r, and. the ether evaporates under reduced pressure

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710 g of the diester of malic acid and 1-phenyl-i-propanol.

Example 3 Diesters of malic acid and 2-phenyl-2-propanol

134 g of malic acid (1 mol) and 500 g of 2-phenyl-2-propanol (molar excess) are added. The mixture is heated to 150 ° C. for 6 hours, the reaction water being used lets evaporate, and then evaporates the unreacted excess alcohol under reduced pressure. Man takes up in 2 l of methanol, decolorized with 30 g of charcoal, filtered and the methanol is evaporated off under reduced pressure. You get 330 g of the diester of malic acid and 2-phenyl-2-propanol.

Example 4- Monoester of malic acid and 3-phenyl-1-butyn-3-ol

134 g of malic acid (1 mol) are placed in a 500 ml reactor and 146 g of 3-phenyl-1-butyn-3-ol (1 mole). The mixture is heated to 200 ° C. for 4 hours, the water of esterification being allowed to evaporate. It is allowed to cool, taken up in 1 l of acetone, decolorized with 20 g of charcoal, filtered and the acetone is driven off under reduced pressure Pressure off. 220 g of the crystallized monoester are obtained.

First, animal tests were carried out to determine the harmlessness and to detect the activity of the esters according to the invention, which are applied topically as a cream. Here was the skin tolerance of the excipient alone and the determined the cream containing malic acid ester.

The experiments were carried out on adult male Wistar hats carried out. The animals were in groups of 5 Rats with practically the same weight were divided, treated under the same environmental conditions and received the same lining. One group was made up of the malic acid esters containing cream and treated with a group treated with the excipient alone and with a comparison group compared.

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on

The product was applied twice a day, by massaging / one approximately

ρ
4 cm large, previously depilated area on the stomach with scissors. The same hair removal was done every week. The treatment was carried out for four consecutive weeks.

At the end of the experiment, the only objective observation was a clear inflammation of the fur in the depilated area "found in the comparison groups, probably caused by external contact in the places where the hair grew back. This look was practically off identify the groups associated with the malic acid esters containing cream or with the carrier alone "treated became. .

The animals were then sacrificed, followed by samples of the fur were taken. The skin samples were after Bouin-Hollande fixation subjected to an anatomic-pathological examination.

The histological examination of the rat fur was carried out by Comparative evaluation of the components of the fur made: In the case of the epidermis, the thickness of the papillae, the keratin reserve and the number of cell layers of the epidermis is determined; in the case of the dermis, the thickness of the dermis layer, "the Strength of the elastic fiber bundles (faisceaux conjonctifs), their cellular properties and finally the cytological structure

fixed see the "annexes dermiques'V. Bexm subcutaneous cell tissue was essentially determined the thickness in comparison with that of the dermis. In the skin muscles the strength of the Muscle bundles examined in comparison to the elements of the totality of the samples taken. After a thorough investigation All layers of the removed skin could be confirmed that the application of the malic acid ester containing. Cream as well as the auxiliary stolff alone on a previously depilated The surface of the fur of rats does not show any pathological changes from the structural point of view as well as from the

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Position of the cells. In particular, it should be noted that that the mitoses in the generating layer (l'assise generatrice) are numerical in the treated animals are not increased and have shown no sign of abnormality. It can therefore be based on the complete compatibility of the Try to close used products.

The favorable result of the preliminary tests described above justified the tests on humans in a second phase.

W It is of course difficult to objectively assess the effect a beauty cream has on the face. For this purpose, the procedure was as follows: Each person's observation slip is divided into three fields. On the first field, which schematically describes a face, the observer has entered his personal impressions of the face after the examination with the magnifying glass: fat and dry areas, enlarged pores, lichen or ulcers, wrinkles and sagging and withered areas. In the second field the patient has entered his subjective impressions during the treatment, in the third field the objective impressions of the examiner after the treatment after viewing with the magnifying glass are recorded. Eight people were tested:

™ Six women applied the cream in the morning and in the evening after the Toilet open. Some put on make-up, some didn't. Two Men applied the cream to their face in the morning before or after shaving. The trial was carried out on 15 consecutive Days. The following observations were made:

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1 * Ms. G., 30 years, brunette:

Observation; before

Oily skin, enlarged pores, especially on the car and around the nose; the nose contrasts with the dry appearance the forehead and chin.

Subjective impression

Impression of freshness and relaxation on the face after application. The nose is no longer shiny. Applying make-up is easier.

Observation afterwards

Disappearance of the fat areas, narrowing of the pores. The complexion, which takes on a generally duller appearance becomes clear more even.

2. Miss. 0. «24 years, blond :

Dry skin, easily red spots, allergic to many products.

3 Ms. A., 54 years old, brunette :

Oily skin in the middle areas and dry skin on the sides, crow's feet in the corners of the eyes

4. Mrs. Z. «38 years, blond :

Very fine and very delicate skin. Does not tolerate any make-up.

Immediate impression of freshness and suppleness. The skin is finer and the complexion clearer. The skin is no longer spoiled by wind and cold.

The complexion is clearer, the skin gentler and smoother. The cream is pleasant to use and works very quickly absorbed and not greasy.

Good day cream. Not very fat for the night. Suitable not for any make-up.

Appearance of better nourished and healthy skin. Disappear the soldering.

The complexion becomes more even, the oily areas disappear. Small wrinkles become more blurred and less deep.

Always very delicate and fine skin, but a little dry.

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cn co

5th FrI. S., 25 years, maroon:

Observation beforehand

Bold sections with extended
Pores on the cheeks and on
the nose. Pimples in the corners of the mouth.

Subjective impression

Very pleasant cream, refreshing, closes pores and eliminates the pimples. The skin becomes finer and the complexion clearer.

Observation afterwards

The complexion becomes even, the pores close and the pimples disappear.

6. Ms. B., 50 years old, brunette:

Dry skin and wrinkles in
the corners of the mouth and eyes. Wrinkles on the forehead,
under the eyes.

7. Mr S., 42 years old, brunette:

^ Rasp-like appearance of the skin
- »after the electric shave. Top
-Everyone hands dry, keeps them
°> Soap solid, little flaking.

Revitalizing skin that appears both thicker and smoother. Disappearance of the complexions reminiscent of paper mache.

Makes the electric shave easier and allows you to forget about it. Leaves the roughness and that Soap deposits on the top of the hands will disappear. Better nourished skin, smoother and firmer. You can no longer remember, the wrinkles are smoothed and the bags under the eyes less limp and withered.

The skin of the face looks smoother, finer and better nourished after an electric shave and on the top of the hands. "

8. Mr. A., 16 years old, brunette;

Very oily skin, advanced
Pores and blackheads. Remains of
Acne junenilis. Always shave
difficult even with an electric shaver.

Shave much easier and more comfortable. Bring the blackheads and those Pimples to go away without being uncomfortable to use. Doesn't stick to the face. Reduces irritation from the razor. Very marked effect on seborrhea, disappearance the blackhead. The pores have closed and the acne has weakened.

CO NJ CO

The above results can be viewed the following findings:

1) The cream is pleasant to use; she is fresh, will quickly recorded and leaves no trace.

2) The cream is particularly effective on oily and advanced skin Pores. It gives the skin the suppleness of a healthy one and young skin and acts on the small wrinkles that it easily removes.

3) The cream allows the skin to nourish itself more properly, and makes lichen and pimples go away. she enables the skin to defend itself against infection and makes redness disappear and soothe the acne

4-) The cream gives the skin of hands tainted by soap restore vitality and make the electric shaver easier to slide on.

5) The effect of the cream is less rapid on very dry skin, for which a thicker fatty phase must be used.

In all cases, the cream ensures uniformity and Clarity of the complexion, i.e. the two essential basic properties of the skin.

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Claims (2)

Claims 1.) Cosmetic preparations, in particular beauty creams and shaving creams, containing one or more esters Malic acid and lipophilic and hydrophobic alcohols. 2.) Cosmetic preparations according to claim 1, containing esters of malic acid and 1-phenyl-1-propanol, 2-phenyl-2-propanol, 2-phenyl-l-ethanol or ^ - 3 ·) Cosmetic preparations according to claim 1 or 2, containing in addition, esters of the alcohols mentioned with acetic acid, citric acid, a-ketoglutaric acid, pyruvic acid or Oxaloacetic acid. 109847/1764