EP0185688A1

EP0185688A1 - Cosmetic product for the treatment of the skin

Info

Publication number: EP0185688A1
Application number: EP19850902439
Authority: EP
Inventors: Kurt F. Stocker; Roland Eichenberger
Original assignee: Pentapharm AG
Current assignee: DSM Nutritional Products AG
Priority date: 1984-06-15
Filing date: 1985-06-13
Publication date: 1986-07-02
Also published as: WO1986000015A1; CH658785A5

Abstract

Utilisation de phospholipides ou de mélanges de phospholipides et/ou de sphingolipides ou de mélanges de sphingolipides servant d'additifs à action hémostyptique topique et/ou à action de régénération sur la barrière de perméabilité de la peau, dans des produits cosmétiques pour les soins cutanés, et produits cosmétiques contenant ces additifs. Les lipides mentionnés peuvent être obtenus par extraction de tissus ou de cellules animales.Use of phospholipids or mixtures of phospholipids and / or sphingolipids or mixtures of sphingolipids serving as additives with topical haemostyptic action and / or with regenerative action on the permeability barrier of the skin, in cosmetic products for skin care , and cosmetic products containing these additives. The lipids mentioned can be obtained by extraction from tissues or animal cells.

Description

Cosmetic product for skin care

The present invention relates to cosmetic products for skin care which contain phospholipids and / or sphingolipids as additives having a superficially haemostatic effect and / or regenerating the skin's permeability barrier.

It was found that many of the shaving aid on the market, treatment compositions such as foaming or non-foaming shaving creams, and Rasiernachbehand- containing eg shaving lotions and Rasierpuder, substances which ^j to the skin, and in particular the so-called permeability barrier of the stratum corneum, exert a damaging effect. The permeability barrier, which has the function of preventing excessive transcutaneous water loss and reducing the skin's permeability to pollutants, consists of intercellularly embedded lipid layers [see PM ELIAS, Lipids and the Epidermal Permeability Barrier, Arch. Derma - tol. Res. 2 0, 95-117 (1981)]. Damage to these lipid layers causes the skin to dry out and become rough. It has been found that the skin-damaging effect of shaving aids and shaving aftertreatment agents can be reduced or eliminated by giving them lipids which occur in animal tissues, in particular phospholipids or phospholipid mixtures and / or

Sphingolipids or sphingolipid mixtures. The effect of these lipids is probably that they prevent the damage to the permeability barrier or promote the regeneration of the damaged permeability barrier.

The surprising finding was also made that the phospholipids, in addition to their ability to regenerate the permeability barrier, also have a superficial hemostatic effect, which is of great practical importance.

As is well known, shaving often leads to skin injuries, sometimes even to bleeding skin wounds. In order to prevent infections of such wounds, after-shaving so-called aftershaves are applied. Aftershaves are usually alcoholic-water mixtures with bactericidal activity, which can contain additives with moisturizing and / or lipid-replenishing effects, bactericidal substances and astringent, epithelizing or anti-inflammatory active substances. In the formulation of aftershave, their influence on the natural has been evident

Disregarded hemostasis. The aftershaves available on the market do not influence haemostasis and blood clotting at all or even exert a more or less strong inhibition of haemostasis and blood clotting.

64 commercially available aftershaves were tested in order to determine their effect on the skin bleeding caused by the shave. This investigation found that 36 of these aftershaves were natural Hemostasis had neither an inhibiting nor a promoting influence, while the remaining 28 aftershaves delayed hemostasis to a great or very great extent. In order to obtain reliable comparative values, the individual aftershaves were subjected to the following test:

The aftershave to be tested was concentrated, whereupon the residue was taken up in a volume of 0.025 molar calcium chloride solution equivalent to the used aftershave volume. 0.2 ml of the sample containing calcium chloride was added to 0.2 ml of human citrate plasma a at 37 ° C., after which the time elapsing before coagulation occurred was measured. For comparison, the clotting time of a plasma blank sample was measured using calcium chloride alone. The anticoagulant effect of the examined samples appears in the coagulation time, which is longer than that of the blank sample. The disadvantageous effects of conventional aftershaves on haemostasis and blood coagulation are due to their acidity and / or their content of other substances which inhibit haemostasis and blood coagulation. These substances can be divided into four categories. The first category includes substances which inhibit the adhesion, aggregation and release reactions of the platelets. These substances include, for example, salicylic acid and its derivatives (methyl salicylate), which are often added to aftershaves as bactericides. Substances that bind calcium ions, such as citric acid, phosphoric acid, ethylenediaminetetraacetic acid and their salts, fall into the second category. The third category contains surface-active substances which are used as lipid replenishing and skin conditioning agents and partly as solubilizers, which destroy the molecular order of the phospholipid micelles of the blood which are essential for the normal course of the hemostasis process. For this class of substance belong in particular to the so-called surfactants, which can be anionic, cationic or non-ionic in nature. Compounds of different substance classes fall into the fourth category, which inhibit blood coagulation factors due to their general protein-denaturing effect. Examples of such substances are strong anionic or cationic surfactants, strong anionic or cationic film formers with high protein affinity, for example quaternized copolymers of vinyl pyrrolidone and dimethylaminoethyl methacrylate and acrylic acid polymers, quaternary ammonium bases, which are often used as bactericides Shaving waters are used, and acidic metal salts, for example Al "(SO) _, ZnSO. and alum.

The present invention relates Applicable methods fertil ^'by certain naturally occurring lipids, more particularly sondere phospholipids and mixtures thereof and / or sphingolipids, or mixtures thereof, as a topically effective hae¬ mostyptisch and / or the permeability barrier of the skin regenerating additives generally in the Hautpfle- serving cosmetic products and especially in shaving aids and after-treatment agents.

The invention further relates to the cosmetic products containing the additives defined above.

As lipid-containing additives in aliphatic halogenated hydrocarbons, e.g. Methylene chloride,

Chloroform, etc. genkohlenwasserstoffen or in mixtures of aliphatic and Halo¬ aliphatic alcohols, for example methanol, ethanol, etc., soluble, however, insoluble in acetone and slightly soluble in pure aliphatic alcohols extracts of organs or cells, ^'for example, brain,

Spinal cord, adrenal glands, lungs, liver, skin or erythrocytes, from slaughter animals, e.g. Beef, pork or sheep.

Extracts which are predominantly or only phospholi- pide can be obtained, for example, by degreasing adrenal glands using acetone, extracting the defatted tissue using an aliphatic chlorinated hydrocarbon, eg chloroform or methylene chloride, concentrating the extract to dryness, dissolving the residue in ether, filtering the solution and precipitating using ethyl alcohol become.

Extracts which contain predominantly or only sphingolipids can be obtained, for example, by lyophilization of bovine brain, extraction of the lyophilisate with methanol, extraction of the residues with a mixture of an aliphatic chlorinated hydrocarbon and an aliphatic alcohol, concentration of the extract by distillation in vacuo, cooling the Concentrates and separation of the excreted lipid mixture are obtained by filtration.

Extracts which contain both phospholipids and sphingolipids can be obtained, for example, by extracting bovine brain with acetone, extracting the defatted residue with methanol, extracting the solid

Residue can be obtained with a mixture of an aliphatic halogenated hydrocarbon and an aliphatic alcohol and removal of the solvent in vacuo.

The phospholipids used as topical hemostyptic additives and regenerating the permeability barrier form a class of substances which can be defined by the following formula:

R ¹ -0-CH2-C _| H-CH2-0-P02_-R ³ I

0-R in which R is an alkanoyl radical with 14 to 26 carbon atoms

2 atoms, R is an unsaturated aliphatic acyl radical with 16 to 22 carbon atoms and 1 to 6 double bonds

3 represent and _, τRR, 3 and 2-aminoethoxy, seryl or inosityl groups. The sphingolipids used according to the invention as regenerating the permeability barrier form a class of substances which can be defined by the following formula:

in which Ri represents a ~ en-alkyl, alkenyl, hydroxyalkyl or hydroxyalkenyl radical having 15 to 23 carbon atoms, the hydroxyl group with a saturated or unsaturated fatty acid or hydroxy fatty acid with up to

2 18 carbon atoms can be esterified, R one from

Carbohydrate residue consisting of glucose, galactose, N-acetylglucosamine, N-acetylgalactosamine and / or N-acetylneuraminic acid units, in which a hydroxy group can be esterified with a saturated or mono- or polyunsaturated fatty acid, or a phosphorylcho represents linrest and n denotes an integer from 12 to 18. '

A description of the phospholipids and the sphingolipids can be found in "Biochemistry" by G. ZUBAY, 1983, pages 505 ff, Addison-Wesley Publishing Company. The phospholipids or phospholipid mixtures (animal organ or cell extracts) are particularly suitable as additives in shaving aids, for example foaming or non-foaming shaving creams, or in shaving aftertreatment agents, for example shaving lotions or shaving powders, which are both topically hemostatic and permeable regenerating effectiveness should be borrowed.

The phospholipid-containing additives can be added in amounts of about 1 to 20 mg, preferably 3 to 5 mg, of solid substance per 100 g of finished shaving aid or after-treatment agent.

The pH of an aftershave is also important for achieving an optimal hemostatic effect. The pH is preferably adjusted such that when the aftershave comes into contact with the blood, a pH of about 6 to 9, preferably 7 to 8, which is favorable for blood coagulation, is established.

In order to enhance the regenerating effect of the permeability barrier, sphingolipids (animal organ or cell extracts containing sphingolipids) can also be added to the shaving aids and aftertreatment agents, for example in amounts of about 1 to 20 mg, preferably 3 to 5 mg, of solid substance for every 100 g of finished shaving aid or after-treatment agent.

When formulating the shaving aids and post-treatment agents according to the invention, it is essential not to use any of the substances mentioned above which inhibit hemostasis and blood coagulation.

The following substances can be used in shaving aids and aftertreatment agents, for example, as further additives which do not inhibit haemostasis and blood clotting: polyols, for example glycerol, sorbitol and butanetriol as humectants; Alkyl esters of dicarboxylic acids, for example diisopropyl adipate, and aliphatic carboxylic acid esters of polyols, for example triacetylglycerol as refatting agents; Polyvinylpyrrolidones and their copolymers with vinyl acetate or with long-chain olefins and polyglycols as film formers; Esters of p-hydroxybenzoic acid, phenylalkanols, for example phenylethyl alcohol, phenol and phenol derivatives, phenylurcuric compounds and thymol as Bak- tericides; and as a surfactant, for example, a compound of the formula

CH "-CH -0H I 2 2

in which R is a coconut fatty acid residue (for example, representing the branded product Gafteric ^® CM-2 / N, GAF Corporation, New

York). It is easy to determine whether one intended as an additive in shaving aids or after-treatment agents

A substance that inhibits hemostasis and blood clotting may or may not have an effect by subjecting the substance in question to the blood coagulation test described above.

The phospholipids and sphingolipids (e.g. the lipid fractions obtained by extraction from animal tissues or cells) can also be added to other cosmetic products which do not have to have topical hemostatic activity, but only that

Protect the permeability barrier or which are intended to regenerate the permeability barrier damaged by internal or external influences, for example washing processes or light radiation. For example, the abovementioned lipids or lipid mixtures can be creams, in particular oil-in-water creams, liquid emulsions (lotions), for example of the oil-in-water type, friction, facial tonic, aqueous or aqueous-alcoholic - Gels, body powders, cosmetic sunscreen preparations, etc., are incorporated. The phospholipids or their mixtures and / or the sphingolipids or their mixtures can also be used as such as finished (complete) cosmetic products alone, ie in the absence of other cosmetic additives, in the form of aqueous or aqueous-alcoholic solutions . example 1

To produce an aftershave additive with a hemostatic effect, 2 g of commercially available cephaline (phospholipid mixture) from bovine brain in 200 ml of dist. Water was added and so much NaOH 1 N was added with constant stirring that a pH of 7.5 to 8.0 was established and a homogeneous, opalescent suspension was formed. The volume of this aqueous suspension was distilled with dist. Add water to 250 ml. 250 g of propylene glycol and then 500 g of dibutyl adipate were then added. This mixture was processed into a stable emulsion using a homogenizer.

20 g of this emulsion with the addition of a suitable amount of perfume oil and aqueous ethyl and / or isopropyl alcohol gave 60 to 90% by volume, an aftershave with hemostatic properties.

Example 2

5 kg of acetone dry powder from bovine adrenal glands were extracted with chloroform, the extract was evaporated to dryness, the residue (200 g) dissolved in 400 ml of ether, mixed with 2 l of ethyl alcohol, the precipitated cephaline was separated off by decanting and dried in vacuo .

The 40 g of cephalin obtained were together with 40 g of methyl p-oxybenzoate and 80 g of polyvinylpyrrolidone with an average molecular weight of 630,000 in 15 l of dist. Water with constant pH adjustment to 7.5 to 8.0 using 1N sodium hydroxide solution until a homogeneous cephaline suspension was formed. The volume was then distilled. Water added to 20 1.

0.2 ml of the in calcium chloride solution 0.025 M 1:50 Dilute cephaline suspension caused 0.2 ml of human citrate plasma to clot in less than 100 seconds at 37 ° C., while a blank value with calcium chloride alone caused a clotting time of more than 150 seconds. 1 kg of cephaline suspension, 1.5 kg of diisopropyl adipate, 500 g of sorbitol and 1.5 kg of perfume essence, dissolved in 85% ethyl alcohol, gave 50 l of aftershave with hydrating, lipid-replenishing and hemostatic properties.

Example 3

2 g of commercial cephalin from bovine brain, 1 g of benzoic acid and 50 (poration Gafteric ^® CM-2 / N, GAF Cor¬, New York) g B _j S-hydroxyethyl-N -carboxymethyl- coconut fatty acid-amidoäthylamin were dissolved in distilled water, Homogenized to 7.5 to 8 with pH adjustment using 1 N sodium hydroxide solution.

0.2 ml of the solution diluted in calcium chloride solution 0.025 M in a ratio of 1:50 brought 0.2 ml of human citrate plasma to a coagulation in less than 100 seconds, while a blank value with calcium chloride caused a coagulation time of more than 150 seconds .

^' 200 ml of this cephaline suspension, 1 1 propylene glycol, 150 g propylene glycol alginate, 200 g perfume oil and 8.45 1 distilled water provided a skin care gel with hemostatic properties.

Example 4

100 g of raw cephaline (produced from bovine adrenal glands according to Example 2) were further purified by chromatography on silica gel. The coagulation-active fractions were based on their accelerating effect determined on the recalcification time of human citrate plasma. The combined active fractions, evaporated to dryness in vacuo, gave 16 g of purified cephalin. Various cephaline concentrations in 0.025 molar calcium chloride solution on human citrate plasma were tested to test the blood-clotting activity. The following results were obtained:

μg purified coagulation time cephaline per ml (seconds)

0 (CaCl ₂ alone) 121

4 110

10 80

13 76 20 70

27 68

40 65

200 60

10 g of purified Nebennierenkephalin, 25 g of B ~ ß-hydroxyethyl-N - ^ - carboxymethylkokosfettsäure amidoäthyl--amine (Gafteric ^® CM-2 / N, GAF Corporation, New York) and 1 g of methyl p-oxybenzoate were dissolved in distilled water up ¬ taken, the volume to 500 ml and the pH to 7.5 - 8.0. A clear solution was obtained which was particularly suitable as a hemostyptically active raw material for incorporation into personal care products with a low alcohol content and poor solution properties.

Example 5 To obtain a Sphingolipidfraktion with re¬ generating effect on the permeability barrier wur¬ the 10 kg bovine brain in the cutter homogenized lyophilized on stainless steel plates and the dry product ^'twice during one hour each with 100 1 of methanol and once for 30 minutes with 50 1 Stirred methanol and filtered through a suction filter.

The filter residue was extracted for one hour with 100 1 methylene chloride 40% by volume in methanol and then, in a further operation, with 100 1 methylene chloride 50% by volume in methanol.

The combined methylene chloride-methanol extracts were concentrated to 5 l in vacuo and the concentrate for separating the sphingolipid mixture was kept at + 4 C for 24 hours. The excreted lipids were separated by filtration and dried in vacuo; 30 g of dry matter were obtained.

2 g of dried Sphingolipidfraktion, 10 g of B-.beta.-hydroxyethyl-N-ß-carboxymethylkokosfettsäure amidoäthyl--amine (Gafteric ^® CM-2 / N, GAF Corporation, New York) and 3 g of methyl p-oxybenzoate in distilled water were homoge ¬ nized and the volume to 1 1 and the pH with sodium hydroxide solution 1 N to 6.8. In this way, a stable suspension of sphingolipids was obtained, which was suitable as a base material for the production of various skin care products with a regenerating effect on the permeability barrier of the skin.

Example 6

For manufacturing a face cream with regenerated Bonded effect on the permeability barrier of the epidermis, 2 g of ge according to Example 5 from bovine brain wonnenen Sphingolipidfraktion, 10 g of B _j S-hydroxyethyl-N - ^ - carboxymethylkokosfettsäure-amidoäthylamin (Gafteric ^® CM 2 / N, GAF Corporation, New York) and 3 g of methyl p-benzoate oxyben- in distilled water and homogenized ge to 1 1 illustrates. A stable, opalescent suspension was obtained.

To prepare a cream based on an oil-in-water emulsion, 30 g of polyoxyethylene glycerol fatty acid ester (Tagat ^® S, Th. Goldschmidt AG, Essen, FRG), 20 g of glycerol fatty acid ester (Tagat ^® M), 50 g of cetyl alcohol, 50 g Isopropyl myristate and 2 g of methyl paraben melted at 60 ° C. A solution of 20 g propylene glycol, 100 g sphingolipid suspension, 3 g imidazolidinyl urea in 725 ml distilled water was worked into the molten mixture with constant stirring. After cooling, the mixture was rolled into a homogeneous cream.

Example 7

For the preparation of a fraction containing phospholipid and sphingolipid, 10 kg of fresh bovine brain were homogenized in the cutter, and for degreasing extracted once with 40 1 and once with 30 1 acetone and each filtered through a Nutsche. To remove phosphatidylcholine (lecithin), the residue was stirred twice with 50 l of methanol for 3 hours at 20-25 ° C. and filtered through a Nutsche.

The lecithin-free residue was then stirred twice with 50 liters of a mixture of methanol and methylene chloride in a ratio of 60:40 parts by volume for 3 hours at a time of 20-25 ° C. and each was filtered through a suction filter.

The combined filtrates were concentrated to 2 l by vacuum distillation and the concentrate in vacuo at max. 40 C dried.

4 g of this lipid fraction, 50 g of B-ß-hydroxyethyl-N-ß-carboxymethylkokosfettsäure amidoäthylamin (Gafteric ^® CM-2 / N, GAF Corporation, New York) and 3 g of methyl p-oxy benzoate were homogenized in distilled water and the volume set to 1 1 and the pH to 6.8. A stable lipid suspension was obtained which was suitable as a base material for the production of skin care products with a hemostatic and regenerating effect as well as the permeability barrier of the skin.

Example 8

A shaving cream with both hemostyptic and skin permeability barrier regenerating properties as an aid for brushless shaving was obtained by adding 45 g of cetyl palmitate, 110 g of glycerol monostearate, 25 g of coconut oil, 5 g of coconut fatty acid and 7 g of B-hydroxyethyl-N -j'-carboxymethylkokosfettsäure-amino doäthylamin (Gafteric ^®, GAF Corporation, New York) brought at 60 C to melt and this melt slowly into a solution of 20 g of zube¬ according to example 7 ready before lipid suspension, 20 g of methyl stirring p-oxybenzoate, 70 g glycerol and .708 g dist. Water incorporated. Finally 10 g of perfume oil were added and the resulting cream was homogenized by machine.

Claims

1. Cosmetic product for skin care, characterized in that it contains at least one phospholipid and / or as an additional or sole additive that regenerates the skin permeability barrier and acts as a topically hemostatic additive that also regenerates the skin permeability barrier Contains sphingolipid.

2. Cosmetic product according to claim 1, characterized in that it acts as a hemostyptic and regenerating the permeability barrier additive at least one phospholipid of formula I. in which R is an alkanoyl radical with 14 to 26 carbon atoms

3 gen and R represent a 2-aminoethoxy, seryl or inosityl group contains.

3. Cosmetic product according to claims 1 and 2, characterized in that the haemostypically active additive and the permeability barrier regenerating additive by extraction of slaughter animal organs or animal cells, e.g. Skin, brain, spinal cord, lung, liver, adrenal gland or erythrocyte, extract is obtainable which contains at least one phospholipid of the formula given in claim 2.

4. Cosmetic product according to claim 3, characterized in that the hemostatic active and regenerating the permeability barrier regenerating an additive by degreasing adrenal glands by means of acetone, extraction of the degreased tissue by means of an aliphatic chlorinated hydrocarbon, for example chloroform or methylene chloride, Concentration of the extract to dryness, dissolving the residue in ether, filtering the solution and precipitation using ethyl alcohol.

5. Cosmetic product according to claim 1, characterized in that it as the regenerating the permeability barrier regenerating additive at least one Sphingolipid of the formula

in which R represents an alkyl, alkenyl, hydroxyalkyl or hydroxyalkenyl radical with 15 to 23 carbon atoms, the hydroxyl group with a saturated or unsaturated fatty acid or hydroxy fatty acid with up to

2 18 carbon atoms can be esterified, R one from

Carbohydrate residue consisting of glucose, galactose, N-acetylglucosamine, N-acetylgalactosamine and / or N-acetylneuraminic acid units, in which a hydroxy group can be esterified with a saturated or mono- or polyunsaturated fatty acid, or a phosphorylcho - represents linrest and n denotes an integer from 12 to 18.

6. Cosmetic product according to patent claims 1 and 5, characterized in that the additive regenerating the permeability barrier regenerates a by lyophilization of bovine brain, extraction of the lyophilisate with methanol, extraction of the residues with a mixture of an aliphatic chlorinated hydrocarbon and of an aliphatic alcohol, concentration of the extract by distillation in a vacuum, cooling the concentrate and separating the excreted lipid mixture by filtration obtainable extract.

7. Cosmetic product according to claims 2 and 5, characterized in that it contains, as an additive, a lipid fraction which is both hemostyptically active and regenerates the permeability barrier, which is obtained by extraction of bovine brain with acetone, extraction of the defatted residue with methanol Extraction of the solid residue with a mixture of an aliphatic halogenated hydrocarbon and an aliphatic alcohol and removal of the solvent is obtainable in vacuo and which comprises at least one phospholipid of the formula I given in claim 2 and at least one sphinolipid given in claim 5 Formula II ent ent.

8. A shaving aid or after-treatment agent, characterized in that it is free from substances which inhibit haemostasis and blood coagulation and that it is at least one phospholipid and / or as additive which has a topical hemostatic effect and at the same time regenerates the skin's permeability barrier contains at least one sphingolipid as an additional or sole additive which regenerates the skin permeability barrier.

9. shaving aid or after-treatment agent according to claim 8, characterized in that it contains as an additive at least one phospholipid of the formula I given in claim 2 and / or at least one sphingolipid of the formula II given in claim 5.

10. shaving aid or after-treatment agent according to claims 8 and 9, characterized in that it contains 1-20 mg, preferably 3-5 mg, phospholipid or phospholipid mixture and / or 1-20 mg sphingolipid or sphingolipid mixture per 100 g of finished product .

11. Use of phospholipids of the formula I specified in claim 2 as topically hemostatic additives and regenerating the skin permeability barrier and / or of sphingolipids of the formula II specified in claim 5 as regenerating additives for the skin permeability barrier in cosmetic products for skin care.