GB2181647A

GB2181647A - Compositions based on lysine and arginine salts

Info

Publication number: GB2181647A
Application number: GB08623076A
Authority: GB
Inventors: Jean Morelle; Eliane Lauzanne
Original assignee: Individual
Current assignee: Individual
Priority date: 1985-10-01
Filing date: 1986-09-25
Publication date: 1987-04-29
Also published as: FR2587900A1; JPS6289646A; DE3633453A1; GB2181647B; FR2587900B1; GB8623076D0

Abstract

Compositions for cosmetic, dermatological and/or alimentary use comprise salts resulting from the association of fatty acids with lysine or arginine of formula: <IMAGE> where R is a hydrocarbon radical straight or branched, saturated or mono-unsaturated comprising from 4 to 30 carbon atoms; and R' is -CH2- for lysine or <IMAGE> for arginine.

Description

SPECIFICATION Compositions based on lysine and arginine The invention relates to new compositions based on salts of lysine and of arginine, in which these basic amino acids are associated with fatty acids. Such associations have antioxidant, emulsifying and antiirritant properties, and can be used in cosmetic, dermatological, and even alimentary compositions, by reason of their biological nature and as they provide protection againsttheformation of pipoperoxides.

These compounds or associations correspond to thefollowing general formula:

in which R represents a hydrocarbon radical, straight or branched, saturated or mon-unsaturated comprising from 4to 30 carbon atoms, R' represents -CH2-for lysine or the guanidyl residue -C-NH-for arginine.

{ NH Experience has shown thatthe use of polyunsaturated fatty acids leads to compositions which are badly tolerated on the skin surface.

These amino acid-fatty acid compounds can be produced by neutralization of the fatty acid with the basic amino acid, in such mannerthata hydroalcoho licsolutioncontaining 10% of one of the compounds shows a pH between 6.5 and 7.5. By way of example, one molecule of oleic acid (about 282 g) is dissolved in 500 to 750 ml of ethanol on a water bath at 50 C with agitation. One molecule of one ofthe amino acids is added slowly, (about 146 g for lysine or 174 g for agrinine). At a temperature not exceeding 55 C, in orderto avoid discolouration, and under reduced pressure, the alcohol and eventually the water is eliminated from the lysine base. In the case of unsaturated fatty acids like oleic or linoleic acids, gels of variable consistency are obtained.Saturated acids yield a solid mass, which can be ground and reduced to powder, and which is of colourvarying between white and beige.

The following Table gives the yields of fatty acids-amino acids, both theoretical and found, as well as the contents of total nitrogen, which determine the degree of purity ofthe product. The mono-unsaturated fatty acid derivatives give with water, in the cold, gels which liquefy on heating. They are soluble in ethanol pure and hydrated, in propylene glycol, and chloroform, but insoluble in acetone, and ethyl acetate. The saturated fatty acid derivatives take the form of powder, and are soluble, after heating, in propyleneglycol, and in glycerol. Theyform gels with water.They are partly soluble in chloroform and sparingly soluble in fats, like stearine, polyox yethylenefatty alcohols, and cetyl alcohol.

Calculated on the anhydrous products Fatty Theoretical mood Acid No. Fatty Amino Nitrogen Fatty Amino Mitrogen Acid Acid Acid Acid Derivates of Lyslne Stearic I 431| 65-8%| 34.2% 421 6.511 66.4k1 33.6% 6.3+ Palmitic 402 63.7%| 36.3% 6,9 % 6.9 64.8% 35.2% 6.72 Oleic 1 428 68.% 24,2% 6.5 % 66-8% 33.2% 6.4 Derivatives of Arginine Stearic 488 62.0% 62.0% 38.0% 12.22% 62.8% 62.8% 37.2%t 11.8% Oleic 486 456| 61.8% 38,2% 12,28% 61.2% 2.8% 12.2%

Identification a) Melting Points (Maquenne Block) Lysine oleate 150 +5 Arginine oleate 170 +5 Lysine palmitate 185 Arginine palmitate 135 Lysinestearate 190 " Argininestearate 170" Lysine myristate 189 " b) Colour Reactions 1 - Into 2 ml of a hydroalcoholic solution, some drops of a ninhydrin solution are poured. The solution is held for some minutes on a boiling water bath. In all cases, there is obtained a brown violet colour.

2-Into 2 ml of a hydroalcoholicsolution, some drops of a sulphuric solution of paradimethylbenzaldehyde are poured. Awhite precipitate is produced.

The mixture is held over a water bath for some minutes, the precipitate disappears, and the solution take on a rose colour.

c) Examination by chromatographic plate For characterization by yield of amino acid, there is usedthefollowing migration solvent: chloroform-methanol-ammonia: 20/20/10.

Migration period: about 30 minuts development: ninhydrin solution, methyl red of bromocresol purple.

Rf Rf Lysine 0.35 Arginine 0.38 Lysine oleate 0.24 Arginine oleate 0.33 Lysine palmitate 0.23 Arginine palmitate 0.33 Lysinestearate 0.23 Argininestearate 0.33 Caprylate 0.23 For characterization by yield of fatty acid, there is used the following migration solvent: petroleum etherdiethylether: 50/50.

Developer: 2-7 dichlorofluorescein or methyl red.

After spraying with a solution of methyl red, the plate iswarmedandexposedwith ammoniavapour.The fatty acids and their amino acid derivatives remain red, while the exposed end of the plate becomes yellow. With the dichlorofluorescein, the plate is exposed to U.V. at 366 nm.

Rf Rf Oleicacid 0.88 Arginineoleate 0.71 Stearic acid 0.66 Argininepalmitate 0.61 Palmitic acid 0.63 Arginine stearate 0.52 Lysine palmitate 0.61 Lysineoleate 0.72 Lysine stearate 0.55 d) Dosages By acidification with hydrochloric acid of a solution of one ofthe derivatives given below, the fatty acid is easily separatedfrom the amino acid. The fatty acid becomes supernatant, whilethe amino acid remains in the water phase in the form of hydrochloride. For the fatty acid, it is sufficientto determine the acidity index to know its identity. Forthatthe amino acid, a test for nitrogen can be effected on the solution, or formaldehyde filtration may be effected.

These fatty acid-amino acid associations ofthe invention can be used alone as emulsifying and emollient agents, or in association with other emui- sifying agents, ionic ornon-ionic according to the final properties desired. Such substances can advan tageously be incorporated in compositions intended to be applied to the skin to remedy a deficiency in lipids as in water. They lead to a particularly oily touch without the inconvenience of a "greasy" character.

The principle other interest of these substances is their antioxidant property. Peroxides have a toxic characterwhich is not negligible, and the free radicals ofwhich are formed (peroxides and hydroperoxides) are not physiologically acceptable. Several authors have shown that it is wrong to attribute to peroxidation and radical oxidation in vivo an important part in the determination ofthe process of aging (HAR MANN d-Free radicaltheoryofaging-J. Geront.

1968/23/476. Prolongation of life, Role ofthefree radical reaction in aging -J. Amer, Geront, Soc.

1969-17-721. HOCHSCHILD R-Lysosomes mem branes and aging Exp. Geront. 1971-6-153. TAPPELA L-Free radical lipid peroxydation damm and its inhibition by vitamin E and selenium - Fed. Proc.

1965-24-73). Ultraviolet radiation leads to theformation of peroxides (SHERVIN E Oxidation and antioxidants in fats and oil processing -J.A.O.C.S.

1978-55-809-VIGNERON M,Autoxidation. Mea suresforprevention 1956-Companyfor Pharmaceutical and Scientific Editions, Paris).These are factors in the aging ofthe skin, showing themselves by a loss of elasticity with the formation of wrinkles.

Protection against peroxidation is of interest, above all in summer because ofthe relatively high intensity of natural ionizing radiation.

Fatty acids like oleic acid are sensitive to autooxidation when not protected, and become antioxidants when they are associated with amino acids.

This is a particularly interesting property according to the invention.

The determination ofthe antioxidant properties of the lipid derivatives of lysine and of arginine has been the subject of numerous treatments of peroxide, after bubbling with air and with oxygen, and principally afterexposureto ultraviolet radiation. Measurements have been carried out on emulsions made with fatty acid-amino acid associations only, as the preparation of cosmetic compositions concerns above all emulsions. Comparative emulsions have been tested which do not contain test substances, but comprise only a polyoxythylenefatty alcohol inthe presence of oil. Multiple oils, as well as oils emulsified with fatty acid-amino acid associations have been tested. The comaprisons have been made with common antiox idant agents: butyl-hydroxytoluene (BHT) or butyl hydroxy anisole (BHA). Oxidation ofthe oils was by bubbling airfor one hourat 50"C, in the presence of 2% and of 4% of lysine oleate, in comparison to an oil not treated but heated and an oil containing 0.1 % of BHT: a) after bubbling; b) after6days; and c) after21 days.

TABLE 1

Content Neutral BHT Oils tested Time of Air Oleate test test after oleate treatment Sesame a) 2% 1.9 1.0 1.5 1.3 b) " 4.9 3.4 4.3 3.6 Carnation a) " 2.4 2.2 1.5 1.4 b) " 4.9 5.7 5.9 5.4 Sunflower a) " 1.4 3.5 1.6 0.4 b) " 3.8 3.5 3.3 3.2 Sweetalmond a) " 5.4 2.1 5.1 1.2 c) " 21.1 6.5 20.6 4.0 Soya a) " 15.0 8.4 17.4 18.1 c) " 29.4 20.4 31.3 27.1 Maize a) " 21.5 22.3 32.0 35.2 c) " 59.4 45.0 61.1 60.2 Peanut a) " 0.8 0.8 0.4 1.1 Olive a) " 2.9 3.8 1.8 1.3 Sweetalmond a) 4% 5.4 0.9 5.1 1.1 Olive a) " 2.9 1.2 1.8 1.3 The figures correspond to the numberofml of sodium hyposu Ifite N/200 per 1 g of oil.

Oxidation of oil by bubbling of oxygen during one hourat50eC. Measurements carried out immediately after treatm ent - Neutra i test without passage of 02.

Oxidation of oils. under U.V. at 50 --A)for 8 hours -B)for 12 hours. Comparison of protection between 2% lysine oleate and 0.1% BHT.

TABLE 2

Oleate Neutral BHT Test Oils Content Oxygen Oleate Test Test Carnation 2% 3.6 2.2 1.9 2.1 Hazelnut " 11.7 1.5 12.4 11.6 Second test " 11.7 1.4 12.3 11.7 Sesame " 1.4 1.2 lA 0.9 Oleicacid " 17.7 10.2 10.6 10.4 Sunflower 14.6 12.6 6.7 13.2 Peanut " 1.5 0.5 1.0 0.8 ; Glycerol Trioleate Sweet almond " 2.7 2.5 0.1 1.7 Sweet almond 4% 2.7 1.1 0.1 1.7 TABLE 3

Tested Oils Period of Test Oleate BHT Exposure Sunflower A 10.5 2.8 5.2 Peanut " 1.7 2.5 4.5 Carnation " 16.0 0.6 11.0 Maize " 9.7 0.7 7.6 Soya " 5.2 0.4 7.5 SweetAlmond" 7.1 1.7 3.8 Sesame " 3.8 0.7 2.2 Glycerol Trioleate Peanut B 4.1 1.4 3.2 Sesame " 10.3 3.2 6.2 Hazelnut " 16.5 2.1 5.8 SweetAlmond " 7.1 4.2 3.8 2% oleate SweetAlmond " " 7.1 1.8 3.8 4% oleate Oxidation of oils under U.V. for 10 hours Comparison of protection between 4% lysine stearate and 0.1 BHT.

TABLE 4

Oils tested Test Stearate BHT Sunflower 12.5 3.0 8.0 Carnation 13.2 0.5 8.5 Maize 10.7 0.6 3.5 Comparison of the antioxidant properties between 0.1% BHT, lysine oleate, and 5% lysine stearate, in the form of emulsion. Test: 5% test oil, 5% polyoxyethylene fatty acid 0.1% BHTintestoil-5% oleateand stearate, 5% test oil.

TABLE 5

Oils tested Test BHT Oleate Stearate Carnation 9.5 2.3 3.4 1.4 Sesame 22.5 3.7 4.4 1.4 SweetAlmond 12.0 2.0 2.1 0.6 Soya 11.4 4.2 4.6 2.3 Comparison of the antioxidant properties of different derivatives of lysine and ofarginine with BHT in different emulsified oils.

Test: polyoxyethylene alcohol 5% -5% oil -90% water BHT: 0.1 % in test emulsion Amino acid derivatives: 5% - 5% oil - 90% water Exposure U.V.:12 hours at 50 .

TABLE 6

Amino acid Oils Tested BHT Test Derivatives Lysine oleate Carnation 2.2 9.5 3.4 Sesame 3.7 22.1 4.4 Olive 2.2 8.4 2.0 SweetAlmond 2.0 12.0 2.1 Soya 4.0 11.5 4.6 Sunflower 2.8 36.0 1.5 Lysine Stearate Sesame 2.0 7.5 1.4 Carnation 1.4 2.2 1.4 Soya 3.0 15.5 2.3 Sweet Almond 1.5 7.6 0.7 Sunflower 2.8 36.0 4.1 Olive 2.2 8.4 1.5 Lysine Palmitate Sweet Almond 2.2 4.5 2.2 Sunflower 1.5 8.1 1.6 Arginine Oleate Sweet Almond 2.3 4.5 2.4 Sunflower 1.5 8.1 1.6 Arginine Palmitate Sweet Almond 2.3 4.5 2.1 Sunflower 1.5 - 8.1 1.3 Arginine Stereate Sweet Almond 2.3 4.7 1.8 Sunflower 1.5 9 1.2 Comparison ofthe antioxidant properties of different associations, fattyacid-amino acid with BHT, accordingto their introduction into the oily phase or the aqueous phase of an emulsion. Exposure to U.V.

18 hours at 22 . Emulsion, according toTable 6aqueous phase: (1)--oily phase (2). BHT is introduced only into the oily phase.

TABLE 7

Test oils in emulsion Amino acid derivatives Olive Sunflower Sweet Almond BHT 5 3.1 4 Test: fatty alcohol 13.5 13.1 10.2 +oil Lysine oleate (1) 5.7 4.7 2.0 (2) 3.2 3.4 1.7 Lysine stearate(1) 4.1 4.6 7.8 (2) 1.7 1.2 3.0 Lysinepalmitate(1) 1.6 4.4 4.8 (2) 1 0.8 3.2 Lysine myristate (1) 2.8 5.0 4.7 1.7 3.7 2.2 Arginineoleate(1) 4.4 5.2 5.5 (2) 3.5 2.6 3.2 Lysine caprylate (1) 4.5 6.0 5.8 2.7 4.4 3.8 The fatty acid-amino acid associations cannot be put in parallel with classical chemical antioxidants, which are used in a weak dose, such as BHT and BHA for example. These associations are not properly called antioxidants; they are principally emulsifying agents, with interesting emollient properties, char acterised by antioxidant properties, which avoid having to use chemical antioxidants.

In the light of numerous determinations of indices of peroxide, shown in the Tables, the following results are put in evidence: 1-By bubbling air or oxygen for one hourat 50 , lysine oleate is observed to lead to an antioxidant protection near or attimes superiorto that of BHT, according to the nature ofthe test oils (Tables 1 and 2).

2-By exposure to ultraviolet radiation during a period between 8 and eighteen hours, both the oleate and the stearate of lysine are effective antioxidants (Tables 3 and 4).

3-In the case of emulsions comprising different oils, exposed to U.V. during 18 hours, lysine stearate leads to results superiorto those obtained with the oleate (Table 5).

4-All the saturated fatty acid or mono-unsaturated fatty acid associations with lysine or arginine are endowed with antiperoxidant properties.

5-The antioxidant protection is higher when the amino acid derivatives are introduced into the oily phase of an emulsion, than in the aqueous phase.

By reason ofthe important of protection against ultraviolet radiation, it will be particularly advantageous to use this kind of substance, of strictly biological character the same as fatty acids and as freeorcombined lysineorarginine,which are normallyfound in tissue, and in particular at the level of the corneal layer, which allows themselves to opposethe disturbing action of solar radiation, relativetothe activity of peroxides.

Use of associations of faffy acids--lysine orarginine Given on the one hand, as has been stated, that there is interest in introducing these associations into fats to protect against auto-oxidation, but on the other hand the fact of high melting points, it is difficult to obtain a homogeneous and limpid mixture, without causing modification ofthe colour ofthe fat, it is preferableto solubilize them in polya Icohols like propyleneglycol or glycerol for example and to introduce this mixture into the fat. Thus there is obtained a limpid mass which, on addition of water, leads to the desired emulsion. Emulsions are then obtained of which the pH is about 7 and which are characterised by a remarkable emollient action.

Byway of non-limiting examples, there are cited as emulsion compositions: 1) Lysineoleate 5 Propyleneglycol 10 Cetyl .................................... alcohol 5 Stearine ...... ... ... 10 Water 100 Preservative qs 2) Lysinestearate 5 5 Propyleneglycol ............................... 10 Stearine 10 Polyoxyethylene fatty alcohol 5 Sweetalmondoil 5 Water 100 Preservative qs 3) Arginineoleate ................................. 5 Glycerol ........................................ 10 Sunflower 10 Polyoxyethylenecetylalcohol 10 Stearine .......... ............. ............ 8 Lipoaminoacid 3 Waterqs 100 Preservative qs One can use, equally, advantageously these associations in hygiene products, such as soaps, shampoos by reason of their emollient and very slippery properties. It will be the same for the preparation of permanent waving solutions in which this kind of association will permit an increase in activity of reducing components, by virtue oftheirtensioactivity, on the one hand and on the other hand by reason ofthe biological nature ofthis kind of substance.

As non-limiting examples, there is mentioned: 1) Toilet soap Cocoa-pa Imistic soap 95 Lysineoleate 5 Coconut oil ................................ soap 95 Lysinestearate 5 2) Shampoos Sodium laurylsulphate 30 Lysineoleate 5 Water ........................................ 65 Etherlaurylsulphate 20 Sodium laurylcollagenate ................. 10 Lysineoleate 5 Water ........................................ 65 3) Permanent waving lotion Ammoniumthiolactate 15 15 Lysineoleate 2 Ammonia ........................................ 70 Water ............... ....... . 73

Claims

1. Compositionsforcosmetic, dermatological andlor alimentary use which comprise salts resulting from the association of fatty acids with Iysine or arginine, corresponding to the following general formula:

in which R represents a hydrocarbon radical straight or branched, saturated or mono-unsaturated comprising from 4to 30 carbon atoms; and R' represents -CH2-for lysine ora guanidyi residue -C-NH-forarginine.

# NH

2. Cosmeticand/ordermatological compositions according to claim 1 in combination with other emulsifiers.

3. Cosmetic, dermatological and/or alimentary compositions according to claim 1 substantially as herein described.

4. A process of producing a composition according to claim 1 which comprises neutralization ofthe fatty acid with the basic amino acid.

5. A process according to claim 4 which is performed in a hydroalcoholic solution at a pH between

6.5 and

7.5.