WO1987005503A1

WO1987005503A1 - Cosmetic compositions and process for preparing the same

Info

Publication number: WO1987005503A1
Application number: PCT/HU1987/000012
Authority: WO
Inventors: Károly FÁBIÁN; Katalin Michnay; Erzsébet BENKO^"; István DÖMÖTÖR; Péter MAJOROS
Original assignee: Karoly Fabian; Katalin Michnay; Benkoe Erzsebet; Doemoetoer Istvan; Majoros Peter
Priority date: 1986-03-11
Filing date: 1987-03-11
Publication date: 1987-09-24
Also published as: JPH01502428A; FI884143A; EP0296173A1; FI884143A0

Abstract

The present invention provides a process for preparing biologically active ligands from plant material containing histones. Another object of the invention is the preparation of biologically active ion-ligand complexes by the reaction of plant histone hydrolisates and metal salts. Another object of the present invention is a cosmetic composition, characterized by consisting of at least two components wherein each of the components contains at least one metal ion or metal ion complex, at least one of the components contains the metal in the lowest oxidation degree thereof, the said metal ions or metal ion complexes of the individual components forming a galvanic chain and being non-reactive with each other.

Description

COSMETIC COMPOSITIONS AND PROCESS FOR PREPARING THE SAME

Technical field

The present invention relates to a process for preparing biologieally active ligancs and metal ion-ligand complexes as well as to cosmetic preparations comprising metal ions or metal ion complexes.

Background art

Cosmetic compositions of different types have always been used during history. These serve mainly for retaining and enhancing the elasticity and freshness of ageing skin. The first cosmetics were vegetable oils which later were transformed to emulsions

/creams/ by adding emulsifiers and water thereto, thus enhancing the effect of natural oils and fats, likeoliveoil, peanut oil, seal oil, cod-liver oil, etc.

Nowadays, a large number of oils, fats and derivatives thereof are used in the cosmetic industry. Most of the compositions also contain so-called "active agents" which are added to the aqueous or the oil phase. These active ingredients are added in order to keep the ageing skin fresh intensively. These active ingredients include e. g. vitamines, such as A, B, D, E, K, F, panthotenic acid, and the like, provitamines, such as beta-carotine, Riper-complex, proteins, vegetable extracts, extract of sea living organisms, including algae, etc. For therapeutic purposes medicines may also be mixed to the creams, i. e. some medicines are also present in the form of cream. This form of medicine is especially desired if it should be administered intradermally. These creams may contain antiphlogistica, such as

Chlorocid-H ^R, Tetran^R, etc., antiall ergistic agents, such as

Prednisolon-J^R, Locoid ^R, Kydrocortison ^R, Nicoflex ^R, antirheumatic drugs, such as Bayolin ^R, Phogosam ^R, Arthrofluor ^R, etc. In case of creams containing the medicines, side effects can also appear, most of which being non-desired. These side effects are especially frequent in case of an ti rheumatic compositions, see

Knoll, Jόzsef: Gyόgyszertan, Schroder, Rufer and Schmie chen:

Pharmazeutische Chemie. It is well known that the function of nervous system in high class organism is characterized by electric phenomena, the so-called "action potentials". When stimulating the neuron membrane, e. g. by light, sound, acupuncture, laser puncture, etc., the inflow and outflow of Na⁺ and K⁺ ions through the membrane will substantially change. As a result of complicated processes stimulus conduction cakes place, wherein chemical substances, such as acetyl choline, adrenaline, noradrenaline dopamine gamma-amino butyric acid, etc. play also a substantial role. According to certain theories, stimulus may also be transmitted from one cell to the other without chemical transmitters. These processes, however, are very complicated and most of them have not been clarified.

The role of metal ions in human organism is a well discovered area. E. g. the role of the above Na⁺ , K⁺, Ca²⁺ and Mg²⁺ ions in the stimulus conduction is well known but also many metal ions are of additional vital importance.

The enzymes are special proteins of the human organism and act as catalyst. For the proper action thereof metal ions are also essential. Such enzymes include e. g. the metallo-enzymes, such as carbonic acid anhydrace /Zn/, methylmalonyl-CoA-mutase /Co/, xanthine oxidase /Mo/, the metallic ion activated enzymes, such as arginase /Mn/, acylase /Zn/, etc. Certain metals having more valence state play an important role in the redox reactions /Fe, Cu, Mo, Co, V, Cr, Sn/, see e. g. Friedem M.: Protein-Metall Interaction, "Advances in Experimental Medicine and Biology " Vol. 48, Plenum Press, New York, 1974.

The mechanism of uptake of metal»ions is as follows: in the first step either the metal ion is bound to the surface or a complex forming ligandum /L/ reacts with the metal ion:

Subsequently, exchange of ligandum might take place, wherein the metal ion penetrates into the biological system, e. g. by permeating the cell membrane and/or the oxidation degree of the metal might also be changed and finally reaches the active centre of the protein in the form of ML₁ or ML₂, see Frusta da Siliva, Williams, R. J. P.: The Uptake of Elements by Biological Systems, Structure and Bonding, 29, 67/1977. Generally metals are more active in their reduced state, such as Fe²⁺, Mo³⁺, Cr²⁺, Vc₂ ⁺ , etc.

From the foregoing it can be concluded that metal ions are of vital importance for the organism. The ability of organism to uptak the same depends to agreat extent on the surrounding, as well as on the internal conditions. The most important characteristics in this respect are the pH, ion strength, redox potential, the chemical environment and the like.

Disclosure of Invention

The present invention provides a process for preparing ciollogically active ligands from plant material containing histones.

Another object of the invention is the preparation of iologically acvive ion-ligani complexes by the reaction of plant histone hydrolisates and metal salts.

Another object of the present invention is a cosmetic composition, characterized by consisting of at least two components wherein each of the components contains at least one metal ion or metal ion complex, at least one of the components contains the metal in the lowest oxidation degree thereof, the said metal ions or metal ion complexes of the individual components forming a galvanic chain and being non-reactive with each other.

The present invention, provides a process for introducing metel ions into the organism through the skin while providing an optimal pH,ion strength, redox potential and chemical environment /ligandum/.

The novel body care composition of the present invention not only performs the hydratization and thus refreshing and softening the skin, but also regenerates the complete organism due to the electric and bioactive effect thereof. Thus, refreshment of the entire body will be obtained and the pains caused by certain ach ing body parts will be reduced and eliminated, respectively.

It has been found that the ligands bound to metal ions used according to the present invention can preferably be handled at a pH value of 5 to 6 and the preparation of creams and body care compositions can be accomplished easily by using the same. An ion strength of 0,3 may easily be maintained when preparing the compositions with tap water of .sufficient purity. The essence of the invention is the formation of the redox system. According to the present invention the redox system is established by dividing the metal ions of varying valence so that they form a galvanic element by acting as redox electrodes. Examples of the molecular galvanic chain to be used according to the invention are as follows:

1/ Galvanic chain without ligand: Au //SnCl₂ + SnCl₄/FeCl₃ + FeCl₂ // Au 2/ Galvanic chain with ligand:

Au // Sn/L_χ/Cl₂ + Sn/L_y/Cl₄/Fe/L_v/Cl₃ + Fe/L_z/Cl₂//Au

Obviously, the complete galvanic chain may not be present within the same cream, as the equilibrium would set in in a very short period due to discharge. According to the invention one of the electrodes /in the present example Au//SnCl₂ + SnCl₄/ should be present in a first cream, while the other electrode /Au//FeCl₃ + FeCl₂/ should be incorporated in an other cream. During makeup the skin is treated with one of the creams and after a few minutes with the other one. Thus, the redox reaction which by all probability also includes the exchange of ligands, takes place in the lower layers of skin and provides a preferred curative effect.

The electrodes of the aforesaid galvanic chains are separated from each other by incorporating the same into divided units /cream A, B/. More than two galvanic chain members can also be prepared of course, in this case more than two divided units should be prepared /A, B, C, etc./. An example of a three-components composition is the following:

Au//SnCl₂ + SnCl₄/FeCl₃ + FeCl₂//Au//MnCl₂ + MnCl₃//Au "A" "B" "C" The creams obtained according to example 5 were tested on patients suffering from different disorders, such as spinal complaints, spinal sclerosis, tennis-cramp, facial neuritis, Mastered burns, nodding muscle catalepsy, shoulder and upper arm arthritis. By treating the said body parts twice daily, pains of the 55 patients treated disappeared in every case.

The ligands used according to the present invention can be prepared by hydrolyzing suitable histones. The curative effect of certain vegetable histones, such as beets, see J. R. Hafferl, W. Sci. Pharm.27, 230 /1959/, mistletoe, see Belgian Patent No. 646095 and the like had already been known. By separating and subsequently hydrolizing the extracts polipeptyde chains of good complex forming ability may be obtained. During a preferred embodiment of the process according to the invention the pulp of the plant is acidified to pH = 1,0 by a strong mineral acid and then pressed. The liquor thus obtained is centrifuged and dried. The crude extract thus obtained is purified by chromatography. For this purpose cation exchange resins, such as IRC-50 ^R, Dowex 50W ^R, DEAE cellulose and the like or adsorption resins, such as Amberlite XAD-2 ^R,

DiaionHP-20^R and the like may be used. The purified products are transformed to acid addition salt thereof formed by organic acids and then hydrolized at 120 to 150 °C for 1 to 10 hours.

The corresponding metal ions are added to the hydrolysate thus obtained and under ambient conditions metal ion-ligand complexes are formed.

The details of the invention are illustrated by the following examples without limiting anyway the scope of protection thereon.

Best Mode of Carrying out the Invention

Example 1

Preparation of histone-based complex-forming ligands

1 kg of red beet including leaves was pulped and then acidifie to pH = 1,0 with 6 N hydrochloric acid. After standing for 2-1 hours the pulp was pressed through a grape-squeezer. The mass was resuspended in 0,25 liter of water and squeezed again. The press liquor of cca. 0,9 liter thus obtained was made alkaline to pH = 11,5 with 4 N sodium hydroxide. The mixture was allowed to stand in refrigerator over night and then centrifuged. The wet material thus obtained was dried at a temperature of max. 60 to 70°C. Thus, 21 g of crude material was obtained which was dissolved in pH = 6 phosphate buffer and applied on a 5 × 80 cm glass column packed with IRC-50 ^R /carboxyl function/ cation exchanger. The column was eluted with pH = 8 phosphate buffer. The fractions containing the histones were combined, evaporated in vacuo and dried over phosphorous pentoxide in vacuo . Thus , 5 g of purified protein /histone / was obtained to which 2,5 g of citric acid was added and hydroiized at 125 ºC for one hour . The hydrolysis product was evaporated in vacuo and dried over phosphorous pentoxide in vacuo , thus obtaining 7 ,4 g product.

Example 2

Preparation of histone-based complex forming ligands

The process according to example 1 was followed by using mistletoe /whole plant/ instead of red beet.

Example 3

Preparation of histone-based complex forming ligands

The proce ss de scribed in example 1 was followed with the difference that the crude product obtained was purified on an adsorption re sin instead of the cation exchanger. To 20 g of crude product 10 g of fumaric acid we re added and dis solved in 100 ml of water and subsequently 30 ml of acetone were added to the solution. The mixture was applied on 5 x 80 cm chromatography column packed with XAD -2 ^R re sin pre -treated with a mixture of water and acetone /40:50/. The column was eluted with water-acetone mixtures containing descending amount of acetone . The protein-containing fractions were combined and evaporated in vacuo to 1 /20 of the original volume . The concentrate was hydroiized at 110 °C for 5 hours and dried in vacuo , thus obtaining 14, 5 g product .

Example 4 Preparation of body care creams without complex forming ligand

Component "A" /containing metal ions of high oxidation degree/ :

To 800 ml of water 1 g of sodium potassium tartrate was added and 1,0 mg of NiSO₄. 7H₂O_, 0,0025 mg of NH₄VO₃, 2,0 mg of CuSO₄.5H₂O, 10,0 mg of ZnSO₄. 7H₂O, 1,0 mg of /NH₄/₆Mo₇O₂₄ . 4H₂O, 1,5 mg of [Co/NH₃/6]Cl₃, 20,0 mg of Fe₂/SO₄/₃, 8,0 mg of MgSO₄. 7H₂O, 1,0 mg of MnSO₄. H₂O and 2,5 mg of H₃BO₃ were dissolved therein. The pH of the solution was adjusted to 5,5 with sodium hydrogen carbonate and mixed at 70 °C with the fatty phase consisting of the following ingredients: 90 g of white vaseline, 50 g of cetyl alcohol, 35 g of white oil and and 25 g of

TWEEN-60 ^R. The emulsion was cooled to ambient temperature while stirring.

Component "B" /containing metal ions of low oxidation degree/:

50 mg of sodium potassium tartrate and subsequently 33,5 mg of SnCl₂. 4H₂O and 8,5 mg of gold chloride were dissolved in 800 ml of distilled water. The pH of the solution was adjusted to

5,5 by the addition of sodium hydrogen carbonate and mixed at 70 ºC with die fatty phase consisting of the following ingredients: 90 g of white vaseline, 50 g of cetyl alcohol, 35 g of white oil and 25 g of TWEEN-60 ^R. The emulsion was cooled to ambient temperature while stirring.

Component "C" /containing metal ions of low oxidation degree, forms redox system with components "A" and "B"/:

In 800 ml of distilled water 50 mg of sodium potassium tartrate was dissolved and 0,0025 mg of CrSO₄. 7H₂O was added to the solution. The pH of the solution was adjusted to 5,5 by the addition of sodium hydrogen carbonate and mixed at 70 °C with the fatty phase consisting of the following ingredients: 90 g of white vaseline, 50 g of cetyl alcohol, 35 g of white oil and 25 g of TWEEN-60^R The emulsion was cooled to ambient temperature while stirring.

Example 5 Body care composition containing metal ion-ligand complex

Component "A" /metal ions of high oxidation degree/:

10 g of hydrolisate according to example 1 were dissolved in 700 ml of tap water and then 1,0 mg of NiSO₄. 7H₂O, 0,0025 mg of NH₄VO₃, 2,0mg of CuSO₄. 5H₂O, 10,0 mg of ZnSO₄. 7H₂O, 1,0 mg of /NH₄/₆Mo₇O₂₄. 4H₂O, 1,5 mg of [Co/NH₃/₆]Cl₃, 20,0 mg of Fe₂/SO₄/₃, 8,0 mg MgSO₄. 7H₂O, 1,0 mg of MnSO₄. H₂O and 2,5 mg of H₃BO₃ were added thereto. The pH of the solution thus obtained was adjusted to 5,5 and then mixed at 70 ºC with the fatty phase consisting of the following ingredients: 70 g of stearyl-monogiyceride, 70 g of white vaseline, 82 g of cetyl alcohol, 30 g of maize oil, 30 g of TWEEN-60 ^R and 0,2 g of butyl-hydroxy toluene. The emulsion was cooled to ambient temperature while stirring. Component ''B" /metal ions of low oxidation degree/:

10 g of hydrolisate according to example 1 were dissolved in 700 ml of tap water and 33,5 mg of SnCl₂. 4H₂O and 8,5 mg of gold chloride were added. The pH of the solution thus obtained was adjusted to 5,5 and then mixed at 70°C with the fatty phase consisting of the following ingredients: 70 g of stearyl-mono glyceride, 70 g of white vaseline, 82 g of cetyl alcohol, 30 g of maize oil, 30 g

TWEEN-60^R and 0,2 g of butyl-hydroxy toluene. The emulsion was cooled to ambient temperature while stirring.

Example 6 Body care jelly containing metal ion-ligand complex

Component "A" /metal ions of high oxidation degree/:

10 g of hydrolisate according to example 1 was dissolved in 300 ml of tap water, the metal salts specified at component "A" of example 5 were added and the pH of the solution was adjusted to 5,5 by the addition of sodium hydrogen carbonate. 10 g of

Carbopol-940 ^R were swelled in 700 ml of tap water, the two solutions were combined and the jelly was prepared by the addition of 13 g of triethanol amine.

Component "B " /metal ions of low oxidation degree / :

10 g of hydrolysate according to example 1 were dissoived in 300 ml of tap water and 33, 5 mg of SnCl₂ . 4H₂O and 8, 5 mg of gold chloride were added and the pH of the solution was adjusted to 5,5 by the addition of sodium hydrogen carbonate . 10 g of

Carbopol-940 ^R were swelled in 700 ml of tap water, the two solution were combined and the jelly was prepared by the addition of 13 g of triethanol amine .

Claims

1. Process for preparing biologically active ligands , c h a r a ct e ri z e d in that plants containing histones are pulped, the pulp is treated with an aqueous strong mineral acid of pH 1 to 3 and pressed, the liquid phase is adjusted to a pH of at least 12 and the protein-rich precipitate is separated, purified on a cation exchange or adsorption resin and the purified product is transformed to the acid addition salt thereof with an organic acid in a 1 to 30 % by weight aqueous solution and hydroiized at 120 to 150 °C for 1 to 10 hours.

2. The process according to claim 1, ch a r a ct e ri ze d in that as plant material beet species, such as red beet or mistletoe are used.

3. The process according to any of claims 1 and 2, c h ar a c t e rized in that as organic acid acetic acid, citric acid, tartaric acid or fumaric acid are used.

4. Process for preparing biologically active meral ion-ligand complexes , c h a r a c t e r i z e d in that plant histone hydrolyzate is reacted with metal salts at ambient temperature at a metal ion concentration of max. 10^-1 mol/liter.

5. Cosmetic composition, ch a rac t e r i z ed in that it consists of at least two components, wherein each of the components contains at least one metal ion or metal ion complex, at least one of the components contains the metal in the lowest oxidation degree there the said metal ions or metal ion complexes of the individual components forming a galvanic chain and being non-reactive with each other.

6. The composition according to claim 5, c h a r a c te ri z¬e d in that the metal ion is in the form of a complex formed with a simple complex forming molecule known per se.

7. The composition according to claim 5, c ha r ac t e ri z ed in that the metal ion is in the form of a complex formed with a plant histone-hydrolisate ligand.

8. The composition according to any of claims 5 to 7, c har a ct e r i z e d by containing in the component containing the last member of the redox chain molecularily divided Au as redox electrode.