WO2004024115A1

WO2004024115A1 - Leguminous plant pigments used for revitalizing human skin

Info

Publication number: WO2004024115A1
Application number: PCT/DE2003/002766
Authority: WO
Inventors: Paul-Alexander Hallmann
Original assignee: Paul-Alexander Hallmann
Priority date: 2002-09-05
Filing date: 2003-08-20
Publication date: 2004-03-25
Also published as: DE10393714D2; DE10240984B4; DE10240984A1; AU2003266172A1

Abstract

The invention relates to the use of hemoproteins made from leguminous rhizome extracts. Leguminous hemoproteins or leghemoglobins that are external agents for cosmetic and medicinal applications can normalize and improve states of hypoxia of the skin in a pH-stabilized vesicular liposome preparation (lotion/creme) or in a dispersed form as W/O microemulsions or O/W microemulsions by increasing the supply of oxygen to the epidermis. In addition, the different conveying systems of the oxygen carrier (vesicle, liposome, microemulsion), which comprise variable lipid matrices, allow the cosmetic and medicinal target areas to be better targeted.

Description

PLANT PIGMENTS FROM LEGUMINOS FOR REVITALIZATION OF HUMAN SKIN Description

The invention relates to preparations: and preparations with plant pigments from legumes. The products, which are primarily developed for cosmetic but also for medical applications, are characterized not only by skin-coloring properties but also by remarkable reversible oxygen binding properties. Stocks.

Due to the spectroscopic and biochemical properties, which correspond relatively well to those of hemoglobin and myoglobin in mammals, H. KUBO (1), who in 1939 isolated these natural substances belonging to the class of hemoproteins for the first time, called "leghemoglobins".

The idea of using oxygen carriers of animal origin (porcine hemoglobin) for cosmetic applications when the skin is deficient in oxygen was first introduced by W.K.R. BARNIKOL (2) and his working group have been developed and described.

Vegetable oxygen donors such as leghemoglobins, which are comparable to mammalian myoglobins in terms of their oxygen binding properties, represent a connecting group to mammalian hemoglobins that is even more selective for the reversibility of oxygen release (3).

The use of this vegetable oxygen carrier as an external ingredient in the cosmetic and medical field can be traced back to the following considerations:

In the microscopic picture, the epidermis appears as a cell cluster made of keratinocytes, the majority of which are present, with the deeply vital (stratum basale) and dead cell layers that die and close to the visible surface of the skin, the stratum corneum disjunctum (4).

The entire epidermis is supplied with oxygen to about 50% via the Dennis arterial capillary system, the remaining oxygen requirement is covered from the outside by the atmospheric oxygen diffusing into the cell clusters (5).

Is the amount of oxygen required for "cell respiration" internal due to reduced blood flow to the skin - due to narrowing of the 'arteries / arteries Oil and / or accumulation backlog in the capillary network and / or in the veins - or externally reduced by oxygen diffusion inhibition in the stratum corneum conjunctum due to physiologically / morphologically changed and deposited keratinocytes, so medium to deep hypoxic areas are formed.

The consequence of this painting function is a more or less pronounced structural and functional change in the dermis and epidermis, which is first visible on the surface of the skin, e.g. in the appearance of a thin or lackluster and rough epidermis, turgorless, with more or less pronounced wrinkles and fine lines, up to the clinical manifestation of arterial occlusive diseases with tissue breakdown, e.g. Venous leg ulcer or compression anemia (6).

The oxygen deficiency of this problem skin can be treated internally with vasodilating drugs via the bloodstream, as well as externally, which is associated with not inconsiderable side effects (5).

The problem of external therapy treating hypoxic skin areas with oxygen-containing or oxygen-releasing preparations or gassing the skin with pure oxygen consists in the fact that high concentrations of free oxygen and oxygen radicals occur locally in the tissue, which lead to the oxidative degradation of the cell wall components and trigger lytic processes in the cell structure.

A successful treatment of these skin problems with oxygen can only consist in establishing natural conditions with regard to bioavailability in the cell tissue, i.e. Oxygen must be available in small quantities, but permanently for consumption.

These conditions are influenced by an oxygen carrier adapted to the biological requirements, e.g. the hemoglobin is sufficiently fulfilled, which due to its characteristic binding affinity for oxygen only releases the amounts of oxygen required for cell metabolism.

In view of the fact that the deeper lying epidermal cell assemblies (stratum granulosunV-spinosum) can cover part of their oxygen requirements through the oxygen in the air, i.e. externally via diffusion, the idea is obvious, by initiating a relieved one and directed oxygen diffusion ad externa, i.e. via the tissue itself, to counteract the cellular oxygen deficit.

In order to initiate this sensitive balance of bound, readily available and free oxygen, an incorporation of an oxygen source into the S.corneum was considered, the biological reversibility of the oxygen uptake corresponding to the requirements of the cell assembly.

The object of the present invention is to preserve and assemble a plant oxygen carrier obtained by gentle isolation and in its biological activity in such a way that after application to and into the epidermis it also retains its biological activity of reversible oxygen absorption and reaches a certain depth of penetration. with the aim of creating an external oxygen pool for the upper and lower skin cell groups.

Furthermore, the preparation components, which mainly serve as a transport medium for the oxygen donor, should have good skin care properties in order to protect the hemoprotein in a stabilizing manner.

The objective of the cosmetic area is the development of preparations for external application, which eliminate skin dysfunctions and improve skin breathing, heal light and heat damage in a gentle and natural way and use preventively, counteract the beginning of relaxation and wrinkling of the skin.

The field of application of the preparations in the medical sector includes the dermatological problem area of arterial occlusive diseases with tissue decay, e.g. Ulcus cruris venosum or compression anemia etc. (see textbooks of dermatology and veneralogy).

Experimental part

Isolation and conservation of leghemoglobins

Leg hemoglobin, was obtained from aqueous macerates of fresh root nodules of the respective legume genus in different amounts (1) and ligated with carbon monoxide to stabilize the insulation (7).

The accompanying proteins of leghemoglobin are separated by fractional precipitation with ammonium sulfate.

Removal of the accompanying salts of the leghemoglobin preparation and transfer to the appropriate buffer medium while adjusting the pH to 7.5 are carried out according to the methods usual in experimental biochemistry (volume exclusion chromatography, dialysis etc.) (3).

Dissolved in the buffer medium and CO-ligated, the purified CO leghemoglobin remains functional for approx. 1 to 1.5 years at a storage temperature between 0.0 and 4.0 degrees Celsius.

Preparation of microscopic slides

The application forms (cream, lotio, etc.) of the oxygen carrier leghemoglobin described here can be produced using generally known standard methods for producing cosmetic products and liposomal dispersions:

- a) Cream preparations (8)

- b) Lotio preparations (8)

- c) Vesicular-liposomal preparations with a defined particle size (9, 10)

- d) W / O microemulsions (11, 12)

- e) 0 / W micro / nanoemulsions (9)

application Forms

The chemical composition of the individual active substance carriers (lecithins / oils) is matched to the stability of oxy-leghemoglobin, which is just before released from the carbonylated form or used directly in the carbonated form:

If treatment forms a), b) or d) are used, the depot-CO-leghemoglobin is activated with pure oxygen in the first step. The oxy-leghemoglobin solution is then dispersed or dissolved in the prefabricated carrier preparation and this is then applied to the skin.

If one chooses the preparation form c) or e), the oxygen carrier is activated by means of oxygen during or after application to the skin.

literature

1.) Kubo H., Acta Phytochim., 11, 195 (1939)

2.) Barnikol W.K.R., DE 100 34 970 AI

3.) Lehniger A.L., Biochemie, Verlag Chemie (1979)

4.) Jung E.G., (publisher), dermatology, Hippokrates Verlag Stuttgart (4th ed.)

5.) Großmann et al, Adv. Physiol. Be. 25 (1981)

6.) Braun-Falco O., Dermatology and Veneralogy, Springer Verlag (1997)

7.) Keilin P., Nature, Lond., 155 (1945), 227

8.) Grubenmann A., formulation technology, Willey-Verlag Chemie D-Wh.

9.) Ostro M.J., (Hersg.), Liposomes, Marcel Dekker, New York (1983)

10.) Barenholtz et al., FEBS Lett. 99, (1979), 210

11.) L.Engström, J. Dispersion Sei. Technol. 11: 479 (1990)

12.) L. Moberger et al., J. Dispersion Sci. Technol. 8: 207 (1985)

Claims

claims

1.) Externally applicable preparation containing leg hemoglobins, characterized in that leg hemoglobins are present in a disperse distribution in the form of lipoid emulsions (lotions or creams).

2.) Externally applicable preparation containing leg hemoglobins, characterized in that leg hemoglobins are present in a vesicular-liposomal preparation.

3.) Externally applicable preparation containing leg hemoglobins, characterized in that leg hemoglobins are present in W / O micro or "- nano" emulsions.

4.) Externally applicable preparation containing leg hemoglobins, characterized in that leg hemoglobins are present in O / W micro or "nano" emulsions.

5.) Externally applicable preparation according to claim 1 to 4, characterized in that leg hemoglobins are isolated and selected from the legume genus:

a) Albizza, or b) Amorpha, or c) Arachis, or d) Astragalus, or e) Canavalia, or f) Cassia, or g) Crotalaria, or h) Desmodium, or i) Glycine, or j) Indigofera, or k) Kummerovia, or 1) Lathyrus, or m) Lespedeza, or n) Lotus, or o) Lupinus, or p) Medicago, or q) Phaseolus, or r) Pisum, or s) Pueraria, or t) Sophora, or u) Trifolium, or v) Vicia, or w) Vigna, or x) Wistaria, or y) Leghemoglobin mixtures from the genera mentioned under a) to x).

6.) Externally applicable preparation according to claim 1 to 5, characterized in that leg hemoglobins are ligated to protect against oxidation and denaturation with carbon monoxide (CO).

7.) Externally applicable preparation according to claim 1 to 6, characterized in that leg hemoglobins in non-buffered or buffered solution, preferably phosphate buffer of concentration 1 to 145 mM, in the pH range 4.0 to 9.5, preferably 7.5 to 8.0, is present.

8.) Externally applicable preparation according to claim 1 to 7, characterized in that Leg hemoglobins is present in a concentration between 0.05% to 20.0%.

9.) Externally applicable preparation according to claim 1 to 8, characterized in that phospholipid cholesterol components are present in a concentration between 0.3% to 30.0%.

10.) Externally applicable preparation according spoke 1 to 9, characterized in that emulsifiers with micelle-forming properties (up to 95%), preservatives (up to 1%), and fragrances (up to 0.5%>) are used as additives.

11.) Externally applicable preparation according to claim 1 to 10, characterized in that bidistilled water is used in a concentration of up to 95%.

12.) Externally applicable preparation according to claim 1 to 11, characterized in that mineral or vegetable oils are used in a concentration of up to 95%.

13.) Use of an externally applicable preparation according to claim 1 to 12, characterized in that oxygen deficiency states of the skin are treated.

14.) Use according to claim 12, characterized in that the

Lack of oxygen is degenerative, radiation or thermal.

15.) Use of an externally applicable preparation according spoke 1 to 12, characterized in that oxygen deficiency states of the skin and aging skin are treated preventively and care.

16.) Use of an externally applicable preparation according to spoke 1 to 12 as a cosmetic, characterized in that the skin-care and revitalizing properties are used.

17.) Use of an externally applicable preparation according to spoke 1 to 12 as a cosmetic, characterized in that the coloring properties are used.