Preparation for topical use

The invention relates to a preparation for topical use, having light protection properties and in a special application form. In the known light protection agents containing the naturally occurring active compound melanin, the problem is inadequate transport of the melanin to its site of action. According to the invention, this problem is solved by a preparation for topical use which is characterised in that it contains melanin, dissolved or dispersed in one or more fluorocarbons, which are present as asymmetric lamellar phospholipid aggregates in an aqueous system together with a phospholipid, with a particle size of the aggregates in the range from 200 to 3000 nm.

The invention relates to a cosmetic or dermatological composition having 
light protection properties in a special application form, in which 
fluorocarbon-containing asymmetric lamellar phospholipid aggregates 
function as carriers of melanin. 
It is known that short-wave UV light (UV/A, UV/B, UV/C, wavelength ranges 
from 400 to 200 nm) can have a damaging effect on the skin and is a 
significant factor for premature skin aging. In extreme form, the action 
can consist in a cytogenetic change in individual skin cells and lead to 
the formation of skin carcinomas (melanomas). These hazards have 
continuously increased due to environmentally related factors (ozone hole) 
with an increased UV burden. In order to overcome this fact, it is 
customary, by means of special cosmetics and dermatological agents, to 
protect the exposed skin tissue by the use of special UV light protection 
filters. The active compound of these compositions is based on the 
following principles: 
1. Absorption of UV light by the use of UV-active organic compounds 
2. Scattering of UV light by finely dispersed titanium dioxide or other 
micropigments 
The efficacy of these systems, which can be detected simply by recording 
their UV absorption maxima in the wavelength range 250-400 nm or by 
scattering curves, is evident. The problem, however, is the biological 
acceptability of the substances, in particular the possible chemical 
substance alterations under the influence of energy-rich radiation. 
A further critical point is the depth of penetration of the UV filter into 
the skin when it is used as a constituent of a cosmetic or dermatological 
agent. The suitable site of action is the region between the horny layer 
and basal layer. In order to meet these demands, testing for one year is 
necessary, as has been previously prescribed for pharmacological active 
compounds. Accordingly to their intended use and their individual 
efficacy, the UV filters are applied topically in a suitable medium in a 
wide concentration range between 1 and 10%. 
Thus, e.g., DE-A-3242385 (Zabotto) describes a cosmetic composition which, 
in addition to other active compounds, contains 1.5% Parsol Ultra 
(Givaudan) for the reduction of skin aging due to the action of light. 
Melanin, which also occurs in human and animal cells, the melanocytes, is 
known as a natural light protection active compound in higher organisms. 
Melanin is a brown to black-coloured polymeric pigment of the vertebrates, 
which is formed, inter alia, from the amino acid tyrosine and pigments 
both skin, hair and iris. The melanin formed in the melanocytes of the 
skin migrates into the basal layer of the epidermis and there releases the 
pigment into the epidermal cells. Since melanin, as a polymeric substance, 
hardly dissolves, the previous attempts to bring this substance to its 
site of action by means of topical applications are to be regarded as not 
thoroughly successful. 
The invention has set the object of making possible topical use of melanin 
at its site of action. 
According to the invention, a preparation for topical use having light 
protection properties is characterised in that it contains melanin which 
is dissolved or dispersed in one or more lipophilic fluorocarbons which 
are present as asymmetric lamellar phospholipid aggregates in an aqueous 
system together with a phospholipid, with a particle size of the 
aggregates gates in the range from 200 to 3000 nm. 
The naturally obtained (e.g. from Sepia officinalis) or synthetically 
produced (oxidation of tyrosine, e.g. with H.sub.2 O.sub.2) melanin is 
present, dissolved or suspended by the fluorocarbon, encapsulated in the 
core of the asymmetric lamellar phospholipid aggregates. The structural 
arrangement in the lamellar aggregates is fundamentally different from 
that of aqueous liposomes (vesicles). The hydrophobic nature of the 
fluorocarbon calls for a reversal in the polarity of the phospholipid 
molecule such that the lipophilic fatty acid radicals interact with the 
fluorocarbon in the core of the aggregate gate by dispersive forces. In 
this arrangement, further phospholipid bilayer films are constructed to 
give asymmetric metric lamellar globular aggregates according to specified 
conditions. 
The novel asymmetric structure was confirmed by .sup.31 P-NMR 
investigations and spectroscopic investigations. The exceptional stability 
of the aggregates results from their lamellar structure and from the 
corresponding surface charge. 
A plurality of fluorocarbons can be employed, e.g. aliphatic straight-chain 
and branched fluoroalkanes, mono- or bicyclic and optionally 
fluoroalkyl-substituted fluorocycloalkanes, perfluorinated aliphatic or 
bicyclic amines, bis(perfluoroalkyl)ethenes, perfluoropolyethers and 
mixtures thereof. Particularly preferred fluorocarbons are those such as 
perfluorodecalin, F-butyltetra-hydrofuran, perfluorotributylamine, 
perfluorooctyl bromide, bis-fluoro(butyl)ethene or 
bis-fluoro(hexyl)-ethene or C.sub.6 -C.sub.9 -perfluoroalkanes. The amount 
of fluoro-carbons here is in the range from 20 to 100% w/v, preferably in 
the range from 40 to 100%. A particularly preferred range is that from 70 
to 100% w/v. 
It was possible to determine the dependence of the penetration rate and the 
depth of penetration on the particle size of the aggregates experimentally 
by separate investigations using labelled encapsulated fluorocarbons. 
According to these experiments, smaller particles migrate more rapidly and 
more deeply into the skin tissue than larger particles. The choice of 
fluorocarbons or their mixtures according to their lipid solubility 
(represented by their critical solubility temperature CST in n-hexane) 
allows, as a further important criterion, the regulation of the residence 
time in the tissue. While, e.g. perfluorotributylamine (F-TBA, CST 
59.degree. C.) having a high CST value and poor lipid solubility has a 
relatively high residence time, in contrast to this perfluorodecalin (PFD, 
CST 22.degree. C.) but also F-butyltetra-hydrofuran, F-hexane and others 
are released correspondingly more rapidly from the tissue. With the aid of 
fluorocarbon mixtures, systems with desired CST values, i.e. lipid and 
membrane solubilities, can be prepared specifically with respect to the 
intended use. 
The content of the fluorocarbons in the lamellar. aggregates can vary 
between 1 and 100% w/v according to the intended use. Suitable 
fluorocarbons are in particular: 
aliphatic straight-chain and branched alkanes having 6 to 12 carbon atoms, 
e.g. perfluorohexane, perfluorooctane, perfluorononane; 
mono- or bicyclic cycloalkanes, which are optionally F-alkyl-substituted, 
e.g. perfluoromethylcyclohexane, perfluorodecalin; 
aliphatic tertiary amines, N-containing polycycles, e.g. 
perfluorotripopylamine [sic], perfluorotributylamine, 
F-cyclohexylmethylmorpholine; 
perfluoroethers, such as aliphatic ethers, F-alkylfurans, bicyclic and 
substituted bicyclic ethers having two or three oxygen atoms in the 
molecule, e.g. perfluorodihexyl ether, perfluorobutyltetrahydrofuran, 
perfluoropoly-ethers; 
perfluoroalkyl halides, e.g. perfluorooctyl bromide, perfluorohexyl 
bromide, perfluorooctyl chloride; Bis-F(alkyl)ethenes, e.g. 
bis-F(butyl)ethene, bis-F(hexyl)ethene. 
The term "fluorocarbons" used here is understood as meaning perfluorinated 
or highly fluorinated carbon compounds or mixtures which are able to 
transport gases such as O.sub.2 and CO.sub.2. Partially fluorinated 
hydrocarbon compounds within the context of this invention are those in 
which most of the hydrogen atoms are replaced by fluorine atoms, e.g. the 
bis-F(alkyl)ethenes which, as far as can be detected, are chemically and 
biologically inert and thus non-toxic. This is usually achieved when 
approximately up to 90% of the hydrogen atoms are replaced by fluorine 
atoms. Preferred fluorocarbons within the context of the present invention 
are those in which at least 955 of the hydrogen atoms are replaced, more 
preferably 98% and most preferably 100%. 
Suitable phospholipids are naturally occurring phospholipids such as soya 
or egg lecithin, and also lecithins (phospholipids) which can be prepared 
synthetically and which overall are known as being skin-compatible and 
good for the skin. Because of the advantageous action on the stability of 
the asymmetric lamellar aggregates, phospholipid mixtures having a content 
from 10 to 99%, preferably 30 to 99%, in particular 60 to 90% of 
phosphatidylcholine in addition to other naturally occurring accompanying 
products are preferably used. The phospholipid content in the topical 
formulation varies between 0.5 and 20%, preferably 10 to 20%. 
The particle sizes of the aggregates, and the phospholipids are selected 
such that a penetration into deeper layers of the skin, e.g. into the 
epidermis or the dermal region does not take place and the light 
protection filter according to the invention thus reaches its site of 
action after it has penetrated the horny layer. The particle sizes are in 
the range from 200 to 3000 nm, preferably in the range from 250 to 1000 
nm. 
The invention also relates to a process for the production of preparations 
for topical use, which is characterised in that melanin is dissolved or 
dispersed in one or more fluorocarbons and this dispersion is converted by 
homogenisation with a phospholipid in an aqueous system into asymmetric 
lamellar phospholipid aggregates containing the fluorocarbons and melanin, 
having particle sizes between 200 and 3000 nm. 
The solubility of the polymeric melanin can be increased by addition of 
lipophilic substances to the fluorocarbon as solubilisers. Suitable 
lipophilic substances are native oils, triglycerides or aliphatic alkanes, 
selected from the group consisting of olive oil, soya bean oil, sunflower 
oil, pentane, heptane, nonane, decane or mixtures thereof. 
The homogenisation can be effected by customary processes, e.g. using a 
high-speed stirrer (12,000 to 15,000 rpm), by ultrasound or by means of 
pressure homogenisation such that the particle size is ensured.