Process for improving transcutaneous and transfollicular absorption of cosmetic compositions

Benzyl alcohol is employed in an amount of 5.0 to 33.33% by weight of cosmetic composition as an absorption activator.

BACKGROUND OF THE INVENTION 
The present invention refers to an activator for the absorption of cosmetic 
compositions, as well as to a series of new compositions for cosmetic use. 
The activator, consisting of a specific component, that is, benzyl alcohol, 
has the function of facilitating the mechanism for the absorption of the 
other components through the skin and its associated organs. 
Several chemical and physical properties and pharmacological activities of 
benzyl alcohol have been known for a long time, but it has never been 
thought to connect these with what may be one of its specific uses in 
cosmetics and dermopharmacy, as is now, however, the object of the present 
invention. 
Benzyl alcohol, C.sub.7 H.sub.8 O, also called phenylcarbinol and 
.alpha.-hydroxytoluene, corresponds to the following chemical structure: 
##STR1## 
Its molecular weight, for this formula, is 108.13; the theoretical 
elementary analysis gives: C 77.75%, H 7.46%, O 14.80%. This is a natural 
constituent of the essential oils of jasmin, hyacinth, ylang-ylang and of 
balsams of Peru and Tolu, as well as storax. Commercially it is obtained 
by synthesis, starting from benzyl chloride, by reflux in the presence of 
sodium or potassium carbonate, in an anhydrous environment (R. E. Kirk and 
D. F. Othmer, Editors, Encyclopedia of Chemical Technology, Vol. 2, 
Interscience Encyclopedia, New York 1948, pp. 483-486). At ordinary 
temperatures and pressures it is a limpid, colourless, mobile and 
refracting liquid with a slight, aromatic, pleasing odour, of density 
(20.degree. C.) 1.04535; melting point--15.19.degree. C.; boiling point 
204.7.degree. C. (760 mm of Hg), 80.8.degree. C. (5 mm of Hg). Soluble in 
about 25 parts of water and in 1.5 parts of 1:1 water--ethanol; miscible 
with ethanol, ethyl ether, chloroform and many other polar or apolar 
organic solvents (The Merck Index, Ninth Ed., No. 1138, p. 148, Rahway, 
N.J., 1976). It is used in the manufacture of perfumes, pharmaceutical and 
parapharmaceutical products and its esters are used in soaps, in perfumes 
and in food flavourings (A. K. Doolittle, The Technology of Solvents and 
Plasticizers, Wiley, N.Y. 1954, p. 672; I. Mellan, Industrial Solvents, 
Reinhold, N.Y. 1950, p. 86, p. 519). 
Its local antiseptic and anaesthetic properties are currently used, and 
this use is favoured by the fact that its acute toxicity is very low 
(LD.sub.50 =3100 mg/kg, oral, rat), while toxic effects in subacute or 
chronic measure have not been recorded, above all because of the fact that 
it is rapidly oxidised within the organism and eliminated in the form of 
hippuric acid or benzoyl glycine (H. F. Smyth, Jr., C. P. Carpenter and C. 
S. Weil, Arch.Ind.Hyg. Occupational Med., 4, 119; 1951). Within 6 hours of 
the oral ingestion of 1.5 g of benzyl alcohol human subjects eliminate 
75-85% of the dose in the urine as hippuric acid (I. Snapper, A. Grunbaum 
and S. Sturkop, Biochem.Z., 155, 163; 1925; see also: J. A. Stekol, 
J.Biol. Chem., 128, 199; 1939). 
SUMMARY OF THE INVENTION 
The present invention takes advantage, however, of unforeseen 
characteristics due to which benzyl alcohol, the structure of which is the 
simplest possible in which an aromatic nucleus (lipophile) and an 
hydroxymethyl group (hydrophile) co-exist, may serve as the ideal vehicle 
to favour the transcutaneous and transfollicular absorption of substances 
particularly active and useful in the field of cosmetics and 
dermopharmacy. 
As is well known, the study of the mechanisms of absorption through 
organized cellular barriers has assumed a particular importance in 
cosmetology and in dermopharmacy in recent times. In each biological 
membrane concerned with exchange with the environment, one or more layers 
of polymeric molecules of lipid nature are present, with polar extremities 
oriented in a uniform manner. In the particular case which forms the 
subject of the present invention, it follows that the protective function 
exercised by the cutaneous covering is permitted, by inter alia its 
restricted permeability to most of the extraneous substances with which it 
may come into contact, in as much as these are either insufficiently 
hydrophilic or insufficiently lipophilic. The part of the skin which 
contributes more than any other to this defence is represented, as is 
readily understood, by the horny layer. 
If the chemical and physical parameters which regulate the action of the 
motive forces responsible for the cutaneous absorption are examined, one 
sees that the diffusion process may be embodied as a passive transport 
scheme, being determined mainly by the limit of diffusibility and by the 
extremely complex fine structure of the intercellular keratin. 
Nevertheless, even if the skin functions in this way as a sufficiently 
effective barrier against penetration of different substances, it was a 
serious error to have considered it at one time as only an inert shield. 
It represents on the other hand a morphological and structural unity which 
exhibits specific affinities for different substances with which it comes 
into contact, and the skin, even through the associated organs which are 
concerned primarily with excretive functions, can therefore, behave as an 
organ which is variously selective with regard to absorbtion. 
One can therefore consider a direct mechanism for the cutaneous absorption 
of various substances, when the latter are of a lipoid nature and have 
relatively simple structures; in such a case they dissolve in the 
covering, and transepidermal absorption takes place. If, on the other 
hand, the passage of extraneous substances takes place through the 
cutaneously associated organs by an indirect mechanism, transglandular and 
transfollicular absorption takes place. 
In the second case many physical and chemical factors come into play 
because the absorption takes place through organs which are very different 
from one another, such as piliferous follicles, sebaceous glands and 
sudoriparous glands. Among the various factors, it is necessary to record 
the maximum or minimum surface activity of the compound or compounds 
applied, their degree of moisture, the temperature of application, their 
emulsifying ability, the energy with which the rubbing or massaging is 
carried out during the application, and so on. 
One chemical and physical explanation which is accepted as defining the 
phenomena of permeability on the basis of transport mechanisms through 
biomembranes, imposes a consideration of the skin as a bioactive membrane, 
all the transport phenomena which take place in it being considered not 
according to the criteria of equilibria studied by classical 
thermodynamics, but according to those of non-equilibria on which the 
thermodynamics of irreversible processes are based (O. Caldini, M. 
Mannelli and C. Pisaturo), Boll. Chim Farm. 114, 545-553; 1975; see also 
C. Botre, "Thermodynamics of irreversible processes," ed. Bulzoni, Roma 
1971, passim). 
The data of solubility and permeability lead us to consider that non-polar 
solutes, as much as polar solutes, diffuse through the horny layer by 
different molecular mechanisms of permeation. In fact the water-soluble 
molecules and the liposoluble ones are characterised by very different 
values of free energy of activation, diffusion and activation for 
diffusion. The coefficients of distribution in membranes for water-soluble 
compounds are nearly all near to unity and thus indicate that they 
dissolve in hydrated regions, for example in keratinal zones. The ingress 
of water-molecules or of other highly polar molecules should then be 
explained as a tendency to diffuse within these aqueous regions, probably 
localized near the external surfaces of fibres, or in those parts of the 
corneal layer characterised by intracellular keratin, rather than deep 
within the semicrystalline parts. On the contrary, lipid molecules and 
other non-polar molecules should dissolve and diffuse in the lipid zone 
comprising the fibres of the eukeratinal fine structure. 
It has now been discovered that the benzyl alcohol molecule is such that it 
can take advantage of both means of passage thus acting as an ideal 
vehicle, which accordingly forms the subject of the present invention. 
Most of the preparations for cutaneous application are based on the use of 
compounds of a non-polar nature. These are then conveyed into the aqueous 
phase by means of surface-active agents of various types, thus giving rise 
to emulsions or particulate suspensions. If the nature of the vehicular 
substances and the degree to which they can retain the active principles 
are not considered, it is observed that the determining factor for the 
taking up and diffusion of the various molecules in the tissue is given by 
the endogenous hydration at the level of the corneal layer; and what is 
more, it is just this diffusion which basically determines the speed of 
the process in its entirety. If, therefore, there are added to the water 
molecules, which thus exercise the basic function in such processes, 
molecules, structurally not much more complex, of benzyl alcohol, in which 
an aromatic lipophilic component is present, the mobility of the entire 
active unit applied to the skin is increased surprisingly thereby. In 
fact, when a particular compound is sufficiently liposoluble, the aqueous 
regions of the keratin are not necessarily involved in the dissolving 
process, and the passage can even take place according to the coefficient 
of distribution between the water and horny layer; roughly the same 
relationships also apply in the case of the transglandular and 
transfollicular passage. 
It was not foreseeable however that such theoretical considerations would 
be confirmed by practical experience. In fact, surprisingly, it has been 
found that benzyl alcohol is a substance which, because of the extreme 
simplicity of its molecular structure, both in its aromatic half 
(lipophilic) and in its aliphatic part (hydrophilic), acts as an ideal 
vehicle for favouring the transcutaneous, transfollicular and 
transglandular absorption of active components in formulations of cosmetic 
and dermopharmaceutical products. Benzyl alcohol, because of its function 
as a lipo-hydrophilic vehicle, is readily introduced into such 
dermopharmaceutical and cosmetic formulations, in concentrations between a 
minimum of 5% and a maximum of 33.3%. 
In the preparation of dermopharmaceutical and cosmetic compositions 
containing benzyl alcohol as an activator for cutaneous absorption, its 
distribution, in the case of emulsions, takes place equally well in the 
continuous or the disperse phase, independently of the nature of one or 
the other, that is, independently of whether the emulsion is of the 
oil-in-water type or the water-in-oil type. In the case of single-phase 
formulations (lotions, jellies, alcoholates, ointments etc.) the 
solubility of benzyl alcohol is such that the system is homogeneous within 
the limits of concentration mentioned above. 
In any case it must be remembered that the benzyl alcohol favours the 
absorption mechanisms mentioned above, both in the sense of the lipophilic 
manner and in the hydrophilic manner, because of its elementary 
lipohydrophilic structure (HLB=5.74). 
An object of the present invention is, therefore, an absorption activator 
for cosmetic compositions, consisting of benzyl alcohol, employed in a 
quantity of between 5.00 and 33.3% by weight of the said benzyl alcohol 
with respect to the total weight of the composition. 
A further object of this invention is a cosmetic composition containing 
benzyl alcohol as an absorption activator in a quantity of between 5.00 
and 33.3% by weight of the said benzyl alcohol with respect to the total 
weight of the composition. 
Cosmetic compositions according to this invention may be: a lotion for 
reactivating the hair, a reactivating jelly, a tonic milk, a reactivating 
cream, a cleansing lotion, an antihyperkeratosis cream, an antigrease 
cream. 
In the following examples, purely and simply for the purpose of 
illustration, and without restricting the scope of this invention in any 
way, it is possible to give a few dermopharmaceutical and cosmetic 
formulations in which benzyl alcohol is employed in concentrations of 
between 5.00 and 33.33% by weight, alongside other known and variably 
active components, for the aforesaid purposes. The chosen range for the 
absorption action which forms the subject of the present invention is 
explained by what has been said at the beginning, that is to say, that 
other characteristics and other activities were known for benzyl alcohol: 
for example, below a concentration of 5.00% an antimicrobic action is 
manifested, while for local-anaesthetising and anti-pruroginic action one 
resorts to concentrations not lower than 33.33%. The concentrations lying 
within the chosen range for the field of application of the present 
invention have been found to be the most suitable, however, for favouring 
the transcutaneous absorption processes of the active principles of 
dermopharmaceutical and cosmetological interest, in particularly stable 
and balanced formulations. In the following examples the percentages are 
by weight.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
______________________________________ 
"Reactivating Lotion for the Hair" 
______________________________________ 
Benzyl alcohol 12% 
Nicotinyl alcohol 0.5% 
Resorcinol 0.5% 
Propylene glycol 4.0% 
Polyoxyethylene sorbitan monooleate 
(Polysorbate 80) 1.0% 
Polyethylene glycol 600 2.0% 
Perfume 1.0% 
Ethyl alcohol 95% (V/V) 47.5% 
De-ionised water 31.5% 
______________________________________ 
By comparison with the same formula in which the benzyl alcohol is replaced 
by proportional parts of water and of ethyl alcohol, it is possible to 
establish, in groups of 5-7 subjects in normal conditions, that after a 
standard treatment for four weeks (application of the lotion after the 
morning toilet; neutral shampoo once per week), the count of hairs 
remaining on the comb was reduced by on average 45-55% with respect to the 
values established before the treatment, and 40-45% with respect to values 
obtainable following the treatment without benzyl alcohol (stimulating 
action of nicotinyl alcohol and resorcinol). 
______________________________________ 
Reactivating Jelly 
______________________________________ 
(A) Benzyl alcohol 4.0% 
Diethanolamine 0.7% 
Ethyl alcohol 95% (V/V) 
11.6% 
Richter Collagen 5.0% 
Perfume 0.1% 
De-ionised water 11.6% 
(B) Carboxypolymethylene (Carbopol 940) 
1.0% 
De-ionised water 60.0% 
Propylene glycol 6.0% 
______________________________________ 
A and B are blended together slowly. By comparison with the same formula in 
which the benzyl alcohol is replaced by proportional parts of water and 
ethyl alcohol, it is possible to observe that the aesthetic conditions of 
the skin (hands, neck, face) in groups of 4-5 female subjects, aged from 
35 to 46 years, are notably improved with the constant use of the formula 
in which benzyl alcohol is present. The increase in the cutaneous 
reflection, measured with a light meter and a photo-electric cell on the 
back of the hand, was on average between 37-46% with respect to the values 
established before the treatment, and 31-38% with respect to the values 
obtainable following the treatment without benzyl alcohol (hydrating 
action of the collagen and of the propylene glycol). 
EXAMPLE III 
______________________________________ 
Tonic Milk 
______________________________________ 
(A) Benzyl alcohol 5.0% 
Self-emulsifying glyceryl monostearate 
1.5% 
Polyoxyethylene lauryl ether (Brij 35 Atlas) 
1.2% 
Propylene glycol 2.0% 
Isopropyl myristate 7.0% 
Cetyl-stearyl alcohol 0.75% 
(B) Carboxypolymethylene (Carbopol 934) 
0.3% 
Sodium carboxymethylcellulose 
0.5% 
Hydrating mucopolysaccharides 
3.0% 
Extract of Hamamelis Virginiana leaves 
2.0% 
Benzyl alcohol 5.0% 
Methyl p-hydroxybenzoate 0.15% 
Propyl p-hydroxybenzoate 0.05% 
De-ionised water 70.52% 
(C) Triethanolamine 0.23% 
Perfume 0.80% 
______________________________________ 
A is poured into B, under agitation, at 75.degree. C., and C, followed by 
the perfume, is added to the emulsion at 40.degree. C. The comparison with 
the same formula in which the benzyl alcohol is replaced by proportional 
parts of water and of ethyl alcohol was carried out in Example II and 
provided similar results, with the percentage increase in the cutaneous 
reflection (in the zigomatic periobitary region) of the same order of 
magnitude (activation by the hydrating action of the mucipolysaccharides 
and of propylene glycol). 
EXAMPLE IV 
______________________________________ 
Reactivating Cream 
______________________________________ 
(A) Benzyl alcohol 2.00% 
Self-emulsifying glyceryl monostearate 
13.00% 
Cetyl-stearyl alcohol 1.00% 
Isopropyl myristate 8.00% 
Propylene glycol 2.00% 
(B) Glycerine 8.00% 
Benzyl alcohol 6.50% 
Lettuce extract 2.00% 
Richter Collagen 5.00% 
Sodium Stearate 0.10% 
Methyl p-hyrdoxybenzoate 
0.15% 
Propyl p-hydroxybenzoate 
0.05% 
De-ionised water 51.20% 
(C) Perfume 1.00% 
______________________________________ 
A is poured into B, under agitation, at 70.degree. C., and C is added to 
the emulsion, at 40.degree. C. The comparison with the same formula in 
which benzyl alcohol was replaced by equal parts of water was carried out 
as in Example II and produced analogous results, with percentage increases 
in the cutaneous reflection (antero-lateral region of the neck) of the 
same order of magnitude (activation by the hydrating action of the 
vegetable extract, collagen, propylene glycol and of glycerine). 
EXAMPLE V 
______________________________________ 
Cleansing Lotion 
______________________________________ 
Benzyl alcohol 33.33% 
Glycerine 2.00% 
Propylene glycol 5.00% 
Thymol 0.40% 
Polyethylene glycol 600 
3.00% 
Ethyl alcohol 95% (V/V) 
33.33% 
De-ionised water 22.94% 
______________________________________ 
By comparison with the same formula in which the benzyl alcohol was 
replaced by proportional parts of water and ethyl alcohol, it was possible 
to observe that the aesthetic condition of the cutaneous area subjected to 
treatment (cheeks, nose, throat, neck etc.) in groups of 4-5 female 
subjects aged between 18 and 34 years, was effectively improved by the 
constant use of the formula in which benzyl alcohol was present. The count 
of the blackheads was reduced by 40-44% with respect to the values 
established before the treatment, and by 36-39% with respect to the values 
obtainable following treatment without the benzyl alcohol (purifying 
action of the thymol and of the glycols). 
EXAMPLE VI 
______________________________________ 
Antihyperkeratosis Cream 
______________________________________ 
(A) Benzyl alcohol 3.00% 
Self-emulsifying glyceryl monostearate 
13.00% 
Isopropyl myristate 8.00% 
Propylene glycol 2.00% 
(B) C. L. Richter biosulphur liquid (solubilized sulfur) 
0.20% 
Benzyl alcohol 8.00% 
Allantoin 0.50% 
Sodium stearate 0.10% 
Anhydrous sodium acetate 0.20% 
De-ionised water 64.40% 
(C) Perfume 0.60% 
______________________________________ 
A is poured into B, under agitation, at 70.degree. C., and C is added to 
the emulsion at 40.degree. C. By comparison with the same formula in which 
the benzyl alcohol was replaced by proportional parts of isopropyl 
myristate and of water, it was possible to observe that the aesthetic 
conditions of a hyperkeratosic skin (hands, neck, face, lower limbs etc.) 
in groups of 4-5 female subjects, aged between 34 and 46 years, was 
effectively improved by the constant use of the formula in which benzyl 
alcohol was present. In the absence of a method suitable for ensuring the 
objectiveness of the results, a favourability test according to the double 
blind technique was carried out using the formula without the benzyl 
alcohol as a placebo. In each case the response in favour of the formula 
with benzyl alcohol exceeded significantly values of between 65 and 80%. 
EXAMPLE VII 
______________________________________ 
Antigrease Cream 
______________________________________ 
(A) Benzyl alcohol 12.50% 
Liquid paraffin 5.00% 
Apicerol (Lanolin and Beeswax) 
6.00% 
Ethoxylated lanolin 4.00% 
Oleyl alcohol (Eutanol Henkel) 
2.00% 
(B) Crystalline sorbitol 
3.00% 
Benzyl alcohol 6.50% 
Liquid extract of ivy 
1.00% 
Liquid extract of birch 
1.00% 
Liquid extract of horse chestnut 
0.25% 
Escin 0.30% 
Anhydrous sodium acetate 
0.20% 
De-ionised water 57.65% 
(C) Perfume 0.60% 
______________________________________ 
A is poured into B, under agitation, at 70.degree. C., and C is added to 
the emulsion at 40.degree. C. By comparison with the same formula in which 
the benzyl alcohol was replaced by proportional parts of oleyl alcohol and 
of water, a significant flattening of the kymographic traces indicating 
the nodular relief of the skin (thighs, buttocks) was found along 
pre-established lines. In particular, the comparison with the data taken 
before treatment, in groups of female subjects aged between 34 and 49 
years, was considered using the other thigh or the other buttock of the 
same subject treated with the formulation devoid of benzyl alcohol as the 
control. The treatment consisted of massaging the nodular area, affected 
by mesenchyma (generally and improperly called "cellulite"), for 5 
minutes, twice a day at a fixed time, with ten grams of one or the other 
formula, the kymographic relief being carried out after 10-15-20 days of 
treatment. The flattening of the trace with the use of the formula 
containing benzyl alcohol was, on average about 65-76%; with the use of 
the formula not containing benzyl alcohol this was on average, 36-45% 
(vascularizing and restoring action of the vegetable extract and of the 
escin). 
It is clear that in every formula of the examples recorded above, and in 
any other which may be given as non-limitative examples, qualitative and 
quantitative variations in the compositions, as far as possible, fall 
within the field of the present invention, since the general phenomenon on 
which it is based, as well as the particular field in which it is usefully 
employed, is clear. 
It is, therefore, understood that the invention is not limited to the 
embodiments described above, but that all the variations of execution and 
of use which will be seen as obvious to the experts in this art fall 
within its scope.