WO2014076642A1

WO2014076642A1 - Topical composition for the transepidermal or transdermal delivery of paracetamol

Info

Publication number: WO2014076642A1
Application number: PCT/IB2013/060104
Authority: WO
Inventors: Vittorio Bertelli
Original assignee: Laboratori Fitocosmesi E Farmaceutici S.R.L.
Priority date: 2012-11-19
Filing date: 2013-11-13
Publication date: 2014-05-22
Also published as: ITMI20121965A1

Abstract

A transepidermal or transdermal topical composition comprising paracetamol, pharmaceutically or cosmetically acceptable excipients and a transepidermal o transdermal carrier agent consisting of acidic electrolyzed water and a polyacrylate is described. The invention further relates to cosmetic and pharmaceutical formulations comprising said transepidermal or transdermal topical composition and their use as adjuvants in the treatment of skin lesions, arthritis, atopic dermatitis, wrinkles, liposclerosis, decubitus ulcers, varicose and diabetic ulcers.

Description

Topical composition for the transepidermal or transdermal delivery of paracetamol

FIELD OF THE INVENTION

The present invention relates to a transepidermal or transdermal topical composition comprising paracetamol, pharmaceutically or cosmetically acceptable excipients and a transepidermal or transdermal carrier agent consisting of acidic electrolyzed water and a polyacrylate. The invention further relates to cosmetic and pharmaceutical formulations comprising said transepidermal or transdermal topical composition and their use as adjuvants in the treatment of skin lesions, atopic dermatitis, wrinkles, liposclerosis, decubitus ulcers, varicose and diabetic ulcers.

STATE OF THE ART

Paracetamol (or acetaminophen) (N-acetyl-para-aminophenol) is a very small molecule of a lipophilic nature and is known for its analgesic and antipyretic action, for example in regular over-the-counter preparations for viral forms of cold, or in drugs for treating acute and chronic pain.

It is generally administered alone or in combination with other therapeutically active ingredients in oral dosage units of 500 mg or 1 g. However, such an administration is not satisfactory. In fact, when paracetamol molecules are introduced in the esophagus and stomach, they are subjected to the so called "first digestive passage" effect, i.e. alterations and dispersions due to the environment of the stomach or to intestinal physiological changes. They are then subjected to the so-called "first hepatic passage" which triggers their metabolism and/or their more or less intense degradation, with the formation of several metabolites, predominantly inactive or toxic, without considering that paracetamol is toxic for the liver when administered at a dosage greater than 4 g.

Therefore, the dose of active ingredient actually available is low, on average between 60 and 75% of the administered dose, without considering the multiple inter- and intra-subject variables. Furthermore, the half-life of paracetamol is relatively short, that is 1 to 3 hours. Because it poorly binds to plasma proteins due to its lipophilic nature, the molecule of paracetamol rapidly distributes in the majority of the compartments of the body. Thus, a significant portion of the administered dose is diluted in the vasculature of the body and at the same time in extravascular, organic and especially tissue spaces, thus reducing the percentage of paracetamol actually available which may access the central brain receptors in order to carry out its short-acting therapeutic activity.

Moreover, the start of the therapeutic efficacy for the patient requires 30 to 60 minutes after administration, corresponding to the steps of digestive absorption, metabolization and vascular as well as tissue diffusion.

Therefore, two major problems are identified. The first problem is that it becomes necessary to administer an adequate dose to the patient considering the dilution and dispersion in the body, so that the significantly active part reaching the central effectors is effective. In fact, a relevant problem associated with oral administration of drugs is that the concentration level that must be reached in blood has to be significant in order to effectively treat the distal areas of pain or inflammation. These levels are very often higher than it would be necessary if it were possible to precisely address the particular site to be treated.

The second problem is the latency time due to the metabolism and distribution in the body before the molecule may act and the patient benefit from it.

From this, side effects result which are associated with the use of paracetamol, in particular hepatotoxicity and, in rare cases, nephrotoxicity in humans and experimental animals. Paracetamol overdosing causes dose-dependent and partially fatal hepatic necrosis as well as, in rare cases, kidney tubular necrosis and hypoglycemia.

Therefore, there is a need to administer an amount of paracetamol immediately bioavailable, allowing paracetamol to exert its function in a rapid and effective way, potentially in situ, so as to avoid the risk of overdosing in order to reach the required amount.

An object of the present invention is, therefore, to find an effective product for the above mentioned objects, but that at the same time is highly biocompatible and tolerable.

SUMMARY OF THE INVENTION

The object indicated above has been achieved by a transepidermal or transdermal topical composition comprising paracetamol, pharmaceutically or cosmetically acceptable excipients and a transepidermal or transdermal carrier agent consisting of acidic electrolyzed water having a pH of 1.0 to 4.0 and comprising clusters of water, having 5 to 10 molecules of water per cluster, and a polyacrylate.

'Polyacrylate' means polyacrylate of sodium, potassium, lithium, ammonium or a mixture thereof. In another aspect, the present invention relates to a pharmaceutical or cosmetic formulation comprising the transepidermal or transdermal topical composition and at least one pharmaceutical or cosmetic agent selected from wetting agent, soothing agent, softening agent, preservative agent, chelating agent, thickening agent, antioxidant agent and a mixture thereof.

In a further aspect, the present invention relates to the use of a pharmaceutical or cosmetic formulation as an adjuvant for the treatment of skin lesions, arthritis, atopic dermatitis, wrinkles, liposclerosis, decubitus ulcers, varicose and diabetic ulcers.

DESCRIPTION OF THE FIGURES

The characteristics and advantages of the present invention will become apparent from the following detailed description and the working examples provided for illustrative purposes, as well as from the appended Figures, wherein:

- Figure 1 shows the NMR spectrum of the samples of Example 13; and

- Figure 2 shows the NMR spectrum of a sample of Example 13 one year after the preparation.

DETAILED DESCRIPTION OF THE INVENTION

The invention therefore relates to a transepidermal or transdermal topical composition comprising paracetamol, pharmaceutically or cosmetically acceptable excipients and a transepidermal or transdermal carrier agent consisting of acidic electrolyzed water having a pH of 1.0 to 4.0 and comprising clusters of water, having 5 to 10 molecules of water per cluster, and a polyacrylate.

Surprisingly, it was found that such a composition is particularly effective in transepidermal and transdermal administration of paracetamol, as will be shown in the Examples provided below.

In the composition of the invention, paracetamol can be in an amount of 0,005 to 15% by weight, on the weight of the composition.

Preferably, in the composition of the invention, paracetamol can be in an amount of 0.01 to 5% by weight, on the weight of the composition.

More preferably, in the composition of the invention, paracetamol can be in an amount of 0.05 to 2% by weight, on the weight of the composition.

Polyacrylate has been selected because makes possible to attain a number of advantages. In fact, in terms of formulation, polyacrylate offers high processability and dispersibility in water, so as to avoid the undesired formation of lumps or aggregates; moreover, as it will be apparent from the following examples, polyacrylate advantageously stabilizes for a long time the clusters present in the acidic electrolyzed water according to the present invention. A further advantage is observed in the final formulations, in that they are highly spreadable on skin and pleasant to the touch, which conveniently enhance patients' compliance. In fact, in patients suffering for example from atopic dermatitis, the administration of a formulation according to the present invention may envisage constant and subsequent applications for 4-8 weeks. Therefore, for the purposes of the long-term treatment of atopic dermatitis or other skin diseases, it is extremely important to have an adequate compliance, which on the contrary is not obtained with other rheological agents, such as carrageenin, which, despite somehow allowing to stabilize electrolyzed water in vitro, are however poorly processable and give formulations that are less spreadable and therefore less topically effective and less pleasant for patients.

Preferably, said polyacrylate is sodium polyacrylate.

Preferably, said polyacrylate is in an amount of 0.0001 to 5% by weight, on the weight of the transepidermal or transdermal carrier agent.

More preferably, said polyacrylate is in an amount of 0.001 to 2% by weight, on the weight of the transepidermal or transdermal carrier agent.

The transepidermal or transdermal carrier agent of the composition of the invention further comprises acidic electrolyzed water having a pH of 1.0 to 4.0 and comprising clusters of water having 5 to 10 molecules of water per cluster.

For the purposes of the present invention, said 'acidic electrolyzed water' is water that can be obtained by a process wherein a solution of distilled water and an electrolyte, preferably an inorganic salt, is subjected to electrolysis by applying a potential difference of 10-100 Volts. Said inorganic salt can be for example NaCl, Na₂S0₄, KI, CuCl₂, SnCl₄. Preferably, said inorganic salt is in a concentration of 0.20-2.00 g/1 and the potential difference applied is 30-100 Volts for a period of at least 5 minutes. In the surroundings of the cathode of the electrolytic cell there concentrates alkaline electrolyzed water, while in the surroundings of the anode there concentrates acidic electrolyzed water.

In a preferred embodiment, bidistilled water supplemented with NaCl is used in a concentration of 0.30-0.80 g/1, more preferably 0.40-0.70 g/1; a potential difference is therefore applied of 50-100 Volts for at least 10 minutes. As a result of electrolysis, the clusters of molecules of water naturally present in aggregates of up to 10-20 molecules of water each, become smaller in size down to 5-10 molecules of water each, preferably 5-6 molecules of water each. This is extremely advantageous in that clusters of such sizes easily go beyond the epidermal barrier, surprisingly succeeding in transporting paracetamol, which otherwise may not be administered transdermally. In fact, paracetamol is typically administered by oral, rectal or injection route, causing the above mentioned drawbacks.

At the end of the electrolysis process, an aqueous solution is separated in the acid fraction and in the basic fraction, thereby obtaining 'acidic electrolyzed water' and 'basic electrolyzed water', respectively. The thus separated acidic electrolyzed water has a pH of 1.0 to 4.0, preferably 2.0 to 3.0.

According to a preferred embodiment, the pH of acidic electrolyzed water is 2.2.

Pharmaceutically or cosmetically acceptable excipients suitable for the composition of the invention can be selected from plasticizers, disintegrants, glidants, coloring agents, lubricants, stabilizers, adsorbents, preservatives, delivery retarders and mixtures thereof. Therefore, it should understood that the composition of the present invention advantageously does not require the use of absorption enhancers, which are responsible for undesirable skin irritations. In this respect, the transepidermal or transdermal topical composition of the invention consists essentially of paracetamol, pharmaceutically or cosmetically acceptable excipients and a transepidermal or transdermal carrier agent consisting of acidic electrolyzed water having a pH of 1.0 to 4.0 and comprising clusters of water having 5 to 10 molecules of water per cluster, and a polyacrylate, since such a combination of components allows an adequate transepidermal or transdermal delivery of paracetamol owing to the sole presence of the transepidermal or transdermal carrier agent described above, thus advantageously excluding the presence of absorption enhancers. According to a preferred embodiment, the composition of the invention consists of paracetamol, pharmaceutically or cosmetically acceptable excipients and a transepidermal or transdermal carrier agent consisting of acidic electrolyzed water having a pH of 1.0 to 4.0 and comprising clusters of water, having 5 to 10 molecules of water per cluster, and a polyacrylate.

In another aspect, the composition of the invention is for both cosmetic and pharmaceutical external use, in particular as a skin hydrating agent and as an agent for transepidermal or transdermal administration of paracetamol.

In another aspect, the present invention relates to a pharmaceutical or cosmetic formulation comprising the transepidermal or transdermal topical composition described above and at least one pharmaceutical or cosmetic agent selected from wetting agent, soothing agent, softening agent, preservative agent, chelating agent, thickening agent, antioxidant agent and a mixture thereof.

Preferably said pharmaceutical or cosmetic agent is panthenol, glycerin, mannitol, sodium citrate, acetyl tetrapeptide-15, imidazolidinyl urea, phenoxyethanol, methyl -paraben, ethyl- paraben, propyl-paraben, butyl-paraben, EDTA, disodium EDTA, diglycerine, olive oil, salicylate de silanodiol, rice bran oil, oligosaccharide alpha-glucan, vitamin E, vitamin A, ascorbyl palmitate, lipoic acid, horse chestnut extract, Gingko Biloba extract, or tocopheryl nicotinate.

According to a preferred embodiment, the pharmaceutical or cosmetic formulation of the invention further comprises hyaluronic acid.

Preferably, the formulation of the invention is for external use and is in the form of a cream, oil, emulsion, milk, spray, lotion, protective mask, foundation, lipstick, lipogel or gel.

In a further aspect, the present invention relates to the use of the pharmaceutical or cosmetic formulation described above as an adjuvant for the treatment of skin lesions, arthritis, atopic dermatitis, wrinkles, liposclerosis, decubitus ulcers, varicose and diabetic ulcers.

For the purposes of the present invention, with the term 'skin lesions' is meant maculae, papulae, vesicles, bullae, pustulae, cysts, erosions, abrasions, rash, ulcers, fissures, sores, telangectasia, scales, erythema, burns, crusts, lichenifications, excoriations, callosities, cuts, lacerations, or atrophies.

In fact, as it will become apparent from the following Examples, such a formulation once applied topically has shown to have good efficacy in promoting a healthy state of the skin by effectively and quantitatively carrying both paracetamol and the pharmaceutical and cosmetics agents present therein.

The composition and the formulation of the present invention are prepared through mixing of the ingredients.

Below are reported the working examples provided for illustrative purposes. EXAMPLES

Example 1

According to the present invention, a composition having the following composition A was prepared:

⁽*^} filler, glidants, plasticizers, fragrance

Example 2

According to the present invention, a composition having the following composition B was prepared:

⁽*' filler, glidants, fragrance

Example 3

According to the present invention, a composition having the following composition C was prepared:

⁽*' filler, glidants, fragrance

Example 4

According to the present invention, a composition having the following composition D was prepared:

I I wt % I paracetamol 0.1

acidic electrolyzed water (pH 2.2) 73.3

sodium polyacrylate 0.5 (0.67% on carrier) excipients ^ 26.2

⁽*' filler, glidants, fragrance

Example 5

According to the present invention, a composition having the following composition E was prepared:

⁽*' filler, glidants, fragrance

Example 6

According to the present invention, a composition having the following composition F was prepared:

^C*^J filler, glidants, fragrance

Example 7

According to the present invention, a composition having the following composition G was prepared:

filler, glidants, fragrance Example 8

According to the present invention, a formulation using the composition A of Example 1 was prepared:

This formulation is applied as an adjuvant in the treatment of sun burns and erythema.

Example 9

According to the present invention, a formulation using the composition B of Example 2 was prepared:

This formulation is applied as an adjuvant in the treatment of atopic dermatitis.

Example 10

According to the present invention, a formulation using the composition C of Example 3 was prepared:

wt %

Composition C 89.4

panthenol, glycerol 1.0 diglycerin 3.2

olive oil 0.5

tocopheryl acetate 0.5

ascorbyl palmitate 3.0

lipoic acid 2.0

Preservatives 0.4

This formulation is applied as an adjuvant in the treatment of wrinkles and as an anti-age product.

Example 11

According to the present invention, a formulation using the composition D of Example 4 was prepared:

This formulation is applied as an adjuvant in the treatment of liposclerosis.

Example 12

According to the present invention, a formulation using the composition E of Example 5 was prepared:

wt %

Composition E 90.7

panthenol, glycerol 1.0

diglycerin 3.4

olive oil 0.5

tocopheryl acetate 0.5

ascorbyl palmitate 3.0 Preservatives 0.4

Hyaluronic acid 0.5

Example 13

Assessment of the stability over time of clusters of water molecules in the transepidermal or transdermal carrier agent of the invention

Such assessment was carried out by means of a nuclear magnetic resonance study performed on oxygen isotope 17 (^I70-NMR).

The following samples were prepared and analyzed:

- sample A = distilled water

- sample B = acidic electrolyzed water (pH 2.2) + sodium polyacrylate (0.001% by weight on the weight of sample B)

- sample C = sample B 1 month after preparation

17

The analyses by means of "O-NMR allow to assess the status of aggregation of molecules of H₂0, providing a signal or peak the width of which (measured at half maximum) denoted as Δν^ and the resonance frequency δ (measured in Hertz or parts per million, Hz or δ/ppm, respectively) are parameters strictly correlated to the number of molecule making up the clusters: in particular, the smaller the amplitude of the NMR signal, the lower the number of molecules of H₂0 making up a cluster.

In fact, the NMR spectroscopy is extremely sensitive to the surroundings of cores and their interactions, thus even small variations in the geometry of the cluster and/or changes in the associating forces between molecules may generate significant variations in the times of relaxation of water and, as a result, in the aspect of NMR signals.

17

Parameters of acquisition of O-NMR spectra:

Spectral Width SW = 200 ppm

Acquisition Times AQ = 1.0 sec

Number of Scans NS = 350

Delay Dl = 0.5 ^'sec

Line broadening (before Fourier Transform) 1 Hz

Figure 1 reports the spectra of the three samples above.

The resonance frequency for the three samples is: δ = 2.671. The spectra refer to the resonance peak ^I70 of external deuterated water (D₂0): δ = 0

Results

It was noted that the differences among the respective line widths (Δνι_/2: signal width at half maximum) were significantly different:

Sample A: Δνι_/2 = 112 Hz

Sample B: Δνι_/2 = 58 Hz

Sample C: Δνι_/2 = 56 Hz

Such differences were representative of the fact that distilled water (sample A) comprises clusters of 10-15 molecules of H₂0, while the acidic electrolyzed water used in the carrier agent of the invention comprises clusters of as few as 5-6 molecules of H₂0. Such result remained unchanged also one month after the preparation of sample B, as shown by the spectrum of sample C.

Such result is considerably advantageous in that acidic electrolyzed water comprising clusters of such sizes is absorbed into the skin much more effectively than distilled water.

Moreover, as a transepidermal or transdermal carrier agent according to the present invention, said acidic electrolyzed water is also conveniently very stable.

One year later, sample C was analyzed again and, as Figure 2 shows, resulted completely unchanged, thus confirming an excellent stability over time.

Example 14

Assessment of the ability of the composition of the invention to carry paracetamol

On the composition of Example 1 an in-vitro assessment was carried out of the percutaneous absorption of paracetamol on reconstituted epidermis able to simulate the in- vivo conditions.

Said reconstituted epidermis represents a tridimensional cell model and consists of normal human primary keratinocytes, allowed to grow in vitro so as to simulate the multilayered architecture of human epidermis, with a well-differentiated horny layer. The model was purchased from CellSystems® (Troisdorf, Germany Batch EST-120625-001)

A cross section of said model cultured in vitro showed the different layers of the epidermis and a well-differentiated pink horny layer on the surface. The product to be tested was applied to the horny layer, while beneath the epidermis a semi-permeable membrane was found which communicated with the lower well where the culture medium was.

The units of artificial epidermis (0.5cm ) were treated with the sample of Example 1 by dosing it accurately through a special positive-displacement pipette for dense liquids PI 00 Gilson and applying 30μ1 of each sample containing paracetamol, that is about 150μg of active ingredient.

The samples and controls were incubated at 37°C, 5% C0₂ and the exposure was carried out for 30', 2 and 6 hours. The sample was tested in triplicate.

At different exposure times, samples of the subnatant were withdrawn with a pipette. The thus obtained samples were immediately frozen at -20°C and afterwards thawed for quantitative chromatographic tests.

The amount of paracetamol permeated underneath the epidermis was diluted in equal parts with methanol. The thus obtained solution was quantified through HPLC and DAD detector. The method of analysis was developed according to the provisions of the European Pharmacopoeia for the compound Paracetamol Method 01/2008:0049 corrected 6.0.

The culture medium, with the unknown amount of paracetamol coming from percutaneous absorption, was supplemented with an equal amount of methanol (1 :1). The thus obtained solution was prepared for injection in HPLC.

The values expressed in Table 1 below therefore relate to the total amounts of paracetamol permeated in the subnatant and their respective percentages as compared to the initial total amount considering density = 1.0 and active titer 0.5%.

Table 1. Average % of paracetamol present in the subnatant

The HPLC-DAD analysis therefore detected at 6 hours the maximum delivery of paracetamol, in the subnatant, equal to 16.7%. Surprisingly, it was also found that after only 30 minutes, paracetamol was already detectable in the subnatant, indicating the immediate percutaneous absorption owing to the composition of the present invention. An MTT test was also carried out to assess the cytotoxicity of the composition of the invention 6 hours after starting the application on reconstituted epidermis. The result of such test is reported in Table 2 below.

Table 2. % cell viability

The samples of Example 1, therefore, showed an adequate biocompatibility towards epidermis after 6 hours of treatment.

Example 15

Treatment of atopic dermatitis

Atopic dermatitis is a chronic or chronic-relapsing eczema. Atopic dermatitis is characterized by a reduction in epidermal ceramides which determines a weakening of the skin barrier function, greater irritability and an increase in transepidermal water loss which may increase if there is a concurrent inflammatory state of epidermis. This facilitates the skin penetration of allergens and haptens which bind to keratinocytes and Langerhans cells, activating them. Skin subject to atopic dermatitis is more susceptible to infections due to high levels of inflammatory cytokines such as IL-4 or IL-13.

Composition A of Example 1 was formulated with rice bran oil to form an oil-in-water emulsion.

Twenty patients suffering from atopic dermatitis were enrolled.

Each patient applied the oil-in-water emulsion topically twice daily for 30 consecutive days.

At the end of the treatment, the state of hydration of the areas affected by atopic dermatitis was assessed, adopting a scale 'excellent=>good=>low=>very low'.

Furthermore, patients were asked to assess the final result by adopting a scale 'very satisfied=>satisfied=>not satisfied', and to assess the treatment compliance, by adopting the scale 'very pleasant=>pleasant=>not pleasant'.

Patients were eventually asked to report the occurrence of any side effects.

Results

In 80% of cases, the state of hydration of the areas affected from atopic dermatitis showed a significant improvement. It is believed that such improvement is due to the rapidity of hydration provided by acidic electrolyzed water comprising clusters of water, having 5 to 10 molecules of water per cluster. Surprisingly, this further allows to administer paracetamol directly to the area to be treated, with excellent efficacy, but advantageously using reduced amounts of active ingredient.

More than 70% of patients reported to be very satisfied or satisfied of the results obtained with the treatment of the invention.

Similarly, more than 70% of patients found the product to be very pleasant or pleasant. None of the patients reported side effects nor did they have to suspend the treatment.

Example 16

Treatment of first-degree burns

In the present study, first-degree burns caused by exposure to heat sources or the sun have been considered.

Twenty 18 to 60-year old patients not suffering from diabetes or from kidney or heart diseases have been enrolled.

Each patient applied the formulation of Example 8 topically twice daily for 7 consecutive days.

At the end of the treatment, the state of improvement of the areas affected by burns was assessed by the investigator.

Moreover, patients were asked to assess the sensation of pain and to assess the treatment compliance.

Patients were eventually asked to report the occurrence of any side effects.

Results

A sharp improvement of the areas affected from burns was observed in all patients, having further observed over the 7 days of treatment a constant regression of burns.

More than 70% of patients reported a relief from pain already a few hours after the first application. It is believed that such rather immediate relief is due to the presence of paracetamol rapidly made available through the cell membrane, by the carrier action of acidic electrolyzed water comprising clusters of water, having 5 to 10 molecules of water per cluster. Surprisingly, this allows to administer paracetamol directly to the area to be treated, with excellent efficacy, but advantageously using reduced amounts of active ingredient.

90% of patients was pleased with the product and assessed its compliance very positively. None of the patients reported side effects nor did they have to suspend the treatment.

From the detailed description and the Examples reported above, the advantages achieved by the composition of the present description become apparent. In particular, such composition proved surprisingly and advantageously capable of administering an immediately bioavailable amount of paracetamol, such that it allows paracetamol to carry out its function in a rapid and effective way. Furthermore, the fact that the molecule is administrable transepidermally or transdermally owing to the suitable selection of the carrier agent is even more surprising.

Claims

17 CLAIMS

1. A transepidermal or transdermal topical composition comprising paracetamol, pharmaceutically or cosmetically acceptable excipients and a transepidermal or transdermal carrier agent consisting of acidic electrolyzed water having a pH of 1.0 to 4.0 and comprising clusters of water, having 5 to 10 molecules of water per cluster, and a polyacrylate.

2. The composition of claim 1, wherein paracetamol is in an amount of 0.01 to 5% by weight, on the weight of the composition.

3. The composition of claim 2, wherein paracetamol is in an amount of 0.05 to 2% by weight, on the weight of the composition.

4. The composition according to any one of claims 1-3, wherein said polyacrylate is in an amount of 0.0001 to 5% by weight, on the weight of the transepidermal or transdermal carrier agent.

5. The composition of claim 4, wherein said polyacrylate is in an amount of 0.001 to 2% by weight, on the weight of the transepidermal or transdermal carrier agent.

6. The composition according to any one of claims 1-5, wherein said polyacrylate is sodium polyacrylate.

7. The composition according to any one of claims 1-6, wherein said acidic electrolyzed water is water that can be obtained by means of a process wherein a solution of distilled water and an electrolyte is subjected to electrolysis by applying a potential difference of 10-100 Volts.

8. The composition of claim 7, wherein said acidic electrolyzed water is obtainable by a process wherein a solution of bidistilled water and an inorganic salt at a concentration of 0.20-2.00 g/L is subjected to electrolysis by applying a potential difference of 30-100 Volts for a period of at least 5 minutes.

9. The composition according to any one of claims 1-8, wherein said acidic electrolyzed water has a pH of 2.0 to 3.0.

10. A pharmaceutical or cosmetic formulation comprising the transepidermal or transdermal topical composition of any one of claims 1 -9, and at least one pharmaceutical or cosmetic agent selected from wetting agent, soothing agent, softening agent, preservative agent, chelating agent, thickening agent, antioxidant agent and a mixture thereof.

1 1. The pharmaceutical or cosmetic formulation of claim 10, wherein said pharmaceutical or cosmetic agent is panthenol, glycerin, mannitol, sodium citrate, acetyl tetrapeptide-15, imidazolidinyl urea, phenoxyethanol, methyl-paraben, ethyl-paraben, propyl-paraben, butyl-paraben, EDTA, disodium EDTA, diglycerine, olive oil, salicylate de silanodiol, rice bran oil, oligosaccharide alpha-glucan, vitamin E, vitamin A, ascorbyl palmitate, lipoic acid, horse chestnut extract, Gingko Biloba extract, or tocopheryl nicotinate.

12. The pharmaceutical or cosmetic formulation of claim 10 or 11, further comprising hyaluronic acid.

13. Use of the cosmetic formulation of any one of claims 10-12, as an adjuvant in the treatment of skin lesions, arthritis, atopic dermatitis, wrinkles, liposclerosis, decubitus ulcers, varicose and diabetic ulcers.

14. The pharmaceutical formulation of any one of claims 10-12, for use as an adjuvant in the treatment of skin lesions, atopic dermatitis, wrinkles, liposclerosis, decubitus ulcers, varicose and diabetic ulcers.