WATER HOMEOSTASIS OF THE SKIN

The present invention relates to topical compositions comprising Ν,Ο-carboxymethylchitosan and sucrose octasulfate sodium or potassium salt as active ingredients. The compositions of the invention are useful for maintaining and restoring the water homeostasis of the skin, and can be used in dermatology and cosmetology.

Prior art

Transepidermal water loss (TEWL) is a physiological phenomenon consisting of continuous diffusion of water from the deepest layers to the outermost layers of the skin, where the water evaporates; said physiological process ensures the water homeostasis, which is crucial to maintain the integrity, health and good condition of the skin.

However, various chemical, physical, environmental and pathological causes can alter the water homeostasis of the skin with sometimes serious repercussions on its integrity, health and appearance.

A correct water homeostasis allows the performance of the physiological functions of the skin, such as the barrier function, which counteracts excessive evaporation of water originating from the deepest layers of the skin. Conversely, when the water homeostasis is incorrect, the skin lacks plasticity and elasticity, and cannot effectively prevent the penetration of aggressive, allergenic, irritant and toxic foreign substances. An altered skin water homeostasis predisposes the individual to numerous disorders, such as local irritative conditions, redness caused by nappies or clothes rubbing, by stagnation of bodily fluids or by burns, bedsores, vascular disorders and early skin aging.

In order to restore and maintain the correct water homeostasis of the skin, compounds are used which are classified according to their function, for example occluding substances such as oils or silicones; hydrating and hygroscopic substances; lipid substances that restore the barrier function; and substances that stimulate deep hydration. However, said substances can have adverse effects; for example, occluding substances prevent the physiological evaporation of the water in the outermost layers of the skin (TEWL), leading to alteration of the surface cells and imbalance of the cutaneous microbial flora, with a consequent risk of bacterial, fungal or viral infections. Hygroscopic substances can irritate the skin over time; barrier function regulators, which basically have a lipid nature, readily break down, leading to the formation of irritant and toxic substances, and deep hydration stimulants can interfere with the physiological composition of the skin.

Description of the invention

It has now surprisingly been found that the combination of

Ν,Ο-carboxymethylchitosan and sucrose octasulfate in the form of water-soluble salts slows but does not prevent TEWL, thus giving rise to marked, lasting hydration of the skin by the water deriving from the physiological function of TEWL (endogenous water).

The combination of the invention also lacks the adverse effects of the skin hydration compounds known to date.

Ν,Ο-Carboxymethylchitosan (NOCMC) is a known compound whose preparation is reported in US 4,619,995. It is readily available on the market, for example from Heppe Medical Chitosan GmbH, under the trademark Chitoceuticals®.

NOCMC is known in the odontostomatological field for its hydrating and film- forming properties, protection of the mucosa against pathogens, and buffering of the physiological pH of the oral cavity.

The sucrose octasulfate (SOS) aluminium salt/complex, known as sucralfate, has long been used in gastroenterology in the treatment of duodenal and gastric ulcers and oesophagitis, in maintenance treatment of peptic ulcers, and in the treatment and prophylaxis of chemotherapy-induced stomatitis.

When applied by external topical administration, SOS as aluminium salt/complex is used in skin and mucosa treatment compositions for its wound-healing, anti-inflammatory and protective properties. SOS as aluminium salt/complex is not suitable for the purposes of the invention, because it is practically insoluble in water and has no hydrophilic properties, unlike its sodium or potassium salts, which exhibit a high level of water-solubility and no topical or systemic toxicity.

The sodium salt is readily available on the market, in solid form or aqueous solution. A 20% w/w aqueous solution is marketed by Euticals S.p.A. (Lodi, Italy).

Disclosure of the invention

It has now been found that the combination of Ν,Ο-carboxymethylchitosan and sucrose octasulfate sodium or potassium salt has advantageous properties associated with a synergic effect on hydrophilia, which allows water to be absorbed and retained effectively, slowing transepidermal water loss without preventing it.

The object of the invention is therefore topical compositions designed to be applied to the skin and mucosa, comprising Ν,Ο-carboxymethylchitosan and sucrose octasulfate sodium or potassium salt as active ingredients, mixed with appropriate excipients and/or carriers suitable for cosmetic and/or dermato logical use.

The compositions of the invention are particularly suitable for use in the paediatric and geriatric fields.

Ν,Ο-Carboxymethylchitosan is present in the compositions of the invention in percentages ranging between 0.005%) and 8% by weight, preferably between 0.009%) and 5%) w/w, and more preferably between 0.010%> and 3%.

Sucrose octasulfate sodium or potassium salt is present in the compositions of the invention in percentages ranging between 0.010%> and 5.0%> by weight, preferably between 0.050%> and 3.0%>, and more preferably between 0.100%> and 1.0%.

The compositions of the invention can contain other active ingredients commonly used in dermatology and cosmetology, and can be prepared by conventional methods such as those described in Remington, The Science and Practice of Pharmacy, 20th Edition, using suitable excipients or carriers, as described, for example, in Handbook of Pharmaceutical Excipients, 6th Edition, Pharmaceutical Press. Examples of preferred formulations are lotions, gels, oil in water (o/w) or water- in-oil (w/o) emulsions, creams, ointments, sprays and foams. Compositions containing water as carrier are particularly preferred.

The examples given below further exemplify the invention.

The percentages are expressed as parts by weight of the total volume of the composition

Example 1 - Liquid composition

Sucrose octasulfate sodium salt 1.000%

Ν,Ο-Carboxymethylchitosan 3.000%

Preservative q.s.

Purified water q.s. to 100%

Example 2 - Gel composition

Sucrose octasulfate potassium salt 0.100%>

Ν,Ο-Carboxymethylchitosan 0.010%

Hydroxyethylcellulose 3.000%

Preservative q.s.

Purified water q.s. to 100%

Example 3 - Cream composition

Sucrose octasulfate sodium salt 0.500%)

Ν,Ο-Carboxymethylchitosan 0.300%

Squalane 5.000%

Lactic acid q.s. to pH 5.5

Salcare SC91 3.000%

Preservative q.s.

Purified water q.s. to 100%) Example 4 - Spray composition for preventing bedsores

Sucrose octasulfate sodium salt 0.250%

Ν,Ο-Carboxymethylchitosan 0.500%

Distilled chamomile water 5.000%

Distilled witch-hazel water 5.000%

Horse-chestnut mother tincture 10.000%

Preservative q.s.

Purified water q.s. to 100%

Example 5 - Composition for paediatric use

Sucrose octasulfate sodium salt 0.250%

Ν,Ο-Carboxymethylchitosan 0.100%

Distilled cornflower water 5.000%

Distilled chamomile water 5.000%

Allantoin 0.100%

Preservative q.s.

Sepigel 305 3.000%

Purified water q.s. to 100%

Example 6 - Composition for geriatric use

Sucrose octasulfate sodium salt 1.000%

Ν,Ο-Carboxymethylchitosan 1.000%

Sodium pyrrolidone carboxylate 0.100%

Alpha-tocopherol 0.050%

Glycyrrhetic acid 0.050%

Allantoin 0.050%

Lactic acid q.s. to pH 5.i

Squalane 7.000%

Salcare SC 91 2.500%

Preservative q.s.

Purified water q.s. to 100%