ITUB20159582A1 - Composition, for topical use, useful for the prevention of inflammatory and / or infectious mucosal disorders. - Google Patents

Description

FIELD OF THE INVENTION

The present invention relates to a new composition for topical use, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, essential oil extracted from the Melaleuca plant (hereinafter referred to as "tea tree oil) and Hypericum oil, useful for the prevention of inflammatory and / or infectious disorders of the mucous membranes.

In particular, the present invention relates to a new composition for topical use, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, useful for the prevention of inflammatory and infectious disorders both vulvar and of the external anal sphincter.

Vulvar inflammations and infections affect the vaginal mucosa and vulva. After menopause, the vagina and vulva can undergo an involution linked to the lack of estrogen, although this process is not the same in all women, many can complain of dryness and pain in intercourse. This is due to a thinning of the mucosa which loses its surface cells and reduces its elastic component and consequently causes a reduction in lubrication and a decrease in the extensibility of the vagina as a whole which causes problems / disturbances in sexual intercourse.

Many women, both young and in menopause, are affected by bacterial vaginosis, this is a female disease in which the normal vaginal ecosystem is altered and some bacteria proliferate more than normal. The most frequent symptoms of these disorders are losses, even foul-smelling, pain, itching or irritation. Bacterial vaginosis is the most common vaginal infection among women of childbearing age and also frequent among pregnant women. This disorder accounts for about 60% of all vulvo vaginal infections. At the local level, the concentration of anaerobic pathogens such as Bacteroides sp, Peptostreptococcus sp, Gardnerella vaginalis and G. mobiluncus, increases ten to one hundred times. Risk factors for developing this infection include the presence of a sexually transmitted disease, numerous sexual partners, and the use of an intrauterine contraceptive device (IUD).

Yeast or fungal infections account for 30-35% of vaginal infections and most of them are due to Candida albicane. Yeasts colonize 15-20% of non-pregnant women and 20-40% of pregnant women. Typical symptoms include vaginal itching with or without vulvar itching, burning or irritation.

The symptoms of vaginal Candida infections are quite varied; the main symptom is certainly itching, possible, albeit rare, burning (more frequent, however, in infections with Candida glabrata). Dyspareunia and dysuria are often reported.

Dyspareunia described as a recurrent or persistent genital pain that appears during sexual intercourse, from which a large number of women suffer, finds its etiology in numerous biological causes. It affects 15-19% of women of childbearing age and up to 33-39% of postmenopausal women. In relation to the location of the pain, three types of dyspareunia can be distinguished:

• introital or superficial

• mediovaginal

• deep

Introital and mediovaginal dyspareunia cause "pain at the onset of sexual intercourse <55> and can be caused by infections (in more than half of cases there is a history of chronic candida, and often of recurrent bacterial infections and / or vaginosis), inflammation and / or poor lubrication of the vaginal mucosa.

Hemorrhoids are inflammations of the external anal sphincter that cause pain due to swelling of the veins around or inside the anal sphincter.

The fissures are small but deep skin erosions, which can affect various body regions and in particular the anus. Specifically, the anal fissure is a small "cut" that is created on the homonymous opening, due to excessive dilation during the passage of feces. Here the presence of abundant nerve endings makes the disorder particularly irritating and painful. The painful pangs become more intense at the time of defecation, especially when hard and bulky stools are expelled which, by friction, favor the lesion of the anal folds. In addition to aggravating this annoying disorder, constipation is also one of the main causal agents.

Given the spread of the problem of constipation, it is therefore not surprising that anal fissures are a frequently encountered condition in proctological practice.

Perianal abscesses are generally an inflammatory reaction of the organism to the development of certain bacteria (staphylococci, streptococci), which, carried by the blood or lymphatic circulation, reach the anus where they cause an acute infection. An abscess is the last stage of a tissue infection that begins with an inflammatory process. Many different agents can cause abscesses, the most common being pus-forming bacteria (pyogens), such as Staphylococcus aureus, which is almost always the cause of abscesses under the skin. Abscesses around the anus can be caused by any of the numerous bacteria found within the large intestine.

Further inflammation and infections of the external anal sphincter can be caused by gonorrhea, chlamydia, herpes, psoriasis or dermatitis.

These mucosal disorders are well known to those skilled in the art. Allantoin is the final product of the oxidation of uric acid which is catalyzed by the enzymes urate oxidase and 5-hydroxyurate hydrolase. In nature it is found in the borraginacea plant Symphytum officinale L., but the synthetic one is usually used. Allantoin is active at low concentrations (0.1-0.5%) as a moisturizer and anti-reddening, while at higher concentrations (1-5%) it has action and displacing and is able to promote cell proliferation.

Allantoin, thanks to its various functions, can be used in after-shave products, in paidosmetics and in formulas intended to alleviate skin imperfections such as acne, boils, wrinkles, burns, scars and bruises. Classified by the FDA (Food and Drug Administration) as a safe and effective substance as a skin protector.

Calendula officinalis is an annual herbaceous plant, known for a long time by the name of "orange flower". The stems of the marigold can reach a height of about 70 cm and have various ramifications, at the end of which yellow-orange flowers are gathered in flower heads; it is the latter that constitute the drug of cosmetic and phytotherapeutic interest obtained from the plant. The flowers of the calendula contain essential oil consisting of over 45 substances including Flavonoids, Triterpenoids, Sterols, Carotenoids and Pyrogallic Tannins.

Calendula is known to be useful for treating skin infections, for skin care and cleaning, for accelerating wound healing, for lowering blood cholesterol and triglyceride levels and as an adjunct in care to promote regularization of the menstrual cycle, particularly in women who are anemic and prone to nervous breakdowns; it also alleviates menstrual pains, pressure sores.

"Tea tree oil" is also known as "tea tree essential oil" and is extracted from the leaves of the Melaleuca alternifolia tree, a plant species native to Austraba. Tea tree essential oil comes in natural cosmetics for its healing and disinfectant properties such as antibacterial, healing, antifungal and anti-odorant, as well as in household cleansing.

St. John's wort (hypericum perforatum) is also called St. John's wort or witch's wort. From St. John's wort flowers an intense red oil is obtained which is used directly on the parts to be treated. St. John's wort oil is known for its healing properties in case of burns, scalds, wounds and pressure sores; emollient, antiseptic (antiviral and antifungal), anesthetic, astringent, purifying, decongestant, anti-inflammatory and stimulating cell regeneration.

TECHNIQUE NOTE

US201 10152335A1 describes the use of allantoin in cosmetic compositions for topical use for skin protection, in combination with anionic and non-anionic emulsifiers, and further comprising anionic polymers, antioxidant herbal extracts and excipients.

WO 2005063266 A1 describes the use of calendula officinalis in combination with hypericum perforatum in pharmaceutical compositions for the treatment of dermatoses.

US7311928B2 describes the topical use of "tea tree oil" for the treatment of viral lesions caused by molluscum contagiosum, papillomavirus and / or herpes simplex virus.

Further publications mention the use of these compounds for medical and cosmetic uses, but none of these publications describes or suggests the composition according to the invention for the claimed uses.

DESCRIPTION OF THE INVENTION

It has now been found that a composition for topical use, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, shows an unexpected synergism in the prevention or to soothe vulvar and anal mucosal disorders caused by inflammatory and / or infectious processes.

The object of the present invention is therefore a composition which can be administered topically, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, and one or more pharmaceutically acceptable excipients and / or diluents.

A further object of the present invention is a composition that can be administered topically, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil,

in which:

- micronized allantoin is present at a dose of 0.05-5%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.5%,

- the alcoholic tincture of calendula is present at a dose of about 0.15-15%, preferred is a dose of about 1-10%, much preferred is a dose of 1.5%;

- tea tree oil is present at a dose of 0.05-5%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.5%;

- Hypericum folio is present at a dose of 0.04-4%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.4%;

and one or more pharmaceutically acceptable excipients and / or diluents.

A further object of the present invention is a composition that can be administered topically, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, and one or more pharmaceutically acceptable excipients and / or diluents, useful in prevention or to soothe vulvar and anal mucosal disorders caused by inflammatory and / or infectious processes.

A further object of the present invention is a composition which can be administered topically, comprising:

Micronized allantoin at a dose of 0.5%

Tea tree oil at a dose of 0.5%

Alcoholic tincture of calendula at a dose of <5> 1.5%

Hypericum oil at a dose of 0.4%

Vegetable glycerol at a dose of <5> 81.6%

Carbopol 940 at a dose of 0.5%

Purified water 15%

Triethanolamine to taste at pH 5.5.

A further object of the present invention is a composition for topical use, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, for use to prevent or soothe lesions and / or disorders of the vulvar mucosa and anal caused by inflammatory and / or infectious processes.

A further object of the present invention is topical buso of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, for the preparation of a composition useful for preventing or soothing disorders or lesions of the vulvar or anal mucous membranes caused by inflammatory and / or infectious processes.

A further object of the present invention is topical buso of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, for the preparation of a composition useful for preventing or soothing lesions or disorders of the vulvar mucosa selected from the group consisting of of vaginal sores, lesions or cracks, vaginal pain, dyspareunia, vaginal dryness and vaginal itching.

A further object of the present invention is a topical buso of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, for the preparation of a composition useful for preventing or soothing lesions or disorders of the anal mucous membranes selected from the group consisting of of fissures, hemorrhoids, anal pain and anal itching.

A further object of the present invention is topical buso of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, for the preparation of a composition with a healing action of anal or vulvar lesions selected from the group consisting of lesions, sores, cracks or fissures.

A further object of the present invention is topical buso of the

- micronized allantoin at a dose of 0.05-5%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.5%,

- alcoholic tincture of calendula at a dose of about 0.15-15%, preferred is a dose of about 1-10%, much preferred is a dose of <5> 1.5%;

- tea tree oil at a dose of 0.05-5%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.5%;

St. John's wort oil at a dose of 0.04-4%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.4%;

and one or more pharmaceutically acceptable excipients and / or diluents,

for the preparation of a composition useful for preventing or soothing disorders or lesions of the vulvar or anal mucous membranes caused by inflammatory and / or infectious processes.

A further object of the present invention is the topical use of

Micronized allantoin at a dose of 0.5%

Tea tree oil at a dose of 0.5%

Alcoholic tincture of calendula at a dose of <5> 1.5%

and one or more pharmaceutically acceptable excipients and / or diluents, for the preparation of a composition useful for preventing or soothing disorders or lesions of the vulvar or anal mucous membranes caused by inflammatory and / or infectious processes.

A further object of the present invention is the topical use of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, for the preparation of a cosmetic or pharmaceutical composition, further comprising anionic polymers, antioxidant herbal extracts and excipients. .

A further object of the present invention is the topical use of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, for the preparation of a cosmetic or pharmaceutical composition, in solid, semi-solid, liquid or spray form. .

A further object of the present invention is the topical use of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, for the preparation of a cosmetic or pharmaceutical composition, in the form of lotion, ointment, semi-fluid cream. , fluid cream, gel or spray.

The composition according to the present invention has been conceived in response to the need to favor the healing of lesions that occur in chronic pathologies and following oncological treatments that have the skin as primary target and support therapeutic protocols that of from time to time they are used on patients being treated for these skin disorders.

The composition according to the invention, for topical use, can be formulated as a pharmaceutical composition for medical or cosmetic use; or as a medical device to support the therapies for which it is indicated.

The pharmaceutical or cosmetic composition according to the invention may further comprise one or more skin disinfectants selected from the group consisting of chlorhexidine; chlorhexidine gluconate; trichloro 2-hydroxydiphenylether, detergent based on thyme extract, chamomile and zinc complex with acid pH, iodopovidone with active iodine, didecyldimethylammonium chloride or amuchins or their mixtures. The person skilled in the art will be able to recommend further disinfectants, in the required form, based on their experience and knowledge.

The pharmaceutical or cosmetic composition according to the present invention can further comprise one or more excipients and optionally one or more agents useful in the cosmetic field selected from the group consisting of:

a) a suitable surfactant selected from: sodium dodecyl sulfate; cationic surfactant based amino acid based on, for example, L-arginine, DL-pyrrolylone carboxylic, coconut fatty acids; o amino acids based on non-ionic surfactants;

b) Thickening agents, stabilizers, gelling agents, emulsifiers, moisturizers and / or pH regulators, such as for example xanthan, carrageenan, gelatin, karaya, pectin; vinyl polymers, carbopol; glycerol and / or Triethanolamine, in any proportion suitable and well known to the person skilled in the art; and

c) at least one active ingredient useful for the prevention or treatment of skin disorders chosen from:

- Agents that support microcirculation which include, but are not limited to, extracts of Gingko biloba, butcher's broom, sweet clover, red vine, viburnum;

- Lipolysis activating agents which include, but are not limited to, extracts of earth ivy (Glechoma), Angelica root, Paulinia extract, modest or xanthic bases such as caffeine, theobromine and theophylline;

- Anti-inflammatory compounds which include, but are not limited to, Γ rosmarinic acid, glycyrrizinate derivatives, alpha bisabolol, azulene and its derivatives, asiaticoside, sericoside, ruscogenin, aescin, escolin, quercetin, rutin, Betulinic acid and its derivatives, catechin and their derivatives;

- Skin stripping compounds which include, but are not limited to, ferulic acid, hydroquinone, arbutin and kojic acid;

- Antioxidants and anti-wrinkle compounds which include, but are not limited to, retinol and derivatives, tocopherol and derivatives, salicylates and their derivatives;

- Agents which improve the penetration of the active agents hence the pharmacological and cosmetic activity of the composition according to the invention which include, but are not limited to, monocarboxylic acids comprising glycolic acid, mandelic acid and their mixtures;

- Essential fatty acids (E FA) playing an important role in the defense of the skin against oxidative stress, entering the lipid biosynthesis of the epidermis and providing lipids for the formation of the epidermis barrier; The preferred essential fatty acids are selected from the group consisting of linoleic acid, gamma-linolenic acid, homo-gamma-linolenic acid, columbinic acid, eicosa- (n-6,9,13) -trienoic acid, arachidonic acid, gamma-linolenic acid. 'acid, timnodonic acid, hexaenoic acid and their mixtures; or

- Sunscreens, for example, derivatives of Para Amino Acid benzoic (PABA), cinnamate and benzophenone derivatives such as octyl methosynnamate and 2-hydroxy-4-methoxy-benzophenone; 3-hydroxy quynurenine (3-HKG) or their derivative;

The pharmaceutical or cosmetic composition according to the present invention can optionally contain:

- Useful agents to prevent the growth of microorganisms selected from the group consisting of: alkyl esters of p-hydroxybenzoic acid, hydantoin derivatives, propionate salts, methyl parabens, propyl parabens, imidazolidinyl urea, sodium dehydroxyacetate, benzyl alcohol, cetostearyl alcohol, tartrate potassium acid, sodium tartrate and quaternary ammonium compounds. Preservatives, if present, are added in any suitable proportion, well known to those skilled in the art; - Silicone polymers;

- Emollients, useful in the preparation of creams in which the active agents according to the present invention can be dissolved or dispersed. Said emollients can be present in the cosmetic composition of the invention in any suitable proportion, well known to the skilled in the art; examples of suitable emollients classified into general chemical categories are: esters, fatty acids and alcohols, polyols and hydrocarbons; examples of fats and esters include: dibutyl adipate, diethyl sebacate, diisopropyl dimerate, propylene glycol acetate myristyl ether, diisopropyl adipate, and dioctyl succinate; an example of branched chain fatty esters include 2-ethyl-hexyl myristate, isopropyl stearate and isostearyl palmitate; an example of tribasic acid esters include triisopropyl trilinoleate, trilauryl citrate, tributyrin, and saturated or unsaturated vegetable oils; examples of straight chain fatty esters include lauryl palmitate, myristyl lactate, oleyl eurcate, coco-caprylate / caprate stearyl oleate, and cetyl octanoate; an example of fatty and acidic alcohols are C10-C20 compounds such as cetyl, myristyl, paimitic and stearyl alcohols and acids; an example of polyols are linear and branched chain polyhydric alkyl compounds, such as propylene and butylene glycol, glycerin, sorbitol and polymeric polyols such as polypropylene glycol and polyethylene glycol; an example of hydrocarbons are linear C12-C30 hydrocarbon chains such as mineral oil, petroleum jelly, squalene and isoparaffins; water; dyes, opacifiers; perfumes. In accordance with the present invention, micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, in the form of a cosmetic or pharmaceutical composition, can be administered topically in the form of liquid, semi-liquid, cream or lotion. The topical composition of the present invention can be formulated in all cosmetic forms used in beauty care: lotion, fluid cream, cream or gel. The composition can be packaged in a suitable container based on the viscosity and intended use by the user. For example, a fluid lotion or cream may be packaged in a bottle, roll applicator, capsule, patch, aerosol device, or hand dispenser (finger operated mechanical pump).

When the composition according to the invention is in the form of a cream, it can be stored in a non-deformable bottle or in a compression container, for example a tube or a jar with a lid.

For each particular cosmetic form in accordance with the present invention, suitable excipients and / or diluents can be used, by way of example, the following can be mentioned: propylene glycol, glycerin, cetyl alcohol, cetostearyl alcohol, rosemary oil, potassium bitartrate, sodium tartrate, polyols, salicylic acid, lauric acid, parabens, methyl paraben, pro pii parabens, water, phospholipids in liposomes or not, vegetable and animal oils, minerals, preservatives, thickeners, stabilizers and emulsifiers, suitable for the purpose.

By “water <55>, according to the present invention we mean distilled water or mineral water, such as for example Vichy mineral / thermal water; or sulphurous and / or geothermal mineral waters such as mineral / thermal water containing hydrogen sulphide from the Smrdàky thermal baths (S K / Slovak Republic). In accordance with the present invention, the above-mentioned types of "mineral / low-mineral" water are used as diluents of the composition according to the invention.

The term "cosmetically acceptable ingredients" in accordance with the present invention includes products that are suitable for their use in cosmetic treatments, for example those included in the INCI list drawn up by the "Buropean Cosmetic Toiletry and Perfumery Association (COLIPA) and ìssued in 96 / 335 / EC "Annex to Commission Decision of 8 May 1996".

The following examples illustrate the invention without limiting it.

DETAILED DESCRIPTION OF THE INVENTION

EXAMPLE 1

Ability of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and hypericum oil, administered topically, to reduce the number of vaginal sores and / or to soothe vaginal dryness, vaginal itching and dyspareunia.

The topical efficacy of the administration of the composition according to the invention in the prevention or reduction of the number of sores and / or to soothe vaginal dryness, vaginal itching and dyspareunia (pain appearing at the beginning and / or during sexual intercourse), was evaluated on 30 women between the ages of 30 and 60 who regularly had at least two sexual intercourse per week. The subjects were selected based on the presence of the symptoms or disorders mentioned above.

All the subjects enrolled were healthy women in menopause and not, with no known allergies, in particular to cosmetic or toilet products; they did not show acute or chronic diseases; they were not pregnant or nursing; they weren't in any diet or weight reduction program. None of the subjects enrolled was affected by infections and / or cytological pathologies at the gynecological level (evaluated before the start of treatment by means of a suitable gynecological examination with "smear / sampling / vaginal examination).

Before the start of the treatment, 3 qualified technicians interviewed the selected women, taking note of the characteristics and intensity of the pain and the number of sore spots and their location. The selected persons were divided into three groups and treated with the preferred composition according to the present invention in the form of a gel, or with the same gel containing allantoin in combination with an alcoholic tincture of calendula; or with a gel containing tea tree oil and St. John's wort oil, at the same doses.

The subjects were treated for 3 weeks, topically locally on the vagina at least twice a day for three weeks.

Subjects were instructed not to use their normal pain reliever or lubricant products (to avoid confusion in interpretation of results), not to enter any diet or weight loss program, or any regular exercise program immediately before or during the course of the study.

Each subject was also instructed to keep a daily diary to document the compliance of the treatment and any perceived improvements.

The results obtained are reported in the following tables 1-2.

TABLE 1

DISPAREUNIA

(PAIN AT THE BEGINNING AND / OR DURING SEXUAL RELATIONSHIP - VALUE FROM 1-10)

INDIVIDUAL INVENTION

Allantoin Calendula N ° Tea tree oil Hypericum oil Allantoin Tea

tree oil Calendula (10 individuals) (10 individuals) Hypericum oil

(10 individuals)

START END START END START END

1 7 0 6 6 4 4

2 6 2 7 6 5 5

3 7 1 4 4 6 5

4 4 0 6 5 7 6

5 5 0 4 4 4 4

6 7 2 7 7 7 5

7 7 2 5 5 7 6

8 6 0 7 6 4 4

9 4 0 7 6 7 7

10 7 1 6 5 6 6 TABLE 2

NUMBER OF CRACKS / PEAK INJURIES / PI NEEDLES

Allantoin

Individual INVENTION Calendula Tea tree oil

N ° Allantoin Tea

tree oil Calendula Hypericum Oil (10 individuals)

Hypericum oil

(10 individuals) (10 individuals)

START END START END START END

1> 10 0 6 6 4 4

2 2 0> 10 9 7 7

3> 10 0 4 3 4 4

4 2 0 2 2> 10> 10

5 1 0 3 2 7 6

6 1 0> 10> 10> 10 9

7> 10 0 1 1> 10> 10

8 4 0> 10 8 4 4

9 5 0> 10> 10> 10 9

10> 10 0 5 5 4 4 The composition according to the invention shows an unexpected synergistic effect in the treatment of pain at the beginning or during sexual intercourse (dyspareunia) and in healing cracks and sores at the vaginal level, reducing them in a statistically significant way compared to use of single components or minimal combinations between them.

Furthermore, the individuals treated with the composition according to the invention reported having solved the problems of vaginal dryness and intimate itching (during the treatment period) while the subjects treated with the two minimum combinations did not find improvement of these two disorders.

In this experimental model, different minimum possible compositions, with one, two or three active elements, did not show any improvement compared to the complete composition according to the invention (data not shown).

EXAMPLE 2

Ability of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, administered topically in the perianal area, to heal fissures and to relieve pain caused by defecation.

The topical efficacy of the administration of the composition according to the invention in healing the fissures and relieving the pain caused by defecation was evaluated on 30 individuals of both sexes (60% women) and aged between 20 and 65 years.

All the subjects enrolled were healthy subjects, with no known allergies, in particular to cosmetic or toilet products; they did not show acute or chronic diseases; were not pregnant or nursing; they weren't in any diet or weight reduction program. None of the subjects enrolled was affected by infections and / or cytological pathologies in the vaginal and / or perianal area (evaluated before the start of treatment through a suitable visit and histological examination if necessary).

Before the start of treatment, 3 qualified technicians interviewed the individuals enrolled, taking note of the intensity of pain during defecation and the number of fissures. The subjects were divided into three groups and treated with the preferred composition according to the present invention in the form of a gel, or with the same gel containing allantoin in combination with an alcoholic tincture of calendula; or with a gel containing tea tree oil and St. John's wort oil, at the same doses.

The subjects were treated for 3 weeks, topically locally on the perianal area at least twice a day.

Subjects were instructed not to use their normal pain relievers (to avoid confusion in interpreting the results).

Each subject was also instructed to keep a daily diary to document the compliance of the treatment and any perceived improvements.

The results obtained are reported in the following tables 3-4.

TABLE 3

Individual PAIN DURING DEFECATION

No.

(VALUE FROM 1-10)

Allantoin

INVENTION Calendula

Tea tree oil

Allantoin Tea

tree oil Calendula Hypericum Oil (10 individuals)

Hypericum oil

(10 individuals) (10 individuals)

START END START END START END

1 7 0 7 6 4 4

2 7 1 6 6 7 5

3 9 1 7 5 6 6

4 6 0 4 4 8 6

5 5 0 7 5 4 4

6 9 1 5 5 7 5

7 9 0 8 6 7 6

8 7 1 7 6 7 5

9 6 0 7 6 7 6

10 9 2 7 6 6 6 TABLE 4

Individual NUMBER OF RAGADI

N ° Allantoin

INVENTION Calendula

Tea tree oil

Allantoin Tea

tree oil Calendula Hypericum Oil (10 individuals)

Hypericum oil

(10 individuals) (10 individuals)

START END START END START END

1 1 0 2 2 1 1

2 1 0 1 1 2 2

3 2 0 1 1 1 1

4 1 0 1 0 2 1

5 1 0 2 2 1 1

6 2 0 1 1 2 2

7 1 0 2 2 1 1

8 2 0 1 1 2 2

9 1 0 2 2 1 0

10 2 0 1 1 1 1 The results shown in Tables 3 and 4 show that the composition according to the invention shows an unexpected synergistic effect in the treatment of pain during defecation and in healing anal fissures significantly compared to the use of the single components or minimal combinations between them.

Also in this experimental model different minimum possible compositions, with one, two or three active elements did not show any improvement with respect to the complete composition according to invention (data not shown).

Allantoin, Tea tree oil, Calendula and St. John's Wort oil are compounds known in the art for use in humans, extensively tested, and readily available on the market.

Although the daily dose will depend, according to the judgment of the treating physician, on the basis of the weight, age and general condition of the subject, it is generally advisable to administer the composition according to the present invention more than once a day, topically, on the parts to be treated. .

Non-limiting examples of compositions according to the present invention (which can be administered topically) are reported below.

COMPOSITION 1 (preferred)

Micronized allantoin 0.5%

Tea tree oil 0.5%

Alcoholic tincture of calendula 1,5%

Hypericum oil 0.4%

Excipients and diluents.

COMPOSITION 2

Micronized allantoin 1% Tea tree oil 0.5% Alcoholic tincture of calendula 1, 5% Hypericum oil 0.4% Excipients and thinners.

COMPOSITION 3

Micronized allantoin 0.25% Tea tree oil 0.5% Alcoholic tincture of calendula 1, 5% Hypericum oil 0.4% Excipients and thinners.

COMPOSITION 4

Micronized allantoin 0.75% Tea tree oil 0.5% Alcoholic tincture of calendula 1, 5% Hypericum oil 0.4% Excipients and thinners.

COMPOSITION 5

micronized allantoin 0.05-5% calendula alcohol tincture 0.15-15% tea tree oil 0.05-5% St. John's wort oil 0.04-4% excipients and / or diluents.

COMPOSITION 6

Micronized allantoin 0.5%

Tea tree oil 0,5% Alcoholic tincture of calendula 1,5%

Hypericum oil 0.4% Vegetable glycerol 81.6% Carbopol 940 0.5% Purified water 15% Triethanolamine q.s. at pH 5.5.

Claims (10)

CLAIMS 1. Composition that can be administered topically, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, and one or more pharmaceutically acceptable excipients and / or diluents. 2. Composition of claim 1, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, in which: Micronized fallati toma is present at a dose of 0.05-5%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.5%, the alcoholic tincture of calendula is present at a dose of about 0.15-15%, preferred is a dose of about 1-10%, much preferred is a dose of <5> 1.5%; tea tree oil is present at a dose of 0.05-5%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.5%; Hypericum folio is present at a dose of 0.04-4%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.4%; and one or more pharmaceutically acceptable excipients and / or diluents. 3. The composition of claim 1, comprising: Micronized allantoin at a dose of 0.5% Tea tree oil at a dose of 0.5% Alcoholic tincture of calendula at a dose of <5> 1.5% Hypericum oil at a dose of 0.4% Vegetable glycerol at a dose of <5> 81.6% Carbopol 940 at a dose of 0.5% Purified water 15% T riethanolamine to taste at pH 5.5. and optionally and one or more pharmaceutically acceptable excipients and / or diluents. 4. Composition for topical use, comprising as active ingredients micronized allantoin in combination with alcoholic tincture of calendula, tea tree oil and St. John's wort oil, for use to prevent or soothe lesions and / or disorders of the vulvar and anal mucous membranes caused by inflammatory processes and / or infectious. 5. Use of micronized allantoin, in combination with alcoholic tincture of calendula, tea tree oil and hypericum oil, for the preparation of a composition, for topical use, useful for preventing or soothing disorders or lesions of the vulvar or anal mucous membranes caused by processes inflammatory and / or infectious, in which said disorders or lesions are selected from the group consisting of: vaginal sores, vaginal lesions, vaginal cracks, vaginal pain, dyspareunia, vaginal dryness and vaginal itching; anal fissures, hemorrhoids, anal pain or anal itching. Use according to claim 5, comprising: micronized allantoin at a dose of 0.05-5%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.5%, calendula alcohol tincture at a dose of about 0.15-15%, preferred is a dose of about 1-10%, very preferred is a dose of <5> 1.5 %; tea tree oil at a dose of 0.05-5%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.5%; St. John's wort oil at a dose of 0.04-4%, preferably at a dose of 0.1-1%; most preferably at a dose of 0.4%; and one or more pharmaceutically acceptable excipients and / or diluents. 7. Use according to claim 5, comprising: Micronized allantoin at a dose of 0.5% Tea tree oil at a dose of 0.5% Alcoholic tincture of calendula at a dose of <5> 1.5% Hypericum oil at a dose of 0.4% Vegetable glycerol at a dose of <5> 81.6% Carbopol 940 at a dose of 0.5% Purified water 15% Triethanolamine to taste at pH 5.5. Use according to claims 5-7, optionally further comprising microelements, polymers, anionic polymers, skin disinfectants, herbal extracts and antioxidants. Use according to claim 5-8, wherein the composition is for medical, cosmetic or medical device use, in solid, semi-solid, liquid or spray form. Use according to claim 9, in the form of lotion, ointment, semi-fluid cream, fluid cream, gel or spray.