WO2014076533A1

WO2014076533A1 - Composition of a cleansing foam based on natural extracts for the cleansing of the anal area

Info

Publication number: WO2014076533A1
Application number: PCT/IB2013/002476
Authority: WO
Inventors: Vincenzo Russo
Original assignee: Vi.Rus Srl Unipersonale
Priority date: 2012-11-19
Filing date: 2013-11-07
Publication date: 2014-05-22
Also published as: ITBO20120631A1

Abstract

Composition in the form of rinse-off foam for the cleansing of the anal mucosa in the presence of proctologic pathologies and/or after surgical interventions. The composition comprises bisabolol in a quantity between 0.05% and 0.5%, escin in a quantity between 0.01 % and 0.5%, Calendula officinalis glycolic extract in a quantity between 0.1% and 5.0%, Centella asiatica glycolic extract in a quantity between 0.1 % and 10%, sweet almond oil in a quantity between 0.005%) and 0.2%, menthyl lactate in a quantity between 0.01% and 0.5%, peppermint essential oil in a quantity between 0.05% and 0.5%, chlorhexidine digluconate in a quantity between 0.1%) and 1%, glycerin in a quantity between 0.1% and 10%. Liquid soaps on the market, in order to carry out their cleansing action, must be applied by the user through a mechanical rubbing action on the inflamed and injured mucosa. This rubbing action turns out to be painful. The composition object of the invention is directly dispensed on the anal mucosa through the help of a gas mixture and cleans by staying in place for about 30 seconds, with no need to rub.

Description

DESCRIPTION

Attached to a patent application for INDUSTRIAL INVENTION entitled:

COMPOSITION OF A CLEANSING FOAM BASED ON NATURAL

EXTRACTS FOR THE CLEANSING OF THE ANAL AREA

*****

TECHNICAL FIELD

The present invention concerns the realization of a new formulation in the form of foam with soothing, protective and refreshing action which allows a gentle cleansing, without rubbing, of the anal mucosa. Such formulation is characterized by the association of bisabolol, escin, Calendula officinalis glycolic extract, Centella asiatica glycolic extract, sweet almond oil, glycerin, sodium lauroyl sarcosinate, cocamidopropyl hydroxysultaine, sodium cocoamphoacetate, menthyl lactate, peppermint essential oil, chlorhexidine digluconate, PEG- 12 dimethicone, citric acid, mixture of n-butane, isobutane and propane, water.

BACKGROUND ART

The hemorrhoidal disease accounts for over 90% of the problems related to the repairing process of the ano-rectal canal. The word hemorrhoids refers to the abnormal swelling of the hemorrhoidal veins, which are proximal to the anus. Hemorrhoids are one of the most common diseases and, despite being completely benign, they can cause discomforts which can limit the daily activities. They are more common in civilized countries, where an estimated 4-5 people out of 100 suffer from it; between 45 and 65 years hemorrhoids are more common and they affect 1 person out of 2. This disorder mainly affects pregnant women; in fact, during pregnancy the weakness of the tissues due to the hormonal changes of gestation, the increased pressure on the abdomen from the enlarging uterus and increased blood flow may easily result in hemorrhoids.

In rare cases, however, hemorrhoids may be a secondary manifestation of more serious diseases.

This disorder is mainly caused by the need and habit of "emptying" the rectal ampulla, the natural container of stools, only when there is the condition for doing it. This mechanism causes an overload of the anal region, worsened by the force of gravity, and then the stagnation of blood in the hemorrhoidal veins. If the tissue surrounding these veins is not sufficiently stable, the veins can also break down and slide downwards , up to developing the hemorrhoids.

The main symptoms are:

• Sensation of heaviness and discomfort in the anal area, associated with difficulty in evacuation.

• Tenesmus, that is the sensation of a desire to defecate when the defecation has been completed.

• Loss of blood in the hemorrhoids. It mostly appears at a later time when the sensation of swelling near the anus has already come out. The bleeding associated with hemorrhoids is generally very limited, and it occurs after the evacuation.

· Severe pain. This should lead to think that the situation is worsening, because normally the pain is almost completely absent and when it appears it is an indication of a hemorrhoidal "crisis". This condition is due to the protrusion of • the swelling veins through the anal canal. When this happens, the "swollen" veins are compressed by the anal sphincter, and thus they cause pain. The aggravation may also cause complications, which may be potentially very serious, such as the "throttling" of hemorrhoids.

Hemorrhoids are classified according to the degree of bleeding and severity of prolapse, in particular:

• First-degree hemorrhoids: they are completely internal in the anal canal . They may bleed, but do not protrude outside, even during exertion or emission of stools.

Generally, at this stage, they do not cause discomfort and pain.

• Second-degree hemorrhoids: they have an increased volume resulting from the increased venous pressure caused by a muscular strain. They tend to come out (prolapse) from the anal canal, but they reduce and retract spontaneously in the canal when the stimulus is over.

• Third-degree hemorrhoids: they prolapse outside spontaneously or under strain and must be pushed back into the anal canal by hand.

• Fourth-degree hemorrhoids: they are permanently prolapsed outside and they can no longer be pushed back by hand.

At this stage the pain and other symptoms are very distressing and they affect the quality of life of the person who suffer from them.

Frequently, hemorrhoids have complications such as:

• chronic constipation, due to an attempt to avoid discomfort during defecation;

• itching in the anus, due to local circulatory problems. Sometimes the circulatory difficulties may contribute to the onset of small eczema around the anal area.

Hemorrhoids are an anatomical alteration, and as such they can't be completely eliminated with medicines only. The drugs, used both locally and systemically, can keep the situation under control and reduce the risk of complications, but they can't correct the structural modification of the veins. Therefore, the treatment should be chosen on a case by case basis, according to the condition.

Generally, in the early stages, a regular application of ointments, gels or ointments containing lubricants and emollients decreasing the mechanical strain during defecation can be useful, but also containing anaesthetics to relieve the pain. In addition, they may be associated with drugs for the venous circulation, in order to reinforce the walls and, if necessary, with derivatives of cortisone, in order to control the inflammation associated with the venous swelling. Through this medical approach, and by paying close attention to the hygiene, it is possible to delay the need for surgical treatment which is the treatment of choice for third and fourth degree hemorrhoids, while first and second degree hemorrhoids (and the third degree waiting for a decisive operation), which are, by the way, the most common forms of clinical observation, are well suitable for medical treatment.

The usual hygienic-dietetic measures, such as the introduction of fiber and liquids in the diet associated with a proper local hygiene, should be recommended together with the pharmacological treatment.

In association with the topical or systemic drugs, it is useful to maintain a proper local hygiene through the use of cleansers containing active substances to be applied directly in the area to be treated in order to soothe and refresh the inflamed area. Proctitis, cnptitis, anal fissures, fissures, perianal fistulas are others and less common 95 proctologic diseases.

Proctitis may have an unknown etiology (eg., ulcerative proctitis or Crohn's disease) or can result from sexually transmitted diseases or other infections (eg., Campylobacter, Shigella, Salmonella). The patient suffers from rectal bleeding or secretion of mucus often associated with anorectal pain, symptoms of an inflamed 100 rectal mucosa.

Criptits are another less common pathology, which causes pain in the anal area during evacuation.

Anal fissure is a small "nick" on the homonym opening, due to excessive dilation during the passage of stools. Here, the presence of many nerve endings makes this 105 disorder particularly irritating and painful. The pain typically begins during or immediately after defecation, lasts for several hours and then ceases until the following evacuation.

An aggravation of the anal fissure leads to an acute fissure.

The perianal fistulas consists in the formation of a tube-shaped canal that opens 1 10 between the anal canal on one side and, usually, the perianal skin on the other side.

Even for these proctological diseases it is important to maintain a proper daily hygiene through the use of specific cleansers.

DISCLOSURE OF INVENTION

The composition object of the invention is proposed in the form of rinse-off foam for 1 15 topical use, indicated for the daily cleansing of the anal mucosa in particular after surgical interventions and/or in the presence of proctological diseases in order to maintain a proper hygiene in the area. To date the liquid soaps on the market, in order to carry out their cleansing action, must be applied by the user through a mechanical rubbing action on the inflamed and

120 injured mucosa. This rubbing action turns out to be painful in the presence of proctological diseases or after surgery. The foam formulation object of this invention is dispensed directly on the anal mucosa and it carries out its cleansing action by staying in place for about 30 seconds with no need to rub. Consequently, the formulation gently cleanses the inflamed surface and carries out a refreshing action

125 of the anal mucosa, thus avoiding an increase of the irritation and giving a sensation of immediate relief.

Bisabolol, one of the most important active ingredients of camomile (Matricaria recutita), has known calming and soothing properties (Guy P.P. Kamatou, Alvaro M. Viljoen. A review of the application and pharmacological properties of bisabolol and 130 bisabolol-rich ils. Journal of the American Oil Chemists ' Society, Volume 87, Issue 1, January 2010, Pages 1-7).

Escin is a mixture of saponins (terpene glycosides) extracted from the Aesculus hippocastanum with soothing, anti-edemigenous and vasoprotective action (A. Bruni. Farmacognosia Generale e Applicata. Piccin Nuova Libraria, 1999, p.339).

135 The anti-edemigenous and soothing activity of escin is due to its action on the vascular walls. In case of increased permeability due to inflammation, escin reduces the exudation, by limiting the extravasation of liquids in the tissue and by accelerating the absorption of the exiting edema. Escin increases the resistance of the involved capillaries, by changing their permeability, thereby reducing the passage of

140 liquids from capillaries to tissues.

The β-escin, in particular, is considered the main molecule responsible for the vasoprotective effects with a trophic effect on the microcirculation (Cesare R. Sirtori. Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacological Research Volume 44, Issue 3, September 2001, Pages 183-193).

145 The extract of Calendula officinalis is rich in triterpenes, flavonoids, polysaccharides, carotenes and phytosterols. It has remarkable soothing properties thanks to its unsaponifiable component constituted by flavonoids and mucilages. The active ingredients of the extract of Calendula officinalis, the flavonoids in particular, have a soothing effect on the inflamed and sensitive skin, stimulate the re-

150 epithelialization, accelerate the epidermal turn-over and promote the activity of the fibroblasts of the dermis by helping the synthesis of collagen (Leila Maria Leal Parente, Ruy de Souza Lino Junior, Leonice Manrique Faustino Tresvenzol, Marina Clare Vinaud, Jose Realino de Paula, and Neusa Margarida Paulo. Wound Healing and Anti-Inflammatory Effect in Animal Models of Calendula

155 officinalis L. growing in Brazil. Evidence-Based Complementary and Alternative Medicine, Volume 2012).

The extract of Centella asiatica contains many active ingredients, such as tannins, flavonoids, sugars, free acids and terpenes with important antioxidant, wound healing, vasoprotective functions. It has been demonstrated that Centella asiatica 160 improves the microcirculation, capillary flow and vascular tone, and reinforces the connective tissue of the perivascular amorphous substrate even in the case of hemorrhoids (MacKay D. Hemorrhoids and varicose veins: a review of treatment options. Alternative Medicine Review: a Journal of Clinical Therapeutic 2001, 6(2): 126-140).

165 Sweet almond oil contains many vitamins (A and B), carbohydrates, proteins and minerals, and has emollient, softening, soothing and nourishing properties. It is useful for softening the skin, for the treatment of redness and cracking, for the protection of the delicate skin and for helping to reduce the scars (Ahmad Z. The uses and properties of almond oil. Plastic and Reconstructive Surgery, Salisbury General 170 Hospital, Salisbury, Wiltshire, UK. Complement Ther Clin Pract. 2010 Feb; 16(1): 10-2).

Sodium lauroyl sarcosinate, also known as sarkosyl, is an anionic surfactant with excellent cleaning properties (Lu Yun Chen Yanni Wu Hao Xiao Shenxiu. Sodium Lauroyl Sarcosinate. Fine and Specialty Chemicals 2001 -13).

175 Cocamidopropyl hydro ysultaine and sodium cocoamphoacetate both belong to the class of amphoteric surfactants. This type of surfactants have less cleansing power and less foaming characteristics than the other types of surfactants, but they are less aggressive and are irritating in a limited way (Blake-Has kins, JC, Scala, D, Rhein, LD, Robbins, CR. Predicting surfactant irritation from swelling response of a

180 collagen film. J Soc Cosmet Chem 37: 199-210, 1986).

Cocamidopropyl hydroxysultaine is used as a foam booster, viscosity builder and antistatic agent (Guin JD. Reaction to cocamidopropyl hydroxysultaine, an amphoteric surfactant and conditioner. Contact Dermatitis 42 (5): 284, 2000).

Sodium cocoamphoacetate, derived from coconut oil, has a foam booster and

185 conditioning power. Thanks to its sweetness and its ability to promote the "sliding" of the product on the skin, it makes the product more easy to apply and rinse.

The action of amphoteric surfactants on the damaged skin and mucosa is less aggressive than that of anionic surfactants, for this reason the two compounds are mixed together in the formulation. 190 Menthyl lactate is an ester obtained from two molecules of natural origin, menthol and lactic acid.

Its component in lactic acid maintains the pH of the skin to physiological levels. The menthol stimulates the cold receptors of the skin.

Since it is a derivative of menthol, its refreshing action is more delicate and therefore 195 more pleasant (XIE Wei-yue, SHE Guang-qian, FENG Zhang-ming, NIE Hui, JIANG You-qing. Synthesis of L-menthyl lactate and its applications in personal care products. China Surfactant Detergent & Cosmetics, 2009-04). It does not change the skin temperature, but gives a sensation of natural freshness.

The peppermint oil is used, in association with methyl lactate, because of its delicate 200 refreshing action (Damonte SP, Selem C, Parente ME, Ares G, Manzoni AV.

Freshness evaluation of refreshing creams: influence of two types of peppermint oil and emulsion formulation. J Cosmet Sci. 2011 Nov-Dec;62(6):525-33).

Chlorhexidine digluconate carries out a preservative action thanks to its antiseptic, disinfectant, bacteriostatic and fungistatic properties. Chlorhexidine digluconate is a 205 good alternative to the available antiseptics for the skin, since it has a fast broad- spectrum antimicrobial action, with an extremely low potential to stimulate the skin reactions {Rosenberg A, Alatary SD, Peterson AF. Safety and efficacy of the antiseptic chlorhexidine gluconate. Surgery, Gynecology & Obstetrics 1976, 143(5): 789-92).

210 MODE FOR CARRYING OUT THE INVENTION

The foam formulation is dispensed through the help of a gas mixture (n-butane, isobutane, propane), which allows the application of the product directly on the area to be cleansed, with no need to touch the inflamed and/or damaged surface. The composition according to the invention contains:

- from 0.05% to 0.5% of bisabolol

- from 0.01 % to 0.5% of escin

from 0.1 % to 5% of Calendula officinalis glycolic extract

from 0.1%) to 10% of Centella asiatica glycolic extract

- from 0.005% to 0.2% of sweet almond oil

- from 1 % to 40% of sodium lauroyl sarcosinate

from 1% to 15%) of cocamidopropyl hydroxysultaine

from 1%) to 10%) of sodium cocoamphoacetate

- from 0.01%) to 0.5% of menthyl lactate

from 0.05%) to 0.5%> of peppermint essential oil

- from 0.1%) to 1% of chlorhexidine digluconate

- from 0.1 % to 10% of glycerin

- from 0.1% to 2% of PEG- 12 dimethicone

- from 0.1 % to 2% of citric acid

- from 4%) to 10%> of mixture of n-butane, isobutane and propane

- from 20% to 60% of water

A particularly preferred example for a composition in the form of rinse-off foam for topical use, indicated for the cleansing of the anal mucosa contains the following substances:

- 0.10% di bisabolol

- 0.05% of escin

1.00% of Calendula officinalis glycolic extract

1.00%) of Centella asiatica glycolic extract 0.01% of sweet almond oil

20.00% of sodium lauroyl sarcosinate

8.00% of cocamidopropyl hydroxysultaine,

8.00% of sodium cocoamphoacetate

0.15% of menthyl lactate

0.20% of essential oil

0.45% of chlorhexidine digluconate

5.00% of glycerin

0.45% of PEG- 12 dimethicone

0.32% of citric acid

7.00% of mixture of n-butane, isobutane and propane 48.27% of water

Claims

1. Composition comprising bisabolol, escin, Calendula officinalis glycolic extract, 255 Centella asiatica glycolic extract, sweet almond oil, menthyl lactate, peppermint essential oil, chlorhexidine digluconate, glycerin, in the following concentrations:

- bisabolol in a quantity comprised between 0.05% and 0.5%;

- escin in a quantity comprised between 0.01 % and 0.5%;

- Calendula officinalis glycolic extract in a quantity comprised between 0.1 % and 260 5.0%;

- Centella asiatica glycolic extract in a quantity comprised between 0.1 % and 10%;

- sweet almond oil in a quantity comprised between 0.005% and 0.2%;

- menthyl lactate in a quantity comprised between 0.01% and 0.5%;

265 - peppermint essential oil in a quantity comprised between 0.05% and 0.5%;

- chlorhexidine digluconate in a quantity comprised between 0.1 % and 1 %;

- glycerin in a quantity comprised between 0.1 % and 10%.

2. Composition, as claimed in claim 1, in the form of rinse-off foam for topical use.

3. Composition, as claimed in claims 1 and 2, for the cleansing of the anal mucosa in the presence of proctologic pathologies and/or after surgical interventions.

4. Composition, as claimed in claims 1, 2 and 3, which is directly dispensed on the anal mucosa through the help of a gas mixture and which cleanses by staying in place for about 30 seconds, with no need to rub.

5. Composition, as claimed in claims 1, 2, 3 and 4, containing:

- 0.10% of bisabolol;

- 0.05% of escin; 1.00% of Calendula officinalis glycolic extract;

1.00% of Centella asiatica glycolic extract;

0.01 % of sweet almond oil;

20.00% of sodium lauroyl sarcosinate;

8.00% of cocamidopropyl hydroxysultaine;

8.00% of sodium cocoamphoacetate;

0.15% of menthyl lactate;

0.20% of peppermint essential oil;

0.45% of chlorhexidine digluconate;

5.00% of glycerin;

0.45% of PEG- 12 dimethicone;

0.32% of citric acid;

7.00% of n-butane, isobutane, propane mixture; 48.27% of water.