WO2008047394A1

WO2008047394A1 - Composmons for eyelid and periocular hygiene with enhanced ocular and skin tolerability

Info

Publication number: WO2008047394A1
Application number: PCT/IT2007/000663
Authority: WO
Inventors: Giulia Falcone; Enrico Boldrini
Original assignee: Opocrin S.P.A.
Priority date: 2006-10-16
Filing date: 2007-09-25
Publication date: 2008-04-24
Also published as: ITRM20060557A1

Abstract

Cleansing emollient preparation for eyelid and periocular hygiene, consisting of an aqueous solution comprising, as main ingredients, one or more surfactants, one or more antiseptic or bactericide agents and one or more emollient agents, and containing α-bisabolol as the antiirritant agent. The composition is generally usable for daily eyelid and eyelash hygiene, but is particularly indicated for the treatment of inflammatory and infective pathologies such as blepharitis and blepharoconjunctivitis, due to its capacity to limit irritation and burning sensation. In particular, the product can be supplied in the form of packaged sterile gauzes or wipes premoistened with the concerned preparation.

Description

COMPOSITIONS FOR EYELID AND PERIOCULAR HYGIENE WITH ENHANCED OCULAR AND SKIN TOLERABILITY

The present invention concerns compositions for eyelid and pe- riocular hygiene with enhanced ocular and skin tolerability. More specifically, the invention concerns compositions indicated for deterging the ocular region and usable in general for the everyday hygiene of eyelids and eyelashes, but particularly suitable - owing to their capacity to limit irritation and burning sensations - for the treatment of inflammatory and infec- tive pathologies such as blepharitis and blepharoconjunctivitis, specially in the form of pads or wipes pre-moistened with the composition.

As is known, blepharitis is a widespread inflammatory pathology that involves redness, swelling, the formation of scabs, or even scales or ulcers, on eyelid margins, and may arise either alone or in combination with the inflammation of other surrounding regions such as the skin, conjunctiva and cornea. Anterior blepharitis, which mainly affects the front external part of the eyelids, normally arises with more marked symptoms in the morning, such as a burning sensation and localised itching accompanied by slight photophobia, and may be of bacterial, seborrheic or, less frequently, of mixed origin. Bacterial blepharitis is mostly caused by staphylococci which concentrate at the base of the eyelashes to cause the infection of the mucosa and of the surrounding skin, and leads to hyper- aemia with blood vessel dilatation (rosettes) and the appearance of hard and friable scales around the eyelashes. If removed, the scales could also reveal small bleeding ulcers beneath. Hypersensitivity to staphylococcus toxins can lead to papillary conjunctivitis, corneal epiteliopathy and marginal keratitis. Blepharitis of seborrheic origin is instead probably caused by a dysfunction of the secretion of the eyelids glands with an overproduction of fatty acids which causes the formation of greasy scaling. The lid margin appears greasy and the eyelashes greasy and matted. The scales are soft and evenly distributed, and do not leave ulcerations when removed. Posterior blepharitis affects the internal part of the eyelid and is caused by dysfunctions of the glands situated immediately behind the eyelashes - Meibomian glands - which normally secrete lipid materials necessary for the maintenance of the tear film on the surface of the cornea, as well as for the lubrication of the eyelids themselves. A typical sign is the presence of foaming in the lachrymal fluid, due to excess lipids, which have also undergone saponification processes. This secretion may also involve the onset of irritation and slight blurry vision, and small oily globules can come out of the gland orifices. In some cases the secretion stasis may favour the onset of chalazion. Secondary effects are papillary conjunctivitis, keratopathy and lachrymal stability disorders.

In general, blepharitis may also be caused by environmental factors such as dusts or smoke, or by allergic or endocrine factors, or may be secondary to avitaminosis or food poisoning. In all cases, the pathology may be difficult to cure and is recurrent, also tending to become chronic.

The therapy for blepharitis includes the use of compositions based on antibiotics and corticosteroids in the form of eye drops and ophthalmic ointments, which can be used particularly in the acute phase. In any case, proper eyelid hygiene is recommended, both during the therapy itself and for a long time afterwards in order to avoid any recurrence of the disorder.

Often, the prescribed treatment is exclusively or mainly based on hot compresses and on the careful hygiene of the lid margin. The importance of delicate but regular cleansing is because any stagnation of secretions, scales and bacteria on the eyelids and in the periocular region leads to further irritation and creates a vicious circle favouring a chronici- sation of the pathology. While the drainage of the gland ducts is further hindered, the pathogenic bacteria find the substrate ideal for their proliferation. Proper hygiene is thus fundamental also because, since it does not have any side effects as may be the case with a pharmacological type approach, it may be conducted over long periods thereby consolidating the results achieved. The aforesaid considerations also hold in cases where the eyelid is secondarily involved in another pathology (such as a chalazion or a stye), in anterior segment affections (such as conjunctivitis and keratitis) or dermatological problems. Even the follow-up to surgery may benefit from careful eye hygiene in order to minimise the effects of irritation and the risks of infection.

For eyelid and periocular hygiene in the case of blepharitis, a delicate detergent is often recommended, such as a neutral or baby shampoo, which must be diluted with water by the patient, however. In view of the frequency of application, at least once a day, and the considerable length of the treatment, the laboriousness of this operation inevitably creates problems of compliance. Moreover, hair shampoo products, however delicate they may be, can still have an irritant effect when used in the vicinity of the eye, also due to components such as dyes or perfumes, which are not justifiable in a detergent for periocular hygiene to be used by subjects already suffering from an ophthalmic pathology underway.

On the basis of these considerations, US patent no. 5000868 (Wittpenn et al.) proposes the use of a specially designed detergent for periocular hygiene that is essentially made up of an anionic surfactant with marked detergent and foaming properties, in combination with one or more non-ionic surfactants that reduce the irritant effect of the anionic surfactants, and with a further agent, defined as an induced non-ionic surfactant. The latter component has the task of contributing to increasing the foaming properties and of limiting the irritating characteristics of the ani- onic surfactant. Suifosuccinates are proposed as the anionic surfactants, while the non-ionic surfactants are selected from among the ethoxylated mono- and diglycerides and alkanolamides, and the induced non-ionic surfactant is an amine oxide. The formulation can contain other ingredients such as antimicrobial agents and disodium edetate as a preservative. According to the PCT patent application, published with No.

93/13750 (Allergan), the previously used anionic surfactants still tend to be irritating for eye tissues and thus an alternative formulation is proposed, containing exclusively non-ionic surfactants that present, in combination with one another, particularly marked detergent properties. The proposed combination consists of two ethoxylated agents and namely two different block copolymers of polyoxyethylene and polyoxypropylene, both com- mercially available under the Pluronic^® trademark. To this, another auxiliary surfactant may be added, also of a non-ionic ethoxylated type, such as octylphenol ethoxylate, as well as the usual buffers and preservatives. The document also mentions the possibility of including hydrating and emollient agents in the preparation and cites, as examples, products de- rived from glycerine, hyaluronic acid and hydroxypropyl cellulose.

Although formulations of the aforesaid type are undoubtedly effective as regards detergent capacity, the ocular and skin tolerability, including the mucosa, and the delicateness with regard to the natural moisturising and lubrication of the skin - which are essential features of prod- ucts designed for periocular hygiene and treatment - are certainly susceptible to improvement. In fact, some of the surfactants proposed in the past for use in eyelid hygiene preparations are rather aggressive and not really suitable for cleansing the eyelid margin, particularly when it is already irritated due to blepharitis or to some other ophthalmic pathology. This holds not only for products of an ionic nature, but also for ethoxylated non-ionic surfactants, which can excessively dehydrate and degrease the skin, at least as regards the application considered here.

In general, the surfactants present in preparations for eyelid hygiene, be they ionic, non-ionic or amphoteric, are all intrinsically aggres- sive to a greater or lesser extent, particularly as regards the mucosa, and are thus not acceptable in ocular surface pathologies such as blepharitis and blepharoconjunctivitis with an inflammatory and/or infective component.

In view of the above, an object of the present invention is, therefore, to provide a preparation which, besides assuring a delicate and effective cleansing of the periocular region, thereby enabling the removal of debris and secretions that can build up around the eyelid margin, can also contribute to preventing the onset of irritation, which could be caused either by the presence of partly aggressive ingredients, such as detergents and preservatives, in the detergent formulation, or by the action of rubbing the affected area with the gauze or tissue employed for cleansing it. More- over, the preparation according to the present invention must contribute to limiting any development of the inflammatory process underway, and to reducing microbial growth in the affected ocular region.

According to the present invention, it was found that by including an agent with specific "anti-irritant" properties, and namely α-bisabolol, in the detergent and emollient preparation largely based on the kind of surfactants conventionally used for periocular hygiene, it is possible to obtain considerably more tolerable preparations, particularly in terms of a lower capacity to cause irritation and/or burning sensation, compared to similar preparations not containing the said ingredient. In practice, bisabolol serves to reduce the irritation potentially caused by other "more irritating" ingredients contained in the product - and particularly the surfactants and preservatives. α-bisabolol [(R*,R*)-α,4-dimethyl-α-(4-methyl-3-pentenyl)-3-cy- clohexene-1 -methanol] is a natural monocyclic sesquiterpene alcohol which can be isolated from the essential oils of various plants including, first of all, German camomile Matricaria chamomilla (or Matricaria recutita or Chamomilla recutita). This plant is mainly grown in central and eastern Europe, Egypt and Argentina, and its flowers provide 0.5-1.5% of an essential oil containing the sesquiterpenes α-bisabolol (10-15%), bisabolol oxide A and B (10-25%) and chamazulene (0-15%), the latter being responsible for the bright blue or blue-green colour of the essential oil. Both bisabolol and chamazulene contribute to the known anti-inflammatory properties of camomile essential oil.

The extracts or essential oils of matricaria have been used for centuries in the preparation of creams and ointments, used both in treating skin inflammations and as antibacterial agents, and also as anti-irritants in cosmetics. The bisabolol component prevalently found in these natural extracts is the laevorotatory enantiomer α-(-)-bisabolol, even if another three stereoisomers have been isolated in much smaller quantities: α-(+)- bisabolol and the (-)-epi and (+)-epi forms.

According to the present invention, a specific chemical compo- nent of the essential oil of camomile, α-bisabolol, and preferably not the natural molecule in the laevorotatory form, but the bisabolol racemate, α- (±)-bisaboIol, obtainable synthetically, when included in detergent and emollient preparations mainly based on surfactants and preservatives or antiseptics for eyelid and periocular hygiene and care, effectively performs a long-term anti-irritant action, limiting the irritation effect of these ingredients and contributing to treating the ocular signs and symptoms of any inflammation underway (blepharitis or blepharoconjunctivitis).

Therefore, the present invention specifically provides a cleansing emollient preparation for eyelid and periocular hygiene, consisting of an aqueous solution containing, as main ingredients, one or more surfactants, one or more antiseptic or bactericide agents and one or more emollient agents, and characterised by the fact that it comprises α-bisabolol as an anti-irritant agent. The proposed preparation, indicated for daily eyelid and periocular hygiene and also for the treatment of eyelid margin pa- thologies and/or conjunctivitis, contains ingredients that are useful for cleansing and disinfecting, contributes in the treatment of ocular symptoms of inflammation and is also devoid of any aggressive property with regard to both healthy or damaged skin tissues and mucosa.

As already noted, in the proposed composition the said α- bisabolol is preferably α-bisabolol racemate (α-(±)-bisabolol), which turned out to be much more stable in an aqueous solution than the corresponding laevorotatory enantiomer of natural extraction, as the latter degrades quite quickly in the same conditions.

In the preferred formulations according to the present invention, the said one or more surfactants are one or more non-ionic surfactants, and may, in general, include all those already known and used in the phar- pharmaceutical field, such as: the fatty acids esters of sucrose, the ethers of fatty alcohols and oligoglycosides (such as the alkyl polyglycosides known by the name "Triton^®"), the fatty acids esters of glycerine (such as glycerine mono/distearate or glycerol monolaurate), the fatty acids esters of sorbitan (such as "Span^®"), as well as the ethoxylated non-ionic surfactants, whose molecule contains polyoxyethylene chains (which are also known by other names, common or registered ones, including polyethylene glycol, polyethylene oxide, POE, PEG, PEO, Macrogol, Carbowax, Polyox or Polyoxyl). Ethoxylated non-ionic surfactants, which are the preferred category for the proposed preparation, specifically include the polyoxyethy- lated esters of fatty acids and sorbitan (that is, polysorbates such as "Tween^®"), the esters of fatty acids with polyoxyethylene (such as the polyoxyethylene stearates), the ethers of fatty acids and polyoxyethylene (such as polyoxyethylate lauryl ether, polyoxyethylene tridecyl ether or "Trideceth^®"), the ethers of alkyl phenols and polyoxyethylene (such as octylphenol polyoxyethylate), the block copolymers polyoxyethylene- polyoxypropylene (also known as poloxamers, such as "Pluronic^®"), and ethoxylated fats and oils (such as ethoxylated or polyethoxyated castor oil, also known as polyethylene glycol glycerol triricinoleate).

According to some preferred embodiments of the present invention, the said one or more ethoxylated non-ionic surfactants are selected from polyethoxyated or polysorbate fatty acids esters of sorbitan (Tween^®), ethers of fatty alcohols and polyoxyethylene (Trideceth^®) and their mixtures, and in particular consist of polyoxyethylene-10-tridecyl ether (Trideceth^®- 10) and polisorbate 20 or PEG(20)sorbitan-monolaurate (Tween^®-20). The first one is used as an emulsifier, detergent and solubi- liser, and is approved by the FDA (Food and Drug Administration, USA) for topical use. The second one is used as a detergent, solubiliser, emulsifier and dispersing agent and, like all polysorbates, is used also in the preparation of injectables, since it is non-pyrogenic, non-haemolytic and non- irritating.

Preferably, the one or more antiseptic or bactericide agents are selected from among chlorhexidine or one of its salts or esters, benzalk- onium chloride and sodium merthiolate or thiomersal. The first one of these is an antibacterial agent effective against a broad range of Gram- positive and Gram-negative organisms, particularly used in the form of an ester (acetate, digluconate) as a preservative for eyedrops and in the form of hydrochloride salt as a local antiseptic; the second one is widely used in the ophthalmic field as a topical antiseptic and antimicrobial agent, while the third one is an organomercurial, anti-fungal and bacteriostatic antiseptic used both for topical use and as a pharmaceutical preservative. The main antiseptic or bactericide agent included in the composition is preferably chlorhexidine digluconate (1 ,1'-hexamethylene bis[5-(4-chloro- phenyl)biguanide] di(D-digluconate), which has broad ranging bactericide and antiseptic properties and is widely used in dentistry, gynaecology and dermatology.

Moreover, in a composition to be used for cleansing an eyelid margin already irritated due to blepharitis or to another ophthalmic pathology, it is extremely desirable for the emollient and hydrating action to be particularly marked, in order to soften and easily remove the debris of dead cells found on the eyelid margin and the secretions matted on eyelashes. To this end, the proposed composition contains at least one moisturising, emollient and/or hydrating agent such as propylene glycol or glycerine and their derivatives, or the derivatives of cellulose such as hy- droxypropylcellulose. Propylene glycol, which is preferably included in the composition according to the present invention, has moisturising properties and facilitates water penetration in the tissues; moreover, by acting as a co-solvent, it helps to maintain the components in solution.

Besides the aforesaid ingredients, the preparation according to the present invention should preferably also include preserving agents and additional antimicrobial agents, particularly chosen from among benzalk- onium chloride, sodium merthiolate or thiomersal, methyl-, ethyl- and pro- pyl-paraben (methyl-, ethyl- and propyl-p-hydroxybenzoate), chlorobutha- nol, benzil alcohol, as well as chelant or sequestering agents such as ede- tates or EDTA. Preferably, the said preserving and antimicrobial agent is composed of methyl-p-hydroxybenzoate and propyl-p-hydroxybenzoate. The proposed composition also preferably includes one or more tonicity adjusting agents which are often included in products for ophthalmic use in order to provide the solution with an osmolarity value near to the physiological one (around 300 mθsm/kg). To this end, the composition can include one of the products conventionally used in the pharmaceutical art, such as sodium or potassium chloride, mannitol, dextrose, boric acid, or balanced saline solution. The preferred isotonising agent in the composition according to the present invention is mannitol.

Other ingredients which can be added, similarly to what is already known in the pharmaceutical art, are acids or bases acting as pH correctors, as well as buffers such as the monosodium phosphate - diso- dium phosphate system (Sørensen phosphate buffer) or the acetate - acetic acid system, in order to take and maintain the pH of the solution within limits guaranteeing product tolerability. The preferred pH values are between 5.0 and 7.5. Finally, the composition for periocular hygiene according to the present invention may also include other natural extracts with a hydrating, skin protective, refreshing, tonic, moisturising, emollient and soothing action.

According to a preferred form of realisation of the present in- vention, the detergent emollient composition contains the following components in an aqueous solution: polyoxyethylene-10-tridecyl ether, poly- sorbate 20, chlorhexidine digluconate, propylene glycol, α-bisabolol race- mate, methyl-paraben, propylparaben, mannitol, Sørensen phosphate buffer. A particularly preferred formulation for the composition proposed is the one described below as Example 1.

According to a further aspect therof, the present invention also concerns a new emollient detergent wipe for eyelid and periocular hy- giene. The wipe consists of a sterile substrate composed of absorbent material moistened with the aforesaid emollient detergent composition. In effect, eyelid and eyelash hygiene may be easily guaranteed by using tow- elettes or wipes containing both disinfectant agents and detergents, which are ideal for daily use, also in the presence of ophthalmic pathologies, because they are made of particular types of tissues that do not leave any residues, they contain useful ingredients for cleansing and disinfecting, they treat the periocular signs and symptoms of inflammation, they do not have any aggressive action for the eyes and are packaged in particular aluminium sealed sachets thereby avoiding contamination.

According to some preferred embodiments, the sterile substrate of absorbent material is moistened with a total quantity of preaparation ranging between 1 ml and 3 ml, and preferably with a quantity of 2 ml.

The specific features of the invention, as well as its advantages, will be more evident with reference to the detailed description presented merely for exemplificative purposes below, along with the results of the experiments carried out on it and the data for comparison with the prior art. Some of the experimental results are also illustrated in the attached drawings, wherein: Figure 1 shows a chromatogram of the preaparation according to the present invention, which highlights the peaks of the two preserving and antimicrobial agents contained therrein, methyl- and propyl-p-hydroxy benzoate.

EXAMPLE 1 Wipes pre-moistened with the solution

The preferred formulation according to the present invention had the following composition:

Components % p/p

Chlorhexidine digluconate, 20% aq. solution 0.18 Trideceth^®-10 1.00

Tween^®-20 0.80

Propylene glycol 0.60 Bisabolol racemate 0.20

Methyl p-hydroxy benzoate 0.065

Propyl p-hydroxy benzoate 0.035

Sørensen phosphate buffer pH= 7.00; 33.33 mM, isotonised with mannitol q.s. to 100

The method for preparing the composition was as follows: the following components are placed inside a vessel in this order: Trideceth^®-10 (Sigma-Aldrich, Milan, Italy), Tween^®-20 (Sigma-Aldrich, Milan, Italy), bis- abolol racemate (BASF Italia Spa, Milan, Italy), propylene glycol (A.C.E.F. Spa, Piacenza, Italy) and the digluconate chlorhexidine solution (A.C.E.F. Spa, Piacenza, Italy). The mixture was stirred at room temperature for about 10 minutes.

The Sørensen phosphate buffer solution was prepared by dissolving 1.84 g of NaHbPO₄ H₂O (monohydrated monobasic sodium phosphate) and 3.57 of Na₂HPO₄ 2HbO (dihydrated dibasic sodium phosphate) in 1 litre of deionised water. The quantity of mannitol necessary to reach isotony was 13.52 g/l.

The preservatives methyl-p-hydroxy benzoate and propyl p- hydroxy benzoate (Esperis, Milan, Italy) were dissolved hot (80°C) in the previously prepared buffer solution. The buffer solution containing the preservatives was finally added, after cooling, to the first prepared mixure. The final formulation was then stirred, not vigorously, for about 30 minutes.

The preparation thus obtained was then used to moisten some 130x175 cm sterile wipes consisting of 40 g/m² pure viscous nonwoven material, according to the following procedure: the wipe is first folded and placed within a polyester-alluminium-polythene sachet and then imbued with a dosed quantity of solution (2 ml in the preferred form); the sachet is finally heat sealed. EXAMPLE 2 FOR COMPARISON

Wipes pre-moistened with solution

In order to assess the performance of the composition accordinα to the present invention in comparison with a preparation containing the same potentially aggressive ingredients but without bisabolol, a composition was prepared with the following components: Components % p/p Digluconate chlorhexidine, 20% solution 0.18

Trideceth^®-10 1.00

Tween^®-20 0.80

Propyl glycol 0.60

Methyl p-hydroxy benzoate 0.065 Propyl p-hydroxy benzoate 0.035

The materials were the same as those of Example 1 and the preparation of the liquid solution was carried out according to the same procedure, but without using the ingredient α-bisabolol. Also the packaging in the form of wipes was carried out with the same procedure as described for the previous example. Characteristics and physico-chemical stability

The physico-chemical characteristics of the preparation according to the present invention, realised as described in Example 1 , that were measured were pH, osmotic pressure, surface tension, density and wettability (contact angle); the values are reported in Table 1 below, as the average of ten measurements.

The stability of the prepared composition was evaluated as re- gards its chemical-physical properties and with regard to any changes in the appearance of the solution. In particular, the preparation was stored in closed glass vials at temperatures of 4, 25 and 37°C. TABLE 1

Chemical-physical characteristics of the composition after preparation and after storage at various temperatures

After 90 days of storage, no precipitation or changes in colour were found in the composition. Moreover, the pH, osmotic pressure, surface tension, density and contact angle remained unchanged, as shown in the table. Analysis and stability of the preservatives

The quantitative determination of the preservatives present in the composition was carried out by means of high performance liquid chromatography (HPLC). The HPLC equipment consisted of a Shimadzu LC- 10ADvp system with UV SPD-10AVvp detector and CromatoPlus^® integration software. The injection valve was a Rheodyne with 20 μl capacity. The inverse phase column was a HyperClone C18 (5 μm, 250 x 4,60 mm, Phenomenex^®). The mobile phase consisted of 40% of an aqueous solution of KH₂PO₄ (potassium phosphate dibasic anhydrous) 0.05M and 60% of acetonitrile; the flow was of 1 ml/min and the detection wavelength was 260 nm.

The quantitative determination was carried out via a comparison with an external standard curve. The retention time was 5.5 minutes for methyl p-hvdroxv benzoate. and 5 minutes for πrπnvl

h^p>nrnnt<-> The attached Figure 1 reports an example chromatogram.

The analytical method was as follows: a suitably measured quantity (100 μl) of the composition was diluted by adding 5 ml of acetonitrile. The suspension thus obtained first underwent vigorous stirring by means of a vortex and was then filtered (Minisart RC 25, 0,20 μm, Sartorius). The filtered solution was finally analysed in triplicate by HPLC with the aforesaid procedure. Table 2, below, reports the data on the stability of the preservatives after 90 days at a temperature of 4, 25 and 37⁰C.

TABLE 2

Data on the stability of the preservatives in the composition after 90 days at the three temperatures concerned

Ocular irritation trials

New Zealand albino rabbits weighing 3.0-3.5 kg were used in the ocular irritation trials, which were carried out by instilling a drop of 50 μl in the lower conjuctival sack of only one eye, while the contralateral one was used as control. Administration was repeated every 5 minutes for a total duration of 30 minutes. A total of 20 rabbits were used.

The results show that the tested preapration appears well toler- ated since no visible symptoms of irritation were seen: the composition did not seem to cause any burning sensation at the time of instillation, nor was there any conjunctival reddening, induced lachrymation, edema or corneal opacification.

In the two davs followinα aDolication the? animals' RVRR WΩΓR oh- served with a slit lamp: in no case was there any scaling or corneal ulceration. Clinical study

In order to demonstrate the effectiveness of the composition with α-bisabolol according to the present invention in trials on patients, a clinical study was carried out. The results are summarised below.

The aim was to evaluate the soothing effect, as well as the emollient and deterging effect and tolerability (with particular regard to irritation and burning sensations) of the preparations described in the aforesaid Ex- amples 1 and 2. These two preparations differed, respectively, for the presence or absence of α-bisabolol.

Disposable wipes packaged in sachets, as described in Example 1 , were moistened with 2 ml of both preparations, respectively.

The study envisaged 6 day-hospital subjects (making a total of 12 eyes) aged between 15 and 60 years and suffering from acute or chronic blepharoconjunctivitis or blepharitis (even if already undergoing drug therapy) with the presence of mucous pus-filled discharge, rheums and crusting on the eyelid margin.

The subjects were instructed on how to use the wipes and on the judgements they had to make. They were asked to cleanse their right eye with the sachet composition of Example 1 and their left eye with the sachet composition of Example 2 every morning for five consecutive days. At the end of the trial, the patients were asked about the emollient-detergent effect, tolerability (irritation and burning sensation) and usability of the wipes. The results of the evaluation are reported in the following table. TABLE 3

Comparative clinical study of compositions with and without α-bisabolol

DETERGING AND

EMOLLIENT IRRITATION BURNING

ACTIVITY SENSATION

Composition Suff. 0 Yes 0 None 6 with Slight 0 α-bisabolol

Good 6 No 6 Intense 0

Composition Suff. 0 Yes 3 None 2 without Slight 4 α-bisabolol

Good 6 No 3 Intense 0

The above table shows that, for all the patients, both compositions were equally satisfactory for their cleansing effect and capacity to soften and solubilise the debris on eyelid margins. On the other hand, 50% of the patients reported irritation to a greater or lesser degree after using the wipe formulated without α-bisabolol, and 67% felt a slight burning sensation with the same wipe type.

It may be concluded that the wipes moistened with the product of Example 1 (i.e., the ones containing α-bisabolol) were effective not only in guaranteeing adequate hygiene of the eyelid margin, but also in appreciably limiting the bothersome irritation and burning sensation that can derive from cleansing and disinfecting components coming into contact with the damaged tissue.

The present invention has been disclosed with reference to some specific embodiments thereof, but it is to be understood that variations or modifications can be brought by persons skilled in the art without departing from the scope of the appended claims.

Claims

1. A cleansing emollient preparation for eyelid and periocular hygiene, consisting of an aqueous solution containing, as main ingredients, one or more surfactants, one or more antiseptic or bactericide agents and one or more emollient agents, and characterised by the fact that it comprises α-bisabolol as an anti-irritant agent.

2. A preparation according to claim 1 , wherein the said α- bisabolol is α-bisabolol racemate.

3. Apreparation according to claims 1 or 2, wherein the said one or more surfactants are one or more non-ionic surfactants.

4. A preparation according to claim 3, wherein the said one or more non-ionic surfactants are ethoxylated non-ionic surfactants.

5. A preparation according to claim 4, wherein the said one or more ethoxylated non-ionic surfactants are selected from the group consisting of: polyethoxylated or polysorbate sorbitan esters of fatty acids, ethers of fatty alcohols with polyoxyethylene and their mixtures.

6. A preparation according to claim 5, wherein the said one or more ethoxylated non-ionic surfactants are polyoxyethylene-10-tridecyl ether and polysorbate 20.

7. A preparation according to any one of claims 1-6, wherein the said one or more antiseptic or bactericide agents are selected from among chlorhexidine or one of its salts or esters, benzalkonium chloride and sodium merthiolate or thiomersal.

8. A preparation according to claim 7, wherein the said one or more antiseptic or bactericide agents consist of chlorhexidine diglucon- ate or chlorhexidine acetate.

9. A preparation according to any one of claims 1-8, wherein the said one or more emollient agents are selected from among propyl glycol, glycerine and their derivatives, and the derivatives of cellulose.

10. A preparation according to claim 9, wherein the said one or more emollient agents consist of propylene glycol.

11. A preparation according to any one of claims 1-10, also comprising one or more preservatives and additional antimicrobial agents selected from among benzalkonium chloride, sodium merthionate or timerosal, methyl-, ethyl- and propylparaben, phenylmercuric nitrate or acetate, phenylethyl alcohol, chlorobuthanol, benzyl alcohol, edetates or EDTA.

12. A preparation according to claim 11 , wherein the said one or more preservatives and additional antimicrobial agents consist of methyl-paraben and propylparaben.

13. A preparation according to any one of claims 1-12, also comprising one or more tonicity-regulating agents selected from the group consisting of: sodium or potassium chloride, mannitol, dextrose, boric acid or balanced saline solution.

14. A preparation according to any one of claims 1-13, also comprising one or more pH correctors or buffers selected from the mono- sodium phosphate - disodium phosphate system or the acetate - acetic acid system.

15. A preparation according to claim 14, wherein the said pH corrector or buffer is the Sørensen phosphate buffer, isotonised with man- nitol.

16. A cleansing emollient preparation for eyelid and periocular hygiene according to any one of claims 1-15, having the following components in an aqueous solution: polyoxyethylene-10-tridecyl ether, poli- sorbate 20, chlorhexidine digluconate, propylene glycol, α-bisabolol race- mate, methyl-paraben, propyl-paraben, mannitol, Sørensen phosphate buffer.

17. A preparation according to claim 16, having the following components in the following proportions:

Components % p/p Chlorhexidine digluconate, 20% solution 0.18

Trideceth^®-10 1.00

Tween^®-20 0.80 Propylene glycol 0.60

Bisabolol racemate 0.20

Methyl p-hydroxy benzoate 0.065

Propyl p-hydroxy benzoate 0.035 Sørensen phosphate buffer pH= 7.00; 33.33 mM, isotonised with mannitol q.s. to 100

18. A cleansing emollient wipe for eyelid and periocular hygiene consisting of a sterile substrate made of absorbent material moistened with the cleansing emollient preparation as defined in any one of claims 1- 17.

19. A wipe according to claim 18, moistened with a total quantity of preparation ranging between 1 ml and 3 ml.

20. A wipe according to claim 19, moistened with a total quantity of preparation equal to 2 ml.