AU776900B2 - Sunscreen formulations - Google Patents

Description

WO 01/03663 PCT/AU00/00814 1 SUNSCREEN FORMULATIONS BACKGROUND TO THE INVENTION: The present invention relates to a novel composition, being an alcoholic spray or gel that, when applied to the skin, provides protection against the harmful effects of solar ultraviolet radiation and is resistant to wash-off by water.

An increased awareness by the public of the damage that exposure to solar radiation can cause has led to demands for products that can provide high protection against these harmful effects.

Ultraviolet, visible and infrared radiation from the sun have all been implicated in skin damage. The ultraviolet radiation band has been divided by scientists into three portions, UVC, UVB and UVA. UVC radiation (wavelength 280 nm) is highly carcinogenic, but fortunately it is filtered out by the ozone layer in the upper layers of the Earth's atmosphere. Artificial sources such as arc welders can generate UVC, but in general UVC is of little concern. UVB radiation(wavelength 280nm-320nm), which consists of around 5-10% of the total ultraviolet radiation that reaches the Earth's surface, is also carcinogenic, and can lead to the development of non-melanoma (basal and squamous cell) carcinomas and malignant melanoma-type skin cancers. UVB radiation is the primary cause of the often painful erythemal reaction associated with sunburn and photo-aging, and recently has been shown to be implicated in a suppression of the immune system which can lead to increased outgrowth of skin tumors. UVB radiation does not penetrate the skin beyond the epidermis.

UVA(wavelength 320nm 400 nm) radiation, however, penetrates deeply into the dermis, has been widely implicated in damage leading to premature skin aging, and is believed to be carcinogenic. It causes alterations to the immune system, which may lead WO 01/03663 PCT/AU00/00814 2 to susceptibility to cancer in the form of basal and squamous cell carcinomas, and possibly even melanomas.

The effects of infrared and visible radiation upon the skin are not considered as important as those caused by ultraviolet radiation, and are the subject of ongoing research. The literature contains several references to the harmful effects of infrared radiation, including enhancement of UV-induced damage, elastosis, genetic damage and premature aging.

Visible radiation has been implicated in genetic damage, photoallergy and phototoxicity.

The ability of a sunscreen formulation to protect an individual from the harmful effects of solar radiation (as outlined above) is determined by an in vivo test procedure which quantifies protection as a Sun Protection Factor (SPF) and reflects the time taken to develop an erythema when a volunteer is irradiated by a solar simulator with a set amount of the test sunscreen applied to the back, compared to the time taken to develop an erythema without sunscreen. For instance, if a subject develops an erythema in minutes without sunscreen and develops an erythema in 300 minutes with sunscreen applied, the SPF is 300/10 30. This test is applied internationally, albeit with minor variations from country to country. As the understanding of the dangers of solar radiation has grown, so concerned authorities in various countries have raised the limits that a product may claim. For instance, in USA and Australia, the maximum allowable SPF claim is 30+ (a shift from the previous upper limit of SPF The growing recognition of the dangers of UVA by health authorities has led to concerns about the amount of this radiation being received by the population. Early sunscreen formulations only filtered UVB radiation and, since this is the portion of the WO 01/03663 PCT/AUOO/00814 3 spectrum that is mainly responsible for erythema, ie sunburn, the early warning system that too much solar radiation was being absorbed was effectively removed. UVA radiation penetrates the skin deeply and makes up 90-95% of incident UV radiation; therefore, the potential for significant irreversible damage to the skin and health is present. For this reason, a growing trend in modem sunscreen formulations has been to filter both UVA and UVB radiation; these products are referred to as being broad spectrum.

The water resistance claims of sunscreen formulations have also been subject to close regulatory control, with a growing number of countries allowing only the postimmersion SPF to be claimed. An SPF 30+ sunscreen formulation that claims two hours water resistance must then be shown by clinical evaluation to be SPF 30+ after two hours immersion in water.

These changes have presented considerable challenges to the formulators of sunscreens.

The traditional emulsion-based sunscreen formulations have been the subject of a large number of patents which claim to provide improved benefits to the consumer. The high SPF's achieved using an emulsion-based vehicle result from the emulsion's ability to form a uniform, thick, non-transparent sunscreen film, that allows minimal interaction between the sunscreening actives and the rest of the formulation ingredients. Further, they can be formulated to contain a wide variety of actives and other ingredients and also to contain a significant percentage of water, and hence be cost effective. If formulated skilfully, emulsions can leave the skin feeling smooth, with a silky, nongreasy feel. Emulsions do have disadvantages, however they are prone to microbial contamination, high water resistance is difficult to achieve in a cost-effective manner, they are difficult to stabilize and the products are difficult to use on hairy parts of the body.

WO 01/03663 PCT/AU00/00814 4 Sprays containing sunscreens have been formulated and in general fall into four different categories: oil-based emulsion-based water-based alcohol-based.

Oil-based sprays are the oldest and most easily formulated sunscreen vehicle. They usually display excellent product stability and, because the sunscreening agents are lipophilic, they are readily dissolved. Oil-based sprays also spread rapidly over the skin to form a uniform continuous film and they can be easily formulated to provide water resistance. As they contain no water at all, the microbiological problems are reduced.

They do have some negative features, however they are expensive, they exhibit the poorest SPF of any vehicle due to the tendency to spread to a very thin transparent film, and non-polar oils have a tendency to shift the wavelength of maximum UV absorption of sunscreening agents to lower wavelengths than those required for maximum protection.

The emulsion-based sprays usually consist of very thin oil-in-water emulsions which have the all the advantages of creams and lotions, but are difficult to stabilize because of the need for a low viscosity for spraying, particularly at elevated temperatures. Also, the necessity to keep the oil phase to a minimum, to aid stability, results in a thin film of oil being deposited on the skin, leading to poor SPF results. Clear micro-emulsions have been formulated and they have an excellent skin feel, while providing a smooth uniform film on the skin. They require, however, the use of very high levels of surfactants, which leads to a costly product that is very difficult to make water-resistant. Also, the high level of surfactants can be very irritating to the skin.

WO 01/03663 PCT/AU00/00814 The water-based sprays generally contain water-soluble sunscreening agents that are mainly ionic in nature and not as effective as the oil-soluble sunscreening agents; also, water resistance is impossible to achieve. Contamination by microorganisms is also a problem that must be addressed through the use of appropriate preservatives.

Alcoholic sprays have several advantages they have an inherent anti-microbial action, alleviating the need for the use of preservatives, and the alcohol will generally dissolve most lipophilic sunscreening agents in stable solution, reducing the need for solubilizers or surfactants. A real benefit is the refreshing, cooling effect when applied on a warm summer's day. The disadvantages include ease of wash-off by water; by incorporating resins or film formers, water resistance can be improved, but the inherent nature of the vehicle limits its effectiveness. Efficacy has been a serious disadvantage of this type of vehicle since, in order to achieve a high SPF value, a thick, continuous film must be laid down upon the skin. On exposure to heat and sunlight, the alcohol in the formulation evaporates, leaving a porous and discontinuous film on the skin. The use of film formers can help, but the most usual way to overcome this problem is to use very high levels of sunscreening agents. The disadvantage of that approach is the cost and associated risk of dermatological problems associated with excessively high concentrations of sunscreening agents.

Gels are thickened versions of the sprays and, aside from being pourable and nonsprayable, share the same advantages and disadvantages as the sprays. One additional benefit of a gel is the potential to incorporate insoluble sunscreening agents, such as zinc oxide and titanium dioxide.

Alcoholic sprays and gels therefore have numerous advantages over alternative vehicles. However, they are not widely used because of the low SPF achievable for WO 01/03663 PCT/AU00/00814 6 quantities of sunscreening agents equivalent to those used in other vehicles, and the difficulty in making the products water-resistant.

SUMMARY OF THE INVENTION: The aim of this invention is to produce an alcoholic sunscreen spray or gel which has a high SPF, is water-resistant, cost effective and of low dermatological risk to the user.

The low efficacy SPF results achieved by alcoholic sprays and gels result from the poor film-forming ability of the product, once the alcohol has evaporated. It has now been discovered by the present inventors that a combination of a hydrophobic fumed silica (preferably 1-20% such as silica dimethyl silylate or silica silylate; a volatile silicone (preferably 1-25% such as cyclomethicone; and an emollient (preferably 0.5-25% such as caprylic/capric triglyceride, octyldodecyl neopentanoate or a mixture thereof; will gel upon the skin as the alcohol evaporates, leaving a thick, continuous, uniform film on the skin. The latter properties of the film make it an ideal carrier for sunscreening agents; in addition, the efficacy of the UV absorbance of the sunscreening agents is maximised at the most critical erythema-inducing waveband by the polarity of the oils in the film. The film produced by the combination of the fumed silica, volatile silicone and emollient is also highly water-resistant, due to the hydrophobic nature of the oil film.

The inventors have discovered that a hydrophobic fumed silica (eg silica dimethyl silylate or silica silylate), when used in an alcohol-based spray or gel, forms a hydrophobic layer on the skin that repels water and provides water resistance to the spray or gel. This has previously been unachievable.

WO 01103663 WO 0103663PCT/AUOO/0081 4 7 Accordingly, the present invention relates to an alcohol-based sunscreen spray or gel comprising a hydrophobic fumed silica, a volatile silicone, an emollient and an effective amount of one or more sunscreening agents.

For dermatological reasons, the alcohol used is preferably ethanol, eg 95% or absolute ethanol, which may also contain a denaturant. However, n-propanol or isopropanol may be used, either alone or in combination with ethanol.

The sunscreening agents that can be used in the spray or gel include, but are not lim-ited to, 4-aminobenzoic acid, N-propoxylated ethyl 4-aminobenzoate, N-ethoxylated-ethyl4.

aminobenzoate, 2 -amyl-4-dimethyl-am-inobenzoate, glycero-1-(4-aminobenzoate), octyldirnethyl-para-axniinobenzoic acid, homomenthyl salicylate, octyl salicylate, 4isopropylbenzyl salicylate, octyl methoxy cinnamate, isopentyl-4-methoxycinnamate, 2ethoxyethyl-4-methoxycinnamnate, diethanolamine-4-methoxycinnamate, 2-hydroxy4methoxy-berizophenone, 2 -hydroxy.- 4 -methoxy-benzophenone-5-sulphornic acid, 2,2dihydroxy4-methoxybenzophenone, 2 -hydroxy-4-methoxy.4'-methylbenzophenone, octocrylene, 2 -phenylbenzirnidazole-5-sulphonic acid, benzylidene camphor sulphonic acid, 4-methylbenzylidene camphor, 3-benzylidene camphor, 47-isopropyldibenzoylmethane, butylmethoxydibenzoylmethane, urocaruic acid, octyl triazone, NN,N-ftmethy1-4-(2-oxobom-3-bornylidene-methyl)anilrjium methyl sulphate and menthyl anthranilate.

The inorganic sunscreerung agents that can be incorporated in the gel include micronised titanium dioxide and zinc oxide, whether coated by organic or inorganic compounds or not.

WO 01/03663 PCT/AU00/00814 8 DETAILED DESCRIPTION OF THE INVENTION: The invention will now be further described with respect to the following examples, which are illustrative but not restrictive of the present invention.

EXAMPLE 1: Sunscreen Spray Formulation SPF 30+, 2 hour water resistant A typical Sunscreen Spray formulation according to the present invention is prepared as described below: Component 1. ALCOHOL SMF2 (95SG/F2) 2. SILICA DIMETHYL SILYLATE 3. CITRIC ACID ANHYD. FINE GRANULAR 4. CAPRYLIC/CAPRIC TRIGLYCERIDE OCTYLDODECYL NEOPENTANOATE 6. OCTYL METHOXY CINNAMATE 7. BUTYL METHOXYDIBENZOYLMETHANE 8. 4-METHYLBENZYLIDENE CAMPHOR 9. CYCLOMETHICONE Quantity 49.2300 ml 4.0000 g 0.2500 g 18.4200 g 5.0000 g 9.5000 g 1.5000 g 4.0000 g 8.0000 g 0.1000 g

METHOD:

Mix components 3, 4,5,6,7,8 and 9 at room temperature and stir until a clear solution is obtained.

Add component 2 to the mixture and stir in slowly until a clear gel is obtained.

WO 01/03663 PCT/AUOO/00814 9 Add component 1 very slowly to the mixture ensuring that each addition is thoroughly mixed in.

Add component 10 and stir to form a mobile solution.

EXAMPLE 2: Sunscreen Spray Formulation Component 1. ALCOHOL SMF2 (95SG/F2) 2. SILICA DIMETHYL SILYLATE 3. CITRIC ACID ANHYD. FINE GRANULAR 4. CAPRYLIC/CAPRIC TRIGLYCERIDE OCTYLDODECYL NEOPENTANOATE 6. OCTYL METHOXY CINNAMATE 7. OCTOCRYLENE 8. 4-METHYLBENZYLIDENE CAMPHOR 9. CYCLOMETHICONE Quantity 49.2300 ml 4.0000 g 0.2500 g 18.4200 g 5.0000 g 9.5000 g 1.5000 g 4.0000 g 8.0000 g 0.1000 g

METHOD:

Mix components 3, 4,5,6,7,8 and 9 at room temperature and stir until a clear solution is obtained.

Add component 2 to the mixture and stir in slowly until a clear gel is obtained.

Add component 1 very slowly to the mixture ensuring that each addition is thoroughly mixed in.

Add component 10 and stir to form a mobile solution.

WO 01/03663 PCT/AU00/00814 EXAMPLE 3: Sunscreen Gel Formulation A typical Sunscreen Gel formulation according to the present invention is prepared as described below: Component 1. ALCOHOL SMF2 (95SG/F2) 2. SILICA DIMETHYL SILYLATE 3. CAPRYLIC/CAPRIC TRIGLYCERIDE 4. OCTYLDODECYL NEOPENTANOATE OCTYL METHOXY CINNAMATE 6. BUTYL METHOXYDIBENZOYLMETHANE 7. 4-METHYLBENZYLIDENE CAMPHOR 8. CYCLOMETHICONE 9. FRAGRANCE Quantity 28.0000 ml 6.0000 g 20.0000 g 10.0000 g 9.5000 g 1.50 00 g 4.0000 g 20.

9 0000g 0.1000 g

METHOD:

Mix components 3, 4,5,6,7 and 8 at room temperature and stir until a clear solution is obtained.

Add component 2 to the mixture and stir in slowly until a clear gel is obtained.

Add component 1 very slowly to the mixture ensuring that each addition is thoroughly mixed in.

Add component 9 and stir to ensure dissolution.

Claims (17)

1. An alcohol-based sunscreen formulation being a spray or gel comprising a hydrophobic fumed silica, a volatile silicone, an emollient, an effective amount of one or more sunscreening agents and an alcohol-based carrier vehicle.

2. A sunscreen formulation according to claim 1, comprising 1-20% w/v of the hydrophobic fumed silica.

3. A sunscreen formulation according to claim 1 or 2, wherein the hydrophobic fumed silica is silica dimethyl silylate or silica silylate.

4. A sunscreen formulation according to any one of claims 1 to 3, comprising 1-25% w/v of the volatile silicone.

A sunscreen formulation according to any one of claims 1 to 4, wherein the volatile silicone is cyclomethicone.

6. A sunscreen formulation according to any one of claims 1 to 5, comprising w/v of the emollient.

7. A sunscreen formulation according to any one of claims 1 to 6, wherein the emollient is caprylic/capric triglyceride, octyldodecyl neopentanoate or a mixture thereof.

8. A sunscreen formulation according to any one of claims 1 to 7, wherein the alcohol-based carrier vehicle comprises ethanol. WO 01103663 WO 0103663PCT/AUOO/0081 4 12

9. A sunscreen formulation according to claim 8, wherein the alcohol-based carrier vehicle further comprises a denaturant.

A sunscreen formulation according to any one of claims 1 to 7, wherein the alcohol-based carrier vehicle comprises n-propanol or isopropanel, each of which is either alone or in combination with ethanol.

11. A sunscreen formulation according to any one of claims 1 to 10, wherein the one or more sunscreeming agents comprise one or more of the following compounds: 4-aminobenzoic acid, N-propoxylated ethyl 4-aminobenzoate, N-ethoxylated- eth-yl-4- aminobenzoate, 2 -amyl-4-dimnethyl-aminobenzoate, glycero-l-(4-an-inobenzoate), octyl- dimethyl-para-aminobenzoic acid, homomenthyl salicylate, octVl salicylate, 4- isopropylbenzyl salicylate, octyl methoxy cinnamate, isopentyl-4-methoxycinnamate, 2- ethoxyethyl-4.-methoxycinnamate, diethanolamine-4-methoxycinnamate, 2-hydroxy-4- methoxy-benzophenone, 2 -hydroxy-4-methoxy-benzophenone-5-sulphonic acid, 2,2- dihydroxy-4-methoxybcnzophenone, 2 -hydroxy-4-methoxy-4'-mnethylbenzophenone, octocrylene, 2-phenylbenzimidazole-5-sulphonic acid, benzylidene camphor sulphonic acid, 4-methylbenzylidene camphor, 3-benzylidene camphor, 4-isopropyl- dibenzoylmethane, butylmethoxydibenzoyimethane, urocanic acid, octyl triazone, N,N,N-trimethyl-4(2-oxoborn-3-bornylidene-methyl)apilinium methyl sulphate and menthyl anthranilate.

12. A sunscreen formulation according to any one of claims 1 to 11, wherein the one or more sunscreening agents comprise titanium oxide or zinc oxide.

13. A sunscreen formulation according to claim 12, wherein the titanium oxide or zinc oxide is micronised. WO 01/03663 PCT/AU00/00814 13

14. A sunscreen formulation according to claim 12 or 13, wherein the titanium oxide or zinc oxide is coated by an organic or inorganic compound.

A sunscreen formulation according to any one of claims 1 to 14, being in the form of a spray.

16. A sunscreen formulation according to any one of claims 1 to 14, being in the form of a gel.

17. A sunscreen formulation according to any one of claims 1 to 16, substantially as described herein and with reference to any one of Examples 1 to 3.