WO2018087749A1

WO2018087749A1 - Magnesium-based protectant against skin irritation

Info

Publication number: WO2018087749A1
Application number: PCT/IL2017/051195
Authority: WO
Inventors: Mohammed ABUELHAIGA; Nikolay Fux; Ariel PELEG; Meyrav Abecassis Wolfovich; Ganit Levi-Ruso; Smadar SWISSA
Original assignee: Dead Sea Bromine Company Ltd.
Priority date: 2016-11-14
Filing date: 2017-11-02
Publication date: 2018-05-17
Also published as: WO2018087749A8

Abstract

This invention provides anti-irritant topical formulations comprising a magnesia based material, particularly efficient in handling diaper rash.

Description

MAGNESIUM-BASED PROTECTANT

AGAINST SKIN IRRITATION

Field of the Invention

The present invention relates to topical formulations for use in treating dermatitis. Particularly, the invention relates to ointments and creams for handling skin irritation. More particularly, the invention relates to zinc free ointments and creams for handling diaper rash.

Background of the Invention

Skin irritations belong among the most common nuisances in humans. Various microorganisms, mostly fungi such as yeasts, or pollutants and allergens may be among the causes or among the aggravating factors in developing contact dermatitis on the skin, primary symptom of which is pruritus. The problem is commonplace in people using diapers, including elderly and children, and particularly in babies in which it can manifest as diaper rash. Various treatments may include fungicides, topical corticosteroids, or various antipruritics. Since the use of active agents like corticosteroids is quite restricted, the common skin irritations are usually treated with traditional antipruritics, among which zinc oxide ointments have been used for years. In view of the sharp growth of allergic reactions and sensitivities in the human population, and in view of ever increasing number of new environment-related or health-related regulations, there is increasing demand for new compositions, either including new material combinations or excluding traditional ingredients! this is still more valid about formulations for mitigating the skin irritations. It is therefore an object of the invention to provide a zinc-free formulation for mitigating skin irritation.

It is another object of this invention to provide a topical formulation for preventing or mitigating diaper rash. It is a further object of the invention to provide a method of manufacturing an ointment and cream for preventing or mitigating contact dermatitis.

It is a still further object of this invention to provide a formulation for treating skin irritation or contact dermatitis, particularly irritation or dermatitis caused or aggravated by urine or feces.

It is also an object of this invention to provide a formulation comprising magnesium species for mitigating symptoms of contact dermatitis or atopic dermatitis.

This invention also aims at providing an active agent lacking zinc to be admixed in topical means for alleviating or preventing the symptoms of contact dermatitis, skin irritation, and atopic dermatitis.

This invention further aims at providing a means for alleviating pruritus in elderly and children, including babies.

Other objects and advantages of present invention will appear as description proceeds.

Summary of the Invention

The invention provides a formulation comprising from 7% to 60%, preferably from 10% to 50%, of a magnesium-based material and from 12% to 75% lipids, preferably from 15% to 75% lipids, frequently from 35% to 55% of lipids, for use in treating or preventing a condition selected from the group consisting of diaper rash, skin irritation, contact dermatitis, and atopic dermatitis, wherein said magnesium based material comprises magnesium oxide or magnesium hydroxide. The magnesium oxide in the formulation according to the invention may be, in one aspect, a material obtained from essentially pure magnesium oxide (MgO, magnesia) by a partial reaction with water and/or with carbon dioxide; such a partially hydrating and/or carbonating process may convert a part of MgO to magnesium hydroxide and/or carbonate. The magnesium oxide in the formulation according to the invention may be, in another aspect, a material obtained from essentially pure magnesium hydroxide by calcining, usually employing heating at a temperature between 400°C and 900°C, which converts magnesium hydroxide to MgO; in one preferred embodiment, the resulting material comprises MgO and about 10% magnesium hydroxide. The magnesium oxide used for manufacturing the anti-irritant skin formulation according to the invention is usually a fine powder comprising at least 90% MgO and up to 10% magnesium hydroxide.

Magnesium oxide before, during, or after preparing an anti-irritant skin formulation of the invention may undergo hydration or carbonation! such hydration or carbonation, whether regulated or spontaneous, may be called weathering. In a preferred embodiment, said weathering of MgO in an anti- irritant skin formulation according to the invention is only partial. For example, if between 10 and 90 molar % of an initial amount of MgO weathers to magnesium hydroxide, the resulting magnesia based mixture will contain between 87% and 7% MgO; if between 10 and 90 molar % of an initial amount of MgO weathers to magnesium carbonate, the resulting magnesia based mixture will contain between 81% and 5% MgO. In one embodiment of the invention, the initial magnesia based material employed in preparing the anti-irritant formulation comprises preferably at least 80% MgO, more preferably 90% MgO. The magnesia based material in the anti-irritant formulation according to the invention comprises preferably at least 5% MgO.

In a preferred embodiment, the invention provides an anti-irritant skin formulation which comprises magnesia based material selected from the group consisting of hydrated magnesium oxide, carbonated magnesium oxide, weathered magnesium oxide, calcined magnesium hydroxide, and a mixture thereof, wherein said material may be only partially hydrated, or carbonated or weathered. Said magnesia based material comprises less than 0.05% (relatively to MgO) metals other than magnesium. In one preferred embodiment, the formulation of the invention comprises from 12% to 45% of magnesium oxide, from 40% to 50% lipids, and up to 20% cosmetic clay. The formulation of the invention may comprise up to 68% water (for example water-based pump formulations), such as up to 45% water, for example from about 1 to about 40% water. The formulation according to the invention may comprise from 5 to 20% magnesium hydroxide. In a preferred embodiment, the formulation of the invention comprises from 35% to 45% magnesium oxide (MgO), from 40% to 50% lipids, and from 12 to 18% cosmetic clay. The formulation of the invention usually comprises less than 10% magnesium hydroxide, for example up to 5%. The formulation of the invention usually comprises less than 10% magnesium carbonate, for example up to 5%. In one embodiment of the invention, the anti-irritant formulation comprises up to 5% magnesium hydroxide, up to 5% magnesium carbonate, and up to 5% water. Said cosmetic clay may comprise talc; said cosmetic clay may comprise basic magnesium carbonate or magnesium carbonate; said cosmetic clay may comprise talc mixed with basic magnesium carbonate or magnesium carbonate.

In one aspect, the invention provides a skin topical formulation which comprises from 30% to 50% MgO, from 35 to 55% lipids, and from 10% to 20% cosmetic clay! in another aspect, the invention provides the use of the same formulation in treating or preventing a condition selected from the group consisting of diaper rash, skin irritation, contact dermatitis, and atopic dermatitis. In one embodiment, the formulation of the invention comprises from 35% to 50% magnesia based material, from 35 to 55% lipids, and from 10% to 20% cosmetic clay wherein said magnesia based material comprises at least 90% MgO. In one embodiment, the formulation of the invention comprises from 35% to 45% of MgO, from 35% to 55% lipids, and from 10% to 20% cosmetic clay. In a preferred embodiment, the formulation of the invention comprises from 35% to 45% MgO, from 40% to 50% lipids, and from 10% to 20% cosmetic clay. In other preferred embodiment, the formulation of the invention comprises from 35% to 45% MgO, from 40% to 50% lipids, and about 15% cosmetic clay. In a preferred embodiment of the invention, the anti-irritant formulation comprises 29% to 35% paraffin, from 6% to 10% waxes, from 12% to 18% cosmetic clay, and from 3% to 5% caprylic/capric triglycerides. In one embodiment, the formulation of the invention comprises from 36% to 44% magnesium oxide, from 29% to 35% paraffin, from 6% to 10% waxes, from 12% to 18% talc, and from 3% to 5% caprylic/capric triglycerides.

The invention is directed to a formulation comprising from 7% to 60%, such as from 10% to 50%, of a magnesium-based material selected from magnesium oxide, magnesium hydroxide, magnesium carbonate, and mixtures thereof, and from 15% to 75%, such as 35% to 55% lipids for use in treating or preventing contact dermatitis, skin irritation, or atopic dermatitis. In one embodiment, the formulation comprises from 30% to 50% of magnesium oxide and from 35% to 55% lipids. The formulation of the invention is advantageously used in alleviating or preventing the symptoms associated with contact dermatitis, skin irritation, and diaper rash. The formulation is useful in alleviating or preventing pruritus, particularly pruritus associated with using diapers, in adults and children, including babies. The formulation of the invention has a consistence of paste, ointment, or cream. The consistence of the formulation according to the invention may be regulated by incorporating diluent according to the need, wherein the diluent may be aqueous or non-aqueous. In one embodiment, the formulation of the invention is employed for treating skin irritation or contact dermatitis, particularly irritation or dermatitis caused or aggravated by urine or feces. In a preferred embodiment, the anti-irritant skin formulation of the invention is used in preventing and mitigating diaper rash. In one embodiment, the invention provides a zinc-free ointment or cream for mitigating skin irritation. In other embodiment, the invention provides a zinc-free, dehydrating ointment for mitigating skin irritation.

The invention provides a method of manufacturing an ointment for preventing or mitigating contact dermatitis, skin irritation, atopic dermatitis, or diaper rash, comprising i) providing a solid phase of pharmaceutically acceptable magnesium oxide comprising up to 5% magnesium hydroxide, up to 5% magnesium carbonate, up to 5% water, and less than 0.05% metals other than magnesium! ii) providing a powder of cosmetic clay! iii) providing a liquid phase of cosmetically acceptable lipids! and iv) combining said liquid phase of step iii with said solid phase of step i and with said powder of step ii, thereby obtaining a homogenous paste! wherein said phase of magnesium oxide constitutes from 35% to 45% of said homogeneous paste, said powder of clay constitutes from 12% to 18% of said homogeneous paste, and said lipids constitute from 40% to 50% of said homogeneous paste. Said liquid phase of the lipids is obtaining by heating the lipids to a temperature higher than ambient temperature. Said step iv may further comprise admixing diluents, preservatives, perfumes, additional pharmaceutically active agents, or other agents adjusting the biological properties, physico-chemical properties, or visual properties of the formulation. Said solid phase of magnesium oxide is preferably a powder comprising up to 10% magnesium hydroxide, obtained by calcining magnesium hydroxide at a temperature of from 400°C to 900°C. Said cosmetic clay may be talc, and said liquid phase of cosmetically acceptable lipids comprises paraffins, waxes, and caprylic/capric triglycerides.

The invention is directed to method of treating or preventing a condition selected from the group consisting of contact dermatitis, skin irritation, atopic dermatitis, diaper rash, and pruritus, comprising applying onto the skin of a subject, preferably a subject using a diaper, a paste comprising from 10% to 50% of a magnesium-based material and from 35% to 55% lipids, wherein said magnesium based material is selected from the group consisting of magnesium oxide, magnesium hydroxide, hydrated magnesium oxide, carbonated magnesium oxide, weathered magnesium oxide, calcined magnesium hydroxide, and mixtures thereof. In a preferred embodiment, said magnesium-based material is calcined magnesium hydroxide, preferably containing at least 90% magnesium oxide, and said lipids comprise paraffin, wax, talc, caprylic/capric triglycerides, and optionally an agent selected from preservatives, perfumes, diluents, and additional active agents. In a preferred embodiment, said paste comprises from 30% to 50% magnesium oxide, from 35% to 55% lipids, and from 10% to 20% cosmetic clay.

In some embodiments, the formulation comprising magnesium based material of the invention is used for treating or preventing a condition selected from diaper rash, skin irritation, contact dermatitis, and atopic dermatitis, while employing sprays, spray systems, pumps, and Bag-on-Valve (BoV) systems.

Detailed Description of the Invention

It has now been found that a paste formulation containing magnesia based material exhibits very good recovery effects on SDS-irritated skin. For example, a zinc free paste containing calcined magnesium hydroxide material with a magnesium oxide content of at least 90%, paraffin, wax, talc, and caprylic/capric triglycerides shows the same or better mitigating features than classic zinc oxide baby ointment. Without relating to any particular theory, it seems that the combination of the main components is benign for handling the skin irritation, such as diaper rash! magnesium oxide, and particularly magnesium oxide prepared by calcining magnesium hydroxide, may function as antimicrobial agent and possibly also as dehydrating agent, while adsorbing/absorbing eventual irritants, and so it may act synergistically with the other components of the mixture in neutralizing the organisms or chemicals which typically contribute to the skin irritation. The anti-irritant skin formulation of the invention may comprise Mg-based materials selected from magnesium oxide, magnesium hydroxide, hydrated magnesium oxide, carbonated magnesium oxide, weathered magnesium oxide, calcined magnesium hydroxide, and mixtures thereof, in an amount of 10 to 50% and from 35 to 55% lipids. In one aspect of the invention, the formulation is an anti-irritant cream comprises from 10 to 30% magnesium oxide, from 35 to 55% lipids, and from 30 to 50% water. In a preferred aspect of the invention, the formulation is an anti-irritant ointment comprising from 30 to 50% magnesium oxide, from 35 to 55% lipids, and from 10 to 20% cosmetic clay.

The formulation of the invention is preferably prepared by including 10-50% of magnesia based material selected from the group consisting of magnesium oxide, hydrated magnesium oxide, carbonated magnesium oxide, weathered magnesium oxide, and calcined magnesium hydroxide. The recited magnesia based material is mixed with lipids, and optionally with water and cosmetic clay, wherein the initial MgO content in the formulation is usually 10-45%, such as 12-36%, and it may decrease in time due to the weathering reactions. In one preferred embodiment, an anti-irritant ointment of the invention is prepared by mixing magnesia based material, lipids, and cosmetic clay, in relative amounts of 35-45%, 40-50%, and 10-20%, wherein said magnesia based material initially comprises at least 90% MgO and up to 10% magnesium hydroxide. The ointment comprises, in one embodiment, from 30 to 45% MgO; from 25 to 40%, such as from 29 to 35% paraffin; from 10 to 20%, such as from 12% to 18% talc; from 4 to 12%, such as from 6% to 10% waxes; from 2 to 6%, such as from 3% to 5% caprylic/capric triglycerides. The ointment may comprise up to 5% magnesium hydroxide. The water content of the ointment is usually lower than 3%, such as up to 2%, for example up to 1%. The anti-irritant formulation according to the invention preferably comprises a magnesia-based material and cosmetically acceptable ingredients! in some embodiments, the formulation is a paste or an ointment and comprises from 30 to 60% lipids and from 10 to 20% cosmetic clay, or it is a cream and comprises from 30 to 60% lipids and from 30 to 50% water, or it is a spray and comprises from 65 to 75% lipids, or it is a water-based pump formulation and comprises from 50 to 68% water and between 12 and 20% lipids, such as about 15% lipids. The formulation according to the invention usually comprises preservatives or stabilizers, such as BHT and methylparaben. The composition may further comprise non-irritating diluents or fillers, non-irritating perfumes, etc. For special needs, the composition comprises additional active agents to address eventual other problems, including antiseptic agents, antibacterial agents, antifungal agents, antihistamines, anti-inflammatory agents, and others. For eons, most of the baby ointments have comprised zinc oxide; the zinc-free compositions of the invention broadens the range of available anti-irritants and antipruritics for the child care realm. The cream or ointment of the invention, as well as contactless means like spray systems, aim at preventing or relieving the symptoms of contact dermatitis or skin irritation. Said dermatitis and skin irritation may be caused or aggravated by variety of factors, comprising parasites, microorganisms, pollutants, and allergens! the irritation materials may originate from urine or faces. New means for protecting the afflicted skin, particularly in children, are in high demand. The skin irritation can be manifested by visible skin changes, but most distressing, for the children and parents as well, may be the resulting pruritus. A protecting layer of the zinc- free cream or ointment according to the invention neutralizes at least some of the mentioned irritating factors or reduces their access to the skin. The zinc- free and non- aqueous ointment of the invention combines said neutralizing activities with its benign dehydrating effects, providing a particularly efficient means for handling diaper rash.

Incontinence is a general problem in older adults, bringing painful challenges. Creams and talc have been broadly used to protect the skin exposed to the irritating matter, but the need for new means in the effort to keep skin healthy in the users of incontinence pads or adult diapers has never been fully satisfied. Moreover, hand contact between an adult user and the treating person may sometimes be embarrassing. The invention provides new formulations which can assist in treating and protecting the skin, which prevent skin irritation, diaper rash, and the resulting infections, and particularly it provides spray formulations, avoiding manual application onto the skin and allowing pleasant treatment, while minimizing any embarrassment of inconvenience.

Mg-based materials which may be employed in preparing the anti-irritant formulation of the invention include a pharmaceutically acceptable component selected from the group consisting of magnesium oxide, magnesium hydroxide, magnesium carbonate, and a mixture thereof. In a preferred embodiment, the magnesium-based material comprises at least 80%, such as at least 90% MgO before combining with lipids. The lipids may comprise paraffin and wax, wherein said paraffin may be a pharmaceutically acceptable mixture of hydrocarbons having mostly between 15 and 40 carbon atoms, and having a suitable consistence! said wax is preferably a pharmaceutically acceptable wax, such as lanolin.

The invention aims at treating and preventing skin conditions associated with skin irritation, inflammation, or allergy, particularly conditions resulting in pruritus, comprising topically applying a layer of pharmaceutically acceptable cream, ointment, paste, aerosol sprays or pump sprays containing magnesia based material in an amount of between 7 and 60%, such as from 30 to 45%, for example from 35 to 45%. In a preferred embodiment, the magnesia based material is obtained by calcining magnesium hydroxide and it comprises at least 90% MgO. The invention thus provides a topical treatment of conditions associated with skin inflammation or pruritus. In some embodiments, the topical treatment is accompanied with systemic treatment. Usually, the treatment will aim at suppressing or reducing pruritus and diaper rash in adults and children.

The invention is thus directed to providing magnesia based protectant against skin irritation in the form of anti-irritant topical formulations comprising magnesia based materials, the protectant preferably comprising at least 7% MgO. Provided is an ointment and a cream, the use thereof, and a method for manufacturing them. The magnesia based formulations are efficient in mitigating symptoms of skin conditions such as contact dermatitis or atopic dermatitis, and they are particularly useful for managing diaper rash, including preventing or mitigating diaper rash. The invention provides needed means for alleviating pruritus in elderly and children, including babies. The magnesium-based formulations of the invention, or their use, may comprise creams, ointments, sprays or spray systems, pumps, Bag-on- Valve (BoV) systems, etc.

The invention will be further described and illustrated by the following examples.

Examples

Example 1

Preparing magnesium-based materials for anti-irritation formulations

Magnesium hydroxide (MH, prepared by thermal decomposition of magnesium chloride, Israel Chemicals Ltd.) was calcined at a temperature of from 400°C to 900°C, converting the material to magnesium oxide with residual magnesium hydroxide of up to 10% - denoted here as CareMag B. For the purpose of comparison, several comparative samples were prepared as follows. A partially converted sample of MH was obtained - denoted here as MMO. A sample of partially carbonated magnesium oxide (containing about 5% magnesium carbonate) was obtained by soaking CareMag B with carbon dioxide under ambient temperature at high humidity - denoted here MB9.

Example 2

Preparing anti-irritation formulations

A cream for use as anti-irritation formulation in accordance with one embodiment of the invention was prepared by mixing MgO-based material CareMag B, described in Example 1, with other ingredients in the amounts presented in Table 1. The resulting cream is denoted here as AntiRashl3. Tab. 1 The ingredients for preparing an Anti-Rash Cream

according to the invention (AntiRash 13)

Ingredient Content (wt%)

Water 39.60

Methyl paraben 0.20

Magnesium sulfate - heptahydrate 0.70

Mineral oil 14.00

Vaseline 18.00

Paraffin wax 2.00

Dimethicon 1.00

Bees wax 4.00

PEG-30 Dipolyhydroxystearate 3.00

Polyglyceryl-3 diisostearate 2.00

Sorbitan sesquioleate 1.00

Vitamin E acetate 0.30 Propyl paraben 0.20

Phenoxyethanol 0.70

CareMag B 13.00

Aloe vera gel 0.20

Perfume 0.10

A method for preparing anti-irritation ointments according to one embodiment of the invention was employed, wherein MgO -based materials as described in Example 1 were slowly mixed with other ingredients in the amounts presented in Table 2, at a temperature of between 70 and 80°C, usually 75 °C, for two hours.

The ingredients for preparing anti-irritant ointments in a method according to the invention

The obtained ointments were tested in regard to the effects on the skin. Some of the results are presented below. Example 3

Skin sensitivity test with CareMag B ointment

Anti-irritation ointment prepared from CareMag B in accordance with Example 2 (named as AntiRash 40), was characterized in dermatology tests on 50 volunteers in The Institute for Skin Reseach, Tel Aviv.

A. In one series, the skin was exposed to 15 mg of the paste for 48h followed by examination.

B. In another series, sensitizing properties by Draize repeated insult patch (RIPT) was tested by exposing the skin to 15 mg paste for 24 hours, repeated nine times, followed by examination.

No volunteers showed any allergic reaction or sensitivity.

Example 4

Testing the efficiency of anti-irritation ointments in the skin recovery

The skin barrier patch test (testing recovery from disturbed barrier function) was performed in the institute proDERM, Germany, employing 22 volunteer subjects. To determine the recovery effect of several anti-irritant ointments described in Example 2 in the patch test, the skin barrier was damaged on Day 1 by a four hours patch with 10% sodium dodecyl sulfate (SDS). Afterwards, the tested product was applied for 4 days. Starting on Day 2, an objective dermatological evaluation was performed at all assessment times. The tested products were also compared with a damaged but untreated control area.

no erythema

faint or diffuse erythema

moderate to severe erythema, possibly slight edema, but the skin without papules

severe erythema, possibly moderate edema, eventually a few papules or deep fissures, or other defects of the skin surface, or moderate to severe erythema in the fissures 3 = very severe erythema (beet redness), generalized papules or vesicles, and/or defects of the skin surface extending beyond test site

4 = very severe erythema with edema extending beyond test site and vesicles or eschar formation.

The score was evaluated from Day 2 to Day 5 on 22 volunteers, by a trained evaluator. The following materials and treatments were compared:

A. An ointment comprising Mg-based material CareMag B and prepared as described in Example 2 (AntiRash 40) was applied after 10% SDS.

B. An ointment comprising Mg-based material MH and prepared as described in Example 2 was applied after 10% SDS.

C. An ointment comprising Mg-based material MB9 and prepared as described in Example 2 was applied after 10% SDS.

D. An ointment comprising Mg-based material MMO and prepared as described in Example 2 was applied after 10% SDS.

E. A commercial baby paste ("Desitin-Maximum Strength", denoted here as Desitin 40) having essentially the same composition as ointments A to E but lacking Mg-based material and containing 40% ZnO was applied after 10% SDS.

F. An ointment comprising all ingredients as shown in Table 2 in Example 2 except for the Mg-based material, which was replaced with talc, was applied after 10% SDS. The materials were compared with two controls:

G. Damaged (10% SDS) and untreated skin.

H. Undamaged and untreated skin.

The score of H (undamaged and untreated skin) was 0 throughout the assessment time. The scores of A to G were between 1.3 to 1.5 on Day 2, and they decreased to between 0.4 and 0.6 on Day 5. The scores for Day 2, 3, 4, and 5 were averaged for each treatment, as showed in Tab. 3. In addition the mean score of day 2 is presented in the table.

Tab. 3 Comparing dermatological treatments results on the

skin damaged by 10% SDS; erythema mean score on day 2, and averaged over days 2 to 5 for each treatment

From the above table it can be seen that an anti-irritant ointment comprising a Mg-based material (A to D) in accordance with the invention provides better recovery of damaged skin than a lipid ointment without the Mg-based material (F), and the attained effects are even better than for a commercial zinc oxide paste (E). The best results were provided by an anti- irritation ointment comprising 40% CareMag B - denoted here as AntiRash40. In should also be noted that on day 2 AntiRash 40 performed significantly better than Desitin 40 (p=0.031, using Wilcoxon Signed Ranks test). Example 5

Testing calming efficacy of AntiRash40

Calming efficacy of an ointment according to the invention, AntiRash40, to be used as a baby diaper ointment, was tested on 10 volunteers subjects in the Institute for Skin Research, Tel Aviv, Israel. Skin was irritated by exposing to 0.5% SDS for 24 hours, followed by applying an ointment patch. Erythema was characterized by measuring the skin redness by Derma- spectrometer of Cortex Technology within 1-6 hours after applying the patch. The redness rise of SDS-irritated skin versus non-irritated skin was much lower in case of the skin treated with AntiRash40 paste of the invention. The redness rise of the treated skin was less than 30% of the redness rise observed in the untreated skin, over the whole time interval of 6 hours.

Example 6

Skin scratch test

The test, performed on 22 volunteers in the institute proDERM, Germany (different time and different subjects than in Example 4), aimed at evaluating levels of the skin irritation caused by repeated application of the substance to pre-damaged (scarified) skin. This test did not deal with beneficial effects of the substance. Three applications were performed onto the scratched skin of volar forearms for 23 hours with a patch test system. One hour after removal of patches, a visual assessment was performed on Day 2, Day 3, and Day 4. On Day 2 and Day 3, immediately after visual evaluation, re-application of fresh samples was performed.

Materials, including AntiRash40 according to the invention and Desitin 40 as described above were compared. Magnesia based AntiRash40 exhibited lower level of irritation on the skin than ZnO based Desitin 40. Example 7

Easy use of the paste on the skin

Five persons compared four formulations on their skin - two ointments and two creams. The creams were commercial "Desitin-Rapid Relief (comprising 13% ZnO) versus AntiRashl3 according to the invention as described in Example 2 above (comprising 13% MgO). The ointments were "Desitin- Maximum Strength" (Desitin 40 as described above, comprising 40% ZnO) versus AntiRash40 (comprising 40% MgO-based material as described in Examples 2 and 4 above). All volunteers reported that both magnesia based AntiRash formulations were easier to spread and provided better feeling on the skin than the commercial Desitin formulations.

Example 8

Preparing gas spray formulations

Five formulations for gas sprays were prepared by heating components no. 1 to no. 5 of Table 4 at 70°C followed by cooling to RT. The remaining ingredients were added at room temperature (RT) during stirring and the formulations were filled to spray cans. The gas was added to the cans using an aerosol filling machine. The gas/liquid ratio was 85/15. Formulation no. 2 had an extra addition of Vaseline, formulation no. 3 of magnesium, formulation no. 4 of Vaseline and magnesium, and formulation no. 5 of calendula.

Tab. 4 The ingredients for preparing five spray anti-irritant

formulations according to the invention

Contents of the components (wt%)

Ingredients

1 2 3 4 5

1. Mineral oil 41.52 36.33 38.89 33.00 36.33

2. Capric / caprylic triglyceride 18.68 18.68 17.68 17.68 18.68

3. BHT 0.05 0.05 0.06 0.06 0.05 4. Lanolin USP 5.19 5.19 5.89 5.89 5.19

5. Vaseline (petrolatum ) 0.00 5.19 0.00 5.89 0.00

6. L-alpha-bisabolol 0.21 0.21 0.24 0.24 0.21

7. Famesol 0.31 0.31 0.35 0.35 0.31

8. Ethylhexylglycerin 0.31 0.31 0.35 0.35 0.31

9. Calendula 5.19 lO.Caprylic/capric triglyceride &

propylene carbonate & 6.23 6.23 7.07 7.07 6.23 stearalkonium hectorite

11. CareMag B 25.95 25.95 29.46 29.46 25.95

12. Basic magnesium carbonate 1.56 1.56 1.56

Example 9

Preparing water-based pump formulations

A formulation for pump sprays was prepared by heating components no. 1 to no. 3 of Table 5 at 85°C, followed by adding component 4 with high- shearing. Components no. 5 to 13 were prepared in a different vessel at 80°C (oil phase). The oil phase was added to the aqueous phase with mixing, followed by cooling to 40°C. The remaining ingredients were added at this temperature during stirring. The formulation was poured into the container.

The ingredients for preparing pump spray anti-irritant formulations according to the invention

Ingredients Contents of the components (wt%)

1. Water 64.2

2. Disodium EDTA 0.1

3. Glycerin 3 4. Microcrystalline cellulose &

1.5

cellulose gum

5. Caprylic / capric triglyceride 10

6. Lanolin USP 3

7. Dimethicone 1

8. Sorbitan stearate 0.8

9. Alpha bisabolol 0.1

10. Glyceryl stearate SE 1.5

11. Mg-based material 10

12. Basic magnesium carbonate 3

13. Ethylhexylglycerin &

1

Phenoxyethanol

14. Aloe Vera gel 0.2

15. Chamomile extract 0.1

16. Perfume 0.5

While the invention has been described using some specific examples, many modifications and variations are possible. It is therefore understood that the invention is not intended to be limited in any way, other than by the scope of the appended claims.

Claims

1. A formulation comprising from 7% to 60% of a magnesium-based material and from 15% to 75% lipids for use in treating or preventing a condition selected from the group consisting of diaper rash, skin irritation, contact dermatitis, and atopic dermatitis, wherein said magnesium based material comprises magnesium oxide or magnesium hydroxide.

2. The formulation of claim 1, wherein said magnesium-based material is selected from the group consisting of hydrated magnesium oxide, carbonated magnesium oxide, weathered magnesium oxide, calcined magnesium hydroxide, and a mixture thereof, and wherein said material comprises less than 0.05% of metals other than magnesium.

3. The formulation of claim 1, comprising from 10% to 50% of magnesium oxide and from 35% to 55% lipids.

4. The formulation of claim 1 comprising from 12% to 45% of magnesium oxide, from 40% to 50% lipids, and up to 20% cosmetic clay.

5. The formulation of claim 1 comprising from 1 to 68% water.

6. The formulation of claim 1 comprising from 5 to 20% magnesium hydroxide.

7. The formulation of claim 1 comprising from 35% to 45% magnesium oxide (MgO), from 40% to 50% lipids, and from 12 to 18% cosmetic clay.

8. The formulation of claim 1, comprising up to 5% magnesium hydroxide, up to 5% magnesium carbonate, and up to 5% water.

9. The formulation of claim 1 comprising from 36% to 44% magnesium oxide, from 29% to 35% paraffin, from 6% to 10% waxes, from 12% to 18% talc, and from 3% to 5% caprylic/capric triglycerides.

10. The magnesia based formulation of claim 1, for use in alleviating or preventing the symptoms associated with contact dermatitis, skin irritation, and diaper rash.

11. The magnesia based formulation of claim 1, for use in alleviating or preventing pruritus, particularly pruritus associated with using diapers.

12. The magnesia based formulation of claim 1, which is a paste, ointment, cream, aerosol spray or water based spray (pump) for use in treating skin irritation or contact dermatitis, particularly irritation or dermatitis caused or aggravated by urine or feces.

13. The magnesia based formulation according to claim 7, comprising from 35% to 45% magnesium oxide (MgO), from 40% to 50% lipids, and from 12 to 18% cosmetic clay, for use in preventing and mitigating diaper rash.

14. The formulation of claim 1, being an anti-irritant formulation comprising from 35% to 45% magnesium oxide (MgO), from 40% to 50% lipids, and from 12 to 18% cosmetic clay.

15. The formulation of claim 1, which is a zinc-free ointment or cream for mitigating skin irritation.

16. The formulation of claim 7, which is a zinc-free, dehydrating ointment for mitigating skin irritation.

17. The formulation of claim 1, further comprising additional active agents selected from the group consisting of antiseptic agents, antibacterial agents, antifungal agents, antihistamines, and anti-inflammatory agents.

18. A method of manufacturing a magnesia based ointment for preventing or mitigating contact dermatitis, skin irritation, atopic dermatitis, or diaper rash, comprising

i) providing a solid phase of magnesium oxide comprising up to 5% magnesium hydroxide, up to 5% magnesium carbonate, up to 5% water, and less than 0.05% metals other than magnesium; ii) providing a powder of cosmetic clay!

iii) providing a liquid phase of cosmetically acceptable lipids; and iv) combining said liquid phase of step iii) with said solid phase of step i) and with said powder of step ii), thereby obtaining a homogenous paste;

wherein said phase of magnesium oxide constitutes from 35% to 45%, said powder of clay constitutes from 12% to 18%, and said lipids constitute from 40% to 50% of said homogeneous paste.

19. The method of claim 18, wherein said step iv) further comprises admixing diluents, preservatives, or perfumes.

20. The method of claim 18, wherein said solid phase of magnesium oxide is a powder comprising up to 10% magnesium hydroxide, obtained by calcining magnesium hydroxide at a temperature of from 400°C to 900°C.

21. The method of claim 18, wherein said cosmetic clay is talc, and said liquid phase of cosmetically acceptable lipids comprises paraffins, waxes, and caprylic/capric triglycerides. The method of treating or preventing a condition selected from the group consisting of contact dermatitis, skin irritation, atopic dermatitis, diaper rash, and pruritus, comprising applying onto the skin of a subject afflicted by said condition, preferably a subject using a diaper, a non^¬ aqueous, zinc-free, anti-irritant paste comprising from 30% to 45% magnesium oxide, from 35% to 55% lipids, and from 10% to 20% cosmetic clay.

The formulation of claim 1, wherein said treating or preventing comprises an item selected from the group consisting of sprays, spray systems, pumps, and Bag-on- Valve (BoV) systems.