NITROUS OXIDE CONTAINING DERMATOLOGICAL COMPOSITION_____________

Abstract: Dermatological compositions comprising nitrous oxide and at least one essential fatty acid or lower alkyl ester thereof in a dermatologically acceptable carrier medium is useful in the treatment of a variety of skin, muscle and joint disorders including psoriasis, shingles, fever blisters, chicken pox, acne, chilblains, eczema, chloasmas, alopecia, dermatitis, ringworm and burn wounds. The composition preferably also includes additional ingredients selected from coal tar, collagen, nicotinamide, nicotinic acid, lanolin, vitamin E, methyl salicylate, arnica, and H1-antagonist antihistamines or combinations thereof.

Description: NITROUS OXIDE CONTAINING DERMATOLOGICAL COMPOSITION FIELD OF THE INTENTION THIS invention relates to dermatological compositions. The compositions of this invention are suitable to be applied to the human skin for the treatment of a variety of skin, muscular, joint and peripheral circulation conditions. BACKGROUND OF THE INVENTION It is known in the field of dermatology to make use of coal tar preparations in the treatment of certain skin conditions, for example, psoriasis [Hunter J.A.A., Savin J.A. and Dahl M.V. , Clinical Dermatology, Blackwell Scientific Publications p.49]. It has also been suggested that essential fatty acids, including evening primrose oil may be used in the treatment of skin conditions such as eczema [see references cited by July Graham, Evening Primrose Oil, Thorsons, pp. 127-128]. Various other compositions are known to be used in the treatment of these and other skin conditions. OBJECT OF THE INVENTION It is an object of the present invention to provide novel dermatological compositions. SϋMMASY OF THE INVENTION According to the present invention there is provided a dermatological composition having as active ingredients nitrous oxide and at least one essential fatty acid or ester thereof selected from the group consisting of linoleic acid, arachidonic acid, linolenic acid, gamma-linolenic acid, and the lower alkyl esters thereof in a dermatologically acceptable carrier. The composition may further include one or more supple¬ mentary ingredients selected from the group consisting of liquid picus car . [also known as coal tar solution], collagen, nicotinamide, nicotinic acid, lanolin, vitamin E, methyl salicylate, and known H^-antagonist antihistamines. In the "preferred form of the invention the composition is saturated with nitrous oxide. Also in the preferred form of the invention the essential fatty acid component of the composition comprises a mixture of esters of the fatty acids listed above. Thus in the most preferred form of the invention the fatty acid component of the composition is constituted by the complex known as Vitamin F and in this regard it is preferred to make use of the ester form of Vitamin F known as Vitamin F Ethyl Ester. This product is commercially available under the trade description of Vitamin F Ethyl Ester CLR 110 000 Sh.L. U./g from CLR Chemicals Laboratorium Dr. Kurt Richter GmbH, of Berlin, Germany. The typical fatty acid distribution of this product is as follows: In one preferred form of the invention the composition comprises only coal tar solution as a supplementary active ingredient. In this form of the invention the composition is useful in the treatment of psoriasis, fever blisters, herpes simplex, shingles, chicken pox and eczematous conditions of the skin and scalp. In another form of the invention the composition comprises coal tar solution in combination with one of collagen, nicotinamide, and lanolin. In these forms of the invention the composition has been shown to be BSTITUTE SHEET useful for the treatment of acne, conditions involving poor peripheral circulation, such as chilblains, and ichtyoses respectively. In an alternative form of the invention the composition may contain coal tar solution in combination with an antihistamine selected from the Hi-antagonist group and be used for the treatment of atopic and allergic conditions manifesting in skin irritations, such as eczema, dermatitis and ringworm. In a further form of the invention the supplementary ingredient may comprise methyl salicylate in which form the composition is useful in the treatment of muscle and joint pains. The composition may finally comprise collagen and lanolin as supplementary ingredients in which form it is useful in cosmetic preparations, or for the treat¬ ment of alopecia or minor skin ailments, such as chloasmas. The composition may be formulated to have any dermatologically acceptable consistency, i.e. as a lotion, cream, ointment or gel. EXAMPLES OF THE INVENTION Without thereby limiting the scope of the invention some examples will now be described to illustrate the invention . E X A M P L E 1 Dermatological composition useful in treatment of psoriasis Five litres of water was saturated with N2O at room temperature in a pressure vessel . 75g of vitamin F ethyl ester, 50g vitamin E and 50g chre aphor was mixed and heated to about 80 C C and the mixture was emulsified in the N2O saturated water with stirring. 500ml of a prepared coal tar solution BP73 [also known as liquid picus carb. ] was produced by dissolving 100 g of prepared coal tar BP73 in 375 g of ethyl alcohol with the addition of Polysorbate 80. The coal tar solution was saturated with N2O in a pressure vessel and mixed with the above emulsion. The viscosity of the solution was modified according to technique known in the trade i.e. with xanthan gum to provide a gel. In this regard it is preferred to use Keltrol A TF, a product marketed commercially by the Kelco Division of Merck & Co., Inc. If desired a suitable preservative such as a parabenz compound may be added. The resulting gel was used in the treatment of 53 psoriasis sufferers. All these sufferers had previously attempted alternative forms of psoriasis medication and treatment and without success. Such treatments included UV radiation, coal tar, cortizone and etretmate preparations and even Dead Sea baths. The patients applied the gel as described above to the affected areas 2 or 3 times daily. Of those treated 88, 1% reported a definite improvement in their condition. On average the period of treatment before positive results were seen was 3 weeks. In 6 of the cases it took more than 6 weeks of treatment before improvements were seen. 72% of the patients treated were considered to have derived long term results from the use of the gel described above as evidenced by the clearing and sustained absence of lesions for a period of more than 3 months. Such long term results were achieved on average after 8,5 weeks of treatment. In treating patients with a gel it is preferred to use a suitable skin moisturiser with the gel to prevent drying out of the skin. Such moisturising ingredients may of course also be incorporated into the composition of the invention to produce -a cream formulation which may then be used as a supplementary treatment with the gel formulation. E X A P L E Zoster infection] ana eczematous skin conαitions An alternative dermatological composition was made up to contain the following ingredients m the quantities stated per 100 g of final product : gram Prepareα coal tar BP1973 1,00 Vitamin F Ethyl Ester 1,50 Nitrous Oxide [N2O] qs Poiysorbate 80 [emulsifier] 0,25 Ethyl Alcohol [ solvent/dispersant ] 3,75 PEG-40 [Hydrogenateα caster oil - as solubilizer] 0,45 Vitamin E [dl-alpha Tocopherol - as antioxidant] 0,30 Sodium propyl paraben [as preservative] 0,05 Methyl paraben [as preservative] 0,10 Xanthan Gum 0,8 - 0,9 Water balance 100 Tne coal tar and poiysorbate 80 [Crillet 4] were mixed with warming to renαer it fluiα and poured into about 755. of the ethyl alcohol witn stirring whicn was continued for 1 hour to acmeve dispersion. The mixture was alloweα to cool for 24 nours, the super¬ natant was decanted through a filter and the mixing vessel and filter were washeα with part of the remain- mg alcohol added tnereto. The resulting solution was SUBSTITUTE SHEET charged with N2O gas by maintaining the solution in a pressure vessel under N2O at 2 bar for 96 hours. The N2O charged coal tar solution was stored in a cool place. The water fraction of the composition was prepared by charging the water with N2O for 48 hours at 2 bar as described above. Again, the N2O charged water was kept in a cool place. A third sub-mixture was prepared by mixing together and heating to 80°C the Vitamin F, Vitamin E and PEG-40 hydrogenated castor oil. Once mixed the methyl paraben was added with stirring to obtain a homogenous mixture of oil miscible fractions. This mixture was kept at 80°C and added with stirring into part of the N2O charged water which had previously been prepared and provided with the sodium propyl paraben to produce an oil-in-water emulsion. Finally, the balance of the N2O charged water, the charged coal tar solution and the oil-in-water emulsion were mixed with stirring while granulated xanthan gum was slowly added to the mixture in sufficient quantity to achieve a viscosity of 1740 cps. The gel is passed through a 60 mesh sieve and packaged into sealable containers. SUBSTITUTE SHEET The gel formulated as set out above is presently undergoing double blind crossover clinical trials against aqueous cream as placebo for the treatment of fever blisters [Herpes Zoster infection]. It is expected that the results will confirm earlier results obtained in uncontrolled trials in which the composition was found effective against such infections as well as to provide relief to patients suffering from shingles, chicken pox, psoriasis and eczeraatous conditions of the skin. E X A M P L E 3 Dermatological composition for use in the treatment of eczema and dermatitis A composition having the components as set out in Example 2 but with the addition of 1 g diphenhydramine hydrochloride and made up as therein described was found in uncontrolled trials to bring relief and remission to patients suffering from atopic eczema as well as to patients suffering from dermatitis. E X Δ M P L E 4 ComDOSition for treatment of chilblains A composition as described in Example 2 to which 1 g of B TITUTE SHEET nicotinic acid had been added was reported by patients to relieve the symptoms of chilblains and to restore healthy skin. E X A M P L E 5 Composition for treatment of acne and scar tissue A composition as described in Example 2 was made up with the further addition of 1,5 g collagen and 1,5 g lanolin . This composition was successfully tested on persons suffering from acne vulgaris and was found not only to clear up the condition but also to result in visual improvement of appearance of the formerly heavily blemished skin. The same composition was also used by a 13 year old patient some one year after she had suffered extensive third degree burn wounds on the face, shoulders and back. Encouraging signs of repair of the scarred skin was observed. E X A M P L E 6 Composition for treatment of fibrositis, muscle cramps and improvement of peripheral circulation BSTITUTE SHEET A composition as described in Example 2 but not including coal tar, poiysorbate 80 and alcohol was made up substantially as therein described. This composition was found in several trials to give substantial relief of fibrositis and muscular cramps when topically applied. It was also reported by patients to relieve swelling following tissue trauma such as caused by bumps or falls giving rise to impaired blood circulation. Some patients found that the effect of this composition was enhanced after the addition thereto of methyl silicate or arnica. E X A M P L E 7 Cosmetic composition A composition as described in Example 2 but omitting the coal tar, poiysorbate 80 and alcohol and with the addition ■ of 1,5 g collagen, 1,5 g lanolin and 1,5 g additional Vitamin E resulted in a cosmetic product which was found to be suitable for the removal of chloasmas, warts and moles and which also stimulated hair growth in alopecia cases. Many variations of the invention may be devised without departing from the scope and spirit of the invention. SUBSTITUTE SHEET

Claims: CLAIMS 1. A dermatological composition having as active ingredients nitrous oxide and at least one essential fatty acid or ester thereof selected from the group consisting of linoleic acid, arachidonic acid, linolenic acid, gamma-linolenic acid, and the lower alkyl esters thereof in a dermatologically acceptable carrier. 2. The composition of claim 1 includes a supplement- ary active ingredient selected from the group consisting of liquid picus carb. [also known as coal tar solution], collagen, nicotinamide, nicotinic acid, lanolin, vitamin E, methyl salicylate, and a H^-antagonist antihistamines. 3. The composition of claim 2 saturated with nitrous oxide. 4. The composition of claim 1 wherein the essential fatty acid component of the composition comprises a mixture of esters of the fatty acids set out therein. 5. The composition of claim 4 in which the fatty acid component of the composition is selected from the complex known as Vi amin F and Vitamin F Ethyl UBSTITUTESHEET Ester. 6. The composition of claim 2 which has coal tar solution as a supplementary active ingredient for use in the treatment of psoriasis, fever blisters, herpes simplex, shingles, chicken pox and eczematous conditions of the skin. 7. The composition of claim 2 which has coal tar solution in combination with one of collagen, nicotinamide, and lanolin as supplementary active ingredients for use in the treatment of acne, conditions involving poor peripheral circulation, chilblains, ichtyoses and scar tissue. 8. The composition of claim 2 which has coal tar solution in combination with an antihistamine selected from the H^-antagonist group as supple¬ mentary active ingredients for use in the treat¬ ment of atopic and allergic conditions manifesting in skin irritations, eczema, dermatitis and ring¬ worm. 9. The composition of claim 2 which has as supple¬ mentary ingredient the compound methyl salicylate for use in the treatment of muscle and joint pains. SUBSTITUTE SHEET 10. The composition of claim 2 which has collagen and lanolin as supplementary ingredients for use as a cosmetic preparations, for the treatment of alopecia and in the treatment of minor skin ail- ments, such as chloasmas. 11. A method of treating a skin condition comprising the application of a dermatological composition as claimed in claim 1 to a patient in need of such treatment. 12. The use of nitrous oxide in the manufacture of a dermatological composition for use in the treat¬ ment of skin conditions. SUBSTITUTE SHEET

Inventors: MEYER PETRUS JOHANNES, MEYER, PETRUS, JOHANNES
Applicants: MEYER PETRUS JOHANNES, PITMY INT NV, PITMY INTERNATIONAL N.V.
Application year: 1993
Main classification: A61K33
IPC codes: A61K8, A61K33, A61P17, A61Q5, A61Q7, A61Q19