Skin care composition

Abstract

The present disclosure relates to a skin care composition comprising masticinic acid and vitamin B12 or a derivative thereof. The composition can be advantageously used in a method for the treatment of skin conditions, disorders or diseases, in particular psoriasis, more particularly plaque psoriasis.

Description

[0001] The present disclosure relates to a skin care composition comprising boswellic acid and vitamin B12 or a derivative thereof. The composition of the present disclosure can be advantageously used in a method of treating a skin condition, disorder or disease, particularly psoriasis, particularly plaque psoriasis. Background Art

[0002] Psoriasis is a chronic, non-contagious, inflammatory skin disease characterized by abnormal raised areas of skin. These areas may be red or purple, dry, itchy, and often contain plaques of silvery white scales. The underlying disease mechanism involves the immune system's response to skin cells. Psoriasis varies in severity, ranging from small localized patches to full-body coverage. Psoriasis is generally considered a genetic disease triggered by environmental factors, and about one-third of affected patients are affected due to genetic factors. Environmental factors (e.g., infection, exposure to UV radiation, stress, artificial foods, alcohol, smoking, or various medications) can further induce or aggravate the disease. Sometimes, psoriasis is accompanied by joint diseases or autoimmune diseases. Symptoms are often worse in the winter and with the concomitant use of certain medications (e.g., beta-blockers or NSAIDs). The disease affects 2-4% of the population, and the disease can begin at any age, but usually begins in adulthood. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphoma, cardiovascular disease, Crohn's disease, and depression. In particular, many patients with severe psoriasis experience invalidating itch and discomfort, and experience a significant reduction in their quality of life. Psoriatic arthritis affects up to 30% of psoriasis patients.

[0003] The main types of psoriasis are plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis, also known as psoriasis vulgaris, accounts for about 90% of cases. It usually appears as red patches with white scales on them. The most commonly affected areas of the body are the back of the forearms, calves, navel area, and scalp.

[0004] There is no known cure for psoriasis, but various treatments can help control symptoms. These treatments include steroid creams, vitamin D3 creams, ultraviolet light, and immunosuppressant drugs such as methotrexate. More severe forms of the disease often must be treated systemically with photochemotherapy, retinoids, methotrexate, hydroxyurea, azathioprine, or cyclosporine. However, some of these treatments have serious side effects and / or are not effective for some patients. In addition, treatments for more severe forms of psoriasis are expensive and often have adverse side effects and vary in effectiveness.

[0005] Therefore, there is a need in the art for more effective topical treatment alternatives.

[0006] WO 2006 / 022762 A1 discloses treatment of hyperproliferative skin diseases wherein the treatment regimen is oral ingestion and topical application of a natural dual-acting inhibitor of 5-lipoxygenase and human leukocyte elastase such as boswellic acid, in combination with an orally ingested bioavailable organic selenium supplement. The topical formulation disclosed as part of the treatment regimen contains 5% boswellic acid.

[0007] Giada Maramaldi et al., Clinical, Cosmetic and Investigational Dermatology, 2014: 7, 321-327, discloses that in patients with psoriasis, the use of a 0.5% boswellic acid-containing The cream improved the scaling.

[0008] Del Duca Ester et al., International Journal of Immunopathology and Pharmacology, Vol. 30, No. 4, December 2017, pp. 439-444, discloses that an ointment containing 0.07% vitamin B12 (cyanocobalamin) is effective for mild to moderate plaque psoriasis.

[0009] Hagemann Ingke et al., Acta Derm Venerol (Stockh) 1996; 76, 353-356 disclose that an ointment containing 10% urea (carbamide) improves plaque psoriasis.

[0010] Therefore, the technical problem underlying the present invention is to provide improved topical compositions for the treatment of psoriasis, in particular for the treatment of plaque psoriasis. These methods should be effective and significantly improve symptoms, and should have no or only mild side effects.

[0011] The solution to the above technical problem is achieved by the composition of the present invention.

[0012] Vitamin B12 (cyanocobalamin or cobalamin) is a water-soluble vitamin involved in DNA synthesis and fatty acid and amino acid metabolism. It is important for the normal function of the nervous system through its role in myelin synthesis and is important for the maturation of red blood cells in the bone marrow in the circulatory system. The term "vitamin B12 or its derivatives" as used herein includes all forms of vitamin B12 and any compound having vitamin B12 activity. In particular, the term includes cobalamin, hydroxycobalamin, cyanocobalamin, methylcobalamin, adenosylcobalamin, 5'-deoxyadenosyl-cobalamin, hydrocobalamin and nitrosocobalamin.

[0013] Boswellic acid is an organic acid composed of a pentacyclic triterpene, a carboxyl group, and at least one other functional group. 30 H 48 O3) have additional hydroxyl groups and differ only in their triterpenoid structures. 32 H 50 O4), the hydroxyl group is replaced by an acetyl group. Other boswellic acids include keto-boswellic acid and its acetyl counterpart. Boswellic acid is produced by plants of the genus Boswellia. Like many other terpenes, boswellic acid appears in the resins of plants that secrete them, and boswellic acid can be extracted from the trunks of, for example, Boswellia serrata, Boswellia carterii, and various plants of the same genus. It is estimated that boswellic acid accounts for 30% of the resin of Boswellia serrata. Extracts of Boswellia serrata contain various derivatives of boswellic acid, including β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid, and acetyl-11-keto-β-boswellic acid. Boswellic acid is known to exhibit anti-inflammatory behavior.

[0014] WO2006 / 022762 describes a composition comprising 5% A topical cream is disclosed, and the use of, for example, the disclosed topical cream is applied three times a day for 150 days to treat patients with psoriasis.

[0015] US 2011 / 0165136 describes a skin care composition for treating psoriasis comprising 0.3-1% of a Boswellia extract. Summary of the invention

[0016] It is an object of the present disclosure to provide an improved skin care composition for treating psoriasis.

[0017] It is another object of the present disclosure to provide an improved method for treating psoriasis.

[0018] The present inventors have surprisingly found that boswellic acid and vitamin B12 provide a synergistic effect in treating psoriasis, particularly plaque psoriasis. The present inventors believe that boswellic acid is effective in inhibiting the anti-inflammatory response that leads to psoriasis, while vitamin B12 is believed to reduce the level of NO (nitrogen oxide) that acts as a tissue skin irritant.

[0019] The synergistic effect is particularly reflected in the embodiments of the present disclosure.

[0020] Therefore, in a first aspect, the present invention relates to a skin care composition for treating psoriasis, comprising 1-10% of boswellic acid and 0.02-2% of vitamin B12 or a derivative thereof.

[0021] In a preferred embodiment, the composition comprises 1-9%, such as 1-8%, such as 1-7%, such as 1-6%, such as 1-5%, such as 1-4%, such as 1-3%, such as 2.5% of boswellic acid. In another embodiment, the composition comprises 1.5-10%, such as 1.75-10%, such as 2-10%, such as 2.5% of boswellic acid. In another embodiment, the composition comprises 1.5-7%, such as 1.75-4.5%, such as 2-3%, such as 2.5% of boswellic acid.

[0022] In another preferred embodiment, the composition comprises 0.03-2%, such as 0.04-2%, such as 0.05-2%, such as 0.06-2%, such as 0.07% vitamin B12 or its derivatives. In another embodiment, the composition comprises 0.03-1.5%, such as 0.03-1.2%, such as 0.03-1%, such as 0.03-0.9%, such as 0.03-0.8%, such as 0.07% vitamin B12 or its derivatives. In another embodiment, the composition comprises 0.03-1%, such as 0.04-0.5%, such as 0.05-0.4%, such as 0.06-0.5%, such as 0.06-0.1%, such as 0.07% vitamin B12 or its derivatives.

[0023] Therefore, in a preferred embodiment, the composition comprises 1.5-7%, such as 1.75-4.5%, such as 2-3%, such as 2.5% boswellic acid and 0.03-1%, such as 0.04-0.5%, such as 0.05-0.4%, such as 0.06-0.5%, such as 0.06-0.1%, such as 0.07% vitamin B12 or a derivative thereof.

[0024] Preferably, the boswellic acids are derived from extracts of the genus Boswellia. Boswellia species are medium-sized flowering plants, including both trees and shrubs, and are native to tropical regions of Africa and Asia. The four main species of Boswellia are B. sacra (synonyms B. carterii and B. bhaw-dajiana), B. frereana, B. papyrifera, and B. serrata, and each resin extract is available in various grades. For example, the grade depends on the time of harvest. Boswellia extracts are available from many commercial sources, and the extracts used to prepare the composition of Example 1 of the present disclosure were purchased from Shaanxi Yuantai Biological Technology Co., Ltd. The Boswellia extract is described by the manufacturer as a gum resin extract exuded after cutting on the trunk of the Oleaceae plant Boswellia carterii and various plants of the same genus. The extract used contains over 95% boswellic acids.

[0025] Therefore, in a preferred embodiment of the present invention, the boswellic acids are derived from an extract of a plant of the genus Boswellia.Preferably, the major part of the boswellic acids is derived from an extract of the plant Boswellia sacra (Boswellia carterii).

[0026] The inventors have further discovered that carbamide further contributes to the therapeutic activity of the composition. Urea is an organic compound with the chemical formula CO(NH2)2. Urea is commonly used as a moisturizer and exfoliant in topical creams. In the present context, it is believed that urea has a keratolytic effect and enhances the penetration of both boswellic acid and vitamin B12 through the surface layers of the skin.

[0027] Therefore, in a second aspect, the present invention relates to a composition comprising boswellic acid, urea and vitamin B12 or a derivative thereof.

[0028] More specifically, in a second aspect, the present invention relates to a skin care composition for treating psoriasis, characterized in that it comprises 2-20% urea, 1-10% boswellic acid and 0.02-2% vitamin B12 or its derivatives.

[0029] In a preferred embodiment, the composition of the present invention comprises 2-20%, such as 5-15%, such as 5-14%, such as 5-13%, such as 5-12%, such as 5-11%, such as 10% urea. In a preferred embodiment, the composition of the present invention comprises 6-20%, such as 7-20%, such as 8-20%, such as 9-20%, such as 10% urea. In a preferred embodiment, the composition of the present invention comprises 6-14%, such as 7-13%, such as 8-12%, such as 9-11%, such as 10% urea.

[0030] The compositions of the present invention are intended for topical application, i.e. they are formulated to be suitable for topical application. Preferably, the compositions of the present invention are in the form of a cream, lotion, ointment, gel, emulsion, solution or skin patch, wherein a cream is particularly preferred. Methods for formulating the compositions of the present invention as a cream, lotion, ointment, gel, emulsion, solution or skin patch are not particularly limited and are known in the art.

[0031] Therefore, the composition of the present invention further comprises one or more components selected from the group consisting of pharmaceutically and / or cosmetically acceptable excipients, solvents, preservatives, antioxidants, humectants, thickeners, gelling agents, waxes, surfactants, emollients, emulsifiers, oil bases, ointment bases, penetration enhancers, solubilizers, softeners, chelating agents, fragrances and buffers. Each component is not particularly limited and is known in the art.

[0032] A specific example of a pharmaceutically and / or cosmetically acceptable solvent is water.

[0033] In addition to the active ingredients (boswellic acid, vitamin B12 or its derivatives and optionally urea), the composition of the present invention preferably comprises 20-40% of an emollient. Preferred emollients are selected from almond oil (Prunus Amygdalas Dulcis), jojoba seed oil (Simmondsia chinensis), caprylic / capric triglyceride and liquid paraffin.

[0034] In addition, the composition of the present invention preferably comprises 1-10% of an emulsifier. Preferred emulsifiers are selected from cetearyl alcohol, myristyl alcohol, cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20, and steareth-20.

[0035] Furthermore, the composition of the present invention preferably comprises 0-10% of a humectant.Preferred humectants are selected from shea butter (Butyrospermum Parkii).

[0036] Furthermore, the composition of the present invention preferably comprises 0-2% of a preservative. Preferred preservatives are selected from sodium benzoate, potassium benzoate and phenoxyethanol.

[0037] Furthermore, the compositions of the present invention preferably comprise 0-10% of an emollient. A preferred emollient is glycerol.

[0038] Furthermore, the composition of the present invention preferably comprises 0-10% wax, such as 1-10%.Preferred waxes are selected from sumac wax and carnauba wax.

[0039] Furthermore, the composition of the present invention preferably comprises 0-10% of an antioxidant. A preferred antioxidant is tocopherol.

[0040] Furthermore, the composition of the present invention preferably comprises 0-10% of a thickener. A preferred thickener is Kahlgum.

[0041] Furthermore, the composition of the present invention preferably comprises 20-60% of water.

[0042] Therefore, in a preferred embodiment, in addition to the active ingredients (boswellic acid, vitamin B12 or its derivatives and optionally urea), the composition of the present invention preferably comprises the following amounts of additional components:

[0043] Table 1

[0044] Function ％ Emollients 20-40％ Emulsifier 1-10％ Moisturizer 0-10％ preservative 0-2％ Softener 0-10％ wax 0-10％ Antioxidants 0-10％ Thickener 0-10％ water 20-60％

[0045] As demonstrated in the following examples, the composition of the present invention is unexpectedly effective in the treatment of psoriasis. In particular, the significant reduction in itching and the significant reduction in the presence of scaling indicate that the composition is unexpectedly effective in the treatment of plaque psoriasis.

[0046] Additionally, the compositions can be generally used to reduce the presence of scaling on human skin.

[0047] Additionally, the composition can be used to reduce itching of human skin in general.

[0048] In addition, the present disclosure relates to a method of treating psoriasis, comprising applying the composition of the present invention to an area of ​​skin in need of treatment. In particular, it has been observed that twice daily application of the composition showed that many patients already benefited significantly after only 3 weeks of treatment, and were almost completely relieved after only 4 weeks of twice daily treatment.

[0049] The present disclosure has been described with reference to preferred embodiments. However, the scope of the present invention is not limited to the embodiments shown, and changes and modifications may be made without departing from the scope of the present invention. Example

[0050] Example 1

[0051] A skin care composition comprising the ingredients listed in Table 2 below was made as follows:

[0052] Urea and water are mixed 24 hours before use. Apricot kernel oil, sumac wax, jojoba oil, cetearyl alcohol, myristyl alcohol, carnauba wax, tocopherol, liquid paraffin, cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20, steareth-20 and Kahlgum are mixed and heated to 75°C to form a fat phase. Glycerin, water, sodium benzoate and potassium sorbate are mixed, and then cyanocobalamin dissolved in water is added. The mixture is heated to 75°C to form an aqueous phase. The fat phase is transferred to the aqueous phase and the resulting mixture is emulsified. After cooling to 35°C, boswellic acid and urea are added. The pH is adjusted to 5.0-5.5 with citric acid.

[0053] Table 2: List of ingredients

[0054]

[0055]

[0056] Example 2

[0057] The skin care composition provided in Example 1 was delivered to 24 subjects, all of whom had moderate to severe psoriasis, under confidentiality. The subjects were aged 21-73 years (median 39 years), and were asked to apply the composition of Example 1 only to one selected skin site that needed treatment, while other sites of their skin were not treated (or treated according to the normal procedures of the respective subjects). The subjects were also asked to continue any medical treatment that the subjects were currently using, such as any topical treatment for the remaining skin sites that needed treatment. The subjects were asked to apply the composition once or twice a day (depending on the severity of psoriasis) for 4 weeks, and to apply the composition in a thin layer. The subjects were asked to take and record their skin before and after the 4-week treatment. Each subject completed a questionnaire after the 4-week treatment.

[0058] Table 3: Age of subjects

[0059]

[0060]

[0061] General Results

[0062] 23 of the 24 subjects experienced significant improvement or even complete remission of symptoms, and only one subject would not recommend the composition to others with psoriasis. None of the subjects reported any negative side effects. Subjects were generally well-suffered from their respective diseases, regardless of whether they had previously followed other treatment regimens.

[0063] Questionnaire Results

[0064] Each subject completed an electronic questionnaire after 4 weeks of treatment. The questionnaire included the following questions as well as questions related to other treatments on the market.

[0065] How would you describe your skin before applying this composition? (Subjects were allowed to select multiple answers)

[0066] red Stimulate Raised skin Itching Eczema Scaly 66.67％ 58.33％ 45.83％ 70.83％ 45.83％ 100％

[0067] After applying the composition, how would you describe your skin? (Subjects were allowed to select multiple answers)

[0068] smooth Flexible No bulges on the skin No itching Uniform Scaly 33.33％ 33.33％ 37.50％ 70.83％ 8.33％ 12.50％

[0069] Please describe how itchy your skin was before applying the composition?

[0070]

[0071] Please describe how itchy your skin felt after applying the composition?

[0072]

[0073] Please describe how red your skin was before applying the composition?

[0074]

[0075] Please describe how red your skin was after applying the composition?

[0076]

[0077] Would you recommend this combination to others for the treatment of psoriasis?

[0078] yes no have no idea Unanswered 70.73％ 4.17％ 16.67％ 8.33％

[0079] Before applying this composition, was your quality of life reduced by your psoriasis?

[0080] yes no have no idea Unanswered 75.00％ 20.83％ 4.17％ 0％

[0081] After applying this composition, has your quality of life improved due to skin relief?

[0082] yes no have no idea Unanswered 41.67％ 29.17％ 35.50％ 0％

[0083] Example 3

[0084] Forty patients with psoriasis participated in the trial of 3 different preparations.

[0085] 20 randomly selected patients were given a skin care composition provided in Example 1 containing active ingredients cyanocobalamin (0.07%), boswellic acid (2.5%) and urea (carbamide) (10%). 10 randomly selected patients were given a comparative skin care composition containing vitamin B12 (0.07%) as an active ingredient. The remaining 10 patients were given a comparative skin care composition containing boswellic acid (2.5%) as an active ingredient. The skin care compositions were otherwise identical.

[0086] Psoriasis patients were asked to apply the cream twice daily, in the morning after showering and in the evening, and to apply the cream at the same times throughout the study period.

[0087] result

[0088] Patients were examined at the beginning of the trial (baseline) and after 4 weeks of application of the skin care composition. Patients receiving the comparative skin care composition were evaluated only after 4 weeks, after which they switched to the skin care composition of Example 1 due to its greater efficacy. Patients receiving the skin care composition of the Example were also evaluated after 8 weeks.

[0089] The patients were examined by scoring the following parameters on a scale of 0-4 (0 = none, 4 = maximum); bleeding (0-4), burning sensation (0-4), itching (0-4), scaling (0-4), redness of the skin (0-4), tightness of the skin (0-4). The mean results of the study groups are shown in Table 4 below:

[0090] Table 4: Average scores of each group

[0091]

[0092] in conclusion:

[0093] The results showed that the active ingredients boswellic acid and vitamin B12 had synergistic effects on the parameters of bleeding, burning sensation, itching, skin redness and skin tightness.

[0094] Furthermore, a significant synergistic effect on scaling was observed, presumably mainly due to the presence of urea (10%) in the composition of Example 1.

[0095] Conclusions: This study showed a synergistic effect of combining boswellic acid and vitamin B12 as active ingredients in an ointment for the treatment of psoriasis. In addition, this study showed a synergistic effect of combining boswellic acid, vitamin B12, and urea as active ingredients in an ointment for the treatment of psoriasis.

[0096] Case Report

[0097] Patient #2:

[0098] A 74-year-old woman with psoriasis. The disease started on her elbows at age 54 and has now spread to other parts of her body, including her ears, neck, and knees.

[0099] She is currently receiving treatment, and experienced scaly, red eczema with significant itching but no pain.

[0100] After applying the composition of Example 1 once a day to the elbow, the scaling and red eczema were significantly reduced. After 6 weeks of treatment, both were almost completely gone and she no longer used

[0101] Patient #8:

[0102] A 56-year-old woman with severe psoriasis that began at age 10 and has now spread to 50% of her skin surface.

[0103] She is currently receiving treatment, and experienced scaly, red eczema with significant itching and pain.

[0104] The scaling and red eczema were significantly reduced after applying the composition of Example 1. The scaling, itching and pain have now disappeared and she wishes to receive more of the composition of Example 1 and finds it to be having a significant effect.

[0105] Patient #11:

[0106] A 31-year-old male with severe psoriasis. The disease started on his arms at age 14 and disappeared after treatment with hormonal creams. At age 21, the disease reappeared and has now spread significantly to his knees, elbows and legs. He has tried a range of medications, but nothing has worked. He never wears shorts and does not want to expose his affected skin to the public.

[0107] He experiences scaly, red eczema. The skin is painful when stretched and has a tendency to bleed from small scratches caused by the disease.

[0108] He was skeptical about the efficacy of the composition of Example 1. However, after only one week of treatment with the composition of Example 1, the pain and itching he experienced completely disappeared. He now has a better quality of life.

[0109] Patient #16:

[0110] A 51-year-old woman with severe psoriasis. The disease started on her arms and legs at age 21 and has now spread to 80% of her skin surface, including her face. She is fatigued and has been diagnosed with psoriatic arthritis.

[0111] She has tried a range of treatments and is currently receiving treatment. She experienced scaly, red eczema with significant itching and pain. She also received climatic treatment.

[0112] After applying the composition of Example 1 twice a day, the scaling and red eczema were significantly reduced. The skin is now moist and soft, and the itching and pain have disappeared. She now treats with the composition of Example 1 Treatment (once every 3-4 days) is combined. She describes the composition of Example 1 as the first cream to date that has a truly significant effect.

Claims

1. A skin care composition comprising 1% to 10% of boswellic acid and 0.02% to 2% of vitamin B12 or a derivative thereof, wherein the vitamin B12 or a derivative thereof is selected from the group consisting of cobalamin, hydroxycobalamin, cyanocobalamin, methylcobalamin, adenosylcobalamin, 5′-deoxyadenosyl-cobalamin, hydrocobalamin and nitrosocobalamin.

2. A skin care composition according to claim 1, comprising 0.03% to 1%, such as 0.04% to 0.5%, such as 0.05% to 0.4%, such as 0.06% to 0.5%, such as 0.06% to 0.1%, such as 0.07% of vitamin B12 or a derivative thereof, wherein the vitamin B12 or a derivative thereof is selected from the group consisting of cobalamin, hydroxycobalamin, cyanocobalamin, methylcobalamin, adenosylcobalamin, 5′-deoxyadenosyl-cobalamin, hydrocobalamin and nitrosocobalamin.

3. A skin care composition according to claim 1 or 2 comprising 1.5% to 7%, such as 1.75% to 4.5%, such as 2% to 3%, such as 2.5%, of boswellic acid.

4. A skin care composition according to any one of the preceding claims, comprising 2% to 3%, e.g. 2.5%, of boswellic acid and 0.06% to 0.1%, e.g. 0.07%, of vitamin B12 or a derivative thereof selected from the group consisting of cobalamin, hydroxycobalamin, cyanocobalamin, methylcobalamin, adenosylcobalamin, 5′-deoxyadenosyl-cobalamin, hydrocobalamin and nitrosocobalamin.

5. A skin care composition as claimed in any one of the preceding claims, wherein The boswellic acids are derived from extracts of Boswellia spp.

6. A skin care composition as claimed in any preceding claim comprising 2% to 20%, such as 5% to 15%, such as 5% to 14%, such as 5% to 13%, such as 5% to 12%, such as 5% to 11%, such as 10% urea.

7. A skin care composition according to any one of the preceding claims, comprising 2% to 20% urea, 1% to 10% boswellic acid and 0.02% to 2% vitamin B12 or a derivative thereof selected from the group consisting of cobalamin, hydroxycobalamin, cyanocobalamin, methylcobalamin, adenosylcobalamin, 5′-deoxyadenosyl-cobalamin, hydrocobalamin and nitrosocobalamin.

8. A skin care composition according to any preceding claim for use in the treatment of psoriasis.

9. The skin care composition according to claim 8, wherein The psoriasis is plaque psoriasis.

10. A skin care composition as claimed in any one of the preceding claims, wherein: The composition is a cream.

11. Use of a skin care composition as claimed in any preceding claim for the treatment of psoriasis.

12. A method for treating psoriasis, the method comprising applying the composition of any one of the preceding claims 1 to 10 to an area of ​​skin in need of treatment.

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