Treatment of psoriasis

Abstract

The present invention relates to a topical formulation comprising, as active ingredients, one or more Group 6 inefficient corticosteroids, an emulsified ointment BP, honey, one or more natural oils and optionally salicylic acid; a method of making such topical formulations; and a method of treating psoriasis or a symptom thereof in a subject by applying the topical formulation of the invention to a subject in need thereof.

Description

Technical Field

[0001] This invention relates to the treatment of psoriasis. Background Technology

[0002] Psoriasis is an inflammatory condition characterized by a variety of symptoms, most typically a rash of itchy, scaly plaques, most commonly found on the knees, elbows, trunk, and scalp. Psoriasis is a common, long-term, i.e., chronic skin disease.

[0003] In addition, psoriasis symptoms may alternate between periods of severe flare-ups and periods of remission where symptoms disappear. A remission period typically lasts one to twelve months. However, the duration of both flare-ups and remission periods is difficult to predict.

[0004] Therefore, psoriasis can be basically divided into three stages: ●The acute phase is characterized by itching and scaling / rash rupture. ●The scaling stage, characterized by thickening and / or discoloration of the affected area, and ● Remission period, during which there is no itching, but the skin may have mild peeling, dryness, or redness.

[0005] There are several existing products commercially available for the treatment of psoriasis and its symptoms, some of which are listed in Table 1: Table 1: Existing products for treating psoriasis and its symptoms However, as a pharmacist with over 20 years of experience, the applicant found that these preparations were not effective in the long term, and that patients could only temporarily relieve their psoriasis symptoms for a short period of time before the symptoms rebounded to the original severity of psoriasis.

[0006] It would be useful if an alternative product could be developed that could provide long-term relief for psoriasis and its symptoms. Summary of the Invention

[0007] According to a first aspect of the invention, a topical formulation is provided comprising or consisting of one or more Class 6 low-potency corticosteroids as active ingredients, emulsified ointment BP, honey, one or more natural oils, and optionally salicylic acid.

[0008] In one possible embodiment of the first aspect of the invention, the topical formulation comprises one or more Class 6 low-potency corticosteroids as active ingredients, emulsified ointment BP, honey, one or more natural oils, and optionally salicylic acid.

[0009] It should be understood that the six classes of ineffective corticosteroids are well known to those skilled in the art. However, in particular, the six classes of ineffective corticosteroids may be selected from the group consisting of any one or more Class B triamcinolone acetonide-type corticosteroids or any one or more Class D betamethasone dipropionate-type corticosteroids or any combination thereof.

[0010] For example, the type B triamcinolone acetonide corticosteroids may be selected from any one or more of the following: Desonide 0.05% (w / w); Fluocinol acetate 0.01% (w / w); Triamcinolone acetonide 0.025% (w / w); or Triamcinolone diacetate 0.025% (w / w) or any combination thereof.

[0011] For example, the type D betamethasone dipropionate corticosteroid may be selected from any one or more of the following: Aclomethasone dipropionate 0.05% (w / w); or Betamethasone valerate 0.1% (w / w) or any combination thereof.

[0012] In one possible embodiment of the first aspect of the invention, the six types of ineffective corticosteroids are fluocinolone acetonide. Specifically, fluocinolone acetonide may have the chemical name pregn-1,4-diene-3,20-dione, 6,9-difluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-,(6α,11β,16α) and the structural formula shown in Formula I. .

[0013] The formulation may contain about 0.0025% to about 0.2% by weight of the total formulation, including about 0.0025% to about 0.025% of the six classes of ineffective corticosteroids.

[0014] In one possible embodiment of the invention, the formulation comprises between about 0.00625% and 0.01% of the six types of ineffective corticosteroids by weight of the total formulation, including about 0.0025% of the six types of ineffective corticosteroids.

[0015] In another possible embodiment of the invention, the formulation comprises about 0.025% of the six classes of ineffective corticosteroids by weight of the total formulation.

[0016] In yet another possible embodiment of the invention, the formulation comprises about 0.2% by weight of the six classes of ineffective corticosteroids.

[0017] In one possible embodiment of the invention, the six types of ineffective corticosteroids are fluocinolone acetonide.

[0018] The one or more corticosteroids may be formulated into creams, foams, or ointments. In particular, the formulation may be an ointment.

[0019] The honey is preferably unprocessed raw honey. In this regard, the honey refers to the honey in its original form as found in the honeycomb from which it was produced. In particular, the preparation may contain about 5% to about 10% of the honey by weight of the total preparation. For example, the preparation may contain about 5%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10% of the honey by weight of the total preparation.

[0020] The one or more natural oils are preferably olive oil. More specifically, the olive oil is extra virgin olive oil extracted by a cold-processing method. The formulation may contain about 5% to about 10% of the one or more natural oils by weight of the total formulation. For example, the formulation may contain about 5%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10% of the one or more natural oils by weight of the total formulation.

[0021] In a particular embodiment, the emulsified ointment BP comprises the following: Emulsified wax - 30% (w / w); White soft paraffin - 50% (w / w); and Liquid paraffin – 20% (w / w).

[0022] Typically, the formulation comprises an emulsified ointment BP to bring the final formulation to 100% by weight of the total formulation.

[0023] The salicylic acid can be, in particular, salicylic acid of formula II. .

[0024] The formulation may contain about 2% to about 10% salicylic acid by weight. For example, the formulation may contain about 2%, or about 3%, or about 4%, or about 5%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10% of the salicylic acid by weight of the total formulation.

[0025] According to a second aspect of the invention, an formulation according to the first aspect of the invention is provided for treating psoriasis or at least one symptom caused by psoriasis in a subject in need.

[0026] Specifically, the subject is a human being. The formulation may be in the form of a cream or ointment. Specifically, the formulation may be an ointment.

[0027] According to a third aspect of the invention, the use of a compound is provided for preparing an formulation for treating psoriasis or at least one symptom caused by psoriasis in a subject in need, said compound being selected from the group comprising or consisting of: one or more of the six classes of low-potency corticosteroids as described in the first aspect of the invention, emulsified ointment BP, honey, one or more natural oils, and optionally salicylic acid.

[0028] Specifically, the subject is a human being. The formulation may be in the form of a cream or ointment. Specifically, the formulation may be an ointment.

[0029] According to a fourth aspect of the invention, a method is provided for treating psoriasis or at least one symptom caused by psoriasis in a subject in need, the method comprising topically applying an preparation according to a first aspect of the invention to a skin area of ​​the subject affected by psoriasis or at least one symptom caused by psoriasis.

[0030] The method may include a first step of selecting a specific formulation according to a first aspect of the invention, wherein the specific formulation contains a certain concentration of one or more of the six class of low-potency corticosteroids suitable for a specific phase of psoriasis or its symptoms in the subject. The specific phase may be selected from one of the following: The acute phase, which is typically characterized by itching, inflammation, scaling, and / or rash; The scaling stage, typically characterized by thickening and / or discoloration of the affected area and scaling; and During the remission period, there is usually no itching, but the skin may have mild peeling, dryness, and / or inflammation.

[0031] In one possible embodiment of the fourth aspect of the invention, when the subject is in the acute phase, the formulation may be an acute-phase formulation having a concentration of about 0.0125% by weight of one or more of the six class of low-potency corticosteroids. Optionally, in this embodiment of the fourth aspect of the invention, the formulation contains salicylic acid. For example, the formulation may contain about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% of the salicylic acid by weight of the total formulation.

[0032] In this embodiment of the invention, the formulation may be applied twice daily to the affected skin area of ​​the subject until the acute symptoms of psoriasis subside, at which point the subject enters the remission phase. The acute-phase formulation is then discontinued in stages, including once-daily application for approximately 5 days, followed by once-daily application every other day for the next approximately 10 days. Typically, the subject may then use the formulation of the first aspect of the invention during the remission phase, the formulation having a concentration of approximately 0.0025% by weight of one or more of the six class of low-potency corticosteroids (i.e., the remission-phase formulation). Typically, the remission-phase formulation does not contain salicylic acid.

[0033] In another possible embodiment of the fourth aspect of the invention, when the subject is in the scaly phase, the concentration of the one or more Class 6 low-potency corticosteroids in the formulation may be about 0.00625% by weight (i.e., the scaly phase formulation) and the formulation may further contain about 2% by weight to about 10% by weight of salicylic acid. For example, the formulation may contain about 2%, or about 3%, or about 4%, or about 5%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10% of the salicylic acid by weight of the total formulation.

[0034] In this embodiment of the invention, the scaly phase formulation may be applied twice daily to the affected skin area of ​​the subject until the scaly phase symptoms of psoriasis subside, at which point the subject enters the remission phase. The subject then discontinues the scaly phase formulation in stages, including once-daily application for approximately 5 days, followed by once-daily application every other day for the next approximately 10 days. Typically, the subject can then use the formulation of the invention during the remission phase, which has a concentration of approximately 0.0025% by weight of one or more of the six class of low-potency corticosteroids (i.e., the remission phase formulation). Typically, the remission phase formulation does not contain salicylic acid.

[0035] In yet another possible embodiment of the fourth aspect of the invention, when the subject is in the remission phase, the concentration of the one or more Class 6 low-potency corticosteroids in the formulation may be about 0.0025% by weight (i.e., the remission phase formulation). Typically, the remission phase formulation does not contain salicylic acid.

[0036] According to a fifth aspect of the invention, a method for producing an formulation according to a first aspect of the invention is provided, the method comprising mixing one or more Class 6 low-potency corticosteroids as described in the first aspect of the invention, emulsified ointment BP, honey, one or more natural oils and optionally salicylic acid. Detailed Implementation

[0037] Example The subject matter of this disclosure will now be described more fully below with reference to the accompanying embodiments, which illustrate representative implementations. However, the subject matter of this disclosure may be embodied in different forms and should not be construed as limiting to the implementations described herein. Rather, these implementations are provided so that this disclosure will be comprehensive and complete, and will fully convey the scope of the implementation to those skilled in the art.

[0038] Comparison of the formulation of this invention with existing commercially available products The following describes the observations from five anecdotal case studies, comparing the efficacy of the topical formulations of this invention with existing commercially available products prescribed by the patients' physicians. Different formulations of this invention were applied according to the stage of the illness, namely: ●P1 used in the acute phase ●P2 for the scaly stage ●P3 used during remission Therapeutic agents P1 for acute phase treatment 100g formula -Class 6 ineffective corticosteroids, such as fluocinolone acetonide- 0.0125% (w / w) -Raw honey- 5% (w / w) -Olive oil- 5% (w / w) - Emulsify ointment to 100 g (w / w) -Optional salicylic acid- 5% (w / w) If the product contains salicylic acid, first weigh out the salicylic acid and grind it into powder. Next, add 0.00625% (w / w) of a type 6 low-potency corticosteroid and mix thoroughly until homogeneous. If the product does not contain salicylic acid, first weigh out the required amount of the emulsified ointment BP, then add the type 6 low-potency corticosteroid and mix thoroughly until homogeneous. Gradually add honey and olive oil, mixing continuously until homogeneous.

[0039] The resulting product is a smooth, stable, and pleasantly scented cream, applied only twice daily to the affected area.

[0040] After achieving remission, apply the product daily for five days, then every other day for the next ten days, and discontinue use for two weeks. The subject will then be in remission and can use the remission treatment described below.

[0041] P2 for treating the scaly stage 100g formula -Class 6 ineffective corticosteroids, such as fluocinolone acetonide- 0.00625% (w / w) -Raw honey- 5% (w / w) -Olive oil- 5% (w / w) -Salicylic acid- 5% (w / w) - Emulsify ointment to 100 g (w / w) First, weigh out the salicylic acid and grind it into powder. Next, add 0.00625% (w / w) of a type 6 low-potency corticosteroid and mix thoroughly until homogeneous. Weigh out the required amount of the emulsified ointment BP, then add the type 6 low-potency corticosteroid and mix thoroughly until homogeneous. Finally, gradually add the honey and olive oil, mixing continuously until homogeneous.

[0042] The resulting product is a smooth, stable, and pleasantly scented cream, applied only twice daily to the affected area.

[0043] Since the scaly stage is characterized by hard, scaly, dry, and even itchy skin, it is necessary to add salicylic acid, which has the function of separating the stratum corneum.

[0044] After achieving remission, apply the product daily for five days, then every other day for the next ten days, and discontinue use for two weeks. The subject will then be in remission and can use the remission treatment described below.

[0045] P3 for remission treatment 100g formula -Class 6 ineffective corticosteroids, such as fluocinolone acetonide- 0.0025% (w / w) Raw honey - 10% (w / w) -Olive oil- 10% (w / w) - Emulsify ointment to 100 g (w / w) Weigh out the required amount of emulsified ointment PB, and add 0.0025% (w / w) of a type 6 low-potency corticosteroid and mix thoroughly until homogeneous. Finally, gradually add honey and olive oil, mixing continuously until homogeneous.

[0046] The resulting product is a smooth, stable, and pleasantly scented cream, applied sparingly twice daily to the affected area.

[0047] Treatment with this same preparation targeting the acute and scaly phases will inevitably have an impact when used in the remission phase.

[0048] During remission, the goal is to keep the skin 'calm' to prevent relapse. Surprisingly, a very small amount (0.0025% w / w) of a class 6 low-potency corticosteroid was found to be effective in preventing inflammation and eliminating itching that may occur during remission.

[0049] Case Studies Case 1 A 50-year-old adult male had been treated for approximately one year with a combination of commercially available medications: chlorpheniramine hydrochloride (Allergex®) cream; Nomospore (bacitracin, neomycin, polymyxin B, cocoa butter, cottonseed oil, olive oil, sodium pyruvate, vitamin E, and white mineral oil); and clobetasol propionate (Dovate®). Upon initial treatment with the formulation P1 of this invention, the subject presented with itchy, broken skin, including sores on the lower legs caused by acute psoriasis.

[0050] By the end of week 1 of treatment with formulation P1, subjects reported relief of itching within 2 to 3 days, and their skin appearance showed less inflammation than at the start of treatment. By the end of week 2, wounds began to heal, and the skin appearance showed less inflammation than at week 1. By the end of week 3, the subjects' skin appearance was almost normal. At the end of week 4, subjects were given formulation P3 to maintain their psoriasis, and no flare-ups were observed after three months of follow-up.

[0051] Case 2 A 35-year-old adult male had been treated for over 3 years with a combination of commercially available medications, namely chlorpheniramine hydrochloride (Allergex®) tablets and cream Vaseline® (petroleum jelly, palmitic acid, stearic acid, mineral oil, glycerin, glyceryl stearate, cetyl alcohol, and potassium hydroxide); and Dovonex® cream (calcipotriol monohydrate equivalent to 50 μg / g anhydrous calcipotriol in a cream base of cetearyl alcohol, ceteth-20, diazoalkyl urea, dichlorobenzyl alcohol, sodium dibasic phosphate, disodium edetate, dl-α-tocopherol, glycerin, mineral oil, and petrolatum). Upon initial treatment with formulation P2 of this invention, the subject presented with scaly psoriasis on both legs from the ankles upwards, exhibiting very dry, scaly, and itchy skin.

[0052] By the end of week 1 of treatment with formulation P2, the subject reported reduced itching compared to the start of treatment, and the skin appearance showed that most of the scales had receded. By the end of week 2 of treatment, the subject was able to switch to formulation P3 to maintain their psoriasis. One month into treatment, the subject experienced a mild flare, which resolved after two days of treatment with formulation P1, and the subject was then able to resume using formulation P3 to maintain their psoriasis without further flare-ups.

[0053] Case 3 A six-year-old girl had been treated with an aqueous emulsified ointment (Unguentum emulsificans aquosum) for approximately two years. Upon initial treatment with the remission formulation P3 of this invention, the subject developed highly itchy, inflammatory patches on her skin. The subject reported relief within one week of treatment and remained symptom-free for six months while using the P3 formulation.

[0054] Case 4 A 65-year-old adult woman had been treated for approximately 2 years with a combination of commercially available medications: Skincalm™ (infused oils (calendula, Oregon grape root, comfrey leaf, comfrey root, chamomile, olive oil), distilled water, shea butter, glycerin, beeswax, vegetable emulsifying wax, borage oil, emu oil, vitamin E, potassium sorbate); and Zam-buk™ (paraffin, light-colored resin (rosin), eucalyptus oil, camphor, thyme oil, and safrole oil). Upon initial treatment with the remission formulation P3 of this invention, the subject presented with dry, itchy, and discolored skin on both shins due to psoriasis. The subject reported remission within one week of treatment and remained symptom-free for 6 months while using the P3 formulation.

[0055] Case 5 An 8-year-old girl had been treated for approximately 6 months with a combination of commercially available medications, namely olive oil, followed by a mixture of Dovate®, coal tar, and salicylic acid. Upon initial treatment with the psoriatic phase formulation P2 of this invention, the subject presented with dry, itchy skin on the back of the neck and dry, scaly scalp due to psoriasis. The subject reported relief and scaling within 3 days of treatment with P2. The subject then switched to the remission formulation P3 and remained symptom-free and flare-free for 8 months.

Claims

1. A topical formulation comprising as active ingredients one or more Class 6 low-potency corticosteroids, emulsifying ointment BP, honey, one or more natural oils, and optionally salicylic acid.

2. The topical formulation according to claim 1 consisting of as active ingredients one or more Class 6 low-potency corticosteroids, emulsifying ointment BP, honey, one or more natural oils, and optionally salicylic acid.

3. The topical formulation according to claim 1 or 2, wherein the Class 6 low-potency corticosteroid is selected from the group consisting of any one or more Class B triamcinolone type corticosteroids or any one or more Class D beclometasone dipropionate type corticosteroids or any combination thereof.

4. The topical formulation according to claim 3, wherein the Class B triamcinolone type corticosteroid is selected from any one or more of the following: Dinoprostone 0.05% (w / w); Fluorocinolone acetonide 0.01% (w / w); Triamcinolone acetonide 0.025% (w / w); or Triamcinolone acetonide 0.025% (w / w), or any combination thereof.

5. The topical formulation according to claim 3, wherein the Class D beclometasone dipropionate type corticosteroid is selected from any one or more of the following: Alclometasone dipropionate 0.05% (w / w); or Beclometasone dipropionate 0.1% (w / w), or any combination thereof.

6. The topical formulation according to any one of claims 1 to 4, wherein the Class 6 low-potency corticosteroid is fluorocinolone acetonide having the chemical name Pregn-1,4-diene-3,20-dione, 6,9-difluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-, (6a,11b,16a) and the structural formula as shown in Formula I 。 7. The topical formulation according to any one of claims 1 to 6, comprising about 0.0025% to about 0.0125% of the Class 6 low-potency corticosteroid by weight of the total formulation.

8. The topical formulation according to claim 7, comprising about 0.0125% of the Class 6 low-potency corticosteroid by weight of the total formulation.

9. The topical formulation according to claim 7, comprising about 0.00625% of the Class 6 low-potency corticosteroid by weight of the total formulation.

10. The topical formulation according to claim 7, comprising about 0.0025% of the Class 6 low-potency corticosteroid by weight of the total formulation.

11. The topical formulation according to any one of claims 1 to 10, wherein the one or more corticosteroids are formulated as a cream, foam or ointment.

12. The topical formulation according to any one of claims 1 to 11, wherein the honey is unprocessed raw honey.

13. The topical formulation according to claim 12, wherein the formulation comprises about 5% to about 10% of the honey by weight of the total formulation.

14. The topical formulation according to any one of claims 1 to 13, wherein the one or more natural oils is olive oil, including virgin olive oil extracted by cold processing methods.

15. The topical preparation of claim 14, wherein the preparation comprises about 5% to about 10% by weight of the total preparation of the one or more natural oils.

16. The topical preparation of any one of claims 1 to 15, wherein the emulsifying ointment BP consists of: Emulsifying wax - 30% (w / w); White soft paraffin - 50% (w / w); and Liquid paraffin - 20% (w / w).

17. The topical preparation of any one of claims 1 to 16, wherein the preparation comprises a weight of emulsifying ointment BP to bring the final preparation concentration to 100% by weight.

18. The topical preparation of any one of claims 1 to 17, wherein the salicylic acid has the formula of Formula II 。 19. The topical preparation of any one of claims 1 to 18, wherein the preparation comprises about 2% to about 10% by weight of salicylic acid by weight of the total preparation.

20. The topical preparation of any one of claims 1 to 19, in the form of a cream or ointment.

21. The topical preparation of any one of claims 1 to 20, for use in a method of treating psoriasis or at least one symptom caused by psoriasis in a subject in need thereof.

22. Use of one or more class 6 low potency corticosteroids, emulsifying ointment BP, honey, one or more natural oils, and optionally salicylic acid in the manufacture of a preparation for treating psoriasis or at least one symptom caused by psoriasis in a subject in need thereof.

23. The use of claim 22, wherein the preparation is in the form of a cream or ointment.

24. A method of treating psoriasis or at least one symptom caused by psoriasis in a subject in need thereof, the method comprising topically applying to an area of skin of the subject affected by psoriasis or at least one symptom caused by psoriasis a preparation according to any one of claims 1 to 20 until the psoriasis or at least one symptom caused by it subsides.

25. The method of claim 24, wherein the method comprises a first step of selecting a particular preparation having a certain concentration of the one or more class 6 low potency corticosteroids and optionally salicylic acid in the preparation suitable for a particular phase of the psoriasis or symptom thereof of the subject, wherein the particular phase is selected from one of: an acute phase comprising symptoms of itching, inflammation, scaling, and / or skin rash; a scaling phase comprising symptoms of thickening and / or discoloration of the affected area and comprising scaling formation; and a remission phase wherein there is no itching but comprising symptoms of mild desquamation, dryness, and / or inflammation of the skin, and the suitable concentration of the one or more class 6 low potency corticosteroids and optionally salicylic acid is selected from one of: about 0.1% to about 1% by weight of the total preparation; and about 1% to about 2% by weight of the total preparation. wherein the subject is in the acute phase, the formulation is an acute phase formulation having a concentration of about 0.0125% of the one or more Class 6 less potent corticosteroids by weight of the total formulation, and optionally, about 2% to about 10% salicylic acid in the formulation; wherein the subject is in the acute phase, the formulation is an acute phase formulation having a concentration of about 0.0125% of the one or more Class 6 less potent corticosteroids by weight of the total formulation, and optionally, about 2% to about 10% salicylic acid in the formulation; wherein the subject is in the acute phase, the formulation is an acute phase formulation having a concentration of about 0.0125% of the one or more Class 6 less potent corticosteroids by weight of the total formulation, and optionally, about 2% to about 10% salicylic acid in the formulation; 26. The method of claim 25, wherein wherein the subject is in the acute phase, the formulation is applied to the affected skin area of the subject twice daily until the acute phase symptoms of psoriasis have subsided, at which time the subject enters the remission phase, followed by a phased discontinuation of the acute phase formulation, including application once daily for about 5 days, followed by application once daily every other day for the next about 10 days, and finally, treating the subject with the remission phase formulation as needed by the subject.

27. The method of claim 25, wherein wherein the subject is in the acute phase, the formulation is applied to the affected skin area of the subject twice daily until the acute phase symptoms of psoriasis have subsided, at which time the subject enters the remission phase, followed by a phased discontinuation of the acute phase formulation, including application once daily for about 5 days, followed by application once daily every other day for the next about 10 days, and finally, treating the subject with the remission phase formulation as needed by the subject.

28. The method of claim 25, wherein wherein the subject is in the acute phase, the formulation is applied to the affected skin area of the subject twice daily until the acute phase symptoms of psoriasis have subsided, at which time the subject enters the remission phase, followed by a phased discontinuation of the acute phase formulation, including application once daily for about 5 days, followed by application once daily every other day for the next about 10 days, and finally, treating the subject with the remission phase formulation as needed by the subject.

29. The method of any one of claims 25 to 28, wherein the remission phase formulation is applied by the subject to the affected skin in need of treatment about twice daily.

30. A method of making the topical formulation of any one of claims 1 to 20, the method comprising mixing the one or more Class 6 less potent corticosteroids, the emulsifying ointment BP, the honey, the one or more natural oils, and optionally, the salicylic acid until mixed uniformly.

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