Compositions and methods for treating skin disorders

Abstract

The present invention provides a topical composition comprising a water-soluble material and a water-insoluble material. The composition further comprises a therapeutic agent useful in the treatment of a skin disorder. The present invention also provides methods of using the topical composition to treat a skin disorder.

Description

Technical Field

[0001] This application claims priority to Australian Provisional Patent Application No. 2024900656, filed on 13 March 2024, the entire contents of which are incorporated herein by reference. Background Technology

[0002] This invention relates to a topical composition comprising a water-soluble substance and a water-insoluble substance. The composition also comprises a therapeutic agent for treating skin diseases. The invention further provides a method for treating skin diseases using the topical composition. Summary of the Invention

[0003] Eczema is a term used to describe a group of skin conditions that cause inflammation of the epidermis. The term broadly applies to a range of persistent skin conditions characterized by one or more symptoms, including redness, swelling (thickness), itching and dryness, crusting, scaling, blistering, fissuring, oozing, or bleeding. Itchy rashes are particularly noticeable on the head and scalp, neck, inner elbows, behind the knees, and buttocks. There are many types of eczema, such as atopic eczema, asteatotic eczema, contact eczema, allergic contact eczema, seborrheic eczema, nummular eczema, pompholyx, herpetic dermatitis, stasis dermatitis, and neurodermatitis. The condition usually presents in infancy and sometimes disappears in adulthood. In some cases, it may first appear in adulthood.

[0004] Although eczema is a common condition affecting 10-20% of children and 1-3% of adults in developed countries, its exact cause remains unclear. It is thought to be related to immune system disorders and appears to have a genetic component, with higher prevalence in certain family and ethnic groups. It can cause considerable psychological and physical distress, such as persistent itching, dry skin, and unsightly rashes; in the most severe cases, it can even lead to debilitating conditions requiring hospitalization.

[0005] There is currently no cure for eczema. The goal of eczema treatment is to relieve and prevent itching. Treatment methods include using moisturizing lotions, applying occlusive dressings to extremely dry areas, topical or oral anti-inflammatory corticosteroids, and anesthetics. Over-the-counter versions of these treatments are often ineffective. While prescription corticosteroids are the most commonly used treatment, they can cause serious side effects. Topical corticosteroids can cause thinning of the skin, red lesions, and acne, while oral corticosteroids can cause mood swings, glaucoma, weight gain, high blood pressure, cataracts, and osteoporosis; these side effects often require discontinuation of treatment.

[0006] Other treatments for eczema include antihistamines, tar therapy, phototherapy, cyclosporine, and topical immunomodulators. Anesthetics and antihistamines provide only limited relief in most moderate to severe clinical cases. UVB phototherapy is commonly used to treat severe eczema with significant efficacy, but it can have adverse side effects, such as an increased risk of skin cancer and phototoxic reactions. Topical immunomodulators can prevent eczema flare-ups, but their use is also associated with an increased risk of cancer.

[0007] Although many products for treating eczema have been developed, there is still an urgent need for effective eczema treatment compositions with minimal or no side effects. Overview

[0008] This invention relates to a topical composition comprising: a water-soluble substance selected from organic acids, metal salts and neutral substances or combinations thereof, and a water-insoluble substance.

[0009] The composition may also contain therapeutic agents for treating skin diseases.

[0010] In some embodiments, the organic acid included in the composition is selected from malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, citric acid, malonic acid, and lactic acid.

[0011] In some embodiments, the metal salts included in the composition are selected from sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, sodium sulfate, sodium chloride, sodium fumarate, sodium phosphate, potassium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium sulfate, potassium chloride, potassium fumarate, magnesium sulfate, magnesium chloride, calcium chloride, sodium ascorbate, and aluminum chloride.

[0012] In some embodiments, the neutral substance included in the composition is selected from maltodextrin, mannitol, sorbitol, monosaccharides (including galactose, fructose and glucose), disaccharides (including maltose and sugar), PEG 200 to PEG 20000, polypropylene glycol copolymer, sodium docusate, glyceryl monostearate, glycerol, polysorbate (including Tween 20, Tween 40, Tween 60 and Tween 80), and sodium dodecyl sulfate.

[0013] In some embodiments, the composition is formulated as an ointment containing, in addition to water-soluble chemicals, a water-insoluble substance selected from glyceryl monostearate, stearic acid, petrolatum, liquid paraffin, glycerin, wax, lanolin, mineral oil, and fatty alcohols.

[0014] In some embodiments, the composition is formulated as a powder and contains, in addition to water-soluble chemicals, a water-insoluble substance selected from talc, sublimed sulfur, sulfur, calamine, zinc oxide, calcium carbonate, microcrystalline cellulose, starch (including pregelatinized starch), corn starch, rice starch, sweet potato starch, cassava starch, and magnesium stearate.

[0015] In some embodiments, the therapeutic agent is selected from glucocorticoid steroids, including ancinonide, beclomethasone, betamethasone, clobetasol, cicotinide, desotinide, dexamethasone, fludrocortisone acetate, fluocinolone acetonide, fluocinolone acetonide, flunisolone, flucotropin, fluticasone, halcinonide, hydrocortisone, mometasone, prednisolone, tesotropide pitava and triamcinolone acetonide or their salts; tacrolimus, pimecrolimus and criborone; antihistamines, including doxepin hydrochloride, diphenhydramine and loratadine; and JAK1 / JAK2 inhibitors, including dapoxetine, utpatinib and ruxolitinib.

[0016] In some embodiments, the composition is substantially anhydrous.

[0017] In some embodiments, the water weight percentage in the composition is less than about 5%.

[0018] In some embodiments, the water weight percentage in the composition is less than about 3%.

[0019] In some embodiments, the water-soluble substance in the composition comprises about 0.5% to about 99% by weight.

[0020] In some embodiments, the water-soluble substance in the composition is present in a weight percentage of about 10% to about 50%.

[0021] In one embodiment, the composition is formulated as a powder, and the water-soluble substance in the composition is selected from organic acids, metal salts, and neutral substances or combinations thereof, by weight percentage from about 0.5% to about 99%.

[0022] In one embodiment, the composition comprises: a water-soluble substance selected from metal salts, organic acids, and neutral substances; and a water-insoluble substance selected from sublimed sulfur, sulfur, calamine, zinc oxide, starch, calcium carbonate, microcrystalline cellulose, or combinations thereof, wherein the water contained in the composition comprises less than about 5% of the total weight of the composition, and the composition is formulated into a powder.

[0023] In some embodiments, the water-soluble substance is an organic acid selected from malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, malonic acid, and citric acid, or combinations thereof.

[0024] In some embodiments, the water-soluble substance is a metal salt selected from sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, sodium fumarate, sodium sulfate, sodium chloride, sodium phosphate, potassium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium fumarate, potassium sulfate, potassium chloride, magnesium sulfate, magnesium chloride, calcium chloride, and aluminum chloride, or combinations thereof.

[0025] In some embodiments, the water-soluble substance is a neutral substance selected from maltodextrin, mannitol, sorbitol, monosaccharides (including galactose, fructose, and glucose), disaccharides (including maltose and sugar), PEG 200 to PEG 20000, polypropylene glycol copolymers, sodium docusate, glycerol, polysorbates (including Tween 20, Tween 40, Tween 60, and Tween 80), and sodium dodecyl sulfate, or combinations thereof.

[0026] In one embodiment, the composition is formulated as an ointment, the composition comprising: a water-soluble substance selected from salts, organic acids and neutral substances; and a water-insoluble substance selected from the group consisting of glyceryl monostearate, stearic acid, petrolatum, liquid paraffin, glycerin, wax, lanolin, mineral oil and fatty alcohols, wherein the water content in the composition (by total weight of the composition) is less than about 5%.

[0027] In one embodiment, the composition is formulated as an ointment, and the composition comprises: a water-soluble substance selected from the group consisting of salts, organic acids, and neutral substances; a therapeutic agent selected from glucocorticoid steroids (including ancinonide, beclomethasone, betamethasone, clobetasol, cicotinide, desotinide, dexamethasone, fludrocortisone acetate, fluocinolone acetonide, fluocinolone acetonide, fluticasone, fluticasone, halcinonide, halometasone, hydrocortisone, mometasone, prednisolone, tesocrotonate pitava and triamcinolone acetonide or salts thereof), tacrolimus, pimecrolimus, and criboroxone; an antihistamine (including doxepin hydrochloride, diphenhydramine, and loratadine); and a JAK1 / JAK2 inhibitor (including dapoxetine, utpatinib, and ruxolitinib). And a water-insoluble substance selected from the group consisting of glyceryl monostearate, stearic acid, petrolatum, liquid paraffin, glycerin, wax, lanolin, mineral oil, and fatty alcohol, wherein the water content in the composition accounts for about 5% of the total weight of the composition.

[0028] In some embodiments, the composition is formulated as a powder, and the water-soluble substance is selected from the group consisting of magnesium sulfate, sodium chloride, sodium sulfate, sodium phosphate, maltodextrin, mannitol, sorbitol, PEG 1200 to PEG 20000, polypropylene glycol copolymer, sodium docusate, or combinations thereof, wherein the water-soluble substance accounts for about 0.5% to about 50% of the total weight of the composition.

[0029] In some embodiments, the composition is formulated as a powder, wherein the water-soluble substance is selected from the group consisting of sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, sodium fumarate, sodium sulfate, sodium chloride, sodium phosphate, potassium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium fumarate, potassium sulfate, potassium chloride, magnesium sulfate, magnesium chloride, calcium chloride, and aluminum chloride, or combinations thereof, wherein the water-soluble substance comprises about 0.5% to about 95% of the total weight of the composition.

[0030] In some embodiments, the composition is formulated as a powder, wherein the water-soluble substance is selected from organic acids including malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, malonic acid and citric acid, or combinations thereof, and the water-soluble substance accounts for about 0.5% to about 95% of the total weight of the composition.

[0031] In some embodiments, the composition is formulated as a powder, and the water-soluble substance is an organic acid.

[0032] This invention relates to a topical composition comprising: a water-soluble substance selected from magnesium sulfate, sodium sulfate, sodium chloride, potassium chloride, potassium sulfate, polypropylene glycol copolymer, and PEG 200 to PEG 20000, or combinations thereof; a water-insoluble substance selected from liquid paraffin, petrolatum, and lanolin, or combinations thereof; and a glucocorticoid or a salt thereof, wherein the water-soluble substance comprises about 0.5% to about 80% (by weight) of the total weight of the composition, the water content in the composition comprises less than about 5% (by weight) of the total weight of the composition, and the composition is formulated as an ointment.

[0033] On the other hand, the present invention relates to a topical composition comprising: a water-soluble substance selected from polypropylene glycol copolymers or PEG with a molecular weight of 200 to 20,000 or combinations thereof; a water-insoluble substance selected from liquid paraffin, petrolatum and lanolin or combinations thereof; and wherein the water-soluble substance comprises about 0.5% to about 80% (by weight) of the total weight of the composition, the water content in the composition comprises less than about 5% (by weight) of the total weight of the composition, and the composition is formulated as an ointment.

[0034] This invention relates to a topical composition comprising: a water-soluble substance selected from polysorbate or combinations thereof with a molecular weight of Tween 20, Tween 40, Tween 60 to Tween 80; and a water-insoluble substance selected from liquid paraffin, petrolatum, and lanolin or combinations thereof; wherein the water-soluble substance comprises about 0.5% to about 80% (by weight) of the total weight of the composition, the water content in the composition comprises about 5% (by weight) of the total weight of the composition, and the composition is formulated as an ointment.

[0035] This invention relates to a topical composition comprising: a water-soluble substance selected from sodium sulfate, magnesium sulfate, and poloxamer, and a water-insoluble substance selected from liquid paraffin, petrolatum, and lanolin, or combinations thereof. The water-soluble substance comprises about 0.5% to about 80% (by weight) of the total weight of the composition, the water content in the composition comprises less than about 5% (by weight) of the total weight of the composition, and the composition is formulated as an ointment.

[0036] This invention relates to a topical composition comprising: a water-soluble substance selected from polypropylene glycol copolymers or PEG 200 to PEG20000 or combinations thereof; a water-insoluble substance selected from liquid paraffin, petrolatum and lanolin or combinations thereof; and a glucocorticoid or a salt thereof, wherein the water-soluble substance comprises about 0.5% to about 80% (by weight) of the total weight of the composition, wherein the water content in the composition comprises about 5% (by weight) of the total weight of the composition, and wherein the composition is formulated as an ointment.

[0037] This invention relates to a topical composition comprising: a water-soluble substance selected from polysorbate or combinations thereof with a molecular weight of Tween 20, Tween 40, Tween 60 to Tween 80; a water-insoluble substance selected from liquid paraffin, petrolatum and lanolin or combinations thereof; and a glucocorticoid steroid or a salt thereof, wherein the water-soluble substance comprises about 0.5% to about 80% (by weight) of the total weight of the composition, wherein the water content in the composition comprises less than about 5% (by weight) of the total weight of the composition, and wherein the composition is formulated as an ointment.

[0038] This invention relates to a topical composition comprising: a water-soluble substance including sodium sulfate, magnesium sulfate, and poloxamer; a water-insoluble substance selected from liquid paraffin, petrolatum, and lanolin, or combinations thereof; and a glucocorticoid steroid or a salt thereof, wherein the water-soluble substance comprises about 0.5% to about 80% (by weight) of the total weight of the composition, wherein the water content of the composition comprises less than about 5% (by weight) of the total weight of the composition, and wherein the composition is formulated as an ointment.

[0039] In some embodiments, the glucocorticoids are selected from the group consisting of: 0.1% mometasone, 0.1%–0.5% hydrocortisone, 0.1%–0.5% triamcinolone, 0.05% dexamethasone, 0.1% betamethasone, 0.05% flumethasone, 0.025% fludrocortisone acetate, 0.02% clobetasol, 0.1% ancinonide, 0.05% desonide, 0.1% halcinonide, 0.05% fluticasone, and 0.5% prednisolone.

[0040] The present invention relates to a third aspect, a method for treating a skin disease in a subject, comprising the steps of: a) administering to the subject a topical therapeutic agent for treating the skin disease; b) administering to the subject an effective amount of the topical composition of the first aspect, wherein the topical composition is formulated as a powder.

[0041] The present invention relates to a method for treating a skin disease in a subject, the method comprising administering to the subject an effective amount of the topical composition described in the first or second aspect.

[0042] This invention relates to a method for treating a subject’s skin disease, the method comprising administering to the subject an effective amount of a powder or ointment-like topical composition containing a water-soluble substance.

[0043] In some embodiments, the skin disease is selected from eczema, atopic eczema, neurodermatitis, contact dermatitis, chronic eczema, infantile eczema, milia, diaper rash, psoriasis, and diabetic ulcers.

[0044] This invention relates to a composition for a topical medication for treating skin diseases, the composition comprising a water-soluble substance selected from organic acids, metal salts of acids and neutral substances or combinations thereof, and a water-insoluble substance, wherein the medication is substantially anhydrous.

[0045] This invention relates to a topical pharmaceutical composition comprising a water-soluble substance selected from organic acids, metal salts of acids, and neutral substances or combinations thereof, as well as a water-insoluble substance. definition

[0046] The terms “eczema” and “dermatitis” are used interchangeably. As used herein, the term “eczema” refers to a group of skin conditions characterized by dry, swollen, irritated, and / or itchy skin. The compositions and methods of the present invention can be used to treat a variety of types of eczema, including but not limited to atopic dermatitis, nummular dermatitis, seborrheic dermatitis, irritant contact dermatitis, allergic contact dermatitis, pompholyx, hand dermatitis, neurodermatitis, occupational dermatitis, and stasis dermatitis. The term “skin condition” as used herein includes, but is not limited to, eczema, atopic eczema, neurodermatitis, contact dermatitis, chronic eczema, infantile eczema, miliaria, diaper rash, psoriasis, and diabetic ulcers.

[0047] The term "skin" is intended to encompass all the skin on the body, including the scalp, forehead, head, neck, arms, legs, etc. The term "skin" also aims to include all layers of the skin, such as the stratum corneum, epidermis, and dermis.

[0048] The terms “disease,” “disorder,” and “condition” used in this article are used interchangeably to refer to an abnormal physiological state of the subject.

[0049] As used herein, the term “anhydrous” means that the water content in the composition (by total weight of the composition) is less than about 5%. In some embodiments, the water content in the composition may be less than about 4%, about 3%, about 2%, about 1%, about 0.5%, or about 0.1%, or may be completely anhydrous.

[0050] The use of the terms "water-soluble substances" and "water-insoluble substances" in this article has practical significance. For example, "water-soluble substances" does not necessarily mean that the substance can form an aqueous solution as referred to in the term "solution" in chemistry textbooks. If a more precise mathematical distinction is required, "water-soluble substances" refer to substances with a solubility in water exceeding 1 wt%, while "water-insoluble substances" refer to substances with a solubility in water less than 0.1 wt%.

[0051] Unless otherwise stated, all percentages, parts and proportions herein are based on the total weight of the compositions of the invention.

[0052] The term “and / or” as used in this article should be understood as “one or both,” meaning that they coexist in some cases and exist separately in others.

[0053] In this specification, unless the context clearly specifies otherwise, the word "comprising" or variations thereof, such as "constituting," "including," or "comprises," shall be understood to include the said element, integer, or step, or group of elements, integers, or steps, but does not exclude any other element, integer, or step, or group of elements, integers, or steps.

[0054] Unless the context otherwise requires or explicitly states otherwise, when an integer, step, or element in the art described herein appears in the singular form, it obviously encompasses both the singular and plural forms of the integer, step, or element.

[0055] In this specification, "a" and "an" are used to refer to one or more (i.e., at least one) of the text's grammatical objects. For example, "an element" refers to one element, or multiple elements.

[0056] In this specification, the term "approximately" refers to a value that is not an absolute value, but rather includes a range of deviations. This range should be within the understanding of someone skilled in the art, including typical error ranges or instrument limitations. In other words, the term "approximately" refers to a range or approximation that someone skilled in the art considers equivalent to the stated value, provided that the same function or result is achieved.

[0057] As used herein, the term “treatment” or “treatment of a skin disease” means: (1) preventing or delaying the onset of one or more symptoms of a skin disease (e.g., eczema) in an individual who is susceptible to such a disease but has not yet developed symptoms; (2) suppressing a skin disease, i.e., preventing or reducing the development or progression of a skin disease or one or more symptoms thereof; or (3) alleviating a skin disease, even if the skin disease or at least one of its symptoms subsides or reverses. The benefit obtained by the individual receiving treatment should be statistically significant, or at least perceptible to the individual with the skin disease and / or to the physician. Therefore, terms such as “treatment” or “therapy” should be understood in their broadest context, including curing, improving, or reducing the severity of a skin disease or one or more associated symptoms thereof. For the purposes of this invention, “treatment” or “therapy” may refer to the skin condition compared to when no treatment was received.

[0058] "Effective dose" and "therapeutic effective dose" refer to the amount of a therapeutic agent (e.g., a glucocorticoid or antihistamine) or composition sufficient to produce the intended therapeutic or pharmacological effect in a subject. These terms are synonymous and are intended to define the dosage of each therapeutic agent or composition to achieve the goal of improving disease severity and / or the frequency of disease occurrence, while preferably avoiding or minimizing adverse side effects, including those commonly associated with other therapies. The "effective dose" or "therapeutic effective dose" will vary depending on the therapeutic agent or composition, the severity of the disease, and the age, physical condition, and responsiveness of the individual being treated.

[0059] The terms “subject,” “patient,” and “individual” are used interchangeably and include any human or non-human mammal. Therefore, the methods and compositions of the present invention are applicable not only to human treatment but also to veterinary treatment of mammals, including companion animals and farm animals, such as, but not limited to, dogs, cats, horses, cattle, sheep, and pigs. In some embodiments, the subject is a human.

[0060] In this specification, "administration" and variations thereof, including "administration" and "administration," include contacting, applying, delivering, or providing to a subject the therapeutic agents (e.g., glucocorticoids or antihistamines) or compositions of the present invention by any appropriate means.

[061] Any documents, actions, or knowledge items mentioned or discussed in this specification are provided only to provide background information for the invention. It is not implied or indicated that, as of the priority date, such matters or any combination thereof constitute common knowledge or are related to solving any problem addressed in this specification.

[0061] Those skilled in the art will understand that the technology described herein can be varied and modified in addition to the specific description. It should be understood that the technology includes all such variations and modifications. For the avoidance of doubt, the technology also includes all steps, features, and compounds mentioned or specified in this specification, whether individually or collectively, and any combination of any two or more of the stated steps, features, and compounds.

[0062] To better understand the present invention, preferred embodiments will be described below with reference to the accompanying drawings and examples. Implementation Example Description Composition

[0063] This invention relates to topical compositions for treating skin diseases such as eczema and psoriasis. The compositions of this invention comprise a water-soluble substance selected from organic acids, metal salts of acids, and neutral substances or combinations thereof, as well as a water-insoluble substance. In one embodiment, the topical composition further comprises a therapeutic agent for treating skin diseases (e.g., a glucocorticoid or a salt thereof, an antihistamine, or a JAK1 / JAK2 inhibitor). In some embodiments, the topical compositions of this invention are substantially anhydrous (i.e., anhydrous).

[0064] In some embodiments, the compositions of the present invention comprise therapeutic agents known for treating skin diseases. In one embodiment, the compositions of the present invention do not contain therapeutic agents known for treating skin diseases.

[0065] The topical composition of the present invention comprises a water-soluble substance selected from organic acids, metal salts, and neutral substances or combinations thereof. In some embodiments, the organic acid may be malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, citric acid, malonic acid, or lactic acid, or any combination thereof. In some embodiments, the metal salt of the acid may be sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, sodium sulfate, sodium chloride, sodium fumarate, sodium phosphate, potassium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium sulfate, potassium chloride, potassium fumarate, magnesium sulfate, magnesium chloride, calcium chloride, or aluminum chloride, or any combination thereof. In one embodiment, the neutral substance may be maltodextrin, mannitol, sorbitol, monosaccharides (including galactose, fructose, and glucose), disaccharides (including maltose and sugar), PEG 200 to PEG 20000, polypropylene glycol copolymer, sodium docusate, glyceryl monostearate, glycerol, polysorbate (including Tween 20, Tween 40, Tween 60, and Tween 80), and sodium dodecyl sulfate or combinations thereof.

[0066] The topical composition of the present invention comprises a water-insoluble substance. In some embodiments, the water-insoluble substance may be glyceryl monostearate, stearic acid, petrolatum, liquid paraffin, glycerin, wax, lanolin, mineral oil, fatty alcohol, or any combination thereof. In one embodiment, the water-insoluble substance may be talc, calcium carbonate, sublimed sulfur, calamine, zinc oxide, starch (including pregelatinized starch), corn starch, rice starch, sweet potato starch, tapioca starch, or magnesium stearate, or any combination thereof.

[0067] The topical compositions of the present invention can be provided in a variety of forms. Those skilled in the art can select a suitable water-soluble substance according to the desired form of administration. For example, in the form of powder or ointment.

[0068] In some embodiments, the topical composition further comprises a therapeutic agent for treating skin conditions such as eczema. For example, the therapeutic agent may be a glucocorticoid such as ancinonide, beclomethasone, betamethasone, clobetasol, cicotinide, desotinide, dexamethasone, fludrocortisone acetate, fluocinolone acetonide, flunisolone, fluocinolone, fluticasone, halcinonide, halometasone, hydrocortisone, mometasone, prednisolone, texacosolvan pitava, triamcinolone acetonide, or salts thereof; tacrolimus, pimecrolimus, criboroxetine; antihistamines such as doxepin hydrochloride, diphenhydramine, and loratadine; or JAK1 / JAK2 inhibitors such as dapoxetine, utpatinib, and ruxolitinib.

[0069] The compositions of the present invention can be formulated into a variety of forms suitable for topical administration. Standard pharmaceutical formulation techniques known to those skilled in the art can be used to prepare these formulations. Topical skin treatment compositions can be in any form, including, for example, emulsions, oils, creams, ointments, powders, gels, lotions, pastes, moisturizers, skin patches, foams, sprays, aerosols, etc., comprising microemulsions and liposome formulations. Preferably, the topical composition is in powder or ointment form.

[0070] In some embodiments, the topical compositions of the present invention are substantially anhydrous (i.e., water-free). In some embodiments, the water content in the compositions of the present invention is about 15% of the total weight of the composition. In some embodiments, the water content in the compositions of the present invention is about 10% of the total weight of the composition. In some embodiments, the water content in the compositions is less than about 5%, about 4%, about 3%, about 2%, about 1%, or about 0.5% of the total weight of the composition, respectively. Preferably, the water content in the compositions is less than about 5% of the total weight of the composition. Therefore, ointments and powders are preferred embodiments of the present invention because they are generally anhydrous.

[0071] In some embodiments, the topical composition comprises about 0.5% to about 100% (by weight) of a water-soluble substance (based on the total weight of the composition). In some embodiments, the composition comprises about 0.5% to about 5%, about 5% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, or about 10% to about 20% (by weight) of a water-soluble substance (based on the total weight of the composition).

[0072] In some embodiments, the amount of water-soluble substance contained in the composition will vary depending on the specific water-soluble substance used and the severity of the skin condition to be treated. Typically, the amount of water-soluble substance in the composition is sufficient to relieve itching in a subject suffering from a skin condition such as eczema or psoriasis. In some embodiments, the amount of water-soluble substance is from about 10 mg to about 990 mg of the total weight of the composition, representing about 1% to about 99% of the total weight of the composition. Preferably, the proportion is from about 10% to about 80% of the total weight of the composition.

[0073] In some embodiments, the water-insoluble substance contained in the composition is at least about 10% (w / w), at least about 20% (w / w), at least about 30% (w / w), and up to about 98% (w / w) of the total weight of the composition. Therefore, the total amount of water-insoluble substance in the composition can be from about 10% (w / w) to about 98% (w / w) of the composition. In some embodiments, the total amount of water-insoluble substance in the composition is from about 20% (w / w) to about 80% (w / w) of the composition. In some embodiments, the total amount of water-insoluble substance in the composition is from about 50% (w / w) to about 60% (w / w) of the composition.

[0074] In some embodiments, the compositions of the present invention may be formulated with another substance, such as an excipient comprising one or more dermatologically acceptable ingredients or carriers. As used herein, the term "excipient" refers to a liquid, solid, or semi-solid matrix made from dermatologically acceptable excipients or carriers. The term "dermatologically acceptable" as used herein means that the carrier or solvent is suitable for contact with human or animal keratinized tissue, particularly eczematous skin, without causing excessive toxicity, incompatibility, instability, allergic reactions, etc. Many topical carrier materials known in the art, such as water, alcohols, aloe vera gel, allantoin, glycerin, vitamin A and E oils, mineral oil, propylene glycol, etc., can be used to prepare such formulations.

[0075] In some embodiments, the composition is formulated as an aqueous solution or ointment comprising a water-soluble substance comprising an organic acid selected from malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, citric acid, malonic acid, and lactic acid; a neutral substance selected from sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, sodium fumarate, sodium chloride, sodium sulfate, sodium phosphate, potassium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium fumarate, potassium chloride, potassium sulfate, magnesium sulfate, magnesium chloride, aluminum chloride, and calcium chloride; and a neutral substance selected from maltodextrin, monosaccharides including galactose, fructose, and glucose, disaccharides including maltose and sugars, PEG 200 to PEG 20000, and polypropylene glycol copolymers. The ointment composition comprises glyceryl monostearate, glycerin, polysorbate (containing Tween 20, Tween 40, Tween 60 and Tween 80), sodium dodecyl sulfate or combinations thereof, poloxamer (polyethylene glycol-propylene glycol copolymer or polyoxyethylene-polyoxypropylene copolymer), sodium docusate, alcohols or combinations thereof, and water-insoluble substances selected from liquid paraffin, waxes, petrolatum and lanolin. Preferably, the water content in the ointment composition is less than about 5%, more preferably less than about 3% (by total weight of the composition).

[0076] In some embodiments, the composition is formulated as an anhydrous ointment comprising a glucocorticoid, a water-soluble substance (comprising an organic acid selected from malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, citric acid, malonic acid, and lactic acid), a metal salt (selected from sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, sodium fumarate, sodium chloride, sodium sulfate, sodium phosphate, potassium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium fumarate, potassium chloride, potassium sulfate, magnesium sulfate, magnesium chloride, aluminum chloride, and calcium chloride), and a neutral substance (selected from maltodextrin, mannitol, sorbitol, PEG 200 to PEG 20000, monosaccharides (including galactose, fructose, and glucose) and disaccharides). The ointment composition contains maltose and sugar, glyceryl monostearate, glycerin, polysorbates (containing Tween 20, Tween 40, Tween 60 and Tween 80), and sodium lauryl sulfate or combinations thereof, poloxamer (polyethylene glycol-propylene glycol copolymer or polyoxyethylene-polyoxypropylene copolymer), and sodium docusate or combinations thereof, as well as water-insoluble substances selected from liquid paraffin, waxes, petrolatum, and lanolin. Preferably, the water content in the ointment composition is less than about 5%, more preferably less than about 3% (by total weight of the composition).

[0077] In some embodiments, the composition is formulated as an anhydrous ointment comprising a water-soluble substance selected from citric acid, lactic acid, magnesium sulfate, sodium sulfate, sodium chloride, poloxamer, polysorbate, sorbitol, mannitol, and PEG 200 to 20000, a water-insoluble substance selected from liquid paraffin, petrolatum, and lanolin, or any combination thereof, and a glucocorticoid, wherein the composition comprises about 1% to about 50% (by weight) of the water-soluble substance, and the composition comprises less than about 5% (by weight) of water. Available glucocorticoids include: 0.1% mometasone, 0.1%–1% (e.g., 0.1%–0.5%) hydrocortisone, 0.1%–0.5% triamcinolone, 0.05% dexamethasone, 0.1% betamethasone, 0.05% flumethasone, 0.025% fludrocortisone acetate, 0.02% clobetasol, 0.1% ancinonide, 0.05% desonide, 0.1% halcinonide, 0.05% fluticasone, and 0.5% prednisolone.

[0078] In some embodiments, the composition is formulated as an anhydrous ointment comprising a water-soluble substance selected from sodium sulfate, magnesium sulfate, and sodium chloride; a water-insoluble substance selected from liquid paraffin, petrolatum, and lanolin, or any combination thereof; and a glucocorticoid, wherein the composition comprises about 0.5% to about 50% (by weight) of the water-soluble substance (by weight) as a percentage of the total weight of the composition, and the composition comprises less than about 5% (by weight) of water (by weight) as a percentage of the total weight of the composition. The following medications can be used as glucocorticoids: 0.1% mometasone, 0.1%-1% (e.g., 0.1%-0.5%) hydrocortisone, 0.1%-0.5% triamcinolone, 0.05% dexamethasone, 0.1% betamethasone, 0.05% flumethasone, 0.025% fludrocortisone acetate, 0.02% clobetasol, 0.1% ancinonide, 0.05% desonide, 0.1% halcinonide, 0.05% fluticasone, and 0.5% prednisolone.

[0079] In some embodiments, the composition is formulated as an anhydrous ointment comprising liquid paraffin, petrolatum, 5% to 25% sodium sulfate, and less than 5% water by weight of the total composition.

[0080] In some embodiments, the composition is formulated as an anhydrous ointment comprising liquid paraffin, petrolatum, 5% to 40% sodium dodecyl sulfate, and less than 5% water by weight of the total composition.

[0081] In some embodiments, the composition is formulated as an anhydrous ointment comprising liquid paraffin, petrolatum, 5% to 40% of PEG 6000 to PEG 20000, and less than 5% by weight of water in the total composition.

[0082] In some embodiments, the composition is formulated as an anhydrous ointment comprising liquid paraffin, petrolatum, 5% to 40% of polysorbate with a molecular weight of Tween 20, Tween 60 to Tween 80, and less than 5% water by weight of the total composition.

[0083] In some embodiments, the composition is formulated as an anhydrous ointment comprising liquid paraffin, petrolatum, 5% to 20% sodium docusate, 5% to 20% glycerin, and less than 5% water by weight of the total composition.

[0084] In some embodiments, the composition is formulated as an anhydrous powder comprising a water-soluble substance (which includes an organic acid selected from malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, and citric acid) and a water-insoluble substance (which includes sublimed sulfur, sulfur, calamine, zinc oxide, and magnesium stearate) and starch (which includes pregelatinized starch, corn starch, rice starch, sweet potato starch, and tapioca starch). Preferably, the water content in the powder composition is less than about 5%, more preferably less than about 3% (by total weight of the composition).

[0085] In some embodiments, the composition is formulated as an anhydrous powder comprising a water-soluble substance comprising a metal salt selected from sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, sodium fumarate, sodium chloride, sodium sulfate, sodium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium fumarate, potassium chloride, potassium sulfate, potassium phosphate, magnesium sulfate, magnesium chloride, aluminum chloride, and calcium chloride, and an insoluble substance selected from sublimed sulfur, calamine, zinc oxide, calcium carbonate, microcrystalline cellulose, magnesium stearate, and starch, wherein the starch includes corn starch, pregelatinized starch, rice starch, sweet potato starch, and cassava starch. Preferably, the water content in the powder composition is less than about 5%, more preferably less than about 3% (by total weight of the composition).

[0086] In some embodiments, the composition is formulated as an anhydrous powder comprising a sodium salt of an acid (including sodium chloride), sodium sulfate, sodium ascorbate, calamine, zinc oxide, magnesium stearate, and starch (including corn starch); the powder composition comprises about 5% (by weight) of the total weight of the composition.

[0087] In some embodiments, the composition is formulated as an anhydrous powder comprising potassium salts of acids (including potassium malate), potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium fumarate, potassium chloride, potassium sulfate, potassium phosphate, zinc oxide, magnesium stearate, and starch (including corn starch); the powder composition comprises about 5% (by weight) of the total weight of the composition.

[0088] In some embodiments, the composition is formulated as an anhydrous powder comprising a magnesium salt of an acid (including magnesium sulfate and magnesium chloride), zinc oxide, magnesium stearate, and starch (including corn starch). The powder composition comprises approximately 5% (by weight) of the total weight of the composition.

[0089] In some embodiments, the composition is formulated as an anhydrous powder comprising calcium chloride, zinc oxide, magnesium stearate and starch (including corn starch); the powder composition comprises about 5% (by weight) of the total weight of the composition.

[0090] In some embodiments, the composition is formulated as an anhydrous powder comprising carbohydrates (including maltodextrin, mannitol or sorbitol, galactose, fructose, glucose, maltose and sugar), zinc oxide, magnesium stearate and starch (including corn starch); the powder composition comprises about 5% (by weight) of the total weight of the composition.

[0091] In some embodiments, the composition is formulated as an anhydrous powder comprising maltodextrin, PEG 200 to PEG 20000, monosaccharides (including glyceryl monostearate), glycerin, polysorbates (including Tween 20, Tween 40, Tween 60, and Tween 80), and sodium dodecyl sulfate or combinations thereof, poloxamer (polyethylene glycol-propylene glycol copolymer or polyoxyethylene-polyoxypropylene copolymer), and sodium docusate or combinations thereof, and a water-insoluble substance selected from liquid paraffin, waxes, petrolatum, and lanolin. Preferably, the water content in the ointment composition is less than about 5%, more preferably less than about 3% (by total weight of the composition).

[0092] In some embodiments, the composition is formulated as an anhydrous powder comprising a potassium salt of an acid, including potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium fumarate, potassium chloride, potassium sulfate, potassium phosphate, calamine, zinc oxide, microcrystalline cellulose, magnesium stearate, and starch, including corn starch; the powder composition constitutes less than about 5% of the total weight of the composition.

[0093] In some embodiments, the composition is formulated as an anhydrous powder comprising a water-soluble substance comprising a neutral substance selected from maltodextrin, mannitol, sorbitol, PEG 1200 to PEG 20000 and sodium docusate or combinations thereof, and a water-insoluble substance selected from sublimed sulfur, sulfur, calamine, zinc oxide, magnesium stearate and starch (including pregelatinized starch, corn starch, rice starch, sweet potato starch and tapioca starch). Preferably, the water content in the powder composition is less than about 5%, more preferably less than about 3% (by total weight of the composition).

[0094] In some embodiments, the composition is formulated as an anhydrous powder comprising a water-soluble substance (including magnesium sulfate, sodium sulfate, sodium chloride, mannitol, sorbitol, or combinations thereof) and a water-insoluble substance (selected from sublimed sulfur, sulfur, calamine, zinc oxide, magnesium stearate, and starch, including pregelatinized starch, corn starch, rice starch, sweet potato starch, and tapioca starch). Preferably, the water content in the powder composition is less than about 5%, more preferably less than about 3% (by total weight of the composition). method

[0095] The compositions of the present invention are particularly suitable for treating skin diseases, including severe eczema and psoriasis. Therefore, in one embodiment, the present invention relates to a method of treating skin diseases by applying the compositions of the present invention. In another embodiment, the present invention relates to using the compositions of the present invention to prepare a medicament intended for topical application to a patient suffering from a skin disease.

[0096] Those skilled in the art will understand that the compositions of the present invention can be used to treat a variety of skin diseases and conditions, including but not limited to eczema and psoriasis. Eczema refers to several diseases with similar patterns of skin surface changes. Eczema manifests as flare-ups of skin inflammation, which may include itching, scaling, and erythema. When it develops into a long-term condition (chronic eczema), it can lead to thickened, scaly, peeling, dry, and discolored skin. There are many types of eczema depending on the cause, shape, and location of the rash. Some types of eczema are associated with allergies or contact with irritating chemicals. Some types are associated with or caused by underlying conditions that lead to fluid retention in the legs.

[0097] The terms “eczema” and “dermatitis” are used interchangeably; both aim to define inflammation affecting the epidermis and superficial dermis, characterized by redness and heat of the skin. In some cases, dermatitis can also present with edema, leading to blisters within the dermis that ooze fluid to the skin surface, accompanied by crusting, scaling, and cracking.

[0098] As used in this article, the term "skin disease" refers to various types of inflammatory skin conditions or disorders. Therefore, skin diseases as used herein can include eczema, milia, diaper rash, psoriasis, and diabetic ulcers. Types of eczema include, but are not limited to: atopic dermatitis, hand eczema, infantile eczema, childhood eczema, adult eczema, keratosis pilaris, ichthyosis vulgaris, hand and foot dermatitis, pompholyx, discoid eczema, nummular eczema, allergic contact dermatitis, irritant contact dermatitis, overtreated dermatitis, neurodermatitis, asteatotic eczema, stasis dermatitis, chronic simple lichen simplex, nodular prurigo, seborrheic dermatitis, and psoriasis.

[0099] Eczema can be divided into endogenous and exogenous eczema. Endogenous eczema includes at least various types of atopic dermatitis (e.g., infantile eczema, childhood eczema, adult eczema, keratosis pilaris, and ichthyosis vulgaris), pompholyx, discoid eczema, and nummular eczema. Exogenous eczema includes at least allergic contact dermatitis, irritant contact dermatitis, and hand eczema. Furthermore, the term "eczema" may also encompass stasis dermatitis, asteatotic eczema, chronic lichen simplex, psoriasis, seborrheic dermatitis, and seborrheic dermatitis.

[0100] In some embodiments, the present invention relates to a method of treating a subject’s skin disease (e.g., eczema) using a topical composition that does not contain a therapeutic agent for treating skin diseases.

[0101] In some embodiments, the topical composition of the present invention and known therapeutic agents can be used in combination. For example, the composition and therapeutic agent of the present invention can be administered sequentially to achieve the beneficial effects of the combined drug. Alternatively, the composition and known therapeutic agent of the present invention can be administered substantially simultaneously, for example, as a single formulation (i.e., the same composition) in a fixed proportion or as multiple separate formulations of each drug. In some embodiments, the combination therapy has a synergistic effect, particularly for severe eczema, where the observed beneficial effects are greater than those produced by administering each compound alone.

[0102] In some embodiments, a method of treating a subject's skin condition (e.g., eczema) includes the steps of: a) administering a topical therapeutic agent (e.g., a corticosteroid or a salt thereof, an antihistamine, or a JAK1 / JAK2 inhibitor) to the subject; and b) administering an effective amount of the topical composition of the present invention to the subject. Preferably, the topical composition is formulated as a powder. For example, a method of treating eczema may include: applying a therapeutic cream containing a corticosteroid (e.g., hydrocortisone) to the skin lesion, and then sprinkling the powder composition of the present invention onto the same skin lesion covered with the therapeutic cream. Preferably, the eczema is severe eczema. Therefore, the present invention also relates to a kit for treating skin conditions, the kit comprising: a) a topical therapeutic agent (e.g., a cream of a corticosteroid or a salt thereof, an antihistamine, or a JAK1 / JAK2 inhibitor); and b) the topical powder composition of the present invention.

[0103] The effective dosage and dosing regimen of topical compositions used to treat skin conditions such as eczema, milia, diaper rash, psoriasis, and diabetic ulcers depend on a variety of factors, including the patient's age, weight, sex, and health status, the area of ​​skin inflammation, the severity of the disease, the route and frequency of administration, and whether other therapeutic agents are being used concurrently, and therefore can vary considerably. Such treatments may be administered frequently as needed and for a period of time at the discretion of the treating physician. Those skilled in the art will understand that the dosing regimen or therapeutically effective dose of a topical composition may require optimization.

[0104] The topical composition of the present invention can be administered multiple times daily (e.g., twice, three, or six times daily), once daily, once every two days, once every three days, once every four days, or once every five days, once weekly, or as needed. Preferably, the topical composition is used one to three times daily.

[0105] Those skilled in the art will understand that dosage depends on the specific composition, the proportion or percentage of water-soluble substances in the composition, its potency, and whether other therapeutic agents are used concurrently. The dosage of a topical composition should be sufficient to produce the intended effect, namely, improvement or reversal of skin conditions such as eczema and their associated symptoms, but not so high as to cause uncontrollable side effects. However, it should be understood that the specific dosage for a subject depends on a variety of factors, including the subject's weight, overall health condition, sex and diet, previous use of other medications or therapies, and the severity of the disease, which is well understood by those skilled in the art. A physician may also adjust the dosage if any complications occur.

[0106] Those skilled in the art will understand that many variations and / or modifications can be made to this invention without departing from the spirit or scope thereof, as shown in the specific embodiments. Therefore, these embodiments should be considered exemplary rather than restrictive in all respects.

[0107] Embodiments of the invention will now be discussed in more detail with reference to specific examples, which are for illustrative purposes only and should not be construed as limiting the scope of the invention in any way. Example

[0108] General methods for preparing powder compositions

[0109] One or more water-soluble substances, including: organic acids selected from malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, citric acid, malonic acid, and lactic acid; metal salts selected from sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, and sodium fumarate; neutral substances selected from sodium chloride, sodium sulfate, sodium phosphate, potassium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium fumarate, potassium chloride, potassium sulfate, potassium lactate, magnesium sulfate, magnesium chloride, calcium chloride, zinc carbonate, calcium carbonate, and aluminum chloride; or neutral substances selected from maltodextrin, mannitol, sorbitol, PEG 1200 to PEG 20000, sodium docusate, and sodium dodecyl sulfate. The above mixture is added to a mixer. One or more water-insoluble substances (including microcrystalline cellulose, calamine, sulfur, zinc oxide, or starch) are then added to a mixer containing one or more water-soluble substances and mixed mechanically to form a powder mixture. This powder is further mixed in a wet granulator or ground into a fine powder using a grinder or pulverizer. The fine powder is collected, sieved, and then packaged into granule bags or plastic bottles.

[0110] General methods for preparing ointment compositions

[0111] One or more water-soluble substances, including: organic acids selected from malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, propionic acid, malonic acid, citric acid, malonic acid, and lactic acid; metal salts selected from sodium acetate, sodium propionate, sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, and sodium fumarate; neutral substances selected from maltodextrin, mannitol, sorbitol (3% to 90% by weight of the total composition), PEG 1200 to PEG 20000, sodium docusate, and sodium dodecyl sulfate, or combinations thereof, added to the mixer. Then, one or more water-insoluble substances (including glyceryl monostearate, stearic acid, petrolatum, liquid paraffin, glycerin, wax, lanolin, mineral oil, and fatty alcohols) are added to a mixer containing one or more water-soluble substances and mixed with water comprising less than 5% of the total weight of the composition. The mixture is then dissolved in a water bath at a temperature above 60°C to form a transparent liquid. The liquid is sheared and dispersed using a high-speed shearing machine to obtain a homogeneous ointment composition. The homogeneous ointment is collected and filled into plastic bottles.

[0112] Example 1: Anhydrous powder composition containing malic acid

[0113] Mix 500 g of malic acid, 490 g of corn starch, and 10 g of magnesium stearate, and grind them using a grinder. Pass the resulting powder through a 120-mesh sieve, and take 50 g of the powder mixture and put it into a bottle.

[0114] Example 2: Anhydrous powder composition containing magnesium sulfate

[0115] Mix 120 g magnesium sulfate, 60 g maltodextrin, 60 g mannitol, 60 g PEG 6000, 60 g calamine, 60 g zinc oxide, 280 g corn starch, and 10 g magnesium stearate, and grind them using a grinder. Pass the resulting powder through a 120-mesh sieve, and take 50 g of the powder mixture and put it into a bottle.

[0116] Example 3: Anhydrous powder composition containing maltodextrin

[0117] Mix 200g of maltodextrin, 120g of magnesium sulfate, 670g of corn starch, and 10g of magnesium stearate, and grind them using a grinder. Pass the resulting powder through a 120-mesh sieve, collect the powder mixture, and bottle it.

[0118] Example 4: Anhydrous powder composition containing PEG 6000 and malic acid

[0119] Mix 100 g PEG 6000, 200 g malic acid, 690 g corn starch and 10 g magnesium stearate, and grind them using a grinder. Pass the resulting powder through a 120-mesh sieve, collect the powder mixture and bottle it.

[0120] Example 5: Anhydrous powder composition containing mannitol

[0121] Mix 200 g mannitol, 790 g corn starch, and 10 g magnesium stearate, and grind them using a grinder. Pass the resulting powder through a 120-mesh sieve, collect the powder mixture, and bottle it.

[0122] Example 6: Anhydrous powder composition containing maltodextrin, magnesium sulfate and malic acid

[0123] Mix 100 g magnesium sulfate, 100 g maltodextrin, 200 g malic acid, 590 g corn starch, and 10 g magnesium stearate, and grind them using a grinder. Pass the resulting powder through a 120-mesh sieve, collect the powder mixture, and bottle it.

[0124] Example 7: Anhydrous powder composition containing sodium sulfate

[0125] Mix 400 g sodium sulfate, 590 g corn starch, and 10 g magnesium stearate, and grind them using a grinder. Pass the resulting powder through a 120-mesh sieve, collect the powder mixture, and bottle it.

[0126] Example 8: Anhydrous powder composition containing magnesium sulfate

[0127] Mix 400 g magnesium sulfate, 590 g corn starch, and 10 g magnesium stearate, and grind them using a grinder. Pass the resulting powder through a 120-mesh sieve, collect the powder mixture, and bottle it.

[0128] Example 9: An ointment composition comprising hydrocortisone butyrate, white petrolatum, liquid paraffin, and butyric acid.

[0129] Place 18.18 g of liquid paraffin and 162.28 g of white petrolatum in a beaker and heat in a 75°C water bath until liquid. After the liquid paraffin and petrolatum have completely dissolved into a clear solution, add 200 mg of hydrocortisone butyrate and 19.96 g of butyric acid to the beaker. Mix with a high-speed stirrer. The resulting solution is homogeneous and poured into a bottle. The butyric acid (as well as propionic acid and acetic acid) has a very strong, unpleasant acidic taste.

[0130] Example 10: Dexamethasone acetate ointment containing malic acid (10g:5mg)

[0131] Place 200g of liquid paraffin and 600g of white petrolatum in a beaker and heat in a 70°C water bath until liquid. Add 500mg of dexamethasone acetate to the beaker. Then add 200g of malic acid to the same beaker and stir well. Transfer 50g of the ointment to a bottle. A uniform, slightly milky-white ointment will form. After cooling, no particles or lumps should be visible to the touch.

[0132] Example 11: Dexamethasone acetate ointment containing sodium malate (10g:5mg)

[0133] Place 200 g of liquid paraffin and 600 g of white petrolatum in a beaker and heat in a 70°C water bath until liquid. Add 500 mg of dexamethasone acetate to the beaker. Then add 200 g of sodium malate to the same beaker and stir until homogeneous. Transfer 50 g of the ointment to a jar. A homogeneous, slightly milky-white ointment is formed.

[0134] Example 12: Talcum powder containing sodium lactate and maltodextrin

[0135] Mix 100g sodium lactate, 300g maltodextrin, 590g corn starch, and 10g magnesium stearate, and grind them using a grinder. Pass the resulting powder through a 120-mesh sieve, collect the powder mixture, and bottle it.

[0136] Example 13: Ointment containing petrolatum, liquid paraffin and sodium ascorbate

[0137] Place 30g of liquid paraffin and 120g of petroleum jelly in a beaker and heat in a 60°C water bath until liquid. Then add 15g of sodium ascorbate to the beaker. Stir with a high-speed stirrer until homogeneous. Transfer the ointment into aluminum tubes and seal.

[0138] Example 14: Ointment containing petrolatum, liquid paraffin and malic acid

[0139] Place 18 g of liquid paraffin and 162 g of white petrolatum in a beaker and heat in a water bath at 75-80°C until liquid. Then add 20 g of malic acid to the beaker. Stir with a high-speed stirrer until homogeneous. Transfer the ointment into aluminum tubes and seal.

[0140] Example 15: Ointment containing petrolatum, liquid paraffin and tartaric acid

[0141] Place 18 g of liquid paraffin and 162 g of petroleum jelly in a beaker and heat in a water bath at 75-80°C until liquid. Then add 20 g of tartaric acid to the beaker. Stir the contents with a high-speed mixer until homogeneous. Fill the ointment into aluminum tubes and seal.

[0142] Example 16: An ointment comprising petrolatum, liquid paraffin, and sodium lactate

[0143] Place 40 g of liquid paraffin and 120 g of petroleum jelly in a beaker and heat in a water bath at 75-80°C until liquid. Then add 40 g of sodium lactate to the beaker. Stir with a high-speed stirrer until homogeneous. Pour the ointment into aluminum tubes and seal.

[0144] Example 17: An ointment comprising petrolatum, liquid paraffin, and sodium docusate.

[0145] Place 100 g of liquid paraffin and 325 g of petroleum jelly in a beaker and heat in a water bath at 80°C until liquid. Then add 75 g of sodium docusate to the beaker. Stir with a high-speed stirrer until homogeneous. Fill the ointment into aluminum tubes and seal.

[0146] Example 18: An ointment comprising petrolatum, liquid paraffin and 3% sodium lauryl sulfate (SDS).

[0147] Place 120g of liquid paraffin and 171g of petroleum jelly in a beaker and heat in an 80°C water bath until liquid. Then add 9g of sodium dodecyl sulfate to the beaker. Stir with a high-speed stirrer until a homogeneous liquid is obtained. Fill the ointment into aluminum tubes and seal them.

[0148] Example 19: An ointment comprising petrolatum, liquid paraffin and 15% sodium lauryl sulfate

[0149] Place 40 grams of liquid paraffin and 130 grams of petroleum jelly in a beaker and heat in an 80°C water bath until liquid. Then add 30 grams of sodium dodecyl sulfate to the beaker. Stir with a high-speed stirrer until a homogeneous liquid is obtained. Fill the ointment into aluminum tubes and seal them.

[0150] Example 20: An ointment comprising petrolatum, liquid paraffin, 9% sodium lauryl sulfate and 0.1% triamcinolone acetonide

[0151] Place 122.7 g of liquid paraffin and 150 g of petroleum jelly in a beaker and heat in an 80°C water bath until liquid. Then add 0.3 g of triamcinolone acetonide and 27 g of sodium dodecyl sulfate to the beaker. Stir with a high-speed stirrer until a homogeneous liquid is obtained. Fill the ointment into aluminum tubes and seal them.

[0152] Example 21: An ointment comprising petrolatum, liquid paraffin and 10% PEG 6000

[0153] Place 70 g of liquid paraffin and 110 g of petroleum jelly in a beaker and heat in a 75°C water bath until liquid. Then add 20 g of PEG 6000 to the beaker. Stir with a high-speed stirrer until homogeneous and liquid. Fill the ointment into aluminum tubes and seal.

[0154] Example 22: A talcum powder comprising sodium sulfate, sodium chloride, sodium lauryl sulfate, magnesium sulfate, magnesium chloride, and microcrystalline cellulose.

[0155] Mix 400g sodium sulfate, 400g sodium chloride, 400g sodium dodecyl sulfate, 400g magnesium sulfate, 400g magnesium chloride, 400g ascorbic acid, and 3600g microcrystalline cellulose in a mixer. Sift the resulting powder through a 120-mesh sieve. Add 100g magnesium stearate to the mixer containing the fine powder and mix for 20 minutes. Take 60g of the powder and seal it in a plastic bottle.

[0156] Example 23: A talcum powder containing maltodextrin, mannitol, polyethylene glycol, and sodium docusate.

[0157] Mix 500g maltodextrin, 500g mannitol, 500g polyethylene glycol 6000, 500g sodium docusate, 500g sodium lauryl sulfate, and 3500g microcrystalline cellulose in a mixer. Sift the resulting powder through a 120-mesh sieve. Add 100g magnesium stearate to the mixer containing the fine powder and mix for 20 minutes. Take 60g of the powder and seal it in a plastic bottle.

[0158] Example 24: A composition comprising 65% white petrolatum, 20% liquid paraffin, and 15% poloxamer

[0159] Place 100 g of liquid paraffin and 325 g of white petrolatum in a beaker and heat in an 80°C water bath until completely dissolved, forming a clear liquid and thoroughly mixed. Then add 75 g of poloxamer to the beaker and stir for 15 minutes until the poloxamer melts, forming a uniformly colored liquid. Transfer the mixture into an aluminum tube and seal it.

[0160] Case Study 1

[0161] A patient with eczema was initially treated with hydrocortisone butyrate cream, followed by a powdered topical composition (the ingredients of the powdered composition are shown in Table 1).

[0162] Apply hydrocortisone butyrate cream to the affected skin, then apply the powder over the cream. The patient used this treatment twice daily for two consecutive days. After two days of this combined treatment, the itching symptoms disappeared, and the eczema symptoms were further reduced compared to using hydrocortisone butyrate cream alone once or several times daily for two weeks. Table 1. Talcum powder containing sodium tartrate

[0163] Case Study 2

[0164] An 80-year-old patient with eczema was treated with a talcum powder composed of sodium sulfate, magnesium sulfate, 55% starch, microcrystalline cellulose, calamine, zinc oxide, and ascorbic acid. The patient had abrasions with bleeding and itching. The talcum powder was applied directly to the patient's skin. The itching stopped within 60 minutes after application. The patient used the talcum powder three to four times daily as needed. After approximately 15 days of treatment, the itching and swelling disappeared, and the eczema symptoms subsided. Table 2. Pharmaceutical Powder Compositions

[0165] Table 2 lists 17 pharmaceutical powder compositions and their components (in grams). Each component was ground into powder using a grinder. The resulting powder was passed through a 120-mesh sieve, and the powder mixture was collected and bottled.

Claims

1. A topical composition comprising: a water-soluble substance selected from organic acids, metal salts of acids, and neutral substances or combinations thereof, and a water-insoluble substance.

2. The composition according to claim 1 further comprises a therapeutic agent for treating skin diseases.

3. The composition according to claim 1 or 2, wherein the organic acid is selected from malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, citric acid and malonic acid.

4. The composition according to any one of claims 1 to 3, wherein the metal salt is selected from sodium, potassium, magnesium, calcium and aluminum salts of acids.

5. The composition of claim 4, wherein the acid is selected from mineral acids (including sulfuric acid, hydrochloric acid, and phosphoric acid) and organic acids (including acetic acid, propionic acid, malonic acid, malic acid, succinic acid, maleic acid, citric acid, tartaric acid, lactic acid, ascorbic acid, and fumaric acid).

6. The composition of claim 4, wherein the sodium salt is selected from sodium acetate, sodium propionate, sodium malonate, sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, sodium sulfate, sodium chloride, sodium fumarate, sodium phosphate, and sodium dodecyl sulfate.

7. The composition of claim 4, wherein the potassium salt is selected from potassium acetate, potassium propionate, potassium malonate, potassium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium sulfate, potassium chloride, potassium fumarate, and potassium dodecyl sulfate.

8. The composition of claim 4, wherein the magnesium salt is magnesium sulfate or magnesium chloride.

9. The composition of claim 4, wherein the metal salt is calcium chloride or aluminum chloride.

10. The composition of claim 4, wherein the metal salt is calcium chloride.

11. The composition of any one of claims 1 to 10, wherein the neutral substance is selected from maltodextrin, mannitol, sorbitol, monosaccharides, disaccharides, PEG 200 to PEG 20000, polypropylene glycol copolymers, sodium docusate, polysorbate, poloxamer, and sodium dodecyl sulfate.

12. The composition of any one of claims 1 to 11, wherein the composition is an anhydrous powder comprising a water-soluble substance, a water-insoluble substance and less than 5% water.

13. The composition according to any one of claims 1 to 11, wherein the amount of the water-soluble substance is 2% to 99% of the total weight of the composition.

14. The composition of any one of claims 1 to 11, wherein the composition is an anhydrous ointment comprising more than 3% water-soluble substance, a water-insoluble ointment base, and less than 5% water.

15. The composition of any one of claims 1 to 11, wherein the composition is an anhydrous ointment comprising 3% to 90% by weight of a water-soluble substance, a water-insoluble ointment base, and less than 5% water.

16. The composition of claim 1, wherein the composition is a powder comprising sodium sulfate, sodium chloride, sodium dodecyl sulfate, magnesium sulfate, ascorbic acid, microcrystalline cellulose, and water comprising less than 5% by weight of the total composition.

17. The composition of any one of claims 1 to 11, wherein the composition is formulated into an ointment, wherein the water-insoluble substance is selected from glyceryl monostearate, stearic acid, petrolatum, liquid paraffin, glycerin, wax, lanolin, mineral oil, and fatty alcohols.

18. The composition of any one of claims 1 to 11, wherein the composition is formulated as a powder, wherein the water-insoluble substance is selected from talc, sublimed sulfur, sulfur, calamine, zinc oxide, starch (including pregelatinized starch), corn starch, rice starch, sweet potato starch, cassava starch, and magnesium stearate.

19. The composition of any one of claims 1 to 18, further comprising a therapeutic agent selected from the group consisting of: glucocorticoids, including ancinonide, beclomethasone, betamethasone, clobetasol, cicotinide, dexamethasone, fludrocortisone acetate, fluocinolone acetonide, flunitrothione, fluticasone, halcinonide, flumethasone, hydrocortisone, mometasone, prednisolone, tesotropium pitava and triamcinolone acetonide or salts thereof; tacrolimus, pimecrolimus and criborone; antihistamines, including doxepin hydrochloride, diphenhydramine and loratadine; and JAK1 / JAK2 inhibitors, including dapoxetine, utpatinib and ruxolitinib.

20. The composition of any one of claims 1 to 19, wherein the composition is substantially anhydrous and the water content (by total weight of the composition) is less than about 5%.

21. The composition of any one of claims 1 to 20, wherein the composition comprises about 2% to about 90% (by weight) of a water-soluble substance (based on the total weight of the composition).

22. The composition of any one of claims 1 to 13, 16 or 18 to 21, wherein the composition is formulated as a powder, and wherein the composition comprises about 3% to about 99% (by weight) of a water-soluble substance selected from organic acids, metal salts and neutral substances or combinations thereof (by total weight of the composition).

23. The composition of claim 1, wherein the water-soluble substance of the composition comprises: a metal salt selected from sodium acetate, sodium propionate, sodium malonate, sodium malate, sodium citrate, sodium succinate, sodium lactate, sodium tartrate, sodium maleate, sodium sulfate, sodium chloride, sodium fumarate, sodium phosphate, sodium acetate, potassium propionate, potassium malonate, potassium phosphate, potassium malate, potassium citrate, potassium succinate, potassium lactate, potassium tartrate, potassium maleate, potassium sulfate, potassium chloride, potassium fumarate, magnesium sulfate, magnesium chloride, calcium chloride, and aluminum chloride; or b. an organic acid selected from malic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid, citric acid, and malonic acid; or c. a substance selected from maltodextrin, mannitol, sorbitol, PEG 1000 to PEG. 20,000, a neutral substance comprising monosaccharides (including galactose, fructose, and glucose), disaccharides (including maltose and sugar), glycerol, polysorbates (including Tween 20, Tween 40, Tween 60, and Tween 80), sodium dodecyl sulfate or combinations thereof, poloxamer and sodium docusate or combinations thereof; and a water-insoluble substance selected from sublimed sulfur, sulfur, calamine, zinc oxide, starch, or combinations thereof, wherein the water content in the composition (by total weight of the composition) is less than about 5%, and wherein the composition is formulated as a powder.

24. The composition of any one of claims 1 to 23, wherein the water-soluble substance is a neutral substance selected from monosaccharides (including galactose, fructose, and glucose), disaccharides (including maltose and sugars), maltodextrin, mannitol, sorbitol, PEG 1200 to PEG 20000, sodium docusate, glycerol, polysorbates (including Tween 20, Tween 40, Tween 60, and Tween 80), poloxamer, and sodium dodecyl sulfate, or combinations thereof.

25. The composition of claim 1 or 2, wherein the composition is formulated as an ointment, wherein the composition comprises: a water-soluble substance selected from metal salts, organic acids and neutral substances; and a water-insoluble substance selected from petrolatum, liquid paraffin and glycerin, wherein the water content in the composition is less than 5% by weight of the total composition.

26. The composition of claim 1 or 2, wherein the composition comprises magnesium sulfate, sodium chloride, sodium sulfate, maltodextrin, mannitol, sorbitol, PEG 1200 to PEG 20000, sodium docusate or a combination thereof, and water comprising less than 5% by weight of the total composition.

27. The topical composition of claim 1 or 2, comprising: a water-soluble substance selected from magnesium sulfate, sodium sulfate, sodium chloride, potassium chloride, potassium sulfate, polypropylene glycol copolymer, PEG 200 to PEG 20000, sodium dodecyl sulfate, or combinations thereof; a water-insoluble substance selected from liquid paraffin, petrolatum, and lanolin, or combinations thereof; and a glucocorticoid or a salt thereof, wherein the water-soluble substance comprises about 3% to about 60% (by weight) of the total weight of the composition, wherein the water content in the composition comprises less than about 5% (by weight) of the total weight of the composition, and wherein the composition is formulated as an ointment.

28. The topical composition of claim 27, wherein the glucocorticoid is selected from a combination containing about 0.1% mometasone, 0.1% to 0.5% hydrocortisone, 0.1% to 0.5% triamcinolone, 0.05% dexamethasone, 0.1% betamethasone, 0.05% flumethasone, 0.025% fludrocortisone acetate, 0.02% clobetasol, 0.1% ancinonide, 0.05% desonide, 0.1% halcinonide, 0.05% fluticasone and 0.5% prednisolone.

29. The topical composition of claim 1, wherein the composition is an ointment comprising liquid paraffin, petrolatum, and a soluble substance comprising 3% to about 60% by weight of the total composition, said soluble substance comprising sodium sulfate, magnesium sulfate, sodium dodecyl sulfate (SDS), PEG 400 to PEG 20000, polysorbate, Tween 20, Tween 40, Tween 60 or Tween 80, and wherein the water content of the composition is less than about 5% by weight of the total composition.

30. The topical composition of claim 1, wherein the composition is an ointment comprising liquid paraffin, petrolatum, and sodium chloride in an amount of 5% to about 15% by weight of the total composition, and wherein the composition comprises water in an amount of less than about 5% by weight of the total composition.

31. The topical composition of claim 1, wherein the composition is an ointment comprising liquid paraffin, petrolatum, and sodium dodecyl sulfate in an amount of 3% to about 60% by weight of the total composition, and wherein the composition comprises water in an amount of less than about 5% by weight of the total composition.

32. The topical composition of claim 1, wherein the composition is an ointment comprising liquid paraffin, petrolatum and PEG 1000 to PEG 10000 in a weight of 3% to about 60% of the total weight of the composition, wherein the water content in the composition is less than about 5% of the total weight of the composition.

33. The topical composition of claim 1, wherein the composition is an ointment comprising liquid paraffin, petrolatum and polysorbate, Tween 20, Tween 40, Tween 60 or Tween 80 in a weight of 3% to 60% of the total composition, wherein the water content in the composition is less than about 5% of the total composition weight.

34. The topical composition of claim 1, wherein the composition is an ointment comprising liquid paraffin, petrolatum, and sodium docusate in an amount of 3% to about 60% by weight of the total composition, and wherein the composition comprises less than about 5% by weight of water in the total composition.

35. A method of treating a skin disease in a subject, comprising administering to the subject an effective amount of any one of claims 1 to 34 of a topical composition, wherein the topical composition is formulated as a powder or ointment.

36. The method of claim 35, wherein the skin disease is selected from eczema, atopic eczema, neurodermatitis, contact dermatitis, chronic eczema, infantile eczema, miliaria, diaper rash, psoriasis, and diabetic ulcers.

37. A composition for manufacturing a topical medicine for treating skin diseases, the composition comprising a water-soluble substance selected from organic acids, metal salts of acids and neutral substances or combinations thereof, and a water-insoluble substance, wherein the medicine is substantially anhydrous.

38. The composition for manufacturing a topical medicament for treating skin diseases according to any one of claims 1 to 34, wherein the medicament is substantially anhydrous.

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