Method for treatment of psoriasis

Abstract

The present invention provides a method for treating or alleviating psoriasis and / or promoting or accelerating the healing of psoriasis, comprising administering a pharmaceutical composition containing an effective amount of an immunomodulatory protein derived from Ganoderma.

Description

Technical Field

[0001] This invention relates to a method for treating psoriasis, and more specifically, to a method utilizing an immunomodulatory protein derived from Ganoderma lucidum. Prior Technology

[0002] Psoriasis is a persistent, non-contagious autoimmune disease characterized by raised areas of abnormal skin, most commonly on the knees, elbows, trunk, and scalp. These areas are often red or purple in individuals with darker, dry, itchy, and scaly skin. It tends to flare up periodically, with sudden onset lasting weeks or months, followed by resolution or remission. Common triggers for psoriasis include stress, alcohol, injury, and medications.

[0003] The severity of psoriasis can range from localized small spots to full-body coverage, and the possible mechanisms are complex and systemic. Managing psoriasis safely and economically remains a challenge.

[0004] When a large area of ​​skin is affected, such as 10% or more of the body surface area, systemic therapy is used, such as methotrexate or biologics, such as etanercept, adalimumab, and infliximab. For large numbers of psoriasis cases, systemic therapy is less effective, and in most such cases, topical medications are considered a safer and more cautious alternative. Topical therapies include anti-inflammatory corticosteroids, particularly highly effective ones, such as halobetasol propionate; vitamin D derivatives, such as calcipotriene; retinoids called tazarotene; and coal tar. While each of these topical therapies offers a certain degree of effectiveness, there are limitations in the extent to which they improve psoriatic plaques or the adverse effects they may produce. Summary of the Invention

[0005] This invention has unexpectedly discovered that immunomodulatory proteins derived from Ganoderma lucidum, or their recombinants, provide beneficial effects in treating or alleviating psoriasis and / or promoting or accelerating the healing of psoriasis. Therefore, this invention provides a method for treating psoriasis using immunomodulatory proteins derived from Ganoderma lucidum.

[0006] In one embodiment, the present invention provides a method for treating or alleviating psoriasis and / or promoting or accelerating the healing of psoriasis, comprising administering a pharmaceutical composition to an individual in need. The pharmaceutical composition comprises an effective amount of an immunomodulatory protein derived from Ganoderma lucidum, or a recombinant or fragment thereof.

[0007] In some embodiments of the present invention, the immunomodulatory protein comprises the amino acid sequence of SEQ ID NO: 3 or 4. In some embodiments of the present invention, the fragment of the immunomodulatory protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to 2.

[0008] The sequences of SEQ ID NO: 1 to 4 are as follows.

[0009] In some embodiments of the present invention, the pharmaceutical composition further comprises a gelling agent.

[0010] In some embodiments of the present invention, the amount of gelling agent in the pharmaceutical composition is about 0.1% (w / w) to about 2% (w / w), about 0.15% (w / w) to about 1.95% (w / w), about 0.2% (w / w) to about 1.9% (w / w), about 0.25% (w / w) to about 1.85% (w / w), about 0.3% (w / w) to about 1.8% (w / w), about 0.35% (w / w) to about 1.75% (w / w), about 0.4% (w / w) to about 1.7% (w / w), about 0.45% (w / w) to about 1.65% (w / w), about 0.5% (w / w) to about 1.6% (w / w), about 0.55% (w / w) to about 1.55% (w / w), or about 0.6% (w / w) to about 1.5%. (w / w), about 0.65% (w / w) to about 1.45% (w / w), about 0.7% (w / w) to about 1.4% (w / w), about 0.75% (w / w) to about 1.35% (w / w), about 0.8% (w / w) to about 1.3% (w / w), about 0.85% (w / w) to about 1.25% (w / w), about 0.9% (w / w) to about 1.2% (w / w), about 0.95% (w / w) to about 1.15% (w / w), about 1.0% (w / w) to about 1.1% (w / w). In some embodiments, the amount of gelling agent is in the range of about 0.5% (w / w) to about 2.0% (w / w), about 0.5 (w / w) to about 1.5% (w / w), about 0.5 (w / w) to about 1.2% (w / w), about 0.5 (w / w) to about 1.0% (w / w), about 0.1 (w / w) to about 1.5% (w / w), about 0.1 (w / w) to about 1.0% (w / w), about 0.1 (w / w) to about 0.5% (w / w), about 1.0% (w / w) to about 2.0% (w / w), or about 1.5% (w / w) to about 2% (w / w).

[0011] In some embodiments of the present invention, the amount of immunomodulatory protein in the pharmaceutical composition is about 0.0001% (w / w) to about 0.05% (w / w), about 0.0001% (w / w) to about 0.05% (w / w), about 0.0005% (w / w) to about 0.045% (w / w), about 0.001% (w / w) to about 0.04% (w / w), about 0.005% (w / w) to about 0.035% (w / w), about 0.001% (w / w) to about 0.03% (w / w), about 0.005% (w / w) to about 0.025% (w / w), about 0.01% (w / w) to about 0.02% (w / w), about 0.0001% (w / w) to about 0.05% (w / w), or about 0.0001%. (w / w) to about 0.05% (w / w), about 0.0001% (w / w) to about 0.05% (w / w), about 0.0001% (w / w) to about 0.05% (w / w), about 0.0001% (w / w) to about 0.05% (w / w), about 0.0001% (w / w) to about 0.05% (w / w), about 0.0001% (w / w) to about 0.05% (w / w), about 0.0001% (w / w) to about 0.05% (w / w). In some embodiments, the amount of immunomodulatory protein is in the range of about 0.0001% (w / w) to about 0.03% (w / w), about 0.0001% (w / w) to about 0.01% (w / w), about 0.0001% (w / w) to about 0.03% (w / w), about 0.0001% (w / w) to about 0.01% (w / w), about 0.0001% (w / w) to about 0.005% (w / w), about 0.0001% (w / w) to about 0.003% (w / w), about 0.0001% (w / w) to about 0.001% (w / w), or about 0.0001% (w / w) to about 0.0005% (w / w).

[0012] Examples of gelling agents include, but are not limited to, polyethylene glycol (PEG) diacrylate, PEG-acrylate, PEG-thiol, PEG-azide, PEG-acetylene, chitosan, hyaluronic acid, collagen, fibroin, gum arabic, alginate, natto gum, aloe vera, bentonite, carbomer, carboxymethyl cellulose, ethyl cellulose, gelatin, elastin, hydroxypolyamide, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, magnesium aluminum silicate, methyl cellulose, poloxamer, polyvinyl alcohol, sodium alginate, tragacanth gum, xanthan gum, gelatin, carboxyvinyl polymers, starch, water-swellable hydrocolloids, carrageenan, hyaluronic acid, agarose, alginate, acrylates, and acrylamide dimethyl taurate / vinylpyrrolidone (VP) copolymer.

[0013] In some embodiments, the gelling agent is xanthan gum, methylcellulose, or ammonium acrylamide dimethyl taurate / VP copolymer.

[0014] In one embodiment, the pharmaceutical composition has a pH value in the range of about 5.5 to about 7.5. In some embodiments, the pH is in the range of about 6.0 to about 7.5, about 6.5 to about 7.5, about 5.5 to about 7.0, about 6.0 to about 7.0, about 6.5 to about 7.0, about 5.5 to about 6.5, or about 6.0 to about 6.5.

[0015] In one embodiment, the pharmaceutical composition has a viscosity in the range of about 0.05 Pa·s to about 200 Pa·s. In some embodiments, the viscosity is in the range of about 0.1 Pa·s to about 200 Pa·s, about 0.5 Pa·s to about 200 Pa·s, about 1.0 Pa·s to about 200 Pa·s, about 5 Pa·s to about 200 Pa·s, about 10.0 Pa·s to about 200 Pa·s, about 20.0 Pa·s to about 200 Pa·s, about 40.0 Pa·s to about 200 Pa·s, about 60.0 Pa·s to about 200 Pa·s, about 80.0 Pa·s to about 200 Pa·s, about 100.0 Pa·s to about 200 Pa·s, about 120 Pa·s to about 200 Pa·s, about 140 Pa·s to about 200 Pa·s, about 160 Pa·s to about 200 Pa·s, about 0.05 Pa·s to about 160 Pa·s, about 0.05 Pa·s to about 140 Pa·s, 0.05 Pa·s to about 20 ... The range is approximately 120 Pa·s, 100 Pa·s, 80 Pa·s, 60 Pa·s, 40 Pa·s, 20 Pa·s, 10 Pa·s, 50 Pa·s, 30 Pa·s, or 1.0 Pa·s.

[0016] In some embodiments, the pharmaceutical composition is applied to the psoriasis area.

[0017] In one embodiment, the pharmaceutical composition is surface-applied to the psoriasis area, and the effective amount of the immunomodulatory protein is in the range of about 1 mcg / cm² to about 100 mcg / cm², about 1 mcg / cm² to about 80 mcg / cm², about 1 mcg / cm² to about 60 mcg / cm², about 1 mcg / cm² to about 40 mcg / cm², about 1 mcg / cm² to about 20 mcg / cm², about 1 mcg / cm² to about 10 mcg / cm², about 1 mcg / cm² to about 5 mcg / cm², about 5 mcg / cm² to about 100 mcg / cm², about 10 mcg / cm² to about 100 mcg / cm², about 20 mcg / cm² to about 100 mcg / cm², about 40 mcg / cm² to about 100 mcg / cm². 2. Approximately 60 mcg / cm² to approximately 100 mcg / cm² or approximately 80 mcg / cm² to approximately 100 mcg / cm² within the psoriasis area.

[0018] In some embodiments of the present invention, the pharmaceutical composition is administered orally to an individual.

[0019] In some embodiments of the present invention, the pharmaceutical composition is administered orally to an individual, and the effective amount of the immunomodulatory protein is in the range of about 0.01 mg / kg to about 5 mg / kg. In some embodiments, the effective amount is from about 0.01 mg / kg to about 4 mg / kg, from about 0.01 mg / kg to about 4.5 mg / kg, from about 0.01 mg / kg to about 4 mg / kg, from about 0.01 mg / kg to about 3.5 mg / kg, from about 0.01 mg / kg to about 3 mg / kg, from about 0.01 mg / kg to about 2.5 mg / kg, from about 0.01 mg / kg to about 2 mg / kg, from about 0.01 mg / kg to about 1.5 mg / kg, from about 0.01 mg / kg to about 1 mg / kg, from about 0.01 mg / kg to about 0.5 mg / kg, from about 0.05 mg / kg to about 5 mg / kg, from about 0.05 mg / kg to about 4.5 mg / kg, from about 0.05 mg / kg to about 4.5 mg / kg, from about 0.05 mg / kg to about 3.5 mg / kg, from about 0.05 mg / kg to about 3 mg / kg. mg / kg, about 0.05 mg / kg to about 2.5 mg / kg, about 0.05 mg / kg to about 2 mg / kg, about 0.05 mg / kg to about 1.5 mg / kg, about 0.05 mg / kg to about 1 mg / kg, about 0.05 mg / kg to about 0.5 mg / kg, about 0.1 mg / kg to about 5 mg / kg, about 0.1 mg / kg to about 4.5 mg / kg, about 0.1 mg / kg to about 4 mg / kg, about 0.1 mg / kg to about 3.5 mg / kg, about 0.1 mg / kg to about 3 mg / kg, about 0.1 mg / kg to about 2.5 mg / kg, about 0.1 mg / kg to about 2 mg / kg, about 0.1 mg / kg to about 1.5 mg / kg, about 0.1 mg / kg to about 1 mg / kg, about 0.1 mg / kg to about 0.5 mg / kg, about 0.5 mg / kg to about 5 mg / kg, about 1 mg / kg to about 5 mg / kg The range is approximately 1.5 mg / kg to approximately 5 mg / kg, approximately 2 mg / kg to approximately 5 mg / kg, approximately 2.5 mg / kg to approximately 5 mg / kg, approximately 3 mg / kg to approximately 5 mg / kg, approximately 3.5 mg / kg to approximately 5 mg / kg, or approximately 4 mg / kg to approximately 5 mg / kg.

[0020] In one embodiment, the method further comprises administering one or more additional therapeutic agents to the individual. In some embodiments, the therapeutic agents include topical medications (e.g., corticosteroids, vitamin D analogs, retinoids, calcineurin inhibitors, salicylic acid, coal tar, anthraquinone), light (e.g., sunlight, broad-spectrum UVB, narrow-spectrum UVB, psoralen + UVA (PUVA), excimer laser), or oral or intravenous administration (e.g., steroids, retinoids, methotrexate, cyclosporine, etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), ustekinumab (Stelara), secukinumab (Cosentyx), ixekizumab (Taltz), thioguanine (Tabloid), hydroxyurea (Droxia, Hydrea), apremilast (Otezla)).

[0021] In some embodiments, psoriasis is plaque psoriasis, pustular psoriasis, reversal psoriasis, diaper psoriasis, punctate psoriasis, oral psoriasis, erythrodermic psoriasis, seborrheic dermatitis-like psoriasis, nail psoriasis, or psoriatic arthritis.

[0022] In some embodiments, psoriasis is familial psoriasis. Simple Explanation of the Diagram

[0023] Figures 1(A) and 1(B) illustrate the effect of the hydrogel of the present invention in treating psoriasis according to Patent 1. Figure 1(A): Before treatment; Figure 1(B): After 2 months of treatment.

[0024] Figures 2(A) and 2(B) illustrate the effect of the capsules of this invention in treating psoriasis according to Patent 1. Figure 2(A): Before treatment; Figure 2(B): After 4 months of treatment.

[0025] Figures 3(A) to 3(C) illustrate the effect of the capsules of this invention in treating psoriasis according to Patent 2. Figure 3(A): Treatment at week 3; Figure 3(B): Treatment at week 12 (skin); Figure 3(C): Treatment at week 12 (nail).

[0026] Figures 4(A) to 4(C) illustrate the effect of the capsules of this invention in treating psoriasis according to Patent 3. Figure 4(A): Before treatment; Figure 4(B): Treatment at week 2; Figure 4(C): Treatment at week 4. Implementation

[0027] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although similar or equivalent methods and materials may be used to practice or test the invention, preferred methods and materials are currently described. All disclosures mentioned herein are incorporated herein by reference.

[0028] In this application, unless otherwise specifically stated, the use of the singular includes the plural, the article "a / an" means "at least one", and the use of "or" means "and / or".

[0029] The term "surface" refers to the application or delivery of a compound by applying it to the surface of a body part.

[0030] As used herein, the terms "promote," "increase," "promoting," and "increasing" are used interchangeably. These terms refer to an increase in a measured parameter in a treated cell, tissue, or individual compared to an untreated cell, tissue, or individual. Comparisons can also be made between the same cells, tissue, or individual before and after treatment. In some embodiments, the treated cells, tissue, or individual show an increase of at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 1, 2, 3, 4, or more times compared to an untreated cell, tissue, or individual.

[0031] As used herein, the term "individual" refers to vertebrates, such as humans or non-human animals, such as mammals. Mammals include (but are not limited to) humans, primates, livestock, locomotor animals, rodents, and pets. Non-limiting examples of non-human animal individuals include rodents such as mice, rats, hamsters, and guinea pigs; rabbits; dogs; cats; sheep; pigs; goats; cattle; horses; and non-human primates such as apes and monkeys.

[0032] As used herein, the term "treating" or "treatment" (and its grammatical variations such as "treat") refers to a clinical intervention that attempts to alter the course of disease in the treated individual or cells, and may be performed for preventative or therapeutic purposes or during the course of a clinicopathological course. The therapeutic effects of treatment include, but are not limited to, preventing the onset or recurrence of disease, relieving symptoms, reducing any direct or indirect pathological consequences of disease, preventing cancer metastasis, slowing the rate of disease progression, improving or mitigating the disease state, and alleviating or improving prognosis.

[0033] The term "effective amount" for an active ingredient, as used herein, means the amount of the ingredient sufficient to provide the necessary regulation for the desired function. As will be noted below, the exact amount required will vary from person to person, depending on individual disease condition, physical condition, age, sex, species and weight, the specific composition and formulation of the compound, etc. Dosing regimens can be adjusted to induce an optimal therapeutic response. For example, several divided doses may be administered daily, or the dose may be reduced proportionally as indicated by the urgency of the treatment situation. Therefore, an exact "effective amount" is not always specified. However, an appropriate effective amount can usually be determined by a person skilled in the art using routine experiments.

[0034] As used herein, the term "surface formulation" (or "surface composition") refers to a pharmaceutical preparation intended for surface or topical application to a diseased area of ​​an individual in need.

[0035] As used herein, the term "medically acceptable" is defined as meaning, within the bounds of reasonable medical judgment, that compounds, materials, compositions, and / or dosage forms are suitable for contact with the tissues of an individual (e.g., a mammal or a human) without excessive toxicity, irritation, allergic reactions, or other problematic complications, and that are commensurate with a reasonable benefit / risk ratio.

[0036] The present invention provides a method for treating or alleviating psoriasis and / or promoting or accelerating the healing of psoriasis, the method comprising administering a pharmaceutical composition to an individual in need, wherein the pharmaceutical composition comprises an effective amount of an immunomodulatory protein derived from Ganoderma lucidum or its recombinant form or fragment.

[0037] In one embodiment, the immunomodulatory protein, or its recombinant form or fragment thereof, is derived from *Ganoderma lucidum*, *Ganoderma tsugae*, *Ganoderma microsporum*, or *Ganoderma sinensis*. In some embodiments, the immunomodulatory protein is an immunomodulatory protein comprising the amino acid sequence of SEQ ID NO: 3 or 4, or its recombinant form. In some embodiments, a fragment of the immunomodulatory protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to 2. The preparation of the immunomodulatory protein or its recombinant form has been described in US 7,601,808.

[0038] In some embodiments, treating or alleviating psoriasis and / or promoting or accelerating the healing of psoriasis may include reducing inflammation and scaling, slowing skin cell growth, and / or removing plaques.

[0039] The immunomodulatory proteins, recombinants, fragments, or pharmaceutical compositions disclosed herein may be administered to an individual alone or as pharmaceutical compositions, wherein they are mixed with suitable carriers and excipients. The immunomodulatory proteins, recombinants, fragments, or pharmaceutical compositions disclosed herein may be administered non-enterally, such as by intravenous injection or infusion, intraperitoneal injection, subcutaneous injection, or intramuscular injection. The immunomodulatory proteins, recombinants, fragments, or pharmaceutical compositions disclosed herein may be administered orally or rectally by appropriate formulation with carriers and excipients to form tablets, pills, capsules, liquids, gels, syrups, slurries, suspensions, and the like. The immunomodulatory proteins, recombinants, fragments, or pharmaceutical compositions disclosed herein may be administered topically, such as by skin patches. The immunomodulatory proteins, recombinants, fragments, or pharmaceutical compositions disclosed herein may be formulated as topical creams, skin or mucosal patches, or liquids or gels suitable for topical application to skin or mucosal surfaces. Immunomodulatory proteins, recombinants thereof, fragments thereof, or pharmaceutical compositions disclosed herein can be administered to the respiratory tract via inhalation for local or systemic treatment of psoriasis.

[0040] The dosage of immunomodulatory proteins, or their recombinants or fragments, or pharmaceutical compositions can be determined by those skilled in the art based on the disclosure herein. The formulation contains an effective dose (depending on the route of administration and pharmacokinetics) of a suitable pharmaceutical carrier and excipient for a specific route of administration (i.e., oral, non-enteral, surface, or inhalation) appropriate to the formulation. Immunomodulatory proteins, or their recombinants or fragments, are formulated into pharmaceutical compositions by means of mixing, dissolving, granulation, tablet preparation, emulsification, encapsulation, coating, or lyophilization processes. Pharmaceutical compositions intended for non-enteral administration include aqueous solutions of the polypeptides of the present invention in a water-soluble form. Alternatively, suspensions of the polypeptides of the present invention can be prepared as oily injectable suspensions. Suitable lipophilic solvents or mediators include fatty oils, such as sesame oil; or synthetic fatty acid esters, such as ethyl oleate or triglycerides; or liposomes. Aqueous injectable suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Suspensions may contain stabilizers or reagents that increase the solubility of complexes or combinations to allow for solutions with higher concentrations, depending on the situation.

[0041] In some embodiments, the pharmaceutical composition is intended to be applied topically in various ways, which will be further described. For example, the pharmaceutical composition may be provided as a hydrogel. In some embodiments of the invention, the pharmaceutical composition further comprises a gelling agent.

[0042] In some embodiments of the present invention, the amount of gelling agent in the pharmaceutical composition is from about 0.1% (w / w) to about 2% (w / w).

[0043] In some embodiments of the present invention, the amount of immunomodulatory protein in the pharmaceutical composition is from about 0.0001% (w / w) to about 0.05% (w / w).

[0044] The pharmaceutical compositions of the present invention also include a gelling agent to form a surface gel product with a viscosity in the range of about 0.05 Pa·s to about 200 Pa·s.

[0045] The pharmaceutical composition of the present invention is formulated to have a pH value of 5.5 to 7.5. In one embodiment, the pH value of the aqueous medium can be adjusted by means of a low concentration of a suitable biocompatible buffering component, non-limiting examples of which are thiamethoxam, sodium carbonate and sodium bicarbonate, and sodium dihydrogen phosphate and disodium hydrogen phosphate.

[0046] The pharmaceutical compositions of the present invention may also include other additives, such as solvents, gelling / polymerizing agents, viscosity increasers, emulsifiers, antioxidants, preservatives, pH adjusters, propellants, and combinations thereof.

[0047] In some embodiments of the invention, the pharmaceutical composition is administered orally to an individual. A carrier serves as a transporter and / or diluent and / or adjuvant, or as a medium for delivering a therapeutic agent to an individual, or is added to the formulation to improve its handling or storage properties, or allows or facilitates the formation of discrete articles of dosage units of the composition, such as capsules or tablets suitable for oral administration. Suitable carriers are well known to those skilled in the art of manufacturing pharmaceutical formulations or food products. By way of description and not limitation, a carrier may include buffers, diluents, disintegrants, binders, adhesives, wetting agents, polymers, lubricants, slip agents, substances added to mask or counteract unpleasant tastes or odors, flavoring agents, dyes, fragrances, and substances added to improve the appearance of the composition. Acceptable carriers include citrate buffer, phosphate buffer, acetate buffer, bicarbonate buffer, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphate and sulfate, magnesium carbonate, talc, gelatin, gum arabic, sodium alginate, pectin, dextrin, mannitol, sorbitol, lactose, sucrose, starch, gelatin, cellulose materials (such as cellulose alkyl esters and cellulose alkyl esters), low-melting-point wax cocoa butter, amino acids, urea, alcohols, ascorbic acid, phospholipids, proteins (e.g., serum albumin), ethylenediaminetetraacetic acid (EDTA), dimethyl methoxide (DMSO), sodium chloride or other salts, liposomes, mannitol, sorbitol, glycerol or powder, polymers (such as polyvinylpyrrolidone, polyvinyl alcohol, and polyethylene glycol), and other pharmaceutically acceptable materials. The carrier should not impair the pharmacological activity of the therapeutic agent and should be non-toxic when administered at a dose sufficient to deliver a therapeutic amount of the therapeutic agent.

[0048] In some embodiments of the present invention, the pharmaceutical composition is administered orally to an individual, and the effective amount of the immunomodulatory protein is in the range of about 0.01 mg / kg to about 5 mg / kg. In some other embodiments of the present invention, the effective amount of the immunomodulatory protein is in the range of about 0.1 mg / kg to about 3 mg / kg.

[0049] In some embodiments, the method further comprises administering one or more additional therapeutic agents to an individual. The therapeutic agents may be any known medications for treating psoriasis, such as topical medications (e.g., corticosteroids, vitamin D analogs, retinoids, calcineurin inhibitors, salicylic acid, coal tar, anthraquinone), light (e.g., sunlight, broadband UVB, narrowband UVB, psoralen + UVA (PUVA), excimer laser), or oral or injectable medications (e.g., steroids, retinoids, methotrexate, cyclosporine, etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), ustekinumab (Stelara), seckugenumab (Cosentyx), icoziamate (Taltz), thioguanine (Tabloid), hydroxyurea (Droxia, Hydrea), apremilast (Otezla)), and may be used in combination with or directly incorporated into the pharmaceutical compositions of the present invention.

[0050] The dosage of the pharmaceutical composition suitable for use according to the present invention can be determined by those skilled in the art based on the disclosure herein. The formulation will contain an effective dose (depending on the route of administration of the active agent and pharmacokinetics) of a suitable pharmaceutical carrier and excipient suitable for the surface administration route of the formulation.

[0051] In one embodiment, the dosing regimen is repeated, i.e., once, twice, three times, or more; for example, repeated over the remaining lifespan of the individual in need. In another embodiment, the patient is treated with a dosing regimen utilizing the pharmaceutical composition according to the invention for 14 days. In yet another embodiment, the patient is treated with a dosing regimen utilizing the pharmaceutical composition according to the invention two or three times a day for 2 weeks, 3 weeks, 4 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

[0052] This invention provides pharmaceutical compositions and methods for treating psoriasis. Although the pathogenesis of psoriasis is not fully understood, substantial evidence suggests that epidermal changes occur as a secondary immune response to infiltrating the skin. Psoriasis is characterized by discrete areas of skin inflammation, accompanied by redness, thickening, dense scaling, and, in some cases, itching. The disease has a significant impact on the quality of life of affected individuals, both physically and psychologically. In one embodiment, treatment aims to reduce the severity and extent of psoriasis plaques and related symptoms. The primary measure used by the U.S. Food and Drug Administration to evaluate the treatment success of products for treating psoriasis is a significant overall improvement in the severity of psoriasis, based on a researcher's overall assessment. The following examples are provided to illustrate, but do not limit, the claimed invention. [Example] [] [Example] [1] [Preparation of the hydrogel of this invention] []

[0053] The pharmaceutical composition may be provided as a hydrogel. Examples of formulations of the hydrogel are listed below. Table 1 serial number gelling agent Immunomodulatory proteins Ultrapure water pH A 0.8% (w / w) Ammonium acrylamide dimethyl taurate / VP copolymer 0.005% (w / w) margin Approximately 6.5 B 2% (w / w) Aloe Vera 0.05% (w / w) margin Approximately 6 C 0.1% (w / w) methylcellulose 0.0001% (w / w) margin Approximately 6.5 D 0.5% (w / w) xanthan gum 0.001% (w / w) margin Approximately 7 E 1% (w / w) Sodium alginate 0.01% (w / w) margin Approximately 5.5

[0054] An immunomodulatory protein having SEQ ID NO: 4 was added to ultrapure water and then mixed thoroughly. Subsequently, a gelling agent was added to the resulting mixture with continuous stirring until a gel was formed. The resulting gel was incubated in a refrigerator at 4°C for at least 16 hours. The resulting gel was then stored in a suitable container. [Example] [2] [Preparation of the capsule of this invention] []

[0055] The pharmaceutical composition may be provided in capsule form. Each capsule contains 350 μg of an immunomodulatory protein having SEQ ID NO: 3 or 4. [Example] [3] Treatment of Psoriasis [-] [patient] [1] []

[0056] An 80-year-old female patient 1 has suffered from psoriasis on both legs for 60 years, since the age of 20. Patient 1 has tried many known prescriptions, but the symptoms remain almost uncontrolled.

[0057] After applying the hydrogel from Example 1 to the left leg twice a day for 2 months, the psoriasis symptoms on the left leg were relieved (Figures 1(A) to 1(B)).

[0058] After applying three capsules containing SEQ ID NO: 4 from Example 2 daily for four months, the symptoms of psoriasis on the left leg were relieved (Figures 2(A) to 2(B)). [Example] [4] Treatment of Psoriasis [-] [patient] [2] []

[0059] A 53-year-old female patient 2 has suffered from psoriasis on both legs for 33 years, since the age of 20. Patient 2 has tried many known prescriptions, but the symptoms remain almost uncontrolled.

[0060] After applying three capsules containing SEQ ID NO: 3 from Example 2 daily for three weeks, psoriasis symptoms on the skin were relieved in week 3 (Fig. 3(A)) and significantly improved in week 12 (Fig. 3(B)). Furthermore, psoriasis symptoms on the nails were significantly improved in week 12 (Fig. 3(C)). [] [Example] [5] Treatment of familial psoriasis [-] [patient] [3] []

[0061] The 17-year-old male patient 3 has familial psoriasis, and the psoriatic lesions appear on the skin.

[0062] After applying three capsules containing SEQ ID NO: 4 from Example 2 daily for three weeks, psoriasis symptoms on the skin were significantly relieved in week 2 (Figures 4(A) to 4(B)) and week 4 (Figure 4(C)). Furthermore, the symptoms remained recurrence-free for seven months.

[0063] <![CDATA[ <110> Xin Shaoqi (HSIN, SHAOCHI)]]> <![CDATA[ <120> Treatment methods for psoriasis]]> <![CDATA[ <130> none]]> <![CDATA[ <150> US 63 / 187,092 <![CDATA[ <151> 2021-05-11 <![CDATA[ <160> 4 ]]> <![CDATA[ <170> PatentIn version 3.5]]> <![CDATA[ <210> 1]]> <![CDATA[ <211> 6]]> <![CDATA[ <212> PRT]]> <![CDATA[ <213> Small-spore Ganoderma lucidum]]> <![CDATA[ <400> 1]]> Leu Ala Trp Asn Val Lys 1 5 <![CDATA[ <210> 2]]> <![CDATA[ <211> 10]]> <![CDATA[ <212> PRT]]> <![CDATA[ <213> Small-spore Ganoderma lucidum]]> <![CDATA[ <400> 2]]> Asp Leu Gly Val Arg Pro Ser Tyr Ala Val 1 5 10 <![CDATA[<210> 3]]> <![CDATA[<211> 111]]> <![CDATA[<212> PRT]]> <![CDATA[<213> Ganoderma microsporum]]> <![CDATA[<400> 3]]> Met Ser Asp Thr Ala Leu Ile Phe Thr Leu Ala Trp Asn Val Lys Gln 1 5 10 15 Leu Ala Phe Asp Tyr Thr Pro Asn Trp Gly Arg Gly Arg Pro Ser Ser 20 25 30 Phe Ile Asp Thr Val Thr Phe Pro Thr Val Leu Thr Asp Lys Ala Tyr <00​​​​​​​​Thr Tyr Arg Val Val Val Ser Gly Lys Asp Leu Gly Val Arg Pro Ser 50 55 60 Tyr Ala Val Glu Ser Asp Gly Ser Gln Lys Ile Asn Phe Leu Glu Tyr 65 70 75 80 Asn Ser Gly Tyr Gly Ile Ala Asp Thr Asn Thr Ile Gln Val Tyr Val 85 90 95 Ile Asp Pro Asp Thr Gly Asn Asn Phe Ile Val Ala Gln Trp Asn 100 105 110 <![CDATA[<210> 4]]> <![CDATA[<211> 140]]> <![CDATA[<212> PRT]]> <![CDATA[<213> Artificial Sequence]]> <![CDATA[<220>]]> <![CDATA[<223> Recombinant protein]]> <![CDATA[<400> 4]]> Glu Ala Glu Ala Glu Phe Met Ser Asp Thr Ala Leu Ile Phe Thr Leu 1 5 10 15 Ala Trp Asn Val Lys Gln Leu Ala Phe Asp Tyr Thr Pro Asn Trp Gly 20 25 30 Arg Gly Arg Pro Ser Ser Phe Ile Asp Thr Val Thr Phe Pro Thr Val 35 40 45 Leu Thr Asp Lys Ala Tyr Thr Tyr Arg Val Val Val Ser Gly Lys Asp 50 55 60 Leu Gly Val Arg Pro Ser Tyr Ala Val Glu Ser Asp Gly Ser Gln Lys 65 70 75 80 Ile Asn Phe Leu Glu Tyr Asn Ser Gly Tyr Gly Ile Ala Asp Thr Asn 85 90 95 Thr Ile Gln Val Tyr Val Ile Asp Pro Asp Thr Gly Asn Asn Phe Ile 100 105 110 Val Ala Gln Trp Asn Tyr Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 115 120 125 Leu Asn Ser Ala Val Asp His His His His His His 130 135 140

[0064]

Claims

1. Use of a pharmaceutical composition for manufacturing an agent for treating or relieving psoriasis and / or promoting or accelerating the healing of psoriasis, wherein the pharmaceutical composition comprises an effective amount of an immunomodulatory protein derived from Ganoderma, wherein the immunomodulatory protein is composed of the amino acid sequence of SEQ ID NO: 3 or 4.

2. As claimed in claim 1, wherein the pharmaceutical composition further comprises a gelling agent.

3. As claimed in claim 2, wherein the amount of the gelling agent in the pharmaceutical composition is from 0.1% (w / w) to 2% (w / w) and the amount of the immunomodulatory protein is from 0.0001% (w / w) to 0.05% (w / w).

4. As claimed in claim 2, wherein the gelling agent is polyethylene glycol (PEG) diacrylate, PEG-acrylate, PEG-thiol, PEG-azide, PEG-acetylenite, chitosan, hyaluronic acid, collagen, fibroin, gum arabic, alginate, natto gum, aloe vera, bentonite, carbomer, carboxymethyl cellulose, ethyl cellulose, gelatin, elastin, hydroxypolyamide, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, magnesium aluminum silicate, methyl cellulose, poloxamer, polyvinyl alcohol, sodium alginate, tragacanth gum, xanthan gum, gelatin, carboxyvinyl polymer, starch, water-swellable hydrocolloid, carrageenan, hyaluronic acid, agarose, alginate, acrylate, or acrylamide dimethyl taurate / vinylpyrrolidone (VP) copolymer or a combination thereof.

5. As claimed in claim 2, wherein the gelling agent is xanthan gum, methylcellulose, natto gum, aloe vera, or acrylamide dimethyl taurate / VP copolymer.

6. The use as claimed in claim 2, wherein the pharmaceutical composition has a pH value in the range of 5.5 to 7.

5.

7. The use as claimed in claim 2, wherein the pharmaceutical composition has a viscosity in the range of 0.05 Pa·s to 200 Pa·s.

8. As claimed in claim 2, wherein the amount of the immunomodulatory protein is in the range of 0.0001% (w / w) to 0.03% (w / w).

9. As claimed in claim 2, wherein the amount of the gelling agent is in the range of 0.5 (w / w) to 1.2% (w / w).

10. The use as claimed in claim 2, wherein the pharmaceutical composition is applied topically to the psoriasis area.

11. As claimed in claim 10, wherein the effective amount of the immunomodulatory protein is in the range of 1 mcg / cm2 to 100 mcg / cm2 in the psoriasis area.

12. As claimed in claim 1, wherein the pharmaceutical composition is administered orally to the individual.

13. As claimed in claim 12, wherein the effective amount of the immunomodulatory protein is in the range of 0.01 mg / kg to 5 mg / kg.

14. As claimed in claim 12, wherein the effective amount of the immunomodulatory protein is in the range of 0.1 mg / kg to 3 mg / kg.

15. As claimed in claim 1, wherein the medicine further comprises one or more therapeutic agents.

16. As requested in claim 1, wherein the psoriasis is plaque psoriasis, pustular psoriasis, reversal psoriasis, diaper psoriasis, punctate psoriasis, oral psoriasis, erythrodermic psoriasis, seborrheic dermatitis-like psoriasis, nail psoriasis, or psoriatic arthritis.

17. As requested in claim 1, wherein the psoriasis is familial psoriasis.

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