Methods for treating psoriasis

Abstract

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

Description

[Technical Field]

[0001] This disclosure relates to methods for the treatment of psoriasis, in particular to methods utilizing immunomodulatory proteins derived from the genus Ganoderma. [Background technology]

[0002] Psoriasis is a long-term, non-contagious, autoimmune disease characterized by abnormal, raised areas of skin, most commonly on the knees, elbows, torso, and scalp. These areas are typically red or purple, and in some people, they are accompanied by darker, dry, itchy, and scaly skin. Psoriasis tends to occur cyclically, worsening over several weeks or months before subsiding or going into remission. Common triggers for psoriasis include stress, alcohol, trauma, and medication.

[0003] The severity of psoriasis varies greatly, from small, localized patches to complete body coverage, and the possible mechanisms are complex and systemic. Managing psoriasis in a safe and economical way remains challenging.

[0004] When skin lesions are widespread, for example, covering more than 10 percent of the body surface area, systemic therapies such as methotrexate or biologics such as etanercept, adalimumab, and infliximab are used for treatment. A large number of patients with psoriasis do not have such widespread effects, and topical medication is considered a relatively safe and sensible option in the majority of these cases. Topical therapies include anti-inflammatory corticosteroids, particularly very potent types such as halobetazole propionate, vitamin D derivatives such as calcipotriene, retinoids known as tazarotene, and coal tar. While each of these topical therapies offers a certain degree of effectiveness, there are limitations to the extent to which they can improve psoriatic plaques or to the adverse effects that may occur. [Overview of the Initiative]

[0005] This disclosure has surprisingly found that immunomodulatory proteins or recombinants derived from the genus Ganoderma offers advantageous efficacy in treating or alleviating psoriasis and / or promoting or accelerating the healing of psoriasis. Therefore, this disclosure provides a method for treating psoriasis using immunomodulatory proteins derived from the genus Ganoderma.

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

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

[0008] The sequence of elements 1-4 is as follows: LAWNVK(Sequence ID 1) DLGVRPSYAV(Sequence ID 2) MSDTALIFTLAWNVKQLAFDYTPNWGRGRPSSFIDTVTFPTVLTDKAYTY RVVVSGKDLGVRPSYAVESDGSQKINFLEYNSGYGIADTNTIQVYVIDPD TGNNFIVAQWN(Sequence ID 3) EAEAEFMSDTALIFTLAWNVKQLAFDYTPNWGRGRPSSFIDTVTFPTVLT DKAYTYRVVVSGKDLGVRPSYAVESDGSQKINFLEYNSGYGIADTNTIQV YVIDPDTGNNFIVAQWNYLEQKLISEEDLNSAVDHHHHHH(Sequence ID 4).

[0009] In some embodiments of this disclosure, the pharmaceutical composition further comprises a gel-forming agent. In some embodiments of this disclosure, the gel-forming agent is present in the pharmaceutical composition at approximately 0.1% (w / w) to approximately 2% (w / w), approximately 0.15% (w / w) to approximately 1.95% (w / w), approximately 0.2% (w / w) to approximately 1.9% (w / w), approximately 0.25% (w / w) to approximately 1.85% (w / w), approximately 0.3% (w / w) to approximately 1.8% (w / w), approximately 0.35% (w / w) to approximately 1.75% (w / w), approximately 0.4% (w / w) to approximately 1.7% (w / w), approximately 0.45% (w / w) to approximately 1.65% (w / w), approximately 0.5% (w / w) to approximately 1.6% (w / w), and approximately The amounts are approximately 0.55%(w / w) to 1.55%(w / w), approximately 0.6%(w / w) to 1.5%(w / w), approximately 0.65%(w / w) to 1.45%(w / w), approximately 0.7%(w / w) to 1.4%(w / w), approximately 0.75%(w / w) to 1.35%(w / w), approximately 0.8%(w / w) to 1.3%(w / w), approximately 0.85%(w / w) to 1.25%(w / w), approximately 0.9%(w / w) to 1.2%(w / w), approximately 0.95%(w / w) to 1.15%(w / w), and approximately 1.0%(w / w) to 1.1%(w / w). In some embodiments, the amount of gel-forming agent is in the range of approximately 0.5% (w / w) to approximately 2.0% (w / w), approximately 0.5 (w / w) to approximately 1.5% (w / w), approximately 0.5 (w / w) to approximately 1.2% (w / w), approximately 0.5 (w / w) to approximately 1.0% (w / w), approximately 0.1 (w / w) to approximately 1.5% (w / w), approximately 0.1 (w / w) to approximately 1.0% (w / w), approximately 0.1 (w / w) to approximately 0.5% (w / w), approximately 1.0% (w / w) to approximately 2.0% (w / w), or approximately 1.5% (w / w) to approximately 2% (w / w).

[0010] In some embodiments of this disclosure, the immunomodulatory protein is present in the pharmaceutical composition at concentrations of approximately 0.0001% (w / w) to approximately 0.05% (w / w), approximately 0.0001% (w / w) to approximately 0.05% (w / w), approximately 0.0005% (w / w) to approximately 0.045% (w / w), approximately 0.001% (w / w) to approximately 0.04% (w / w), approximately 0.005% (w / w) to approximately 0.035% (w / w), approximately 0.001% (w / w) to approximately 0.03% (w / w), approximately 0.005% (w / w) to approximately 0.025% (w / w), and approximately 0.01% (w / w) The amounts are approximately 0.02% (w / w), approximately 0.0001% (w / w) to approximately 0.05% (w / w), approximately 0.0001% (w / w) to approximately 0.05% (w / w), approximately 0.0001% (w / w) to approximately 0.05% (w / w), approximately 0.0001% (w / w) to approximately 0.05% (w / w), approximately 0.0001% (w / w) to approximately 0.05% (w / w), approximately 0.0001% (w / w) to approximately 0.05% (w / w), and approximately 0.0001% (w / w) to approximately 0.05% (w / w). In some embodiments, the amount of immunomodulatory protein is in the range of approximately 0.0001%(w / w) to approximately 0.03%(w / w), approximately 0.0001%(w / w) to approximately 0.01%(w / w), approximately 0.0001%(w / w) to approximately 0.03%(w / w), approximately 0.0001%(w / w) to approximately 0.01%(w / w), approximately 0.0001%(w / w) to approximately 0.005%(w / w), approximately 0.0001%(w / w) to approximately 0.003%(w / w), approximately 0.0001%(w / w) to approximately 0.001%(w / w), or approximately 0.0001%(w / w) to approximately 0.0005%(w / w).

[0011] Examples of gel-forming agents include, but are not limited to, polyethylene glycol (PEG) diacrylate, PEG acrylate, PEG thiol, PEG azide, PEG alkyne, chitosan, hyaluronic acid, collagen, fibrin, gum arabic, alginic acid, natto gum, aloe vera, bentonite, carbomer, carboxymethylcellulose, ethylcellulose, gelatin, elastin, hydroxypolyamide, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, magnesium aluminum silicate, methylcellulose, poloxamer, polyvinyl alcohol, sodium alginate, tragacanth, xanthan gum, gelatin, carboxyvinyl polymer, starch, water-swellable hydrophilic colloid, carrageenan, hyaluronic acid, agarose, alginate, acrylate, and ammonium acryloyldimethyltaurate / vinylpyrrolidone (VP) copolymer. In some embodiments, the gel-forming agent is xanthan gum, methylcellulose, or ammonium acryloyldimethyltaurate / VP copolymer.

[0012] In one embodiment, the pharmaceutical composition has a pH 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.

[0013] 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 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, 0.05 Pa·s to about 140 Pa·s, 0.05 Pa·s to about 120 Pa·s, 0.05 Pa·s to about 100 Pa·s, 0.05 Pa·s to about 80 Pa·s, 0.05 Pa·s to about 60 Pa·s, 0.05 Pa·s to about 40 Pa·s, 0.05 Pa·s to about 20 Pa·s, 0.05 Pa·s to about 10 Pa·s, 0.05 Pa·s to about 5.0 Pa·s, 0.05 Pa·s to about 3.0 Pa·s or 0.05 Pa·s to about 1.0 Pa·s. In some embodiments, the pharmaceutical composition is administered topically onto the area of psoriasis.

[0014] In one embodiment, the pharmaceutical composition is administered topically onto the area of psoriasis, and the effective amount of the immunomodulatory protein is about 1 mcg / cm 2 to about 100 mcg / cm 2 ; about 1 mcg / cm 2 to about 80 mcg / cm 2 ; about 1 mcg / cm 2 to about 60 mcg / cm 2 ; about 1 mcg / cm 2 to about 40 mcg / cm 2 ; about 1 mcg / cm 2 to about 20 mcg / cm 2 ; about 1 mcg / cm 2 to about 10 mcg / cm 2 ; about 1 mcg / cm 2 to about 5 mcg / cm 2 ; about 5 mcg / cm 2 to about 100 mcg / cm2 , about 10mcg / cm 2 ~About 100mcg / cm 2 , about 20mcg / cm 2 ~About 100mcg / cm 2 , about 40mcg / cm 2 ~About 100mcg / cm 2 , about 60mcg / cm 2 ~About 100mcg / cm 2 Or approximately 80 mcg / cm³ 2 ~About 100mcg / cm 2 This is the area of ​​psoriasis.

[0015] In some embodiments of this disclosure, the pharmaceutical composition is administered orally to the subject. In some embodiments of this disclosure, the pharmaceutical composition is administered orally to a subject, and the effective dose of the immunomodulatory protein is in the range of about 0.01 mg / kg to about 5 mg / kg. In some embodiments, the effective dose is about 0.01 mg / kg to about 4 mg / kg, about 0.01 mg / kg to about 4.5 mg / kg, about 0.01 mg / kg to about 4 mg / kg, about 0.01 mg / kg to about 3.5 mg / kg, about 0.01 mg / kg to about 3 mg / kg, about 0.01 mg / kg to about 2.5 mg / kg, about 0.01 mg / kg to about 2 mg / kg, about 0.01 mg / kg to about 1.5 mg / kg, or about 0.01 mg / kg to about 1 mg / kg. g, about 0.01 mg / kg to about 0.5 mg / kg, about 0.05 mg / kg to about 5 mg / kg, about 0.05 mg / kg to about 4.5 mg / kg, about 0.05 mg / kg to about 4.5 mg / kg, about 0.05 mg / kg to about 4mg / kg, about 0.05mg / kg to about 3.5mg / kg, about 0.05mg / kg to about 3mg / kg, about 0.05mg / kg to about 2.5mg / kg, about 0.05mg / kg to about 2mg / kg, about 0.05mg / kg ~1.5mg / kg, 0.05mg / kg~1mg / kg, 0.05mg / kg~0.5mg / kg, 0.1mg / kg~5mg / kg, 0.1mg / kg~4.5mg / kg, 0.1mg / kg kg~about 4mg / kg, about 0.1mg / kg~about 3.5mg / kg, about 0.1mg / kg~about 3mg / kg, about 0.1mg / kg~about 2.5mg / kg, about 0.1mg / kg~about 2mg / kg, about 0.1mg / kg The ranges are approximately ~1.5 mg / kg, approximately 0.1 mg / kg to approximately 1 mg / kg, approximately 0.1 mg / kg to approximately 0.5 mg / kg, approximately 0.5 mg / kg to approximately 5 mg / kg, approximately 1 mg / kg to approximately 5 mg / kg, 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.

[0016] In one embodiment, the method further includes administering to the subject one or more additional therapeutic agents. In some embodiments, the therapeutic agents include topical pharmaceuticals (e.g., corticosteroids, vitamin D analogs, retinoids, calcineurin inhibitors, salicylic acid, coal tar, anthralin), light (e.g., sunlight, broadband UVB, narrowband UVB, psoralen plus ultraviolet A (PUVA), excimer laser), or oral or intravenous applications (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)).

[0017] In some embodiments, the psoriasis is plaque psoriasis, pustular psoriasis, inverse psoriasis, napkin psoriasis, guttate psoriasis, oral psoriasis, erythrodermic psoriasis, seborrheic-like psoriasis, nail psoriasis, or psoriatic arthritis. In some embodiments, the psoriasis is familial psoriasis.

Brief Description of the Drawings

[0018] [Figure 1A] It is a diagram showing the effect of treating psoriasis using the hydrogel agent of the present disclosure in Patient 1. Figure 1(A): Before treatment. [Figure 1B] It is a diagram showing the effect of treating psoriasis using the hydrogel agent of the present disclosure in Patient 1. Figure 1(B): After 2 months of treatment. [Figure 2A] It is a diagram showing the effect of treating psoriasis using the capsule agent of the present disclosure in Patient 1. Figure 2(A): Before treatment. [Figure 2B] It is a diagram showing the effect of treating psoriasis using the capsule agent of the present disclosure in Patient 1. Figure 2(B): After 4 months of treatment. [Figure 3]This figure shows the efficacy of the capsule formulation of this disclosure in treating psoriasis in Patient 2. Figure 3(A): Treatment at 3 weeks; Figure 3(B): Treatment at 12 weeks (skin); Figure 3(C): Treatment at 12 weeks (nails). [Figure 4] This figure shows the efficacy of the capsule formulation of this disclosure in treating psoriasis in patient 3. Figure 4(A): Before treatment; Figure 4(B): Treatment at 2 weeks; Figure 4(C): Treatment at 4 weeks. [Modes for carrying out the invention]

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this invention pertains. Any methods and materials similar or equivalent to those described herein may be used in the practice or testing of this invention, but preferred methods and materials are described herein. All publications mentioned herein are incorporated herein by reference.

[0020] In this application, unless otherwise specifically stated, the use of the singular form includes the plural form, the article "a" or "an" means "at least one", and the use of "or" means "and / or". The term "localized" refers to the administration or delivery of a compound by applying it to the surface of a body part.

[0021] As used herein, “promote” or “increase,” or “to promote” or “to increase,” are interchangeable. These terms mean an increase in a measured parameter in treated cells, tissues, or subjects compared to untreated cells, tissues, or subjects. Comparisons may also be made with the same cells, tissues, or subjects before and after treatment. In some embodiments, the increase in treated cells, tissues, or subjects is at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 1x, 2x, 3x, 4x, or more compared to untreated cells, tissues, or subjects.

[0022] As used herein, the term “subject” refers to a vertebrate, such as a human or a non-human animal, e.g., a mammal. Mammals include, but are not limited to, humans, primates, livestock, sports animals, rodents, and pets. Non-exclusive examples of non-human animal subjects 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.

[0023] As used herein, the terms “to treat” or “to treat” (and its grammatical variations such as “to treat”) mean a clinical intervention to alter the course of a disease in an individual or cell being treated, which may be performed either preventively or during the course of a clinicopathological disease. The therapeutic effects of treatment include, but are not limited to, preventing the onset or recurrence of the disease, reducing symptoms, eliminating any direct or indirect pathological outcome of the disease, preventing metastasis, slowing the rate of disease progression, improving or mitigating the disease state, and achieving remission or an improved prognosis.

[0024] As provided herein, the term “effective dose” of an active ingredient means a sufficient amount of the ingredient to provide the desired modulation of the desired function. As noted below, the exact amount required will vary from subject to subject depending on the subject’s disease state, health status, age, sex, species and weight, the specific nature and formulation of the composition, etc. The dosing regimen can be adjusted to induce the optimal therapeutic response. For example, several divided doses may be administered daily, or the dose may be proportionally reduced as indicated by the urgency of the treatment situation. In other words, it is not possible to determine the exact “effective dose.” However, an appropriate effective dose can be determined by those skilled in the art using only conventional experiments.

[0025] As used herein, the term “topical preparation” (or “topical composition”) is used to mean a pharmaceutical preparation intended for topical or localized application to an affected area of ​​a subject requiring it.

[0026] As used herein, the term “pharmaceutically acceptable” is defined herein to mean a compound, material, composition and / or dosage form that is suitable for contact with a subject, e.g., mammalian or human tissue, within the bounds of reasonable medical judgment, without excessive toxicity, irritation, allergic reactions and other problematic complications that do not outweigh the reasonable benefit / risk ratio.

[0027] This disclosure provides a method for treating or alleviating psoriasis and / or promoting or accelerating the healing of psoriasis, comprising the step of administering a pharmaceutical composition to a subject in need thereof, wherein the pharmaceutical composition comprises an effective amount of an immunomodulatory protein of the genus Ganoderma, or a recombinant or fragment thereof.

[0028] In one embodiment, the immunomodulatory protein or its recombinant 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 or its recombinant comprising the amino acid sequence of SEQ ID NO: 3 or 4. In some embodiments, the fragment of the immunomodulatory protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-2. The preparation of the immunomodulatory protein or its recombinant is described in U.S. Patent No. 7,601,808.

[0029] In some embodiments, treating or alleviating psoriasis, and / or promoting or accelerating the healing of psoriasis, may include reducing inflammation and scaling, delaying the proliferation of skin cells, and / or reducing plaque.

[0030] The immunomodulatory proteins or their recombinants or fragments or pharmaceutical compositions disclosed herein may be administered to a subject either alone or in a pharmaceutical composition mixed with suitable carriers and excipients. The immunomodulatory proteins or their recombinants or fragments or pharmaceutical compositions disclosed herein may be administered parenterally, such as by intravenous infusion or fluid infusion, intraperitoneal infusion, subcutaneous infusion, or intramuscular infusion. The immunomodulatory proteins or their recombinants or fragments or pharmaceutical compositions disclosed herein may be administered orally or rectally through appropriate formulation with carriers and excipients to form tablets, pills, capsules, liquids, gels, syrups, slurries, suspensions, etc. The immunomodulatory proteins or their recombinants or fragments or pharmaceutical compositions disclosed herein may be administered topically, such as by skin patches. The immunomodulatory proteins or their recombinants or fragments or pharmaceutical compositions disclosed herein can be formulated into topical creams, skin or mucous membrane patches, or liquids or gels suitable for topical application to skin or mucous membrane surfaces. The immunomodulatory proteins or their recombinants or fragments or pharmaceutical compositions disclosed herein can be administered by inhalation into the airways for topical or systemic treatment of psoriasis.

[0031] 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 disclosures herein. The pharmaceuticals will contain effective dosages (depending on the route of administration and the pharmacokinetics of the active agent) of suitable pharmaceutical carriers and excipients, appropriate for a specific route of administration of the formulation (i.e., oral, parenteral, topical, or inhalation). Immunomodulatory proteins or their recombinants or fragments are incorporated into pharmaceutical compositions using mixing, dissolution, granulation, sugar-coated tablet production, emulsification, capsule encapsulation, encapsulation, or lyophilization processes. Examples of pharmaceutical compositions for parenteral administration include aqueous solutions of the polypeptides of the present invention in water-soluble forms. In addition, suspensions of the polypeptides of the present invention can be prepared as oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol, or dextran. The suspension may optionally contain stabilizers or agents to increase the solubility of the complex or combination in order to enable a more concentrated solution.

[0032] 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 agent. In some embodiments of this disclosure, the pharmaceutical composition further comprises a gel-forming agent. In some embodiments of this disclosure, the gel-forming agent is present in an amount of about 0.1% (w / w) to about 2% (w / w) of the pharmaceutical composition. In some embodiments of this disclosure, the immunomodulatory protein is present in an amount of about 0.0001% (w / w) to about 0.05% (w / w) of the pharmaceutical composition. The pharmaceutical compositions of this disclosure also comprise a gel-forming agent, which forms a topical gel product having a viscosity in the range of about 0.05 Pa·s to about 200 Pa·s.

[0033] The pharmaceutical compositions of this disclosure are formulated to have a pH of 5.5 to 7.5. In one embodiment, the pH of the aqueous medium can be adjusted using a low concentration of a suitable biocompatible buffering component, non-limiting examples of which buffering components include tromethamine, sodium carbonate and sodium bicarbonate, as well as sodium dihydrogen phosphate and disodium hydrogen phosphate.

[0034] The pharmaceutical compositions of this disclosure may also include further additives such as solvents, gel-forming agents / polymers, thickeners, emulsifiers, antioxidants, preservatives, pH adjusters, propellants, and combinations thereof.

[0035] In some embodiments of this disclosure, the pharmaceutical composition is administered orally to a subject. Carriers are used as carriers and / or diluents and / or adjuvants, or as vehicles for the delivery of the therapeutic agent to the subject, or are added to the formulation to improve its handling or storage properties, or to enable or facilitate the formation of dose units of the composition into separated articles such as capsules or tablets suitable for oral administration. Suitable carriers are well known to those skilled in the art of the field of pharmaceutical formulation or food manufacturing. Examples and non-limiting examples of carriers include buffers, diluents, disintegrants, binders, adhesives, wetting agents, polymers, lubricants, flow enhancers, substances added to mask or neutralize unpleasant tastes or odors, flavorings, colorants, 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 phosphoric acid and sulfate, magnesium carbonate, talc, gelatin, gum arabic, sodium alginate, pectin, dextrin, mannitol, sorbitol, lactose, sucrose, starch, gelatin, cellulose materials (such as cellulose esters and alkyl cellulose esters of alkanates), low-melting-point wax cocoa butter, amino acids, urea, alcohol, ascorbic acid, phospholipids, proteins (e.g., serum albumin), ethylenediaminetetraacetic acid (EDTA), dimethyl sulfoxide (DMSO), sodium chloride or other salts, liposomes, mannitol, sorbitol, glycerol or powders, polymers (such as polyvinylpyrrolidone, polyvinyl alcohol, and polyethylene glycol), and other pharmaceutically acceptable materials. The carrier must not disrupt the pharmacological activity of the therapeutic agent and must be non-toxic when administered in a dose sufficient to deliver a therapeutic amount of the drug.

[0036] In some embodiments of this disclosure, the pharmaceutical composition is administered orally to a subject, and the effective dose of the immunomodulatory protein is in the range of about 0.01 mg / kg to about 5 mg / kg. In some further embodiments of this disclosure, the effective dose of the immunomodulatory protein is in the range of about 0.1 mg / kg to about 3 mg / kg.

[0037] In some embodiments, the method further includes the step of administering one or more therapeutic agents to a subject. The therapeutic agent may be any known pharmaceutical for the treatment of psoriasis, such as topical pharmaceuticals (e.g., corticosteroids, vitamin D analogues, retinoids, calcineurin inhibitors, salicylic acid, coal tar, anthraline), light (e.g., sunlight, broadband UVB, narrowband UVB, psoralen + ultraviolet A (PUVA), excimer laser), or oral or injectable pharmaceuticals (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)), which may be used in combination with or directly incorporated into the pharmaceutical compositions of the Disclosure.

[0038] The dosage of a pharmaceutical composition suitable for use in accordance with this disclosure can be determined by those skilled in the art based on the disclosures herein. The pharmaceutical will contain an effective dosage (depending on the route of administration and the pharmacokinetics of the active agent) of a suitable pharmaceutical carrier and excipient, which is suitable for the topical administration route of the formulation.

[0039] In one embodiment, the medication regimen is repeated, i.e., once, twice, three times or more; for example, over the remainder of the subject's life as required. In another embodiment, the patient is treated with a 14-day medication regimen using a pharmaceutical composition according to the Disclosure. In yet another embodiment, the patient is treated with a medication regimen of two or three doses per day using a pharmaceutical composition according to the Disclosure over a period of two weeks, three weeks, four weeks, three weeks, four weeks, five weeks, six weeks, four weeks, six weeks, six weeks, six months, eight months, nine months, ten months, eleven months, or twelve months.

[0040] This disclosure provides pharmaceutical compositions and methods for the treatment of psoriasis. While the etiology of psoriasis is not fully understood, significant evidence suggests that epidermal changes occur as a secondary response to cellular immunity infiltrating the skin. Psoriasis is characterized by isolated areas of skin inflammation, accompanied by redness, thickening, severe desquamation, 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, the treatment aims to reduce the severity and degree of psoriatic plaques and associated symptoms. The primary measure of therapeutic success used by the U.S. Food and Drug Administration in evaluating products for the treatment of psoriasis is a significant overall improvement in psoriasis severity based on the Investigators Global Assessment. The following examples are provided to illustrate, but not to limit, the claimed invention. This application provides the following: 1. Use of a pharmaceutical composition in the manufacture of a medicament for treating or alleviating psoriasis and / or promoting or accelerating the healing of psoriasis, wherein the pharmaceutical composition comprises an effective amount of an immunomodulatory protein of the genus Ganoderma, or a recombinant or fragment thereof. 2. The use described in paragraph 1 above, wherein the immunomodulatory protein comprises the amino acid sequence of SEQ ID NO: 3 or 4. 3. The use described in 1 above, wherein the immunomodulatory protein fragment comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 2. 4. The use described in paragraph 1 above, wherein the pharmaceutical composition further comprises a gel-forming agent. 5. The use described in item 4 above, wherein the gel-forming agent is present in an amount of about 0.1% (w / w) to about 2% (w / w) of the pharmaceutical composition, and the immunomodulatory protein is present in an amount of about 0.0001% (w / w) to about 0.05% (w / w). 6. The use described in 4 above, wherein the gel-forming agent is polyethylene glycol (PEG) diacrylate, PEG-acrylate, PEG-thiol, PEG-azide, PEG-alkyne, chitosan, hyaluronic acid, collagen, fibrin, gum arabic, alginic acid, natto gum, aloe vera, bentonite, carbomer, carboxymethylcellulose, ethylcellulose, gelatin, elastin, hydroxypolyamide, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, magnesium aluminum silicate, methylcellulose, poloxamer, polyvinyl alcohol, sodium alginate, tragacanth, xanthan gum, gelatin, carboxyvinyl polymer, starch, water-swellable hydrophilic colloid, carrageenan, hyaluronic acid, agarose, alginate, acrylate, or ammonium acryloyldimethyltaurate / vinylpyrrolidone (VP) copolymer or a combination thereof. 7. The use described in 4 above, wherein the gel-forming agent is xanthan gum, methylcellulose, natto gum, aloe vera, or ammonium acryloyldimethyltaurate / VP copolymer. 8. The use described in 4 above, wherein the pharmaceutical composition has a pH value in the range of 5.5 to 7.5. 9. The use described in 4 above, wherein the pharmaceutical composition has a viscosity in the range of about 0.05 Pa·s to about 200 Pa·s. 10. The use described in item 4 above, wherein the amount of the immunomodulatory protein is in the range of approximately 0.0001% (w / w) to approximately 0.03% (w / w). 11. The use described in item 4 above, wherein the amount of the gel-forming agent is in the range of approximately 0.5 (w / w) to approximately 1.2% (w / w). 12. The use according to item 4 above, wherein the pharmaceutical composition is administered topically to an area of ​​psoriasis. 13. The effective amount of the immunomodulatory protein is approximately 1 mcg / cm³. 2 ~About 100mcg / cm 2 Use as described in item 12 above, within the scope of the psoriatic area. 14. The use described in paragraph 1 above, wherein the pharmaceutical composition is administered orally to the subject. 15. The use described in item 14 above, wherein the effective amount of the immunomodulatory protein is in the range of approximately 0.01 mg / kg to approximately 5 mg / kg. 16. The use described in item 14 above, wherein the effective amount of the immunomodulatory protein is in the range of approximately 0.1 mg / kg to approximately 3 mg / kg. 17. The use described in paragraph 1 above, wherein the pharmaceutical further comprises one or more therapeutic agents. 18. The use described in paragraph 1 above, wherein the psoriasis is psoriasis vulgaris, pustular psoriasis, psoriatic inverse, napkin psoriasis, guttate psoriasis, oral psoriasis, erythrodermic psoriasis, seborrheic psoriasis, onychopsoriasis, or psoriatic arthritis. 19. The use described in item 1 above, wherein the psoriasis is familial psoriasis. [Examples]

[0041] Example 1: Preparation of the hydrogel preparation according to the present disclosure The pharmaceutical composition can be provided as a hydrogel. Embodiments of the hydrogel formulation are listed below.

[0042] [Table 1]

[0043] An immunomodulatory protein having sequence number 4 was added to ultrapure water and then thoroughly mixed. Subsequently, a gel-forming agent was added to the resulting mixture by continuous stirring until a gel formed. The resulting gel was incubated in a refrigerator at 4°C for at least 16 hours. The resulting gel was placed in a suitable container for storage.

[0044] Example 2: Preparation of the capsules of the present disclosure The pharmaceutical composition may be provided as capsules. Each capsule contains 350 μg of immunomodulatory protein having SEQ ID NO: 3 or 4.

[0045] Example 3: Treatment of Psoriasis Patient 1 Patient 1 is an 80-year-old woman who has suffered from psoriasis on both legs for 60 years, starting at age 20. Patient 1 has tried numerous conventional prescription medications, but her condition has been largely uncontrolled. After applying the hydrogel formulation from Example 1 to the left leg twice a day for two months, the symptoms of psoriasis on the left leg were reduced (Figures 1(A) to 1(B)). After applying three capsules containing Sequence ID No. 4 of Example 2 daily for four months, the symptoms of psoriasis on the left leg were reduced (Figures 2(A) to 2(B)).

[0046] Example 4: Treatment of psoriasis patient 2 Patient 2 is a 53-year-old woman who has suffered from psoriasis on both legs for 33 years, starting at age 20. Patient 2 has tried numerous conventional prescription medications, but her condition has been largely uncontrolled. After applying three capsules containing Sequence ID No. 3 of Example 2 daily for three weeks, the symptoms of psoriasis on the skin were reduced in the third week (Figure 3(A)) and significantly improved in the twelfth week (Figure 3(B)). Furthermore, the symptoms of psoriasis on the nails also significantly improved in the twelfth week (Figure 3(C)).

[0047] Example 5: Treatment of 3 patients with familial psoriasis Patient 3 is a 17-year-old male with familial psoriasis and psoriatic lesions appearing on the skin. After applying three capsules containing Sequence ID No. 4 of Example 2 daily for three weeks, the symptoms of psoriasis on the skin were significantly reduced in the second week (Figures 4(A) to 4(B)) and the fourth week (Figure 4(C)). Furthermore, there was no recurrence of symptoms over a period of seven months.

Claims

1. Use of a pharmaceutical composition in the manufacture of a medicament for treating or alleviating psoriasis and / or promoting or accelerating the healing of psoriasis, wherein the pharmaceutical composition comprises an effective amount of an immunomodulatory protein derived from the genus Ganoderma, the immunomodulatory protein comprising the amino acid sequence of SEQ ID NO: 3 or 4.

2. The use according to claim 1, wherein the pharmaceutical composition further comprises a gel-forming agent.

3. The use according to claim 2, wherein the gel-forming agent is present in an amount of about 0.1% (w / w) to about 2% (w / w) of the pharmaceutical composition, and the immunomodulatory protein is present in an amount of about 0.0001% (w / w) to about 0.05% (w / w).

4. The use according to claim 2, wherein the gel-forming agent is polyethylene glycol (PEG) diacrylate, PEG-acrylate, PEG-thiol, PEG-azide, PEG-alkyne, chitosan, hyaluronic acid, collagen, fibrin, gum arabic, alginic acid, natto gum, aloe vera, bentonite, carbomer, carboxymethylcellulose, ethylcellulose, gelatin, elastin, hydroxypolyamide, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, magnesium aluminum silicate, methylcellulose, poloxamer, polyvinyl alcohol, sodium alginate, tragacanth, xanthan gum, gelatin, carboxyvinyl polymer, starch, water-swellable hydrophilic colloid, carrageenan, hyaluronic acid, agarose, alginate, acrylate, or ammonium acryloyldimethyltaurate / vinylpyrrolidone (VP) copolymer or a combination thereof.

5. The use according to claim 2, wherein the gel-forming agent is xanthan gum, methylcellulose, natto gum, aloe vera, or ammonium acryloyldimethyltaurate / VP copolymer.

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

5.

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

8. The use according to claim 2, wherein the amount of the immunomodulatory protein is in the range of about 0.0001% (w / w) to about 0.03% (w / w).

9. The use according to claim 2, wherein the amount of the gel-forming agent is in the range of about 0.5 (w / w) to about 1.2% (w / w).

10. The use according to claim 2, wherein the pharmaceutical composition is administered topically to an area of ​​psoriasis.

11. The effective amount of the aforementioned immunomodulatory protein is approximately 1 mcg / cm³. 2 ~About 100mcg / cm 2 The use according to claim 10, within the scope of a psoriatic area.

12. The use according to claim 1, wherein the pharmaceutical composition is administered orally to the subject.

13. The use according to claim 12, wherein the effective amount of the immunomodulatory protein is in the range of about 0.01 mg / kg to about 5 mg / kg.

14. The use according to claim 12, wherein the effective amount of the immunomodulatory protein is in the range of about 0.1 mg / kg to about 3 mg / kg.

15. The use according to claim 1, wherein the pharmaceutical further comprises one or more therapeutic agents.

16. The use according to claim 1, wherein the psoriasis is psoriasis vulgaris, pustular psoriasis, psoriatic inverse, napkin psoriasis, guttate psoriasis, oral psoriasis, erythrodermic psoriasis, seborrheic psoriasis, onychopsoriasis, or psoriatic arthritis.

17. The use according to claim 1, wherein the psoriasis is familial psoriasis.

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