Pregnenolone-17a-propionate combinations for the treatment of acne

Abstract

The present disclosure relates to methods of treating or preventing acne, such as facial acne vulgaris, comprising administering to a subject in need thereof an effective amount of a combination of phytocortisone-17a-propionate and an effective amount of one or more second anti-acne agents. The second anti-acne agents used in combination with phytocortisone-17a-propionate can be oral or topical agents. The second anti-acne agents can be administered in a combined formulation or independently in a sequential manner. The present disclosure also relates to topical formulations comprising phytocortisone-17a-propionate, at least one topical anti-acne agent, and a pharmaceutically acceptable carrier.

Description

Background Technology

[0001] Acne vulgaris is a common skin condition characterized by blockage or inflammation of the pilosebaceous unit of the skin, resulting in non-inflammatory, inflammatory, or both acne. While it most commonly affects adolescents, 12% of adult women and 3% of adult men still have acne in their 50s. Acne can affect any skin type on the body, but it most commonly occurs on the face, neck, and back. Chronic acne can lead to scarring and disfigurement, in addition to mood disturbances, decreased confidence, depression, anxiety, and other detrimental mental health consequences. The direct costs of acne are estimated to exceed $3 billion annually, but the indirect costs may be significantly higher.

[0002] While Propionibacterium acnes (C. acnes) is generally considered the primary cause of acne vulgaris, other factors such as environment, medication use, hormones, genetics, and diet can also influence the severity of the condition. Propionibacterium acnes is a resident bacterium of hair follicles, but bacterial overgrowth can exacerbate inflammation and progress the condition. Treatment options for acne vulgaris are recommended based on both the severity of inflammation and the patient's clinical characteristics affecting severity (e.g., age, sex, metabolic status, and reproductive health).

[0003] Although there are currently treatment options available for acne vulgaris, there is still a need for effective treatments for different patient groups. Summary of the Invention

[0004] It has been unexpectedly found that the combination of corticosterone-17α-propionate and a second anti-acne agent can effectively treat acne. In some respects, the combination provides a synergistic effect, allowing for surprisingly low effective amounts of each active ingredient to be used for effective treatment. As a result of this combination therapy, favorable clinical outcomes can be achieved after appropriate durations of administration (e.g., days, weeks, or months).

[0005] Therefore, this disclosure provides a method for treating or preventing acne, the method comprising topically applying to a subject in need an effective amount of cortexolone-17α-propionate (CTX), in combination with an effective amount of one or more second anti-acne agents.

[0006] In some respects, one or more secondary anti-acne agents are oral.

[0007] In some respects, oral preparations are antibiotics, hormones, retinoids, dietary supplements, or combinations thereof.

[0008] In some cases, antibiotics include amoxicillin, azithromycin, cephalexin, doxycycline, erythromycin, minocycline, tetracycline, trimethoprim, and sulfamethoxazole. Azole, or combinations thereof.

[0009] In some respects, the hormone agent is flutamide, spironolactone, cyproterone acetate, norethindrone, diacetylnorethindrone, levonorgestrel, norgestrol acetate, desogestrel, pregnadienone, drospirenone, ethinylestradiol, or combinations thereof.

[0010] In some respects, retinoids are isotretinoin.

[0011] In some respects, dietary supplements are vitamins A, C, D, E, K, biotin, niacin, zinc, selenium, iron, copper, omega-3 fatty acids, or combinations thereof.

[0012] In some respects, one or more secondary anti-acne agents are one or more secondary topical anti-acne agents.

[0013] In some aspects, one or more second topical anti-acne agents and corticosterone-17α-propionate are provided as a topical composition comprising corticosterone-17α-propionate, one or more second anti-acne agents, and at least one pharmaceutically acceptable carrier.

[0014] In some respects, the topical composition is a gel, cream, lotion, solution, suspension, foam, ointment, wash-off agent, hydrogel patch, microemulsion, or pledget.

[0015] In some aspects, the local composition is prefabricated.

[0016] In some aspects, one or more second topical anti-acne agents and corticosteroid-17α-propionate are provided as separate topical compositions, each topical composition comprising at least one active agent and at least one pharmaceutically acceptable carrier.

[0017] In some respects, separate local compositions are combined prior to adjacent use.

[0018] In some cases, separate local compositions are applied sequentially.

[0019] In some aspects, each topical composition is independently selected from gels, creams, lotions, solutions, suspensions, foams, ointments, washes, hydrogel patches, microemulsions, and medicated swabs.

[0020] In some respects, at least one second topical anti-acne agent is an antiseptic, an antibiotic, a retinoid, an antioxidant, an organic acid, a corticosteroid, an antiparasitic agent, sulfur, urea, or a combination thereof.

[0021] In some respects, the antibacterial agent is benzoyl peroxide; the antibiotics are clindamycin, erythromycin, naflufloxacin, metronidazole, sulfamidophos, minocycline, sodium sulfacetamide, diaminodiphenyl sulfone, or combinations thereof; the retinoids are retinoic acid, adapalene, tazarotene, trifarotene, or combinations thereof; the antioxidant is L-ascorbic acid-2-phosphate sodium; the organic acids are resorcinol, azelaic acid, salicylic acid, glycolic acid, or combinations thereof; the corticosteroids are hydrocortisone, triamcinolone, or combinations thereof; and the antiparasitic agent is ivermectin.

[0022] In some respects, acne is mild, moderate, or severe acne vulgaris.

[0023] In some respects, acne vulgaris is facial acne vulgaris.

[0024] This disclosure also provides a topical composition comprising corticosterone-17α-propionate, at least one topical anti-acne agent, and a pharmaceutically acceptable carrier.

[0025] In some respects, topical anti-acne agents are antibacterial agents, antibiotics, retinoids, antioxidants, organic acids, corticosteroids, antiparasitic agents, sulfur, urea, or combinations thereof.

[0026] In some respects, the antibacterial agent is benzoyl peroxide.

[0027] In some respects, antibiotics are clindamycin, erythromycin, naflufloxacin, metronidazole, sulfamidophos, minocycline, sodium sulfacetamide, diaminodiphenyl sulfone, or combinations thereof.

[0028] In some respects, retinoids are retinoic acid, adapalene, tazarotene, trofarotine, or combinations thereof.

[0029] In some cases, the antioxidant is sodium L-ascorbic acid-2-phosphate or nicotinamide.

[0030] In some respects, the organic acid is resorcinol, azelaic acid, salicylic acid, glycolic acid, or a combination thereof.

[0031] In some respects, corticosteroids are hydrocortisone, triamcinolone, or combinations thereof.

[0032] In some respects, the antiparasitic agent is ivermectin.

[0033] In some respects, the composition is in the form of cream, lotion, gel, ointment, mousse, spray solution, suspension, emulsion, wash, patch, or medicated swab.

[0034] In another embodiment, the topical pharmaceutical preparation of this disclosure is used to treat or prevent acne in subjects who require it. Detailed Implementation

[0035] definition

[0036] Unless the context clearly indicates otherwise, the singular form “a / one / kind” includes the plural referent.

[0037] The term “or” as used herein is a logical disjunction (i.e., and / or) and does not indicate exclusive disjunction unless explicitly indicated by the terms “any,” “unless,” “alternatively,” and similar words.

[0038] As used herein, the term "about" means ±10% of the value unless otherwise stated, and unless the upper limit of the range would exceed 100%, in which case the upper limit of the range is limited to 99.99%. Thus, by way of example only, a formulation containing about 10% by weight of a given ingredient may have between 9% by weight and 11% by weight of that ingredient. Similarly, a formulation containing about 95% by weight of a given ingredient may have between 85.5% by weight and 99.99% by weight of the ingredient in the formulation.

[0039] As used in this article, the term “treatment” and its variations refer to any type of intervention or process performed on a subject, or the application of an active agent to a subject, with the aim of reversing, reducing, improving, inhibiting, slowing down, or preventing the progression, development, severity, or recurrence of symptoms, complications, conditions, or biochemical indicators associated with acne vulgaris.

[0040] As used herein, the term "effective amount" refers to the amount of a given active agent, when applied by the methods of this disclosure, sufficient to effectively treat a target condition or disease in a subject in need.

[0041] As used herein, the term "co-administration" and its variations refer to the simultaneous (i.e., at the same time) or sequential (i.e., one after another) administration of two or more active agents, including embodiments in which the administration of a first active agent overlaps with the administration of a second or subsequent active agent, and embodiments in which the administration of the first active agent is separated by an appropriate time period before the administration of the second active agent. An appropriate time period can be determined by those skilled in the art and can be, for example, about 30 seconds, about 1 minute, about 10 minutes, about 15 minutes, about 30 minutes, about 1 hour, about 2 hours, about 6 hours, about 12 hours, about 24 hours, about 36 hours, or about 48 hours. Co-administered active agents can be administered as part of a combination formulation or via separate formulations. Similarly, co-administered active agents can be delivered via the same or different routes of administration. For example, two or more active agents can be co-administered topically (as part of a combination formulation or as two separate formulations), or one active agent can be administered topically while another is administered orally. Co-application can be performed at appropriate intervals. For example, two or more active agents can be co-application as follows: once or more daily (e.g., once daily, twice daily, three times daily, four times daily, etc.); once or more every other day (e.g., once every other day, twice every other day, three times every other day, four times every other day, etc.); once or more every three days (e.g., once every three days, twice every three days, three times every three days, four times every three days, etc.); at least once, twice, or three times per week; weekly; or less frequently until the condition being treated (i.e., acne) is reduced or alleviated. In some respects, co-application can be tailored to an initial loading dose of one or two active ingredients, which can then be reduced to a maintenance level of one or two active ingredients if needed or desired. Similarly, and in some respects, the co-application can be carried out for about 1 to about 30 days at any of the above appropriate intervals, for example, at least about 1, at least about 2, at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 11, at least about 12, at least about 13, at least about 14, at least about 15, at least about 16, at least about 17, at least about 18, at least about 19, at least about 20, at least about 21, at least about 22, at least about 23, at least about 24, at least about 25, at least about 26, at least about 27, at least about 28, at least about 29 or about 30 days. In other respects, co-application may be carried out for a period of at least about 30 days, at least about 45 days, at least about 60 days, at least about 75 days, at least about 90 days, at least about 120 days, at least about 150 days, at least about 180 days, at least about 210 days, at least about 240 days, at least about 270 days, at least about 300 days, at least about 1 year or longer, until the treated condition, i.e., acne, is adequately controlled.

[0042] The terms “comprising,” “having,” “including,” “containing,” and their variations, as used herein, are open-ended terms meaning “including but not limited to.” With regard to the inclusion / comprising of certain elements in a given embodiment disclosed herein, it should be understood that this disclosure also specifically considers and discloses embodiments “consisting substantially of those elements” and “composed of those elements.”

[0043] Corticosterone-17α-propionate, also known as 17α-propionyloxy-21-hydroxy-pregn-4-ene-3,20-dione and clascoterone (“CTX”), is a topical antiandrogen that inhibits the binding of androgens (such as testosterone and dihydrotestosterone) to androgen receptors in the sebaceous glands. While its exact mechanism of action is not fully understood, corticosterone-17α-propionate is known to be suitable for the treatment of acne, alopecia, and other skin and skin appendage disorders. See, for example, U.S. Patent Nos. 8,143,240 and 8,865,690, and PCT Publications WO 2009 / 019138 and WO 2016 / 207778. Several different crystalline polymorphs of this compound are also known, each with unique properties. See, for example, U.S. Patent No. 8,785,427. Each of these publications is incorporated herein by reference in its entirety.

[0044] This disclosure provides various compositions and methods for treating acne vulgaris, including administering an effective amount of CTX and a second active agent to a subject in need. In some aspects, the CTX and the second active agent can be formulated into a composition suitable for topical application, i.e., a formulation comprising CTX, the second active agent, and one or more pharmaceutically acceptable excipients. In some aspects, the CTX and the second active agent can be formulated in separate formulations and administered simultaneously. Alternatively, the CTX and the second active agent can be formulated in separate formulations, and the second active agent can be administered before or after the application of the CTX-containing formulation. In still other aspects, this disclosure provides a method of treating acne comprising topically applying a CTX formulation and orally administering the second active agent.

[0045] Suitable secondary activators include, but are not limited to, antibiotics, hormones, retinoids, dietary supplements, antibacterial agents, antioxidants, organic acids, corticosteroids, antiparasitic agents, sulfur, urea, and combinations thereof.

[0046] Exemplary antibiotics include, but are not limited to, amoxicillin, azithromycin, cephalexin, doxycycline, erythromycin, minocycline, tetracycline, trimethoprim, and sulfamethoxazole. Azole, clindamycin, naflufloxacin, metronidazole, sodium sulfacetamide, diaminodiphenyl sulfone, and combinations thereof.

[0047] Exemplary hormonal agents include, but are not limited to, flutamide, spironolactone, cyproterone acetate, norethindrone, diacetylnorethindrone, levonorgestrel, norgestrol acetate, desogestrel, pregnadienone, drospirenone, ethinylestradiol, and combinations thereof.

[0048] Exemplary dietary supplements include, but are not limited to, vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, biotin, niacin, zinc, selenium, iron, copper, omega-3 fatty acids, and combinations thereof.

[0049] Exemplary retinoids include, but are not limited to, retinoic acid, adapalene, tazarotene, trofarotin, and combinations thereof.

[0050] Exemplary antimicrobial agents include, but are not limited to, benzoyl peroxide.

[0051] Exemplary antioxidants include, but are not limited to, sodium L-ascorbic acid-2-phosphate and nicotinamide.

[0052] Exemplary organic acids include, but are not limited to, azelaic acid, salicylic acid, and resorcinol.

[0053] Exemplary corticosteroids include, but are not limited to, hydrocortisone, triamcinolone, and combinations thereof.

[0054] Exemplary antiparasitic agents include, but are not limited to, ivermectin.

[0055] Formulations containing CTX and secondary anti-acne agents

[0056] In some aspects, this disclosure provides combination formulations comprising CTX and one or more secondary anti-acne agents. In some aspects, the combination formulation may be a gel, cream, lotion, solution, suspension, foam, ointment, cleanser (e.g., soap), hydrogel patch, microemulsion, or medicated swab. The secondary anti-acne agent may be selected from antibacterial agents, antibiotics, retinoids, antioxidants, organic acids, corticosteroids, antiparasitic agents, sulfur, urea, and combinations thereof.

[0057] In some aspects, the second anti-acne agent in the combination formulation may be an antibacterial agent. In some aspects, the antibacterial agent may be benzoyl peroxide. In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 25.0% (w / w) of benzoyl peroxide, about 0.1% (w / w) to 10.0% (w / w) of benzoyl peroxide, about 0.1% (w / w) to 7.5% (w / w) of benzoyl peroxide, about 0.1% (w / w) to 6.0% (w / w) of benzoyl peroxide, about 0.1% (w / w) of CTX, and about 0.1% (w / w) of CTX. Benzoyl peroxide from about 5.0% (w / w), about 0.1% (w / w) to 4.0% (w / w), about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), about 0.1% (w / w) to 1.0% (w / w), or about 0.1% (w / w) to 0.5% (w / w).

[0058] Although benzoyl peroxide can be directly combined with CTX, it is more typically encapsulated because benzoyl peroxide is generally considered reactive. For example, in some aspects, benzoyl peroxide can be encapsulated in microparticles containing a solid core comprising solid particulate matter of benzoyl peroxide, CTX, or another secondary anti-acne agent, wherein the solid core may be coated with a metal oxide or inorganic polymer layer, as described in U.S. Patent Nos. 8,617,580 or 8,110,284, each of which is incorporated herein by reference in its entirety.

[0059] In some aspects, the secondary anti-acne agent in the combination formulation may be an antibiotic. In some aspects, the antibiotic may be selected from clindamycin, erythromycin, naflufloxacin, metronidazole, sulfamidone, minocycline, sodium sulfacetamide, diaminodiphenyl sulfone, and combinations thereof. In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 12.0% (w / w) of antibiotics, about 0.1% (w / w) to 10.0% (w / w) of antibiotics, about 0.1% (w / w) to 8.0% (w / w) of antibiotics, about 0.1% (w / w) to 6.0% (w / w) of antibiotics, and about 0.1% (w / w) of... % (w / w) to 4.0% (w / w) of antibiotics, about 0.1% (w / w) to 3.0% (w / w) of antibiotics, about 0.1% (w / w) to 2.0% (w / w) of antibiotics, or about 0.1% (w / w) to 1.0% (w / w) of antibiotics, about 0.1% (w / w) to 0.5% (w / w) of antibiotics, or about 0.1% (w / w) to 0.1% (w / w) of antibiotics.

[0060] In some respects, the antibiotic may be clindamycin. In some respects, the combination preparation may contain about 0.5% (w / w) to about 6.0% (w / w) of clindamycin. In some respects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0061] In some respects, the antibiotic may be erythromycin. In some respects, the combination preparation may contain about 0.5% (w / w) to about 6.0% (w / w) of erythromycin. In some respects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0062] In some respects, the antibiotic may be naflufloxacin. In some respects, the combination formulation may contain about 0.5% (w / w) to about 6.0% (w / w) of naflufloxacin. In some aspects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w) of naflufloxacin.

[0063] In some respects, the antibiotic may be metronidazole. In some respects, the combination preparation may contain about 0.5% (w / w) to about 6.0% (w / w) of metronidazole. In some respects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0064] In some respects, the antibiotic may be sulfamiron. In some respects, the combination formulation may contain about 0.5% (w / w) to about 6.0% (w / w) of sulfamiron. In some aspects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0065] In some respects, the antibiotic may be minocycline. In some respects, the combination formulation may contain about 0.5% (w / w) to about 6.0% (w / w) of minocycline. In some respects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0066] In some aspects, the antibiotic may be sodium sulfacetamide. In some aspects, the combination formulation may contain about 0.5% (w / w) to about 15.0% (w / w) of sodium sulfacetamide. In some aspects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), approximately 4.5% (w / w), approximately 4.75% (w / w), approximately 5.0% (w / w), approximately 5.25% (w / w), approximately 5.5% (w / w), approximately 6.0% (w / w), approximately 6.25% (w / w), approximately 6.5% (w / w), approximately 6.75% (w / w), approximately 7.0% (w / w), approximately 7.25% (w / w), approximately 7.5% (w / w), approximately 7.75% (w / w), approximately 8.0% (w / w), approximately 8 0.25% (w / w), approximately 8.5% (w / w), approximately 8.75% (w / w), approximately 9.0% (w / w), approximately 9.25% (w / w), approximately 9.5% (w / w), approximately 9.75% (w / w), approximately 10.0% (w / w), approximately 10.25% (w / w), approximately 10.5% (w / w), approximately 10.75% (w / w), approximately 11.0% (w / w), approximately 11.25% (w / w), approximately 11.5% (w / w), approximately 11.75% Sodium sulfacetamide (w / w), approximately 12.0% (w / w), approximately 12.25% (w / w), approximately 12.5% ​​(w / w), approximately 12.75% (w / w), approximately 13.0% (w / w), approximately 13.25% (w / w), approximately 13.5% (w / w), approximately 13.75% (w / w), approximately 14.0% (w / w), approximately 14.25% (w / w), approximately 14.5% (w / w), approximately 14.75% (w / w), or approximately 15.0% (w / w).

[0067] In some aspects, the antibiotic may be diaminodiphenyl sulfone. In some aspects, the combination formulation may contain about 0.5% (w / w) to about 15% (wt / wt) of diaminodiphenyl sulfone. In some aspects, the combination formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), or about 4.0% (w / w). Approximately 4.25% (w / w), approximately 4.5% (w / w), approximately 4.75% (w / w), approximately 5.0% (w / w), approximately 5.25% (w / w), approximately 5.5% (w / w), approximately 6.0% (w / w), approximately 6.25% (w / w), approximately 6.5% (w / w), approximately 6.75% (w / w), approximately 7.0% (w / w), approximately 7.25% (w / w), approximately 7.5% (w / w), approximately 7.75% (w / w), approximately 8.0% (w / w), approximately 8 0.25% (w / w), approximately 8.5% (w / w), approximately 8.75% (w / w), approximately 9.0% (w / w), approximately 9.25% (w / w), approximately 9.5% (w / w), approximately 9.75% (w / w), approximately 10.0% (w / w), approximately 10.25% (w / w), approximately 10.5% (w / w), approximately 10.75% (w / w), approximately 11.0% (w / w), approximately 11.25% (w / w), approximately 11.5% (w / w), approximately 11.75% ( Diaminodiphenyl sulfones, approximately 12.0% (w / w), approximately 12.25% (w / w), approximately 12.5% ​​(w / w), approximately 12.75% (w / w), approximately 13.0% (w / w), approximately 13.25% (w / w), approximately 13.5% (w / w), approximately 13.75% (w / w), approximately 14.0% (w / w), approximately 14.25% (w / w), approximately 14.5% (w / w), approximately 14.75% (w / w), or approximately 15.0% (w / w).

[0068] In some aspects, the second anti-acne agent in a combination formulation may be retinoids. In some aspects, the retinoid may be selected from retinoic acid, adapalene, tazarotene, trafarotine, and combinations thereof. In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to about 7.0% (w / w) of retinoids, about 0.01% (w / w) to 5.0% (w / w) of retinoids, about 0.01% (w / w) to 3.5% (w / w) of retinoids, about 0.01% (w / w) to 2.0% (w / w) of retinoids, about 0.01% (w / w) to 2.0% (w / w) of retinoids, about 0.01% (w / w) to 5.0% (w / w) of CTX, and about 0.01% (w / w) of CTX. From 1.0% (w / w) to 1.0% (w / w) of retinol, or from about 0.01% (w / w) to 0.75% (w / w) of retinol, or from about 0.01% (w / w) to 0.5% (w / w) of retinol, or from about 0.01% (w / w) to 0.25% (w / w) of retinol, or from about 0.01% (w / w) to 0.1% (w / w) of retinol, or from about 0.01% (w / w) to 0.05% (w / w) of retinol.

[0069] In some aspects, retinoids may be retinoic acid. In some aspects, the combination formulation may contain about 0.001% (w / w) to about 0.20% (w / w) of retinoic acid. In some aspects, the combination formulation may contain about 0.001% (w / w), about 0.0025% (w / w), about 0.005% (w / w), about 0.075% (w / w), about 0.010% (w / w), about 0.015% (w / w), about 0.020% (w / w), about 0.025% (w / w), about 0.030% (w / w), about 0. 0.035% (w / w), approximately 0.040% (w / w), approximately 0.045% (w / w), approximately 0.050% (w / w), approximately 0.055% (w / w), approximately 0.060% (w / w), approximately 0.065% (w / w), approximately 0.070% (w / w), approximately 0.075% (w / w), or approximately 0.080% (w / w), approximately 0.085% (w / w), approximately 0.090% (w / w), approximately 0.095% (w / w), or approximately 0.10% (w / w), approximately 0.12% (w / w), approximately 0.125% (w / w), approximately 0.130% (w / w), approximately 0.135% (w / w), approximately 0.140% (w / w), approximately 0.145% (w / w), approximately 0.150% (w / w) Retinoic acid at approximately 0.155% (w / w), approximately 0.160% (w / w), approximately 0.165% (w / w), approximately 0.170% (w / w), approximately 0.175% (w / w), or approximately 0.180% (w / w), approximately 0.185% (w / w), approximately 0.190% (w / w), approximately 0.195% (w / w), or approximately 0.20% (w / w).

[0070] In some respects, the retinoid may be adapalene. In some respects, the combination formulation may contain about 0.010% (w / w) to about 0.50% (w / w) of adapalene. In some aspects, the combination formulation may contain about 0.02% (w / w), about 0.025% (w / w), about 0.030% (w / w), about 0.035% (w / w), about 0.040% (w / w), about 0.045% (w / w), about 0.050% (w / w), about 0.055% (w / w), about 0.060% (w / w), about 0.065% (w / w), about 0.070% (w / w), about 0.075% (w / w), or about 0.080% (w / w), about 0.085% (w / w), about 0.090% (w / w), about 0.095% (w / w), or about 0.10% (w / w), about 0.12% ( Adapalene at approximately 0.125% (w / w), approximately 0.130% (w / w), approximately 0.135% (w / w), approximately 0.140% (w / w), approximately 0.145% (w / w), approximately 0.150% (w / w), approximately 0.155% (w / w), approximately 0.160% (w / w), approximately 0.165% (w / w), approximately 0.170% (w / w), approximately 0.175% (w / w), or approximately 0.180% (w / w), approximately 0.185% (w / w), approximately 0.190% (w / w), approximately 0.195% (w / w), approximately 0.20% (w / w), approximately 0.30% (w / w), or approximately 0.40% (w / w).

[0071] In some respects, the retinoid may be tazarotene. In some respects, the combination formulation may contain about 0.010% (w / w) to about 0.20% (w / w) of tazarotene. In some aspects, the combination formulation may contain about 0.02% (w / w), about 0.025% (w / w), about 0.030% (w / w), about 0.035% (w / w), about 0.040% (w / w), about 0.045% (w / w), about 0.050% (w / w), about 0.055% (w / w), about 0.060% (w / w), about 0.065% (w / w), about 0.070% (w / w), about 0.075% (w / w), or about 0.080% (w / w), about 0.085% (w / w), about 0.090% (w / w), about 0.095% (w / w), or about 0.10% ( Tazarotene at approximately 0.12% (w / w), approximately 0.125% (w / w), approximately 0.130% (w / w), approximately 0.135% (w / w), approximately 0.140% (w / w), approximately 0.145% (w / w), approximately 0.150% (w / w), approximately 0.155% (w / w), approximately 0.160% (w / w), approximately 0.165% (w / w), approximately 0.170% (w / w), approximately 0.175% (w / w), or approximately 0.180% (w / w), approximately 0.185% (w / w), approximately 0.190% (w / w), approximately 0.195% (w / w), or approximately 0.20% (w / w).

[0072] In some respects, the retinoid may be trefaroline. In some respects, the combination formulation may contain about 0.001% (w / w) to about 0.015% (w / w) of trefaroline. In some aspects, the combination formulation may contain about 0.001% (w / w) of trafarotine, or about 0.002% (w / w), about 0.003% (w / w), about 0.004% (w / w), about 0.005% (w / w), about 0.006% (w / w), about 0.007% (w / w), about 0.008% (w / w), about 0.009% (w / w), about 0.010% (w / w), about 0.011% (w / w), about 0.012% (w / w), or about 0.013% (w / w), about 0.014% (w / w), or about 0.015% (w / w) of trafarotine.

[0073] In some aspects, the second anti-acne agent in the combination formulation may be an antioxidant. In some aspects, the antioxidant may be sodium L-ascorbic acid-2-phosphate. In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 7.0% (w / w) of sodium L-ascorbic acid-2-phosphate, or about 0.01% (w / w) to 5.0% (w / w), about 0.01% (w / w) to 3.5% (w / w), about 0.01% (w / w) to 2.0% (w / w), about 0. L-ascorbic acid-2-phosphate sodium at concentrations of 0.01% (w / w) to 1.0% (w / w), or about 0.01% (w / w) to 0.75% (w / w), about 0.01% (w / w) to 0.5% (w / w), about 0.01% (w / w) to 0.25% (w / w), about 0.01% (w / w) to 0.1% (w / w), or about 0.01% (w / w) to 0.05% (w / w).

[0074] In some aspects, the antioxidant in the combination formulation may be nicotinamide. In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 7.0% (w / w) of nicotinamide, or about 0.01% (w / w) to 5.0% (w / w), about 0.01% (w / w) to 3.5% (w / w), about 0.01% (w / w) to 2.0% (w / w), about 0. Nicotinamide in amounts of 0.01% (w / w) to 1.0% (w / w), or about 0.01% (w / w) to 0.75% (w / w), about 0.01% (w / w) to 0.5% (w / w), about 0.01% (w / w) to 0.25% (w / w), about 0.01% (w / w) to 0.1% (w / w), or about 0.01% (w / w) to 0.05% (w / w).

[0075] In some aspects, the secondary anti-acne agent in a combination formulation can be an organic acid. In some aspects, the organic acid may be selected from resorcinol, azelaic acid, salicylic acid, glycolic acid, and combinations thereof. In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 20% (w / w) of organic acid, or about 0.1% (w / w) to 10.0% (w / w), about 0.1% (w / w) to 7.5% (w / w), about 0.1% (w / w) to 6.0% (w / w), about 0.1% (w / w) to 5.0% (w / w), about 0.1% (w / w) to 4.0% (w / w), about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), about 0.1% (w / w) to 1.0% (w / w), or about 0.1% (w / w) to 0.5% (w / w).

[0076] In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 20% (w / w) of resorcinol, or about 0.1% (w / w) to 10.0% (w / w), about 0.1% (w / w) to 7.5% (w / w), or about 0.1% (w / w) to 6.0% (w / w). Resorcinol at approximately 0.1% (w / w) to 5.0% (w / w), approximately 0.1% (w / w) to 4.0% (w / w), approximately 0.1% (w / w) to 3.0% (w / w), approximately 0.1% (w / w) to 2.0% (w / w), approximately 0.1% (w / w) to 1.0% (w / w), or approximately 0.1% (w / w) to 0.5% (w / w).

[0077] In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 25% (w / w) of azelaic acid, or about 0.1% (w / w) to 15.0% (w / w), about 0.1% (w / w) to 10% (w / w), about 0.1% (w / w) to 6.0% (w / w), about 0.1% (w / w) to 5.0% (w / w), about 0.1% (w / w) to 4.0% (w / w), about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), about 0.1% (w / w) to 1.0% (w / w), or about 0.1% (w / w) to 0.5% (w / w).

[0078] In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to about 20% (w / w) of salicylic acid, or about 0.01% (w / w) to 10.0% (w / w), about 0.01% (w / w) to 7.5% (w / w), about 0.01% (w / w) to 6.0% (w / w), about Salicylic acid in amounts of 0.01% (w / w) to 5.0% (w / w), about 0.01% (w / w) to 4.0% (w / w), about 0.01% (w / w) to 3.0% (w / w), about 0.01% (w / w) to 2.0% (w / w), about 0.01% (w / w) to 1.0% (w / w), or about 0.01% (w / w) to 0.5% (w / w).

[0079] In some aspects, the combination formulation may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 70% (w / w) of glycolic acid, or about 0.1% (w / w) to 50.0% (w / w), about 0.1% (w / w) to 30.0% (w / w), or about 0.1% (w / w) to 20.0% (w / w). Glycolic acid in amounts of about 0.1% (w / w) to 15.0% (w / w), about 0.1% (w / w) to 10.0% (w / w), about 0.1% (w / w) to 5.0% (w / w), about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), or about 0.1% (w / w) to 0.5% (w / w).

[0080] In some aspects, the secondary anti-acne agent in a combination formulation may be a corticosteroid. In some aspects, the corticosteroid may be selected from hydrocortisone, triamcinolone, and combinations thereof.

[0081] In some aspects, the combination formulation may comprise about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to about 10.0% (w / w) of hydrocortisone, about 0.01% (w / w) to 5.0% (w / w) of hydrocortisone, about 0.01% (w / w) to 3.0% (w / w) of hydrocortisone, and about 0.01% (w / w) to 2.5% (w / w) of hydrocortisone. Hydrocortisone, about 0.01% (w / w) to 2.0% (w / w) of hydrocortisone, about 0.01% (w / w) to 1.0% (w / w) of hydrocortisone, about 0.01% (w / w) to 0.5% (w / w) of hydrocortisone, about 0.01% (w / w) to 0.1% (w / w) of hydrocortisone, or about 0.01% (w / w) to 0.5% (w / w) of hydrocortisone.

[0082] In some aspects, the combination formulation may comprise about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to about 1.0% (w / w) of triamcinolone acetonide, or about 0.01% (w / w) to 0.20% (w / w) of triamcinolone acetonide, about 0.01% (w / w) to 0.30% (w / w) of triamcinolone acetonide, about 0.01% (w / w) to 0.40% (w / w) of triamcinolone acetonide. Triamcinolone acetonide (w / w), approximately 0.01% (w / w) to 0.50% (w / w) of triamcinolone acetonide, approximately 0.01% (w / w) to 0.6% (w / w) of triamcinolone acetonide, approximately 0.01% (w / w) to 0.7% (w / w) of triamcinolone acetonide, approximately 0.01% (w / w) to 0.8% (w / w) of triamcinolone acetonide, or approximately 0.01% (w / w) to 0.9% (w / w) of triamcinolone acetonide.

[0083] In some aspects, the second anti-acne agent in a combination formulation may be an antiparasitic agent. In some aspects, the antiparasitic agent may be ivermectin. In some aspects, the combination formulation may comprise about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to about 5.0% (w / w) of ivermectin, about 0.01% (w / w) to about 3.0% (w / w) of ivermectin, about 0.01% (w / w) to 2.0% (w / w) of ivermectin, and about 0.01% (w / w) of... Ivermectin in amounts of about 1.0% (w / w), about 0.01% (w / w) to about 0.5% (w / w), about 0.01% (w / w) to about 0.3% (w / w), about 0.01% (w / w) to about 0.1% (w / w), or about 0.01% (w / w) to about 0.5% (w / w).

[0084] In some aspects, the second anti-acne agent in the combination formulation may be elemental sulfur. In some aspects, the combination formulation may contain about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to 15.0% (w / w) of sulfur, about 0.01% (w / w) to 10.0% (w / w) of sulfur, about 0.01% (w / w) to 5.0% (w / w) of sulfur, about 0.01% (w / w) to 2.0% (w / w) of sulfur, about 0.01% (w / w) to 1.0% (w / w) of sulfur, about 0.01% (w / w) to 0.5% (w / w) of sulfur, or about 0.01% (w / w) to 0.1% (w / w) of sulfur. In some aspects, sulfur may be formulated in combination with an effective amount of sodium sulfacetamide. In some applications, sulfur can be combined with an effective amount of resorcinol.

[0085] In some aspects, the second anti-acne agent in the combination formulation may be urea. In some aspects, the combination formulation may contain about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to 50.0% (w / w) of urea, about 0.1% (w / w) to 20.0% (w / w) of urea, about 0.01% (w / w) to 10.0% (w / w) of urea, about 0.01% (w / w) to 5.0% (w / w) of urea, about 0.01% (w / w) to 2.0% (w / w) of urea, about 0.01% (w / w) to 1.0% (w / w) of urea, or about 0.01% (w / w) to 0.5% (w / w) of urea.

[0086] In some aspects, the combination formulation may also contain at least one (e.g., 1, 2, 3, 4, 5, 6, 7 or 8) additive optionally selected from the following: acids, buffers, antioxidants, emulsifiers, penetration enhancers, humectants, preservatives, chelating agents, and combinations thereof.

[0087] In some respects, the combination formulation may be a cream. In some respects, the cream may contain equal parts of oil and water, in the form of an emulsion.

[0088] In some respects, the formulation may be a paste. In some respects, the paste may contain fatty acids (e.g., myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, or combinations thereof), oils, or combinations thereof.

[0089] In some aspects, the formulation may be a gel containing at least one gelling agent. The gelling agent may be, for example, an inorganic gelling agent (e.g., aluminum hydroxide gel, bentonite paste), an organic gelling agent (e.g., carbomer polymer, tragacanth gum), a hydrogel (e.g., an organic hydrogel, a natural or synthetic polymer, or an inorganic hydrogel), an organic gel (e.g., hydrocarbons, vegetable fats, soap-based oils, or hydrophilic organic gels), or a combination thereof. Organic hydrogels may include, for example, pectin paste and tragacanth gum gel. Suitable natural or synthetic polymers include, for example, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and poloxamer. Inorganic hydrogels may include, for example, bentonite gel, montmorillonite (e.g., VEEGUM). TM Vanderbilt Minerals, LLC, Norwalk, CT) or silica. Hydrocarbon-based organic gels may include, for example, mineral esters and mineral oil / polyethylene gels. Vegetable fat-based organic gels may include, for example, cocoa butter. Soap-based oil-based organic gels may include, for example, aluminum stearate and heavy mineral oil gels. Hydrophilic organic gels may include, for example, carbon wax matrices, such as polyethylene glycol (PEG) ointments.

[0090] In some applications, the gelling agent can be a carbomer polymer. The term "carbomer" is a generic name for a high molecular weight acrylic polymer that is lightly crosslinked with allyl ethers of polyols (such as allyl sucrose, allyl pentaerythritol). This term can also be used to describe CARBOPOL. TM Polymer (Lubrizol Corp., Wickliffe, OH).

[0091] In some aspects, the formulation may be an ointment. In some aspects, the ointment may contain hydrocarbons (e.g., paraffin, petrolatum), lanolin, beeswax, polyethylene glycol, emulsifying waxes, alkyltrimethylammonium bromide (e.g., cetrimonium bromide), vegetable oils (e.g., olive oil, jojoba oil, coconut oil, almond oil, cottonseed oil, safflower oil, sunflower oil, sesame oil, soybean oil, castor oil, or calendula oil), or combinations thereof. In some aspects, the ointment may contain about 20% (w / w) or less water.

[0092] In some respects, the combination formulation can be a foaming agent. The foaming formulation can be used in combination with one or more acceptable propellants (e.g., propane, butane, isobutylene, nitrogen, etc.).

[0093] In some aspects, the combination formulation may contain about 0.1% (w / w) to about 50% (w / w) of each additive (e.g., acid, buffer, antioxidant, emulsifier, penetration enhancer, humectant, preservative, chelating agent) relative to the total weight of the formulation (i.e., 100% (w / w)). For example, each additive may be present in amounts ranging from about 0.1% (w / w) to about 45% (w / w), about 0.1% (w / w) to about 40% (w / w), about 0.1% (w / w) to about 35% (w / w), about 0.1% (w / w) to about 30% (w / w), about 0.1% (w / w) to about 25% (w / w), about 0.1% (w / w) to about 20% (w / w), about 0.1% (w / w) to about 15% (w / w), about 0.1% (w / w) to about 10% (w / w), about 0.1% (w / w) to about 5% (w / w), about 0.1% (w / w) to about 2% of the total weight of the formulation. % (w / w), about 0.5% (w / w) to about 50% (w / w), about 0.5% (w / w) to about 45% (w / w), about 0.5% (w / w) to about 40% (w / w), about 0.5% (w / w) to about 35% (w / w), about 0.5% (w / w) to about 30% (w / w), about 0.5% (w / w) to about 25% (w / w), about 0.5% (w / w) to about 20% (w / w), about 0.5% (w / w) to about 15% (w / w), about 0.5% (w / w) to about 10% (w / w), about 0.5% (w / w) to about 5% (w / w), about 0.5% (w / w) to about 2% (w / w), about 1% (w / w) to about 50% (w / w), about 1% (w / w) to about 45% (w / w), about 1% (w / w) to about 40% (w / w), about 1% (w / w) to about 35% (w / w), about 1% (w / w) to about 30% (w / w), about 1% (w / w) to about 25% (w / w), about 1% (w / w) to about 20% (w / w). Approximately 1% (w / w) to approximately 15% (w / w), approximately 1% (w / w) to approximately 10% (w / w), approximately 1% (w / w) to approximately 5% (w / w), approximately 1% (w / w) to approximately 2% (w / w), approximately 50% (w / w), approximately 48% (w / w), approximately 46% (w / w), approximately 44% (w / w), approximately 42% (w / w), approximately 40% (w / w), approximately 38% by weight, approximately 36% (w / w) Approximately 34% (w / w), approximately 2% (w / w), approximately 30% (w / w), approximately 28% (w / w), approximately 26% (w / w), approximately 24% (w / w), approximately 22% (w / w), approximately 20% (w / w), approximately 18% (w / w), approximately 16% (w / w), approximately 14% (w / w), approximately 12% (w / w), approximately 10% (w / w), approximately 8% (w / w), approximately 6% (w / w), approximately 5% It is present in the combination formulation in amounts of approximately 4% (w / w), approximately 3% (w / w), approximately 2% (w / w), approximately 1% (w / w), approximately 0.9% (w / w), approximately 0.8% (w / w), approximately 0.7% (w / w), approximately 0.6% (w / w), approximately 0.5% (w / w), approximately 0.4% (w / w), approximately 0.3% (w / w), approximately 0.2% (w / w), or approximately 0.1% (w / w).

[0094] In some aspects, the formulation may contain an acid to help dissolve one or more active agents, maintain a desired pH, or both. Any suitable acid may be used, such as inorganic acids (e.g., hydrochloric acid, sulfuric acid, nitric acid, or phosphoric acid), organic acids (e.g., citric acid, acetic acid, succinic acid, or maleic acid), or mixtures thereof. Examples of suitable acid additives include, but are not limited to: 1-hydroxy-2-naphthoic acid, 2,2-dichloroacetic acid, 2-hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetaminobenzoic acid, 4-aminosalicylic acid, acetic acid, adipic acid, L-ascorbic acid, L-aspartic acid, benzenesulfonic acid, benzoic acid, (+)-camphoric acid, (+)-camphor-10-sulfonic acid, caproic acid, hexanoic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclohexanesulfonic acid, etc. The following acids are listed: 1,2-disulfonic acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, galactopyric acid, gentian acid, D-glucohepanoic acid, D-gluconic acid, D-glucuronic acid, glutamic acid, glutamate, glutaric acid, glycerophosphate, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, L-malic acid, malonic acid, mandelic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, nicotinic acid, nitric acid, oleic acid, oxalic acid, palmitic acid, palmitic acid, phosphoric acid, propionic acid, L-pyroglutamic acid, salicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, L-tartaric acid, thiocyanate, p-toluenesulfonic acid, and undecenoic acid. In some aspects, acetic acid, citric acid, or lactic acid may be added to the formulation.

[0095] In some aspects, the acid may be added in sufficient amounts such that the pH of the local composition may be about 7.0 or lower (e.g., about 4 to about 7.0, about 4 to about 6.5, about 4 to about 6, about 4 to about 5.5, about 4 to about 5, about 4.5 to about 7.0, about 4.5 to about 6.5, about 4.5 to about 6, about 4.5 to about 5.5, about 4.5 to about 5, about 5 to about 7.0, about 5 to about 6.5, about 5 to about 6, about 5 to about 5.5, about 5.5 to about 7.0, about 5.5 to about 6.5, about 5.5 to about 6, about 6 to about 7.0, or about 6 to about 6.5).

[0096] In some aspects, the combination formulation may contain a buffer to help maintain the pH of the formulation within a desired range. In some aspects, the buffer may be a phosphate buffer, a citrate buffer, a lactate buffer, or a combination thereof. In some aspects, the combination formulation may contain phosphoric acid, citric acid, lactic acid, or a combination thereof.

[0097] In some aspects, the formulation may contain an emulsifier, particularly to provide a solution, suspension, emulsion, or microemulsion. It is not desirable to be bound by any particular theory that an emulsifier, in its presence, facilitates or promotes the dissolution of any solid substance, such as an active agent, in the local composition. However, in other aspects, an emulsifier may be present to promote the incorporation of two immiscible liquids into each other (e.g., to form an emulsion or microemulsion).

[0098] In some respects, and without being bound by any particular theory, emulsifiers can improve the spreadability of a product. For example, and without being bound by any particular theory, when the formulation is a liquid solution, it is believed that the presence of an appropriate amount of emulsifier reduces the surface tension between the local composition and the lipid environment of the skin surface. This makes the local composition easier to spread and is thought to facilitate the penetration of active agents into the skin.

[0099] In some aspects, the emulsifier may be selected from the group comprising: polyethylene glycol (PEG) fatty acid monoesters, such as PEG-15 hydroxystearate (also known as polyoxyethylene-15-hydroxystearate), PEG-30 stearate, PEG-40 laurate, PEG-40 oleate, etc.; polyoxyethylene dehydrated sorbitan fatty acid esters (polysorbates), such as polysorbate 20, polysorbate 60, polysorbate 80, etc.; polyoxyethylene alkyl ethers, such as PEG-20 cetearyl alcohol ether, polyoxyethylene 25 cetearyl alcohol ether, polycetocil 1000 (cetomacrogol) 1000, etc.; sorbitan fatty acid esters, such as sorbitan monolaurate, sorbitan monopalmitate, sorbitan monooleate, etc.; propylene glycol esters of fatty acids; polyglycerol esters of fatty acids; polyoxyethylene castor oil derivatives, such as polyoxyethylene 5 castor oil, polyoxyethylene 15 castor oil, polyoxyethylene 35 castor oil, polyoxyethylene 40 hydrogenated castor oil, etc.; octanoyl octanoyl polyethylene glycol-8 glycerol ester; polyoxyethylene glycerol esters, such as octanoyl hexanoyl polyoxyethylene glycerol ester, lauroyl polyoxyethylene glycerol ester, oleoyl polyoxyethylene glycerol ester, etc.; and any combination thereof. In some aspects, the emulsifier may be polyoxyethylene 40 hydrogenated castor oil, polyoxyethylene-15-hydroxystearate, polysorbate 60, polysorbate 80, or combinations thereof. In some respects, the emulsifier may be a polysorbate, such as polysorbate 60, polysorbate 80, or a combination of polysorbate 60 and polysorbate 80.

[0100] In some aspects, the combination formulation may contain an emulsifier in an amount of up to about 0.5% (w / w) of the total formulation. In some aspects, the emulsifier may be present in an amount of 0.05% (w / w) to 0.2% (w / w). In some aspects, the combination formulation may contain an emulsifier in an amount of up to about 0.1% (w / w), or it may contain about 0.1% (w / w) of emulsifier. In some aspects, the emulsifier may be present in the combination formulation at about 0.1% (w / w).

[0101] In some aspects, the combination formulation may contain one or more penetration enhancers. It is not desirable to be bound by any particular theory that penetration enhancers beneficially influence the delivery of the active agent to the skin. Advantageously, and in some aspects, the solvent or some components of the solvent act as penetration enhancers. For example, in some aspects where the combination formulation contains ethanol and / or diethylene glycol monoethyl ether, these solvents can also be used to enhance the penetration of the active agent into the skin. Despite the presence of ethanol and / or diethylene glycol monoethyl ether, the topical compositions described herein may also contain additional penetration enhancers.

[0102] In some aspects, the penetration enhancer may be selected from hydroxypropyl β-cyclodextrin, glycols, polyols, fatty acids (e.g., myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, or combinations thereof), fatty alcohols, fatty acid esters, surfactants, pyrrolidones, and combinations thereof. Other examples of penetration enhancers that may be incorporated into the formulations described herein include, but are not limited to, polyoxyethylene alkyl ethers, polyoxyglycerol esters, dimethyl sulfoxide, pyrrolidones, N-methyl-2-pyrrolidones, and diethylene glycol monoethyl ethers (e.g., TRANSCUTOL). TM (Gattefossé, France), dimethyl isosorbide, diethyl sebacate, azone, menthol, nerol, camphor, methyl salicylate, polysorbate 80 (e.g., TWEEN) TM 80, Croda, England), SDS, benzalkonium chloride, polyoxyethylene 40 hydrogenated castor oil (CREMOPHOR) TM RH40, KOLLIPHOR TM RH40, BASF, Germany), diecyldimethylammonium bromide (DDAB), diecyltrimethylammonium bromide (DTAB), fatty acid esters (e.g., isopropyl myristate, isopropyl palmitate), fatty acids (e.g., oleic acid, palmitic acid, linoleic acid, and their salts), fatty alcohols (e.g., oleyl alcohol, myristol, and stearyl alcohol), medium-chain triglycerides, and any combination thereof.

[0103] In some aspects, the penetration enhancer may be dimethyl isosorbide. In some aspects, the penetration enhancer may be a mixture comprising dimethyl isosorbide and diethylene glycol monoethyl ether. In some aspects, the penetration enhancer may be dimethyl sulfoxide.

[0104] In some aspects, the penetration enhancer may be present in an amount of about 1% (w / w) to about 50% (w / w) relative to the total weight of the combined formulation. In some aspects, the penetration enhancer may be present in an amount of about 2% (w / w) to about 40% (w / w) relative to the total weight of the combined formulation; or about 5% (w / w) to about 35% (w / w) relative to the total weight of the combined formulation. In some aspects, the penetration enhancer may be present in the combined formulation described herein in an amount of about 1% (w / w), about 2% (w / w), about 5% (w / w), about 10% (w / w), about 15% (w / w), about 20% (w / w), about 25% (w / w), about 30% (w / w), about 35% (w / w), about 40% (w / w), about 45% (w / w), or about 50% (w / w) relative to the total weight of the combined formulation.

[0105] In some aspects, a combination formulation may contain one or more moisturizers. It is not desirable to be bound by a particular theory that moisturizers impart moisture and / or softness to the skin, especially when components known to dry the skin, such as alcohols, are also present in the combination formulation. In some aspects, moisturizers may be fatty alcohols, fatty acids (e.g., myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, or combinations thereof), fatty acid esters, oils, polyethylene glycol, glycerin, alpha-hydroxy acids, or combinations thereof. In some aspects, moisturizers may be cetyl alcohol, cetearyl alcohol, stearyl alcohol, stearic acid, isopropyl myristate, isopropyl palmitate, cocoa butter, lanolin, liquid paraffin, shea butter, silicone oil, castor oil, polyethylene glycol, glycerin, lactic acid, glycolic acid, malic acid, citric acid, tartaric acid, or combinations thereof. In some aspects, moisturizers may be cetyl alcohol, stearyl alcohol, or a combination of cetyl alcohol and stearyl alcohol.

[0106] In some aspects, the combination formulation may contain one or more preservatives (e.g., antibacterial agents, antifungal agents). Suitable preservatives include, for example, parabens (e.g., methylparaben, ethylparaben, propylparaben, butylparaben), benzoates (e.g., sodium benzoate), sorbates (e.g., potassium sorbate), quaternary ammonium compounds (e.g., benzalkonium chloride, benzyl chloride), alcohols (e.g., chlorobutanol, benzyl alcohol, ethanol, phenol, m-cresol, chlorocresol), sodium metabisulfite, imidazolidinyl urea, glycerol, propylene glycol, or combinations thereof.

[0107] In some respects, the combination formulation may contain one or more chelating agents. Suitable chelating agents include, for example, citric acid, phytic acid, sodium phytate, cioquinol, ethylenediaminetetraacetic acid (EDTA) (e.g., disodium EDTA, tetrasodium EDTA), etidronic acid, galactopyric acid, tetrahydroxypropyl ethylenediamine, sodium metasilicate, or combinations thereof.

[0108] In some respects, the combination formulation can be prepared as a cleansing agent. The cleansing agent can be applied to the skin over a period of time, followed by thorough rinsing. In some respects, the combination formulation can be prepared as a cleansing agent that also contains soap or detergent. The cleansing agent can be in the form of a solid bar, solution, suspension, cream, gel, paste, microemulsion, emulsion, or foam.

[0109] In some aspects, the combination formulation can be prepared as a lotion. In some aspects, the lotion may comprise the combination formulation and at least one component selected from moisturizers, occlusives, emollients, emulsifiers, solvents, fragrances, pH adjusters, and preservatives.

[0110] In some aspects, the combination formulation may be prepared as a solution. The solution may be a combination formulation comprising one or more suitable solvents or combinations thereof. In some aspects, the solvent may be water. In some aspects, the solvent may be an alcohol.

[0111] In some aspects, the combination formulation can be prepared as a suspension. The suspension can be a combination formulation comprising one or more suitable solvents or combinations thereof. In some aspects, the solvent can be water. In some aspects, the solvent can be alcohol.

[0112] In some respects, the combination formulation can be prepared as a hydrogel patch. A hydrogel patch may comprise the combination formulation, a film coating, a gel layer, and a backing layer.

[0113] In some respects, combination formulations can be prepared as microemulsions. Microemulsions may comprise combination formulations, oils, water, and one or more surfactants.

[0114] In some cases, combination preparations can be formulated into medicated swabs.

[0115] In some aspects, CTX and secondary anti-acne agents can be provided as separate formulations that can be mixed prior to use to produce a combination formulation. In some aspects, two or more separate formulations containing different active ingredients can be combined into a single combination formulation prior to use. In some aspects, the combination formulation can be prepared by mixing two or more separate formulations together prior to application. In some aspects, the combination formulation can be pre-formulated.

[0116] Treatment methods for acne include the application of combination formulations containing CTX and a secondary anti-acne agent.

[0117] This disclosure also provides methods for treating acne, including topical application of the combination formulation described herein. The combination formulation described herein can be applied to any body surface requiring treatment, such as acne-prone areas of skin. Suitable skin areas include, for example, the face, arms, armpits, legs, chest, abdomen, back, neck, or any combination thereof. In some aspects, the combination formulation is not delivered to the face. In other aspects, the combination formulation can be applied to the face.

[0118] In some aspects, methods of treating acne include applying an effective amount of the combination formulation as described herein at appropriate intervals, such as once or more daily (e.g., once daily, twice daily, three times daily, four times daily, etc.); once or more every other day (e.g., once every other day, twice every other day, three times every other day, four times every other day, etc.); once or more every three days (e.g., once every three days, twice every three days, three times every three days, four times every three days, etc.); at least once, twice, or three times per week; weekly; or less frequently until the treated acne is reduced or relieved. In some aspects, the combination formulation may be delivered to provide an initial loading dose, which may then be reduced to a maintenance level if needed or desired. The amount of the combination formulation to be administered and the loading period may be determined by a physician skilled in the art, as well as by the patient's condition and the disease or ailment to be treated. Although the combination formulation described herein may be administered at any time of day, in some aspects, the formulation may be administered at night.

[0119] In some aspects, methods of treating acne may include administering a combination formulation as described herein to a subject in need for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 days. Alternatively, the combination formulation may be administered for 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, or any other time period determined by a physician skilled in the art.

[0120] In some aspects, methods of treating acne may include applying a combination formulation comprising an effective amount of CTX and benzoyl peroxide. In some aspects, the method may include applying a combination formulation comprising about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 25.0% (w / w) of benzoyl peroxide, about 0.1% (w / w) to 10.0% (w / w) of benzoyl peroxide, about 0.1% (w / w) to 7.5% (w / w) of benzoyl peroxide, and about 0.1% (w / w) to 6.0% (w / w) of benzoyl peroxide. About 0.1% (w / w) to 5.0% (w / w) of benzoyl peroxide, about 0.1% (w / w) to 4.0% (w / w) of benzoyl peroxide, about 0.1% (w / w) to 3.0% (w / w) of benzoyl peroxide, about 0.1% (w / w) to 2.0% (w / w) of benzoyl peroxide, about 0.1% (w / w) to 1.0% (w / w) of benzoyl peroxide, or about 0.1% (w / w) to 0.5% (w / w) of benzoyl peroxide.

[0121] In some aspects, methods of treating acne may include the application of a combination preparation containing an effective amount of CTX and an antibiotic. In some aspects, the antibiotic may be selected from clindamycin, erythromycin, naflufloxacin, metronidazole, sulfamidone, minocycline, sodium sulfacetamide, diaminodiphenyl sulfone, and combinations thereof. In some aspects, the combination preparation suitable for this method may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 12.0% (w / w) of antibiotic, about 0.1% (w / w) to 10.0% (w / w) of antibiotic, about 0.1% (w / w) to 8.0% (w / w) of antibiotic, about 0.1% (w / w) to 6.0% (w / w) of antibiotic, about Antibiotics of 0.1% (w / w) to 4.0% (w / w), or about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), or about 0.1% (w / w) to 1.0% (w / w), about 0.1% (w / w) to 0.5% (w / w), or about 0.1% (w / w) to 0.1% (w / w).

[0122] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and clindamycin. In some aspects, the combination formulation suitable for this method may contain about 0.5% (w / w) to about 6.0% (w / w) of clindamycin. In some respects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0123] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and erythromycin. In some aspects, the combination formulation suitable for this method may contain about 0.5% (w / w) to about 6.0% (w / w) of erythromycin. In some respects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0124] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and naflufloxacin. In some aspects, the combination formulation suitable for this method may contain about 0.5% (w / w) to about 6.0% (w / w) of naflufloxacin. In some aspects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w) of naflufloxacin.

[0125] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and metronidazole. In some aspects, the combination formulation suitable for this method may contain about 0.5% (w / w) to about 6.0% (w / w) of metronidazole. In some respects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0126] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and sulfamidone. In some aspects, the combination formulation suitable for this method may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0127] In some aspects, methods of treating acne may include the application of a combination preparation containing an effective amount of CTX and minocycline. In some aspects, the combination formulation suitable for this method may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about 4.25% (w / w), about 4.5% (w / w), about 4.75% (w / w), about 5.0% (w / w), about 5.25% (w / w), about 5.5% (w / w), or about 6.0% (w / w).

[0128] In some aspects, methods of treating acne may include applying a combination formulation containing an effective amount of CTX and sodium sulfacetamide. In some aspects, the combination formulation suitable for this method may contain about 0.5% (w / w) to about 15.0% (w / w) of sodium sulfacetamide. In some aspects, the formulation may contain about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), about 4.0% (w / w), about... 4.25% (w / w), approximately 4.5% (w / w), approximately 4.75% (w / w), approximately 5.0% (w / w), approximately 5.25% (w / w), approximately 5.5% (w / w), approximately 6.0% (w / w), approximately 6.25% (w / w), approximately 6.5% (w / w), approximately 6.75% (w / w), approximately 7.0% (w / w), approximately 7.25% (w / w), approximately 7.5% (w / w), approximately 7.75% (w / w), approximately 8.0% (w / w), approximately 8 0.25% (w / w), approximately 8.5% (w / w), approximately 8.75% (w / w), approximately 9.0% (w / w), approximately 9.25% (w / w), approximately 9.5% (w / w), approximately 9.75% (w / w), approximately 10.0% (w / w), approximately 10.25% (w / w), approximately 10.5% (w / w), approximately 10.75% (w / w), approximately 11.0% (w / w), approximately 11.25% (w / w), approximately 11.5% (w / w), approximately 11.75% Sodium sulfacetamide (w / w), approximately 12.0% (w / w), approximately 12.25% (w / w), approximately 12.5% ​​(w / w), approximately 12.75% (w / w), approximately 13.0% (w / w), approximately 13.25% (w / w), approximately 13.5% (w / w), approximately 13.75% (w / w), approximately 14.0% (w / w), approximately 14.25% (w / w), approximately 14.5% (w / w), approximately 14.75% (w / w), or approximately 15.0% (w / w).

[0129] In some aspects, methods of treating acne may include applying a combination formulation comprising an effective amount of CTX and diaminodiphenyl sulfone. In some aspects, the combination formulation suitable for this method may comprise about 0.5% (w / w) to about 15% (wt / wt) of diaminodiphenyl sulfone. In some aspects, the combination formulation may comprise about 0.5% (w / w), about 0.75% (w / w), about 1.0% (w / w), about 1.25% (w / w), about 1.5% (w / w), about 1.75% (w / w), about 2.0% (w / w), about 2.25% (w / w), about 2.5% (w / w), about 2.75% (w / w), about 3.0% (w / w), about 3.25% (w / w), about 3.5% (w / w), or about 4.0% (w / w). Approximately 4.25% (w / w), approximately 4.5% (w / w), approximately 4.75% (w / w), approximately 5.0% (w / w), approximately 5.25% (w / w), approximately 5.5% (w / w), approximately 6.0% (w / w), approximately 6.25% (w / w), approximately 6.5% (w / w), approximately 6.75% (w / w), approximately 7.0% (w / w), approximately 7.25% (w / w), approximately 7.5% (w / w), approximately 7.75% (w / w), approximately 8.0% (w / w), approximately 8 0.25% (w / w), approximately 8.5% (w / w), approximately 8.75% (w / w), approximately 9.0% (w / w), approximately 9.25% (w / w), approximately 9.5% (w / w), approximately 9.75% (w / w), approximately 10.0% (w / w), approximately 10.25% (w / w), approximately 10.5% (w / w), approximately 10.75% (w / w), approximately 11.0% (w / w), approximately 11.25% (w / w), approximately 11.5% (w / w), approximately 11.75% ( Diaminodiphenyl sulfones, approximately 12.0% (w / w), approximately 12.25% (w / w), approximately 12.5% ​​(w / w), approximately 12.75% (w / w), approximately 13.0% (w / w), approximately 13.25% (w / w), approximately 13.5% (w / w), approximately 13.75% (w / w), approximately 14.0% (w / w), approximately 14.25% (w / w), approximately 14.5% (w / w), approximately 14.75% (w / w), or approximately 15.0% (w / w).

[0130] In some aspects, methods of treating acne may include the application of a combination formulation comprising an effective amount of CTX and retinoids. In some aspects, the retinoid may be selected from retinoic acid, adapalene, tazarotene, trafarotine, and combinations thereof. In some aspects, the combination formulation suitable for this method may comprise about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to about 7.0% (w / w) of retinoids, about 0.01% (w / w) to 5.0% (w / w) of retinoids, about 0.01% (w / w) to 3.5% (w / w) of retinoids, about 0.01% (w / w) to 2.0% (w / w) of retinoids, and about 0.01% (w / w) of retinoids. % (w / w) to 1.0% (w / w) of retinol, or about 0.01% (w / w) to 0.75% (w / w) of retinol, about 0.01% (w / w) to 0.5% (w / w) of retinol, or about 0.01% (w / w) to 0.25% (w / w) of retinol, about 0.01% (w / w) to 0.1% (w / w) of retinol, or about 0.01% (w / w) to 0.05% (w / w) of retinol.

[0131] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and retinoic acid. In some aspects, the combination formulation suitable for this method may contain about 0.010% (w / w) to about 0.20% (w / w) of retinoic acid. In some aspects, the combination formulation may contain about 0.02% (w / w), about 0.025% (w / w), about 0.030% (w / w), about 0.035% (w / w), about 0.040% (w / w), about 0.045% (w / w), about 0.050% (w / w), about 0.055% (w / w), about 0.060% (w / w), about 0.065% (w / w), about 0.070% (w / w), about 0.075% (w / w), or about 0.080% (w / w), about 0.085% (w / w), about 0.090% (w / w), about 0.095% (w / w), or about 0.10%. Retinoic acid at concentrations of approximately 0.12% (w / w), approximately 0.125% (w / w), approximately 0.130% (w / w), approximately 0.135% (w / w), approximately 0.140% (w / w), approximately 0.145% (w / w), approximately 0.150% (w / w), approximately 0.155% (w / w), approximately 0.160% (w / w), approximately 0.165% (w / w), approximately 0.170% (w / w), approximately 0.175% (w / w), or approximately 0.180% (w / w), approximately 0.185% (w / w), approximately 0.190% (w / w), approximately 0.195% (w / w), or approximately 0.20% (w / w).

[0132] In some aspects, methods of treating acne may include administering a combination formulation containing an effective amount of CTX and adapalene. In some aspects, the combination formulation suitable for this method may contain about 0.010% (w / w) to about 0.50% (w / w) of adapalene. In some aspects, the combination formulation may contain about 0.02% (w / w), about 0.025% (w / w), about 0.030% (w / w), about 0.035% (w / w), about 0.040% (w / w), about 0.045% (w / w), about 0.050% (w / w), about 0.055% (w / w), about 0.060% (w / w), about 0.065% (w / w), about 0.070% (w / w), about 0.075% (w / w), or about 0.080% (w / w), about 0.085% (w / w), about 0.090% (w / w), about 0.095% (w / w), or about 0.10% (w / w), about 0.12% ( Adapalene at approximately 0.125% (w / w), approximately 0.130% (w / w), approximately 0.135% (w / w), approximately 0.140% (w / w), approximately 0.145% (w / w), approximately 0.150% (w / w), approximately 0.155% (w / w), approximately 0.160% (w / w), approximately 0.165% (w / w), approximately 0.170% (w / w), approximately 0.175% (w / w), or approximately 0.180% (w / w), approximately 0.185% (w / w), approximately 0.190% (w / w), approximately 0.195% (w / w), approximately 0.20% (w / w), approximately 0.30% (w / w), or approximately 0.40% (w / w).

[0133] In some aspects, methods of treating acne may include the application of a combination formulation comprising an effective amount of CTX and tazarotene. In some aspects, the combination formulation suitable for this method may comprise about 0.010% (w / w) to about 0.20% (w / w) of tazarotene. In some aspects, the combination formulation may contain about 0.02% (w / w), about 0.025% (w / w), about 0.030% (w / w), about 0.035% (w / w), about 0.040% (w / w), about 0.045% (w / w), about 0.050% (w / w), about 0.055% (w / w), about 0.060% (w / w), about 0.065% (w / w), about 0.070% (w / w), about 0.075% (w / w), or about 0.080% (w / w), about 0.085% (w / w), about 0.090% (w / w), about 0.095% (w / w), or about 0.10% ( Tazarotene at approximately 0.12% (w / w), approximately 0.125% (w / w), approximately 0.130% (w / w), approximately 0.135% (w / w), approximately 0.140% (w / w), approximately 0.145% (w / w), approximately 0.150% (w / w), approximately 0.155% (w / w), approximately 0.160% (w / w), approximately 0.165% (w / w), approximately 0.170% (w / w), approximately 0.175% (w / w), or approximately 0.180% (w / w), approximately 0.185% (w / w), approximately 0.190% (w / w), approximately 0.195% (w / w), or approximately 0.20% (w / w).

[0134] In some aspects, methods of treating acne may include the application of a combination formulation comprising an effective amount of CTX and trafarotine. In some aspects, the combination formulation suitable for this method may comprise about 0.001% (w / w) to about 0.015% (w / w) of trafarotine. In some aspects, the combination formulation may contain about 0.001% (w / w) of trafarotine, or about 0.002% (w / w), about 0.003% (w / w), about 0.004% (w / w), about 0.005% (w / w), about 0.006% (w / w), about 0.007% (w / w), about 0.008% (w / w), about 0.009% (w / w), about 0.010% (w / w), about 0.011% (w / w), about 0.012% (w / w), or about 0.013% (w / w), about 0.014% (w / w), or about 0.015% (w / w) of trafarotine.

[0135] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and an antioxidant. In some aspects, the antioxidant suitable for this method may be sodium L-ascorbic acid-2-phosphate. In some aspects, the combination formulation of this method may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 7.0% (w / w) of sodium L-ascorbic acid-2-phosphate, or about 0.01% (w / w) to 5.0% (w / w), about 0.01% (w / w) to 3.5% (w / w), about 0.01% (w / w) to 2.0% (w / w), about... L-ascorbic acid-2-phosphate sodium at concentrations of 0.01% (w / w) to 1.0% (w / w), or about 0.01% (w / w) to 0.75% (w / w), about 0.01% (w / w) to 0.5% (w / w), about 0.01% (w / w) to 0.25% (w / w), about 0.01% (w / w) to 0.1% (w / w), or about 0.01% (w / w) to 0.05% (w / w).

[0136] In some aspects, methods of treating acne may include applying a combination formulation containing an effective amount of CTX and nicotinamide. In some aspects, the combination formulation suitable for this method may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 7.0% (w / w) of nicotinamide, or about 0.01% (w / w) to 5.0% (w / w), about 0.01% (w / w) to 3.5% (w / w), or about 0.01% (w / w) to 2.0% (w / w). Nicotinamide in amounts of about 0.01% (w / w) to 1.0% (w / w), or about 0.01% (w / w) to 0.75% (w / w), about 0.01% (w / w) to 0.5% (w / w), about 0.01% (w / w) to 0.25% (w / w), about 0.01% (w / w) to 0.1% (w / w), or about 0.01% (w / w) to 0.05% (w / w).

[0137] In some aspects, methods of treating acne may include the application of a combination preparation containing an effective amount of CTX and an organic acid. In some aspects, the organic acid may be selected from resorcinol, azelaic acid, salicylic acid, glycolic acid, and combinations thereof. In some aspects, the combination formulation suitable for this method may comprise about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 20% (w / w) of organic acid, or about 0.1% (w / w) to 10.0% (w / w), about 0.1% (w / w) to 7.5% (w / w), about 0.1% (w / w) to 6.0% (w / w), about 0.1% (w / w) to 5.0% (w / w), about 0.1% (w / w) to 4.0% (w / w), about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), about 0.1% (w / w) to 1.0% (w / w), or about 0.1% (w / w) to 0.5% (w / w).

[0138] In some aspects, methods of treating acne may include applying a combination formulation containing an effective amount of CTX and resorcinol. In some aspects, the combination formulation suitable for this method may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 20% (w / w) of resorcinol, or about 0.1% (w / w) to 10.0% (w / w), about 0.1% (w / w) to 7.5% (w / w), or about 0.1% (w / w) to 6.0% (w / w). Resorcinol, in amounts of about 0.1% (w / w) to 5.0% (w / w), about 0.1% (w / w) to 4.0% (w / w), about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), about 0.1% (w / w) to 1.0% (w / w), or about 0.1% (w / w) to 0.5% (w / w).

[0139] In some aspects, methods of treating acne may include the application of a combination preparation containing an effective amount of CTX and azelaic acid. In some aspects, the combination formulation suitable for this method may comprise about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 25% (w / w) of azelaic acid, or about 0.1% (w / w) to 15.0% (w / w), about 0.1% (w / w) to 10% (w / w), about 0.1% (w / w) to 6.0% (w / w), about 0.1% (w / w) to 5.0% (w / w), about 0.1% (w / w) to 4.0% (w / w), about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), about 0.1% (w / w) to 1.0% (w / w), or about 0.1% (w / w) to 0.5% (w / w).

[0140] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and salicylic acid. In some aspects, the combination formulation suitable for this method may comprise about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 20% (w / w) of salicylic acid, or about 0.1% (w / w) to 10.0% (w / w), about 0.1% (w / w) to 7.5% (w / w), about 0.1% (w / w) to 6.0% (w / w), about 0.1% (w / w) to 5.0% (w / w), about 0.1% (w / w) to 4.0% (w / w), about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), about 0.1% (w / w) to 1.0% (w / w), or about 0.1% (w / w) to 0.5% (w / w).

[0141] In some aspects, methods of treating acne may include applying a combination formulation containing an effective amount of CTX and glycolic acid. In some aspects, the combination formulation suitable for this method may contain about 0.1% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to about 70% (w / w) of glycolic acid, or about 0.1% (w / w) to 50.0% (w / w), about 0.1% (w / w) to 30.0% (w / w), or about 0.1% (w / w) to 20.0% (w / w). Glycolic acid, in amounts of about 0.1% (w / w) to 15.0% (w / w), about 0.1% (w / w) to 10.0% (w / w), about 0.1% (w / w) to 5.0% (w / w), about 0.1% (w / w) to 3.0% (w / w), about 0.1% (w / w) to 2.0% (w / w), or about 0.1% (w / w) to 0.5% (w / w).

[0142] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and a corticosteroid. In some aspects, the corticosteroid may be selected from hydrocortisone, triamcinolone, and combinations thereof.

[0143] In some aspects, methods of treating acne may include applying a combination formulation containing an effective amount of CTX and hydrocortisone. In some aspects, the combination formulation suitable for this method may contain about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to about 10.0% (w / w) of hydrocortisone, about 0.01% (w / w) to 5.0% (w / w) of hydrocortisone, about 0.01% (w / w) to 3.0% (w / w) of hydrocortisone, and about 0.01% (w / w) to 2.5% (w / w) of... Hydrocortisone (w / w), about 0.01% (w / w) to 2.0% (w / w) of hydrocortisone, about 0.01% (w / w) to 1.0% (w / w) of hydrocortisone, about 0.01% (w / w) to 0.5% (w / w) of hydrocortisone, about 0.01% (w / w) to 0.1% (w / w) of hydrocortisone, or about 0.01% (w / w) to 0.5% (w / w) of hydrocortisone.

[0144] In some aspects, methods of treating acne may include applying a combination formulation containing an effective amount of CTX and triamcinolone acetonide. In some aspects, the combination formulation suitable for this method may contain about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to about 1.0% (w / w) of triamcinolone acetonide, or about 0.01% (w / w) to 0.20% (w / w) of triamcinolone acetonide, about 0.01% (w / w) to 0.30% (w / w) of triamcinolone acetonide, and about 0.01% (w / w) to 0.4% (w / w) of triamcinolone acetonide. 0% (w / w) of triamcinolone, about 0.01% (w / w) to 0.50% (w / w) of triamcinolone, about 0.01% (w / w) to 0.6% (w / w) of triamcinolone, about 0.01% (w / w) to 0.7% (w / w) of triamcinolone, about 0.01% (w / w) to 0.8% (w / w) of triamcinolone, or about 0.01% (w / w) to 0.9% (w / w) of triamcinolone.

[0145] In some aspects, methods of treating acne may include the application of a combination formulation containing an effective amount of CTX and an antiparasitic agent. In some aspects, the combination formulation suitable for this method may contain ivermectin. In some aspects, the combination formulation of this method may contain about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to about 5.0% (w / w) of ivermectin, about 0.01% (w / w) to about 3.0% (w / w) of ivermectin, about 0.01% (w / w) to 2.0% (w / w) of ivermectin, and about 0.01%... Ivermectin in amounts of about 1.0% (w / w), about 0.01% (w / w) to about 0.5% (w / w), about 0.01% (w / w) to about 0.3% (w / w), about 0.01% (w / w) to about 0.1% (w / w), or about 0.01% (w / w) to about 0.5% (w / w).

[0146] In some aspects, methods of treating acne may include applying a combination formulation containing an effective amount of CTX and elemental sulfur. In some aspects, the combination formulation suitable for this method may contain about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.01% (w / w) to 15.0% (w / w) of sulfur, about 0.01% (w / w) to 10.0% (w / w) of sulfur, about 0.01% (w / w) to 5.0% (w / w) of sulfur, about 0.01% (w / w) to 2.0% (w / w) of sulfur, about 0.01% (w / w) to 1.0% (w / w) of sulfur, about 0.01% (w / w) to 0.5% (w / w) of sulfur, or about 0.01% (w / w) to 0.1% (w / w) of sulfur. In some aspects, sulfur can be formulated in combination with an effective amount of sodium sulfacetamide. In some aspects of this method, sulfur can be formulated in combination with an effective amount of resorcinol.

[0147] In some aspects, methods of treating acne may include applying a combination formulation comprising an effective amount of CTX and urea. In some aspects, the combination formulation suitable for this method may comprise about 0.01% (w / w) to about 5.0% (w / w) of CTX and about 0.1% (w / w) to 50.0% (w / w) of urea, about 0.1% (w / w) to 20.0% (w / w) of urea, about 0.01% (w / w) to 10.0% (w / w) of urea, about 0.01% (w / w) to 5.0% (w / w) of urea, about 0.01% (w / w) to 2.0% (w / w) of urea, about 0.01% (w / w) to 1.0% (w / w) of urea, or about 0.01% (w / w) to 0.5% (w / w) of urea.

[0148] In some aspects, methods of treating acne may include the administration of a combination formulation containing an effective amount of CTX and more than one secondary anti-acne agent. In some aspects, more than two, three, four, five, six, seven, eight, nine, or ten secondary anti-acne agents may be combined with CTX as a formulation for administration.

[0149] In some aspects, methods of treating acne may include topical application of a combination preparation containing an effective amount of CTX, an antibacterial agent, and a third anti-acne agent. In some aspects, methods of treating acne may include topical application of a combination preparation containing an effective amount of CTX, an antibacterial agent, and an antibiotic. In some aspects, methods of treating acne may include topical application of a combination preparation containing an effective amount of CTX, benzoyl peroxide, and clindamycin.

[0150] In some aspects, methods of treating acne may include topical application of a combination preparation containing an effective amount of CTX, an antibiotic, and a third anti-acne agent. In some aspects, methods of treating acne may include topical application of a combination preparation containing an effective amount of CTX, an antibiotic, and an organic acid. In some aspects, methods of treating acne may include topical application of a combination preparation containing an effective amount of CTX, clindamycin, and salicylic acid.

[0151] In some aspects, methods of treating acne may include the topical application of a combination preparation containing an effective amount of CTX, retinoids, and a third anti-acne agent. In some aspects, methods of treating acne may include the topical application of a combination preparation containing an effective amount of CTX, retinoids, and an antibiotic. In some aspects, methods of treating acne may include the topical application of a combination preparation containing an effective amount of CTX, adapalene, and clindamycin.

[0152] In some aspects, methods of treating acne may include topical application of a combination formulation comprising an effective amount of CTX, an antioxidant, and a third anti-acne agent. In some aspects, methods of treating acne may include topical application of a combination formulation comprising an effective amount of CTX, an antioxidant, and an antibiotic. In some aspects, methods of treating acne may include topical application of a combination formulation comprising an effective amount of CTX, L-ascorbic acid-2-phosphate sodium, and clindamycin.

[0153] In some aspects, methods of treating acne may include the topical application of a combination formulation containing an effective amount of CTX, an organic acid, and a third anti-acne agent. In some aspects, methods of treating acne may include the topical application of a combination formulation containing an effective amount of CTX, an organic acid, and a retinoid. In some aspects, methods of treating acne may include the topical application of a combination formulation containing an effective amount of CTX, azelaic acid, and adapalene.

[0154] In some aspects, methods of treating acne may include the topical application of a combination preparation comprising an effective amount of CTX, a corticosteroid, and a third anti-acne agent. In some aspects, methods of treating acne may include the topical application of a combination preparation comprising an effective amount of CTX, a corticosteroid, and an antibiotic. In some aspects, methods of treating acne may include the topical application of a combination preparation comprising an effective amount of CTX, hydrocortisone, and clindamycin.

[0155] In some aspects, methods of treating acne may include topical application of a combination formulation containing an effective amount of CTX and three anti-acne agents. In some aspects, methods of treating acne may include topical application of a combination formulation containing an effective amount of CTX, retinoids, an antibacterial agent, and an antibiotic. In some aspects, methods of treating acne may include topical application of a combination formulation containing an effective amount of CTX, adapalene, benzoyl peroxide, and clindamycin.

[0156] In some aspects, a method of treating acne may include the following steps: applying a first combination preparation containing an effective amount of CTX and one or more secondary anti-acne agents, followed by applying a second combination preparation containing CTX and one or more secondary anti-acne agents after a delay of seconds, minutes, or hours. For example, and in some aspects, the first combination preparation may be applied in the morning, and the second combination preparation may be applied at night.

[0157] In some aspects, methods of treating acne may include the following steps: applying three anti-acne agents in two separate topical combination formulations after a delay of seconds, minutes, or hours. In some aspects, methods of treating acne may include applying a first topical formulation containing more than one anti-acne agent, followed by applying a second topical formulation containing at least one anti-acne agent after a delay of seconds, minutes, or hours, wherein the at least one formulation contains an effective amount of CTX.

[0158] In some aspects, methods of treating acne may include the following steps: applying more than two anti-acne agents in three separate topical combination formulations. In some aspects, methods of treating acne may include applying a first topical formulation, followed by the application of a second and a third topical formulation, wherein at least one formulation contains an effective amount of CTX, and each formulation is applied after a delay of seconds, minutes, or hours.

[0159] In some aspects, methods of treating acne may include the application of a combination of more than one oral anti-acne agent and more than one topical anti-acne agent. In some aspects, methods of treating acne may include the oral application of a first topical preparation comprising at least one topical anti-acne agent several minutes or hours after the application of the first topical preparation, followed by the application of a second topical preparation comprising at least one topical anti-acne agent after a delay of several seconds, minutes, or hours, wherein at least one topical preparation comprises CTX. For example, and in some aspects, the first anti-acne agent may be applied orally, and the first topical preparation may be applied in the morning, and the second topical preparation containing one or more anti-acne agents may be applied at night, wherein at least one topical preparation comprises CTX. In some aspects, methods of treating acne may include mixing or combining the CTX-containing preparation and the second anti-acne agent immediately before use.

[0160] Methods of treating acne include co-administration of a formulation containing CTX and a second formulation containing one or more secondary anti-acne agents.

[0161] Although CTX and one or more secondary anti-acne agents can be co-formulated, in some aspects CTX and one or more secondary anti-acne agents can be formulated separately but can be co-administered. For example, in some aspects, a method of treating acne may include applying an effective amount of a first formulation containing CTX (e.g., WINLEVI®) and co-administering an effective amount of a second formulation containing one or more secondary anti-acne agents. Any known formulation of a topical secondary anti-acne agent may be used in the co-administration method described herein.

[0162] Suitable second-action formulations containing one or more secondary anti-acne agents include, but are not limited to, ACUATIM cream (1% w / w naflufloxacin), ACANYA (1.2% w / w clindamycin phosphate / 2.5% w / w benzoyl peroxide), ACZONE® (7.5% w / w diaminodiphenyl sulfone), ADULT ACNOMEL (2% w / w resorcinol / 8% w / w thiosulfate), AKLIEF (0.005% w / w trafarotine), AKNE-MYCIN (2% w / w erythromycin), AKTIPAK (3% w / w erythromycin / 5% w / w benzoyl peroxide), ALTRENO (0.05% w / w retinoic acid), AMZEEQ (4% w / w minocycline), ARAZLO (0.045% w / w tazarotene), ATRALIN (0.05% w / w retinoic acid), and ATRIX (0.1%). w / w salicylic acid), AVAGE (0.1% w / w tazarotene), AVAR (10% w / w sodium sulfacetamide / 5% w / w thiocyanate), AVITA (0.025% w / w retinoic acid), AZELEX (20% w / w azelaic acid), BENOXYL (4% w / w benzoyl peroxide), BENZAC AC (2.5% w / w to 10% w / w benzoyl peroxide), BENZACLIN (1% w / w clindamycin / 5% w / w benzoyl peroxide), BENZAMYCIN PAK (3% w / w erythromycin / 5% w / w benzoyl peroxide), BENZEFOAM (5% w / w benzoyl peroxide), BENZEPRO (5.3% w / w benzoyl peroxide), BREVOXYL (4% w / w benzoyl peroxide), CLENIA (10% w / w sodium sulfacetamide / 5% w / w sulfur), Clindaderm (1% w / w clindamycin phosphate), CLINDACIN (1% w / w clindamycin phosphate), Clindagel (1% w / w clindamycin phosphate), Clindamax (1% w / w clindamycin phosphate), Desquum-E (5% w / w benzoyl peroxide), Differin (0.1% w / w adapalene), Duac CS (1.2% w / w clindamycin phosphate / 5% w / w benzoyl peroxide), Effacar DUO (5.5% w / w benzoyl peroxide), Emgel (2% w / w erythromycin), Enzoclear (9.8% w / w benzoyl peroxide), Epidudoo (0.1% w / w adapalene / 2.5% w / w benzoyl peroxide), EPSOLAY (5% w / w benzoyl peroxide), ERYGEL (2% w / w erythromycin), EVOCLIN (1% w / w clindamycin phosphate), FABIOR (0.1% w / w tazarotene), FINACEA (15% w / w azelaic acid), KENALOG (0.025% to 0.5% triamcinolone), KLARON (10% w / w sodium sulfacetamide), NADOXIN (1% w / w naflufloxacin), NEUAC (1.2% w / w clindamycin phosphate / 5% w / w benzoyl peroxide), NUCARARXPAK (1% w / w clindamycin phosphate), NUOX (6% w / w benzoyl peroxide / 3% w / w thiosulfate), OVACE (10% w / w sodium sulfacetamide), PACNEX (7%) (w / w benzoyl peroxide), PANOXYL (benzoyl peroxide 2.5%, 5%, 10% w / w benzoyl peroxide), PLEXION (9.8% w / w sodium sulfacetamide / 4.8% w / w sulfur), PRASCION (10% w / w sodium sulfacetamide / 5% w / w sulfur), REFISSA (0.05% w / w retinoic acid), RENOVA (0.02% w / w retinoic acid), RETIN-A MICRO (0.04% w / w retinoic acid), RETIN-A (0.01% w / w to 0.05% w / w retinoic acid), RIAX (5.5% w / w to 9.5% w / w benzoyl peroxide), ROSANIL (10% w / w sodium sulfacetamide / 5% w / w sulfur), SALEX (6% w / w salicylic acid), SALICYLIX SF12 (12%) (w / w salicylic acid), SALVAX (6% w / w salicylic acid), SEB-PREV (10% w / w sodium sulfacetamide), SOOLANTRA (1% w / w ivermectin), STRIDEX (0.1% w / w salicylic acid), SULFAMYLON (5% w / w sulfamitron acetate), SULFATOL C (10% w / w sodium sulfacetamide / 5% w / w sulfur), SULFOLO (3% w / w sulfur), SUMADAN (9% w / w sodium sulfacetamide / 4.5% w / w sulfur), SUMAXIN (10% w / w sodium sulfacetamide / 4% w / w sulfur), TAZORAC (0.05% w / w to 0.1% w / w tazarotene), TRETIN-X (0.025% w / w retinoic acid), TRIAZ (3% w / w to 9%) w / w benzoyl peroxide), TRIDERM (0.025% to 0.5% triamcinolone), TWYNEO (0.1% w / w retinoic acid / 3% w / w benzoyl peroxide), VELTIN (1.2% w / w clindamycin phosphate / 0.025% w / w retinoic acid), ZACLIR (8% w / w benzoyl peroxide), ZENCIA (9% w / w sodium sulfacetamide / 4% w / w sulfur), and ZIANA (1.2% w / w clindamycin phosphate / 0.025% w / w retinoic acid).

[0163] Treatment methods for acne include topical co-application of CTX in combination with one or more oral secondary anti-acne agents.

[0164] In some aspects, this disclosure provides methods for treating or preventing acne, comprising topically applying an effective amount of a CTX-containing formulation (e.g., WINLEVI®) to a subject in need, and co-administering an effective amount of one or more second oral anti-acne agents orally. In some aspects, the one or more oral second anti-acne agents may be selected from antibiotics, hormones, retinoids, dietary supplements, and combinations thereof. Any known formulation of an oral second anti-acne agent may be used in the co-administration method described herein.

[0165] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of antibiotics selected from amoxicillin, azithromycin, cephalexin, doxycycline, erythromycin, minocycline, tetracycline, trimethoprim, sulfamethoxazole, etc. Azole, diaminodiphenyl sulfone, and combinations thereof. Antibiotics can be delivered orally in any known suitable oral formulation, including in the form of powders, solutions, suspensions, tablets, capsules, compression tablets, or soft gels.

[0166] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of amoxicillin. In some aspects, amoxicillin may be administered orally at a total daily dose of about 50 mg to about 2000 mg, for example, about 100 mg to about 1900 mg daily, about 250 mg to about 1750 mg daily, about 500 mg to about 1500 mg daily, or about 750 mg to about 1000 mg of amoxicillin daily. In some aspects, the total daily dose of amoxicillin may be administered orally in 1, 2, 3, 4, 5, or more doses, each containing about 100 mg to about 600 mg of amoxicillin. In some cases, each dose of amoxicillin may contain approximately 50 mg, approximately 75 mg, approximately 100 mg, approximately 125 mg, approximately 150 mg, approximately 175 mg, approximately 200 mg, approximately 225 mg, approximately 250 mg, approximately 275 mg, approximately 300 mg, approximately 350 mg, approximately 375 mg, approximately 400 mg, approximately 425 mg, approximately 450 mg, approximately 500 mg, approximately 525 mg, approximately 550 mg, approximately 575 mg, or approximately 600 mg of amoxicillin.

[0167] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of azithromycin. In some aspects, azithromycin may be administered orally at doses from about 50 mg to about 2000 mg. In some aspects, azithromycin may be administered once daily at doses from about 500 mg to about 2000 mg. In some formulations, azithromycin can be administered in doses of approximately 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, 950 mg, 975 mg, 1000 mg, 1025 mg, 1050 mg, and 1075 mg. mg, approximately 1100 mg, approximately 1125 mg, approximately 1150 mg, approximately 1175 mg, approximately 1200 mg, approximately 1225 mg, approximately 1250 mg, approximately 1275 mg, approximately 1300 mg, approximately 1325 mg, approximately 1350 mg, approximately 1375 mg, approximately 1400 mg, approximately 1425 mg, approximately 1450 mg, approximately 1475 mg, approximately 1500 mg, approximately 1525 mg, approximately 1550 mg, approximately 1575 mg, approximately 1600 mg, approximately 1625 mg, approximately 1650 mg, approximately 1675 mg, approximately 1700 mg, approximately 1725 mg, approximately 1750 mg, approximately 1775 mg, approximately 1800 mg, approximately 1825 mg, approximately 1850 mg, approximately 1875 mg, approximately 1900 mg, approximately 1925 mg, approximately 1950 mg Azithromycin is administered at doses of approximately 1,975 mg or 2,000 mg. In some cases, after the initial dose regimen, azithromycin administration may be gradually reduced to doses of approximately 50 to approximately 800 mg, approximately 250 mg to approximately 500 mg, once daily for several days.

[0168] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of cephalexin. In some aspects, cephalexin may be administered orally at doses from about 50 mg to about 2000 mg. In some aspects, cephalexin may be administered at doses from about 500 mg to about 2000 mg. In some aspects, cephalexin may be administered at doses from about 200 mg to about 750 mg. In some formulations, cephalexin can be administered in doses of approximately 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, 950 mg, 975 mg, 1000 mg, 1025 mg, 1050 mg, and 1075 mg. mg, approximately 1100 mg, approximately 1125 mg, approximately 1150 mg, approximately 1175 mg, approximately 1200 mg, approximately 1225 mg, approximately 1250 mg, approximately 1275 mg, approximately 1300 mg, approximately 1325 mg, approximately 1350 mg, approximately 1375 mg, approximately 1400 mg, approximately 1425 mg, approximately 1450 mg, approximately 1475 mg, approximately 1500 mg, approximately 1525 mg, approximately 1550 mg, approximately 1575 mg, approximately 1600 mg, approximately 1625 mg, approximately 1650 mg, approximately 1675 mg, approximately 1700 mg, approximately 1725 mg, approximately 1750 mg, approximately 1775 mg, approximately 1800 mg, approximately 1825 mg, approximately 1850 mg, approximately 1875 mg, approximately 1900 mg, approximately 1925 mg, approximately 1950 mg Administered at doses of approximately 1 mg, 1975 mg, or 2000 mg.

[0169] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of doxycycline. In some aspects, doxycycline may be administered orally in doses of about 50 mg to about 500 mg. In some aspects, doxycycline may be administered in doses of about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, or about 500 mg.

[0170] In some aspects, methods of treating acne may include administration of CTX and oral administration of an effective amount of erythromycin. In some aspects, erythromycin may be administered orally at a dose of about 50 mg to about 4000 mg. In some aspects, erythromycin may be administered at a dose of about 500 mg to about 4000 mg. In some aspects, erythromycin may be administered at a dose of about 200 mg to about 750 mg. In some formulations, erythromycin can be available in doses of approximately 50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, 975 mg, and so on. mg, approximately 1000 mg, approximately 1025 mg, approximately 1050 mg, approximately 1075 mg, approximately 1100 mg, approximately 1125 mg, approximately 1150 mg, approximately 1175 mg, approximately 1200 mg, approximately 1225 mg, approximately 1250 mg, approximately 1275 mg, approximately 1300 mg, approximately 1325 mg, approximately 1350 mg, approximately 1375 mg, approximately 1400 mg, approximately 1425 mg, approximately 1450 mg, approximately 1475 mg, approximately 1500 mg, approximately 1525 mg, approximately 1550 mg, approximately 1575 mg, approximately 1600 mg, approximately 1625 mg, approximately 1650 mg, approximately 1675 mg, approximately 1700 mg, approximately 1725 mg, approximately 1750 mg, approximately 1775 mg, approximately 1800 mg, approximately 1825 mg, approximately 1850 mg mg, approximately 1875 mg, approximately 1900 mg, approximately 1925 mg, approximately 1950 mg, approximately 1975 mg, approximately 2000 mg, approximately 2025 mg, approximately 2050 mg, approximately 2075 mg, approximately 2100 mg, approximately 2125 mg, approximately 2150 mg, approximately 2175 mg, approximately 2200 mg, approximately 2225 mg, approximately 2250 mg, approximately 2275 mg, approximately 2300 mg, approximately 2325 mg, approximately 2350 mg, approximately 2375 mg, approximately 2400 mg, approximately 2425 mgmg, approximately 2450 mg, approximately 2475 mg, approximately 2500 mg, approximately 2525 mg, approximately 2550 mg, approximately 2575 mg, approximately 2600 mg, approximately 2625 mg, approximately 2650 mg, approximately 2675 mg, approximately 2700 mg, approximately 2725 mg, approximately 2750 mg, approximately 2775 mg, approximately 2800 mg, approximately 2825 mg, approximately 2850 mg, approximately 2875 mg, approximately 2900 mg, approximately 2925 mg, approximately 2950 mg, approximately 2975 mg, approximately 3000 mg, approximately 3025 mg, approximately 3050 mg, approximately 3075 mg, approximately 3100 mg, approximately 3125 mg, approximately 3150 mg, approximately 3175 mg, approximately 3200 mg, approximately 3225 mg, approximately 3250 mg, approximately 3275 mg, approximately 3300 mg Administered at doses of approximately 3325 mg, approximately 3350 mg, approximately 3375 mg, approximately 3400 mg, approximately 3425 mg, approximately 3450 mg, approximately 3475 mg, approximately 3500 mg, approximately 3525 mg, approximately 3550 mg, approximately 3575 mg, approximately 3600 mg, approximately 3625 mg, approximately 3650 mg, approximately 3675 mg, approximately 3700 mg, approximately 3725 mg, approximately 3750 mg, approximately 3775 mg, approximately 3800 mg, approximately 3825 mg, approximately 3850 mg, approximately 3875 mg, approximately 3900 mg, approximately 3925 mg, approximately 3950 mg, approximately 3975 mg, or approximately 4000 mg.

[0171] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of minocycline. In some aspects, minocycline may be administered orally at a dose of about 50 mg to about 500 mg. In some aspects, minocycline may be administered at doses of about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, or about 500 mg.

[0172] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of tetracycline. In some aspects, tetracycline may be administered orally at a dose of about 50 mg to about 2000 mg. In some aspects, tetracycline may be administered at a dose of about 500 mg to about 2000 mg. In some aspects, tetracycline may be administered at a dose of about 200 mg to about 750 mg. In some formulations, tetracycline can be present in doses of approximately 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, 950 mg, 975 mg, 1000 mg, 1025 mg, 1050 mg, and 1075 mg. mg, approximately 1100 mg, approximately 1125 mg, approximately 1150 mg, approximately 1175 mg, approximately 1200 mg, approximately 1225 mg, approximately 1250 mg, approximately 1275 mg, approximately 1300 mg, approximately 1325 mg, approximately 1350 mg, approximately 1375 mg, approximately 1400 mg, approximately 1425 mg, approximately 1450 mg, approximately 1475 mg, approximately 1500 mg, approximately 1525 mg, approximately 1550 mg, approximately 1575 mg, approximately 1600 mg, approximately 1625 mg, approximately 1650 mg, approximately 1675 mg, approximately 1700 mg, approximately 1725 mg, approximately 1750 mg, approximately 1775 mg, approximately 1800 mg, approximately 1825 mg, approximately 1850 mg, approximately 1875 mg, approximately 1900 mg, approximately 1925 mg, approximately 1950 mg Administered at doses of approximately 1 mg, 1975 mg, or 2000 mg.

[0173] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of trimethoprim. In some aspects, trimethoprim may be administered orally at doses of about 50 mg to about 500 mg. In some aspects, trimethoprim may be administered at doses of about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, or about 500 mg.

[0174] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of sulfamethoxazole. azole. In some respects, sulfamethoxazole... Sulfamethoxazole can be administered orally in doses from about 50 mg to about 1000 mg. In some respects, sulfamethoxazole... Azole can be administered in doses of approximately 50 mg, approximately 75 mg, approximately 100 mg, approximately 125 mg, approximately 150 mg, approximately 175 mg, approximately 200 mg, approximately 225 mg, approximately 250 mg, approximately 275 mg, approximately 300 mg, approximately 325 mg, approximately 350 mg, approximately 375 mg, approximately 400 mg, approximately 425 mg, approximately 450 mg, approximately 475 mg, approximately 500 mg, approximately 600 mg, approximately 700 mg, approximately 800 mg, approximately 900 mg, or approximately 1000 mg.

[0175] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of effective amounts of trimethoprim and sulfamethoxazole. Azole combination. In some respects, trimethoprim and sulfamethoxazole... The combination of azoles can be approximately 40 mg of trimethoprim and approximately 200 mg of sulfamethoxazole. azole, approximately 160 mg of trimethoprim and 800 mg of sulfamethoxazole Or approximately 80 mg of trimethoprim and 400 mg of sulfamethoxazole. The dosage of azole is administered orally.

[0176] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of a hormonal agent selected from spironolactone, flutamide, cyproterone acetate, norethindrone, diacetylnorethinol, levonorgestrel, desogestrel, gestadione, drospirenone, ethinylestradiol, and combinations thereof. In some aspects, the hormonal agent may be administered orally in a cyclical regimen, wherein the dosage regimen alternates between administration of an active dose and an inactive dose. In some aspects, an effective amount of more than one hormonal agent may be in a combined oral formulation. In some aspects, an effective amount of at least one hormonal agent may be in tablet form.

[0177] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of spironolactone. In some aspects, spironolactone may be administered orally at doses of about 50 mg to about 500 mg. In some aspects, spironolactone may be administered at doses of about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, or about 500 mg.

[0178] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of flutamide. In some aspects, flutamide may be administered orally in doses of about 50 mg to about 600 mg. In some aspects, flutamide may be administered in doses of about 50 mg, about 55 mg, about 60 mg, about 70 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, about 500 mg, about 525 mg, about 550 mg, about 575 mg, or about 600 mg.

[0179] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of cyproterone acetate. In some aspects, cyproterone acetate may be administered orally at a dose of about 2 mg to about 200 mg. In some cases, cyproterone acetate can be administered in doses of approximately 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, 150 mg, 155 mg, 160 mg, 165 mg, 170 mg, 175 mg, 180 mg, 185 mg, 190 mg, and 195 mg. Administer at a dose of mg or approximately 200 mg.

[0180] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of cyproterone acetate and ethinylestradiol. In some aspects, cyproterone acetate may be administered orally in combination with about 0.01 mg, about 0.02 mg, about 0.03 mg, about 0.04 mg, about 0.05 mg, about 0.06 mg, or about 0.07 mg of ethinylestradiol.

[0181] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of norethindrone. In some aspects, norethindrone may be administered orally at doses of about 0.5 mg to about 20 mg. In some aspects, norethindrone may be administered at doses of about 0.5 mg, about 0.75 mg, about 1 mg, about 1.5 mg, about 2 mg, about 2.5 mg, about 3 mg, about 4 mg, about 5 mg, about 7.5 mg, about 10 mg, about 12.5 mg, about 15 mg, about 17.5 mg, or about 20 mg.

[0182] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of norethindrone and ethinylestradiol. In some aspects, the combination of norethindrone and ethinylestradiol may be administered orally at a dose of about 0.5 mg norethindrone acetate / 0.005 mg ethinylestradiol or about 0.5 mg norethindrone acetate / 0.0025 mg ethinylestradiol.

[0183] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of norethindrone acetate. In some aspects, norethindrone acetate may be administered in doses of about 0.5 mg to about 5 mg. In some aspects, norethindrone acetate may be administered orally in doses of about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.75 mg, about 0.8 mg, about 0.9 mg, about 1.0 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2 mg, about 2.5 mg, about 3 mg, or about 5 mg.

[0184] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of norethindrone and ethinylestradiol. In some aspects, the combination of norethindrone and ethinylestradiol may be administered orally at doses of about 1 mg norethindrone / 35 mg ethinylestradiol, about 1 mg norethindrone / 50 mg ethinylestradiol, or about 1 mg norethindrone / 75 mg ethinylestradiol.

[0185] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of levonorgestrel. In some aspects, levonorgestrel may be administered orally in doses of about 0.05 mg to about 5 mg. In some aspects, levonorgestrel may be administered in doses of about 0.05 mg, about 0.1 mg, about 0.2 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.75 mg, about 0.8 mg, about 0.9 mg, about 1.0 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2 mg, about 2.5 mg, about 3 mg, about 4 mg, or about 5 mg.

[0186] In some aspects, methods of treating acne may include topical application of CTX and oral administration of a combination of effective amounts of levonorgestrel and ethinylestradiol. In some aspects, the combination of levonorgestrel and ethinylestradiol may be administered orally at a dose of about 0.1 mg levonorgestrel / 0.02 mg ethinylestradiol.

[0187] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective dose of desogestrel of about 0.05 mg to about 5 mg. In some aspects, desogestrel may be administered orally in doses of about 0.05 mg, about 0.10 mg, about 0.15 mg, about 0.20 mg, about 0.25 mg, about 0.30 mg, about 0.40 mg, about 0.50 mg, about 0.60 mg, about 0.70 mg, about 0.75 mg, about 0.80 mg, about 0.90 mg, about 1.0 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, or about 5.0 mg.

[0188] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of desogestrel and ethinylestradiol. In some aspects, the desogestrel and ethinylestradiol combination may be orally administered at doses of about 0.15 mg desogestrel / 0.03 mg ethinylestradiol, about 0.15 mg desogestrel / 0.02 mg ethinylestradiol, about 0.10 mg desogestrel / 0.025 mg ethinylestradiol, about 0.125 mg desogestrel / 0.025 mg ethinylestradiol, or about 0.15 mg desogestrel / 0.025 mg ethinylestradiol.

[0189] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of pregnadienone. In some aspects, pregnadienone may be administered orally at a dose of about 0.020 mg to about 0.10 mg. In some aspects, pregnadienone may be administered at doses of about 0.020 mg, about 0.025 mg, about 0.030 mg, about 0.035 mg, about 0.040 mg, about 0.045 mg, about 0.050 mg, about 0.055 mg, about 0.060 mg, about 0.065 mg, about 0.070 mg, about 0.075 mg, or about 0.080 mg, about 0.085 mg, about 0.090 mg, about 0.095 mg, or about 0.10 mg.

[0190] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of pregnadienone and ethinylestradiol. In some aspects, the combination of pregnadienone and ethinylestradiol may be administered orally at doses of about 0.075 mg pregnadienone / about 0.020 mg ethinylestradiol, about 0.075 mg pregnadienone / about 0.030 mg ethinylestradiol, or about 0.060 mg pregnadienone / about 0.015 mg ethinylestradiol.

[0191] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of drospirenone. In some aspects, drospirenone may be administered orally in doses of about 0.05 mg to about 10 mg. In some aspects, drospirenone may be administered in doses of about 0.05 mg, about 0.1 mg, about 0.2 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.75 mg, about 0.8 mg, about 0.9 mg, about 1.0 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2 mg, about 2.5 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, or about 10 mg.

[0192] In some aspects, methods of treating acne may include topical application of CTX and oral co-administration of an effective amount of drospirenone and ethinyl estradiol. In some aspects, the combination of drospirenone and ethinyl estradiol may be administered orally at a dose of about 3.0 mg drospirenone / 0.020 mg ethinyl estradiol or about 3.0 mg drospirenone / 0.030 mg ethinyl estradiol.

[0193] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of ethinyl estradiol. In some aspects, ethinyl estradiol may be administered orally at doses of about 0.020 mg to about 0.060 mg daily. In some aspects, ethinyl estradiol may be administered at doses of about 0.020 mg, about 0.025 mg, about 0.030 mg, about 0.035 mg, about 0.040 mg, about 0.045 mg, about 0.050 mg, about 0.055 mg, or about 0.060 mg. In some aspects, an effective amount of ethinyl estradiol may be combined with an effective amount of another hormonal agent.

[0194] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of retinoids. In some aspects, the retinoid may be isotretinoin. In some aspects, isotretinoin may be administered orally at a dose of about 0.25 mg / kg / day to about 2.5 mg / kg / day. In some applications, isotretinoin can be administered at doses of approximately 0.25 mg / kg / day, approximately 0.30 mg / kg / day, approximately 0.35 mg / kg / day, approximately 0.40 mg / kg / day, approximately 0.45 mg / kg / day, approximately 0.50 mg / kg / day, approximately 0.55 mg / kg / day, approximately 0.60 mg / kg / day, approximately 0.65 mg / kg / day, approximately 0.70 mg / kg / day, approximately 0.75 mg / kg / day, approximately 0.80 mg / kg / day, approximately 0.85 mg / kg / day, approximately 0.90 mg / kg / day, approximately 0.95 mg / kg / day, approximately 1.0 mg / kg / day, approximately 1.25 mg / kg / day, approximately 1.50 mg / kg / day, approximately 1.75 mg / kg / day, approximately 2.0 mg / kg / day, approximately 2.25 mg / kg / day, or approximately 2.50 mg / kg / day. Administered at a dose of mg / kg / day.

[0195] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of dietary supplements. In some aspects, dietary supplements may be selected from vitamin C, vitamin D, vitamin E, vitamin K, biotin, niacin, zinc, selenium, iron, copper, omega-3 fatty acids, and combinations thereof.

[0196] In some aspects, treatment of acne may include topical application of CTX and oral administration of an effective amount of vitamin C. In some aspects, vitamin C may be administered orally at doses from about 50 mg to about 2000 mg. In some cases, vitamin C can be present in doses of approximately 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, 975 mg, 1000 mg, 1025 mg, 1050 mg, 1075 mg, and 1100 mg. mg, approximately 1125 mg, approximately 1150 mg, approximately 1175 mg, approximately 1200 mg, approximately 1225 mg, approximately 1250 mg, approximately 1275 mg, approximately 1300 mg, approximately 1325 mg, approximately 1350 mg, approximately 1375 mg, approximately 1400 mg, approximately 1425 mg, approximately 1450 mg, approximately 1475 mg, approximately 1500 mg, approximately 1525 mg, approximately 1550 mg, approximately 1575 mg, approximately 1600 mg, approximately 1625 mg, approximately 1650 mg, approximately 1675 mg, approximately 1700 mg, approximately 1725 mg, approximately 1750 mg, approximately 1775 mg, approximately 1800 mg, approximately 1825 mg, approximately 1850 mg, approximately 1875 mg, approximately 1900 mg, approximately 1925 mg, approximately 1950 mg, approximately 1975 mg Administer at a dose of mg, or approximately 2000 mg.

[0197] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of vitamin D. In some aspects, vitamin D may be administered orally at a dose of about 0.010 mg to about 0.060 mg. In some aspects, vitamin D may be administered at doses of about 0.010 mg, about 0.015 mg, about 0.020 mg, about 0.025 mg, about 0.030 mg, about 0.035 mg, about 0.040 mg, about 0.045 mg, about 0.050 mg, about 0.055 mg, or about 0.060 mg.

[0198] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of vitamin E. In some aspects, vitamin E may be administered in doses of about 0.010 mg to about 0.060 mg. In some aspects, vitamin E may be administered orally in doses of about 0.010 mg, about 0.015 mg, about 0.020 mg, about 0.025 mg, about 0.030 mg, about 0.035 mg, about 0.040 mg, about 0.045 mg, about 0.050 mg, about 0.055 mg, or about 0.060 mg.

[0199] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of vitamin K. In some aspects, vitamin K may be administered orally at a dose of about 0.010 mg to about 0.150 mg. In some cases, vitamin E can be administered in doses of approximately 0.010 mg, approximately 0.015 mg, approximately 0.020 mg, approximately 0.025 mg, approximately 0.030 mg, approximately 0.035 mg, approximately 0.040 mg, approximately 0.045 mg, approximately 0.050 mg, approximately 0.055 mg, approximately 0.060 mg, approximately 0.065 mg, approximately 0.070 mg, approximately 0.075 mg, approximately 0.080 mg, approximately 0.085 mg, approximately 0.090 mg, approximately 0.100 mg, approximately 0.110 mg, approximately 0.120 mg, approximately 0.130 mg, approximately 0.140 mg, or approximately 0.150 mg.

[0200] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of biotin. In some aspects, biotin may be administered orally at a dose of about 0.010 mg to about 0.150 mg. In some applications, biotin can be administered at doses of about 0.010 mg, about 0.015 mg, about 0.020 mg, about 0.025 mg, about 0.030 mg, about 0.035 mg, about 0.040 mg, about 0.045 mg, about 0.050 mg, about 0.055 mg, about 0.060 mg, about 0.065 mg, about 0.070 mg, about 0.075 mg, about 0.080 mg, about 0.085 mg, about 0.090 mg, about 0.100 mg, about 0.110 mg, about 0.120 mg, about 0.130 mg, about 0.140 mg, or about 0.150 mg.

[0201] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of niacin. In some aspects, niacin may be administered orally at doses from about 50 mg to about 2000 mg. In some formulations, niacin can be present in doses of approximately 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, 950 mg, 975 mg, 1000 mg, 1025 mg, 1050 mg, 1075 mg, and 1100 mg. mg, approximately 1125 mg, approximately 1150 mg, approximately 1175 mg, approximately 1200 mg, approximately 1225 mg, approximately 1250 mg, approximately 1275 mg, approximately 1300 mg, approximately 1325 mg, approximately 1350 mg, approximately 1375 mg, approximately 1400 mg, approximately 1425 mg, approximately 1450 mg, approximately 1475 mg, approximately 1500 mg, approximately 1525 mg, approximately 1550 mg, approximately 1575 mg, approximately 1600 mg, approximately 1625 mg, approximately 1650 mg, approximately 1675 mg, approximately 1700 mg, approximately 1725 mg, approximately 1750 mg, approximately 1775 mg, approximately 1800 mg, approximately 1825 mg, approximately 1850 mg, approximately 1875 mg, approximately 1900 mg, approximately 1925 mg, approximately 1950 mg, approximately 1975 mg Administer at a dose of mg, or approximately 2000 mg.

[0202] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of zinc. In some aspects, zinc may be administered orally at a dose of about 2 mg to about 20 mg. In some aspects, zinc may be administered at doses of about 2 mg, about 2.5 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, or about 20 mg.

[0203] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of selenium. In some aspects, selenium may be administered orally at a dose of about 0.02 mg to about 0.40 mg. In some cases, selenium can be present in amounts of approximately 0.02 mg, 0.03 mg, 0.04 mg, 0.05 mg, 0.06 mg, 0.07 mg, 0.08 mg, 0.09 mg, 0.10 mg, 0.11 mg, 0.12 mg, 0.13 mg, 0.14 mg, 0.15 mg, 0.16 mg, 0.17 mg, 0.18 mg, 0.19 mg, 0.20 mg, 0.21 mg, 0.22 mg, 0.23 mg, 0.24 mg, 0.25 mg, 0.26 mg, 0.27 mg, 0.28 mg, 0.29 mg, 0.30 mg, 0.310 mg, 0.32 mg, 0.33 mg, 0.34 mg, and 0.35 mg. Administered at doses of approximately 0.36 mg, 0.37 mg, 0.38 mg, 0.39 mg, or 0.40 mg.

[0204] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of iron. In some aspects, iron may be administered orally at doses of about 5 mg to about 28 mg daily. In some aspects, iron may be administered at doses of about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, about 25 mg, about 26 mg, about 27 mg, or about 28 mg.

[0205] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of copper. In some aspects, copper may be administered orally at a dose of about 1 mg to about 4 mg. In some aspects, zinc may be administered at a dose of about 1 mg, about 1.5 mg, about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, or about 4 mg.

[0206] In some aspects, methods of treating acne may include topical application of CTX and oral administration of an effective amount of one or more omega-3 fatty acids. In some aspects, omega-3 fatty acids may be contained in oils selected from fish oil, krill oil, cod liver oil, and algae oil. In some aspects, omega-3 fatty acids may be administered orally at doses from about 200 mg to about 4000 mg. In some cases, omega-3 fatty acids can be present in the following quantities: approximately 200 mg, approximately 225 mg, approximately 250 mg, approximately 275 mg, approximately 300 mg, approximately 325 mg, approximately 350 mg, approximately 375 mg, approximately 400 mg, approximately 425 mg, approximately 450 mg, approximately 475 mg, approximately 500 mg, approximately 525 mg, approximately 550 mg, approximately 575 mg, approximately 600 mg, approximately 625 mg, approximately 650 mg, approximately 675 mg, approximately 700 mg, approximately 725 mg, approximately 750 mg, approximately 775 mg, approximately 800 mg, approximately 825 mg, approximately 850 mg, approximately 875 mg, approximately 900 mg, approximately 925 mg, approximately 950 mg, approximately 975 mg, approximately 950 mg, approximately 975 mg, approximately 1000 mg, approximately 1025 mg, approximately 1050 mg, approximately 1075 mg. mg, approximately 1100 mg, approximately 1125 mg, approximately 1150 mg, approximately 1175 mg, approximately 1200 mg, approximately 1225 mg, approximately 1250 mg, approximately 1275 mg, approximately 1300 mg, approximately 1325 mg, approximately 1350 mg, approximately 1375 mg, approximately 1400 mg, approximately 1425 mg, approximately 1450 mg, approximately 1475 mg, approximately 1500 mg, approximately 1525 mg, approximately 1550 mg, approximately 1575 mg, approximately 1600 mg, approximately 1625 mg, approximately 1650 mg, approximately 1675 mg, approximately 1700 mg, approximately 1725 mg, approximately 1750 mg, approximately 1775 mg, approximately 1800 mg, approximately 1825 mg, approximately 1850 mg, approximately 1875 mg, approximately 1900 mg, approximately 1925 mg, approximately 1950 mg mg, approximately 1975 mg, approximately 2000 mg, approximately 2025 mg, approximately 2050 mg, approximately 2075 mg, approximately 2100 mg, approximately 2125 mg, approximately 2150 mg, approximately 2175 mg, approximately 2200 mg, approximately 2225 mg, approximately 2250 mg, approximately 2275 mg, approximately 2300 mg, approximately 2325 mg, approximately 2350 mg, approximately 2375 mg, approximately 2400 mg, approximately 2425 mg, approximately 2450 mg, approximately 2475 mg, approximately 2500 mg, approximately 2525 mg, approximately 2550 mg, approximately 2575 mg, approximately 2600 mgmg, approximately 2625 mg, approximately 2650 mg, approximately 2675 mg, approximately 2700 mg, approximately 2725 mg, approximately 2750 mg, approximately 2775 mg, approximately 2800 mg, approximately 2825 mg, approximately 2850 mg, approximately 2875 mg, approximately 2900 mg, approximately 2925 mg, approximately 2950 mg, approximately 2975 mg, approximately 3000 mg, approximately 3025 mg, approximately 3050 mg, approximately 3075 mg, approximately 3100 mg, approximately 3125 mg, approximately 3150 mg, approximately 3175 mg, approximately 3200 mg, approximately 3225 mg, approximately 3250 mg, approximately 3275 mg, approximately 3300 mg, approximately 3325 mg, approximately 3350 mg, approximately 3375 mg, approximately 3400 mg, approximately 3425 mg, approximately 3450 mg, approximately 3475 mg Administered at doses of approximately 3500 mg, approximately 3525 mg, approximately 3550 mg, approximately 3575 mg, approximately 3600 mg, approximately 3625 mg, approximately 3650 mg, approximately 3675 mg, approximately 3700 mg, approximately 3725 mg, approximately 3750 mg, approximately 3775 mg, approximately 3800 mg, approximately 3825 mg, approximately 3850 mg, approximately 3875 mg, approximately 3900 mg, approximately 3925 mg, approximately 3950 mg, approximately 3975 mg, or approximately 4000 mg.

[0207] In some respects, methods of treating acne may include topical application of CTX and oral co-administration of a combination of more than one dietary supplement as discussed herein, in the form of an effective amount of multiple vitamins or a combination of dietary preparations.

[0208] Suitable oral secondary anti-acne agents include, but are not limited to, absorbica (10, 20, 30 or 40 mg isotretinoin), accutane (10, 20, 30 or 40 mg isotretinoin), adoxa (75 or 150 mg doxycycline hydrochloride), aldactone (25, 50 or 100 mg spironolactone), and bactrim (400 mg sulfamethoxazole). 80 mg trimethoprim or 800 mg sulfamethoxazole Trimethoprim / 160 mg, BEYAZ (3 mg drospirenone / 20 mcg ethinylestradiol / 0.451 mg levomefolate), CARSPIR (25 mg spironolactone / 5 mL suspension), CLARAVIS (10, 20, 30 or 40 mg isotretinoin), CLEOCIN (75, 150 or 300 mg clindamycin hydrochloride), DORYX (75 or 150 mg doxycycline hydrochloride), ERYTHROCIN (250 mg erythromycin), ESTROSTEP (1 mg norethindrone acetate / 20 mcg ethinylestradiol), EULEXIN (125 mg flutamide), KEFLEX® (250 or 500 mg cephalexin), MINOCIN (50, 100 mg minocycline hydrochloride), MYORISAN (10, 20, 30 or 40 mg levomefolate / 5 mL suspension), MYORISAN (10, 20, 30 or 40 mg levomefolate / 5 mL suspension), BEYAZ (3 mg drospirenone / 20 mcg ethinylestradiol / 0.451 mg levomefolate ... (mg isotretinoin), ORTHO TRI-CYCLEN (0.180 mg oxytocin / 0.035 mg ethinylestradiol), PRIMSOL (50 mg trimethoprim hydrochloride / 5 mL suspension), SEPTRA (400 mg sulfamethoxazole) 80 mg trimethoprim or 800 mg sulfamethoxazole Minocycline hydrochloride (160 mg), SOLODYN (45, 65, 90, 115 or 135 mg), SOTRET (10, 20, 30 or 40 mg), SULFATRIM (200 mg sulfamethoxazole per 5 mL). (e.g., 40 mg trimethoprim), YAZ (0.02 mg ethinylestradiol / 3 mg drospirenone), ZENATANE (10, 20, 30 or 40 mg isotretinoin), and ZITHROMAX (250 mg, 300 mg, 600 mg, 900 mg or 1200 mg azithromycin).

[0209] Example 1: A binary combination topical composition having corticosterone-17α-propionate.

[0210] A combination of corticosterone-17α-propionate (1 wt% (w / w)) and benzoyl peroxide was formulated as a topical therapeutic agent, as described in Table 1.

[0211] Table 1

[0212] Components Amount (g / 100 g) stearic acid 22.2 cetyl alcohol 1.5 Triethanolamine 0.67 mineral oil 1.90 Vitamin E 0.56 Benzoyl peroxide (5% solution) 8.0 Corticosterone-17α-propionate 1.0 water qs to 100 g

[0213] qs – appropriate amount

[0214] Example 2: A ternary topical composition having corticosterone-17α-propionate.

[0215] A combination of corticosterone-17α-propionate (1% by weight (w / w)), clindamycin phosphate (1.2%) and adapalene (0.15%) was formulated as a topical treatment as described in Table 2.

[0216] Table 2

[0217] Components Amount (g / 100 g) stearic acid 22.2 cetyl alcohol 1.5 Triethanolamine 0.67 mineral oil 1.90 Corticosterone-17α-propionate 1.0 Clindamycin phosphate 1.2 Adapalin 0.15 water qs to 100 g

[0218] qs – appropriate amount

[0219] Example 3: A quaternary topical composition having corticosterone-17α-propionate.

[0220] A combination of corticosterone-17α-propionate (1 wt% (w / w)), clindamycin phosphate (1.2%), adapalene (0.15%) and benzoyl peroxide (3.1%) was formulated as a topical treatment, as described in Table 3.

[0221] Table 3

[0222] Components Amount (g / 100 g) stearic acid 22.2 cetyl alcohol 1.5 Triethanolamine 0.67 mineral oil 1.90 Corticosterone-17α-propionate 1.0 Clindamycin phosphate 1.2 Adapalin 0.15 Benzoyl peroxide 3.1 water qs to 100 g

[0223] qs – appropriate amount

[0224] The wording or terminology used herein is for descriptive purposes and not for limitation. Therefore, the terminology and / or wording in this specification should be interpreted by a person skilled in the art based on the teachings and instructions herein.

[0225] The breadth and scope of this invention should not be limited by any of the above exemplary embodiments, but should be defined only by the appended claims and their equivalents.

[0226] All patents, patent applications and other references mentioned or cited in this application are incorporated herein by reference in their entirety.

Claims

1. A method for treating or preventing acne, the method comprising topically applying to a subject in need an effective amount of corticosterone-17α-propionate, in combination with an effective amount of one or more second anti-acne agents.

2. The method of claim 1, wherein one or more second anti-acne agents are oral agents.

3. The method of claim 2, wherein the oral agent is an antibiotic, a hormone, a retinoid, a dietary supplement, or a combination thereof.

4. The method of claim 3, wherein the antibiotic is amoxicillin, azithromycin, cephalexin, doxycycline, erythromycin, minocycline, tetracycline, trimethoprim, or sulfamethoxazole. Azole, or combinations thereof.

5. The method of claim 3 or 4, wherein the hormone agent is flutamide, spironolactone, cyproterone acetate, norethindrone, diacetylnorethindrone, levonorgestrel, norgestrol acetate, desogestrel, pregnadienone, drospirenone, ethinylestradiol, or a combination thereof.

6. The method of any one of claims 3 to 5, wherein the retinoid is isotretinoin.

7. The method of any one of claims 3 to 6, wherein the dietary supplement is vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, biotin, niacin, zinc, selenium, iron, copper, omega-3 fatty acids, or a combination thereof.

8. The method of claim 1, wherein the one or more second anti-acne agents are one or more second topical anti-acne agents.

9. The method of claim 8, wherein the one or more second topical anti-acne agents and corticosteroid-17α-propionate are provided as a topical composition comprising the corticosteroid-17α-propionate, the one or more second anti-acne agents, and at least one pharmaceutically acceptable carrier.

10. The method of claim 9, wherein the topical composition is a gel, cream, lotion, solution, suspension, foam, ointment, wash, hydrogel patch, microemulsion, or medicated swab.

11. The method of claim 9 or 10, wherein the local composition is pre-formulated.

12. The method of claim 8, wherein the one or more second topical anti-acne agents and corticosteroid-17α-propionate are provided as separate topical compositions, each topical composition comprising at least one active agent and at least one pharmaceutically acceptable carrier.

13. The method of claim 12, wherein the separate partial compositions are combined just before use.

14. The method of claim 12, wherein the separate local compositions are applied sequentially.

15. The method of any one of claims 12 to 14, wherein each topical composition is independently selected from gels, creams, lotions, solutions, suspensions, foams, ointments, washes, hydrogel patches, microemulsions, and medicated swabs.

16. The method of any one of claims 8 to 15, wherein the at least one second topical anti-acne agent is an antibacterial agent, an antibiotic, a retinoid, an antioxidant, an organic acid, a corticosteroid, an antiparasitic agent, sulfur, urea, or a combination thereof.

17. The method of claim 16, wherein The antibacterial agent is benzoyl peroxide; The antibiotics are clindamycin, erythromycin, naflufloxacin, metronidazole, sulfamidophos, minocycline, sulfacetamide sodium, diaminodiphenyl sulfone, or combinations thereof; The retinoid is retinoic acid, adapalene, tazarotene, trefarotin, or a combination thereof; The antioxidant is sodium L-ascorbic acid-2-phosphate; The organic acid is resorcinol, azelaic acid, salicylic acid, glycolic acid, or a combination thereof; The corticosteroid is hydrocortisone, triamcinolone, or a combination thereof; and The antiparasitic agent is ivermectin.

18. The method of any one of claims 1 to 17, wherein the acne is mild, moderate or severe acne vulgaris.

19. The method of claim 18, wherein the acne vulgaris is facial acne vulgaris.

20. A topical composition comprising corticosterone-17α-propionate, at least one topical anti-acne agent, and a pharmaceutically acceptable carrier.

21. The topical composition of claim 20, wherein the topical anti-acne agent is an antibacterial agent, an antibiotic, a retinoid, an antioxidant, an organic acid, a corticosteroid, an antiparasitic agent, sulfur, urea, or a combination thereof.

22. The topical composition of claim 21, wherein the antibacterial agent is benzoyl peroxide.

23. The topical composition of claim 21 or 22, wherein the antibiotic is clindamycin, erythromycin, naflufloxacin, metronidazole, sulfamidophos, minocycline, sodium sulfacetamide, diaminodiphenyl sulfone, or a combination thereof.

24. The topical composition of any one of claims 21 to 23, wherein the retinoid is retinoic acid, adapalene, tazarotene, trofarotine, or a combination thereof.

25. The topical composition of any one of claims 21 to 24, wherein the antioxidant is sodium L-ascorbic acid-2-phosphate or nicotinamide.

26. The partial composition of any one of claims 21 to 25, wherein the organic acid is resorcinol, azelaic acid, salicylic acid, glycolic acid, or a combination thereof.

27. The topical composition of any one of claims 21 to 26, wherein the corticosteroid is hydrocortisone, triamcinolone, or a combination thereof.

28. The topical composition of any one of claims 21 to 27, wherein the antiparasitic agent is ivermectin.

29. The topical composition of any one of claims 20 to 28, wherein the composition is in the form of a cream, lotion, gel, ointment, mousse, spray solution, suspension, emulsion, wash, patch, or medicated swab.

30. A combination of corticosterone-17α-propionate for the treatment or prevention of acne with one or more secondary anti-acne agents, characterized in that... They are applied locally to objects.

31. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to claim 30, wherein the one or more second anti-acne agents are oral.

32. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to claim 31, wherein the oral agent is an antibiotic, a hormone, a retinoid, a dietary supplement, or a combination thereof.

33. The combination of corticosteroid-17α-propionate as described in claim 32 with one or more secondary anti-acne agents, wherein said antibiotic is amoxicillin, azithromycin, cephalexin, doxycycline, erythromycin, minocycline, tetracycline, trimethoprim, sulfamethoxazole, etc. Azole, or combinations thereof.

34. The combination of corticosteroid-17α-propionate according to claim 32 with one or more second anti-acne agents, wherein the hormonal agent is flutamide, spironolactone, cyproterone acetate, norethindrone, diacetylnorethindrone, levonorgestrel, norgestrel, desogestrel, pregnadienone, drospirenone, ethinylestradiol, or a combination thereof.

35. The combination of corticosterone-17α-propionate as described in claim 32 with one or more second anti-acne agents, wherein the retinoid is isotretinoin.

36. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to claim 32, wherein the dietary supplement is vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, biotin, niacin, zinc, selenium, iron, copper, omega-3 fatty acids, or a combination thereof.

37. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to claim 30, wherein the one or more second anti-acne agents are one or more second topical anti-acne agents.

38. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to claims 30 to 37, wherein the one or more second topical anti-acne agents and corticosterone-17α-propionate are provided as a topical composition comprising the corticosterone-17α-propionate, the one or more second anti-acne agents, and at least one pharmaceutically acceptable carrier.

39. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to claims 30 to 38, wherein the topical composition is a gel, cream, lotion, solution, suspension, foam, ointment, wash, hydrogel patch, microemulsion, or medicated swab.

40. The combination of corticosterone-17α-propionate as described in claim 39 with one or more second anti-acne agents, wherein the topical composition is pre-formulated.

41. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to claims 30 to 40, wherein the one or more second topical anti-acne agents and corticosterone-17α-propionate are provided as separate topical compositions, each topical composition comprising at least one active agent and at least one pharmaceutically acceptable carrier.

42. The combination of corticosterone-17α-propionate as described in claim 41 with one or more second anti-acne agents, wherein the separate topical compositions are combined just before use.

43. The combination of corticosterone-17α-propionate as described in claim 41 or 42 with one or more second anti-acne agents, wherein the separate topical compositions are applied sequentially.

44. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to claims 41 to 43, wherein each topical composition is independently selected from gels, creams, lotions, solutions, suspensions, foams, ointments, washes, hydrogel patches, microemulsions, and medicated swabs.

45. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to claims 37 to 44, wherein the at least one second topical anti-acne agent is an antibacterial agent, an antibiotic, a retinoid, an antioxidant, an organic acid, a corticosteroid, an antiparasitic agent, sulfur, urea, or a combination thereof.

46. ​​The combination of corticosterone-17α-propionate as described in claim 45 with one or more second anti-acne agents, wherein... The antibacterial agent is benzoyl peroxide; The antibiotics are clindamycin, erythromycin, naflufloxacin, metronidazole, sulfamidophos, minocycline, sulfacetamide sodium, diaminodiphenyl sulfone, or combinations thereof; The retinoid is retinoic acid, adapalene, tazarotene, trefarotin, or a combination thereof; The antioxidant is sodium L-ascorbic acid-2-phosphate; The organic acid is resorcinol, azelaic acid, salicylic acid, glycolic acid, or a combination thereof; The corticosteroid is hydrocortisone, triamcinolone, or a combination thereof; and The antiparasitic agent is ivermectin.

47. The combination of corticosterone-17α-propionate with one or more second anti-acne agents according to any one of claims 30 to 46, wherein the acne is mild, moderate or severe acne vulgaris.

48. The combination of corticosterone-17α-propionate as described in claim 47 with one or more second anti-acne agents, wherein the acne vulgaris is facial acne vulgaris.