Compositions, methods and systems for the treatment of cutaneous disorders

Abstract

To provide compositions, methods, and systems for treating skin conditions, ailments, or diseases, such as skin warts.SOLUTION: Provided is a system for delivering a cantharidin formulation to a subject, including: a reservoir 302 including a cavity containing the cantharidin formulation, wherein the reservoir has a volume of about 10 milliliters (mL) or less, and wherein the reservoir is compressible to induce a pressure increase in the reservoir to a pressure greater than about 1 atmosphere (atm); an applicator unit 303 including an adapter and an applicator tip 304, wherein the applicator tip includes an opening and a channel in fluid communication with the reservoir, and wherein the applicator tip includes an applicator unit that transfers the cantharidin formulation from the reservoir to an exterior of the applicator tip.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] cross reference This application is a joint venture with U.S. Provisional Patent Application No. 61 / 868,525, filed August 21, 2013. This provisional patent application claims priority to the specification, which is incorporated herein by reference. It is assumed that. [Background technology]

[0002] Warts are small superficial skin growths caused by a viral infection and found on the hands or feet. The most common type of wart is called verruca vulgaris, which is caused by the human papillomavirus (HPV). It can be caused by several different strains of HPV. It can affect most parts of the body. In some cases, these warts may be called common warts; however, when on the feet, They are called plantar warts, and when they are on the genitals, they are called genital warts or condylomata. Other superficial viral conditions, such as molluscum contagiosum, resemble warts but are caused by a different virus. These virus-mediated skin growths are unsightly and can lead to cancerous transformation and There may also be a significant risk of infection and transmission, so their elimination is desirable. Other superficial hyperproliferative disorders resemble warts but are caused by non-viral mechanisms. These include, for example, seborrheic keratosis, actinic keratosis, and porokeratosis.

[0003] Several treatments are used to remove warts and related diseases. These treatments include These include cryotherapy; surgical curettage; laser treatment; and irritants such as salicylic acid and zinc oxide. acids such as nitric acid and squaric acid, imiquimod, 2,4-dinitrochlorobenzene, and and Candida antigens, as well as bleomycin, podophyllotoxin, and These include chemotherapy drugs such as 5-fluorouracil. Many of these therapies are painful and While other therapies can leave unsightly scars and / or require daily application. However, perhaps most of the trouble comes from the fact that many of these skin disorders are multi-stage. The small molecule cantharidin has been shown to be effective in treating these The present invention can be used to successfully treat a variety of skin disorders. Summary of the Invention [Means for solving the problem]

[0004] The present disclosure relates to formulations, devices, systems, methods, and compositions for treating skin conditions, such as warts. The present disclosure provides a kit comprising a cantharidin compound for treating warts and other skin conditions. The cantharidin preparation contains cantharidin, which is an intraepidermal foaming agent. The cantharidin formulations of the present disclosure exhibit high single application efficacy, lack of scarring, and mild pain. It may have many advantages over conventional therapies, including improved pain profile. Advantages of the cantharidin formulations herein over other cantharidin formulations include highly volatile Removal of toxic and corrosive solvents, improved safety, and ease of delivery compared to common plastics. The compatibility of the solvents used in the previously described cantharidin preparations Due to the nature of the medium, the application of cantharidin is limited to glass vessels with several limitations. The devices provided herein are commercially available for the treatment of warts and other topical indications. It can be used to precisely apply the lysine formulation.

[0005] An embodiment of the present disclosure provides a method for administering a cannula to a subject, the method comprising: administering a cannula to a subject; The present invention provides a system for delivering a cantharidin formulation, the reservoir containing the cantharidin formulation. The reservoir may include a cavity for receiving the liquid. The reservoir may be about 10 milliliters (mL) or less. The reservoir may have a volume of greater than about 1.0 atmosphere (atm). The applicator unit can be compressible to induce a pressure rise in the applicator. The applicator tip may include an adapter and an applicator tip. , the aperture and / or the channel in fluid communication with the reservoir. The applicator tip transfers the cantharidin formulation from the reservoir to the exterior of the applicator tip. The applicator unit may be configured to cover the applicator tip. The applicator unit may include a transparent cap configured to The transparent cap may include a barrier over the portion. The transparent cap may be configured to puncture the barrier. The adapter may include a piercing device for affixing the adapter to the threaded end of the reservoir. The opening of the applicator tip has a diameter of 5 mm or less. The agent may contain at least about 0.001% (w / v) cantharidin. In some cases, the cantharidin preparation contains at least about 0.01%, 0.1%, or 1% cantharidin. Cantharidin formulations contain 1% (w / v) or more of excipients. The reservoir may have a volume of about 10 mL or less. Cantharidin, cantharidic acid, norcantharidin, or The subject may be diagnosed with a skin disease. The reservoir may have a threaded end at one end.

[0006] Another aspect of the present disclosure is a method for treating cantharidin comprising administering to a patient a cantharidin formulation and an applicator device. The present invention provides a system for delivering a cantharidin formulation comprising an excipient. The applicator device may be configured to deliver the cantharidin formulation. Cantharidin preparations contain at least about 0.001% (w / v) cantharidin. In some cases, the cantharidin preparation contains at least about 0.01%, 0.1%, or 1 % of cantharidin. Cantharidin preparations contain 1% (w / v) or more of excipients. The applicator device may include an applicator unit and one or more The system may include a plurality of reservoirs. Each reservoir may be connected to an applicator unit and a flow channel. The reservoir may include one or more cavities that are in fluid communication with one another. The reservoir may include a screw cap on the end. The reservoir may have a volume of 5 mL or less. The reservoir is compressible to induce a pressure increase in the reservoir above approximately 1.0 atmosphere. The applicator unit may include an applicator tip. The applicator tip may include an internal opening and / or internal fluid communication with the reservoir. The applicator tip may include a channel from the reservoir to the applicator. It can be configured to transfer the cantharidin formulation to the exterior of the chip.

[0007] Another aspect of the present disclosure is a method for treating a vascular endoscopic infection comprising: an applicator unit and one or more reservoirs. The present invention provides an applicator device for delivering a cantharidin formulation to a subject. The cantharidin formulation can be delivered to a subject. Each of the plurality of reservoirs includes one or more reservoirs in fluid communication with the applicator unit. At least one of the cavities may contain a cantharidin formulation. The reservoir may include a threaded end at one end. The reservoir may have a volume of 5 mL or less. The reservoir may be pressurized to a pressure greater than about 1.0 atmosphere. The applicator may be compressible to induce a pressure increase in the reservoir. The unit may include an applicator tip. The applicator may include an opening and The applicator may include an internal channel in fluid communication with the reservoir. The tip is adapted to transfer the cantharidin formulation from the reservoir to the exterior of the applicator tip. The adapter can be adapted to interface with the applicator tip. ,The internal channel is directed from the applicator tip through the adapter to the reservoir. The applicator unit includes a transparent cap configured to cover the applicator tip. The applicator unit may include a barrier over the opening. , the transparent cap may include a piercing device configured to pierce the barrier. The adapter can be fixed to the threaded end of the reservoir. The openings may have a diameter of about 5 mm or less. The cantharidin formulation comprises at least It may contain about 0.001% (w / v) cantharidin. Cantharidin preparations contain at least about 0.01%, 0.1%, or 1% cantharidin. Cantharidin formulations may contain about 1% (w / v) or more of excipients. The reservoir may have a volume of about 1 mL or less. The agent may contain up to about 5% (w / v) cantharidin.

[0008] Another aspect of the present disclosure is an applicator including a reservoir and an applicator unit. By preparing the device and delivering a cantharidin formulation from a reservoir to a subject. The present invention provides a method for delivering a cantharidin formulation to a subject, the reservoir comprising: The applicator unit may contain a fluid reservoir containing the talizin formulation. The cantharidin formulation may contain at least about 0.001% ( In some cases, the cantharidin formulation may contain cantharidin (w / v). and may contain at least about 0.01%, 0.1%, or 1% cantharidin. Cantharidin preparations may contain about 1% (w / v) or more of excipients. The body may have been diagnosed with a skin disorder. Skin disorders can cause epidermal warts. The epithelial warts may be removed from the subject within two weeks of delivery of the cantharidin formulation.

[0009] Another aspect of the present disclosure is an applicator including a reservoir and an applicator unit. The device is used to administer a cantharidin preparation to a subject, thereby treating epithelial warts in the subject. The present invention provides a method for treating molluscum contagiosum, or other skin diseases. The applicator unit may contain a reservoir and a fluid The cantharidin preparation contains at least about 0.001% (w / v) cantharidin. In some cases, the cantharidin formulation may contain at least It may contain about 0.01%, 0.1%, or 1% cantharidin. The pharmaceutical formulation may contain about 1% (w / v) or more of an excipient. The antarizine formulation may be cleared from the subject within two weeks of delivery.

[0010] Another aspect of the present disclosure provides a kit for administering a cantharidin formulation to a subject. The kit may comprise a plurality of separately packaged, individually dispensable liquid or gel forms. In some instances, the dosage unit can be a delivery device or a delivery system. In some cases, the dosage unit is in a packaging unit (e.g., an ampoule). ) inside.

[0011] In some circumstances, the dosage unit contains a cantharidin preparation in an amount of about 0.1 mL to about 10 mL. The cantharidin formulation may contain at least about 0.001% cantharidin. In some cases, the cantharidin formulation contains at least about 0.01%, 0.1%, or 1% cantharidin. The kit may contain active dosage units of The dosage unit containing the cantharidin preparation can be used to administer each of the above. The kit may be therapeutically effective in treating epithelial warts or other lesions in a subject. The packaging unit may contain three dosages containing the cantharidin formulation. The unit reduces the volume of epidermal warts or other lesions by at least about 50% over a period of about 7 days. This can be therapeutically effective.

[0012] Another aspect of the present disclosure provides instructions for optimal treatment schedules. Various doses of squalene, skin pre-treatment, frequency and amount of application to the skin, and post-application skin care methods The time that cantharidin is left in contact with the skin has not been well documented by other investigators. As evidenced by the lack of detailed investigation and variability in peer-reviewed publications, The method of the present invention is directed to the treatment of warts, verrucae, and psoriasis with cantharidin preparations. This allows for optimally effective treatment of molluscum, and / or other skin disorders.

[0013] Another embodiment of the present disclosure is a capsule having at least one cavity containing a cantharidin formulation. A system for delivering a cantharidin formulation to a subject, the system comprising a reservoir for receiving the cantharidin formulation. wherein the reservoir has a volume of about 10 milliliters (mL) or less. and the reservoir induces a pressure rise in the reservoir to a pressure greater than about 1 atmosphere (atm). The system further comprises an adapter that is compressible for and an applicator unit which may include an applicator tip. and wherein the applicator tip has openings and / or channels in fluid communication with the reservoir. and the applicator tip comprises a reservoir from the applicator tip. The cantharidin formulation can be configured to deliver the cantharidin formulation to the exterior of the device.

[0014] In some circumstances, the applicator unit may have a transparent cap that covers the applicator tip. In other circumstances, the applicator unit may include a barrier over the opening. The transparent cap can include a piercing device for piercing a hole in the barrier. The opening in the applicator tip may have a diameter of 5 millimeters (mm) or less. Cut.

[0015] Cantharidin formulations contain at least about 0.001% (w / v) cantharidin. In some cases, the cantharidin preparation may contain at least about 0.01%, 0.1 %, or 1% cantharidin. Cantharidin formulations may further contain 1 % (w / v) or more of excipients. Cantharidin formulations may further contain flavorings. and / or coloring agents.

[0016] In some circumstances, the reservoir may have a volume of about 10 mL or less and may be The cantharidin preparation contains 5% (w / v) or less of cantharidin, cantharidic acid, norcantharidin, The reservoir may contain a combination of naphthalene, naphthalene, or parathonin. The adapter may have a threaded or snap-on cap. The reservoir can be secured to a nap-on cap. The reservoir is stored at a pressure of less than about 10 atmospheres. The pressure can be made compressible to induce a pressure increase in the bar.

[0017] Another embodiment of the present disclosure is a composition comprising at least about 0.001% (w / v) cantharidin and an excipient. The subject may include a reservoir containing a cantharidin formulation that may have a cantharidin formulation. A system for delivering a cantharidin formulation to a subject is provided. The system further comprises a lysate. The apparatus may include an applicator unit in fluid communication with the server, the applicator unit being The unit is capable of delivering a volume of about 10 milliliters (mL) or less of the cantharidin formulation. can.

[0018] Cantharidin preparations contain at least about 0.01%, 0.1%, 0.5%, or 1% cantharidin. The cantharidin formulation may further contain about 0.001% (w / w) cantharidin. v) may contain 0.01%, 0.1%, or 1% or more of excipients.

[0019] In some situations, the reservoir may include a threaded or snap-on cap on one end. (ii) having a volume of about 5 mL or less; and / or (iii) ) compressible to induce a pressure increase in the reservoir to a pressure greater than about 1.0 atmosphere. can be done.

[0020] The applicator unit includes an opening and an internal channel in fluid communication with the reservoir. The applicator tip may include an applicator tip that can be attached to the applicator tip, the applicator tip comprising: The cantharidin formulation can be transferred from the reservoir to the exterior of the applicator tip.

[0021] Another aspect of the present disclosure is one or more gypsum laths each including one or more cavities. and a reservoir of a cantharidin formulation for delivering the cantharidin formulation to a subject. A thermometer device, at least one of the one or more cavities being made of cantharidin. The applicator device further comprises one or The applicator unit may include an applicator unit in fluid communication with the plurality of reservoirs. A Cater unit contains approximately 10 milliliters (mL) or less of cantharidin per use. The formulation can be controllably delivered to the subject.

[0022] In some situations, the reservoir may include a threaded or snap-on cap on one end. (ii) having a volume of about 5 mL or less; and / or (iii) ) compressible to induce a pressure rise in the reservoir above about 1.0 atmosphere. The applicator unit has an internal channel in fluid communication with an orifice and a reservoir. The applicator tip may include an applicator tip that may include a The cantharidin formulation is adapted to transfer from the reservoir to the exterior of the applicator tip. It is possible.

[0023] In some circumstances, the applicator device further includes an adapter that interfaces with the applicator tip. The adapter may include an internal channel extending from the applicator tip through the adapter. The applicator unit is attached to the reservoir so that it covers the applicator tip. The applicator unit may include a transparent cap that may be configured to: A barrier can be included over the opening, and the transparent cap can be configured to puncture the barrier. The adapter may include a piercing device that can be fastened to the threaded end of the reservoir. The opening of the applicator tip may have a diameter of about 5 mm or less. This can be done.

[0024] In some circumstances, the cantharidin preparation contains at least about 0.001% (w / v) cantharidin. Cantharidin formulations may contain at least about 0.01%, 0.1%, or 1% cantharidin. Cantharidin formulations can further include about 1% (w The reservoir may contain one or more excipients (1 mL / v). The reservoir may have a volume of about 1 mL or less. and the cantharidin preparation may contain about 5% (w / v) or less of cantharidin. can.

[0025] Another aspect of the present disclosure is a method for administering a cantharidin formulation to a subject, comprising: (ii) a channel in fluid communication with the reservoir. and providing an applicator device comprising an applicator unit including a reservoir. and delivering the cantharidin formulation to the subject through the channel from the .

[0026] Cantharidin formulations contain at least about 0.001% (w / v) cantharidin. In some cases, the cantharidin preparation may contain at least about 0.01%, 0.1 %, or 1% cantharidin. The cantharidin formulation may further contain about The subject may contain 1% (w / v) or more of excipients. The skin disease may be referred to as epithelial warts. Epithelial warts are The antarizine formulation may be cleared from the subject within two weeks of delivery.

[0027] In some circumstances, application (or delivery) is limited to a volume of about 10 milliliters (mL) or less. The application can include delivering about 5 mL or less of the cantharidin formulation. The application may include delivering about 4 mL or less of the cantharidin formulation. The application may include delivering about 3 mL or less of the cantharidin formulation. The application may include delivering about 2 mL or less of the cantharidin formulation. The application can include delivering about 1 mL or less of the cantharidin formulation. .

[0028] Another aspect of the present disclosure is a method for treating epidermal warts (or other skin conditions) in a subject. a reservoir containing a cantharidin formulation; and a fluid The applicator device includes an applicator unit that is connected to the applicator unit to apply the canthus to the subject. The method includes controllably administering a lysine formulation.

[0029] In some circumstances, the cantharidin preparation contains at least about 0.001% (w / v) cantharidin. In some cases, the cantharidin formulation may contain at least about 0. It may contain .01%, 0.1%, or 1% cantharidin. The formulation may further contain about 1% (w / v) or more of an excipient. After delivery of the cantharidin formulation, it may be removed from the subject within two weeks.

[0030] In some circumstances, the cantharidin formulation may be administered in a time period of about 30 seconds or less. The cantharidin formulation can be administered in a time period of about 20 seconds or less. The cantharidin formulation can be administered within a time period of about 5 seconds or less. can be administered.

[0031] In some circumstances, cantharidin preparations are administered in doses of about 10 milliliters (mL) or less of cantharidin. In other circumstances, the cantharidin preparation may be administered in a volume of about 5 mL or less. The following cantharidin formulations can be administered in their respective volumes:

[0032] Another aspect of the present disclosure is a method for producing a plurality of separately packaged, individually dispensable liquid or A kit for administering a cantharidin formulation to a subject, comprising a dosage unit in gel form. Thus, the dosage unit can be present in a packaging unit, and the dosage unit can be Each kit contains a cantharidin preparation in an amount of about 0.01 mL to 10 mL. Cantharidin preparations should contain at least about 0.001% (w / v) cantharidin. In some cases, the cantharidin preparation may contain at least about 0.01%, 0.1% , or 1% cantharidin.

[0033] In some circumstances, the kit may further include instructional materials for administration of the cantharidin preparation. This educational material may enable subjects to self-administer cantharidin preparations. The instructional material may be for treating epithelial warts in a subject. The kit may include at least The cantharidin formulation may also contain three packaging units. The present invention relates to a method for the removal of epithelial warts from a subject within two weeks of delivery of a dosage unit containing the formulation. It can become something like that.

[0034] Another aspect of the present disclosure is to administer at least about 0.001% (w / v) cantharidin to a subject. a flavoring agent capable of inducing a bitter taste upon ingestion of the formulation by a subject, and The present invention provides a formulation containing a coloring agent capable of enabling detection. The formulation has a maximum of about 10 It may have a volume in milliliters (mL).

[0035] In some circumstances, cantharidin preparations contain at least about 0.001% cantharidin. The cantharidin formulation may have a concentration of at least about 0.01%, 0.1%, 0.5 %, or 1% cantharidin. Flavoring and / or coloring agents are The concentration can be up to about 1% (w / v). The volume should be about 5 mL or less. The formulation may have a Reynolds number of less than about 1500 at 25° C. The formulation may further include a gelling agent. The formulation may contain less than about 1% manganese or magnesium. The flavorings may have an ionic concentration of denatonium, amarogentin, geminate, Anti-pigmented sucrose, octaacetylsucrose, quercetin, brucine, and quasin The coloring agent may be selected from the group consisting of D&C Violet, Isosulfan Blue, Roux, methylene blue, methyl red, methyl orange, Congo red, alizarin yellow Rho, Bromocresol Green, and Gentian Violet. It is possible.

[0036] Another aspect of the present disclosure is a method for treating a skin condition (e.g., a wart) on the skin (or skin site) of a subject. The method of claim 1, further comprising the steps of: (i) administering at least about 0.001% (w / v) of Calcium phosphate; (ii) a flavor capable of inducing a bitter taste in a subject upon ingestion of the formulation by the subject. and a coloring agent that can enable visual detection of the formulation by a subject. and b) preparing a dermatological preparation containing or suspected of containing a dermatological disease. and providing a cantharidin preparation to the site. The preparation may be up to about 10 It may have a volume in milliliters (mL).

[0037] In some circumstances, cantharidin preparations contain at least about 0.001% cantharidin. The cantharidin formulation may have a concentration of at least about 0.01%, 0.1%, 0.5 %, or 1% cantharidin. Flavoring and / or coloring agents are The concentration can be up to about 1% (w / v). The volume should be about 5 mL or less. The formulation may have a Reynolds number of less than about 1500 at 25° C. The method may further include a gelling agent. The formulation may contain less than about 1% manganese or magnesium. The flavorings may have an ion concentration of denatonium, amarogentin, , gentiopicrin, octaacetylsucrose, quercetin, brucine, and quasi The coloring agent may be selected from the group consisting of D&C Violet, Isosulfur Methylene blue, methyl red, methyl orange, Congo red, alizarin Yellow, Bromocresol Green, and Gentian Violet. Skin diseases include warts, molluscum contagiosum, seborrheic keratosis, and actinic keratosis. The disease may be selected from the group consisting of:

[0038] Additional aspects and advantages of the present disclosure are set forth in the following detailed description of exemplary embodiments thereof. As will be readily apparent to those skilled in the art from the following detailed description, The invention is capable of other and different embodiments, and some details may be changed in various Modifications are possible in obvious respects, all of which do not depart from the present disclosure. The diagrams and descriptions should be regarded as illustrative in nature and not restrictive. isn't it.

[0039] Incorporation by Reference All publications, patents, and patent applications mentioned herein are incorporated by reference. to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated in this document. It is incorporated herein by reference.

[0040] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the invention and its advantages will be readily apparent from the following detailed description taken in conjunction with the accompanying drawings, in which: By reference to the following detailed description and the accompanying drawings (also referred to herein as "Figures"), This will be obtained. [Brief description of the drawings]

[0041] [Figure 1A-B] FIG. 2 is a schematic diagram of a reservoir for holding a cantharidin formulation, according to some embodiments of the present disclosure. [Figure 2A-C] 1 is a schematic diagram of an applicator unit according to some embodiments of the present disclosure. [Diagram 3] 1 illustrates an applicator device according to some embodiments of the present disclosure. [Figure 4A-B] FIG. 1 illustrates a kit according to some embodiments of the present disclosure. [Figure 5A-C] 1 is a schematic diagram of a treatment method according to some embodiments of the present disclosure. [Figure 6A-D] 6A and 6C are line drawings and 6B and 6D are three-dimensional (3D) drawings of an applicator device according to some embodiments of the present disclosure. The applicator unit is either connected to a sealing mechanism (FIGS. 6A-6B) or separate from the sealing mechanism (FIGS. 6C-6D). [Figure 7A-B] FIG. 7A is a line drawing of an applicator device according to some embodiments of the present disclosure, and FIG. 7B is a 3D rendering of an applicator device according to some embodiments of the present disclosure. [Figure 8] 1A-1D are line drawings and 3D renderings of an applicator device having a removable cap with vent holes, according to some embodiments of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0042] While various embodiments of the present invention have been shown and described herein, such embodiments It is provided by way of example only and will be apparent to those skilled in the art. Configurations and substitutions may occur to those skilled in the art without departing from the invention. Various alternatives to the embodiments of the invention described herein may be used in practicing the invention. It should be understood that

[0043] As used herein, the term "treatment" or "treating" generally refers to Beneficial effects, including but not limited to therapeutic and / or prophylactic effects, A therapeutic effect refers to the treatment of skin disorders or diseases such as warts. The therapeutic effect refers to the eradication or amelioration of the underlying disorder being treated, such as bronchitis. Improvements were observed in patients, even though they may still be suffering from the underlying disorder. The goal is to achieve a state of health that is markedly improved by the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder, such as the Treatment can include diagnosis of a health condition, such as a wart.

[0044] As used herein, the term "cantharidin" generally refers to a compound of the structure: or derivatives thereof having similar activity in inhibiting protein phosphatases. Compounds in which the nucleus is replaced by boron can also be considered cantharidins. Compounds with carbon isotopes can also be considered cantharidins (e.g., C 14 ). different Compounds with different proportions of oxygen isotopes can also be considered cantharidin (e.g., O 17 ). Compounds with different ratios of hydrogen isotopes can also be considered as cantharidin ( H3 ). Compounds that contain different proportions of isotopes of carbon, oxygen, and hydrogen, or combinations thereof. can also be considered as cantharidin. Cantharidin is a compound that is composed of one or more unstable radioactive Cantharidin does not contain one or more unstable radioactive elements. Cantharidin may include a pharma- ceutically acceptable salt. Cantharidin may include It may not include a pharma- ceutically acceptable salt. [ka]

[0045] Non-limiting examples of cantharidin derivatives include cantharidic acid, norcantharidin, paracantharidin, These include nin, endothal, fostriecin, and okadaic acid. (See above.) Other substituted or unsubstituted compounds with exo,exo-diphenols or exo,exo-diphenol-containing species. Other chemical species which can be metabolized to or absorbed into can also be considered "cantharidin". Other compounds that function as inhibitors of protein phosphatases 1, 2A, 4, or 5 Cantharidin preparations can be considered as "cantharidin alone". or one or more excipients in addition to one or more other chemical species. Cut. [ka]

[0046] Non-limiting examples of substituted exo,exo-diphenols include 2,3-trimethylene anhydride. 5,6-Dehydroanhydride;endo-5-methyl;mono-4-chloro Anilide;endo-5-carboxy;5,6-dehydro;2-bromo;endo-5- Hydroxymethyl is an example.

[0047] Cantharidin is an active ingredient in insecticides including, but not limited to, the Spanish fly beetle (S panish fly beetle, false blister beetle blister beetle, cardinal beetle e), soldier beetle, Chinese blister beetle (Chinese blister beetle), or a combination of these by one or more blister beetles, including The amount of cantharidin produced per blister beetle is about 0.1, 0 .2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2 The blister pack may be about 0.5, 3, 3.5, 4, 4.5, 5, 5.5, or about 6 mg. The amount of cantharidin produced per liter is approximately 0.1, 0.2, 0.3, 0.4, 0. 5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4. It may be more than 5, 5, 5.5, 6 mg or more. The amount of cantharidin produced per day is approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0. 6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, It may be less than 5.5, 6 mg, or less. Cantharidin is produced biosynthetically. In some cases, cantharidin, norcantharidin, cantharidimide (cantharidin, norcantharidimide) aridimide, or norcantharimide The biosynthesis of derivatives can provide a similar therapeutic effect to the user or patient. Cantharidin can be produced completely synthetically or semi-synthetically, for example using natural raw materials. It is possible.

[0048] As used herein, the term "excipient" generally refers to an inactive ingredient as part of a formulation. Excipients refer to ingredients. Examples of excipients include, but are not limited to, colorants, flavorings, binders, skins, etc. These include emollients, fillers, lubricants, antioxidants, skin penetration enhancers, and preservatives. In some cases, the excipients are lactose, dextrose, sucrose, sorbitol, malate, etc. Gluconitol, starch, gum arabic, calcium phosphate, alginate, tragacanth , gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose The liquid may be selected from the group consisting of ethylcellulose, sterile water, syrup, and methylcellulose. In the form, the excipients can be salicylic acid and / or podophyllotoxin.

[0049] As used herein, the term "user" refers generally to a person who administers a cantharidin preparation to himself or herself. or an individual using the delivery device or system to administer to another individual, such as a subject. Point to the body.

[0050] As used herein, the term "subject" refers generally to a subject who has been diagnosed with a disease or refers to an individual suspected of having a disease (e.g., a skin disease) who is under treatment. The body may be under the care of another individual, or may be administered by oneself or a health care provider ( by another individual, such as a physician, practitioner, paramedic, nurse, or caregiver The subject may be an asymptomatic individual or a patient. In some cases, the subject may be a symptomatic individual, such as a person who has been diagnosed with a skin disease. There are times when this happens.

[0051] As used herein, the term "about" means plus or minus (+ / - ) Specify within the range of 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%. vinegar.

[0052] Cantharidin preparations Embodiments of the present disclosure are directed to treating skin conditions, diseases, and / or disorders, such as skin warts. The cantharidin formulation contains a therapeutically effective amount of cantharidin. It can include.

[0053] In some cases, the cantharidin formulation for local delivery comprises a cantharidin and a cantharidin-containing agent for administration to a subject. The amount of cantharidin in the cantharidin formulation is The amount of formulation may not be limited to a therapeutic amount. In some circumstances, e.g., Cantharidin doses far exceeding the nominal therapeutic dose to maximize cantharidin concentrations In other embodiments, it may be advantageous to include a quantification based on toxicity to the subject. It may be advantageous to limit the amount of lysine.

[0054] In some cases, the cantharidin formulation comprises at least about 50% (w / v) cantharidin. , at least about 10% (w / v) cantharidin, at least about 5% (w / v) cantharidin Lysine, at least about 1% (w / v); Cantharidin, at least about 0.75% (w / v ) cantharidin, at least about 0.5% (w / v) cantharidin, at least about 0. 1% (w / v) cantharidin, at least about 0.01% (w / v) cantharidin, or or at least about 0.001% (w / v) cantharidin. Gin is between about 0.001% and 50% by weight, or between about 1% and about 10% by weight, Or it can be present in an amount between about 0.001% and 1% by weight. are approximately 0.001, 0.01, 0.1, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4. 5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, or about 15 grams per milliliter Cantharidin can be present in an amount of about 1, 1.5, 2, 2.5, 3, 3.5 , 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15g Cantharidin can be present in an amount of about 1000 mg / ml or more. , 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5 , 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, Present in amounts less than 13.5, 14, 14.5, 15 grams / ml or less This can be done.

[0055] Cantharidin preparations are available in concentrations of approximately 0.1 mg / mL, 0.2 mg / mL, 0.3 mg / mL, and 0. .4mg / mL, 0.5mg / mL, 0.6mg / mL, 0.7mg / mL, 0.8mg / mL, 0.9mg / mL, 1.0mg / mL, 1.1mg / mL, 1.2mg / mL, 1.3mg / mL, 1.4mg / mL, 1.5mg / mL, 1.6mg / mL, 1.7m g / mL、1.8mg / mL、1.9mg / mL、2.0mg / mL、2.1mg / mL 、2.2mg / mL、2.3mg / mL、2.4mg / mL、2.5mg / mL、2.6 mg / mL、2.7mg / mL、2.8mg / mL、2.9mg / mL、3.0mg / m L、3.1mg / mL、3.2mg / mL、3.3mg / mL、3.4mg / mL、3. 5mg / mL、3.6mg / mL、3.7mg / mL、3.8mg / mL、3.9mg / mL、4.0mg / mL、4.1mg / mL、4.2mg / mL、4.3mg / mL、4 .4mg / mL、4.5mg / mL、4.6mg / mL、4.7mg / mL、4.8mg / mL、4.9mg / mL、5.0mg / mL、5.1mg / mL、5.2mg / mL、 5.3mg / mL、5.4mg / mL、5.5mg / mL、5.6mg / mL、5.7m g / mL、5.8mg / mL、5.9mg / mL、6.0mg / mL、6.1mg / mL 、6.2mg / mL、6.3mg / mL、6.4mg / mL、6.5mg / mL、6.6 mg / mL、6.7mg / mL、6.8mg / mL、6.9mg / mL、7.0mg / m L、7.1mg / mL、7.2mg / mL、7.3mg / mL、7.4mg / mL、7. 5mg / mL、7.6mg / mL、7.7mg / mL、7.8mg / mL、7.9mg / mL、8.0mg / mL、8.1mg / mL、8.2mg / mL、8.3mg / mL、8 .4mg / mL、8.5mg / mL、8.6mg / mL、8.7mg / mL、8.8mg / mL、8.9mg / mL、9.0mg / mL、9.1mg / mL、9.2mg / mL、 9.3mg / mL、9.4mg / mL、9.5mg / mL、9.6mg / mL、9.7m g / mL, 9.8mg / mL, 9.9mg / mL, 10.0mg / mL, 10.1mg / mL, 10.2mg / mL, 10.3mg / mL, 10.4mg / mL, 10.5mg / mL, 10.6mg / mL, 10.7mg / mL, 10.8mg / mL, 10.9mg / mL, 11.0mg / mL, 11.1mg / mL, 11.2mg / mL, 11.3mg / mL, 11.4mg / mL, 11.5mg / mL, 11.6mg / mL, 11.7mg / mL, 11.8mg / mL, 11.9mg / mL, 12.0mg / mL, 12.1mg / mL, 12.2mg / mL, 12.3mg / mL, 12.4mg / mL, 12.5mg / mL, 12.6mg / mL, 12.7mg / mL, 12.8mg / mL, 12.9mg / mL, 13.0mg / mL, 13.1mg / mL, 13.2mg / mL, 13.3mg / mL, 13.4mg / mL, 13.5mg / mL, 13.6mg / mL, 13.7mg / mL, 13.8mg / mL, 13.9mg / mL, 14.0mg / mL, 14.1mg / mL, 14.2mg / mL, 14.3mg / mL, 14.4mg / mL, 14.5mg / mL, 14.6mg / mL, 14.7mg / mL, 14.8mg / mL, 14.9mg / mL, 15.0mg / mL, 15.5mg / mL, 16.0mg / mL, 16.5mg / mL, 17.0mg / mL, 17.5mg / mL, 18.0mg / mL, 18.5mg / mL, 19.0mg / mL, 19.5mg / mL, or 20.0mg / mL cant Cantharidin concentration (milligrams (mg) cantharidin / milliliter (mL) formulation) In some cases, the concentration of cantharidin ranges from 0.5 milligrams (mg) to 20 mg / kg. It is measured in milliliters (ml), or in amounts between 1 mg and 10 mg / ml.

[0056] Alternatively, the cantharidin preparation is at least about 0.1 mg / mL, 0.2 mg / mL , 0.3 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 0.6 mg / mL, 0.7 mg / mL, 0.8 mg / mL, 0.9 mg / mL, 1.0 mg / mL, 1.1 mg / m L, 1.2 mg / mL, 1.3 mg / mL, 1.4 mg / mL, 1.5 mg / mL, 1. 6 mg / mL, 1.7 mg / mL, 1.8 mg / mL, 1.9 mg / mL, 2.0 mg / mL, 2.1 mg / mL, 2.2 mg / mL, 2.3 mg / mL, 2.4 mg / mL, 2 .5 mg / mL, 2.6 mg / mL, 2.7 mg / mL, 2.8 mg / mL, 2.9 mg / mL, 3.0 mg / mL, 3.1 mg / mL, 3.2 mg / mL, 3.3 mg / mL, 3.4 mg / mL, 3.5 mg / mL, 3.6 mg / mL, 3.7 mg / mL, 3.8 m g / mL, 3.9 mg / mL, 4.0 mg / mL, 4.1 mg / mL, 4.2 mg / mL , 4.3 mg / mL, 4.4 mg / mL, 4.5 mg / mL, 4.6 mg / mL, 4.7 mg / mL, 4.8 mg / mL, 4.9 mg / mL, 5.0 mg / mL, 5.1 mg / m L, 5.2 mg / mL, 5.3 mg / mL, 5.4 mg / mL, 5.5 mg / mL, 5. 6 mg / mL, 5.7 mg / mL, 5.8 mg / mL, 5.9 mg / mL, 6.0 mg / mL, 6.1 mg / mL, 6.2 mg / mL, 6.3 mg / mL, 6.4 mg / mL, 6 .5 mg / mL, 6.6 mg / mL, 6.7 mg / mL, 6.8 mg / mL, 6.9 mg / mL, 7.0 mg / mL, 7.1 mg / mL, 7.2 mg / mL, 7.3 mg / mL, 7.4 mg / mL, 7.5 mg / mL, 7.6 mg / mL, 7.7 mg / mL, 7.8 m g / mL、7.9mg / mL、8.0mg / mL、8.1mg / mL、8.2mg / mL 、8.3mg / mL、8.4mg / mL、8.5mg / mL、8.6mg / mL、8.7 mg / mL、8.8mg / mL、8.9mg / mL、9.0mg / mL、9.1mg / m L、9.2mg / mL、9.3mg / mL、9.4mg / mL、9.5mg / mL、9. 6mg / mL、9.7mg / mL、9.8mg / mL、9.9mg / mL、10.0mg / mL、10.1mg / mL、10.2mg / mL、10.3mg / mL、10.4mg / mL、10.5mg / mL、10.6mg / mL、10.7mg / mL、10.8mg / mL、10.9mg / mL、11.0mg / mL、11.1mg / mL、11.2mg / mL、11.3mg / mL、11.4mg / mL、11.5mg / mL、11.6mg / mL、11.7mg / mL、11.8mg / mL、11.9mg / mL、12.0mg / mL、12.1mg / mL、12.2mg / mL、12.3mg / mL、12.4mg / mL、12.5mg / mL、12.6mg / mL、12.7mg / mL、12.8mg / mL、12.9mg / mL、13.0mg / mL、13.1mg / mL、13.2mg / mL、13.3mg / mL、13.4mg / mL、13.5mg / mL、13.6mg / mL、13.7mg / mL、13.8mg / mL、13.9mg / mL、14.0mg / mL、14.1mg / mL、14.2mg / mL、14.3mg / mL、14.4mg / mL、14.5mg / mL、14.6mg / mL、14.7mg / mL、14.8mg / mL、14.9mg / mL、15.0mg / mL、15.5mg / mL、16.0mg / mL、16.5mg / mL、17.0mg / mL、17.5mg / mL、18.0mg / mL, 18.5mg / mL, 19.0mg / mL, 19.5mg / mL, or 20. 0 mg / mL cantharidin concentration (mg cantharidin / mL formulation) In some situations, cantharidin preparations are available in concentrations of about 40 mg / mL, 30 mg / mL, 20 mg / mL, Cantharidin concentrations of 0.01 mg / mL, 10 mg / mL, 5 mg / mL, or 1 mg / mL or less It is possible to have.

[0057] The cantharidin used in the formulation is sufficient to induce a therapeutic effect without toxicity. The purity of cantharidin used in the preparation is 50% to 100%. The purity of the cantharidin used can be between about 70%, 80%, 90%. %, 95%, 98%, 99%, or 99.9% or greater.

[0058] In some embodiments, cantharidin is provided in the form of a solid, semi-solid, gel, or gelatin suitable for local or topical administration. or liquid form preparations, e.g., gels suitable for local or topical administration, water-soluble gels, creams, lotions, suspensions, solutions, foams, powders, slurries, ointments, solutions, Oil, capsule, tablet, paste, suppository, spray, emulsion, saline, dimethyl sulfide The high density carriers can be formulated into DMSO-based solutions. In contrast, solvent / solution formulations may provide areas that are exposed to This can provide a more immediate exposure of the cantharidin to the selected area.

[0059] The cantharidin formulation may also be administered in a suitable solid, semi-solid, gel, or liquid phase carrier or excipient. These can include, for example, glyceryl ethers, which enhance the penetration of therapeutic molecules across the stratum corneum permeability barrier of the skin. Such carriers and excipients are compounds that can mediate or modify the delivery of the drug. Examples of agents include, but are not limited to, disruptive agents (e.g., bases, acids, oxidizing agents, ), crosslinking agents (e.g., formalin or formaldehyde), wetting agents (e.g., urea), Glycols (e.g., propylene glycol), alcohols (e.g., ethanol) , fatty acids (e.g., oleic acid), surfactants (e.g., isopropyl myristate and and sodium lauryl sulfate), pyrrolidones, glycerol monolaurate, sulfoxy Cides, terpenes (e.g., menthol), amines, amides, alkanes, alkane Alcohols, water, calcium carbonate, calcium phosphate, various sugars, starches, cellulose Examples of suitable polymers include cellulose derivatives, gelatin, and polyethylene glycols.

[0060] Cantharidin preparations include, but are not limited to, salicylic acid, trichloroacetic acid The solution may contain an acid or a combination of acids, including hydrochloric acid, formic acid, squaric acid, or nitric acid. Cantharidin preparations can contain podophyllotoxin. The formulation may contain zinc oxide. Cantharidin formulations include imiquimod (2,4- Containing immunotherapeutic agents such as dinitrochlorobenzene and / or Candida antigens Cantharidin preparations are used in combination with bleomycin, podophyllotoxin, and / or Cantharidin preparations can contain chemotherapeutic agents such as fluorouracil. It may contain an oxidizing agent such as hydrogen chloride.

[0061] The cantharidin formulation ensures good solubilization and / or dissolution of cantharidin, and A solubilizing agent may be included to minimize precipitation of cantharidin in the formulation. The agent is used to increase the solubility of cantharidin and / or to provide a stable or uniform solution. It may be added to maintain the composition as a liquid, emulsion, or dispersion.

[0062] Examples of suitable solubilizing agents include, but are not limited to, one or more of the following: A number of alcohols and polyols, such as acetone, ethanol, isopropyl alcohol, Isoopropanol, butanol, benzyl alcohol, ethylene glycol, propylene glycol Licorice, butanediols and their isomers, glycerol, pentaerythritol, Sorbitol, mannitol, transcutol, dimethyl isosorbide, polyethylene Glycol, Polypropylene Glycol, Polyvinyl Alcohol, Hydroxypropyl Methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and and other cellulose derivatives, cyclodextrin and cyclodextrin derivatives; about 20 Ethers of polyethylene glycols having an average molecular weight of 0 to about 6000, such as tetraethyl ethers. tetrahydrofurfuryl alcohol PEG ether (glycofurol) or methoxy PE G; Amides and other nitrogen-containing compounds, e.g., 2-pyrrolidone, 2-piperidone, ε -Caprolactam, N-alkylpyrrolidone, N-hydroxyalkylpyrrolidone, N- Alkyl piperidone, N-caprolactam, dimethylacetamide, and polyvinyl piperidone rolidone; esters, for example, ethyl propionate, tributyl citrate, aryl citrate Cetyl triethyl, acetyl tributyl citrate, triethyl citrate, ethyl oleate ethyl caprylate, ethyl butyrate, triacetin, propylene glycol monoacetate propylene glycol diacetate, ε-caprolactone and its isomers, δ- lactone and its isomers, β-butyrolactone and its isomers; and other possible Solubilizers, such as dimethylacetamide, dimethylisosorbide, N-methylpyrrolidone , monooctanoin, diethylene glycol monoethyl ether, and water.

[0063] Mixtures of solubilizers may also be used. Examples include, but are not limited to: However, triacetin, triethyl citrate, ethyl oleate, ethyl caprylate, dimethicone ethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinyl Hydroxypropyl methylcellulose, Hydroxypropyl cyclodex Torin, polyethylene glycol 200-100, glycofurol, transcutol , propylene glycol, dimethyl isosorbide, sorbitol, glycerol, triethanolamine Cetin, Ethyl Alcohol, PEG-400, Glycofurol, and Propylene Glycosides Examples include

[0064] The amount of a given solubilizer may be limited by biotolerability. In some circumstances, e.g., distillation or Excess solubilizing agent may be removed using conventional techniques, such as evaporation or drying, prior to administering the composition to the subject. In order to maximize drug concentration by removing excess solubilizer, it is often necessary to include amounts of solubilizers that exceed the biotolerable limits. Solubilizers, if present, may be beneficial in reducing the total weight of cantharidin and other excipients. On a weight basis, 10%, 25%, 50%, 100%, or about 200% by weight % by weight. Alternatively, a substantially small amount of a solubilizer may also be present, e.g. , 5%, 2%, 1% by weight or even less of the cantharidin formulation. In some examples, the solubilizer may be present in an amount of from about 1% by weight to about 100% by weight of the cantharidin formulation. %, or from about 5% to about 25% by weight. , cantharidin preparations contain less than the biotolerable amount.

[0065] The cantharidin formulation may include one or more coating agents. The coating agent may be absent from the composition. Some examples of coating agents include but are not limited to the following: Examples of suitable materials include, but are not limited to, nitrocellulose, nitrocellulose derivatives, polyvinylpyrrolidone, and polyvinylpyrrolidone. Lidone, hydroxypropyl methylcellulose, carboxymethylcellulose, and others The coating agent can be dissolved in a solvent. The coating agent can be dissolved in one or more solvents. Cantharidin Preparations The solvent may include one or more solvents. The solvents may be ethanol, acetone, methanol, etc. alcohol, isopropyl alcohol, butyl alcohol, pentanol, ether, water, or In some cases, the solvent is not diethyl ether or The solvent may be acetone. Cantharidin formulations may contain one or The cantharidin formulation may contain one or more plasticizers. Examples of such plasticizers include, but are not limited to, camphor, Cantharidin preparations include one or more water-borne Cantharidin formulations may contain one or more water-borne polymerization agents. Examples of water-borne polymerization agents include, but are not limited to, 2-octyl Examples of cyanoacrylate include ethyl cyanoacrylate and butyl cyanoacrylate. In some cases, the inclusion of a film-forming agent, a plasticizer, a water-borne polymerization agent, or a combination thereof may improve viscosity, flexibility, and the like. The final cantharidin formulation has excellent solubility, durability, strength, toughness, or film-forming properties. can be.

[0066] In some cases, the coating agent or agents comprise between about 0.1% and about 10% by weight / volume. In some cases, the coating agent or agents are present in the cantharidin formulation at a concentration of about It is present in cantharidin preparations at a concentration of 1.25% weight / volume. In some cases, The coating agent or agents are present in cantharidin preparations at a weight / volume concentration of about 2%. In some cases, the coating agent or agents may be present in an amount of about 0.001, 0.01, 0.1, 1, 1.25 , 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.7 5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10 , 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15 , 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20 , present in cantharidin preparations at 21, 22, 23, 24, or 25% weight / volume concentration In some cases, the coating agent or agents may be present in an amount of about 0.001, 0.01, 0.1, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3 .5, 3.75, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 1 4.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 1 Weight / volume concentrations of 9.5, 20, 21, 22, 23, 24, or more than 25% In some cases, the coating agent or agents are present in cantharidin formulations at about 0. 001, 0.01, 0.1, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5, 6, 6.5, 7 , 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5 , 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5 , 18, 18.5, 19, 19.5, 20, 21, 22, 23, 24, 25% or less, is present in cantharidin preparations at weight / volume concentrations less than this.

[0067] In some cases, the one or more solvents are present in a weight / volume concentration of between about 10% and about 95%. In some cases, the solvent or solvents are present in the cantharidin formulation at about 13% In some cases, one or more The solvent is present in the cantharidin formulation at a weight / volume concentration of about 87%. The one or more solvents may be about 10, 15, 20, 25, 30, 35, 40, 45, 50, Available in weight / volume concentrations of 55, 60, 65, 70, 75, 80, 85, 90, or 95%. In some cases, the one or more solvents are present in the antarizine formulation at about 10, 15 , 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, Present in cantharidin preparations at weight / volume concentrations of greater than 85, 90, 95%, or more In some cases, the one or more solvents may be at least about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 120, 130, 140, 150, 160, Less than 5, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95% or less weight / volume concentration in cantharidin formulations.

[0068] When applied to the skin, the cantharidin solution may be applied for, for example, 1 second, 10 seconds, 30 seconds, 1 minute, 5 In one example, the drying time of the cantharidin formulation may be as short as 10 minutes or less. The assay used to assess the effect of 4 microliters on a 3 mm diameter circle of skin. In one example, a cantharidin preparation is applied evenly to the skin using a pipette. The gin formulation dries in less than 2 minutes or 30 seconds.

[0069] In some cases, the one or more plasticizers may be present in an amount between about 0.001% and about 5% by weight / volume. In some cases, plasticizers are present in cantharidin formulations at volumetric concentrations. In some cases, one or more plasticizers are present in a weight / volume concentration of about 5% or less. In some cases, the plasticizer is present in the cantharidin formulation at about 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.5, 2, in cantharidin preparations at weight / volume concentrations of 2.5, 3, 3.5, 4, 4.5, or 5% In some cases, the plasticizer is present at about 0.001, 0.01, 0.1, 0.15, 0 .2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0 .65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.5, 2, 2 .5, 3, 3.5, 4, 4.5, 5% or more weight / volume concentration In some cases, the plasticizer is present in the gin formulation at about 0.001, 0.01, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55 ,0.6,0.65,0.7,0.75,0.8,0.85,0.9,0.95,1,1 .5, 2, 2.5, 3, 3.5, 4, 4.5, 5% or less weight / volume concentration It is present in cantharidin preparations at high concentrations.

[0070] The cantharidin preparation may contain a dye. The cantharidin preparation may contain one or more The cantharidin preparation may contain no dye. Acridines, anthraquinones, and aryls used in concentrations sufficient to control the color of the formulation. Fluorine, azo, diazonium, nitro, phthalocyanine, quinoneimine, tetrazolium , thiazole, xanthene, acid, basic, direct, mordant, natural, or solvent dyes It can be said that:

[0071] The dyes are acridine orange, acriflavine, anthracene blue SWR, and alizarin. , Alizarin Red S (Mordant Red 3), Nuclear Fast Red, Aurami Chromoxane cyanin R, Pararo Zaniline, Rosaniline, Magenta II, New Fuchsine, Methyl Violet 2B, Chill Violet 6B, Crystal Violet, Hoffman Violet, Methyl Glycol ethyl green, acid violet 19, fast red B , Fast Blue B, diazonium chloride, diazonium acid sulfate, diazonium alkyl diazonium sulfate, diazonium chloride, diazonium fulborate borate), or diazonium benzenesulfonate, picric acid, alcyanine Roux, Luxol Fast Blue, Toluidine Blue O, Thionine, Azure A, Azur Color B, Azure C, Neutral Red, Safranin O, Gallocyanine, Galamin Blue -, iodonitrotetrazolium, nitroblue tetrazolium, thioflavin T, pyrrolidin Pyronine Y, Pyronine B, Rhodamine B, Maltese Yellow (Acid Yellow 24), Oshin Y (Acid Red 87), Biebrich Scarlet (Acid Red 66), Sulfonated Pararosaniline (Basic Red 9), Pararosaniline (Basic Red Red 9), Methylene Blue (Basic Blue 9), Congo Red (Direct Red 2 8), Ellie Garnet (Direct Red 10), Sirius Red F3B (Direct Red 80), Hematein (Natural Black 1), Chromoxane Cyanine R (Moda Mordant Blue 3), Celestine Blue B (Mordant Blue 14), Kermes (Natural Red 3), Carmine (Natural Red 3), Lac (Natural Red 25), Hema Tein (Natural Black 1), Saffron (Natural Yellow 6), Sudan III ( Solvent Red 23), Sudan IV (Solvent Red 24), Oil Red O (Sol Vent Red 27), Sudan Black B (Solvent Black 3), or other It can be said that:

[0072] The dye may comprise a phase-change dye. The dye may comprise two or more phase-change dyes. The dyes do not have to include phase change dyes. Some examples of phase change dyes include, but are not limited to: D&C Orange, Neozapon Red 4 92, Orasol Red G, Direct Brilliant Pink B, Direct Red 3BL, Supranol Brilliant Red 3 BW, Lemon Yellow 6G, Light Fast 3G, Aizen Spiron Yellow C-GN H, bemachrome yellow GD sub ), Cartasol Brilliant Yellow 4GF, Cibanone Yellow ellow)2G, Orasol Black RLI, Orasol Black CN, SabiNil Black (savinyl black)RLSN, Pyrazole Black BG, Morphst Black Morfast Black 101, Diazol Black black) RN, thermoplast blue 670 , Orasol Blue GN, Savinyl Blue blue)GLS, luxol fast blue(luxol fast blue)M BSN, Sevron Blue 5GMF, Bass Acid Blue asacid blue) 750, keyplast blue , Neozapon Black X51, Classic Solvent Black (classic solvent black) 7, Sudan Blue 670, Dan Yellow 146, Sudan Red 462, Neptune Red Base red base) NB543, Neopen blue (FF-4) 012, Fatsol Black BR, Molton Molplasma Zenta (Morton Morplas Magenta) 36, or other Some examples include:

[0073] The dyes may include those that function as indicator dyes. The dyes may contain two or more indicator dyes. The dye may include no indicator dye. Some examples of indicator dyes include: Examples include, but are not limited to, D&C Violet, Isosulfan Blue, Methylene Blue, Roux, Methyl Red, Methyl Orange, Congo Red, Alizarin Yellow, Bromocre Examples include Zoll Green, Gentian Violet, or others. The dyes may be one or more phase change dyes and one or more indicator dyes, or The indicator dye may be used in sufficient concentration to detect the cantharidin preparation. The boundaries of the treated area can be defined.

[0074] Cantharidin preparations can contain fluorophores. Cantharidin preparations are divided into two groups: Cantharidin preparations may contain one or more fluorophores. Fluorophores may be used in combination with minerals (e.g., magnesium, calcium, zinc, Copper, iron, lead, cadmium, mercury, nickel, cobalt, aluminum, or lanthanides The fluorophore can indicate the presence of magnesium. Fluorophores can indicate the presence of intracellular magnesium. The formulation may contain a fluorophore that fluoresces under ultraviolet light. Examples of fluorescent indicators that fluoresce under mag- Examples of cantharidin preparations include indo-1 and mag-fura-2. It may contain a fluorophore that fluoresces under visible light. Examples of fluorescent indicators that emit light include, but are not limited to, magnesium green. Examples of suitable antibodies include mag-fluo-4 and mag-fluo-4.

[0075] Cantharidin formulations may contain one or more fluorophores, one or more dyes, or In some cases, one or more fluorophores may be included. The dye or dyes may be at least about 0.00001, 0.00005, 0.0001, 0.0002, 0.0003, 0.0004, 0.0005, 0.0006, 0.000 7, 0.0008, 0.0009, 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0 .2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, or 10% In some cases, one or more of the cantharidin derivatives may be present in the cantharidin formulation in a weight / volume concentration. The fluorophore or dye or dyes may be present at concentrations of approximately 0.00001, 0.00005, 0. 0001, 0.0002, 0.0003, 0.0004, 0.0005, 0.0006, 0.0007, 0.0008, 0.0009, 0.001, 0.002, 0.003, 0 .004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 10 % or more in weight / volume concentrations in cantharidin preparations. In the example, the fluorophore or fluorophores or the dye or dyes are about 0.0000 1, 0.00005, 0.0001, 0.0002, 0.0003, 0.0004, 0. 0005, 0.0006, 0.0007, 0.0008, 0.0009, 0.001, 0 .002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008 , 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.0 7, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, Cantharidin preparations at weight / volume concentrations of 0.8, 0.9, 1, 10% or less In some cases, one or more fluorophores or one or more The pigment is present in cantharidin preparations at weight / volume concentrations between about 0.00001% and about 1%. In some cases, one or more fluorophores or one or more dyes are present. is present in cantharidin preparations at a weight / volume concentration of about 0.005%.

[0076] Cantharidin preparations may contain one or more aversive agents, such as bitter agents or oral deterrents. Bittering agents are an example of flavoring agents. Bittering agents or oral deterrents can be used to improve the oral stability of the formulation. Bittering or oral deterrent agents can be used to prevent or discourage ingestion. Prevent or prevent the patient from licking and / or ingesting the product before, during, or after application to the skin. Bittering agents or oral deterrents are limited to the following: Although not limited thereto, denatonium (e.g., denatonium benzoate, denatonium saccharide), amarogentin, gentiopicrin, octaacetylsucrose, kel Examples of bittering agents include benzoic acid denatonium, brucine, and quasine. Cantharidin can be added to the preparation.

[0077] The aversive agents were approximately 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, and 0.0 7, 0.08, 0.09, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5. 5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 , 15, 16, 17, 18, 19, or approximately 20 parts per million (ppm) In some cases, the aversive agent may be present in the formulation at about 0.01, 0.02 ,0.03,0.04,0.05,0.06,0.07,0.08,0.09,1,1. 5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, It is present in cantharidin preparations at concentrations above 20 ppm or higher. The aversive agents were approximately 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, and 0. 07, 0.08, 0.09, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5 .5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 1 Concentrations of less than 4, 15, 16, 17, 18, 19, and 20 ppm or less In some cases, the aversive agent is present in a concentration of about 0.01 ppm to about 20 ppm. Cantharidin is present in preparations at concentrations between

[0078] In some cases, the aversive agent is present in a weight / volume concentration of about 0.00001% to about 1% of the total liquid volume. In some cases, the aversive agent is present in cantharidin preparations at about 0.000001%. , 0.00001%, 0.0001%, 0.001%, 0.01%, 0.1%, 1%, or Cantharidin is present in formulations at a concentration of about 2% weight / volume. is approximately 0.000001%, 0.00001%, 0.0001%, 0.001%, 0.0 Cantharidin preparations at weight / volume concentrations of 1%, 0.1%, 1%, >2%, or more In some cases, the aversive agent is present in an amount of about 0.000001%, 0.00001%, 0.0001%, 0.001%, 0.01%, 0.1%, 1%, 2% or less The aversive agent is present in cantharidin preparations at a weight / volume concentration of approximately 0.0006%. The aversive agent may be present in the cantharidin formulation at a volume / volume concentration of about 0.000. It can be present in cantharidin formulations at a weight / volume concentration of 1% to about 0.001%. .

[0079] Cantharidin formulations contain one or more pharma- ceutically acceptable additives or excipients. Such additives or excipients include, but are not limited to, Adhesives, defoamers, buffers, polymers, antioxidants, preservatives, chelating agents, viscosity regulators, tonicity agents, flavoring agents, coloring agents, odorants, opacifying agents, suspending agents, binders, fillers, plasticizers, lubricants, and and mixtures thereof.

[0080] In some cases, the cantharidin formulation has a molecular weight of about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, approx. 3.5, approx. 3.6, approx. 3.7, approx. 3.8, approx. 3.9, approx. 4.0, approx. 4.1, approx. 4.2, approx. 4.3, approx. 4.4, approx. 4.5, approx. 4.6, approx. 4.7, approx. 4.8, approx. 4.9, approx. 5.0, approx. 5.1, approx. 5.2, approx. 5.3, approx. 5.4, approx. 5.5, approx. 5.6, approx. 5.7, approx. 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4 7.4, approx. 7.5, approx. 7.6, approx. 7.7, approx. 7.8, approx. 7.9, approx. 8.0, approx. 8.1, approx. 8.2, approx. 8.3, approx. 8.4, approx. 8.5, approx. 8.6, approx. 8.7, approx. 8.8, approx. 8.9, approx. 9.0, approx. 9.1, approx. 9.2, approx. 9.3, approx. 9.4, approx. 9.5, approx. 9.6, approx. 9.7, approx. 9.8, approx. 9.9, approx. 10.0, approx. 10.1, approx. 10.2, approx. 10.3, approx. 10.4, approx. 10.5, approx. 10.6, approx. 10.7, approx. 10.8, approx. 10.9, approx. 11.0, approx. 11.1 , 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11 Alternatively, the cantharidin formulation may have a pH of about 12.0 or about 15. , at least about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6 , approx. 3.7, approx. 3.8, approx. 3.9, approx. 4.0, approx. 4.1, approx. 4.2, approx. 4.3, approx. 4.4 , 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2 , 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0 , 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8 , 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6 , 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4 , approx. 8.5, approx. 8.6, approx. 8.7, approx. 8.8, approx. 8.9, approx. 9.0, approx. 9.1, approx. 9.2 , about 9.3, about 9.4, about 9.5, about 9.6, about 9.7, about 9.8, about 9.9, about 10. 0, approx. 10.1, approx. 10.2, approx. 10.3, approx. 10.4, approx. 10.5, approx. 10.6, approx. 1 0.7, approx. 10.8, approx. 10.9, approx. 11.0, approx. 11.1, approx. 11.2, approx. 11.3, About 11.4, about 11.5, about 11.6, about 11.7, about 11.8, about 11.9, or about It may have a pH of 12.0.

[0081] The cantharidin formulation may be in liquid form. The liquid form is preferably in liquid form, since it is resistant to fluid flow. The liquid form may have a molecular weight of about 4000, 3000, 2000, 1500, 1000, Can have a Reynolds number of less than 500, 400, 300, 200, or 100 The liquid form is available in concentrations of about 0.1, 1, 5, 10, 25, 50, 75, 100, 250, 500 , 1000, 1250, 1500, or about 2000 Reynolds numbers. The liquid form is available in approximately 2000, 1750, 1500, 1250, 1000, 500, and 40 0, 300, 250, 200, 150, 100, 75, 50, 25, 10, 5, 1, 0. It may have a Reynolds number of less than 1, or even less.

[0082] In some cases, the cantharidin formulation has a pH of about 4000, 3000, 2000, or 500 at a temperature of about 25° C. 000, 1500, 1000, 500, 400, 300, 200, or less than 100 The liquid form can have an Inols number of about 1, 5, 10, 2, or 3 at a temperature of about 25° C. 5, 50, 75, 100, 250, 500, 1000, 1250, 1500, 1750, or a Reynolds number of about 2000. The liquid form may have a temperature of about 25° C. , about 2000, 1750, 1500, 1250, 1000, 500, 400, 300, 2 50, 200, 150, 100, 75, 50, 25, 10, 5, less than 1 or less The Reynolds number may be

[0083] The liquid form may have a high viscosity. To prevent substantial spills, drips, flows, spills, leaks, or aerosolization. The liquid form may be viscous, as it adheres to the patient's or user's site of administration. The liquid form may be substantially viscous so that it remains in place after administration by the patient or user. The cantharidin preparation flows, splashes, drips, runs, pours, or leaks from the area It may be substantially sticky so that there is no possibility of

[0084] One or more gelling agents, e.g., dextran, nitrocellulose, hydroxypropyl propyl cellulose, ethyl cellulose, or other to increase viscosity It can be added in liquid form. The viscosity of the liquid form at ambient conditions (e.g., 25°C) is , about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 , 130, 140, 150, 160, 170, 180, 190, 200, 210, 220 , 230, 240, 250, 260, 270, 280, 290, 300, 310, 320 , 330, 340, 350, 360, 370, 380, 390, 400, 410, 420 , 430, 440, 450, 460, 470, 480, 490, 500, 600, 700 , 800, 900, 1,000, 2,000, 3,000, 4,000, 5,000, 6 ,000, 7,000, 8,000, 9,000, 10,000, 15,000, 20, 000, 25,000, 30,000, 35,000, 40,000, 45,000, 5 0,000, 55,000, 60,000, 65,000, 70,000, 75,000 , 80,000, 90,000, 100,000, 110,000, 120,000, 1 30,000, 140,000, 150,000, 200,000, 250,000, 5 00,000, 1,000,000, 1,500,000, or approximately 2,000,000 The viscosity of the liquid form at ambient conditions may be about 10, 20, or 30 centipoise. 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140 , 150, 160, 170, 180, 190, 200, 210, 220, 230, 240 , 250, 260, 270, 280, 290, 300, 310, 320, 330, 340 , 350, 360, 370, 380, 390, 400, 410, 420, 430, 440 , 450, 460, 470, 480, 490, 500, 600, 700, 800, 900 , 1,000, 2,000, 3,000, 4,000, 5,000, 6,000, 7,0 00, 8,000, 9,000, 10,000, 15,000, 20,000, 25,0 00, 30,000, 35,000, 40,000, 45,000, 50,000, 55 ,000, 60,000, 65,000, 70,000, 75,000, 80,000, 90,000, 100,000, 110,000, 120,000, 130,000, 1 40,000, 150,000, 200,000, 250,000, 500,000, 1 ,000,000, 1,500,000, 2,000,000 centipoise or more The viscosity of the liquid form at ambient conditions can be about 10, 20 or more. , 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 14 0, 150, 160, 170, 180, 190, 200, 210, 220, 230, 24 0, 250, 260, 270, 280, 290, 300, 310, 320, 330, 34 0, 350, 360, 370, 380, 390, 400, 410, 420, 430, 44 0, 450, 460, 470, 480, 490, 500, 600, 700, 800, 90 0, 1,000, 2,000, 3,000, 4,000, 5,000, 6,000, 7, 000, 8,000, 9,000, 10,000, 15,000, 20,000, 25, 000, 30,000, 35,000, 40,000, 45,000, 50,000, 5 5,000, 60,000, 65,000, 70,000, 75,000, 80,000 , 90,000, 100,000, 110,000, 120,000, 130,000, 140,000, 150,000, 200,000, 250,000, 500,000, Less than 1,000,000, 1,500,000, or 2,000,000 centipoise, In some cases, the viscosity may be about 10 to 10,000 centipoise. Between Az.

[0085] Cantharidin preparations contain magnesium ions (Mg 2+ ) or magnesium ions The composition may be free of or have reduced levels of reagents that can The formulation contains manganese ions (Mn 2+)or does not contain any reagent that can generate manganese ions. Cantharidin preparations can have low or reduced levels of magnesium. Generate magnesium ions and manganese ions or magnesium ions and manganese ions. The composition may be free of or have reduced levels of the agent that can be used to obtain Mg. 2+ ion and / or Mn 2+ Ions interact with cantharidin to increase its activity (e.g., therapeutic Cantharidin preparations are available at approximately 30, 20, 15, 10, 5, It may contain 4, 3, 2, or about 0.1% magnesium ion. The formulation may contain about 30, 20, 15, 10, 5, 4, 3, 2, 1, 0.1%, or less Cantharidin preparations contain between about 0.1 and 1% magnesium ions. Cantharidin preparations contain less than about 0.1% magnesium ions. Cantharidin preparations contain between about 5 and 0.1% magnesium ions. Cantharidin preparations may contain magnesium ions. The cantharidin preparation may not contain magnesium ions. For the same reason, it does not contain manganese, calcium, sodium, and potassium ions. or reduced levels thereof. For example, the cantharidin preparation may have a cantharidin concentration of about 30 , 20, 15, 10, 5, 4, 3, 2, or about 0.1% manganese ions. Cantharidin preparations are available in concentrations of approximately 30, 20, 15, 10, 5, 4, 3, 2, 1, and 0.1. % or less of manganese ions. Cantharidin preparations contain about 0. Cantharidin preparations contain between about 0.1% and 1% manganese ions. Cantharidin preparations contain between about 5 and 0.1% manganese ions. The cantharidin formulation may include manganese ions. The cantharidin preparation may be free of manganese ions.

[0086] The cantharidin formulation of the present disclosure may contain other topical agents. Non-limiting examples include local anesthetics, local analgesics, antimicrobials, microbicides, Disinfectants, antiseptics, antibiotics, bactericides, bacteriostatic agents, cleaning agents, anti-inflammatory agents, anti-infective agents (e.g., germicides, Antibacterial, Antifungal, Antiviral, Antifungal, Antiseptic, Antifungal, Antifungal, Antifungal, Antiviral, Antifung ...fungal, Antifungal, Antifungal, Antifungal, Antifungal, Antifungal, These include fungicides, antipsoriatics, anthelmintics, and steroid hormones such as corticosteroids. Examples of topical agents include, but are not limited to, Altavax. bax (retapamulin), Amebiv (alefacept), Avita Gel, Bactroban cream, benzamycin, erythromycin, Botox, Cefazolin, Dextrose, Chloraprep (Chlorhexidine gluconate), Clindamycin phosphate, Condilox (co ndylox) (pokofilox), desonate ate) (Desonide), Differin (Adapalene), Dynabac , Elidel, Erivage (vismodegib), Estrostep, Norethindrone Acetate, Ethinyl Estradiol, Extina (Keto Conazole), Fiacea (Azelaic Acid), Finevin in), Firazyr (Icatibant), Gralise (Gabapentin), Horizant (Gabapentin Enacarbil (Gabapentin enacarbil), hydrochloric acid, hydrogen peroxide, Iamin, Invants Invanz, Iontocaine, Ivy Block Block), Klaron (Sodium Sulfacetamide), Lamicin (terbinafine hydrochloride), LaViv (azficel )-T), Lustra, Luxiq (betamethasone valerate) Mentax (Butenafine HCl), MetroLotion n), Minoxidil, Noritate, Nitric Acid, Omnicef ef), Orthotri-Cyclee, Norgestimate, Pica to) (ingenol mebutate), Propecia, Protopic (tacrolimus), Condylox (podophotoxin) , Regranex (becaplermin), Renova, tratinoin (trat inoin), Salagen, Sandalwood Oil, Salicylic Acid, Sklice (Ibel mectin), Stelara (ustokinumab), Sulfamilo Sylatron (peginterferon alpha-2b), Tazo Tazorac, Tefraro (ceftaroline fosamil), Thalomid, Triclosan bromoacetate, Taigacil (tigecycline), Veltin (clindamycin phosphate) Isin, tretinoin, Veregen (green tea sinc catechin atechin), Verdeso (Desonide), Vivative (Terra Vancin), Vibativ (telavancin), Xyzal (levoctyridine (levoct irizine dihydrochloride), Yervoy (ipilimumab), These include Luboraf (vemurafenib) and Zyclara (imiquimod). Can be obtained.

[0087] Cantharidin preparations may have the following ingredients:

[0088] [Table 1]

[0089] [Table 2]

[0090] [Table 3]

[0091] [Table 4]

[0092] [Table 5]

[0093] [Table 6]

[0094] [Table 7]

[0095] The cantharidin solution described in Table 7 can be prepared in the following manner: Add ethanol and nitrocellulose to a glass vial to form a mixture. Add a PTFE-coated stir bar and mix the mixture. Castor oil and camphor are added to the mixture to form a homogeneous sticky mixture. A 1% ethanolic solution of denatonium benzoate can be added to the glass. A 1% solution of gentian violet in ethanol can be added to the glass vial. Cantharidin powder with purity of over 95% can be added to glass vials. The mixture can be mixed to homogeneity. The cellulose is added and the mixture is allowed to mix until completely gelled and homogenous.

[0096] Applicator Devices and Kits Another aspect of the present disclosure is an applicator device, system, and method for treating warts. An applicator device for treating warts or other skin conditions is provided according to the present disclosure. In some cases, the cantharidin formulation can be delivered in a cantharidin formulation. The applicator device for the method comprises at least one reservoir containing a cantharidin formulation. or a chamber in fluid communication with a reservoir for delivering a cantharidin formulation to a subject. and an application unit for

[0097] The system for delivering the cantharidin formulation comprises a cantharidin formulation and a cantharidin-containing and an applicator device configured to deliver the agent. The formulation may include excipients. Cantharidin formulations may be prepared as described above or elsewhere herein. In some examples, cantharidin may have any of the concentrations or compositions described above. The formulation contains at least about 0.001% (w / v) cantharidin. Cantharidin preparations contain at least about 0.01%, 0.1%, or 1% cantharidin. In another example, the cantharidin formulation contains at least about 5% (w / v) of the excipient. Contains agents.

[0098] The applicator device includes an applicator unit and a one or more reservoirs including one or more cavities in fluid communication with the The individual reservoirs can have a variety of shapes. The reservoir may be of circular, triangular, square, rectangular, pentagonal, hexagonal cross section or any of its It may have any partial shape or combination. In some examples, the reservoir is cylindrical. In some cases, the reservoir is spherical or elliptical.

[0099] A system for delivering a cantharidin formulation to a subject contains a cantharidin formulation The reservoir may include a cavity. The reservoir may have a volume of about 10 mL or less. The reservoir can have a pressure of more than about 1.0 atmosphere. Alternatively, a portion of the reservoir may be compressible to induce The syringe may be compressible (e.g., a plunger or The system consists of an applicator that includes an adapter and an applicator tip. The applicator tip may include a nozzle unit. The applicator tip may include an opening and a connection with the reservoir. The applicator tip includes a channel for fluid communication. The applicator tip delivers fluid from the reservoir to an area of ​​the subject (e.g., The cantharidin formulation is adapted to be transferred to the exterior of the applicator tip, e.g., to a skin site. It can be achieved.

[0100] In some cases, the applicator unit is configured to cover the applicator tip. The transparent cap may be made of a plastic (e.g., a thermoplastic). The application unit can be made from any polymeric material. The transparent cap may include a piercing device configured to pierce the barrier. The device may include a device (e.g., a needle).

[0101] The transparent cap may have ventilation holes. For example, FIG. 8 shows applicator tip 803. The filter 802 is contained in a plastic reservoir 801. 1 illustrates an application device having an ampoule with an applicator tip 80. 3 is enclosed in a removable transparent cap 804 having one or more ventilation holes 805. The transparent cap does not need to have any ventilation holes. The transparent cap may have a vent hole so that the solvent can be released (e.g., evaporated). A portion of the solvent can be discharged from the applicator unit. The liquid formulation may be released from the applicator unit by means of a transparent cap so that the liquid formulation is retained within the applicator unit. The cap may have ventilation holes so that the liquid formulation can be retained but the solvent can be released. The transparent cap may have a vent hole. When released from the unit, the liquid formulation may completely or partially solidify. Liquid formulations may solidify completely. Liquid formulations may solidify partially. High Solvents with vapor pressures of up to 100% may be used in the formulations described. In such cases, the solvent may be The solvent may not have a high vapor pressure. The agent can be rapidly released (e.g., evaporated) from the vented applicator unit. In some cases, once the liquid formulation has solidified it cannot be reused.

[0102] In some cases, the adapter is secured to the threaded end of the reservoir, e.g., by a notch. The adapter uses a locking mechanism, such as two flexible prongs, to secure the adapter to the threaded port. It can be fixed.

[0103] The applicator tip openings are approximately 20 millimeters (mm), 18 mm, and 16 mm. , 14mm, 12mm, 10mm, 9mm, 8mm, 7mm, 6mm, 5mm, 4mm, 3mm, 2mm, 1mm, 0.9mm, 0.8mm, 0.7mm, 0.6mm, 0.5m may have a diameter of 0.4 mm, 0.3 mm, 0.2 mm, or 0.1 mm or less. In some circumstances, the size of the opening may vary depending on the amount of cantharidin from the applicator tip. It is adjustable to regulate the rate of release of the formulation.

[0104] The system can include a cantharidin formulation. In some non-limiting examples, cantharidin The formulation may contain at least about 0.001% (w / v) cantharidin. In some cases, the cantharidin preparation contains at least about 0.01%, 0.1%, or 1 % cantharidin. In some non-limiting examples, the cantharidin formulation may contain: It may contain 5% (w / v) or more of an excipient. The preparation should contain 1% (w / v) or less of cantharidin, cantharidic acid, norcantharidin, or may include Parasonin in combination.

[0105] In some non-limiting examples, the reservoir may be about 50 mL, 40 mL, 30 mL, 20 mL, 1 Can have a volume of 0 mL, 5 mL, 1 mL, 0.5 mL, or less than 0.1 mL In some non-limiting examples, the reservoir may be located on or already attached to one end. It can have a screw cap or a snap-on cap. It may include ribs that allow it to be removably secured to the reservoir. The cap can seal the reservoir. In some circumstances, the seal can be an airtight seal. be.

[0106] The applicator may contain a glass ampoule holding the cantharidin preparation. The glass ampoules are designed to be broken or punctured to release the cantharidin preparation. In some cases, the glass ampoule can be broken into several pieces. In some cases, the outer plastic reservoir can be filled with cantharidin. The glass ampoule may be compressed to shatter, releasing the formulation. The ampoules are made of USPI type borosilicate glass, USPII type borosilicate glass, or US It is made of PIII type borosilicate glass. Alternatively, the applicator may be made of plastic or The ampoule may be made from a polymeric material such as rubber. The ampoules may be pierced or crushed to release the cantharidin preparation.

[0107] The applicator unit may include a filter. The applicator unit may have two or more filters. The filter can filter out aggregates, particles, material fragments, etc. The aggregates, particles, or material fragments from these include, but are not limited to, glass particles, It may be plastic particles, precipitates from the liquid formulation, or other aggregates. Before applying to the skin, use one or more cleaning agents to remove any agglomerates, particles, or material fragments. A number of filters may be included in the applicator unit to provide a barrier. One or more filters may be included in the applicator unit. Multiple filters can provide a barrier that can prevent further delivery of the formulation. The filter or filters provide a barrier to prevent further delivery of the solidified formulation. The filter may be made of plastic having one or more holes. or a mesh material (e.g., polyester or polyethylene). .

[0108] In some cases, the system for delivering the cantharidin formulation comprises the cantharidin formulation and and an applicator device. In some non-limiting examples, the cantharidin formulation is The applicator device may include an excipient and is configured to deliver the cantharidin formulation. In some non-limiting examples, the cantharidin formulation has at least about 0.001 % (w / v) of cantharidin. In some non-limiting examples, the composition may comprise cantharidin. The formulation may contain 5% (w / v) or more of an excipient.

[0109] In some cases, the applicator device includes an applicator unit and an applicator unit each having an applicator. one or more cavities in fluid communication with the locator unit. In some non-limiting examples, the reservoir can include a In some non-limiting examples, the reservoir may have a volume of 5 mL or less. In some non-limiting examples, the reservoir may have a reservoir pressure of greater than about 1.0 atmosphere. In some non-limiting examples, the bar can be compressible to induce a pressure increase. The applicator unit includes an aperture and an internal channel in fluid communication with the reservoir. In some non-limiting examples, the applicator tip can include: The cantharidin formulation is configured to be transferred from the reservoir to the exterior of the applicator tip. This can be done.

[0110] FIG. 1A illustrates an example of a reservoir that can hold a cantharidin formulation. The server 101 is attached to another module such as the applicator unit shown in FIG. The reservoir 101 may be equipped with a locking mechanism 102 that can lock the reservoir 101 in place. The upper part of the reservoir 101 may have a hollow screw port 103. Alternatively, the upper part of the reservoir 101 may have a different It may have a cap of any kind or no cap at all. The screw cap may further be equipped with a barrier 104. Alternatively, the hollow screw cap may have a barrier. The barrier 104 may be a foil barrier. 4 may be made of other materials such as natural polymers, synthetic polymers, and metals. The barrier 104 can keep the contents of the reservoir sterile. The barrier 104 may also have other useful functions. do.

[0111] The reservoirs are approximately 1.0, 1.1, 1.2, 1.3, 1.4, and 1. .5 atmosphere, 1.6 atmosphere, 1.7 atmosphere, 1.8 atmosphere, 1.9 atmosphere, 2.0 atmosphere, 3.0 atmosphere , 4.0 atm, 5.0 atm, 6.0 atm, 7.0 atm, 8.0 atm, 9.0 atm, 10 atm Inducing a pressure rise inside the reservoir exceeding 20, 30, or 40 atmospheres. To achieve this, the pressure applicator member (e.g., a plunger or The reservoir can hold approximately 1.0 atmosphere, 1.1 atmosphere, or 1.2 atmosphere. Pressure, 1.3 atm, 1.4 atm, 1.5 atm, 1.6 atm, 1.7 atm, 1.8 atm, 1. 9 atmospheres, 2.0 atmospheres, 3.0 atmospheres, 4.0 atmospheres, 5.0 atmospheres, 6.0 atmospheres, 7.0 atmospheres, Reserve pressure of 8.0, 9.0, 10, 20, 30, or 40 atmospheres or more The bar can be made compressible to induce a pressure rise inside the bar. The maximum pressure of the reservoir is about 100, 50, 40, 30, 20, and 1 0 atmospheres or increased by a factor of 5 atmospheres. In some cases, the reservoir is about 1 atmosphere to 2 atmospheres. Reservoir pressure can be set to 0 atm, 1 atm to 15 atm, 1 atm to 10 atm, or 1 atm to 5 atm. It is allowed to compress to induce a force rise.

[0112] In some cases, the reservoir is at about 1.0 atmosphere, 1.1 atmosphere, 1.2 atmosphere, or 1.3 atmosphere. , 1.4 atm, 1.5 atm, 1.6 atm, 1.7 atm, 1.8 atm, 1.9 atm, 2.0 Atmosphere, 3.0 Atmosphere, 4.0 Atmosphere, 5.0 Atmosphere, 6.0 Atmosphere, 7.0 Atmosphere, 8.0 Atmosphere, 9 Pressure inside the reservoir exceeds 0, 10, 20, 30 or 40 atmospheres. It may be compressible or include a pressure applicator member to induce the force. The reservoir is approximately 1.0 atmosphere or more, 1.1 atmosphere, 1.2 atmosphere, 1.3 atmosphere, 1.4 atmosphere. Pressure, 1.5 atm, 1.6 atm, 1.7 atm, 1.8 atm, 1.9 atm, 2.0 atm, 3. 0 atmospheres, 4.0 atmospheres, 5.0 atmospheres, 6.0 atmospheres, 7.0 atmospheres, 8.0 atmospheres, 9.0 atmospheres, Induce pressures inside the reservoir of 10, 20, 30, or even 40 atmospheres or more In some cases, the reservoir pressure can be increased to a maximum of about 1 00, 50, 40, 30, 20, 10, or 5 atmospheres. In some examples, the reservoir may be at about 1 atmosphere to 20 atmospheres, 1 atmosphere to 15 atmospheres, or 1 atmosphere to Compressible to induce reservoir pressures of 10 atmospheres, or 1 atmosphere to 5 atmospheres .

[0113] Alternatively, the device may deliver cantharidin solution from the end of the reservoir to the applicator tip. Contains a wicking material (e.g., polyester fiber) that can allow the movement of It is possible.

[0114] Alternatively, the device may be activated when a button is pressed or a trigger is pulled or a dial is turned. When rotated, it physically displaces a predetermined amount of cantharidin solution from the applicator tip. It may have a lever or a rotating arm.

[0115] FIG. 1B illustrates another example of a reservoir. Reservoir 105 is a reservoir 101 and The reservoir 105 may have a substantially different shape than the reservoir 101. They can have substantially different sizes.

[0116] The reservoir is about 0.1 mL to 100 mL, or about 0.1 mL to 50 mL, or about 1mL to 20mL, or about 0.1mL to 10mL, or about 0.5 to 5mL, or about The reservoir can have a volume of about 100 mL, about 50 mL, or about 100 mL. mL, approx. 10 mL, approx. 5 mL, approx. 3 mL, approx. 1 mL, approx. 0.5 mL, or approx. 0.1 mL It may have the following volumes:

[0117] The reservoir can have a primarily or substantially cylindrical or spherical shape. Alternatively, the reservoir can have a primarily or substantially rectangular shape. The reservoir can have one edge. Alternatively, the reservoir can have two or more edges. Additionally, the reservoir can have an irregular shape.

[0118] The reservoir may be at least partially or entirely made of a polymeric material (e.g., plastic The plastics used are not limited to the following: However, polypropanol, low density polyethylene, medium density polyethylene, high density polyethylene , or polytetrafluoroethylene, or some combination thereof. Alternatively, the reservoir may be at least partially or entirely made of a metallic material (e.g., The reservoir may be made of a material such as stainless steel or aluminum. is made from a polymeric material and the remainder of the reservoir is made from a metallic material.

[0119] The reservoir may be at least partially or entirely made of a polymeric material (e.g., plastic Alternatively, the reservoir may be at least partially or entirely made of Generally, the device may be made of a metallic material (e.g., stainless steel or aluminum). In the embodiment, a portion of the reservoir is made of a polymer material and the remainder of the reservoir is made of a metal material. It is made.

[0120] The reservoir of the present invention may comprise any of the elements, either alone or in combination, and / or It may include features described above or elsewhere herein.

[0121] FIG. 2A shows an applicator that can be used to deliver the cantharidin formulation. An example of an applicator unit 201 is shown in FIG. The applicator unit 201 can be used to apply and / or store a liquid. 1. A locking mechanism 202 that can be attached to other modules such as the reservoir shown in FIG. Alternatively, the applicator unit 201 may have a locking mechanism. The applicator unit 201 may have a hollow screw port 203. The hollow threaded port 203 fits over a complementary hollow threaded port, such as that of the reservoir shown in FIG. Alternatively, the applicator unit 201 can be attached to a different It may have a cap of some kind or no cap at all. The applicator unit 201 may have a barrier breaker 204. When the unit is attached to the reservoir, the barrier breaker creates a hole in the barrier. The barrier can be a foil barrier of the reservoir shown in FIG. 1A. The applicator unit does not have to have a barrier breaker. The applicator unit may have a seal 205 and may be attached to the reservoir. Once in place, the seal keeps the cantharidin formulation within the reservoir. The reservoir containing the gin formulation can be the reservoir shown in FIG. 1A. Alternatively, the applicator unit may not have a seal. 01 can have a hollow applicator tip 206. Once attached to the applicator unit, the cantharidin formulation is delivered through the hollow applicator tip. In addition, the hollow applicator tip allows the cantharidin formulation to flow. The applicator unit 201 is mounted in a removable carrier. The removable cap 207 may be transparent. The removable cap 207 can contain any leaking solution. The removable cap 207 may allow visualization of the cantharidin formulation prior to application. The removable cap 207 can be adapted for proper disposal. Alternatively, the applicator unit may not have a removable cap.

[0122] FIG. 2B shows an applicator that can be used to deliver the cantharidin formulation. Another example of the applicator unit 208 is shown in FIG. The porous applicator tip 209 can include cantharidin. This can allow for precise application of the solution.

[0123] FIG. 2C illustrates yet another example of an applicator unit. The applicator 210 may have a hollow applicator tip 211 having a porous end 212. A hollow applicator tip 211 having a porous end 212 is provided with a cantharidin dissolving agent. This can allow for precise application of the fluid.

[0124] 7A and 7B illustrate some examples of applicator units. The applicator unit is connected to an applicator tip 703 (e.g., a hollow, A reservoir 701 that can be attached to the The applicator tip can be surrounded by a removable cap 704. It is possible to do so.

[0125] The applicator tip is approximately 0.1 centimeters (cm) to 10 cm, or approximately 0. 1cm~5cm, or about 0.5cm~5cm, or about 0.5cm~3cm, or about It may have a length of 1 cm to 3 cm, or about 1 cm to 2 cm.

[0126] The applicator tip may include a channel. The channel may be a hollow interior channel. The channel may be in fluid communication with the reservoir. The formulation can flow through the channel.

[0127] The applicator tip can include an opening. The opening can be circular, triangular, square, or the like. Shape: rectangular, pentagonal, or hexagonal, or any subshape thereof; In one example, the opening is annular. The opening may be a channel or a flow channel. The cantharidin formulation can be connected to a reservoir (or channel) having the cantharidin formulation. The cantharidin preparation can flow out through the opening. The applicator tip can be soft or rough. Using a cutter tip, gently apply the cantharidin preparation to the skin to limit penetration. The drug may be applied by wiping the drug on the skin or abrading the skin during delivery to facilitate penetration into the skin. be.

[0128] The opening is about 0.1mm~20mm, about 0.1mm~10mm, about 0.1mm~5mm , may have a diameter of about 0.5 mm to 5 mm, or about 0.5 mm to 3 mm. The mouth is about 20 mm, about 10 mm, about 5 mm, about 1 mm, about 0.5 mm, or about 0.1 mm. It may have a diameter of less than or equal to mm.

[0129] The applicator unit of the present disclosure may include any of the following elements, either alone or in combination: and / or may include the features described above or elsewhere herein.

[0130] FIG. 3 illustrates an application that can be used to deliver a cantharidin formulation to a subject. 3 illustrates an example of an application device 301 for applying a cantharidin formulation to a skin. The applicator device 301 can deliver the drug to the patient. The reservoir 302 may include a control unit 303. The reservoir 302 may include a cantharidin formulation. The applicator unit 303 can include an applicator tip 304. It is possible to induce the outflow of the cantharidin preparation into the applicator unit 303. Pressure can be applied to the reservoir 302 to induce the cantharidin formulation. The agent can be applied and / or delivered through the applicator tip 304.

[0131] The applicator tip 304 may be a sealed hollow tip. The empty tip can be pierced by the seal piercing mechanism 305. 5 can be juxtaposed with the sealed hollow tip. Press down on the grip 306 to release the Apply pressure to the hole piercing mechanism 305 to pierce the seal on the applicator tip 304. It is possible.

[0132] The applicator device 301 may have a removable cap 307 . The removable cap 307 may be transparent. 7 can contain any solution that leaks out of the applicator device 301. The removable cap 307 can allow visualization of the solution. The removable cap 307 can be made suitable for disposal. The cap may be attached to the seal piercing mechanism 305. Alternatively, a removable cap may be attached to the seal piercing mechanism 305. The cap 307 does not have to be attached to the seal piercing mechanism 305 .

[0133] The applicator device of the present disclosure may include any of the elements, either alone or in combination, and and / or may include the features described above or elsewhere herein.

[0134] FIG. 4A illustrates an example of a kit for administering a cantharidin formulation to a subject. The kit 401 may include one or more packaging The packaging unit 402 can be composed of a separate package. The packaging units 402 can be individually removable. It is possible.

[0135] Each packaging unit 402 may include an applicator device 403 . The applicator device includes a reservoir 404 and an applicator unit 405. The reservoir 404 can contain a cantharidin formulation.

[0136] FIG. 4B illustrates another example of a kit. The kit 406 includes one or more packages. Each packaging unit 407 may include a plurality of packaging units 407. The reservoir 404 and one or more applicator units 405 may include The reservoir 404 can contain a cantharidin formulation.

[0137] Each packaging unit 402 contains multiple reservoirs 404 and an application Each packaging unit can include a cantharidin-based Each packaging unit may contain one dosage unit of the agent. Each packaging unit may contain two dosage units of the ginseng formulation. Each packaging unit may contain three dosage units of the intalizione formulation. Each packaging unit may contain four dosage units of the cantharidin formulation. Each package may contain 5 dosage units of the cantharidin formulation. A packing unit may contain six dosage units of the cantharidin formulation. The caging unit may contain six or more dosage units of the cantharidin formulation. do.

[0138] In some cases, the dosage units in each packaging unit range from about 0.1 mL to about 100 mL. In mL, 0.1mL-50mL, 0.1mL-10mL, or 0.5mL-5mL volumes In some cases, the dosage in each packaging unit may include cantharidin. Units are approximately 100mL, 50mL, 10mL, 5mL, 3mL, 1mL, 0.5mL, or or less than 0.1 mL of cantharidin.

[0139] The cantharidin preparation in each packaging unit contains at least about 50% (w / v), Approximately 10% (w / v), approximately 5% (w / v), approximately 1% (w / v), approximately 0.5% (w / v), approximately Cantharidin at 0.1% (w / v), approximately 0.01%, or approximately 0.001% (w / v) It can include.

[0140] The kit may contain one packaging unit. Alternatively, the kit may contain: At least 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 3 May contain 0, 40, 50, 60, 80, 100 or 200 packaging units. This can be done.

[0141] After delivery of a dosage unit of the cantharidin formulation to the subject, the epithelial wart or skin lesion is Within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 days After the dosage unit of the cantharidin formulation is delivered to the subject, the epithelial warts may be removed. The wart or skin lesion may be cleared from the subject within 1, 2, 3, 4, 5, or 6 weeks. After delivery of a dosage unit of the cantharidin formulation to the subject, the epithelial warts or skin lesions are The drug may be removed from the subject within 1, 2, or 3 months.

[0142] The kits of the present disclosure may comprise any of the elements, either alone or in combination, and / or as described above. Or it may include properties described elsewhere herein.

[0143] The kits provided herein can include instructional materials. The instructional materials can be used to assist a user in understanding the present disclosure. The present invention may include instructions enabling the application of the intariidine preparations, devices, and systems. The educational material may include a graphical format that can instruct a subject on the administration of the cantharidin preparation. The educational materials may include formulas and / or textual information. Educational materials may be provided, including different doses of cantharidin, cantharidin preparations, Pre-treatment of the skin of the subject to be treated, frequency and amount of application to the skin, before and / or after application How to care for the skin after the treatment and the amount of cantharidin to be left in contact with the skin Educational materials may include the use of cantharidin preparations to treat both warts, molluscum contagiosum, and / or verrucae. In some instances, the educational materials may include: The user interface (e.g., graphical user interface) of the subject's electronic device The information is provided on the

[0144] FIG. 6 shows an example of an antibody that can be used to deliver a cantharidin formulation of the present disclosure to a subject. 6 illustrates another example of an application device. The application device includes a reservoir 601 and The reservoir 601 may have a counterbalance and an applicator unit 602. The applicator unit 602 has a grip 605. The applicator tip 603 may be connected to a sealing mechanism 604 having a 6A-6B). Pressure on the grip 605 can break the sealing mechanism 604 (FIG. 6C-6D). In some cases, in one direction perpendicular to the applicator tip 603, Or apply pressure to the grip 605 with a twisting motion perpendicular to the applicator tip. This can break the sealing mechanism 604, allowing the cantharidin formulation to be released. .

[0145] Methods for Treating a Subject Another aspect of the present disclosure is a method for delivering a cantharidin formulation to a subject, the method comprising administering to said subject a cantharidin formulation to said subject, the cantharidin formulation comprising administering to said subject a cantharidin formulation to said subject or for use in treating skin conditions, diseases, and / or disorders, such as skin lesions. The methods for treating a subject include treating a skin condition, such as a wart, A cantharidin preparation is administered to a subject having or suspected of having a disease or disorder. Using the applicator device, system, or kit of the present disclosure for delivering It can include.

[0146] The disclosed method includes administering cantharidin to a user who delivers the cantharidin formulation to a subject or to himself or herself. The subject to which the lysine formulation is delivered is included.

[0147] The applicator device may include a reservoir and an applicator unit. The reservoir may contain a cantharidin formulation. The applicator unit may include The fluid reservoir may be in fluid communication with the reservoir.

[0148] The subject may have been diagnosed with a skin disorder. The skin disorder may be epidermal warts or other skin The applicator device may be used to treat epithelial warts or skin lesions. The cantharidin preparation can be delivered in a different manner. It is possible to remove epithelial warts or skin lesions from

[0149] 5A-5C show a method for treating a subject having or suspected of having a wart. In FIG. 5A, a subject 501 is treated by administration of a cantharidin formulation. In FIG. 5B, the patient has or is suspected of having a wart 502 that may be a cancer. An applicator device 503 including a bar 504 and an applicator unit 505 is used. The reservoir 504 contains cantharidin. The cantharidin formulation can be administered to the wart 502. As shown in FIG. 5C, administration of the cantharidin preparation resulted in the disappearance of warts 502 from the subject 501. can be removed.

[0150] The applicator device 503 is operated by the subject or another individual, such as a healthcare provider. In some cases, the applicator device 503 is placed in contact with or against the wart 502. is used in close proximity to the wart 502 or the skin adjacent to the wart. A cantharidin preparation is delivered to the area.

[0151] After the cantharidin preparation is delivered to the subject, the epithelial warts are 1, 2, 3, 4, 5, 6, Within 7, 8, 9, 10, 11, 12, 13, or 14 days, weeks, or months from the subject The cantharidin preparation may be administered at least once or twice a day, week, or month. , 3, 4, 5, 6, 7, 8, 9, or 10 times may be delivered to a subject.

[0152] The amount of cantharidin delivered to a subject in a single dose is about 0.001 mg to 100 mg. Approx. 0.1mg~50mg, approx. 0.1mg~10mg, approx. 0.5mg~10mg, approx. 0.5 The dose can be between about 1 mg and 5 mg, about 1 mg and 5 mg, or about 1 mg and 2 mg.

[0153] The cantharidin formulation delivered to the subject comprises at least about 0.001% (weight / volume), 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4% Cantharidin can be used in combination with other cantharidin preparations, such as 5%, 10%, 20%, 30%, 40%, or 50% cantharidin. In some cases, the cantharidin formulation delivered to the subject can be up to about 50% (w / w v) containing 40%, 30%, 20%, or 10%, or 1% cantharidin.

[0154] The cantharidin formulation delivered to the subject may be about 50% (w / v), about 20% (w / v), Approximately 10% (w / v), approximately 5% (w / v), approximately 1% (w / v), approximately 0.5% (w / v), or about 0.1% (w / v) or more of an excipient.

[0155] The delivery device or system may be administered in doses up to 0.00 lmg / day, 0.01 mg / day, or 0.1 mg / day, 0.2mg / day, 0.3mg / day, 0.4mg / day, 0.5mg / day, 0.6mg / day, 0.7mg / day, 0.8mg / day, 0.9mg / day, 1mg / day, 1.5mg / day , 2mg / day, 2.5mg / day, 3.0mg / day, 3.5mg / day, 4.0mg / day, 4 .5mg / day, 5.0mg / day, 5.5mg / day, 6.0mg / day, 6.5mg / day, 7 .0mg / day, 7.5mg / day, 8.0mg / day, 8.5mg / day, 9.0mg / day, 9 .5mg / day, 10.0mg / day, 11mg / day, 12mg / day, 13mg / day, 14mg g / day, 15 mg / day, 16 mg / day, 17 mg / day, 18 mg / day, 19 mg / day, or or 20 mg / day to deliver a cantharidin formulation to a subject. Alternatively, the delivery device or system may provide at least about 0.1 mg / day, 0. 2mg / day, 0.3mg / day, 0.4mg / day, 0.5mg / day, 0.6mg / day, 0. 7mg / day, 0.8mg / day, 0.9mg / day, 1mg / day, 1.5mg / day, 2mg / day day, 2.5mg / day, 3.0mg / day, 3.5mg / day, 4.0mg / day, 4.5mg / day day, 5.0mg / day, 5.5mg / day, 6.0mg / day, 6.5mg / day, 7.0mg / day day, 7.5mg / day, 8.0mg / day, 8.5mg / day, 9.0mg / day, 9.5mg / day day, 10.0mg / day, 11mg / day, 12mg / day, 13mg / day, 14mg / day, 1 5mg / day, 16mg / day, 17mg / day, 18mg / day, 19mg / day, or 20mg It can be used to deliver a cantharidin formulation to a subject at a dose of 0.01 g / day.

[0156] The delivery device or system of the present disclosure may be administered to a subject (e.g., For example, on an area of ​​skin of a subject having or suspected of having a wart or skin lesion. ) can be used to deliver cantharidin formulations. Alternatively or additionally The delivery device or system of the present disclosure delivers a cantharidin formulation to a subject once a day to once a week. Alternatively or additionally, the delivery device of the present disclosure can be used to deliver Or the system should be monitored at least once a day, once every two days, once every three days, once every four days, once every five days Once a year, once every 6 days, once a week, once every 10 days, once every 2 weeks, once every 3 weeks, once a month once every two months, once every three months, once every four months, once every five months, once every six months, once a year or more can be used to deliver the cantharidin formulation to a subject in one dose. Alternatively or additionally, the delivery device or system of the present disclosure may be administered at least once a day, or 2 times a day, or 3 times a day, or 4 times a day, or 5 times a day, or 6 times a day, or 7 times a day, or 8 times a day, or 9 times a day, or 10 times a day, or 11 times a day, or 12 times a day, or 13 times a day, or 14 times a day, or 15 times a day, or 1 6 times a day, or 17 times a day, or 18 times a day, or 19 times a day, or 20 times a day, or Subjects were administered 21 doses per day, 22 doses per day, 23 doses per day, or 24 doses per day. Alternatively or additionally, the present invention can be used to deliver an anticoagulant formulation. The disclosed delivery device or system is adapted to deliver to a subject as soon as the skin begins to epithelialize after a previous treatment. Alternatively or additionally, can be used to deliver cantharidin formulations. The delivery device or system of the present disclosure may be adapted to deliver the following to the skin: It can be used to deliver a cantharidin formulation to a subject. Additionally, the delivery device or system of the present disclosure may be used to treat the ulcers and ulcers as soon as the skin has fully epithelialized after the previous treatment. The cantharidin formulation can be immediately used to deliver the cantharidin formulation to a subject.

[0157] The formulations, delivery devices, or systems of the present disclosure may be administered in untreated, previously treated, or or further used to deliver a cantharidin formulation to the skin of a subject to be treated. Some examples of pre-treatment include, but are not limited to, wound debridement, Removal of scar tissue, scabs, or keratinized tissue by excision, washing, soaking, or surgical excision Previous treatments also include cryotherapy, cauterization, application of acid or base, salicylic acid These include topical application of sebum, laser, surgical debridement, soaks, hydrogen peroxide, or immunotherapy. Pretreatment may also be used to limit the area of ​​skin exposed to the cantharidin preparation. Examples of suitable materials include adhesive tapes, creams, ointments, solutions, waxes, or hydrophobic barriers. Cantharidin preparations can be used to treat the lesions by surgical excision, cryotherapy, cauterization, or application of acid or base. , application of acid, laser, surgical debridement, soaks, hydrogen peroxide, immunotherapy, or occlusive therapy. It may be used prior to or simultaneously with covering the treatment area with a tape or bandage. .

[0158] Cantharidin formulations and related delivery devices or systems are used to treat: It can be used for the treatment of acral fibrokeratosis, acrodermatitis enteropathica, acral keratoelastosis, Actinic keratosis (solar keratosis), sebaceous adenoma, hemangiokeratoma, atopic dermatitis, basal cell carcinoma, Benign fibrous histiocytoma, bladder cancer, Bowen's disease, breast cancer, Buschke-Ollendorff syndrome, uterine Cervical cancer, cervical dysplasia, senile hemangioma, chronic nodular helical chondrodermatitis, cutaneous endometriosis, cutaneous Dermatoleukemia, cutaneous lymphoma, cutaneous meningioma, cutaneous myxoma, Darier disease, dermal dendritic cell hamartoma, Dermatofibroma, Dermatofibrosarcoma protuberans, Exocrine hemangioma hamartoma, Ectodermal dysplasia, Epidermal inclusion cyst , epidermal nevi (including but not limited to sebaceous nevi, comedonic nevi, Proteus syndrome) Becker's nevus, epithelioid cell histiocytoma, familial myxoid angiofibroma myxovascular fibromas), fungal skin diseases (lobomycosis ), granular cell tumors, glucagonoma syndrome, genital warts, ichthyosis (including but not limited to but not ichthyosis vulgaris, lamellar ichthyosis, X-linked ichthyosis, epidermolytic hyperkeratosis, Ichthyosis acquista, and palmoplantar keratoderma (including idiopathic guttate hypomelanosis, infantile acropustulosis, infantile fibromatosis, Kaposi's sarcoma, keloid , Keratoacanthoma, Keratinized cyst, Knuckle pad, Lentigine, Melanoma, Microangiomas (Mi crovenular hemangioma, Morton's neuroma, multifocal intralymphatic Multifocal lymphangioendotheliomatosis s), Multinucleate cell angiohistiocytoma stocytoma, multiple cutaneous leiomyomas, mycosis fungoides, cutaneous neuroma, nerve capsule, inflammation nevus, superficial lipomatous nevus, digital skin hypertrophy, palisade encapsulated neuroma, skin parasitic disease (see below) Including but not limited to: scabies, lice infestation, burrowing fungus, hookworm-associated cutaneous larva migrans (including pityriasis rubra pilaris, leiomyoma of the arrector pilioma, reticular fibrous histiocytic tumor, porokeratosis Porokeratotic eccrine ostia dermal duct nevus), progressive nodular histiocytoma psoriasis (Pr ogressive nodular histiocytoma Psoriasis ) (including but not limited to erythrodermic psoriasis, palmoplantar psoriasis, palmoplantar pustulosis, tumbu Generalized pustular psoriasis, including geographic tongue, porokeratosis, seborrheic dermatitis, seborrheic keratosis, Rhinophyma, solitary cutaneous leiomyoma, spider angioma, target-like hemosiderin hemangioma, squamous cell carcinoma , Hemangioblastoma, Venous Lake, Urticaria Pigmentosa, Xanthelas Mastocytosis moidal mastocytosis), or zosteriform metastasis.

[0159] Other skin conditions, including but not limited to the following, can also be treated with cantharidin preparations: Can cause: benign epidermal cysts, birthmarks, calluses, corns, eczema, freckles, lentigines, pigmentation disorders (drug-induced Hyperpigmentation, hereditary symmetrical pigmentation disorder, hereditary generalized pigmentation disorder, familial progressive pigmentation disorder Hypermelanosis, Galli-Galli disease, Hemosiderin hyperpigmentation, Idiopathic guttate hypomelanosis vitiligo, iron metallic discoloration, white spots , melasma, Mukamel syndrome, Venus neck Necklace of Venus, anemic nevus, depigmented nevus, Pallister Killian syndrome, lobular hypomelanosis, mottling, reticular facial pigmentation atio reticularis faciei et colli), pilonidal cyst, white Pityriasis pityriasis, Sivat polymorphic atrophy, vascular acral polymorphic atrophy (Poikiloder ma vasculare atrophicans), postinflammatory hyperpigmentation, progressive Macular hypomelanosis, pruritus, reticular pigmentosa ented anomaly of the flexures), Kitamura reticular limb acropigmentation infection, Lille melanosis, Schaer-Waardenburg syndrome, shiitake dermatitis, tar melanosis , titanium metal discoloration, transient neonatal pustular melanosis, vagrant white spot melanosis (Vagabond 's leukomelanoderma), vasospastic plaques, Wende-Bax syndrome , X-linked reticular pigment disorder, Yemeni depigmentation syndrome), scarring, filamentous fibroma, tattoo removal vitiligo (including but not limited to non-segmental vitiligo and / or segmental vitiligo) Vitiligo, Quadrichrome vitiligo, Vitiligo punctate ( Vitiligo ponctue).

[0160] Epidermal skin problems such as peeling or flaking of the skin in individuals with sun damage or wrinkles Cantharidin preparations can also be used in rejuvenation methods.

[0161] Its chemotactic properties, ability to induce cell arrest and apoptosis, vesicant activity, and other The therapeutic outcomes of cantharidin preparations have been shown to be indicative of a number of potential therapeutic options, including surgery, x-rays, immunotherapy, and small molecule vectors. Based on the drug, antibody-based drug, recombinant protein-based drug, nucleic acid-based drug, or chemical Cantharidin preparations may also be useful in treating patients with failure of prior therapy. The study has demonstrated utility as a second-, third-, or fourth-line therapy for treating patients with Examples of uses for the cantharidin formulations, devices, and methods of the present disclosure include: Immediately following Mohs micrographic surgery in the treatment of basal cell carcinoma or after surgery in the treatment of mycosis fungoides after failure of systemic chemotherapy or after cryotherapy or surgery in the treatment of actinic keratosis in combination with destructive therapies such as hydrogen peroxide or acid or ingenol mebutate, as a first line therapy in the treatment of porokeratosis or seborrheic keratosis.

[0162] The formulations, delivery devices, or systems of the present disclosure are useful in treating patients who have failed or are refractory to prior therapies. Treat existing warts, molluscum contagiosum, actinic keratosis, seborrheic keratosis, or other skin hyperproliferative disorders Alternatively, the formulation, delivery device, or system of the present disclosure can be used to Alternatively, the formulations, delivery devices, or The system may be used in combination with another first-line therapy.

[0163] Cantharidin preparations can be used to treat cancer patients. Glycans are used to inhibit tumor growth and / or directly kill cancer cells. In some cases, cantharidin preparations can be used to kill cancer stem cells. In some cases, cantharidin preparations can be used to treat benign cancerous lesions. For example, cantharidin preparations can be used to treat cancer cells with a multidrug resistant phenotype. In some circumstances, norcantharidin, can be used to kill the cytoplasmic Thalizimide, or norcantharidimide, or an analogue of cantharidin, is cantharidin. It can be used in place of gin.

[0164] The cantharidin formulations, devices, systems, and methods may be used, for example, in skin grafts. In the production of autologous or allogeneic skin that can be used to treat cancer, or to remove residual cancer cells after surgery It may also be used for other purposes, such as as a blister model to test drugs or procedures for the removal of It can be used.

[0165] Preferred embodiments of the present invention have been shown and described herein; such embodiments include, but are not limited to, It will be apparent to those skilled in the art that the invention is provided herein by way of example only. It is not intended that the invention be limited by the specific examples set forth herein. Although mentioned in connection with the above, the description and illustration of the embodiments herein are not to be construed in a limiting sense. Numerous variations, modifications, and substitutions are possible. It will be apparent to those skilled in the art that such modifications may be made without departing from the invention. The embodiments may vary from the specific depictions, configurations, or aspects shown herein, which depend upon a variety of conditions and variables. It should be understood that the present invention is not limited to the relative proportions described herein. It will be appreciated that various alternatives to the embodiments of the invention described herein may be used in practicing the invention. Accordingly, the present invention also includes any such alternatives, modifications, and variations. , modifications, or equivalents. The scope of the claims defines the scope of the invention, and methods and structures within the scope of these claims and It is intended that equivalents thereof be encompassed by the claims.

Claims

1. 1. A system for delivering a cantharidin formulation to a subject, comprising: A reservoir comprising a cavity containing the cantharidin formulation, The bar has a volume of about 10 milliliters (mL) or less, and the reservoir is at about 1 atmosphere. A reservoir that is compressible to induce a pressure increase in the reservoir to a pressure exceeding 100 atm. Over and An applicator unit including an adapter and an applicator tip, an applicator tip including an opening and a channel in fluid communication with the reservoir; And the applicator tip is a reservoir from the outside of the applicator tip. an applicator unit for transferring the cantharidin formulation to the A system including:

2. The applicator unit includes a transparent cap that covers the applicator tip. The system of claim 1 .

3. the applicator unit includes a barrier over the opening, and the transparent cap The system of claim 2 , further comprising a piercing device for piercing the barrier.

4. The opening in the applicator tip has a diameter of 5 millimeters (mm) or less. The system of claim 1 .

5. The cantharidin formulation comprises at least about 0.01% (w / v) cantharidin; The system of claim 1 .

6. 6. The cantharidin formulation according to claim 5, further comprising 1% (w / v) or more of an excipient. system.

7. 6. The cantharidin formulation according to claim 5, further comprising a flavoring and / or coloring agent. system.

8. The reservoir has a volume of about 10 mL or less, and the cantharidin formulation is 5% (w / v) Combination of the following: cantharidin, cantharidic acid, norcantharidin, or parasonin The system of claim 1 in combination.

9. 2. The method of claim 1, wherein the reservoir has a threaded or snap-on cap at one end.

2. The system described in 1.

10. 10. The method of claim 9, wherein the adapter is secured to a threaded or snap-on cap. system.

11. The reservoir is adapted to induce a pressure increase in the reservoir to a pressure of less than about 10 atmospheres. The system of claim 1 , wherein the system is compressible.

12. 1. A system for delivering a cantharidin formulation to a subject, comprising: A cantharidin solution having at least about 0.001% (w / v) cantharidin and excipients. a reservoir containing the formulation; an applicator unit in fluid communication with the reservoir, The cantharidin formulation is delivered in a volume of about 10 milliliters (mL) or less. The applicator unit and A system including:

13. The cantharidin formulation comprises at least about 0.5% (w / v) cantharidin. The system of claim 12.

14. 13. The cantharidin formulation according to claim 12, further comprising 1% (w / v) or more of said excipient. The system described in

15. (i) the reservoir includes a screw-on or snap-on cap at one end; (ii) has a volume of about 5 mL or less; and / or (iii) is exposed to a pressure of greater than about 1.0 atmosphere.

13. The system of claim 12, wherein the reservoir is compressible to induce a pressure increase in the reservoir. 。

16. The applicator unit has an opening and an internal chamber in fluid communication with the reservoir. and an applicator tip including a nozzle, the applicator tip being configured to 13. The method of claim 12, further comprising transferring the cantharidin formulation from a bur to the exterior of the applicator tip. The system described.

17. 1. An applicator device for delivering a cantharidin formulation to a subject, comprising: one or more reservoirs, each of which contains one or more cavities; At least one of the one or more cavities contains a cantharidin formulation. With Zaver, an applicator unit in fluid communication with said one or more reservoirs, The applicator unit dispenses about 10 milliliters of the cantharidin formulation per use. The present invention relates to an application for controllably delivering the cantharidin formulation to a subject in sub-mL amounts. Tur unit and 13. An applicator device comprising:

18. (i) the reservoir includes a screw-on or snap-on cap at one end; (ii) has a volume of about 5 mL or less; and / or (iii) is exposed to a pressure of greater than about 1.0 atmosphere.

18. The applicator of claim 17, which is compressible to induce a pressure increase in the reservoir. Power supply device.

19. The applicator unit has an opening and an internal chamber in fluid communication with the reservoir. and an applicator tip including a nozzle, the applicator tip being configured to configured to transfer the cantharidin formulation from a burr to the exterior of the applicator tip.

20. The applicator device of claim 18.

20. an adaptor adjacent to the applicator tip, the internal channel extending through the adaptor; an adaptor for directing the applicator tip through the adaptor to the reservoir; 20. The applicator device of claim 19, further comprising:

21. The applicator unit has a transparent plate configured to cover the applicator tip.

20. The applicator device of claim 19, comprising a light cap.

22. the applicator unit includes a barrier over the opening, and the transparent cap The method of claim 21, further comprising: Applicator device.

23. 20. The adapter of claim 19, wherein the adapter is secured to the threaded end of the reservoir. Applicator device.

24. 20. The method of claim 19, wherein the opening in the applicator tip has a diameter of about 5 mm or less.

2. The applicator device according to claim 1 .

25. The cantharidin formulation comprises at least about 0.001% (w / v) cantharidin.

20. The applicator device of claim 17.

26. 26. The method of claim 25, wherein the cantharidin formulation further comprises about 1% (w / v) or more of an excipient.

5. The applicator device as described above.

27. The reservoir has a volume of about 1 mL or less, and the cantharidin formulation is about 5% 18. An applicator device according to claim 17 comprising the following (w / v) cantharidin:

28. 1. A method for delivering a cantharidin formulation to a subject, comprising: A reservoir containing the cantharidin formulation and a channel in fluid communication with the reservoir. providing an applicator device comprising an applicator unit including: Delivering the cantharidin formulation from the reservoir through the channel to the subject. To The method includes:

29. The cantharidin formulation comprises at least about 0.001% (w / v) cantharidin.

30. The method of claim 28.

30. 30. The method of claim 29, wherein the cantharidin formulation further comprises about 1% (w / v) or more of an excipient. The method described.

31. 31. The method of claim 30, wherein the subject has been diagnosed with a skin disorder.

32. The skin disease is epidermal warts, molluscum contagiosum lesions, actinic keratosis, or seborrheic keratosis. The method of claim 31 .

33. The epithelial wart or skin lesion disappears from the subject within two weeks after delivery of the cantharidin formulation. The method of claim 32, wherein the subject is removed.

34. said delivering delivering about 10 milliliters (mL) or less of said cantharidin formulation; 30. The method of claim 28, comprising:

35. 35. The method of claim 34, wherein the delivering comprises delivering about 5 mL or less of the cantharidin formulation. The method according to

36. 36. The method of claim 35, wherein the delivering comprises delivering no more than about 4 mL of the cantharidin formulation. The method according to

37. 37. The method of claim 36, wherein the delivering comprises delivering about 3 mL or less of the cantharidin formulation. The method according to

38. 38. The method of claim 37, wherein the delivering comprises delivering about 2 mL or less of the cantharidin formulation. The method according to

39. 38. The method of claim 37, wherein the delivering comprises delivering about 1 mL or less of the cantharidin formulation. The method according to

40. A method for treating epithelial warts or skin lesions on a subject, comprising: i) treating a cantharis lesion on a patient with a cantharis lesion; and ii) a reservoir containing a cantharidin formulation; and a method for controllably administering the cantharidin formulation to the subject. and an applicator unit in fluid communication with the reservoir for applying the The method includes using a turbocharger device.

41. The cantharidin formulation comprises at least about 0.001% (w / v) cantharidin.

41. The method of claim 40.

42. 42. The method of claim 41, wherein the cantharidin formulation further comprises about 1% (w / v) or more of an excipient. The method described.

43. The epithelial wart is removed from the subject within two weeks after delivery of the cantharidin formulation. The method of claim 40,

44. 41. The method of claim 40, wherein the cantharidin formulation is administered in a time period of about 30 seconds or less. 。

45. 45. The method of claim 44, wherein the cantharidin formulation is administered in a time period of about 20 seconds or less. 。

46. 46. ​​The method of claim 45, wherein the cantharidin formulation is administered in a time period of about 10 seconds or less. 。

47. 47. The method of claim 46, wherein the cantharidin formulation is administered within a period of about 5 seconds or less.

48. The cantharidin formulation is about 10 milliliters (mL) or less of the cantharidin formulation.

41. The method of claim 40, wherein the dose is administered in a volume.

49. The cantharidin formulation is administered in a volume of about 5 mL or less of the cantharidin formulation; 49. The method of claim 48.

50. 1. A kit for administering a cantharidin formulation to a subject, comprising: A plurality of separately packaged, individually dispensable dosage units in liquid or gel form. wherein the dosage unit comprises a dosage unit in a packaging unit; Each of the dosage units contains the cantharidin formulation in an amount of about 0.01 mL to 10 mL. and the cantharidin formulation contains at least about 0.001% (w / v) cantharidin. include, kit.

51. 51. The kit of claim 50, further comprising instructional materials for administering the cantharidin formulation. 。

52. The instructional material enables the subject to self-administer the cantharidin formulation.

52. The kit of claim 51.

53. 52. The method of claim 51, wherein the instructional material is for treating epithelial warts in the subject. kit.

54. 51. The method of claim 50, wherein the kit comprises at least three packaging units. kit.

55. The cantharidin formulation is maintained for 2 weeks after delivery of the dosage unit containing the cantharidin formulation.

51. The kit of claim 50, suitable for removing epithelial warts from the subject within 。

56. at least about 0.001% (w / v) cantharidin, a flavoring agent that induces a bitter taste in a subject upon ingestion of the formulation by the subject; a colorant that allows visual detection of the formulation by the subject; wherein the formulation has a volume of up to about 10 milliliters (mL). Agent.

57. 57. The cantharidin formulation according to claim 56, wherein the cantharidin formulation comprises at least about 0.01% cantharidin. The formulation described in

58. 58. The method of claim 57, wherein the cantharidin formulation comprises at least about 0.5% cantharidin. The formulation described.

59. 6. The flavoring and / or coloring agent of claim 5, wherein the flavoring and / or coloring agent is at a concentration of up to about 1% (w / v).

6. The formulation described in 6.

60. 57. The formulation of claim 56, wherein the volume is about 5 mL or less.

61. 57. The method of claim 56, wherein the formulation has a Reynolds number of less than about 1500 at 25°C. Agent.

62. 57. The formulation of claim 56, further comprising a gelling agent.

63. 2. The method of claim 1, wherein the formulation has an ion concentration of manganese or magnesium of less than about 1%.

56. The formulation described in 56.

64. The above are denatonium, amarogentin, gentiopicrin, octaacetylsucrose 57. The method of claim 56, wherein the glycerol is selected from the group consisting of sucrose, quercetin, brucine, and quasin. The formulation described above.

65. The coloring agent is D&C Violet, Isosulfan Blue, Methylene Blue, Methyl Red, methyl orange, Congo red, alizarin yellow, bromocresol green 57. The formulation of claim 56, wherein the active ingredient is selected from the group consisting of gentian violet, ... and gentian violet. 。

66. 1. A method for treating a skin condition in a subject, comprising: a) providing a cantharidin preparation, said preparation comprising: (i) at least about 0.001% (w / v) cantharidin; (ii) upon ingestion of the formulation by the subject; A flavoring agent that induces a bitter taste, and a coloring agent that allows visual detection of the formulation by the subject. and having a volume of up to about 10 milliliters (mL); b) administering said cantharidin to a site containing or suspected of containing said disease. applying a formulation to the skin; The method includes:

67. 67. The cantharidin formulation according to claim 66, wherein the cantharidin formulation comprises at least about 0.01% cantharidin. The method according to

68. 68. The method of claim 67, wherein the cantharidin formulation comprises at least about 0.5% cantharidin. The method described.

69. The flavoring and / or coloring agent is at a concentration of at least about 1% (w / v). Item 67. The method according to item 66.

70. 67. The method of claim 66, wherein the volume is about 5 mL or less.

71. 67. The method of claim 66, wherein the formulation has a Reynolds number of less than about 1500 at 25°C. Law.

72. 67. The method of claim 66, further comprising a gelling agent.

73. 2. The method of claim 1, wherein the formulation has an ion concentration of manganese or magnesium of less than about 1%.

66. The method according to claim 66.

74. The above are denatonium, amarogentin, gentiopicrin, octaacetylsucrose 67. The method of claim 66, wherein the glycerol is selected from the group consisting of sucrose, quercetin, brucine, and quasin. Method of posting.

75. The coloring agent is D&C Violet, Isosulfan Blue, Methylene Blue, Methyl Red, methyl orange, Congo red, alizarin yellow, bromocresol green 67. The method of claim 66, wherein the fluorescein is selected from the group consisting of fluorescein, fluorene, fluorescein, fluorene fluoride ... 。

76. The skin disease is selected from the group consisting of warts, molluscum contagiosum, seborrheic keratosis, and actinic keratosis.

67. The method of claim 66, wherein the

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