Microneedle patch for delivery of immunostimulatory drug

Abstract

The present application provides a dissolvable microneedle device for delivering an immunostimulant to the skin. The present application also provides a method of treating a skin condition comprising applying a dissolvable microneedle device to the skin.SOLUTION: The dissolvable microneedle patch includes a plurality of microneedles, wherein the microneedles are tapered to facilitate insertion of the microneedles into the skin. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles have a tapered tip portion comprising a therapeutically active ingredient dispersed in a matrix or suspension of a biodegradable polymer.SELECTED DRAWING: Figure 12

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 62 / 939,447, entitled "Microneedle Patch for Immunostimulatory Drug Delivery," filed November 22, 2019, which is incorporated herein by reference in its entirety.

[0002] The present application generally relates to microneedle patch compositions that can provide immediate as well as sustained release of therapeutically active ingredients for local immune stimulation. More specifically, the present application relates to microneedle compositions for stimulating a local immune response using immediate and / or sustained release microneedles intended for the treatment of skin conditions. [Background technology]

[0003] At first glance, transdermal delivery systems appear to be an attractive route of administration, as the large surface area and relative accessibility of the skin allows for direct delivery of drugs to the affected areas of skin diseases. However, in practice, transdermal delivery systems are not suitable for many therapeutic active ingredients, as the skin acts as a barrier, preventing these ingredients from reaching clinically relevant concentrations within the epidermis and dermis.

[0004] The skin's barrier function is primarily due to the lipid-rich outer layer of the epidermis, called the stratum corneum. The lipids in the stratum corneum prevent hydrophilic molecules from crossing the skin barrier. Additionally, the tight junctions between epidermal cells (e.g., adherens junctions, desmosomes, and zonula occludens) prevent substances larger than 500 kilodaltons from penetrating the skin. As a result, large immunogenic proteins and peptides, including those used in cutaneous immunotherapies, cannot be reliably administered to the skin using conventional formulations.

[0005] Several methods have been attempted to enhance the percutaneous absorption of large substances, such as skin immunostimulants. These include the addition of chemical penetration enhancers (e.g., ethanol, propylene glycol, or hydrophobic vesicles) to topical formulations, cell membrane polarization by iontophoresis, and mechanical delivery using cavitational ultrasound. However, these transdermal formulations have two major drawbacks: they are either too toxic to the underlying tissue to allow routine clinical use, and / or are cosmetically unacceptable (i.e., formulations containing chemical enhancers contain a high oil content) or require cumbersome equipment (e.g., cavitational ultrasound, iontophoresis), resulting in too much of a burden for patients.

[0006] Microneedles are another drug delivery approach that has been used to deliver drugs to the epidermis and / or dermis. Microneedles create micron-sized passages or channels in the skin, allowing drugs to be delivered directly to the desired depth within the epidermis and / or dermis, where they can perform their desired function. One subtype of microneedles, degradable microneedles, are composed entirely of degradable polymers complexed with active ingredients. Therefore, once inserted into the skin, they are completely consumed in the process of dissolution.

[0007] Microneedles used to treat skin diseases currently deliver active ingredients that are immunosuppressants (e.g., corticosteroids, calcipotriene, antibiotics) or chemotherapeutic agents (e.g., bleomycin, doxorubicin). Despite over 40 years of research into microneedling, microneedles have never been used to deliver cutaneous immunostimulants with the aim of generating a local immune response to treat skin diseases.

[0008] One group of skin diseases that may benefit from the precise administration of immunostimulants to the skin are infectious and malignant neoplasms, such as viral warts, molluscum contagiosum, and non-melanoma skin cancer. These diseases cannot be adequately treated with immunosuppressant microneedles or chemotherapy for several reasons. Primarily, these neoplasms vary in size and shape, even among lesions occurring in the same patient. To treat these neoplasms with immunosuppressants or chemotherapy, patients must be provided with microneedle patches precisely sized for each neoplasm. Microneedle patches are necessary for such drug administration to ensure that the drug reaches all neoplasms while minimizing damage to surrounding cells. Creating multiple microneedle patch sizes, such as those required for these types of components, is impractical from a manufacturing perspective, thus limiting the use of immunosuppressant and chemotherapy microneedles in the treatment of skin diseases. Furthermore, these types of neoplasms often occur in multiple skin lesions in the same patient. Treating neoplasms with microneedles consisting of immunosuppressants or topical chemotherapy requires applying microneedle patches to each neoplasm individually, which is burdensome from a clinical management perspective.

[0009] One disease for which cutaneous administration of immunostimulants is particularly effective is viral warts. Viral warts are extremely common, affecting nearly 20% of school-age children. Unfortunately, currently available wart treatments are: 1) painful, 2) ineffective, 3) leave scars, 4) require daily application for months, and 5) are frightening to children. These treatments include treatments that destroy wart tissue (e.g., cryotherapy with liquid nitrogen, cantharidin), topical preparations containing salicylic acid that disrupt the adhesion between cells that comprise the wart, and immunostimulants applied topically or injected into the wart. Destructive wart treatments are painful, create open wounds, and can leave permanent scars. Salicylic acid-containing products must be applied daily under closed clothing and worn 24 hours a day for several months, limiting their effectiveness and adhesion to the actual treatment.

[0010] Cutaneous immunotherapy is a type of wart treatment in which immunostimulants are applied topically or injected into the wart to induce a local immune response that recognizes and destroys the viral infection that causes the wart. Clinical use of immunotherapy is limited by issues with current formulations, creams and injectable solutions. Topical creams require daily application for several months, which is burdensome and time-consuming for patients. Immunotherapy creams require multiple applications to be effective because the stratum corneum limits the penetration of topically applied immunotherapy active ingredients into the skin. Injectable immunostimulants penetrate the stratum corneum, requiring fewer administrations than topical formulations. However, the use of injectable immunostimulants is limited by the pain associated with the injection and the inability to reliably place them within the epidermis because intercellular junctions prevent fluid expansion within the epidermis. Furthermore, because wart injections of immunostimulants must be performed by experienced healthcare professionals, their use requires patients to schedule appointments for treatment every 2–4 weeks. These frequent visits create time constraints for both patients and providers and reduce treatment completion rates.

[0011] The world's first skin immunotherapy using dissolving microneedles overcomes current limitations in skin immunotherapy by precisely delivering immunostimulants to the epidermis and dermis, where immune effector cells Langerhans cells and dermal dendritic cells reside. This invention not only enables painless and precise delivery of immunostimulants to the skin for the treatment of skin diseases, but is also the only skin immunotherapy formulation that enables sustained release of immunostimulants, achieving controlled and continuous immune stimulation. Summary of the Invention [Means for solving the problem]

[0012] Embodiments of the present application are directed to a dissolvable microneedle patch for delivery of a therapeutically active ingredient to the skin comprising a plurality of microneedles comprising microneedles of at least two different lengths, and a removable substrate, wherein the plurality of microneedles comprise tapered tips extending away from the removable substrate, the plurality of microneedles comprise a biodegradable polymer and a therapeutically active ingredient dispersed in the biodegradable polymer, and the active ingredient is selected from the group consisting of a vaccine, an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein.

[0013] Embodiments of the present application are directed to a method of treating a skin condition, comprising: i) applying a dissolvable microneedle patch for delivery of a therapeutically active ingredient to the skin, the dissolvable microneedle patch comprising a plurality of microneedles, the plurality of microneedles being microneedles of at least two different lengths, and a removable substrate, wherein the plurality of microneedles are attached to the removable substrate, the plurality of microneedles comprising tapered tips extending away from the removable substrate, the plurality of microneedles comprising a biodegradable polymer and a therapeutically active ingredient dispersed in the biodegradable polymer, wherein the active ingredient is selected from the group consisting of a vaccine, an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein; and ii) applying sufficient force to the dissolvable microneedle patch to enable the microneedles to penetrate to a location selected from the group consisting of the epidermis, the dermis, and the papillary dermis. iii) allowing the plurality of microneedles to remain in the skin until the biodegradable polymer degrades. iv) removing the adhesive substrate from the patch composition.

[0014] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the present invention and, together with the written description, serve to explain the principles, nature and characteristics of the invention. [Brief explanation of the drawings]

[0015] [Figure 1] FIG. 1 is an explanatory diagram of the microneedle patch of the present invention, viewed from above when the adhesive is translucent, so that the conical needles underneath can be seen. [Figure 2] FIG. 2 is an illustrative side view of a microneedle patch of the present invention applied to a patient's skin, with the stratum corneum, epidermis, and dermis labeled to show the penetration of the microneedles in delivering active ingredients through the various layers of the skin. [Figure 3] FIG. 3 is an explanatory diagram of the microneedle patch of the present invention, viewed from above when the adhesive is translucent, so that the conical needles are visible below. [Figure 4] FIG. 4 is an image from a scanning electron microscope of a microneedle patch having microneedles that are 500 microns in length. [Figure 5] FIG. 5 is an image from a scanning electron microscope of a microneedle patch having microneedles that are 800 microns in length. [Figure 6] Figure 6 shows a top view of pig skin after insertion of a microneedle patch containing a blue tissue-labeling dye. [Figure 7] FIG. 7 shows a cross-sectional image of pig skin after insertion of a microneedle patch containing a blue tissue-labeling dye. [Figure 8] FIG. 8 is an image from a scanning electron microscope of a microneedle patch containing 500 micron long immediate release biodegradable polymer microneedles. [Figure 9] FIG. 9 is an image from a scanning electron microscope of a microneedle patch containing 800 micron long immediate release biodegradable polymer microneedles. [Figure 10]FIG. 10 is an illustration of a microneedle patch viewed from the side to show immediate release microneedles of various lengths and microneedles containing one or more water-soluble polymers and one or more active ingredients. [Figure 11] FIG. 11 is a graph of the amount of Candida antigen released from the microneedle array over a 24 hour period. [Figure 12] FIG. 12 is an illustration of a microneedle patch from a side view, comprising two lengths of microneedles, comprising an immediate release, water-soluble polymer and one or more therapeutically active ingredients at the base of the microneedle, and a sustained release polymer and one or more therapeutically active ingredients at the tip of the microneedle. [Figure 13] FIG. 13 shows a treatment regimen consisting of continuous application of microneedle patches containing an immediate release polymer. [Figure 14] FIG. 14 shows a treatment regimen consisting of continuous application of microneedle patches containing sustained release polymers.

[0016] This disclosure is not limited to the specific systems, devices, and methods described, as these may vary. The terminology used in the description is for the purpose of describing the particular versions or embodiments only and is not intended to limit the scope. Such aspects of the disclosure may be embodied in many different forms. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey its scope to those skilled in the art.

[0017] The present disclosure is not limited in terms of the specific embodiments described herein, but are intended as illustrative of various aspects. Many modifications and variations can be made without departing from the spirit and scope of the present disclosure, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the present disclosure, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing description. Such modifications and variations are intended to fall within the scope of the appended claims. The present disclosure is limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled. It is understood that the present disclosure is not limited to particular methods, reagents, compounds, compositions, or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

[0018] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Nothing in this disclosure should be construed as an admission that the embodiments described in this disclosure are not entitled to antedate such disclosure by virtue of prior invention. As used herein, the term "comprising" means, but is not limited to, "including."

[0019] Although various compositions, methods, and devices are described with the term "comprising" various components or steps (which is interpreted to mean "includes but is not limited to"), the compositions, methods, and devices can also "consist essentially of" or "consist of" the various components and steps, and such terms should be interpreted to define a substantially closed group of members.

[0020] With respect to the use of virtually any plural and / or singular term herein, those skilled in the art will be able to convert from plural to singular and / or from singular to plural as appropriate to the context and / or application. Various singular / plural permutations may be expressly set forth herein for clarity.

[0021] In general, it will be understood by those skilled in the art that the terms used in this specification, and particularly in the appended claims (e.g., the body of the appended claims), are generally intended as "open" terms (e.g., the term "including" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "includes" should be interpreted as "includes but is not limited to," etc.). It will be further understood by those skilled in the art that where a specific number of introduced claims is intended, such intention will be expressly set forth in the claim; in the absence of such recitation, no such intention exists. For example, to aid in understanding, the following appended claims include the use of the introductory phrases "at least one" and "one or more" to introduce the claim recitation. However, the use of such phrases should not be construed to imply that the introduction of a claim repeat with the indefinite article "a" or "an" limits any particular claim containing such introduced claim repeat to embodiments containing only one such repeat, even if the same claim also contains the introductory phrases "one or more" or "at least one" and an indefinite article such as "a" or "an" (e.g., "a" and / or "an" should be interpreted to mean "at least one" or "one or more"). The same applies to the use of definite articles used to introduce claim descriptions. Moreover, even when a specific number of introduced claim repeats is explicitly recited, those skilled in the art will recognize that the recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of "two repeats" without any other modifier means at least two repeats, or two or more turns).Furthermore, when phrases similar to "such as at least one of A, B, and C" are used, generally such configurations are intended in the sense that one of ordinary skill in the art would understand the phrase (e.g., "a system having at least one of A, B, and C" would include, but is not limited to, systems having A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.). When terms similar to "such as at least one of A, B, or C" are used, generally such configurations are intended in the sense that one of ordinary skill in the art would understand the term (e.g., "a system having at least one of A, B, or C" would include, but is not limited to, systems having A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C, etc.). Those skilled in the art will further appreciate that virtually any dividing word and / or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibility of including one of the terms, either of the terms, or both terms. For example, the phrase "A or B" would be understood to include the possibilities of "A" or "B" or "A and B."

[0022] Furthermore, when features or aspects of the disclosure are described in terms of a Markush group, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0023] All percentages, parts and ratios are based on the total weight of the composition and all measurements are made at about 25°C unless otherwise specified.

[0024] As will be understood by those skilled in the art, for all purposes, including in terms of providing a written description, all ranges disclosed herein encompass any possible subranges and combinations of subranges. Any recited range can be readily recognized as fully descriptive and allowing for the same range to be broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third, upper third, etc. As will also be understood by those skilled in the art, all language, such as "up to," "at least," etc., includes the recited number and then refers to a range that can be broken down into subranges as described above. Finally, as will be understood by those skilled in the art, a range includes each individual member. Thus, for example, a group having 1 to 3 cells refers to a group having 1, 2, or 3 cells. Similarly, a group having 1 to 5 cells refers to a group having 1, 2, 3, 4, or 5 cells, etc.

[0025] The term "about" as used herein refers to variations in numerical quantities that may occur due to, for example, real-world measurement or handling procedures, inadvertent errors in these procedures, differences in the manufacture, source, or purity of compositions or reagents, etc. Typically, the term "about" as used herein refers to a stated value or range of values ​​that is 1 / 10th the stated value or range of values, e.g., ±10%. The term "about" also refers to variations that would be recognized as equivalent by those of ordinary skill in the art, unless they encompass known values ​​implemented by the prior art. Each value or range of values ​​preceded by the term "about" is intended to encompass embodiments of the stated absolute value or range of values. Quantitative values ​​referred to in this disclosure, whether modified by the term "about," include equivalents to the stated value, e.g., variations in the numerical quantities of that value that may occur but would be recognized as equivalents by those of ordinary skill in the art. If the context of this disclosure indicates otherwise or contradicts such an interpretation, the above interpretation may be modified as would be readily apparent to one of ordinary skill in the art. For example, in a list of numerical values ​​such as "about 49, about 50, about 55," "about 50" means a range spanning less than half the interval(s) between the preceding and succeeding values, e.g., from 49.5 to less than 52.5. Furthermore, expressions referring to values ​​"less than about" or "greater than about" should be understood in light of the definition of the term "about" provided herein.

[0026] As used herein, the term "substantially free" indicates that the particular material being referenced is present in an amount not exceeding 10% by weight or volume of the total composition.

[0027] When a range of values ​​is provided, each intervening value between the upper and lower limits of that range, and other stated or intervening values ​​within that stated range, is intended to be encompassed within the disclosure. For example, if a range of 1 μm to 8 μm is stated, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, and 7 μm are also intended to be expressly disclosed, as are ranges of values ​​above 1 μm and below 8 μm.

[0028] The terms "patient" and "subject" are interchangeable and can be considered to mean any living organism that can be treated with a compound of the invention. As such, the terms "patient" and "subject" can include, but are not limited to, any non-human mammal, primate, or human. In some embodiments, a "patient" or "subject" is a mammal such as a mouse, rat, other rodent, rabbit, dog, cat, pig, cow, sheep, horse, primate, or human. In some embodiments, a patient or subject is an adult, child, or infant. In some embodiments, a patient or subject is human.

[0029] As used herein, the term "animal" includes, but is not limited to, humans and non-human vertebrates such as wild, domestic and farm animals.

[0030] "Tissue" refers to a collection of similar, specialized cells that come together to perform a particular function.

[0031] In this disclosure, the term "disorder" means, and is used interchangeably with, the term disease, condition, or illness, unless otherwise specified.

[0032] As used herein, the term "wart" refers to small, hard, benign growths on the skin caused by a virus.

[0033] As used herein, the terms "administer," "administering," or "administration" refer to either administering a compound (also called a substance of interest) or a pharmaceutically acceptable salt or composition of a compound (substance of interest) directly to a subject.

[0034] As used herein, the terms "treat," "treat," or "treating" refer to both therapeutic treatment and prophylactic or preventative measures, the purpose of which is to reduce the frequency or delay the onset of symptoms of a condition, enhance the feel, appearance, color, sensation, or hydration of the intended tissue treatment area of ​​the tissue surface in a subject compared to a subject not administered the compound or composition, or obtain other beneficial or desired clinical results. For purposes of this invention, beneficial or desired clinical results include, but are not limited to, reversal, alleviation, or alleviation of the symptoms of a condition, a decrease in the extent of a disorder or disease; stabilization (i.e., not worsening); stabilization (i.e., not worsening) of the condition, disorder, or disease state; delay in the onset or slowing of progression of the condition, disorder, or disease; improvement in the condition, disorder, or disease state; and remission (whether partial or total), whether detectable or undetectable, or enhancement or amelioration of the condition, disorder, or disease. Treatment includes eliciting a clinically significant response without undue side effects. Treatment also includes prolonging survival compared to the expected survival if not receiving treatment.

[0035] In some embodiments, the compounds and methods disclosed herein can be utilized with or on a subject in need of such treatment, which may also be referred to as "in need." As used herein, the phrase "in need" means that a subject has been identified as having a need for a particular method or treatment, and that the treatment has been administered to the subject for that specific purpose.

[0036] As used herein, the term "therapeutic agent" or "therapeutic agent" or "pharmaceutically active agent" means an agent utilized to treat, combat, ameliorate, prevent or ameliorate an undesirable condition or disease in a patient.

[0037] As used herein, the term "composition" means a combination or mixture of two or more different components, ingredients, or substances.

[0038] The term "immunostimulant" as used herein refers to an external source that activates the immune system. Immunostimulants can come from multiple sources, including immunogenic antigens such as Candida albicans, Trichophyton phytopathica, and tuberculin; immunogenic organisms such as Corynebacterium parvum, Propionibacterium acnes, and Cutibacterium acnes; and immunogenic molecules such as imidazole. These include immunogenic organisms such as Mycobacterium indicus planii (formerly Mycobacterium w); immunogenic molecules such as imiquimod; and immunogenic vaccines such as human papillomavirus vaccines, measles-mumps-rubella vaccines, mumps vaccines, Bacillus Calmette-Guérin vaccines, and Mycobacterium w vaccines.

[0039] The phrase "therapeutically effective" is intended to modify the amount of active ingredient (ie, compound or derivative thereof) used to treat a disease or disorder or effect a clinical endpoint.

[0040] A "therapeutically effective amount" or "effective amount" of a compound or composition is a predetermined amount calculated to achieve the desired effect, i.e., inhibit, block, or reverse cell activation, migration, or proliferation. The activity contemplated by the methods of the present invention includes both medical and / or prophylactic treatment, as appropriate. The specific dose of a compound administered in accordance with the present invention to achieve a therapeutic and / or prophylactic effect will, of course, be determined by the particular circumstances surrounding the case, including, for example, the compound administered, the route of administration, and the condition being treated. The compounds are effective over a wide dosage range. However, it will be understood that the effective amount to be administered will be determined by the physician in light of the relevant circumstances, including the condition being treated, the choice of compound to be administered, and the selected route of administration, and therefore the dosage ranges set forth above are not intended to limit the scope of the invention in any way. A therapeutically effective amount of a compound of the present invention is typically an amount sufficient to achieve an effective systemic concentration or local concentration in tissues when administered in a physiologically acceptable excipient composition.

[0041] "Inhibiting" includes administering a compound of the invention to prevent the onset of symptoms, alleviate symptoms, relieve symptoms, slow or reduce the progression of the disease and / or its symptoms, or eliminate the disease, condition, or disorder.

[0042] As used herein, the phrase "substantially free of therapeutically active ingredients" refers to an amount of therapeutically active ingredients that does not elicit a physiological response. "Substantially free of therapeutically active ingredients" can be defined as about 10% or less of a therapeutically active ingredient.

[0043] As used herein, the term "excipient" encompasses carriers and diluents and means a material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, that is involved in carrying or transporting a pharmaceutical, cosmetic, or other agent across a tissue layer, such as the stratum corneum or stratum spinosum.

[0044] As used herein, the terms "topically" and "topical" refer to application to skin surfaces, mucosal tissues, and keratinous tissues such as nails and hair.

[0045] As used herein, "skin" refers to the thin tissue that naturally covers the body of humans and animals. Skin is composed of the epidermis and the dermis. As used herein, the outermost layer of the epidermis is the stratum corneum, and the uppermost layer of the dermis is the papillary dermis.

[0046] As used herein, the term "immediate release" refers to a polymer designed to release at least 75% of the therapeutically active ingredient over a timescale of about 0 to about 24 hours.

[0047] As used herein, the term "sustained release" refers to a polymer that does not release 75% or more of the therapeutically active ingredient until greater than about 24 hours after application.

[0048] As used herein, the term "biodegradable polymer" refers to a polymer that degrades or dissolves after being introduced into the skin and releasing the therapeutically active ingredient.

[0049] As used herein, the term "sufficient force" refers to the force required to apply the microneedle patch so that the microneedles penetrate the skin to the desired depth.

[0050] As used herein, the term "sensitization" refers to the administration of a therapeutic or stimulating agent to stimulate the immune system with the intent of obtaining a more robust response with subsequent administration.

[0051] As used herein, the term "hypersensitivity" refers to an unwanted reaction produced by the normal immune system, such as allergy or autoimmunity.

[0052] Less than the full measure of the disclosure may be claimed for any reason, by hereby reserving the right to exclude any individual member of any such group, including any subrange or combination of subranges within such group, which may be claimed according to a range or similar method. Furthermore, less than the full measure of the disclosure may be claimed for any reason, by hereby reserving the right to exclude, by disclaimer, individual substituents, structures, or any members of the group or claimed group. Throughout this disclosure, various patents, patent applications, and publications are referenced. The disclosures of these patents, patent applications, and publications are incorporated by reference in their entireties into this disclosure in order to more fully describe the state of the art as known to those skilled in the art as of the date of this disclosure. The present disclosure applies in the event of a conflict between the cited patents, patent applications, and publications and this disclosure.

[0053] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Nothing in this disclosure should be construed as an admission that the embodiments described in this disclosure are not entitled to antedate such disclosure by virtue of prior invention.

[0054] Dissolving microneedle patch The present embodiment is directed to a dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin. The microneedle patch includes a plurality of microneedles, including microneedles of at least two different lengths, and a removable substrate, the plurality of microneedles being attached to the removable substrate. The plurality of microneedles include tapered tips extending away from the removable substrate. The plurality of microneedles include a biodegradable polymer and a therapeutically active ingredient dispersed in the biodegradable polymer. The therapeutically active ingredient is selected from the group consisting of a vaccine, an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein.

[0055] In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the plurality of microneedles having at least two different lengths selected from the group consisting of lengths terminating in the epidermis and lengths terminating in the reticular or papillary dermis. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles having one to five different lengths. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the plurality of lengths of which may vary based on the location on the body, the age of the patient, or the skin condition to be treated. In some embodiments, the needles of at least two different lengths are of equal proportion. In some embodiments, the needles of at least two different lengths may be of different proportions. In alternative embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles being of a single length. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles being of equal length. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, at least two of which have varying lengths, such as about 10 microns to about 1000 microns, about 10 microns to about 900 microns, about 10 microns to about 800 microns, about 10 microns to about 700 microns, about 10 microns to about 600 microns, about 10 microns to about 500 microns, about 10 microns, about 10 microns to about 400 microns, about 10 microns to about 300 microns, about 10 microns to about 200 microns, about 10 microns to about 100 microns, about 10 microns to about 90 microns, about 10 microns to about 10 ... 0 microns to about 80 microns, about 10 microns to about 70 microns, about 10 microns to about 60 microns, about 10 microns to about 50 microns, about 10 microns to about 40 microns, about 10 microns to about 30 microns, about 10 microns to about 20 microns, about 10 microns to about 15 microns, about 20 microns to about 1000 microns, about 20 microns to about 900 microns, about 20 microns to about 800 microns, about 20 microns to about 700 microns, 20 microns to about 600 microns, 20 microns to about 500 microns, about 20 microns to about 400 microns, about 20 microns to about 300 microns,About 20 microns to about 200 microns, about 20 microns to about 100 microns, about 20 microns to about 90 microns, about 20 microns to about 80 microns, about 20 microns to about 70 microns, about 20 microns to about 60 microns, about 20 microns to about 50 microns, about 20 microns to about 40 microns, about 20 microns to about 30 microns, about 20 microns to about 25 microns, about 50 microns to about 1000 microns, about 50 microns to about 900 microns , about 50 microns to about 800 microns, about 50 microns to about 700 microns, about 50 microns to about 600 microns, about 50 microns to about 500 microns, about 50 microns to about 400 microns, about 50 microns to about 300 microns, about 50 microns to about 200 microns, about 50 microns to about 100 microns, about 100 microns to about 1000 microns, about 100 microns to about 900 microns, about 100 microns to about 800 microns, about 100 Microns to about 700 microns, about 100 microns to about 600 microns, about 100 microns to about 500 microns, about 100 microns to about 400 microns, about 100 microns to about 300 microns, about 100 microns to about 200 microns, about 200 microns to about 1000 microns, about 200 microns to about 900 microns, about 200 microns to about 800 microns, about 200 microns to about 700 microns, about 200 microns to about 600 microns, about It is 200 microns to about 500 microns, about 200 microns to about 400 microns, about 200 microns to about 300 microns, about 500 microns to about 1000 microns, about 500 microns to about 900 microns, about 500 microns to about 800 microns, about 500 microns to about 700 microns, about 500 microns to about 600 microns, about 800 microns to about 1000 microns, about 800 microns to about 900 microns, or a value within these ranges.

[0056] In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles that are tapered to facilitate insertion of the microneedles into the skin, hi some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles that have a tapered tip portion that includes a therapeutically active ingredient dispersed in a matrix or suspension of a biodegradable polymer.

[0057] In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, including microneedles of at least two different lengths, and composed of a biodegradable polymer of equal volume. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, where the volume of each microneedle may remain constant, achieved by varying the diameter of each microneedle as needed. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, where the volumes of each microneedle are unequal. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, where the volume depends on the concentration of the particular immunostimulant used.

[0058] In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles having tip portions. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles having tip portions, the tip portions comprising from about 5% to about 99% of the total volume of the microneedles. In some embodiments, the microneedle tip portions comprise from about 20% to about 90% of the total volume of the microneedles. In some embodiments, the microneedle tip portions comprise about 50% of the total volume of the microneedles. In some embodiments, the microneedle tip portions comprise about 75% of the total volume of the microneedles.In some embodiments, the tip portion of the microneedle is about 5% to about 99%, about 5% to about 95%, about 5% to about 90%, about 5% to about 85%, about 5% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 60%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, 10% to about 99%, about 10% to 95%, about 10% to about 90%, about 10% to about 85%. %, about 90%, about 20%, about 10% to about 80%, about 10% to about 75%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 15% to about 99%, about 15% to about 95%, about 15% to about 90%, about 15% to about 85%, about 15% to about 80%, about 15% to about 75%, about 15% to 70%, about 15% to 60%, about 15% to about 50%, 15% to 40%, About 15% to about 30%, about 15% to about 20%, about 25% to about 99%, about 25% to about 95%, about 25% to about 90%, about 25% to about 85%, about 25% to about 80%, about 25% to about 75%, about 25% to about 70%, about 25% to about 60%, about 25% to about 50%, about 25% to about 40%, about 25% to about 30%, 50 to 99%, 50 to about 95%, about 50 to about 90%, about 50 to 85%, about 50 to 80%, about 50 to about 75%, about 50 to 70%, It may be 50 to about 60%, about 25 to about 95%, about 60% to about 99%, about 60% to about 95%, about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 70 to about 99%, about 70 to about 95%, about 70 to about 90%, about 70 to about 80%, about 70 to about 75%, about 80 to 99%, about 80% to about 95%, about 80 to about 90%, about 90% to about 95%, or a value within these ranges. Specific examples may include about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, or ranges between any two of these values. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient. In some embodiments, each of the plurality of microneedles comprises approximately the same amount of the therapeutically active ingredient.In some embodiments, each of the multiple microneedles comprises a different amount of a therapeutically active ingredient.

[0059] In some embodiments, the method comprises applying the dissolving microneedle patch to treat a skin condition, the skin condition being warts, condyloma acuminata, bowel disease, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, acanthosis nigricans, Gorlin's syndrome, and alopecia areata, vitiligo.

[0060] Certain compounds disclosed herein possess useful immunostimulatory activity and can be used to treat or prevent diseases or conditions in which the immune system may play an active role. In some embodiments, successful delivery of an immunostimulant results in classic clinical signs of inflammation, such as lubolum, tumour, and calorie (redness, swelling, and warmth, respectively). Accordingly, embodiments are also directed to pharmaceutical compositions comprising one or more compounds disclosed herein in association with a pharmaceutically acceptable carrier, as well as methods of making and using the compounds and compositions. Certain embodiments are directed to methods for stimulating the immune system. Other embodiments are directed to methods for treating a skin condition in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound or composition according to the invention. Also provided is the use of certain compounds disclosed herein in the manufacture of a medicament for the treatment of a disease or condition ameliorated by immune system activation.

[0061] In some embodiments, the present invention relates to a method of treating a skin condition by administering a pharmaceutical composition of an embodiment disclosed herein. In some embodiments, the compound is in a therapeutically effective amount. In some embodiments, the therapeutically effective amount is an amount disclosed herein. In some embodiments, administration of the dissolving microneedle patch results in the disappearance of the condition being treated. In some embodiments, administration of the dissolving microneedle patch results in the disappearance of a skin lesion or skin lesions in direct contact with the dissolving microneedle patch. In some embodiments, administration of the dissolving microneedle patch results in the disappearance of a skin lesion or skin lesions adjacent to the dissolving microneedle patch.

[0062] In some embodiments, the plurality of microneedles comprise a therapeutically active ingredient, wherein the therapeutically active ingredient is selected from the group consisting of a vaccine, an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein. In some embodiments, the dissolvable microneedle patch delivers a therapeutically active ingredient to stimulate a local immune response. In some embodiments, the therapeutically active ingredient is a vaccine, wherein the vaccine is selected from the group consisting of a measles-mumps-rubella vaccine, a mumps vaccine, a Bacillus Calmette-Guerin vaccine, a human papillomavirus vaccine, and a Mycobacterium w vaccine. In some embodiments, the therapeutically active ingredient is an immunostimulatory molecule, wherein the immunostimulatory molecule is imiquimod. In some embodiments, the therapeutically active ingredient is an immunostimulatory organism, wherein the immunostimulatory organism is Propionibacterium acnes, Priopionobacterium, and / or Mycobacterium indicus planii (formerly Mycobacterium w). In some embodiments, the therapeutically active ingredient is an immunostimulatory protein, and the immunostimulatory protein is selected from the group consisting of a Candida antigen, a tinea antigen, tuberculin, a purified protein derivative (also), a human papillomavirus surface protein, interferon alpha, interferon beta, and interferon gamma.

[0063] In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, and the therapeutically active ingredient is a Candida antigen. In some embodiments, the therapeutically active ingredient is a Candida antigen. In some embodiments, the Candida antigen is substantially free of glycerin. In some embodiments, the Candida antigen is glycerin-free. In some embodiments, the glycerin-free Candida antigen is lyophilized.

[0064] In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, wherein the therapeutically active ingredient is dispersed throughout the polymer. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, wherein the therapeutically active ingredient is uniformly dispersed throughout the microneedles. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, wherein the therapeutically active ingredient is concentrated at the tip of the microneedle. In some embodiments, the plurality of microneedles comprises microneedles wherein the half of the microneedles closest to the base is substantially free of the therapeutically active ingredient. In some embodiments, the plurality of microneedles comprises microneedles wherein the half of the microneedles closest to the base is free of the therapeutically active ingredient. In some embodiments, the therapeutically active ingredient is a solid powder. In some embodiments, the therapeutically active ingredient is a solid powder dispersed throughout the polymer. In some embodiments, the therapeutically active ingredient is lyophilized. In some embodiments, the therapeutically active ingredient is lyophilized and dispersed throughout the polymer.

[0065] Some embodiments disclosed herein also include pharmaceutical compositions comprising, as an active ingredient, one or more compounds disclosed herein in combination with one or more pharmaceutically acceptable carriers (excipients).

[0066] The active compound is effective over a wide dosage range and can generally be administered in a therapeutically effective amount. However, it is understood that the amount of compound actually administered will usually be determined by a physician depending on the relevant circumstances, including the condition to be treated, the compound actually administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, etc. In some embodiments, the multiple microneedles contain equal amounts of the therapeutically active ingredient. In some embodiments, the multiple microneedles contain unequal amounts of the therapeutically active ingredient.

[0067] The amount of compound or composition administered to a patient will vary depending on the entity being administered, the purpose of administration (e.g., prophylaxis or treatment), the condition of the patient, and the method of administration. For therapeutic use, the composition can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially prevent the symptoms of the disease and its complications. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, and epidermodysplasia verruciformis, and successful treatment of these conditions results in a one-point improvement on any ordinal or interval rating scale, such as the Physician Global Assessment or the Investigator Global Assessment. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and verrucous carcinoma. Successful treatment of epidermodysplasia verruciformis and these conditions results in about 100% loss of skin lesions at the site of patch administration, as assessed by clinical, histopathological, or dermoscopic evaluation, and by optical coherence tomography or confocal microscopy. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and verruca carcinoma, where verruca carcinoma includes warts. Successful treatment of epidermodysplasia verruciformis and these conditions results in about 50% loss of skin lesions at the site of patch administration, as assessed by clinical, histopathological, or dermoscopic evaluation, and by optical coherence tomography or confocal microscopy.In some embodiments, successful treatment of warts, condyloma acuminata, bowel disease, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or epidermodysplasia verruciformis with a dissolvable microneedle patch is characterized by a reduction in skin lesions at the site where the patch is administered of about 50% to about 100%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, or about 50% to about 80%. , about 50% to about 75%, about 50% to about 70%, about 50% to about 65%, about 50% to about 60%, about 50% to about 55%, about 60% to about 100%, about 60% to about 95%, about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70% to 100%, about 70% to about 95%, about 65% to about 95%, about 50% to about 50%. The compound results in a reduction of about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or within these numerical ranges. Specific examples include a reduction of skin lesions by about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or any two ranges between these values, as determined by clinical, histopathological, or dermatological evaluation, as well as by optical coherence tomography or confocal microscopy.

[0068] In some embodiments, successful treatment of warts, condyloma acuminata, bowel disease, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and verrucous epithelial dysplasia with the dissolvable microneedle patch results in a reduction in width, length, or height. Approximately 50% to approximately 100%, approximately 50% to approximately 95%, approximately 50% to approximately 90%, approximately 50% to approximately 85%, approximately 50% to approximately 80%, approximately 50% to approximately 75%, approximately 50% to approximately 70%, approximately 50% to approximately 65%, approximately 50% to approximately 60%, approximately 50% to approximately 55%, approximately 60% to approximately 100%, approximately 60% to approximately 95%, approximately 60% to approximately 90%, approximately 60% to approximately 85%, approximately 60% to approximately 80%, approximately 60% to approximately 75%, approximately 60% to approximately 65 %, about 70% to about 100%, about 70% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 80% to 100%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to 100%, about 90% to about 95%, or within these numerical ranges. Specific examples may include a reduction in the width, length, or height of a skin lesion by about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or within any two of these values, as measured by clinical, histopathological, or dermoscopic evaluation, as well as by optical coherence tomography or confocal microscopy.

[0069] In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in a one-point improvement on any ordinal or interval rating scale, such as Physician Global Assessment or Investigator Global Assessment. In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in about 100% restoration of hair growth at the location where the patch is administered. In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in at least about a 50% increase in hair growth at the location where the patch is administered, as defined by the number of hair follicles with actively growing hair shafts, as seen by clinical, trichoscopic, or histopathological evaluation. In some embodiments, successful treatment of alopecia areata with a dissolvable microneedle patch indicates an increase in hair growth at the location where the patch is administered of about 50% to about 100%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, 50% to 65%, 50% to 60%, about 50% to 55%, 60% to 100%, 60% to 95%, about 60% to about 90%, about It may be 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70% to about 100%, about 70 to about 95%, about 70 to about 90%, about 70 to about 85%, about 70 to about 80%, about 80 to about 75%, about 80 to 100%, about 80 to about 95%, about 80 to about 90%, about 80 to 85%, about 90% to 100%, about 90 to 95%, or a value within these ranges. Specific examples may include an increase in hair growth, as defined by the number of hair follicles with actively growing hair shafts as seen by clinical, trichoscopic, or histopathological evaluation, of about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or ranges between these values.

[0070] In some embodiments, successful treatment of alopecia areata with a dissolving microneedle patch indicates an improvement in the Severity Assessment of Alopecia Tool (SALT) score at the site where the patch was administered, by about 50% to about 100%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, 50% to 65%, about 50% to 60%, about 50% to 55%, about 60% to 100%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, about 50% to about 65%, about 50% to about 60%, about 50% to about 55%, about 60% to about 100%, about 50% to about 95 ... 0%, about 60% to about 95%, about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70 to about 100%, about 70 to 95%, about 70 to 90%, about 70 to 85%, about 70 to 80%, about 80 to 100%, about 80 to 95%, about 80 to 90%, about 80 to 85%, 90 to 100%, 90 to 95% or within these numerical ranges. Specific examples include an improvement in Severity of Alopecia Tool (SALT) score of about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or a range between any two of these values.

[0071] In some embodiments, each dissolving microneedle patch contains a standardized amount of a therapeutically active ingredient.

[0072] In some embodiments, the dissolvable microneedles may comprise from about 1% to about 90% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedles may comprise from about 50% to about 75% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedles may comprise from about 25% to about 50% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedles may comprise from about 25% to about 75% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedles may comprise from about 40% to about 60% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedles may comprise from about 60% to about 80% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the one or more therapeutically active ingredients are present in an amount of about 1% to about 90%, about 1% to about 85%, about 1% to about 80%, about 1% to about 75%, about 1% to about 70%, about 1% to about 65%, about 1% to about 60%, about 1% to about 55%, about 1% to about 50%, about 1% to about 45%, about 1% to about 40%, about 1% to about 35%, about 1% to about 30%, about 1% to about 25%, about 1% to about 20%, about 1% to about 15%, about 1% to about 10%, about 1 to about 5%, about 5 to about 90%, about 1 to about 5%, about 5% to about 85%, about 5% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 65%, about 5% to about 60%, about 5% to about 55%, about 5% to about 50%, about 5% to about 45%, About 5% to about 40%, about 5% to about 35%, about 5% to about 30%, about 5% to about 25%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, about 10% to about 90%, about 10% to about 85%, about 10% to about 80%, about 10% to about 75%, about 10% to about 70%, about 10% to about 65%, about 10% to about 60%, about 5% to about 55%, about 10% to about 60%, about 10% to about 40%, about 40%, about 30%, about 60%, about 10% to about 55%, about 10% to about 50%, about 10% to about 45%, about 10% to about 40%, about 10% to about 35%, about 10% to about 30%, about 10% to about 25%, about 10% to about 20%, about 10% to about 15%, about 15% to about 90%, about 15% to about 85%,About 10% to about 15%, about 15% to about 15%, about 15% to about 15%, about 15% to about 80%, about 15% to about 75%, about 15% to about 70%, about 15% to about 65%, about 15% to about 60%, about 15% to about 55%, about 15% to about 50%, about 15% to about 40%, about 15% to about 35%, about 15% to About 30%, about 15% to about 45%, about 15% to about 45%, about 15% to about 25%, about 15% to about 20%, about 20% to about 90%, about 20% to about 85%, about 20% to about 80%, about 20% to about 75%, about 20% to about 70%, about 20% to about 65%, about 20% to about 60%, about 20% to about 55%, Approximately 20% to approximately 50%, approximately 20% to approximately 45%, approximately 20% to approximately 40%, approximately 20% to approximately 35%, approximately 20% to approximately 30%, approximately 20% to approximately 25%, approximately 25% to approximately 90%, approximately 25% to approximately 85%, approximately 25% to approximately 80%, approximately 25% to approximately 75%, approximately 25% to approximately 70%, approximately 25% to approximately 65%, approximately 25% to Approximately 60%, approximately 25% to approximately 60%, approximately 25% to approximately 55%, approximately 25% to approximately 50%, approximately 25% to approximately 45%, approximately 25% to approximately 40%, approximately 25% to approximately 35%, approximately 25% to approximately 30%, approximately 30% to approximately 90%, approximately 30% to approximately 85%, approximately 30% to approximately 80%, approximately 30% to approximately 75%, approximately 30% to approximately 70%, Approximately 30% to approximately 65%, approximately 30% to approximately 60%, approximately 30% to approximately 55%, approximately 30% to approximately 50%, approximately 30% to approximately 45%, approximately 30% to approximately 40%, approximately 30% to approximately 35%, approximately 35% to approximately 90%, approximately 35% to approximately 85%, approximately 35% to approximately 80%, approximately 35% to approximately 75%, approximately 35% to approximately 70%, approximately 35% to Approximately 65%, approximately 35% to approximately 60%, approximately 35% to approximately 55%, approximately 35% to approximately 50%, approximately 35% to approximately 45%, approximately 35% to approximately 40%, approximately 40% to approximately 90%, approximately 40% to approximately 85%, approximately 35% to approximately 50%, approximately 40% to approximately 60%, approximately 40% to approximately 55%, approximately 40% to approximately 50%, approximately 45% to approximately 90%, Approximately 45% to approximately 85%, approximately 45% to approximately 80%, approximately 90% to approximately 90%, approximately 45% to approximately 75%, approximately 45% to approximately 70%, approximately 45% to approximately 65%, approximately 45% to approximately 60%, approximately 45% to approximately 55%, approximately 50% to approximately 90%, approximately 50% to approximately 85%, approximately 50% to approximately 80%, approximately 50% to approximately 75%, approximately 50% to Approximately 70%, approximately 90% to approximately 90%, approximately 50% to approximately 65%, approximately 50% to approximately 60%, approximately 50% to approximately 55%, approximately 55% to approximately 90%, approximately 55% to approximately 85%, approximately 55% to approximately 80%, approximately 55% to approximately 75%, approximately 55% to approximately 70%, approximately 55% to approximately 65%, approximately 55% to approximately 60%, approximately 60% to approximately 90%,about 50% to about 85%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 65% to about 90%, about 65% to about 85%, about 65% to about 80%, about 65% to about 75%, about 65% to about 70%, about 70% to about 90%, about 60% to about 85%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 85%, about 85% to about 90%, or a value within one of these ranges. Specific examples include about 90%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%, about 2%, about 1%, etc. All of the above represent weight percent of the pharmaceutical composition. In some embodiments, the pharmaceutical composition is suitable for transdermal administration.

[0073] In some embodiments, the therapeutically active ingredient is in a therapeutically effective amount. In some embodiments, a therapeutically effective amount is from about 1 microgram to 999 micrograms, 1 microgram to 100 micrograms, 100 micrograms to 200 micrograms, 200 micrograms to 300 micrograms, 300 micrograms to 400 micrograms, 400 micrograms to 500 micrograms, 500 micrograms to 600 micrograms, 600 micrograms to 700 micrograms, 700 micrograms to 800 micrograms, 800 micrograms to 900 micrograms, 900 micrograms to 999 micrograms, 1 mg to about 1000 mg, about 1 mg to about 900 mg, about 1 mg to about 800 mg, about 1 mg to about 700 mg, about 1 mg to about 600 mg, about 1 mg to about 500 mg, about 1 mg to about 400 mg, about 1 mg to about 900 mg, about 1 mg to about 300 mg, or about 1 mg to about 200 mg, about 1 mg to about 100 mg, about 10 mg to about 1000 mg, about 50 mg to about 1000 mg, about 100 mg to about 1000 mg, about 200 mg to about 1000 mg, about 300 mg to about 1000 mg, about 400 mg ~1000mg, 500mg~1000mg, 10mg~500mg, 500mg~500mg, 1mg~200mg, 1mg~200mg, 1mg~1000mg, 500mg about 1000 mg, about 1 mg to about 400 mg, about 1 mg to about 1000 mg, about 1 mg to about 1000 mg, about 50 mg to about 500 mg, about 100 mg to about 500 mg, about 10 mg to about 300 mg, about 50 mg to about 300 mg, about 100 mg to about 300 mg, about 10 mg to about 150 mg, about 50 mg to about 150 mg, about 60 mg to about 120 mg, about 50 mg to about 120 mg, or a range between any two of these values. Specific examples include, for example, about 1000 mg, about 900 mg, about 800 mg, about 700 mg, about 750 mg, about 600 mg, about 500 mg, about 400 mg, about 450 mg, about 300 mg, about 250 mg, about 200 mg, about 175 mg, about 150 mg, about 125 mg, about 120 mg, about 110 mg, about 100 mg, about 90 mg, about 80 mg, about 70 mg, about 60 mg, about 50 mg, about 30 mg, about 20 mg, or any numerical value between the ranges disclosed above.

[0074] In some embodiments, the therapeutically effective amount may vary depending on, for example, the particular application for which the treatment is being administered, the location of administration of the microneedle patch, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of the compound in the dissolving microneedles may vary depending on many factors, including the dosage, chemical characteristics (e.g., hydrophobicity), and type of microneedle polymer. The dosage will likely depend on variables such as the type and progression of the disease or disorder, the overall health of the particular patient, the relative biological effectiveness of the selected compound, the composition of the excipients, and the location of its administration. Effective amounts can be estimated from dose-response curves derived from in vitro or animal model test systems.

[0075] In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise poly(lactic-co-glycolic acid) (PLGA). In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a polymer selected from PLGA (polylactic-co-glycolic acid), polyglycolic acid, fibroin, PLA (polylactic acid), PVP (polyvinylpyrrolidone), or PCL (polycaprolactone). In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a single biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise two biodegradable polymers. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a plurality of biodegradable polymers.

[0076] In some embodiments, the biodegradable polymer is capable of providing an immediate release of the therapeutically active ingredient after insertion of the microneedle patch into the skin. In further embodiments, the immediate-release biodegradable polymer is water-soluble and comprises carboxymethylcellulose, chondroitin sulfate, dextran, dextrin, polyvinylpyrrolidone, maltose, trelahose, sucrose, galactose, amylopectin, polyvinyl alcohol, and / or polyvinylpyrrolidone-methacrylic acid. In further embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases at least about 75% of the therapeutically active ingredient over a timescale of about 0 to about 24 hours. In some embodiments, the immediate-release biodegradable polymer releases about 100% of the therapeutically active ingredient over a timescale of about 0 to about 24 hours. In some embodiments, the immediate-release biodegradable polymer releases a therapeutically active ingredient in a range of about 75% to about 100%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 100%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 100%, about 85% to about 95%, about 85% to about 90%, about 90% to about 95%, about 95% to about 100%, or any value within these ranges, over a timescale of about 0 to about 24 hours. Specific examples include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, about 100%, or a range between any two of these values.

[0077] In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 10 minutes after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 5 minutes after insertion of the microneedle patch into the skin. In some embodiments, the immediate release biodegradable polymer is administered for about 0 hours to about 24 hours, about 0 hours to about 23 hours, about 0 hours to about 22 hours, about 0 hours to about 21 hours, about 0 hours to about 20 hours, about 0 hours to about 18 hours, about 0 hours to about 16 hours, about 0 hours to about 14 hours, about 0 hours to about 12 hours, about 0 hours to about 10 hours, about 0 hours to about 9 hours, about 0 hours to about 8 hours, about 0 hours to about 7 hours, about 0 hours to about 6 hours, about 0 hours to about 5 hours, or about 0 hours to about 4 hours. hours, about 0 hours to about 3 hours, about 0 hours to about 2 hours, about 0 hours to about 1 hour, about 1 hour to about 24 hours, about 1 hour to about 23 hours, about 0 hours to about 22 hours, about 0 hours to about 3 hours, about 0 hours to about 3 hours, about 0 hours to about 4 hours, about 0 hours to about 25 hours, about 1 hour to about 3 hours, about 1 hour to about 25 hours, about 1 hour to about 25 hours, about 1 hour to about 22 hours, about 1 hour to about 21 hours, about 1 hour to about 20 hours, about 1 hour to about 18 hours, about 1 hour to about 16 hours, about 1 hour to about 14 hours, about 1 hour to about 12 hours, about 1 hour to about 10 hours, about 1 hour to about 9 hours, about 1 hour to about 8 hours, about 1 hour to about 10 hours, about 1 hour to about 10 hours, about 1 hour to about 9 hours, about 1 hour to about 8 hours, about 1 hour to about 7 hours, about 1 hour to about 6 hours, about 1 hour to about 5 hours, about 1 hour to about 4 hours, about 1 hour to about 3 hours, about 1 hour to about 2 hours, about 2 hours to about 24 hours, about 2 hours to about 23 hours, about 2 hours to about 22 hours, about 2 hours to about 2 2 hours, about 2 hours to about 21 hours, about 2 hours to about 20 hours, about 2 hours to about 18 hours, about 2 hours to about 16 hours, about 2 hours to about 14 hours, about 2 hours to about 12 hours, about 2 hours to about 10 hours, about 2 hours to about 9 hours, about 2 hours to about 8 hours, about 2 hours to about 7 hours, about 2 hours to about 6 hours, about 2 hours to about 5 hours, about 2 hours to about 4 hours, about 2 hours to about 3 hours, about 5 hours to about 24 hours, about 5 hours to about 23 hours, about 5 hours to about 22 hours, about 5 hours to about 21 hours,About 5 hours to about 20 hours, about 5 hours to about 18 hours, about 5 hours to about 16 hours, about 5 hours to about 14 hours, about 5 hours to about 12 hours, about 5 hours to about 10 hours, about 5 hours to about 9 hours, about 5 hours to about 8 hours, about 5 hours to about 7 hours, about 5 hours to about 6 hours, about 12 hours to about 24 hours, about 12 hours to about 23 hours, about 12 hours to about 22 hours, about 12 hours to about 21 hours, about 12 hours to about 20 hours, About 12 hours to about 18 hours, 12 hours to about 16 hours, about 12 hours to about 14 hours, about 12 hours to about 13 hours, about 18 hours to about 24 hours, about 18 hours to about 23 hours, about 18 hours to about 22 hours, about 18 hours to about 21 hours, about 18 hours to about 20 hours, about 18 hours to about 19 hours, about 20 hours to about 24 hours, about 20 hours to about 23 hours, about 20 hours to about 22 hours, about 20 hours to about 21 hours, about 0 minutes to about 60 minutes, about 0 minutes to about 50 minutes, about 0 minutes to about 45 minutes, about 0 minutes to about 30 minutes, about 0 minutes to about 15 minutes, about 0 minutes to about 10 minutes, about 0 minutes to about 5 minutes, about 1 minute, about 0 minutes to about 4 minutes, about 0 minutes to about 3 minutes, about 0 minutes to about 2 minutes, about 0 minutes to about 1 minute, about 5 minutes to about 60 minutes, about 5 minutes to about 50 minutes, about 5 minutes to about 45 minutes, about 5 minutes to about 30 minutes, about 5 minutes to about 15 minutes, about 10 minutes to about 60 minutes, about 10 minutes to about 50 minutes, about 10 minutes to 45 minutes, about 10 minutes to about 30 minutes, about 10 minutes to about 15 minutes, about 15 minutes to about 60 minutes, about 15 minutes to about 50 minutes, about 15 minutes to about 45 minutes, about 15 minutes to about 30 minutes, about 15 minutes to about 25 minutes, about 15 minutes to about 20 minutes, about 30 minutes to about 60 minutes, about 30 minutes to about 50 minutes, about 30 minutes to about 45 minutes, about 30 minutes to about 40 minutes, 30 minutes to 35 minutes, about 45 minutes to about 60 minutes, 45 minutes to about 50 minutes, or a value within these ranges. Specific examples include about 24 hours, about 23 hours, about 22 hours, about 21 hours, about 20 hours, about 18 hours, about 16 hours, about 14 hours, about 12 hours, about 10 hours, about 9 hours, about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 60 minutes, about 55 minutes, about 50 minutes, about 45 minutes, about 40 minutes, about 35 minutes, about 30 minutes, about 25 minutes, about 20 minutes, about 15 minutes, about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, about 1 minute, or a range between any two of these values.

[0078] In some embodiments, the biodegradable polymer is capable of providing a sustained release of the therapeutically active ingredient after insertion of the microneedle patch into the skin. In further embodiments, the sustained-release biodegradable polymer is water-soluble and comprises PLGA (polylactic-coglycolic acid), polyglycolic acid, fibroin, PLA (polylactic acid), PVP (polyvinylpyrrolidone), or PCL (polycaprolactone). In further embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the sustained-release biodegradable polymer does not release more than 75% of the therapeutically active ingredient until more than about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the sustained-release biodegradable polymer does not release the therapeutically active ingredient for more than about 24 hours in an amount of about 75% to about 100%, about 75% to about 99%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 100%, about 80% to about 99%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 100%, about 85% to about 99%, 85% to about 95%, about 85% to about 90%, about 90% to about 100%, about 90% to about 99%, about 95% to about 99%, about 99% to about 100%, or any value within these ranges. Specific examples include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, and about 100%.

[0079] In some embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 day to about 30 days. In some embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient over a period of about 2 days to about 21 days. In some embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 day to about 30 days, about 1 day to about 28 days, about 1 day to about 26 days, about 1 day to about 24 days, about 1 day to about 22 days, about 1 day to about 21 days, about 1 day to about 14 days, about 1 day to about 7 days, about 1 day to about 6 days, about 1 day to about 5 days, about 1 day to about 4 days, about 1 day to about 3 days, about 1 day to about 2 days, about 2 days to about 30 days, about 2 days to about 28 days, about 2 days to about 26 days, about 2 days to about 24 days, about 2 days to about 30 ...28 days, about 2 days to about 26 days, about 2 days to about 24 days, about 2 days to about 30 days, about 2 days to about 30 days, about ~ about 22 days, about 2 to about 21 days, about 2 to about 14 days, about 2 to about 7 days, about 2 to about 6 days, about 2 to about 5 days, about 2 to about 4 days, about 2 to about 3 days, about 3 to about 30 days, about 3 to about 28 days, about 3 to about 26 days, about 3 to about 24 days, about 3 to about 22 days, about 3 to about 21 days, about 3 to about 14 days, about 3 to about 7 days, about 3 to about 6 days, about 3 to about 5 days, about 3 to about 4 days, about 4 to about 30 days, about 4 to about 28 Days, about 4 to about 26 days, about 4 to about 24 days, about 4 to about 22 days, about 4 to about 21 days, about 4 to about 14 days, about 4 to about 7 days, about 4 to about 6 days, about 4 to about 5 days, about 5 to about 30 days, about 5 to about 28 days, about 5 to about 26 days, about 5 to about 24 days, about 5 to about 22 days, about 5 to about 21 days, about 5 to about 14 days, about 5 to about 7 days, about 5 to about 6 days, about 7 to about 30 days, about 7 to about 28 days, about 7 to about 26 The therapeutically active agent is released over a period of about 1 day, about 7 to about 24 days, about 7 to about 22 days, about 7 to about 21 days, about 7 to about 14 days, about 14 to about 30 days, about 14 to about 28 days, about 14 to about 26 days, about 14 to about 24 days, about 14 to about 22 days, about 14 to about 21 days, about 21 to about 30 days, about 21 to about 28 days, about 21 to about 26 days, about 21 to about 24 days, about 21 to about 22 days, or within these ranges. Specific examples include about 30 days, about 28 days, about 26 days, about 24 days, about 22 days, about 21 days, about 14 days, about 7 days, about 6 days, about 5 days, about 4 days, about 3 days, about 2 days, about 1 day, or a range between any two of these values.

[0080] In some embodiments, the biodegradable polymer is capable of providing both sustained and immediate release of the therapeutically active ingredient after insertion of the microneedle patch into the skin. In some embodiments, the plurality of microneedles comprises an immediate-release biodegradable polymer and a sustained-release biodegradable polymer. In some embodiments, the plurality of microneedles comprises an immediate-release biodegradable polymer at the base of the microneedles and a sustained-release biodegradable polymer at the tip of the microneedles. In some embodiments, the plurality of microneedles comprises an immediate-release biodegradable polymer at the base of the microneedles and alternating layers of immediate-release biodegradable polymer and sustained-release biodegradable polymer at the tip of the microneedles.

[0081] In some embodiments, the dissolvable microneedle patch is applied onto a skin lesion of a patient in need thereof to treat a skin condition. In some embodiments, the dissolvable microneedle patch is applied adjacent to a skin lesion of a patient in need thereof to treat a skin condition. In some embodiments, the dissolvable microneedle patch is applied to an area of ​​skin determined to be optimal based on the age of the patient. In some embodiments, the dissolvable microneedle patch is applied to an area of ​​skin determined to be optimal based on the type of skin requiring treatment.

[0082] In some embodiments, the dissolvable microneedle patch comprises multiple microneedles, the microneedles being spatially separated within the skin such that one microneedle does not touch another microneedle. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedle patch has at least about 1 to about 200 microneedles per square centimeter, about 1 to about 175 microneedles per square centimeter, about 1 to about 150 microneedles per square centimeter, about 125 microneedles per square centimeter, about 100 microneedles per square centimeter, about 90 microneedles per square centimeter, about 80 microneedles per square centimeter, about 70 microneedles per square centimeter, about 60 microneedles per square centimeter, about 50 microneedles per square centimeter, about 40 microneedles per square centimeter, about 30 microneedles per square centimeter, about 25 microneedles per square centimeter, about 2 ... About 1 to about 15 microneedles, about 1 to about 10 microneedles per square centimeter, about 1 to about 5 microneedles per square centimeter, about 5 to about 200 microneedles per square centimeter, about 5 to about 175 microneedles per square centimeter, about 5 to about 150 microneedles per square centimeter, about 5 to about 125 microneedles per square centimeter, about 5 to about 100 microneedles per square centimeter, about 5 to about 90 microneedles per square centimeter, about 5 to about 80 microneedles per square centimeter, about 5 to about 70 microneedles per square centimeter, about 5 to about 60 microneedles per square centimeter, about 5 to about 50 microneedles per square centimeter, about 5 to about 40 microneedles per square centimeter, about 5 to about 30 microneedles per square centimeter, about 5 to about 25 microneedles per square centimeter,About 5 to about 20 microneedles per square centimeter, about 5 to about 15 microneedles per square centimeter, about 5 to about 20 microneedles per square centimeter, about 10 to about 200 microneedles per square centimeter, about 10 to about 175 microneedles per square centimeter, about 10 to about 150 microneedles per square centimeter, about 10 to about 150 microneedles per square centimeter, about 10 to about 125 microneedles / square centimeter, about 10 to about 100 microneedles / square centimeter inches, about 10 to about 90 microneedles / square centimeter, about 10 to about 80 microneedles / square centimeter, about 10 to about 70 microneedles / square centimeter, about 10 to about 60 microneedles / square centimeter, about 10 to about 50 microneedles / square centimeter, about 10 to about 40 microneedles / square centimeter, about 10 to about 30 microneedles / square centimeter, about 10 to about 25 microneedles / square centimeter, about 10 to about 20 microneedles / square centimeter, about 10 to about 15 microneedles / square centimeter about 25 to about 200 microneedles per square centimeter, about 25 to about 175 microneedles per square centimeter, about 25 to about 150 microneedles per square centimeter, about 25 to about 125 microneedles per square centimeter, about 25 to about 100 microneedles per square centimeter, about 25 to about 90 microneedles per square centimeter, about 25 to about 80 microneedles per square centimeter, about 25 to about 70 microneedles per square centimeter, about 25 to about 100 microneedles per square centimeter, about 25 to about 125 microneedles per square centimeter, about 25 to about 10 ... Approximately 25 to 60 microneedles per square centimeter, approximately 25 to 50 microneedles per square centimeter, approximately 25 to 40 microneedles per square centimeter, approximately 25 to 30 microneedles per square centimeter, approximately 50 to 200 microneedles per square centimeter, approximately 50 to 175 microneedles per square centimeter, approximately 50 to 150 microneedles per square centimeter, approximately 50 to 125 microneedles per square centimeter, approximately 50 to 100 microneedles per square centimeter,About 50 to about 90 microneedles per square centimeter, about 50 to about 80 microneedles per square centimeter, about 50 to about 70 microneedles per square centimeter, about 50 to about 60 microneedles per square centimeter, about 75 to about 200 microneedles per square centimeter, about 75 to about 175 microneedles per square centimeter, about 75 to about 150 microneedles per square centimeter, about 75 to about 125 microneedles per square centimeter, about 75 to about 100 microneedles per square centimeter, about 75 to about 90 microneedles per square centimeter, about 75 to about 80 microneedles, about 100 to about 200 microneedles per square centimeter, about 100 to about 175 microneedles per square centimeter, about 100 to about 150 microneedles per square centimeter, about 100 to about 125 microneedles per square centimeter, 125 to about 200 microneedles per square centimeter, about 125 to about 175 microneedles per square centimeter, about 125 to about 150 microneedles per square centimeter, about 150 to about 200 microneedles per square centimeter, about 150 to about 175 microneedles per square centimeter, about 175 to about 200 microneedles per square centimeter, or values ​​within these ranges. Specific examples may include a dissolvable microneedle patch comprising a plurality of microneedles, the microneedle patch having at least about 200 microneedles per square centimeter, at least about 175 microneedles per square centimeter, at least about 150 microneedles per square centimeter, at least about 200 microneedles per square centimeter, at least about 125 microneedles / square centimeter, at least about 100 microneedles / square centimeter, at least about 90 microneedles / square centimeter, at least about 80 microneedles / square centimeter, at least about 70 microneedles / square centimeter, at least about 60 microneedles / square centimeter, at least about 50 microneedles / square centimeter, at least about 40 microneedles / square centimeter,At least about 30 microneedles / square centimeter, at least about 25 microneedles / square centimeter, at least about 20 microneedles / square centimeter, at least about 15 microneedles / square centimeter, at least about 10 microneedles / square centimeter, at least about 5 microneedles / square centimeter, at least about 4 microneedles / square centimeter, at least about 3 microneedles / square centimeter, at least about 2 microneedles / square centimeter, at least about 1 microneedle / square centimeter, or any two ranges between these values.

[0083] In some embodiments, the dissolvable microneedle patch is of any shape necessary to accommodate the surface topology of the skin. In some embodiments, the dissolvable microneedle patch has any number of sides, n, ranging from about 0 sides to about 1000 sides. In some embodiments, the dissolvable microneedle patch has about 0 sides to about 1000 sides, about 0 sides to about 900 sides, about 0 sides to about 800 sides, about 0 sides to about 700 sides, about 0 sides to about 600 sides, about 0 sides to about 500 sides, or about 0 sides to about 400 sides. Approximately 0 to approximately 300 sides, approximately 0 to approximately 200 sides, approximately 0 to approximately 100 sides, approximately 0 to approximately 90 sides, approximately 0 to approximately 80 sides, approximately 0 to approximately 70 sides, approximately 0 to approximately 60 sides, approximately 0 to approximately 50 sides, approximately 0 to approximately 40 sides, approximately 0 to approximately 30 sides, approximately 0 to approximately 20 sides, approximately 0 to approximately 10 sides, approximately 0 to approximately 9 sides, approximately 0 to approximately 8 sides, approximately 0 to approximately 7 sides, approximately 0 to approximately 6 sides, approximately 0 to approximately 5 sides, approximately 0 to approximately 4 sides, approximately 0 to approximately 3 sides, approximately 0 to approximately 2 sides, approximately 10 to approximately 1000 sides, approximately 10 sides ~approximately 900 sides, approximately 10 sides to approximately 800 sides, approximately 10 sides to approximately 700 sides, approximately 10 sides to approximately 600 sides, approximately 10 sides to approximately 500 sides, approximately 10 sides to approximately 400 sides, approximately 10 sides to approximately 300 sides, approximately 10 sides to approximately 200 sides, approximately 10 sides to approximately 100 sides, approximately 10 sides to approximately 90 sides, approximately 10 sides to approximately 80 sides, approximately 10 sides to approximately 70 sides, approximately 10 sides to approximately 60 sides, approximately 10 sides to approximately 50 sides, approximately 10 sides to approximately 40 sides, approximately 10 sides to approximately 30 sides, approximately 10 sides to approximately 20 sides, approximately 20 sides to approximately 1000 sides 20 sides to approximately 900 sides, approximately 20 sides to approximately 800 sides, approximately 20 sides to approximately 700 sides, approximately 20 sides to approximately 600 sides, approximately 20 sides to approximately 500 sides, approximately 20 sides to approximately 400 sides, approximately 20 sides to approximately 300 sides, approximately 20 sides to approximately 200 sides, approximately 20 sides to approximately 100 sides, approximately 20 sides to approximately 90 sides, approximately 20 sides to approximately 80 sides, approximately 20 sides to approximately 70 sides, approximately 20 sides to approximately 60 sides, approximately 20 sides to approximately 50 sides, approximately 20 sides to approximately 40 sides, approximately 20 sides to 30 sides, approximately 100 sides to approximately 900 sides, approximately 30 sides to approximately 800 sides, approximately 20 sides to approximately 600 sides, approximately 30 sides to approximately 700 sides, approximately 30 sides to approximately 600 sides, approximately 30 sides to approximately 500 sides, approximately 30 sides to approximately 400 sides, approximately 30 sides to approximately 300 sides, approximately 30 sides to approximately 200 sides, approximately 30 sides to approximately 100 sides, approximately 30 sides to approximately 90 sides, approximately 30 sides to approximately 80 sides, approximately 30 sides to approximately 70 sides, approximately 30 sides to approximately 60 sides, approximately 30 sides to approximately 50 sides, approximately 30 sides to approximately 40 sides, approximately 50 sides to approximately 1000 sides, approximately 50 sides to approximately 900 sides, approximately 50 sides to approximately 800 sides, approximately 50 sides to approximately 700 sides,Approximately 50 to 600 sides, approximately 50 to 500 sides, approximately 50 to 400 sides, approximately 50 to 300 sides, approximately 50 to 200 sides, approximately 50 to 100 sides, approximately 50 to 90 sides, approximately 50 to 80 sides, approximately 50 to 70 sides, approximately 50 to 60 sides, approximately 100 sides, approximately 75 to 900 sides, approximately 75 to 80 0 sides, approximately 75 to 700 sides, approximately 600 sides, approximately 75 to 500 sides, approximately 750 to approximately 400 sides, approximately 75 to approximately 300 sides, approximately 75 to approximately 200 sides, approximately 75 to approximately 100 sides, approximately 75 to approximately 90 sides, approximately 75 to approximately 80 sides, approximately 100 sides to approximately 1000 sides, approximately 100 sides to approximately 900 sides, approximately 100 sides to approximately 700 sides, approximately 100 sides ~approx. 600 sides, ~approx. 100 sides to ~approx. 500 sides, ~approx. 100 sides to ~approx. 400 sides, ~approx. 100 sides to ~approx. 300 sides, ~approx. 100 sides to ~approx. 200 sides, ~approx. 150 to 1000 sides, ~approx. 150 to ~approx. 900 sides, ~approx. 250 sides to ~approx. 800 sides, ~approx. 250 sides to ~approx. 700 sides, ~approx. 250 sides to ~approx. 600 sides, ~approx. 250 sides to ~approx. 500 sides, ~approx. 250 It may be about 400 sides, about 250 sides to about 300 sides, about 500 sides to about 1000 sides, about 500 sides to about 900 sides, about 500 sides to about 800 sides, about 500 sides to about 600 sides, about 750 sides to about 1000 sides, about 750 sides to about 900 sides, about 800 sides, about 900 sides to 1000 sides, or a value within these ranges. Specific examples include dissolvable microneedle patches having a diameter of about 1000 sides, about 900 sides, about 800 sides, about 700 sides, about 600 sides, about 500 sides, about 400 sides, about 300 sides, about 200 sides, about 100 sides, about 90 sides, about 80 sides, about 70 sides, about 60 sides, about 50 sides, about 40 sides, about 30 sides, about 20 sides, about 10 sides, about 9 sides, about 8 sides, about 7 sides, about 6 sides, about 5 sides, about 4 sides, about 3 sides, about 2 sides, or a range between any two of these values.

[0084] In further embodiments, the dissolvable microneedle patch may have sides of equal length. In further embodiments, the dissolvable microneedle patch may have sides of unequal length. In some embodiments, the dissolvable microneedle patch is in the shape of a medical bandage. In some embodiments, the dissolvable microneedle patch is in a size range of about 0.1 square centimeters to about 1000 square centimeters, about 0.1 square centimeters to about 900 square centimeters, about 0.1 square centimeters to about 800 square centimeters, about 0.1 square centimeters to about 700 square centimeters, about 0.1 square centimeters to about 600 square centimeters, about 0.1 square centimeters to about 500 square centimeters, about 0.1 square centimeters to about 400 square centimeters, about 0.1 square centimeters to about 300 square centimeters, about 0.1 square centimeters to about 200 square centimeters, about 0.1 square centimeters to about 100 square centimeters, about 0.1 square centimeters to about 90 square centimeters, about 0.1 square centimeters to about 80 square centimeters, about 0.1 square centimeters to about 70 square centimeters, about 0.1 square centimeters to about 60 square centimeters centimeters, about 0.1 square centimeters to about 60 square centimeters, about 100 square centimeters, 1 square centimeter to about 50 square centimeters, about 0.1 square centimeters to about 40 square centimeters, about 0.1 square centimeters to about 30 square centimeters, about 0.1 square centimeters to about 20 square centimeters, about 0.1 square centimeters to about 10 square centimeters, about 0.1 square centimeters to about 5 square centimeters, about 0.1 square centimeters to about 4 square centimeters, about 0.1 square centimeters to about 3 square centimeters, about 0.1 square centimeters to about 3,000 square centimeters, 1 square centimeter to about 2 square centimeters, about 0.1 square centimeters to about 1 square centimeter, about 0.1 square centimeters to about 0.9 square centimeters, about 0.1 square centimeters to about 0.8 square centimeters, about 0.1 square centimeters to about 0.7 square centimeters,Approximately 0.1 square centimeters to approximately 0.6 square centimeters, approximately 0.1 square centimeters to approximately 0.5 square centimeters, approximately 0.1 square centimeters to approximately 100 square centimeters, 1 square centimeter to approximately 0.4 square centimeters, approximately 0.1 square centimeters to approximately 0.3 square centimeters, approximately 0.1 square centimeters to approximately 0.2 square centimeters, approximately 0.5 square centimeters to approximately 1000 square centimeters, approximately 0.5 square centimeters to approximately 900 square centimeters, approximately 0.1 square centimeters to approximately 200 square centimeters meters, 5 square centimeters to about 900 square centimeters, about 0.5 square centimeters to about 800 square centimeters, about 0.5 square centimeters to about 700 square centimeters, about 0.5 square centimeters to about 600 square centimeters, about 0.5 square centimeters to about 1,500 square centimeters, about 0.5 square centimeters to about 1,600 square centimeters, 5 square centimeters to about 500 square centimeters, about 0.5 square centimeters to about 400 square centimeters, about 0.5 square centimeters to about 3 00 square centimeters, about 0.5 square centimeters to about 200 square centimeters, about 0.5 square centimeters to about 100 square centimeters, about 0.5 square centimeters to about 90 square centimeters, about 0.5 square centimeters to about 80 square centimeters, about 0.5 square centimeters to about 60 square centimeters, about 70 square centimeters to about 90 square centimeters, about 40 square centimeters to about 60 square centimeters, about 40 square centimeters to about 40 square centimeters, 5 square centimeters to about 70 square centimeters inches, about 0.5 square centimeters to about 60 square centimeters, about 0.5 square centimeters to about 50 square centimeters, about 0.5 square centimeters to about 40 square centimeters, about 0.5 square centimeters to about 30 square centimeters, about 0.5 square centimeters to about 20 square centimeters, about 0.5 square centimeters to about 10 square centimeters, about 0.5 square centimeters to about 5 square centimeters, about 0.5 square centimeters to about 40 square centimeters, 5 square centimeters to about 4 square centimeters,Approximately 0.5 square centimeters to approximately 3 square centimeters, approximately 0.5 square centimeters to approximately 2 square centimeters, approximately 0.5 square centimeters to approximately 1 square centimeter, approximately 0.5 square centimeters to approximately 0.9 square centimeters, approximately 0.5 square centimeters to approximately 0.8 square centimeters, approximately 0.5 square centimeters to approximately 0.7 square centimeters, approximately 0.5 square centimeters to approximately 0.6 square centimeters, approximately 1 square centimeter to approximately 1000 square centimeters, approximately 1 square centimeter to approximately 900 square centimeters 1 square centimeter to about 800 square centimeters, about 1 square centimeter to about 700 square centimeters, about 1 square centimeter to about 600 square centimeters, about 1 square centimeter to about 500 square centimeters, about 1 square centimeter to about 400 square centimeters, about 1 square centimeter to about 300 square centimeters, about 1 square centimeter to about 200 square centimeters, about 1 square centimeter to about 100 square centimeters, 1 square centimeter to about 90 square centimeters, about 1 square centimeter to about 80 square centimeters, approximately 1 square centimeter to approximately 70 square centimeters, approximately 1 square centimeter to approximately 60 square centimeters, approximately 1 square centimeter to approximately 50 square centimeters, approximately 1 square centimeter to approximately 40 square centimeters, approximately 1 square centimeter to approximately 30 square centimeters, approximately 1 square centimeter to approximately 20 square centimeters, approximately 1 square centimeter to approximately 10 square centimeters, approximately 1 square centimeter to approximately 5 square centimeters, approximately 1 square centimeter to approximately 4 square centimeters, approximately 1 square centimeter to approximately 3 Square centimeters, approximately 1 square centimeter to approximately 2 square centimeters, approximately 10 square centimeters to approximately 1000 square centimeters, approximately 10 square centimeters to approximately 900 square centimeters, approximately 10 square centimeters to approximately 800 square centimeters, approximately 10 square centimeters to approximately 700 square centimeters, 10 square centimeters to approximately 600 square centimeters, approximately 10 square centimeters to approximately 500 square centimeters, approximately 10 square centimeters to approximately 400 square centimeters, approximately 10 square centimeters to approximately 300 square centimeters,Approximately 10 square centimeters to approximately 200 square centimeters, approximately 10 square centimeters to approximately 100 square centimeters, approximately 10 square centimeters to approximately 90 square centimeters, approximately 10 square centimeters to approximately 80 square centimeters, approximately 10 square centimeters to approximately 70 square centimeters, approximately 10 square centimeters to approximately 60 square centimeters, approximately 10 square centimeters to approximately 50 square centimeters, approximately 10 square centimeters to approximately 40 square centimeters, approximately 10 square centimeters to approximately 30 square centimeters, approximately 10 square centimeters to approximately 20 square centimeters, approximately 50 square centimeters to approximately 1000 square centimeters, approximately 50 square centimeters to approximately 900 square centimeters, approximately 50 square centimeters to approximately 800 square centimeters, approximately 50 square centimeters to approximately 700 square centimeters, approximately 50 square centimeters to approximately 600 square centimeters, approximately 50 square centimeters to approximately 500 square centimeters, approximately 50 square centimeters to approximately 400 square centimeters, approximately 50 square centimeters to approximately 300 square centimeters, approximately 50 square centimeters to approximately 200 square centimeters meters, about 50 square centimeters to about 100 square centimeters, about 75 square centimeters to about 1000 square centimeters, about 75 square centimeters to about 900 square centimeters, about 75 square centimeters to about 800 square centimeters, about 75 square centimeters to about 700 square centimeters, about 75 square centimeters to about 600 square centimeters, about 75 square centimeters to about 500 square centimeters, about 75 square centimeters to about 400 square centimeters, about 75 square centimeters to about 300 square centimeters, Approximately 75 square centimeters to approximately 200 square centimeters, approximately 75 square centimeters to approximately 100 square centimeters, approximately 100 square centimeters to approximately 1000 square centimeters, approximately 100 square centimeters to approximately 900 square centimeters, approximately 100 square centimeters to approximately 800 square centimeters, approximately 100 square centimeters to approximately 700 square centimeters, approximately 100 square centimeters to approximately 600 square centimeters, approximately 100 square centimeters to approximately 500 square centimeters, approximately 100 square centimeters to approximately 400 square centimeters,Approximately 100 square centimeters to approximately 300 square centimeters, approximately 100 square centimeters to approximately 200 square centimeters, approximately 250 square centimeters to approximately 1000 square centimeters, approximately 250 square centimeters to approximately 900 square centimeters, approximately 250 square centimeters to approximately 800 square centimeters, approximately 250 square centimeters to approximately 700 square centimeters, approximately 250 square centimeters to approximately 600 square centimeters, approximately 250 square centimeters to approximately 500 square centimeters, approximately 250 square centimeters to approximately 400 square centimeters meters, about 250 square centimeters to about 300 square centimeters, about 500 square centimeters to about 1000 square centimeters, about 500 square centimeters to about 900 square centimeters, about 500 square centimeters to about 800 square centimeters, about 500 square centimeters to about 700 square centimeters, about 500 square centimeters to about 600 square centimeters, about 750 square centimeters to about 1000 square centimeters, about 750 square centimeters to about 900 square centimeters, about 750 square centimeters to about 8 Specific examples of dissolvable microneedle patches are about 1000 square centimeters, about 900 square centimeters, about 800 square centimeters, about 700 square centimeters, about 600 square centimeters, about 500 square centimeters, about 400 square centimeters, about 300 square centimeters, about 200 square centimeters, about 100 square centimeters, about 90 square centimeters, about 80 square centimeters, about 70 square centimeters, about 60 square centimeters, about 80 square centimeters, about 90 square centimeters, about 10 ... Square centimeters, about 50 square centimeters, about 40 square centimeters, about 30 square centimeters, about 20 square centimeters, about 10 square centimeters, about 5 square centimeters, about 4 square centimeters, about 3 square centimeters, about 2 square centimeters, about 1 square centimeter, about 0.9 square centimeters, about 0.8 square centimeters, about 0.7 square centimeters, about 0.6 square centimeters, about 0.5 square centimeters, about 0.4 square centimeters, about 0.3 square centimeters, about 0.2 square centimeters,Approximately 0.1 square centimeters or a range between any two of these values.

[0085] In some embodiments, the dissolvable microneedle patch comprises a backing layer and a microneedle layer. In some embodiments, the dissolvable microneedle patch comprises a backing layer and a microneedle layer, where the microneedle layer is placed directly on the skin. In some embodiments, the dissolvable microneedle patch comprises a backing layer, where the backing layer is comprised of adhesive medical tape. In some embodiments, the dissolvable microneedle patch comprises a backing layer, where the backing layer comprises a therapeutically active ingredient.

[0086] In some embodiments, the dissolvable microneedle patch comprises a backing layer, the backing layer being a removable substrate. In some embodiments, the dissolvable microneedle patch comprises a removable substrate comprising adhesive medical tape. In some embodiments, the backing layer comprises a fast-dissolving polymer. In some embodiments, the dissolvable microneedle patch comprises a removable substrate comprising a therapeutically active ingredient dispersed in the polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles attached to a removable substrate and comprising tapered tips extending away from the removable substrate. In some embodiments, the dissolvable microneedle patch comprises a removable substrate that releases at least about 90% of the microneedles from the adhesive surface within about 20 minutes after application to the skin. In some embodiments, a dissolvable microneedle patch is provided wherein the removable substrate releases at least about 90% of the microneedles from the adhesive surface within about 5 minutes after application to the skin.In some embodiments, 90% of the microneedles are between about 0 minutes and about 20 minutes, about 0 minutes and about 15 minutes, about 0 minutes and about 10 minutes, about 0 minutes and about 9 minutes, about 0 minutes and about 8 minutes, about 0 minutes and about 7 minutes, about 0 minutes and about 6 minutes, about 0 minutes and about 5 minutes, about 0 minutes and about 4 minutes, about 0 minutes and about 3 minutes, about 0 minutes and about 2 minutes, about 0 minutes and about 1 minute, about 1 minute and about 20 minutes, about 1 minute and about 15 minutes, about 1 minute and about 10 minutes, about 1 minute and about 9 minutes, about 1 minute and about 8 minutes, about 1 minute and about 7 minutes, about 1 minute and about 6 minutes, about 1 minute and about 5 minutes, about 1 minute and about 4 minutes, about 1 minute and about 3 minutes, about 1 minute and about 2 minutes, about 2 minutes and about 20 minutes, about 2 minutes and about 15 minutes. minutes, about 2 minutes to about 10 minutes, about 2 minutes to about 9 minutes, about 2 minutes to about 8 minutes, about 2 minutes to about 7 minutes, about 2 minutes to about 6 minutes, about 2 minutes to about 5 minutes, about 2 minutes to about 4 minutes , about 2 minutes to about 3 minutes, about 5 minutes to about 20 minutes, about 5 minutes to about 15 minutes, about 5 minutes to about 10 minutes, about 5 minutes to about 5 minutes, about 5 minutes to about 9 minutes, about 5 minutes to about 8 minutes, about 5 minutes to approximately 7 minutes, approximately 5 minutes to approximately 6 minutes, approximately 10 minutes to approximately 20 minutes, approximately 10 minutes to approximately 15 minutes, approximately 15 minutes to approximately 20 minutes, approximately 0 seconds to approximately 60 seconds, approximately 0 seconds to approximately 45 seconds, about 0 seconds to about 30 seconds, about 0 seconds to about 15 seconds, about 0 seconds to about 10 minutes, about 0 seconds to about 9 seconds, about 0 seconds to about 8 seconds, about 0 seconds to about 7 seconds, about 0 seconds to about Approximately 6 seconds, approximately 0 seconds to approximately 5 seconds, approximately 0 seconds to approximately 4 seconds, approximately 0 seconds to approximately 3 seconds, approximately 0 seconds to approximately 2 seconds, approximately 1 second to approximately 60 seconds, approximately 1 second to approximately 45 seconds, approximately 1 second to approximately Approximately 30 seconds, approximately 1 second to approximately 15 seconds, approximately 1 second to approximately 10 seconds, approximately 1 second to approximately 9 seconds, approximately 1 second to approximately 8 seconds, approximately 1 second to approximately 7 seconds, approximately 1 second to approximately 6 seconds, approximately 1 second to approximately Approximately 5 seconds, approximately 1 second to approximately 4 seconds, approximately 1 second to approximately 3 seconds, approximately 1 second to approximately 2 seconds, approximately 2 seconds to approximately 60 seconds, approximately 2 seconds to approximately 45 seconds, approximately 2 seconds to approximately 30 seconds, approximately 2 seconds ~15 seconds, approximately 2 seconds to approximately 10 seconds, approximately 2 seconds to approximately 9 seconds, approximately 2 seconds to approximately 8 seconds, approximately 2 seconds to approximately 7 seconds, approximately 2 seconds to approximately 6 seconds, approximately 2 seconds to approximately 5 seconds, approximately 2 seconds ~ The dissolvable microneedle patch is released from the adhesive surface within a period of about 4 seconds, about 2 to about 3 seconds, about 5 to about 60 seconds, about 5 to about 45 seconds, about 5 to about 30 seconds, about 5 to about 15 seconds, about 5 to about 10 seconds, about 5 to about 9 seconds, about 5 to about 8 seconds, about 5 to about 7 seconds, about 5 to about 6 seconds, about 10 to about 60 seconds, about 10 to about 45 seconds, about 10 to about 30 seconds, about 10 to about 15 seconds, about 15 to about 60 seconds, about 15 to about 45 seconds, about 15 to about 30 seconds, about 30 to about 60 seconds, about 30 to about 45 seconds, about 45 to about 60 seconds, or within a range of these values.In specific examples, 90% of the microneedles are released from the adhesive surface of the dissolvable microneedle patch within about 20 minutes, about 15 minutes, about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, about 1 minute, about 60 seconds, about 45 seconds, about 30 seconds, about 15 seconds, about 10 seconds, about 9 seconds, about 8 seconds, about 7 seconds, about 6 seconds, about 5 seconds, about 4 seconds, about 3 seconds, about 2 seconds, about 1 second, or a range between any two of these values.

[0087] In some embodiments, a dissolvable microneedle patch in which a backing layer overlies the base of the tip portion such that each microneedle is separated from the other microneedles on the patch and forms a discrete entity when the substrate is removed upon application of the patch to the skin is as follows:

[0088] In some embodiments, the dissolvable microneedle patch comprises the steps of (i) placing the patch on a superficial area of ​​a patient's skin in need of treatment, or in a pre-treatment study to assess hypersensitivity reactions, general tolerability, or other adverse events; (ii) applying sufficient force to the patch composition to cause the microneedles to penetrate the epidermis and enter the papillary dermis; and (iii) allowing the plurality of microneedles to remain within the skin until the biodegradable polymer degrades; and (iv) removing the adhesive substrate from the patch composition, wherein step (ii) is performed by applying finger pressure, the pressure being sufficient to provide a force ranging from about 0 N to about 1,000 N. In a preferred embodiment of the present application, the applied pressure is about 10 N. In an alternative embodiment of the present application, step (ii) is performed by impact insertion using an applicator device, wherein the pressure is sufficient to provide a force ranging from about 0 N to about 1,000 N. In a preferred embodiment of the present application, the applied pressure is about 10 N. In some embodiments, the force applied by a finger or applicator device is from about 0 N to about 1,000 N, from about 0 N to about 900 N, from about 0 N to about 800 N, from about 0 N to about 700 N, from about 0 N to about 600 N, from about 0 N to about 500 N, from about 0 N to about 400 N, from about 0 N to about 300 N, from about 0 N to about 200 N, from about 0 N to about 1 ... Approximately 90N, approximately 0N to approximately 80N, approximately 0N to approximately 70N, approximately 0N to approximately 60N, approximately 0N to approximately 50N, approximately 0N to approximately 40N, approximately 0N to approximately 30N, approximately 0N to approximately 20N, approximately 0N ~approx. 10N, approx. 0N to approx. 9N, approx. 0N to approx. 8N, approx. 0N to approx. 7N, approx. 0N to approx. 6N, approx. 0N to approx. 5N, approx. 0N to approx. 4N, approx. 0N to approx. 3N, approx. N ~ about 1N, about 0N - about 0.9N, about 0N - about 0.8N, about 0N - about 0.7N, about 0N - about 0.6N, about 0N - about 0.5N, about 0N - about 0.4N, about 0N - about 0.3N, about 0N to about 0.3N, about 0N to about 0.2N, about 0.1N to about 1000N, about 0.1N to about 900N, about 0.1N to about 800N, about 0.1N to about 700 N, about 0.1N to about 600N, about 0.1N to about 500N, about 0.1N to about 400N, about 0.2N to about 500N, about 100N to about 500N, about 100N to about 60 0N, about 100N to about 600N, about 0N to about 600N, about 100N to about 600N, about 100N to about 600N, about 1N to about 300N, about 0.1N to about 200N, about 0.1N~approx. 100N, approx. 0.1N~approx. 90N, approx. 0.1N~approx. 80N, approx. 0.1N~approx. 70N, approx. 0.1N~approx. 60N, approx. 0.1N~approx. 50N, approx. 0.1N~approx. 40N, approx. 0.1N~approx. 40N, approx. 100N~approx. 100N, 1N~approx. 30N, approx. 0.1N~approx. 20N, approx. 0.1N~approx. 10N, approx. 9N, approx. 0.1N~approx. 8N, approx. 0.1N ~approx. 7N, approx. 0.1N~approx. 6N, approx. 0.1N~approx. 5N, approx. 0.1N~approx. 4N, approx. 0.1N~approx. 3N, approx. 0.1N~approx. 0.1N, approx. 1N~approx. 2N, approx. 0.1N~approx. 0.9N, approx. 0.1N~approx. 0.8N, approx. 0.1N~approx. 0.7N, approx. 0.1N~approx. 0.6N, approx. 0.1N~approx. 0.5N, approx. 0.1N~approx. 0.4N, 0.1 N ~ approx. 0.3N, 0.1N ~ approx. 0.2N, approx. 1N ~ approx. 1N, approx. 1N ~ approx. 2N, approx. 1N ~ approx. 1N, approx. 1N ~ approx. 2N, approx. 1N ~ approx. 1000N, approx. 1N ~ approx. 900N, approx. 1N ~ approx. 800N, approx. 1N ~ approx. 700N, approx. 1N ~ approx. 600N, approx. 1N ~Approx. 500N, Approx. 1N~Approx. 400N, Approx. 1N~Approx. 300N, Approx. 1N~Approx. 200N, Approx. 1N~Approx. 100N, Approx. 1N~Approx. 90N, Approx. 1N~Approx. 80N, Approx. 1N~Approx. 70N, Approx. 1N~Approx. 60N, Approx. 1N~Approx. 50N, Approx. 1N~Approx. 40N, Approx. 1N~Approx. 30N, Approx. 1N~Approx. 20N, Approx. 1N~Approx. 10N, Approx. 1N~Approx. 9N, Approx. 1N~Approx. 8N, Approx. 1.Approximately 1N to approximately 7N, approximately 1N to approximately 6N, approximately 1N to approximately 5N, approximately 1N to approximately 4N, approximately 1N to approximately 3N, approximately 1N to approximately 2N, approximately 10N to approximately 1000N, approximately 10N to approximately 900N, approximately 10N to approximately 80 0N, about 10N to about 700N, about 10N to about 600N, about 10N to about 500N, about 10N to about 400N, about 10N to about 300N, about 10N to about 200N, about 10N to about 100N , about 10N to about 90N, about 10N to about 80N, about 10N to about 70N, about 10N to about 60N, about 10N to about 50N, about 10N to about 40N, about 10N to about 30N, about 10N to about 20 N, about 50N to about 1000N, about 50N to about 900N, about 50N to about 800N, about 50N to about 700N, about 50N to about 600N, about 50N to about 500N, about 50N to about 400N , about 50N to about 300N, about 50N to about 200N, about 50N to about 100N, about 100N to about 1000N, about 100N to about 900N, about 100N to about 800N, about 100N to about 700N, about 100N to about 600N, about 100N to about 500N, about 100N to about 400N, about 100N to about 300N, about 100N to about 200N, about 200N to about 1000N, about 2 00N to about 900N, about 200N to about 800N, about 200N to about 700N, about 200N to about 600N, about 200N to about 500N, about 200N to about 400N, about 200N to about 300N, about 500N to about 1000N, about 500N to about 900N, about 500N to about 800N, about 500N to about 700N, about 500N to about 600N, or a value within these ranges. In specific examples, the force applied by the finger or applicator device is about 0 N, about 0.1 N, about 0.2 N, about 0.3 N, about 0.4 N, about 0.5 N, about 0.6 N, about 0.7 N, about 0.8 N, about 0.9 N, about 1 N, about 2 N, about 3 N, about 4 N, about 5 N, about 6 N, about 7 N, about 8 N, about 9 N, about 10 N, about 15 N, about 20 N, about 30 N, about 40 N, about 50 N, about 60 N, about 70 N, about 80 N, about 90 N, about 100 N, about 200 N, about 300 N, about 400 N, about 500 N, about 600 N, about 700 N, about 800 N, about 900 N, or ranges therebetween and between any two numerical values.

[0089] skin disease treatment Embodiments of the present application are directed to a method of treating a skin condition comprising applying a dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin, applying sufficient force to the dissolvable microneedle patch to allow the microneedles to penetrate a location selected from the group consisting of the epidermis, the dermis, and the papillary dermis, removing the adhesive matrix from the patch composition, and allowing the plurality of microneedles to remain within the skin until the biodegradable polymer degrades.

[0090] In some embodiments, a method of treating a skin condition comprising applying a dissolvable microneedle patch comprises a plurality of microneedles selected from the group consisting of a length terminating in the epidermis and a length terminating in the reticular dermis or papillary dermis. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles having one to five different lengths. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles of at least two different lengths, which may vary based on location on the body, the age of the patient, or the skin condition being treated. In some embodiments, the needles of at least two different lengths are of equal proportion. In some embodiments, the needles of at least two different lengths may be of different proportions. In alternative embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles are of a single length. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles are of equal length. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the length of the plurality of microneedles being between about 10 microns and about 1000 microns, between about 10 microns and about 900 microns, between about 10 microns and about 800 microns, between about 10 microns and about 700 microns, between about 10 microns and about 600 microns, between about 10 microns and about 500 microns, between about 10 microns and about 400 microns, between about 10 microns and about 300 microns, between about 10 microns and about 200 microns, between about 10 microns and about 100 microns, between about 10 microns and about 90 microns, between about 10 microns and about 80 microns, between about 10 microns to about 70 microns, about 10 microns to about 60 microns, about 10 microns to about 50 microns, about 10 microns to about 40 microns, about 10 microns to about 30 microns, about 10 microns to about 20 microns, about 10 microns to about 15 microns, about 20 microns to about 1000 microns, about 20 microns to about 900 microns, about 20 microns to about 800 microns, about 20 microns to about 700 microns, about 20 microns to about 600 microns, about 20 microns to about 500 microns, about 20 microns to about 400 microns, about 20 microns to about 300 microns, about 20 microns to about 200 microns,About 20 microns to about 100 microns, about 20 microns to about 90 microns, about 20 microns to about 80 microns, about 20 microns to about 70 microns, about 20 microns to about 60 microns, about 20 microns to about 50 microns, about 20 microns to about 40 microns, about 20 microns to about 30 microns, about 20 microns to about 25 microns, about 50 microns to about 1000 microns, about 50 microns to about 900 microns, about 50 microns to about 800 microns, about 50 microns to about 700 microns, about 50 microns to about 600 microns, about 50 microns to about 500 microns, about 50 microns to about 400 microns, about 50 microns to about 300 microns, about 50 microns to about 200 microns, about 50 microns to about 100 microns, about 100 microns to about 1000 microns, about 100 microns to about 900 microns, about 100 microns to about 800 microns, about 100 microns to about 700 microns, about 100 microns to about 600 microns, about 100 microns to about 500 microns, about 100 microns to about 400 microns, about 100 microns to about 300 microns, about 100 microns to about 200 microns, about 200 microns to about 1000 microns, about 200 microns to about 900 microns, about 200 microns to about 800 microns, about 200 microns to about 700 microns, about 200 microns to about 600 microns, about 200 microns The average particle size is about 100 microns to about 500 microns, about 200 microns to about 400 microns, about 200 microns to about 300 microns, about 500 microns to about 1000 microns, about 500 microns to about 900 microns, about 500 microns to about 800 microns, about 500 microns to about 700 microns, about 500 microns to about 600 microns, about 800 microns to about 1000 microns, about 800 microns to about 900 microns, or values ​​within these ranges.

[0091] In some embodiments, a method of treating a skin condition comprises applying a dissolvable microneedle patch comprising a plurality of microneedles, the microneedles tapered at their tips to facilitate insertion of the microneedles into the skin, hi some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles having tapered tip portions comprising a therapeutically active ingredient dispersed in a matrix or suspension of a biodegradable polymer.

[0092] In some embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch comprising a plurality of microneedles, the plurality of microneedles comprising microneedles of at least two different lengths, each containing an equal amount of a biodegradable polymer. In some embodiments, the dissolvable microneedle patch is comprised of a plurality of microneedles, the volume of each microneedle of which can remain constant, achieved by varying the diameter of each microneedle as needed. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, each of which has an unequal volume. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the volume of which depends on the concentration of the particular immunostimulant used.

[0093] In some embodiments, a method of treating a skin condition comprises applying a dissolvable microneedle patch comprising a plurality of microneedles, wherein the tip portions of the microneedles comprise 5-99% of the total volume of the microneedles. In some embodiments, the microneedle tip portions comprise about 20% to about 90% of the total volume of the microneedles. In some embodiments, the microneedle tip portions comprise about 50% of the total volume of the microneedles. In some embodiments, the microneedle tip portions comprise about 75% of the total volume of the microneedles.In some embodiments, the tip portion of the microneedle is about 5% to about 99%, about 5% to about 95%, about 5% to about 90%, about 5% to about 85%, about 5% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 60%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, 10% to about 99%, about 10% to 95%, about 10% to about 90%, about 10% to about 85%. %, about 30 to about 90%, about 10% to about 80%, about 10% to about 75%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 15% to about 99%, about 15% to about 95%, about 15% to about 90%, about 15% to about 85%, about 15% to about 80%, about 15% to about 75%, about 15% to 70%, about 15% to 60%, about 15% to about 50%, 15% to 40%, about 1 5% to approximately 30%, approximately 15% to approximately 20%, approximately 25% to approximately 99%, approximately 25% to approximately 95%, approximately 25% to approximately 90%, approximately 25% to approximately 85%, approximately 25% to approximately 80%, approximately 25% to approximately 75%, approximately 25% to approximately 70%, approximately 25% to approximately 60%, approximately 25% to approximately 50%, approximately 25% to approximately 40%, approximately 25% to approximately 30%, 50 to 99%, 50 to 95%, approximately 50 to 90%, approximately 50 to 85%, approximately 50 to 80%, approximately 50 to approximately 75%, approximately 50 to 70%, approximately 50 to It may be about 60%, about 25 to about 99 to about 99%, about 60% to about 99%, about 60% to about 95%, about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 70 to about 99%, about 70 to about 95%, about 70 to about 90%, about 70 to about 80%, about 70 to about 75%, about 80 to 99%, about 80% to about 95%, about 80% to about 90%, about 90% to about 85%, or a value within these ranges. Specific examples may include about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, or ranges between any two of these values. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient. In some embodiments, each of the plurality of microneedles comprises approximately the same amount of the therapeutically active ingredient.In some embodiments, each of the multiple microneedles comprises a different amount of a therapeutically active ingredient.

[0094] In some embodiments, a method of treating a skin condition comprises applying a dissolving microneedle patch, wherein the skin condition is warts, condyloma acuminata, bowel disease, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, and alopecia areata, vitiligo.

[0095] Certain compounds disclosed herein possess useful immunostimulatory activity and can be used to treat or prevent diseases or conditions in which the immune system may play an active role. In some embodiments, successful delivery of an immunostimulant results in classic clinical signs of inflammation, such as lubolum, tumour, and calorie (redness, swelling, and warmth, respectively). Accordingly, embodiments are also directed to pharmaceutical compositions comprising one or more compounds disclosed herein in association with a pharmaceutically acceptable carrier, as well as methods of making and using the compounds and compositions. Certain embodiments are directed to methods for stimulating the immune system. Other embodiments are directed to methods for treating a skin condition in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound or composition according to the invention. Also provided is the use of certain compounds disclosed herein in the manufacture of a medicament for the treatment of a disease or condition ameliorated by immune system activation.

[0096] In some embodiments, the present invention relates to a method of treating a skin condition by administering a pharmaceutical composition of an embodiment disclosed herein. In some embodiments, the compound is in a therapeutically effective amount. In some embodiments, the therapeutically effective amount is an amount disclosed herein. In some embodiments, administration of the dissolving microneedle patch results in the disappearance of the condition being treated. In some embodiments, administration of the dissolving microneedle patch results in the disappearance of a skin lesion or skin lesions in direct contact with the dissolving microneedle patch. In some embodiments, administration of the dissolving microneedle patch results in the disappearance of a skin lesion or skin lesions adjacent to the dissolving microneedle patch.

[0097] In some embodiments, a method for treating a skin condition includes a plurality of microneedles containing a therapeutically active ingredient, wherein the therapeutically active ingredient is selected from the group consisting of a vaccine, an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein. In some embodiments, a dissolvable microneedle patch delivers the therapeutically active ingredient to stimulate a local immune response. In some embodiments, the therapeutically active ingredient is a vaccine, wherein the vaccine is selected from the group consisting of measles-mumps-rubella vaccine, mumps vaccine, Bacille Calmette-Guérin vaccine, human papillomavirus vaccine, and Mycobacterium w vaccine. In some embodiments, the therapeutically active ingredient is an immunostimulatory molecule, wherein the immunostimulatory molecule is imiquimod. In some embodiments, the therapeutically active ingredient is an immunostimulatory organism, wherein the immunostimulatory organism is Corynebacterium parvum, Propionibacterium acnes, and / or Mycobacterium indicus planii (formerly Mycobacterium w). In some embodiments, the therapeutically active ingredient is an immunostimulatory protein, and the immunostimulatory protein is selected from the group consisting of Candida antigen, Trichophyton antigen, tuberculin, purified protein derivative(s), human papillomavirus surface protein, interferon alpha, interferon beta, and interferon gamma.

[0098] In some embodiments, a method of treating a skin condition includes a plurality of microneedles comprising a therapeutically active ingredient, wherein the therapeutically active ingredient is a Candida antigen. In some embodiments, the therapeutically active ingredient is a Candida antigen. In some embodiments, the Candida antigen is substantially free of glycerin. In some embodiments, the Candida antigen is glycerin-free. In some embodiments, the glycerin-free Candida antigen is lyophilized.

[0099] In some embodiments, a method for treating a skin condition includes a plurality of microneedles comprising a therapeutically active ingredient, wherein the therapeutically active ingredient is dispersed throughout a polymer. In some embodiments, the plurality of microneedles comprise a therapeutically active ingredient, wherein the therapeutically active ingredient is dispersed uniformly throughout the microneedles. In some embodiments, the plurality of microneedles comprise a therapeutically active ingredient, wherein the therapeutically active ingredient is concentrated at the tip of the microneedles. In some embodiments, the plurality of microneedles comprise microneedles wherein the half of the microneedles closest to the base is substantially free of the therapeutically active ingredient. In some embodiments, the plurality of microneedles comprise microneedles wherein the half of the microneedles closest to the base is free of the therapeutically active ingredient. In some embodiments, the therapeutically active ingredient is a solid powder. In some embodiments, the therapeutically active ingredient is a solid powder dispersed throughout a polymer. In some embodiments, the therapeutically active ingredient is lyophilized. In some embodiments, the therapeutically active ingredient is lyophilized and dispersed throughout the polymer.

[0100] Some embodiments disclosed herein also include pharmaceutical compositions comprising, as an active ingredient, one or more compounds disclosed herein in combination with one or more pharmaceutically acceptable carriers (excipients).

[0101] The active compound is effective over a wide dosage range and can generally be administered in a therapeutically effective amount. However, it will be understood that the amount of compound actually administered will usually be determined by a physician depending on the relevant circumstances, including the condition to be treated, the compound actually administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, etc. In some embodiments, the multiple microneedles contain equal amounts of the therapeutically active ingredient. In some embodiments, the multiple microneedles contain unequal amounts of the therapeutically active ingredient.

[0102] The amount of compound or composition administered to a patient will vary depending on the entity being administered, the purpose of administration (e.g., prophylaxis or treatment), the condition of the patient, and the method of administration. For therapeutic use, the composition can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially prevent the symptoms of the disease and its complications. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, and epidermodysplasia verruciformis, and successful treatment of these conditions results in a one-point improvement on any ordinal or interval rating scale, such as the Physician Global Assessment or the Investigator Global Assessment. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and verrucous carcinoma. Successful treatment of epidermodysplasia verruciformis and these conditions results in about 100% loss of skin lesions at the site of patch administration, as assessed by clinical, histopathological, or dermoscopic evaluation, and by optical coherence tomography or confocal microscopy. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and verruca carcinoma, where verruca carcinoma includes warts. Successful treatment of epidermodysplasia verruciformis and these conditions results in about 50% loss of skin lesions at the site of patch administration, as assessed by clinical, histopathological, or dermoscopic evaluation, and by optical coherence tomography or confocal microscopy. In some embodiments, successful treatment of warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or epidermodysplasia verruciformis, where the condition is selected from warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or epidermodysplasia verruciformis, is characterized by about 100% clearance of the skin lesions as assessed by clinical, histopathological, dermoscopic, and optical coherence tomography or confocal microscopy at the site where the patch was administered.Dissolving microneedle patches for epidermodysplasia verruciformis can reduce skin lesions at the site of patch administration by approximately 50% to approximately 100%, approximately 50% to approximately 95%, approximately 50% to approximately 90%, approximately 50% to approximately 85%, approximately 50% to approximately 80%, approximately 50% to approximately 75%, approximately 50% to approximately 70%, approximately 50% to approximately 65%, approximately 50% to approximately 60%, approximately 50% to approximately 55%, approximately 60% to approximately 100%, approximately 60% to approximately 95%, approximately 60% to approximately 90%, approximately 60% to approximately 85%, approximately 60% to approximately 85% This results in a reduction of about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70% to 100%, about 70% to about 95%, about 65% to about 95%, about 50% to about 50%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or within these numerical ranges. Specific examples include a reduction in skin lesions by about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or a range between any two of these values, as assessed clinically, histopathologically, or dermoscopically, as well as by optical coherence tomography or confocal microscopy.

[0103] In some embodiments, methods for treating skin conditions, including successfully treating warts, condyloma acuminata, bowel disease, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and verrucous carcinoma, using a dissolvable microneedle patch results in a decrease in the width, length, or height of the skin lesion where the patch is administered. Dissolving microneedle patches for epidermodysplasia verruciformis can reduce the width, length, or height of the skin lesion at the site where the patch is administered by about 50% to about 100%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, about 50% to about 65%, about 50% to about 60%, about 50% to about 55%, about 60% to about 100%, about 60% to about 95%, about 60% to about 90%, about 60% to about 80%, or about 50% to about 95%. The reduction can be 5%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70 to about 100%, about 70 to about 70%, about 70% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 80% to 100%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to 100%, about 90% to about 95%, or within these numerical ranges. Specific examples may include a reduction in the width, length, or height of a skin lesion by about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or within a range connecting any two of these values, as measured by clinical, histopathological, or dermoscopic evaluation, as well as by optical coherence tomography or confocal microscopy.

[0104] In some embodiments, a method for treating the skin condition alopecia areata with a dissolvable microneedle patch is provided, wherein successful treatment of the condition results in a one-point improvement on any ordered or interval rating scale, such as a physician global assessment or investigator global assessment. In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in a restoration of about 100% hair growth at the site where the patch is administered. In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in at least about a 50% increase in hair growth at the site where the patch is administered, as defined by the number of hair follicles with actively growing hair shafts, as seen by clinical, trichoscopic, or histopathological evaluation. In some embodiments, successful treatment of alopecia areata with a dissolvable microneedle patch indicates an increase in hair growth at the location where the patch is administered of about 50% to about 100%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, 50% to 65%, 50% to 60%, about 50% to 55%, 60% to 100%, 60% to 95%, about 60% to about 90%, about It may be 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70% to about 100%, about 70 to about 95%, about 70 to about 90%, about 70 to about 85%, about 70 to about 80%, about 80 to about 75%, about 80 to 100%, about 80 to about 95%, about 80 to about 90%, about 80 to 85%, about 90% to 100%, about 90 to 95%, or a value within these ranges. Specific examples include an increase in hair growth, as defined by the number of hair follicles with actively growing hair shafts as seen by clinical, triscopic, or histopathological evaluation, of about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or ranges between these values.

[0105] In some embodiments, a method of treating the skin condition alopecia areata with a dissolvable microneedle patch, wherein successful treatment results in an improvement in the Severity Assessment of Alopecia Tool (SALT) score at the location where the patch is administered by about 50% to about 100%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, 50 to 65%, about 50 to 60%, or about 50 to about 55%, as follows: about 60% to about 100%, about 60% to about 95%, about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70% to 100%, about 70% to about 95%, about 70% to about 90%, about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 80% to about 100%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or a numerical value within these ranges. Specific examples include an improvement in Severity of Alopecia Tool (SALT) score of about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or a range between any two of these values.

[0106] In some embodiments, a method of treating a skin condition with dissolvable microneedle patches, wherein each dissolvable microneedle patch contains a standardized amount of a therapeutically active ingredient.

[0107] In some embodiments, methods of treating skin conditions with a dissolvable microneedle patch include dissolvable microneedles that may comprise about 1% to about 90% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles may comprise about 50% to about 75% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles may comprise about 25% to about 50% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles may comprise about 25% to about 75% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles may comprise about 40% to about 60% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles may comprise about 60% to about 80% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the one or more therapeutically active ingredients are in an amount of about 1% to about 90%, about 1% to about 85%, about 1% to about 80%, about 1% to about 75%, about 1% to about 70%, about 1% to about 65%, or about 1% to about 60%. About 1% to about 55%, about 1% to about 50%, about 1% to about 45%, about 1% to about 40%, about 1% to about 35%, about 1% to about 30%, about 1% to about 25%, about 1% to about 20%, about 1% to about 15%, about 1% to about 10%, about 1 to about 5%, about 5 to about 90%, about 1 to about 5%, about 5% to about 85%, about 5% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 65%, about 5% to about 60%, about 5% to about 55%, about 5% to about 50%, about 5% to about 45%, about 5% to about 40%, about 5% to about 35%, about 5% to About 30%, about 5% to about 25%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, about 10% to about 90%, about 10% to about 85%, about 10% to about 80%, about 10% to about 75%, about 10% to about 70%, about 10% to about 65%, about 10% to about 60%, about 5% to about 55%, about 10% to about 60%, about 10% to about 40%, about 40%, about 30%, about 60%, about 10% to about 55%, about 10% to about 50%, about 10% to about 45%, about 10% to about 40%, about 10% to about 35%, about 10% to about 30%,About 10% to about 25%, about 10% to about 20%, about 10% to about 15%, about 15% to about 90%, about 15% to about 85%, about 10% to about 15%, about 15% to about 15%, about 15% to about 15%, about 15% to about 80%, about 15% to about 75%, about 15% to about 70%, about 15% to about 65%, about 15% to About 60%, about 15% to about 55%, about 15% to about 50%, about 15% to about 40%, about 15% to about 35%, about 15% to about 30%, about 15% to about 45%, about 15% to about 45%, about 15% to about 25%, about 15% to about 20%, about 20% to about 90%, about 20% to about 85%, about 20% to about 80%, Approximately 20% to approximately 75%, approximately 20% to approximately 70%, approximately 20% to approximately 65%, approximately 20% to approximately 60%, approximately 20% to approximately 55%, approximately 20% to approximately 50%, approximately 20% to approximately 45%, approximately 20% to approximately 40%, approximately 20% to approximately 35%, approximately 20% to approximately 30%, approximately 20% to approximately 25%, approximately 25% to approximately 90%, approximately 25% to About 85%, about 25% to about 80%, about 25% to about 75%, about 25% to about 70%, about 25% to about 65%, about 25% to about 60%, about 25% to about 60%, about 25% to about 55%, about 25% to about 50%, about 25% to about 45%, about 25% to about 40%, about 25% to about 35%, about 25% to about 30%, Approximately 30% to approximately 90%, approximately 30% to approximately 85%, approximately 30% to approximately 80%, approximately 30% to approximately 75%, approximately 30% to approximately 70%, approximately 30% to approximately 65%, approximately 30% to approximately 60%, approximately 30% to approximately 55%, approximately 30% to approximately 50%, approximately 30% to approximately 45%, approximately 30% to approximately 40%, approximately 30% to approximately 35%, approximately 35% to Approximately 90%, approximately 35% to approximately 85%, approximately 35% to approximately 80%, approximately 35% to approximately 75%, approximately 35% to approximately 70%, approximately 35% to approximately 65%, approximately 35% to approximately 60%, approximately 35% to approximately 55%, approximately 35% to approximately 50%, approximately 35% to approximately 45%, approximately 35% to approximately 40%, approximately 40% to approximately 90%, approximately 40% to approximately 85%, Approximately 35% to approximately 80%, approximately 40% to approximately 80%, approximately 40% to approximately 75%, approximately 40% to approximately 70%, approximately 40% to approximately 65%, approximately 40% to approximately 60%, approximately 40% to approximately 55%, approximately 40% to approximately 50%, approximately 45% to approximately 90%, approximately 45% to approximately 85%, approximately 45% to approximately 80%, approximately 90% to approximately 90%, approximately 45% to Approximately 75%, approximately 45% to approximately 70%, approximately 45% to approximately 65%, approximately 45% to approximately 60%, approximately 45% to approximately 55%, approximately 50% to approximately 90%, approximately 50% to approximately 85%, approximately 50% to approximately 80%, approximately 50% to approximately 75%, approximately 50% to approximately 70%, approximately 90% to approximately 90%, approximately 50% to approximately 65%, approximately 50% to approximately 60%,About 50% to about 55%, about 55% to about 90%, about 55% to about 85%, about 55% to about 80%, about 55% to about 75%, about 55% to about 70%, about 55% to about 65%, about 55% to about 60%, about 60% to about 90%, about 50% to about 85%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 65% to about 90%, about 65% to about 85%, about 65% to about 80%, about 65% to about 75%, about 65% to about 70%, about 70% to about 90%, about 60% to about 85%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 85%, about 85% to about 90%, or a value within one of these ranges. Specific examples include about 90%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%, about 2%, about 1%, etc. All of the above represent weight percent of the pharmaceutical composition. In some embodiments, the pharmaceutical composition is suitable for transdermal administration.

[0108] In some embodiments, a method of treating a skin condition with a dissolvable microneedle patch comprising a therapeutically active ingredient, wherein the therapeutically active ingredient is in a therapeutically effective amount. In some embodiments, a therapeutically effective amount is from about 1 microgram to 999 micrograms, 1 microgram to 100 micrograms, 100 micrograms to 200 micrograms, 200 micrograms to 300 micrograms, 300 micrograms to 400 micrograms, 400 micrograms to 500 micrograms, 500 micrograms to 600 micrograms, 600 micrograms to 700 micrograms, 700 micrograms to 800 micrograms, 800 micrograms to 900 micrograms, 900 micrograms to 999 micrograms, 1 mg to about 1000 mg, about 1 mg to about 900 mg, about 1 mg to about 800 mg, about 1 mg to about 700 mg, about 1 mg to about 600 mg, about 1 mg to about 500 mg, about 1 mg to about 400 mg, about 1 mg to about 900 mg, about 1 mg to about 300 mg, or about 1 mg to about 200 mg, about 1 mg to about 100 mg, about 10 mg to about 1000 mg, about 50 mg to about 1000 mg, about 100 mg to about 1000 mg, about 200 mg to about 1000 mg, about 300 mg to about 1000 mg, about 400 mg ~1000mg, 500mg~1000mg, 10mg~500mg, 500mg~500mg, 1mg~200mg, 1mg~200mg, 1mg~1000mg, 1mg~1000mg 200 mg, about 1 mg to about 1000 mg, about 50 mg to about 1000 mg, about 100 mg to about 1000 mg, about 50 mg to about 500 mg, about 100 mg to about 500 mg, about 10 mg to about 300 mg, about 50 mg to about 300 mg, about 100 mg to about 300 mg, about 10 mg to about 150 mg, about 50 mg to about 150 mg, about 60 mg to about 120 mg, about 50 mg to about 120 mg, or a range between any two of these values.Specific examples include, for example, about 1000 mg, about 900 mg, about 800 mg, about 700 mg, about 750 mg, about 600 mg, about 500 mg, about 400 mg, about 450 mg, about 300 mg, about 250 mg, about 200 mg, about 175 mg, about 150 mg, about 125 mg, about 120 mg, about 110 mg, about 100 mg, about 90 mg, about 80 mg, about 70 mg, about 60 mg, about 50 mg, about 30 mg, about 20 mg, or any numerical value within the ranges disclosed above.

[0109] In some embodiments, a method for treating a skin condition is provided using a dissolvable microneedle patch containing a therapeutically effective amount of an active ingredient, where the therapeutically effective amount can vary depending on, for example, the particular application for which the treatment is being performed, the location of administration of the microneedle patch, the patient's health and condition, and the judgment of the prescribing physician. The proportion or concentration of the compound in the dissolvable microneedles can vary depending on many factors, including the dosage, chemical properties (e.g., hydrophobicity), and type of microneedle polymer. The dosage will likely depend on variables such as the type and progression of the disease or disorder, the overall health of the particular patient, the relative biological effectiveness of the selected compound, the composition of the excipients, and the location of its administration. Effective amounts can be estimated from dose-response curves obtained from in vitro or animal model test systems.

[0110] In some embodiments, a method of treating a skin condition comprising applying a dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise poly(lactic-co-glycolic acid) (PLGA). In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a polymer selected from PLGA (polylactic-co-glycolic acid), polyglycolic acid, fibroin, PLA (polylactic acid), PVP (polyvinylpyrrolidone), or PCL (polycaprolactone). In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a single biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise two biodegradable polymers. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a plurality of biodegradable polymers.

[0111] In some embodiments, a method for treating a skin condition includes applying a dissolvable microneedle patch comprising a biodegradable polymer, wherein the biodegradable polymer is capable of providing immediate release of a therapeutically active ingredient after insertion of the microneedle patch into the skin. In further embodiments, the immediate-release biodegradable polymer is water-soluble and comprises carboxymethylcellulose, chondroitin sulfate, dextran, dextrin, polyvinylpyrrolidone, maltose, trelahose, sucrose, galactose, amylopectin, polyvinyl alcohol, and / or polyvinylpyrrolidone methacrylic acid. In further embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases at least about 75% of the therapeutically active ingredient over a timescale of about 0 to about 24 hours. In some embodiments, the immediate-release biodegradable polymer releases about 100% of the therapeutically active ingredient over a timescale of about 0 to about 24 hours. In some embodiments, the immediate-release biodegradable polymer releases a therapeutically active ingredient in a range of about 75% to about 100%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, or about 75% to about 80% over a timescale of about 0 to about 24 hours. The release may be about 80% to about 100%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 100%, about 85% to about 95%, about 85% to about 90%, about 90% to about 95%, about 95% to about 100%, or any range between these values. Specific examples include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, about 100%, or a range between any two of these values.

[0112] In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 10 minutes after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 5 minutes after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 hours to about 24 hours, about 0 hours to about 23 hours, about 0 hours to about 22 hours, about 0 hours to about 21 hours, about 0 hours to about 20 hours, about 0 hours to about 18 hours, about 0 hours to about 16 hours, about 0 hours to about 14 hours, about 0 hours to about 12 hours, about 0 hours to about 10 hours, about 0 hours to about 9 hours, about 0 hours to about 8 hours, or about 0 hours to about 7 hours. about 0 hours to about 6 hours, about 0 hours to about 5 hours, about 0 hours to about 4 hours, about 0 hours to about 3 hours, about 0 hours to about 2 hours, about 0 hours to about 1 hour, about 1 hour to about 24 hours, about 1 hour to about 23 hours, about 0 hours to about 22 hours, about 0 hours to about 3 hours, about 0 hours to about 3 hours, about 0 hours to about 4 hours, about 0 hours to about 25 hours, about 1 hour to about 25 hours, about 1 hour to about 22 hours, about 1 hour to about 21 hours, about 1 hour to about 20 hours, about 1 hour to about 18 hours, about 1 hour to about 16 hours, about 1 hour to about 14 hours, about 1 hour to about 12 hours, about 1 hour to about 10 hours, about 1 hour to about 9 hours, about 1 hour to about 8 hours, about 1 hour to about 10 hours, about 1 hour to about 9 hours, about 1 hour to about 8 hours, about 1 hour to about 7 hours, about 1 hour to about 6 hours, about 1 hour to about 5 hours, about 1 hour to about 4 hours, about 1 hour to about 3 hours, about 1 hour to about 2 hours, about 2 hours to about 24 hours, about 2 hours to about 23 hours, about 2 hours to about 22 hours, about 2 hours to about 22 hours, about 2 hours to about 21 hours, about 2 hours to about 20 hours, about 2 hours to about 18 hours, about 2 hours to about 16 hours, about 2 hours to about 14 hours, about 2 hours to about 12 hours, about 2 hours to about 10 hours, about 2 hours to about 9 hours, about 2 hours to about 8 hours, about 2 hours to about 7 hours, about 2 hours to about 6 hours, about 2 hours to about 5 hours, about 2 hours to about 4 hours, about 2 hours to about 3 hours, about 5 hours to about 24 hours, about 5 hours to about 23 hours, about 5 hours to about 22 hours, about 5 hours to about 21 hours, about 5 hours to about 20 hours, about 5 hours to about 18 hours,About 5 hours to about 16 hours, about 5 hours to about 14 hours, about 5 hours to about 12 hours, about 5 hours to about 10 hours, about 5 hours to about 9 hours, about 5 hours to about 8 hours, about 5 hours to about 7 hours, about 5 hours to about 6 hours, about 12 hours to about 24 hours, about 12 hours to about 23 hours, about 12 hours to about 22 hours, about 12 hours to about 21 hours, about 12 hours to about 20 hours, about 12 hours to about 18 hours, 12 hours ~ about 16 hours, about 12 hours to about 14 hours, about 12 hours to about 13 hours, about 18 hours to about 24 hours, about 18 hours to about 23 hours, about 18 hours to about 22 hours, about 18 hours to about 21 hours, about 18 hours to about 20 hours, about 18 hours to about 19 hours, about 20 hours to about 24 hours, about 20 hours to about 23 hours, about 20 hours to about 22 hours, about 20 hours to about 21 hours, about 0 minutes to about 60 minutes, about 0 minutes to about 50 minutes, about 0 minutes to about 45 minutes, about 0 minutes to about 30 minutes, about 0 minutes to about 15 minutes, about 0 minutes to about 10 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 4 minutes, about 0 minutes to about 3 minutes, about 0 minutes to about 2 minutes, about 0 minutes to about 1 minute, about 5 minutes to about 60 minutes, about 5 minutes to about 50 minutes, about 5 minutes to about 45 minutes, about 5 minutes to about 30 minutes, about 5 minutes to about 15 minutes, about 10 minutes to about 60 minutes, about 10 minutes to about 50 minutes, about 10 minutes to 45 minutes, about 10 minutes The time is from about 10 minutes to about 30 minutes, from about 10 minutes to about 15 minutes, from about 15 minutes to about 60 minutes, from about 15 minutes to about 50 minutes, from about 15 minutes to about 45 minutes, from about 15 minutes to about 30 minutes, from about 15 minutes to about 25 minutes, from about 15 minutes to about 20 minutes, from about 30 minutes to about 60 minutes, from about 30 minutes to about 50 minutes, from about 30 minutes to about 45 minutes, from about 30 minutes to about 40 minutes, from about 30 minutes to about 35 minutes, from about 45 minutes to about 60 minutes, from about 45 minutes to about 50 minutes, or a value within these ranges. Specific examples include about 24 hours, about 23 hours, about 22 hours, about 21 hours, about 20 hours, about 18 hours, about 16 hours, about 14 hours, about 12 hours, about 10 hours, about 9 hours, about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 60 minutes, about 55 minutes, about 50 minutes, about 45 minutes, about 40 minutes, about 35 minutes, about 30 minutes, about 25 minutes, about 20 minutes, about 15 minutes, about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, about 1 minute, or a range between any two of these values.

[0113] In some embodiments, a method for treating a skin condition includes applying a dissolvable microneedle patch comprising a biodegradable polymer, wherein the biodegradable polymer is capable of providing sustained release of a therapeutically active ingredient after insertion of the microneedle patch into the skin. In further embodiments, the sustained-release biodegradable polymer is water-soluble and comprises PLGA (polylactic-co-glycolic acid), polyglycolic acid, fibroin, PLA (polylactic acid), PVP (polyvinylpyrrolidone), or PCL (polycaprolactone). In further embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the sustained-release biodegradable polymer does not release more than 75% of the therapeutically active ingredient for more than about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the sustained-release biodegradable polymer may be about 75% to about 100%, about 75% to about 99%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 100%, about 80% to about 99%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 100%, about 85% to about 99%, 85% to about 95%, about 85% to about 90%, about 90% to about 100%, about 90% to about 99%, about 95% to about 99%, about 99% to about 100%, or a range thereof, and will not release the therapeutically active ingredient in these amounts for more than about 24 hours. Specific examples include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, and about 100%.

[0114] In some embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 day to about 30 days. In some embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient over a period of about 2 days to about 21 days. In some embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 day to about 30 days, about 1 day to about 28 days, about 1 day to about 26 days, about 1 day to about 24 days, about 1 day to about 22 days, or about 1 day to about 21 days. About 1 to about 14 days, about 1 to about 7 days, about 1 to about 6 days, about 1 to about 5 days, about 1 to about 4 days, about 1 to about 3 days, about 1 to about 2 days, about 2 to about 30 days, about 2 to about 28 days, about 2 to about 26 days, about 2 to about 24 days, about 2 to about 22 days, about 2 to about 21 days, about 2 to about 14 days, about 2 to about 7 days, about 2 to about 6 days, about 2 to about 5 days, about 2 to about 4 days, About 2 to about 3 days, about 3 to about 30 days, about 3 to about 28 days, about 3 to about 26 days, about 3 to about 24 days, about 3 to about 22 days, about 3 to about 21 days, about 3 to about 14 days, about 3 to about 7 days, about 3 to about 6 days, about 3 to about 5 days, about 3 to about 4 days, about 4 to about 30 days, about 4 to about 28 days, about 4 to about 26 days, about 4 to about 24 days, about 4 to about 22 days, about 4 days to Approximately 21 days, approximately 4 to 14 days, approximately 4 to 7 days, approximately 4 to 6 days, approximately 4 to 5 days, approximately 5 to 30 days, approximately 5 to 28 days, approximately 5 to 26 days, approximately 5 to 24 days, approximately 5 to 22 days, approximately 5 to 21 days, approximately 5 to 14 days, approximately 5 to 7 days, approximately 5 to 6 days, approximately 7 to 30 days, approximately 7 to 28 days, approximately 7 to 26 days, approximately 7 to 24 days , about 7 to about 22 days, about 7 to about 21 days, about 7 to about 14 days, about 14 to about 30 days, about 14 to about 28 days, about 14 to about 26 days, about 14 to about 24 days, about 14 to about 22 days, about 14 to about 21 days, about 21 to about 30 days, about 21 to about 28 days, about 21 to about 26 days, about 21 to about 24 days, about 21 to about 22 days, or a value within these ranges. Specific examples include about 30 days, about 28 days, about 26 days, about 24 days, about 22 days, about 21 days, about 14 days, about 7 days, about 6 days, about 5 days, about 4 days, about 3 days, about 2 days, about 1 day, or a range between any two of these values.

[0115] In some embodiments, a method for treating a skin condition comprises applying a dissolvable microneedle patch comprising a biodegradable polymer, the biodegradable polymer being capable of providing both sustained and immediate release of a therapeutically active ingredient following insertion of the microneedle patch into the skin. In some embodiments, the plurality of microneedles comprises an immediate-release biodegradable polymer and a sustained-release biodegradable polymer. In some embodiments, the plurality of microneedles comprises an immediate-release biodegradable polymer at the base of the microneedles and a sustained-release biodegradable polymer at the tip of the microneedles. In some embodiments, the plurality of microneedles comprises an immediate-release biodegradable polymer at the base of the microneedles and alternating layers of immediate-release biodegradable polymer and sustained-release biodegradable polymer at the tip of the microneedles.

[0116] In some embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch onto a skin lesion of a patient in need thereof to treat the skin condition. In some embodiments, the dissolvable microneedle patch is applied adjacent to a skin lesion of a patient in need thereof to treat the skin condition. In some embodiments, the dissolvable microneedle patch is applied to an area of ​​skin determined to be optimal based on the age of the patient. In some embodiments, the dissolvable microneedle patch is applied to an area of ​​skin determined to be optimal based on the type of skin requiring treatment.

[0117] In some embodiments, the method of treating a skin condition comprising applying a dissolvable microneedle patch comprises a plurality of microneedles, wherein the plurality of microneedles are spatially separated within the skin such that one microneedle does not contact another microneedle. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedle patch has at least about 1 to about 200 microneedles per square centimeter, about 1 to about 175 microneedles per square centimeter, about 1 to about 150 microneedles per square centimeter, about 125 microneedles per square centimeter, about 100 microneedles per square centimeter, about 90 microneedles per square centimeter, about 80 microneedles per square centimeter, about 70 microneedles per square centimeter, about 60 microneedles per square centimeter, about 50 microneedles per square centimeter, about 40 microneedles per square centimeter, about 30 microneedles per square centimeter, about 25 microneedles per square centimeter, about 20 microneedles per square centimeter. microneedles, about 1 to about 15 microneedles per square centimeter, about 1 to about 10 microneedles per square centimeter, about 1 to about 5 microneedles per square centimeter, about 5 to about 200 microneedles per square centimeter, about 5 to about 175 microneedles per square centimeter, about 5 to about 150 microneedles per square centimeter, about 5 to about 125 microneedles per square centimeter, about 5 to about 100 microneedles per square centimeter, about 5 to about 90 microneedles per square centimeter, about 5 to about 80 microneedles per square centimeter, about 5 to about 70 microneedles per square centimeter, about 5 to about 60 microneedles per square centimeter, about 5 to about 50 microneedles per square centimeter, about 5 to about 40 microneedles per square centimeter, about 5 to about 30 microneedles per square centimeter,About 5 to about 25 microneedles per square centimeter, about 5 to about 20 microneedles per square centimeter, about 5 to about 15 microneedles per square centimeter, about 5 to about 20 microneedles per square centimeter, about 10 to about 200 microneedles per square centimeter, about 10 to about 175 microneedles per square centimeter, about 10 to about 150 microneedles per square centimeter, about 10 to about 150 microneedles per square centimeter, about 10 to about 125 microneedles per square centimeter $ / cm2, about 10 to about 100 microneedles / cm2, about 10 to about 90 microneedles / cm2, about 10 to about 80 microneedles / cm2, about 10 to about 70 microneedles / cm2, about 10 to about 60 microneedles / cm2, about 10 to about 50 microneedles / cm2, about 10 to about 40 microneedles / cm2, about 10 to about 30 microneedles / cm2, about 10 to about 25 microneedles / cm2, about 10 to about 20 microneedles / cm2 Torr, about 10 to about 15 microneedles per square centimeter, about 25 to about 200 microneedles per square centimeter, about 25 to about 175 microneedles per square centimeter, about 25 to about 150 microneedles per square centimeter, about 25 to about 125 microneedles per square centimeter, about 25 to about 100 microneedles per square centimeter, about 25 to about 90 microneedles per square centimeter, about 25 to 80 microneedles per square centimeter Approximately 25 to 70 microneedles, approximately 25 to 60 microneedles per square centimeter, approximately 25 to 50 microneedles per square centimeter, approximately 25 to 40 microneedles per square centimeter, approximately 25 to 30 microneedles per square centimeter, approximately 50 to 200 microneedles per square centimeter, approximately 50 to 175 microneedles per square centimeter, approximately 50 to 150 microneedles per square centimeter, approximately 50 to 125 microneedles per square centimeter,Approximately 50 to approximately 100 microneedles per square centimeter, approximately 50 to approximately 90 microneedles per square centimeter, approximately 50 to approximately 80 microneedles per square centimeter, approximately 50 to approximately 70 microneedles per square centimeter, approximately 50 to approximately 60 microneedles per square centimeter, approximately 75 to approximately 200 microneedles per square centimeter, approximately 75 to approximately 175 microneedles per square centimeter, approximately 75 to approximately 150 microneedles per square centimeter, approximately 75 to approximately 125 microneedles per square centimeter, approximately 75 to approximately 100 microneedles per square centimeter, approximately 75 to approximately 90 microneedles per square centimeter, approximately 75 to approximately 10 ... The density may be about 75 to about 80 microneedles per meter, about 100 to about 200 microneedles per square centimeter, about 100 to about 175 microneedles per square centimeter, about 100 to about 150 microneedles per square centimeter, about 100 to about 125 microneedles per square centimeter, 125 to about 200 microneedles per square centimeter, about 125 to about 175 microneedles / square centimeter, about 125 to about 150 microneedles / square centimeter, about 150 to about 200 microneedles / square centimeter, about 150 to about 175 microneedles / square centimeter, about 175 to about 200 microneedles / square centimeter, or values ​​within these ranges. Specific examples may include a dissolvable microneedle patch comprising a plurality of microneedles, the microneedle patch having at least about 200 microneedles per square centimeter, at least about 175 microneedles per square centimeter, at least about 150 microneedles per square centimeter, at least about 200 microneedles per square centimeter, at least about 125 microneedles / square centimeter, at least about 100 microneedles / square centimeter, at least about 90 microneedles / square centimeter, at least about 80 microneedles / square centimeter, at least about 70 microneedles / square centimeter, at least about 60 microneedles / square centimeter, at least about 50 microneedles / square centimeter,At least about 40 microneedles / square centimeter, at least about 30 microneedles / square centimeter, at least about 25 microneedles / square centimeter, at least about 20 microneedles / square centimeter, at least about 15 microneedles / square centimeter, at least about 10 microneedles / square centimeter, at least about 5 microneedles / square centimeter, at least about 4 microneedles / square centimeter, at least about 3 microneedles / square centimeter, at least about 2 microneedles / square centimeter, at least about 1 microneedles / square centimeter, or a range between any two of these values.

[0118] In some embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch, the dissolvable microneedle patch being of any shape necessary to accommodate the surface topology of the skin, hi some embodiments, the dissolvable microneedle patch has n sides ranging from about 0 sides to about 1000 sides. In some embodiments, the dissolvable microneedle patch has a viscosity of about 0 to about 1000 sides, about 0 to about 900 sides, about 0 to about 800 sides, about 0 to about 700 sides, about 0 to about 600 sides, about 0 to about 500 sides, about 0 to about 400 sides, about 0 to about 300 sides, about 0 to about 200 sides, about 0 to about 100 sides, about 0 to about 90 sides, about 0 to about 80 sides, about 0 to about 70 sides, about 0 to about 60 sides, about 0 to about 50 sides, about 0 to about 40 sides, about 0 to about 30 sides, about 0 to about 20 sides, about 0 to about 10 sides, about 0 sides to about 9 sides, about 0 sides to about 8 sides, about 0 sides to about 7 sides, about 0 sides to about 6 sides, about 0 sides to about 5 sides, about 0 sides to about 4 sides, about 0 sides to about 3 sides, about 0 sides to about 2 sides, about 10 sides to about 1000 sides, about 10 sides to about 900 sides, about 10 sides to about 800 sides, about 10 sides to about 700 sides, about 10 sides to about 600 sides, about 10 sides to about 500 sides, about 10 sides to about 400 sides, about 10 sides to about 300 sides, about 10 sides to about 200 sides, about 10 sides to about 100 sides, about 10 sides to about 90 sides, about 10 sides to about 80 sides, about 10 sides to about 70 sides, approximately 10 sides to approximately 60 sides, approximately 10 sides to approximately 50 sides, approximately 10 sides to approximately 40 sides, approximately 10 sides to approximately 30 sides, approximately 10 sides to approximately 20 sides, approximately 20 sides to approximately 1000 sides, approximately 20 sides to approximately 900 sides, approximately 20 sides to approximately 800 sides, approximately 20 sides to approximately 700 sides, approximately 20 sides to approximately 600 sides, approximately 20 sides to approximately 500 sides, approximately 20 sides to approximately 400 sides, approximately 20 sides to approximately 300 sides, approximately 20 sides to approximately 200 sides, approximately 20 sides to approximately 100 sides, approximately 20 sides to approximately 90 sides, approximately 20 sides to approximately 80 sides, approximately 20 sides to approximately 70 sides, approximately 20 sides to approximately 60 sides, approximately 20 sides to about 50 sides, about 20 sides to about 40 sides, about 20 sides to 30 sides, about 100 sides to about 900 sides, about 30 sides to about 800 sides, about 20 sides to about 600 sides, about 30 sides to about 700 sides, about 30 sides to about 600 sides, about 30 sides to about 500 sides, about 30 sides to about 400 sides, about 30 sides to about 300 sides, about 30 sides to about 200 sides, about 30 sides to about 100 sides, about 30 sides to about 90 sides, about 30 sides to about 80 sides, about 30 sides to about 70 sides, about 30 sides to about 60 sides, about 30 sides to about 50 sides, about 30 sides to about 40 sides, about 50 sides to about 1000 sidesApproximately 50 to 900 sides, approximately 50 to 800 sides, approximately 50 to 700 sides, approximately 50 to 600 sides, approximately 50 to 500 sides, approximately 50 to 400 sides, approximately 50 to 300 sides, approximately 50 to 200 sides, approximately 50 to 100 sides, approximately 50 to 90 sides, approximately 50 to 80 sides, approximately 50 to 70 sides, approximately 50 to 60 sides , approximately 100 sides, approximately 75 to 900 sides, approximately 75 to approximately 800 sides, approximately 75 to 700 sides, approximately 600 sides, approximately 75 to 500 sides, approximately 700 sides, approximately 75 to approximately 400 sides, approximately 75 to approximately 300 sides, approximately 75 to approximately 200 sides, approximately 75 to approximately 100 sides, approximately 75 to approximately 90 sides, approximately 75 to approximately 80 sides, approximately 100 sides to approximately 1000 sides, approximately 100 sides to approximately 900 sides, approximately 100 to 700 sides, approximately 100 to 600 sides, approximately 100 to 500 sides, approximately 100 to 400 sides, approximately 100 to 300 sides, approximately 100 to 200 sides, approximately 150 to 1000 sides, approximately 150 to 900 sides, approximately 900 sides, approximately 250 sides to 800 sides, approximately 250 sides to 700 sides, approximately 250 sides to 600 sides, approximately 250 sides It may be about 500 sides, about 250 sides to about 400 sides, about 250 sides to about 300 sides, about 500 sides to about 1000 sides, about 500 sides to about 900 sides, about 500 sides to about 800 sides, about 500 sides to about 600 sides, about 750 sides to about 1000 sides, about 750 sides to about 900 sides, about 800 sides, about 900 sides to 1000 sides, or values ​​within these ranges. Specific examples include dissolvable microneedle patches having a diameter of about 1000 sides, about 900 sides, about 800 sides, about 700 sides, about 600 sides, about 500 sides, about 400 sides, about 300 sides, about 200 sides, about 100 sides, about 90 sides, about 80 sides, about 70 sides, about 60 sides, about 50 sides, about 40 sides, about 30 sides, about 20 sides, about 10 sides, about 9 sides, about 8 sides, about 7 sides, about 6 sides, about 5 sides, about 4 sides, about 3 sides, about 2 sides, or a range between any two of these values.

[0119] In further embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch, wherein the dissolvable microneedle patch may have sides of equal length. In further embodiments, the dissolvable microneedle patch may have sides of unequal length. In some embodiments, the dissolvable microneedle patch is in the shape of a medical bandage. In some embodiments, the dissolvable microneedle patch is in a size range of about 0.1 square centimeters to about 1000 square centimeters, about 0.1 square centimeters to about 900 square centimeters, about 0.1 square centimeters to about 800 square centimeters, about 0.1 square centimeters to about 700 square centimeters, about 0.1 square centimeters to about 600 square centimeters, about 0.1 square centimeters to about 500 square centimeters, about 0.1 square centimeters to about 400 square centimeters, about 0.1 square centimeters to about 300 square centimeters, about 0.1 square centimeters to about 200 square centimeters, about 0.1 square centimeters to about 100 square centimeters, about 0.1 square centimeters to about 90 square centimeters, about 0.1 square centimeters to about 80 square centimeters, about 0.1 square centimeters to about 70 square centimeters, about 0.1 square centimeters to about 10 ... Square centimeters to about 60 square centimeters, about 0.1 square centimeters to about 60 square centimeters, about 100 square centimeters, 1 square centimeter to about 50 square centimeters, about 0.1 square centimeters to about 40 square centimeters, about 0.1 square centimeters to about 30 square centimeters, about 0.1 square centimeters to about 20 square centimeters, about 0.1 square centimeters to about 10 square centimeters, about 0.1 square centimeters to about 5 square centimeters, about 0.1 square centimeters to about 4 square centimeters, about 0.1 square centimeters to about 3 square centimeters, about 0.1 square centimeters to about 3,000 square centimeters, 1 square centimeter to about 2 square centimeters, about 0.1 square centimeters to about 1 square centimeter, about 0.1 square centimeters to about 0.9 square centimeters, about 0.1 square centimeters to about 0.8 square centimeters,Approximately 0.1 square centimeters to approximately 0.7 square centimeters, approximately 0.1 square centimeters to approximately 0.6 square centimeters, approximately 0.1 square centimeters to approximately 0.5 square centimeters, approximately 0.1 square centimeters to approximately 100 square centimeters, 1 square centimeter to approximately 0.4 square centimeters, approximately 0.1 square centimeters to approximately 0.3 square centimeters, approximately 0.1 square centimeters to approximately 0.2 square centimeters, approximately 0.5 square centimeters to approximately 1000 square centimeters, approximately 0.5 square centimeters to approximately 90 0 square centimeters, range of about 0.1 square centimeters to about 200 square centimeters, 5 square centimeters to about 900 square centimeters, about 0.5 square centimeters to about 800 square centimeters, about 0.5 square centimeters to about 700 square centimeters, about 0.5 square centimeters to about 600 square centimeters, about 0.5 square centimeters to about 1,500 square centimeters, about 0.5 square centimeters to about 1,600 square centimeters, 5 square centimeters to about 500 square centimeters, about 0.5 Square centimeters to approximately 400 square centimeters, approximately 0.5 square centimeters to approximately 300 square centimeters, approximately 0.5 square centimeters to approximately 200 square centimeters, approximately 0.5 square centimeters to approximately 100 square centimeters, approximately 0.5 square centimeters to approximately 90 square centimeters, approximately 0.5 square centimeters to approximately 80 square centimeters, approximately 0.5 square centimeters to approximately 60 square centimeters, approximately 70 square centimeters to approximately 90 square centimeters, approximately 40 square centimeters to approximately 60 square centimeters 1, about 40 square centimeters to about 60 square centimeters, 5 square centimeters to about 70 square centimeters, about 0.5 square centimeters to about 60 square centimeters, about 0.5 square centimeters to about 50 square centimeters, about 0.5 square centimeters to about 40 square centimeters, about 0.5 square centimeters to about 30 square centimeters, about 0.5 square centimeters to about 20 square centimeters, about 0.5 square centimeters to about 10 square centimeters, about 0.5 square centimeters to about 5 square centimeters,Approximately 0.5 square centimeters to approximately 40 square centimeters, 5 square centimeters to approximately 4 square centimeters, approximately 0.5 square centimeters to approximately 3 square centimeters, approximately 0.5 square centimeters to approximately 2 square centimeters, approximately 0.5 square centimeters to approximately 1 square centimeter, approximately 0.5 square centimeters to approximately 0.9 square centimeters, approximately 0.5 square centimeters to approximately 0.8 square centimeters, approximately 0.5 square centimeters to approximately 0.7 square centimeters, approximately 0.5 square centimeters to approximately 0.6 square centimeters, 6 square centimeters, Approximately 1 square centimeter to approximately 1000 square centimeters, approximately 1 square centimeter to approximately 900 square centimeters, approximately 1 square centimeter to approximately 800 square centimeters, approximately 1 square centimeter to approximately 700 square centimeters, approximately 1 square centimeter to approximately 600 square centimeters, approximately 1 square centimeter to approximately 500 square centimeters, approximately 1 square centimeter to approximately 400 square centimeters, approximately 1 square centimeter to approximately 300 square centimeters, approximately 1 square centimeter to approximately 200 square centimeters, approximately 1 square centimeter to approximately 10 0 square centimeters, 1 square centimeter to about 90 square centimeters, about 1 square centimeter to about 80 square centimeters, about 1 square centimeter to about 70 square centimeters, about 1 square centimeter to about 60 square centimeters, about 1 square centimeter to about 50 square centimeters, about 1 square centimeter to about 40 square centimeters, about 1 square centimeter to about 30 square centimeters, about 1 square centimeter to about 20 square centimeters, about 1 square centimeter to about 10 square centimeters, about 1 square centimeter to about 5 square centimeters, about 1 square centimeter to about 4 square centimeters, about 1 square centimeter to about 3 square centimeters, about 1 square centimeter to about 2 square centimeters, about 10 square centimeters to about 1000 square centimeters, about 10 square centimeters to about 900 square centimeters, about 10 square centimeters to about 800 square centimeters, about 10 square centimeters to about 700 square centimeters, 10 square centimeters to about 600 square centimeters, about 10 square centimeters to about 500 square centimeters,Approximately 10 square centimeters to approximately 400 square centimeters, approximately 10 square centimeters to approximately 300 square centimeters, approximately 10 square centimeters to approximately 200 square centimeters, approximately 10 square centimeters to approximately 100 square centimeters, approximately 10 square centimeters to approximately 90 square centimeters, approximately 10 square centimeters to approximately 80 square centimeters, approximately 10 square centimeters to approximately 70 square centimeters, approximately 10 square centimeters to approximately 60 square centimeters, approximately 10 square centimeters to approximately 50 square centimeters, approximately 10 square centimeters Approximately 10 to approximately 40 square centimeters, approximately 10 to approximately 30 square centimeters, approximately 10 to approximately 20 square centimeters, approximately 50 to approximately 1000 square centimeters, approximately 50 to approximately 900 square centimeters, approximately 50 to approximately 800 square centimeters, approximately 50 to approximately 700 square centimeters, approximately 50 to approximately 600 square centimeters, approximately 50 to approximately 500 square centimeters, approximately 50 to approximately 400 square centimeters inches, about 50 square centimeters to about 300 square centimeters, about 50 square centimeters to about 200 square centimeters, about 50 square centimeters to about 100 square centimeters, about 75 square centimeters to about 1000 square centimeters, about 75 square centimeters to about 900 square centimeters, about 75 square centimeters to about 800 square centimeters, about 75 square centimeters to about 700 square centimeters, about 75 square centimeters to about 600 square centimeters, about 75 square centimeters to about 500 square centimeters, Approximately 75 square centimeters to approximately 400 square centimeters, approximately 75 square centimeters to approximately 300 square centimeters, approximately 75 square centimeters to approximately 200 square centimeters, approximately 75 square centimeters to approximately 100 square centimeters, approximately 100 square centimeters to approximately 1000 square centimeters, approximately 100 square centimeters to approximately 900 square centimeters, approximately 100 square centimeters to approximately 800 square centimeters, approximately 100 square centimeters to approximately 700 square centimeters, approximately 100 square centimeters to approximately 600 square centimeters,Approximately 100 square centimeters to approximately 500 square centimeters, approximately 100 square centimeters to approximately 400 square centimeters, approximately 100 square centimeters to approximately 300 square centimeters, approximately 100 square centimeters to approximately 200 square centimeters, approximately 250 square centimeters to approximately 1000 square centimeters, approximately 250 square centimeters to approximately 900 square centimeters, approximately 250 square centimeters to approximately 800 square centimeters, approximately 250 square centimeters to approximately 700 square centimeters, approximately 250 square centimeters to approximately 600 square centimeters, approximately 250 square centimeters to approximately 500 square centimeters, approximately 250 square centimeters The area may be from about 1 / 4 to about 400 square centimeters, from about 250 square centimeters to about 300 square centimeters, from about 500 square centimeters to about 1000 square centimeters, from about 500 square centimeters to about 900 square centimeters, from about 500 square centimeters to about 800 square centimeters, from about 500 square centimeters to about 700 square centimeters, from about 500 square centimeters to about 600 square centimeters, from about 750 square centimeters to about 1000 square centimeters, from about 750 square centimeters to about 900 square centimeters, from about 750 square centimeters to about 800 square centimeters, or a range between any two of these values. Specific examples of dissolvable microneedle patches range in size from about 1000 square centimeters, about 900 square centimeters, about 800 square centimeters, about 700 square centimeters, about 600 square centimeters, about 500 square centimeters, about 400 square centimeters, about 300 square centimeters, about 200 square centimeters, about 100 square centimeters, about 90 square centimeters, about 80 square centimeters, about 70 square centimeters, about 60 square centimeters, about 50 square centimeters, about 40 square centimeters, about 30 square centimeters, about 20 square centimeters, about 10 square centimeters, about 5 square centimeters, about 4 square centimeters, about 3 square centimeters, about 2 square centimeters, about 1 square centimeter, about 0.9 square centimeters, about 0.8 square centimeters, about 0.7 square centimeters,about 0.6 square centimeters, about 0.5 square centimeters, about 0.4 square centimeters, about 0.3 square centimeters, about 0.2 square centimeters, about 0.1 square centimeters, or a range between any two of these values.

[0120] In some embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch, wherein the dissolvable microneedle patch comprises a backing layer and a microneedle layer. In some embodiments, the dissolvable microneedle patch comprises a backing layer and a microneedle layer, and the microneedle layer is placed directly on the skin. In some embodiments, the dissolvable microneedle patch comprises a backing layer, wherein the backing layer comprises adhesive medical tape. In some embodiments, the dissolvable microneedle patch comprises a backing layer comprising a therapeutically active ingredient.

[0121] In some embodiments, a method for treating a skin condition comprises applying a dissolvable microneedle patch, wherein the dissolvable microneedle patch comprises a backing layer, the backing layer being a removable substrate. In some embodiments, a dissolvable microneedle patch is provided, wherein the removable substrate comprises adhesive medical tape. In some embodiments, the backing layer comprises a fast-dissolving polymer. In some embodiments, a dissolvable microneedle patch is provided, wherein the removable substrate comprises a therapeutically active ingredient dispersed in the polymer. In some embodiments, a dissolvable microneedle patch is provided, wherein a plurality of microneedles are attached to a removable substrate and comprise tapered tips extending away from the removable substrate. In some embodiments, a dissolvable microneedle patch is provided, wherein the removable substrate releases at least about 90% of the microneedles from the adhesive surface within about 20 minutes after application to the skin. In some embodiments, a dissolvable microneedle patch is provided, wherein the removable substrate releases at least about 90% of the microneedles from the adhesive surface within about 5 minutes after application to the skin.In some embodiments, the dissolvable microneedle patch has 90% of the microneedles detached from the adhesive surface within a period of about 0 to about 20 minutes, about 0 to about 15 minutes, about 0 to about 10 minutes, about 0 to about 9 minutes, about 0 to about 8 minutes, about 0 to about 7 minutes, about 0 to about 6 minutes, about 0 to about 5 minutes, or about 0 to about 4 minutes, as follows: about 0 to about 3 minutes, about 0 to about 2 minutes, about 0 to about 1 minute, about 1 to about 20 minutes, about 1 to about 15 minutes, about 1 to about 10 minutes, about 1 to about 9 minutes, about 1 to about 8 minutes, about 1 to about 7 minutes, about 1 to about 6 minutes, about 1 to about 5 minutes, or about 1 to about 4 minutes. minutes, about 1 minute to about 3 minutes, about 1 minute to about 2 minutes, about 2 minutes to about 20 minutes, about 2 minutes to about 15 minutes, about 2 minutes to about 10 minutes, about 2 minutes to about 9 minutes, about 2 minutes to about 8 minutes, about 2 minutes to about 7 minutes, about 2 minutes to about 6 minutes, about 2 minutes to about 5 minutes, about 2 minutes to about 4 minutes, about 2 minutes to about 3 minutes, about 5 minutes to about 20 minutes, about 5 minutes to about 15 minutes, about 5 minutes to about 10 minutes, about 5 minutes to about 9 minutes, about 5 minutes to about 8 minutes, about 5 minutes to about 7 minutes, about 5 minutes to about 6 minutes, about 10 minutes to about 20 minutes, about 10 minutes to about 15 minutes, about 15 minutes to about 20 minutes, about 0 seconds to about 60 seconds, about 0 seconds to about 45 seconds, about 0 seconds to about 30 seconds, about 0 seconds to about 15 seconds, about 0 seconds to approximately 10 minutes, approximately 0 seconds to approximately 9 seconds, approximately 0 seconds to approximately 8 seconds, approximately 0 seconds to approximately 7 seconds, approximately 0 seconds to approximately 6 seconds, approximately 0 seconds to approximately 5 seconds, approximately 0 seconds to approximately 4 seconds, approximately 0 seconds to approximately Approximately 3 seconds, approximately 0 seconds to approximately 2 seconds, approximately 1 second to approximately 60 seconds, approximately 1 second to approximately 45 seconds, approximately 1 second to approximately 30 seconds, approximately 1 second to approximately 15 seconds, approximately 1 second to approximately 10 seconds, approximately 1 second ~9 seconds, approximately 1 second to approximately 8 seconds, approximately 1 second to approximately 7 seconds, approximately 1 second to approximately 6 seconds, approximately 1 second to approximately 5 seconds, approximately 1 second to approximately 4 seconds, approximately 1 second to approximately 3 seconds, approximately 1 second to approximately 2 seconds, approximately 2 seconds to approximately 60 seconds, approximately 2 seconds to approximately 45 seconds, approximately 2 seconds to approximately 30 seconds, approximately 2 seconds to approximately 15 seconds, approximately 2 seconds to approximately 10 seconds, approximately 2 seconds to approximately 9 seconds, approximately 2 seconds to approximately The time may be 8 seconds, about 2 seconds to about 7 seconds, about 2 seconds to about 6 seconds, about 2 seconds to about 5 seconds, about 2 seconds to about 4 seconds, about 2 seconds to about 3 seconds, about 5 seconds to about 60 seconds, about 5 seconds to about 45 seconds, about 5 seconds to about 30 seconds, about 5 seconds to about 15 seconds, about 5 seconds to about 10 seconds, about 5 seconds to about 9 seconds, about 5 seconds to about 8 seconds, about 5 seconds to about 7 seconds, about 5 seconds to about 6 seconds, about 10 seconds to about 60 seconds, about 10 seconds to about 45 seconds, about 10 seconds to about 30 seconds, about 10 seconds to about 15 seconds, about 15 seconds to about 60 seconds, about 15 seconds to about 45 seconds, about 15 seconds to about 30 seconds, about 30 seconds to about 60 seconds, about 30 seconds to about 45 seconds, about 45 seconds to about 60 seconds, or a value within these ranges.In specific examples, 90% of the microneedles are released from the adhesive surface of the dissolvable microneedle patch within about 20 minutes, about 15 minutes, about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, about 1 minute, about 60 seconds, about 45 seconds, about 30 seconds, about 15 seconds, about 10 seconds, about 9 seconds, about 8 seconds, about 7 seconds, about 6 seconds, about 5 seconds, about 4 seconds, about 3 seconds, about 2 seconds, about 1 second, or a range between any two of these values.

[0122] In some embodiments, a method of treating a skin condition comprises applying a dissolvable microneedle patch comprising a backing layer overlying the base of the tip portion such that each microneedle separates from the other microneedles on the patch and forms a discrete entity when the substrate is removed upon application of the patch to the skin.

[0123] In some embodiments, a method for treating a skin condition includes applying a dissolvable microneedle patch, the dissolvable microneedle patch comprising: (i) placing the dissolvable microneedle patch on a surface area of ​​the skin of a patient in need of treatment or performing a pretreatment test to assess for hypersensitivity, general tolerance, or other adverse events; (ii) applying the microneedle patch; (iii) placing the microneedle patch on the surface area of ​​the skin; and (iv) placing the microneedle patch on the surface area of ​​the skin. (ii) applying sufficient force to the patch composition to allow the microneedles to penetrate from the epidermis to the papillary dermis; and (iii) allowing the plurality of microneedles to remain in the skin until the biodegradable polymer degrades; and (iv) removing the adhesive matrix from the patch composition, wherein step (ii) is performed by applying pressure using a finger, the pressure being sufficient to provide a force ranging from about 0 N to about 1000 N. In a preferred embodiment of the present application, the applied pressure is about 10 N. In an alternative embodiment of the present application, step (ii) is performed by impact insertion with an applicator device, wherein the pressure is sufficient to provide a force in the range of about 0 to about 1,000 N. In a preferred embodiment of the present application, the applied pressure is about 10 N. In some embodiments, the force applied by a finger or applicator device is about 0 N to about 1,000 N, about 0 N to about 900 N, about 0 N to about 800 N, about 0 N to about 700 N, about 0 N to about 600 N, about 0 N to about 500 N, about 0 N to about 400 N, about 0 N to about 300 N, about 0 N to about 200 N, about 0 N to about 100 N, about 0 N to about 90 N, about 0 N to about 80 N, about 0 N to about 70 N, about 0 N to about 60 N, about 0 N to about 50 N, about 0 N to about 40 N, about 0 N to about 30 N, about 0 N to about 50 N, about 0 N to about 40 N, about 0 N to about 30 N, about 0 N to about 50 N, about 0 N to about 50 N, about 0 N to about 40 N, about 0 N to about 30 N, about 0 N to about 50 N, about 0 N to about 50 N, about 0 N to about 50 N, about 0 N to about 3 ... ~20N, about 0N to about 10N, about 0N to about 9N, about 0N to about 8N, about 0N to about 7N, about 0N to about 6N, about 0N to about 5N, about 0N to about 4N, about 0N to about 3N, about 0N to about 2N, about 0N to about 1N, about 0N to about 0.9N, about 0N to about 0.8N, about 0N to about 0.7N, about 0N to about 0.6N, about 0N to about 0.5N, about 0N to about 0.4N, about 0N to about 0.3N, about 0N to about 0.3N, about 0N to about 0.2N, about 0.1N to about 1000N, about 0.1N to about 900N, about 0.1N~approx. 800N, approx. 0.1N~approx. 700N, approx. 0.1N~approx. 600N, approx. 0.1N~approx. 500N, approx. 0.1N~approx. 400N, approx. 0.2N~approx. 500N, approx. 100N~approx. 500N, approx. 100N~approx. 600N~approx. 800N, approx. 100N~approx. 600N, approx. 100N~approx. 600N, approx. 150N~approx. 150N, 1N~approx. 300N, approx. 0.1N~approx. 200N, approx. 0.1N~approx. 100N, approx. 0.1N~approx. 90N, approx. 0.1N~approx. 10 ... 80N, approx. 0.1N to approx. 70N, approx. 0.1N to approx. 60N, approx. 0.1N to approx. 50N, approx. 0.1N to approx. 40N, approx. 0.1N to approx. 40N, 1N to approx. 30N, approx. 0.1N to approx. 20N, approx. 0.1N to approx. 10N, approx. 9N, approx. 0.1N to approx. 8N, approx. 0.1N to approx. 7N, approx. 0.1N to approx. 6N, approx. 0.1N to approx. 5N, approx. 0.1N to approx. 4N, approx. 0.1N to approx. 3N, approx. 0.1N to approx. 2N, approx. 0.1N to approx. 3N, 1N to approx. 2N, approx. 0. 1N to approximately 0.9N, approximately 0.1N to approximately 0.8N, approximately 0.1N to approximately 0.7N, approximately 0.1N to approximately 0.6N, approximately 0.1N to approximately 0.5N, approximately 0.1N to approximately 0.4N, 0.1N to approximately 0.3N, 0.1N to approximately 0.2N, approximately 1N to approximately 1N, approximately 1N to approximately 2N, approximately 1N to approximately 2N, approximately 1N to approximately 2N, approximately 1N to approximately 2N, approximately 1N to approximately 1N, approximately 1N to approximately 2N, approximately 1N to approximately 1000N, approximately 1N to approximately 900N Approximately 1N to 800N, approximately 1N to 700N, approximately 1N to 600N, approximately 1N to 500N, approximately 1N to 400N, approximately 1N to 300N, approximately 1N to 200N, approximately 1N to 100N, approximately 1N to 90N, approximately 1N to 80N, approximately 1N to 70N, approximately 1N to 60N, approximately 1N to 50N, approximately 1N to 40N, approximately 1N to 30N, approximately 1N to 20N, approximately 1N to 10N, approximately 1N to 9N, approximately 1N to 8N, approximately 1.Approximately 1N to approximately 7N, approximately 1N to approximately 6N, approximately 1N to approximately 5N, approximately 1N to approximately 4N, approximately 1N to approximately 3N, approximately 1N to approximately 2N, approximately 10N to approximately 1000N, approximately 10N to approximately 900N, approximately 10N to approximately 80 0N, about 10N to about 700N, about 10N to about 600N, about 10N to about 500N, about 10N to about 400N, about 10N to about 300N, about 10N to about 200N, about 10N to about 100N , about 10N to about 90N, about 10N to about 80N, about 10N to about 70N, 10N to about 60N, about 10N to about 50N, about 10N to about 40N, about 10N to about 30N, about 10N to about 20N , about 50N to about 1000N, about 50N to about 900N, about 50N to about 800N, about 50N to about 700N, about 50N to about 600N, about 50N to about 500N, about 50N to about 400N, Approximately 50N to approximately 300N, approximately 50N to approximately 200N, approximately 50N to approximately 100N, approximately 100N to approximately 1000N, approximately 100N to approximately 900N, approximately 100N to approximately 800N, approximately 100N to approximately 700N, approximately 100N to approximately 600N, approximately 100N to approximately 500N, approximately 100N to approximately 400N, approximately 100N to approximately 300N, approximately 100N to approximately 200N, approximately 200N to approximately 1000N, approximately 20 0N to about 900N, about 200N to about 800N, about 200N to about 700N, about 200N to about 600N, about 200N to about 500N, about 200N to about 400N, about 200N to about 300N, about 500N to about 1000N, about 500N to about 900N, about 500N to about 800N, about 500N to about 700N, about 500N to about 600N, or within these numerical ranges. In specific examples, the force applied by the finger or applicator device is about 0 N, about 0.1 N, about 0.2 N, about 0.3 N, about 0.4 N, about 0.5 N, about 0.6 N, about 0.7 N, about 0.8 N, about 0.9 N, about 1 N, about 2 N, about 3 N, about 4 N, about 5 N, about 6 N, about 7 N, about 8 N, about 9 N, about 10 N, about 15 N, about 20 N, about 30 N, about 40 N, about 50 N, about 60 N, about 70 N, about 80 N, about 90 N, about 100 N, about 200 N, about 300 N, about 400 N, about 500 N, about 600 N, about 700 N, about 800 N, about 900 N, or ranges between any two of these values.

[0124] In some embodiments, a method for treating a skin condition includes applying a dissolvable microneedle patch, wherein the dissolvable microneedle patch is placed on a superficial area of ​​the skin of a patient in need of treatment, and includes (i) pre-treatment testing to assess for hypersensitivity reactions, general tolerability, or other adverse events; (ii) applying sufficient force to the patch composition to allow the microneedles to penetrate from the epidermis into the papillary dermis, wherein the sufficient force is applied by impaction using an applicator device. In some embodiments, the sufficient force applied by impaction ranges from 0 N to about 1000 N. In some embodiments, the sufficient force applied by impaction is 10 N.

[0125] In some embodiments, a method of treating a skin condition comprising applying a dissolvable microneedle patch comprising both an immediate release polymer and a sustained release polymer, wherein the skin condition comprises a viral condition or a neoplastic condition.

[0126] In some embodiments, the method comprises applying a dissolvable microneedle patch comprising an immediate release polymer to treat a skin condition, wherein the skin condition comprises alopecia areata or vitiligo. In some embodiments, the method comprises applying a dissolvable microneedle patch comprising an immediate release polymer to treat a skin condition comprising ...

[0127] Embodiments of the present application are directed to a method of testing a patient in need thereof for allergies, comprising applying a dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin, exerting sufficient force on the dissolvable microneedle patch to allow the microneedles to penetrate a location selected from the group consisting of the epidermis, the dermis, and the papillary dermis, removing the adhesive matrix from the patch composition, and allowing the plurality of microneedles to remain within the skin until the biodegradable polymer degrades.

[0128] In some embodiments, a method of testing a patient in need thereof for hypersensitivity comprising applying a dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin, comprising the steps of: applying sufficient force to the dissolvable microneedle patch to allow the microneedles to penetrate a location selected from the group consisting of the epidermis, the dermis, and the papillary dermis; removing the adhesive matrix from the patch composition; and allowing the plurality of microneedles to remain in the skin until the biodegradable polymer degrades.

[0129] In some embodiments, a method of sensitizing a patient in need of an immunostimulatory active ingredient, comprising applying a dissolvable microneedle patch for delivering a therapeutic active ingredient to the skin, comprises applying sufficient force to the dissolvable microneedle patch to allow the microneedles to penetrate a location selected from the group consisting of the epidermis, the dermis, and the papillary dermis; removing the adhesive matrix from the patch composition; and allowing the plurality of microneedles to remain in the skin until the biodegradable polymer degrades.

[0130] Method for manufacturing a dissolving microneedle patch Embodiments of the present application are directed to a method for manufacturing a dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin, the method comprising: dispersing a lyophilized therapeutically active ingredient in a first biodegradable polymer; dispensing the first biodegradable polymer into a mold to form a plurality of microneedles having a tip portion, a body portion, and a base portion; dispensing a second biodegradable polymer onto the first biodegradable polymer to form a backing layer; and applying an adhesive substrate to the second biodegradable polymer, wherein the plurality of microneedles comprises microneedles of at least two different lengths; and the therapeutically active ingredient is selected from the group consisting of a vaccine, and an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein.

[0131] In some embodiments, a method for manufacturing a dissolvable microneedle patch includes a plurality of microneedles, wherein the dissolvable microneedle patch includes microneedles of at least two different lengths, selected from the group consisting of lengths terminating in the epidermis and lengths terminating in the reticular or papillary dermis. In some embodiments, the dissolvable microneedle patch includes a plurality of microneedles having one to five different lengths. In some embodiments, the dissolvable microneedle patch includes a plurality of microneedles, wherein the at least two different lengths may vary based on the location on the body, the age of the patient, or the skin condition being treated. In some embodiments, the needles of at least two different lengths are equal in proportion. In some embodiments, the needles of at least two different lengths may be unequal in proportion. In alternative embodiments, the dissolvable microneedle patch includes a plurality of microneedles, wherein the microneedles are of a single length. In some embodiments, the dissolvable microneedle patch includes a plurality of microneedles, wherein the microneedles are of equal length. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the length of which is between about 10 microns and about 1000 microns, between about 10 microns and about 900 microns, between about 10 microns and about 800 microns, between about 10 microns and about 700 microns, between about 10 microns and about 600 microns, between about 10 microns and about 500 microns, between about 10 microns and about 400 microns, between about 10 microns and about 300 microns, between about 10 microns and about 200 microns, between about 10 microns and about 100 microns, or between about 10 microns and about 90 microns. , about 10 microns to about 80 microns, about 10 microns to about 70 microns, about 10 microns to about 60 microns, about 10 microns to about 50 microns, about 10 microns to about 40 microns, about 10 microns to about 30 microns, about 10 microns to about 20 microns, about 10 microns to about 15 microns, about 20 microns to about 1000 microns, about 20 microns to about 900 microns, about 20 microns to about 800 microns, about 20 microns to about 700 microns, 20 microns to about 600 microns, 20 microns to about 500 microns, about 20 microns to about 400 microns,About 20 microns to about 300 microns, about 20 microns to about 200 microns, about 20 microns to about 100 microns, about 20 microns to about 90 microns, about 20 microns to about 80 microns, about 20 microns to about 70 microns, about 20 microns to about 60 microns, about 20 microns to about 50 microns, about 20 microns to about 40 microns, about 20 microns to about 30 microns, about 20 microns to about 25 microns, about 50 microns to about 1000 microns, about 50 microns about 50 microns to about 900 microns, about 50 microns to about 800 microns, about 50 microns to about 700 microns, about 50 microns to about 600 microns, about 50 microns to about 500 microns, about 50 microns to about 400 microns, about 50 microns to about 300 microns, about 50 microns to about 200 microns, about 50 microns to about 100 microns, about 100 microns to about 1000 microns, about 100 microns to about 900 microns, about 100 microns to about 800 microns, About 100 microns to about 700 microns, about 100 microns to about 600 microns, about 100 microns to about 500 microns, about 100 microns to about 400 microns, about 100 microns to about 300 microns, about 100 microns to about 200 microns, about 200 microns to about 1000 microns, about 200 microns to about 900 microns, about 200 microns to about 800 microns, about 200 microns to about 700 microns, about 200 microns to about 600 microns about 200 microns to about 500 microns, about 200 microns to about 400 microns, about 200 microns to about 300 microns, about 500 microns to about 1000 microns, about 500 microns to about 900 microns, about 500 microns to about 800 microns, about 500 microns to about 700 microns, about 500 microns to about 600 microns, about 800 microns to about 1000 microns, about 800 microns to about 900 microns, or within these numerical ranges.

[0132] In some embodiments, the present invention is directed to a method of manufacturing a dissolvable microneedle patch, wherein the microneedles are tapered to facilitate insertion of the microneedles into the skin, in some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles having tapered tip portions containing a therapeutically active ingredient dispersed in a matrix or suspension of a biodegradable polymer.

[0133] In some embodiments, a method for manufacturing a dissolvable microneedle patch includes a plurality of microneedles, the plurality of microneedles comprising microneedles of at least two different lengths, the microneedles being composed of equal volumes of a biodegradable polymer, the dissolvable microneedle patch comprising a plurality of microneedles. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the volume of each microneedle may remain constant, achieved by varying the diameter of each of the microneedles as needed. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the volumes of each microneedle being unequal. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the volume of each microneedle being dependent on the concentration of the particular immunostimulant used.

[0134] In some embodiments, the method for manufacturing a dissolvable microneedle patch includes a plurality of microneedles, the tip portions of which comprise 5-99% of the total volume of the microneedles. In some embodiments, the microneedle tip portions comprise about 20% to about 90% of the total volume of the microneedles. In some embodiments, the microneedle tip portions comprise about 50% of the total volume of the microneedles. In some embodiments, the microneedle tip portions comprise about 75% of the total volume of the microneedles. In some embodiments, the tip portion of the microneedle is about 5% to about 99%, about 5% to about 95%, about 5% to about 90%, about 5% to about 85%, about 5% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 60%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, 10% to about 99%, about 10% to 95%, about 10% to about 90%, about 10% to about 85%. %, about 90%, about 20%, about 10% to about 80%, about 10% to about 75%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 15% to about 99%, about 15% to about 95%, about 15% to about 90%, about 15% to about 85%, about 15% to about 80%, about 15% to about 75%, about 15% to 70%, about 15% to 60%, about 15% to about 50%, 15% to 40%, About 15% to about 30%, about 15% to about 20%, about 25% to about 99%, about 25% to about 95%, about 25% to about 90%, about 25% to about 85%, about 25% to about 80%, about 25% to about 75%, about 25% to about 70%, about 25% to about 60%, about 25% to about 50%, about 25% to about 40%, about 25% to about 30%, 50 to 99%, 50 to about 95%, about 50 to about 90%, about 50 to 85%, about 50 to 80%, about 50 to about 75%, about 50 to 70%, It may be 50 to about 60%, about 25 to about 95%, about 60% to about 99%, about 60% to about 95%, about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 70 to about 99%, about 70 to about 95%, about 70 to about 90%, about 70 to about 80%, about 70 to about 75%, about 80 to 99%, about 80% to about 95%, about 80 to about 90%, about 90% to about 95%, or a value within these ranges.Specific examples may include about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, or ranges between any two of these values. In some embodiments, a plurality of microneedles comprises a therapeutically active ingredient. In some embodiments, a plurality of microneedles each comprise approximately the same amount of a therapeutically active ingredient. In some embodiments, a plurality of microneedles each comprise different amounts of a therapeutically active ingredient.

[0135] In some embodiments, there is provided a method of manufacturing a dissolvable microneedle patch for treating a skin condition, wherein the skin condition is warts, condyloma acuminata, bowel disease, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, vitiligo, and alopecia areata.

[0136] In some embodiments, a method for manufacturing a dissolving microneedle patch in which certain compounds disclosed herein have useful immunostimulatory activity and can be used to treat or prevent diseases or conditions in which the immune system may play an active role is described below. In some embodiments, successful delivery of the immunostimulant results in classic clinical signs of inflammation, such as lubolum, tumour, and calor (redness, swelling, and warmth, respectively). Accordingly, embodiments are also directed to pharmaceutical compositions comprising one or more compounds disclosed herein together with a pharmaceutically acceptable carrier, as well as methods for making and using the compounds and compositions. Certain embodiments are directed to methods for stimulating the immune system. Other embodiments are directed to methods for treating a skin condition in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound or composition according to the present invention. Also provided is the use of certain compounds disclosed herein in the manufacture of a medicament for the treatment of a disease or condition ameliorated by immune system activation.

[0137] In some embodiments, a method of manufacturing a dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin is provided, the method comprising manufacturing a dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin. In some embodiments, the therapeutically active ingredient is in a therapeutically effective amount. In some embodiments, the therapeutically effective amount is an amount disclosed herein. In some embodiments, administration of the dissolvable microneedle patch results in the disappearance of the condition being treated. In some embodiments, administration of the dissolvable microneedle patch results in the disappearance of a skin lesion or skin lesions in direct contact with the dissolvable microneedle patch. In some embodiments, administration of the dissolvable microneedle patch results in the disappearance of a skin lesion or skin lesions adjacent to the dissolvable microneedle patch. In some embodiments, the dissolvable microneedle patch delivers a therapeutically active ingredient to stimulate a local immune response.

[0138] In some embodiments, a method of manufacturing a dissolvable microneedle patch for delivery of a therapeutically active ingredient, wherein the therapeutically active ingredient is selected from the group consisting of a vaccine, an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein.

[0139] In some embodiments, the therapeutically active ingredient is a vaccine, and the vaccine is selected from the group consisting of measles-mumps-rubella vaccine, mumps vaccine, Bacillus Calmette-Guerin vaccine, human papillomavirus vaccine, and Mycobacterium w vaccine. In some embodiments, the therapeutically active ingredient is an immunostimulatory molecule, and the immunostimulatory molecule is imiquimod. In some embodiments, the therapeutically active ingredient is an immunostimulatory organism, and the immunostimulatory organism is Corynebacterium parvum, Propionibacterium acnes, and / or Mycobacterium. In some embodiments, the therapeutically active ingredient is an immunostimulatory protein, and the immunostimulatory protein is selected from the group consisting of Candida antigen, Trichophyton antigen, tuberculin, purified protein derivative(s), human papillomavirus surface protein, interferon alpha, interferon beta, and interferon gamma.

[0140] Some embodiments are directed to methods of manufacturing a dissolvable microneedle patch for delivery of a therapeutically active ingredient, wherein the therapeutically active ingredient is a Candida antigen. In some embodiments, the therapeutically active ingredient is a Candida antigen. In some embodiments, the Candida antigen is substantially free of glycerin. In some embodiments, the Candida antigen is glycerin-free. In some embodiments, the glycerin-free Candida antigen is lyophilized.

[0141] Some embodiments are directed to a method for making a dissolvable microneedle patch comprising an immunostimulatory compound, comprising adding an immunostimulatory compound to a biodegradable polymer, pouring the composition comprising the biodegradable polymer and the immunostimulatory compound into a microneedle mold, and removing the microneedle mold after the composition comprising the biodegradable polymer and the immunostimulatory compound has solidified. In some embodiments, the immunostimulatory compound comprises glycerin. In some embodiments, the method for making a dissolvable microneedle patch comprising an immunostimulatory compound further comprises removing the glycerin from the immunostimulatory compound. In some embodiments, the method for making a dissolvable microneedle patch comprising an immunostimulatory compound further comprises removing the glycerin from the immunostimulatory compound, wherein the glycerin is removed by dialysis. In some embodiments, the glycerin is removed prior to adding the immunostimulatory compound to the biodegradable polymer.

[0142] In some embodiments, a method of manufacturing a dissolvable microneedle patch for delivering a therapeutically active ingredient, wherein the therapeutically active ingredient is dispersed throughout a polymer. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, wherein the therapeutically active ingredient is uniformly dispersed throughout the microneedles. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, wherein the therapeutically active ingredient is concentrated at the tip of the microneedles. In some embodiments, the plurality of microneedles comprises microneedles wherein the half of the microneedles closest to the base is substantially free of the therapeutically active ingredient. In some embodiments, the plurality of microneedles comprises microneedles wherein the half of the microneedles closest to the base is free of the therapeutically active ingredient. In some embodiments, the therapeutically active ingredient is a solid powder. In some embodiments, the therapeutically active ingredient is a solid powder dispersed throughout a polymer. In some embodiments, the therapeutically active ingredient is lyophilized. In some embodiments, the therapeutically active ingredient is lyophilized and dispersed throughout a polymer.

[0143] Some embodiments disclosed herein also include pharmaceutical compositions comprising, as an active ingredient, one or more compounds disclosed herein in combination with one or more pharmaceutically acceptable carriers (excipients).

[0144] The active compound is effective over a wide dosage range and can generally be administered in a therapeutically effective amount. However, it will be understood that the amount of compound actually administered will usually be determined by a physician depending on the relevant circumstances, including the condition to be treated, the compound actually administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, etc. In some embodiments, the multiple microneedles will contain equal amounts of the therapeutically active ingredient. In some embodiments, the multiple microneedles contain unequal amounts of the therapeutically active ingredient.

[0145] In some embodiments, methods for manufacturing dissolvable microneedle patches for delivery of therapeutically active ingredients are provided, wherein the amount of therapeutically active ingredient administered to a patient varies depending on the entity being administered, the purpose of administration (e.g., prophylaxis or treatment), the condition of the patient, and the method of administration. In therapeutic applications, the composition can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially prevent the symptoms of the disease and its complications. In some embodiments, the condition is selected from warts, condyloma acuminata, bowel disease, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, and epidermodysplasia verruciformis, and successful treatment of these conditions results in a one-point improvement on any ordered or interval rating scale, such as a physician global rating or investigator global rating. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verruca carcinoma, and epidermodysplasia verruciformis, and successful treatment of these conditions is one that results in about 100% loss of skin lesions at the site of patch administration as assessed by clinical, histopathological, or dermoscopic evaluation, and by optical coherence tomography or confocal microscopy. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papilloma, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and verruca carcinoma, and verruca carcinoma includes warts. Successful treatment of epidermodysplasia verruciformis and these conditions results in approximately 50% loss of skin lesions at the site of patch administration as assessed by clinical, histopathological, or dermoscopic evaluation, as well as by optical coherence tomography or confocal microscopy. In some embodiments, successful treatment of warts, condyloma acuminata, bowel disease, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and verrucous carcinoma.Dissolving microneedle patches for epidermodysplasia verruciformis can reduce skin lesions at the site of application by approximately 50% to approximately 100%, approximately 50% to approximately 95%, approximately 50% to approximately 90%, approximately 50% to approximately 85%, approximately 50% to approximately 80%, approximately 50% to approximately 75%, approximately 50% to approximately 70%, approximately 50% to approximately 65%, approximately 50% to approximately 60%, approximately 50% to approximately 55%, approximately 60% to approximately 100%, approximately 60% to approximately 95%, approximately 60% to approximately 90%, approximately 60% to approximately 85%, approximately This results in a reduction of 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70% to about 100%, about 70% to about 95%, about 65% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or within these numerical ranges. Specific examples include a reduction in skin lesions by about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or any two ranges between these values, as assessed clinically, histopathologically, or by dermatology, as well as by optical coherence tomography or confocal microscopy.

[0146] In some embodiments, a method for manufacturing a dissolvable microneedle patch for delivery of a therapeutically active ingredient to treat a skin condition, wherein successful treatment of warts, condyloma acuminata, bowel disease, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or verrucous carcinoma with the dissolvable microneedle patch results in a reduction in the width, length, or height of the skin lesion at the location where the patch is administered, in a range of about 50% to about 100%, about 50% to about 95%, about 50% to about 90%, or about 50% to about 85%. Approximately 50% to approximately 80%, approximately 50% to approximately 75%, approximately 50% to approximately 70%, approximately 50% to approximately 65%, approximately 50% to approximately 60%, approximately 50% to approximately 55%, approximately 60% to approximately 100%, approximately 60% to approximately 95%, approximately 60% to approximately 90%, approximately 60% to approximately 85%, approximately 60% to 80%, approximately 60% to approximately 75%, approximately 60% to approximately 70%, approximately 60% to approximately 65%, approximately 90% to It may be about 95%, about 90% to about 50%, about 70% to about 100%, about 70% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 80% to about 100%, about 80% to about 95%, about 80% to about 90%, about 90% to about 85%, about 90% to 95%, or a value within these ranges. Specific examples include a reduction in the width, length, or height of a skin lesion by about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or a range between these values, as measured by clinical, histopathological, or dermoscopic evaluation, as well as by optical coherence tomography or confocal microscopy.

[0147] In some embodiments, a method for manufacturing a dissolvable microneedle patch for delivering a therapeutic active ingredient for treating the skin condition alopecia areata with the dissolvable microneedle patch, wherein successful treatment of the condition results in a one-point improvement on any ordinal or interval rating scale, such as a physician global assessment or investigator global assessment. In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in a restoration of about 100% hair growth at the site where the patch is administered. In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in at least about a 50% increase in hair growth at the site where the patch is administered, as defined by the number of hair follicles with actively growing hair shafts, as seen by clinical, trichoscopic, or histopathological evaluation. In some embodiments, successful treatment of alopecia areata with a dissolvable microneedle patch indicates an increase in hair growth at the location where the patch is administered, by about 50% to about 100%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, 50% to about 65%, about 50% to about 60%, about 50% to about 55%, about 60% to about 100%, 60% to about 95%, about 60% to about 6 ... 0. about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70% to about 100%, about 70 to about 95%, about 70 to about 90%, about 70 to about 85%, about 70 to about 80%, about 80 to about 75%, about 80 to 100%, about 80 to about 95%, about 80 to about 90%, about 80 to about 85%, about 90% to 100%, about 90 to about 95%, or values ​​within these ranges. Specific examples include an increase in hair growth, as defined by the number of hair follicles with actively growing hair shafts as seen by clinical, trichoscopic, or histopathological evaluation, of about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or ranges between these values.

[0148] In some embodiments, a method of manufacturing a dissolvable microneedle patch for delivering a therapeutic active ingredient for treating the skin condition alopecia areata with a dissolvable microneedle patch is used, wherein successful treatment is measured by an improvement in Severity Assessment of Alopecia Tool (SALT) score at the location where the patch is administered, of between about 50% and about 100%, between about 50% and about 95%, between about 50% and about 90%, between about 50% and about 85%, between about 50% and about 80%, between about 50% and about 75%, between about 50% and about 70%, between about 50% and about 65%, between about 50% to about 60%, about 50% to about 55%, about 60% to about 100%, about 60% to about 95%, about 60% to about 90%, about 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 70% to about 100%, about 70% to about 95%, about 60% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or within these numerical ranges. Specific examples include an improvement in Severity of Alopecia Tool (SALT) score of about 100%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, or a range between any two of these values.

[0149] In some embodiments, a method for making a dissolvable microneedle patch, wherein each dissolvable microneedle patch contains a standardized amount of a therapeutically active ingredient.

[0150] In some embodiments, methods for making a dissolvable microneedle patch include dissolvable microneedles that may comprise about 1% to about 90% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles that may comprise about 50% to about 75% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles that may comprise about 25% to about 50% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles that may comprise about 25% to about 75% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles that may comprise about 40% to about 60% of one or more therapeutically active ingredients disclosed herein. In some embodiments, dissolvable microneedles that may comprise about 60% to about 80% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the one or more therapeutically active ingredients are in an amount of about 1% to about 90%, about 1% to about 85%, about 1% to about 80%, about 1% to about 75%, about 1% to about 70%, about 1% to about 65%, or about 1% to about 60%. about 1% to about 55%, about 1% to about 50%, about 1% to about 45%, about 1% to about 40%, about 1% to about 35%, about 1% to about 30%, about 1% to about 25%, about 1% to about 20%, about 1% to about 15%, about 1% to about 10%, about 1 to about 5%, about 5 to about 90%, about 1 to about 5%, about 5% to about 85%, about 5% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 65%, about 5% to about 60%, about 5% to about 55%, about 5% to about 50%, about 5% to about 45%, about 5% to about 40%, about 5% to about 35%, about 5% to about 30%, About 5% to about 25%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, about 10% to about 90%, about 10% to about 85%, about 10% to about 80%, about 10% to about 75%, about 10% to about 70%, about 10% to about 65%, about 10% to about 60%, about 5% to about 55%, about 10% to about 60%, about 10% to about 40%, about 40%, about 30%, about 60%, about 10% to about 55%, about 10% to about 50%, about 10% to about 45%, about 10% to about 40%, about 10% to about 35%, about 10% to about 30%, about 10% to about 25%,About 10% to about 20%, about 10% to about 15%, about 15% to about 90%, about 15% to about 85%, about 10% to about 15%, about 15% to about 15%, about 15% to about 15%, about 15% to about 80%, about 15% to about 75%, about 15% to about 70%, about 15% to about 65%, about 15% to about 60%, about 15% to About 55%, about 15% to about 50%, about 15% to about 40%, about 15% to about 35%, about 15% to about 30%, about 15% to about 45%, about 15% to about 45%, about 15% to about 25%, about 15% to about 20%, about 20% to about 90%, about 20% to about 85%, about 20% to about 80%, about 20% to about 75%, Approximately 20% to approximately 70%, approximately 20% to approximately 65%, approximately 20% to approximately 60%, approximately 20% to approximately 55%, approximately 20% to approximately 50%, approximately 20% to approximately 45%, approximately 20% to approximately 40%, approximately 20% to approximately 35%, approximately 20% to approximately 30%, approximately 20% to approximately 25%, approximately 25% to approximately 90%, approximately 25% to approximately 85%, approximately 25% to Approximately 80%, approximately 25% to approximately 75%, approximately 25% to approximately 70%, approximately 25% to approximately 65%, approximately 25% to approximately 60%, approximately 25% to approximately 60%, approximately 25% to approximately 55%, approximately 25% to approximately 50%, approximately 25% to approximately 45%, approximately 25% to approximately 40%, approximately 25% to approximately 35%, approximately 25% to approximately 30%, approximately 30% to approximately 90%, Approximately 30% to approximately 85%, approximately 30% to approximately 80%, approximately 30% to approximately 75%, approximately 30% to approximately 70%, approximately 30% to approximately 65%, approximately 30% to approximately 60%, approximately 30% to approximately 55%, approximately 30% to approximately 50%, approximately 30% to approximately 45%, approximately 30% to approximately 40%, approximately 30% to approximately 35%, approximately 35% to approximately 90%, approximately 35% to Approximately 85%, approximately 35% to approximately 80%, approximately 35% to approximately 75%, approximately 35% to approximately 70%, approximately 35% to approximately 65%, approximately 35% to approximately 60%, approximately 35% to approximately 55%, approximately 35% to approximately 50%, approximately 35% to approximately 45%, approximately 35% to approximately 40%, approximately 40% to approximately 90%, approximately 40% to approximately 85%, approximately 35% to approximately 80%, Approximately 40% to approximately 80%, approximately 40% to approximately 75%, approximately 40% to approximately 70%, approximately 40% to approximately 65%, approximately 40% to approximately 60%, approximately 40% to approximately 55%, approximately 40% to approximately 50%, approximately 45% to approximately 90%, approximately 45% to approximately 85%, approximately 45% to approximately 80%, approximately 90% to approximately 90%, approximately 45% to approximately 75%, approximately 45% to Approximately 70%, approximately 45% to approximately 65%, approximately 45% to approximately 60%, approximately 45% to approximately 55%, approximately 50% to approximately 90%, approximately 50% to approximately 85%, approximately 50% to approximately 80%, approximately 50% to approximately 75%, approximately 50% to approximately 70%, approximately 90% to approximately 90%, approximately 50% to approximately 65%, approximately 50% to approximately 60%, approximately 50% to approximately 55%,Approximately 55% to approximately 90%, approximately 55% to approximately 85%, approximately 55% to approximately 80%, approximately 55% to approximately 75%, approximately 55% to approximately 70%, approximately 55% to approximately 65%, approximately 55% to approximately 60%, approximately 60% to approximately 90%, approximately 50% to approximately 85%, approximately 60% to approximately 85%, approximately 60% to approximately 80%, approximately 60% to approximately 75%, approximately 60% to approximately 70%, approximately 60% to approximately 65%, approximately 65% ​​to approximately 90%, approximately 65% ​​to approximately 85%, about 65% to about 80%, about 65% to about 75%, about 65% to about 70%, about 70% to about 90%, about 60% to about 85%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 85%, about 85% to about 90%, or a value within one of these ranges. Specific examples include about 90%, about 99%, about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%, about 2%, about 1%, etc. All of the above represent weight percent of the pharmaceutical composition. In some embodiments, the pharmaceutical composition is suitable for transdermal administration.

[0151] In some embodiments, there is provided a method for making a dissolvable microneedle patch for delivering a therapeutically active agent, wherein the therapeutically active agent is in a therapeutically effective amount. In some embodiments, a therapeutically effective amount is from about 1 microgram to 999 micrograms, 1 microgram to 100 micrograms, 100 micrograms to 200 micrograms, 200 micrograms to 300 micrograms, 300 micrograms to 400 micrograms, 400 micrograms to 500 micrograms, 500 micrograms to 600 micrograms, 600 micrograms to 700 micrograms, 700 micrograms to 800 micrograms, 800 micrograms to 900 micrograms, 900 micrograms to 999 micrograms, 1 mg to about 1000 mg, about 1 mg to about 900 mg, about 1 mg to about 800 mg, about 1 mg to about 700 mg, about 1 mg to about 600 mg, about 1 mg to about 500 mg, about 1 mg to about 400 mg, about 1 mg to about 900 mg, about 1 mg to about 300 mg, or about 1 mg to about 200 mg, about 1mg to about 100mg, about 10mg to about 1000mg, about 50mg to about 1000mg, about 100mg to about 1000mg, about 200mg to about 1000mg, about 300mg to about 1000mg, about 400m g ~ about 1000mg, about 500mg - about 1000mg, about 10mg - about 500mg, about 500mg - about 500mg, about 1mg - about 200mg, about 1mg - about 200mg, about 1mg - about 1000mg, about 500m g to about 1000 mg, about 1 mg to about 500 mg, about 1 mg to about 1000 mg, about 50 mg to about 500 mg, about 50 mg to about 500 mg, about 100 mg to about 500 mg, about 10 mg to about 300 mg, about 50 mg to about 300 mg, about 100 mg to about 300 mg, about 10 mg to about 150 mg, about 50 mg to about 150 mg, about 60 mg to about 120 mg, about 50 mg to about 120 mg, or a range between any two of these values.Specific examples include, for example, about 1000 mg, about 900 mg, about 800 mg, about 700 mg, about 750 mg, about 600 mg, about 500 mg, about 400 mg, about 450 mg, about 300 mg, about 250 mg, about 200 mg, about 175 mg, about 150 mg, about 125 mg, about 120 mg, about 110 mg, about 100 mg, about 90 mg, about 80 mg, about 70 mg, about 60 mg, about 50 mg, about 30 mg, about 20 mg, or any numerical value within the ranges disclosed above.

[0152] In some embodiments, a method for producing a dissolvable microneedle patch containing a therapeutically effective amount of an active ingredient is provided, where the therapeutically effective amount can vary depending on, for example, the particular application for which the treatment is being administered, the location of administration of the microneedle patch, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of the compound in the dissolvable microneedles can vary depending on many factors, including the dosage, chemical characteristics (e.g., hydrophobicity), and type of microneedle polymer. The dosage will depend on variables such as the type and progression of the disease or disorder, the overall health of the particular patient, the relative biological effectiveness of the selected compound, the composition of the excipients, and the location of its administration. Effective amounts can be estimated from dose-response curves derived from in vitro or animal model test systems.

[0153] In some embodiments, there is provided a method for producing a dissolvable microneedle patch comprising a plurality of needles, wherein the plurality of microneedles comprises a biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise poly(lactic-co-glycolic acid). In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a polymer selected from PLGA (polylactic-co-glycolic acid), polyglycolic acid, fibroin, PLA (polylactic acid), PVP (polyvinylpyrrolidone), or PCL (polycaprolactone). In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a single biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise two biodegradable polymers. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedles comprise a plurality of biodegradable polymers.

[0154] In some embodiments, a method for producing a dissolvable microneedle patch comprising a biodegradable polymer, wherein the biodegradable polymer is capable of providing immediate release of a therapeutically active ingredient after insertion of the microneedle patch into the skin. In further embodiments, the immediate-release biodegradable polymer is water-soluble and is comprised of carboxymethylcellulose, chondroitin sulfate, dextran, dextrin, polyvinylpyrrolidone, maltose, trelahose, sucrose, galactose, amylopectin, polyvinyl alcohol, and / or polyvinylpyrrolidone methacrylic acid. In further embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases at least about 75% of the therapeutically active ingredient over a timescale of about 0 to about 24 hours. In some embodiments, the immediate-release biodegradable polymer releases about 100% of the therapeutically active ingredient over a timescale of about 0 to about 24 hours. In some embodiments, the immediate-release biodegradable polymer releases a therapeutically active ingredient in a range of about 75% to about 100%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, or about 75% to about 80% over a timescale of about 0 to about 24 hours. The release may be about 80% to about 100%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 100%, about 85% to about 95%, about 85% to about 90%, about 90% to about 95%, about 95% to about 100%, or any range between these values. Specific examples include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, about 100%, or a range between any two of these values.

[0155] In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 10 minutes after insertion of the microneedle patch into the skin. In some embodiments, the immediate-release biodegradable polymer releases the therapeutically active ingredient within about 0 to about 5 minutes after insertion of the microneedle patch into the skin. In some embodiments, the immediate release biodegradable polymer is administered for about 0 hours to about 24 hours, about 0 hours to about 23 hours, about 0 hours to about 22 hours, about 0 hours to about 21 hours, about 0 hours to about 20 hours, about 0 hours to about 18 hours, about 0 hours to about 16 hours, about 0 hours to about 14 hours, about 0 hours to about 12 hours, about 0 hours to about 10 hours, about 0 hours to about 9 hours, about 0 hours to about 8 hours, about 0 hours to about 7 hours, about 0 hours to about 6 hours, about 0 hours to about 5 hours, or about 0 hours to about 4 hours. hours, about 0 hours to about 3 hours, about 0 hours to about 2 hours, about 0 hours to about 1 hour, about 1 hour to about 24 hours, about 1 hour to about 23 hours, about 0 hours to about 22 hours, about 0 hours to about 3 hours, about 0 hours to about 3 hours, about 0 hours to about 4 hours, about 0 hours to about 25 hours, about 1 hour to about 3 hours, about 1 hour to about 25 hours, about 1 hour to about 25 hours, about 1 hour to about 22 hours, about 1 hour to about 21 hours, about 1 hour to about 20 hours, about 1 hour to about 18 hours, about 1 hour to about 16 hours, about 1 hour to about 14 hours, about 1 hour to about 12 hours, about 1 hour to about 10 hours, about 1 hour to about 9 hours, about 1 hour to about 8 hours, about 1 hour to about 10 hours, about 1 hour to about 9 hours, about 1 hour to about 8 hours, about 1 hour to about 7 hours, about 1 hour to about 6 hours, about 1 hour to about 5 hours, about 1 hour to about 4 hours, about 1 hour to about 3 hours, about 1 hour to about 2 hours, about 2 hours to about 24 hours, about 2 hours to about 23 hours, about 2 hours to about 22 hours, about 2 hours to about 2 1 hour, about 2 hours to about 20 hours, about 2 hours to about 18 hours, about 2 hours to about 16 hours, about 2 hours to about 14 hours, about 2 hours to about 12 hours, about 2 hours to about 10 hours, about 2 hours to about 9 hours, about 2 hours to about 8 hours, about 2 hours to about 7 hours, about 2 hours to about 6 hours, about 2 hours to about 5 hours, about 2 hours to about 4 hours, about 2 hours to about 3 hours, about 5 hours to about 24 hours, about 5 hours to about 23 hours, about 5 hours to about 22 hours, about 5 hours to about 21 hours, about 5 hours to about 20 hours,About 5 hours to about 18 hours, about 5 hours to about 16 hours, about 5 hours to about 14 hours, about 5 hours to about 12 hours, about 5 hours to about 10 hours, about 5 hours to about 9 hours, about 5 hours to about 8 hours, about 5 hours to about 7 hours, about 5 hours to about 6 hours, about 12 hours to about 24 hours, about 12 hours to about 23 hours, about 12 hours to about 22 hours, about 12 hours to about 21 hours, about 12 hours to about 20 hours, about 12 hours to about 18 hours, 12 hours to about 16 hours, about 12 hours to about 14 hours, about 12 hours to about 13 hours, about 18 hours to about 24 hours, about 18 hours to about 23 hours, about 18 hours to about 22 hours, about 18 hours to about 21 hours, about 18 hours to about 20 hours, about 18 hours to about 19 hours, about 20 hours to about 24 hours, about 20 hours to about 23 hours, about 20 hours to about 22 hours, about 20 hours to about 21 hours, about 0 minutes to about 60 minutes, about 0 minutes Approximately 50 minutes, approximately 0 to approximately 45 minutes, approximately 0 to approximately 30 minutes, approximately 0 to approximately 15 minutes, approximately 0 to approximately 10 minutes, approximately 0 to approximately 5 minutes, approximately 1 minute, approximately 0 to approximately 4 minutes, approximately 0 to approximately 3 minutes, approximately 0 to approximately 2 minutes, approximately 0 to approximately 1 minute, approximately 5 to approximately 60 minutes, approximately 5 to approximately 50 minutes, approximately 5 to approximately 45 minutes, approximately 5 to approximately 30 minutes, approximately 5 to approximately 15 minutes, approximately 10 to approximately 60 minutes, approximately 10 to approximately 50 minutes, approximately 10 to 45 minutes, approximately 10 to approximately 30 minutes The therapeutically active ingredient is released within about 10 to about 15 minutes, about 15 to about 60 minutes, about 15 to about 50 minutes, about 15 to about 45 minutes, about 15 to about 30 minutes, about 15 to about 25 minutes, about 15 to about 20 minutes, about 30 to about 60 minutes, about 30 to about 50 minutes, about 30 to about 45 minutes, about 30 to about 40 minutes, about 30 to 35 minutes, about 45 to about 60 minutes, about 45 to about 50 minutes, or within these ranges of the numerical value. Specific examples include about 24 hours, about 23 hours, about 22 hours, about 21 hours, about 20 hours, about 18 hours, about 16 hours, about 14 hours, about 12 hours, about 10 hours, about 9 hours, about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 60 minutes, about 55 minutes, about 50 minutes, about 45 minutes, about 40 minutes, about 35 minutes, about 30 minutes, about 25 minutes, about 20 minutes, about 15 minutes, about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, about 1 minute, or a value between any two of these values.

[0156] In some embodiments, a method for producing a dissolvable microneedle patch comprises a biodegradable polymer, wherein the biodegradable polymer is capable of providing sustained release of a therapeutically active ingredient after insertion of the microneedle patch into the skin. In further embodiments, the sustained-release biodegradable polymer is water-soluble and comprises PLGA (polylactic-coglycolic acid), polyglycolic acid, fibroin, PLA (polylactic acid), PVP (polyvinylpyrrolidone), or PCL (polycaprolactone). In further embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the sustained-release biodegradable polymer does not release more than 75% of the therapeutically active ingredient until more than about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the sustained-release biodegradable polymer does not release the therapeutically active ingredient for more than about 24 hours at a value in the range of about 75% to about 100%, about 75% to about 99%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about 80% to about 100%, about 80% to about 99%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 100%, about 85% to about 99%, 85% to about 95%, about 85% to about 90%, about 90% to about 100%, about 90% to about 99%, about 95% to about 99%, or about 99% to about 100%. Specific examples include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, and about 100%.

[0157] In some embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 day to about 30 days. In some embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient over a period of about 2 days to about 21 days. In some embodiments, the sustained-release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 day to about 30 days, about 1 day to about 28 days, about 1 day to about 26 days, about 1 day to about 24 days, about 1 day to about 22 days, about 1 day to about 21 days, about 1 day to about 14 days, about 1 day to about 7 days, about 1 day to about 6 days, about 1 day to about 5 days, about 1 day to about 4 days, about 1 day to about 3 days, about 1 day to about 2 days, about 2 days to about 30 days, about 2 days to about 28 days, about 2 days to about 26 days, about 2 days to about 24 days, about 2 days to about 30 ...28 days, about 2 days to about 26 days, about 2 days to about 24 days, about 2 days to about 30 days, about 2 days to about 30 days, about ~ about 22 days, about 2 to about 21 days, about 2 to about 14 days, about 2 to about 7 days, about 2 to about 6 days, about 2 to about 5 days, about 2 to about 4 days, about 2 to about 3 days, about 3 to about 30 days, about 3 to about 28 days, about 3 to about 26 days, about 3 to about 24 days, about 3 to about 22 days, about 3 to about 21 days, about 3 to about 14 days, about 3 to about 7 days, about 3 to about 6 days, about 3 to about 5 days, about 3 to about 4 days, about 4 to about 30 days, about 4 to about 28 Days, about 4 to about 26 days, about 4 to about 24 days, about 4 to about 22 days, about 4 to about 21 days, about 4 to about 14 days, about 4 to about 7 days, about 4 to about 6 days, about 4 to about 5 days, about 5 to about 30 days, about 5 to about 28 days, about 5 to about 26 days, about 5 to about 24 days, about 5 to about 22 days, about 5 to about 21 days, about 5 to about 14 days, about 5 to about 7 days, about 5 to about 6 days, about 7 to about 30 days, about 7 to about 28 days, about 7 to about 26 The therapeutically effective substance is released for about 7 days, about 7 days to about 24 days, about 7 days to about 22 days, about 7 days to about 21 days, about 7 days to about 14 days, about 14 days to about 30 days, about 14 days to about 28 days, about 14 days to about 26 days, about 14 days to about 24 days, about 14 days to about 22 days, about 14 days to about 21 days, about 21 days to about 30 days, about 21 days to about 28 days, about 21 days to about 26 days, about 21 days to about 24 days, about 21 days to about 22 days, or within these ranges. Specific examples include about 30 days, about 28 days, about 26 days, about 24 days, about 22 days, about 21 days, about 14 days, about 7 days, about 6 days, about 5 days, about 4 days, about 3 days, about 2 days, about 1 day, or a range between any two of these values.

[0158] In some embodiments, a method for manufacturing a dissolvable microneedle patch comprising a biodegradable polymer capable of providing both sustained and immediate release of a therapeutically active ingredient following insertion of the microneedle patch into the skin. In some embodiments, the plurality of microneedles comprises an immediate-release biodegradable polymer and a sustained-release biodegradable polymer. In some embodiments, the plurality of microneedles comprises an immediate-release biodegradable polymer at the base of the microneedles and a sustained-release biodegradable polymer at the tip of the microneedles. In some embodiments, the plurality of microneedles comprises an immediate-release biodegradable polymer at the base of the microneedles and alternating layers of immediate-release biodegradable polymer and sustained-release biodegradable polymer at the tip of the microneedles.

[0159] In some embodiments, a method for manufacturing a dissolvable microneedle patch for treating a skin condition comprises applying a dissolvable microneedle patch, wherein the dissolvable microneedle patch is applied onto a skin lesion of a patient in need thereof to treat the skin condition. In some embodiments, the dissolvable microneedle patch is applied adjacent to a skin lesion of a patient in need thereof to treat the skin condition. In some embodiments, the dissolvable microneedle patch is applied to an area of ​​skin determined to be optimal based on the age of the patient. In some embodiments, the dissolvable microneedle patch is applied to an area of ​​skin determined to be optimal based on the type of skin requiring treatment.

[0160] In some embodiments, a method for manufacturing a dissolvable microneedle patch comprising a plurality of microneedles, wherein the microneedles are spatially separated within the skin and no one microneedle touches another. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, wherein the microneedle patch has at least about 1 to about 200 microneedles per square centimeter, about 1 to about 175 microneedles per square centimeter, about 1 to about 150 microneedles per square centimeter, about 125 microneedles per square centimeter, about 100 microneedles per square centimeter, about 90 microneedles per square centimeter, about 80 microneedles per square centimeter, about 70 microneedles per square centimeter, about 60 microneedles per square centimeter, about 50 microneedles per square centimeter, about 40 microneedles per square centimeter, about 30 microneedles per square centimeter, about 25 microneedles per square centimeter, about 20 microneedles per square centimeter, about 3 ... Needles, about 1 to about 15 microneedles per square centimeter, about 1 to about 10 microneedles per square centimeter, about 1 to about 5 microneedles per square centimeter, about 5 to about 200 microneedles per square centimeter, about 5 to about 175 microneedles per square centimeter, about 5 to about 150 microneedles per square centimeter, about 5 to about 125 microneedles per square centimeter, about 5 to about 100 microneedles per square centimeter, about 5 to about 90 microneedles per square centimeter, about 5 to about 80 microneedles per square centimeter, about 5 to about 70 microneedles per square centimeter, about 5 to about 60 microneedles per square centimeter, about 5 to about 50 microneedles per square centimeter, about 5 to about 40 microneedles per square centimeter, about 5 to about 30 microneedles per square centimeter,About 5 to about 25 microneedles per square centimeter, about 5 to about 20 microneedles per square centimeter, about 5 to about 15 microneedles per square centimeter, about 5 to about 20 microneedles per square centimeter, about 10 to about 200 microneedles per square centimeter, about 10 to about 175 microneedles per square centimeter, about 10 to about 150 microneedles per square centimeter, about 10 to about 150 microneedles per square centimeter, about 10 to about 125 microneedles per square centimeter $ / cm2, about 10 to about 100 microneedles / cm2, about 10 to about 90 microneedles / cm2, about 10 to about 80 microneedles / cm2, about 10 to about 70 microneedles / cm2, about 10 to about 60 microneedles / cm2, about 10 to about 50 microneedles / cm2, about 10 to about 40 microneedles / cm2, about 10 to about 30 microneedles / cm2, about 10 to about 25 microneedles / cm2, about 10 to about 20 microneedles / cm2 Torr, about 10 to about 15 microneedles per square centimeter, about 25 to about 200 microneedles per square centimeter, about 25 to about 175 microneedles per square centimeter, about 25 to about 150 microneedles per square centimeter, about 25 to about 125 microneedles per square centimeter, about 25 to about 100 microneedles per square centimeter, about 25 to about 90 microneedles per square centimeter, about 25 to 80 microneedles per square centimeter Approximately 25 to 70 microneedles, approximately 25 to 60 microneedles per square centimeter, approximately 25 to 50 microneedles per square centimeter, approximately 25 to 40 microneedles per square centimeter, approximately 25 to 30 microneedles per square centimeter, approximately 50 to 200 microneedles per square centimeter, approximately 50 to 175 microneedles per square centimeter, approximately 50 to 150 microneedles per square centimeter, approximately 50 to 125 microneedles per square centimeter,Approximately 50 to approximately 100 microneedles per square centimeter, approximately 50 to approximately 90 microneedles per square centimeter, approximately 50 to approximately 80 microneedles per square centimeter, approximately 50 to approximately 70 microneedles per square centimeter, approximately 50 to approximately 60 microneedles per square centimeter, approximately 75 to approximately 200 microneedles per square centimeter, approximately 75 to approximately 175 microneedles per square centimeter, approximately 75 to approximately 150 microneedles per square centimeter, approximately 75 to approximately 125 microneedles per square centimeter, approximately 75 to approximately 100 microneedles per square centimeter, approximately 75 to approximately 90 microneedles per square centimeter, approximately 75 to approximately 10 ... The density may be about 75 to about 80 microneedles per meter, about 100 to about 200 microneedles per square centimeter, about 100 to about 175 microneedles per square centimeter, about 100 to about 150 microneedles per square centimeter, about 100 to about 125 microneedles per square centimeter, 125 to about 200 microneedles per square centimeter, about 125 to about 175 microneedles / square centimeter, about 125 to about 150 microneedles / square centimeter, about 150 to about 200 microneedles / square centimeter, about 150 to about 175 microneedles / square centimeter, about 175 to about 200 microneedles / square centimeter, or values ​​within these ranges. Specific examples may include a dissolvable microneedle patch comprising a plurality of microneedles, the microneedle patch comprising at least about 200 microneedles per square centimeter, at least about 175 microneedles per square centimeter, at least about 150 microneedles per square centimeter, at least about 200 microneedles per square centimeter, at least about 125 microneedles / square centimeter, at least about 100 microneedles / square centimeter, at least about 90 microneedles / square centimeter, at least about 80 microneedles / square centimeter, at least about 70 microneedles / square centimeter, at least about 60 microneedles / square centimeter, at least about 50 microneedles / square centimeter,At least about 40 microneedles / square centimeter, at least about 30 microneedles / square centimeter, at least about 25 microneedles / square centimeter, at least about 20 microneedles / square centimeter, at least about 15 microneedles / square centimeter, at least about 10 microneedles / square centimeter, at least about 5 microneedles / square centimeter, at least about 4 microneedles / square centimeter, at least about 3 microneedles / square centimeter, at least about 2 microneedles / square centimeter, at least about 1 microneedles / square centimeter, or any two ranges between these values.

[0161] In some embodiments, a method for manufacturing a dissolvable microneedle patch is provided, wherein the dissolvable microneedle patch is of any shape necessary to accommodate the surface topology of the skin, hi some embodiments, the dissolvable microneedle patch has n sides ranging from about 0 sides to about 1000 sides. In some embodiments, the dissolvable microneedle patch has a viscosity of about 0 to about 1000 sides, about 0 to about 900 sides, about 0 to about 800 sides, about 0 to about 700 sides, about 0 to about 600 sides, about 0 to about 500 sides, about 0 to about 400 sides, about 0 to about 300 sides, about 0 to about 200 sides, about 0 to about 100 sides, about 0 to about 90 sides, about 0 to about 80 sides, about 0 to about 70 sides, about 0 to about 60 sides, about 0 to about 50 sides, about 0 to about 40 sides, about 0 to about 30 sides, about 0 to about 20 sides, about 0 to about 10 sides, about 0 sides to about 9 sides, about 0 sides to about 8 sides, about 0 sides to about 7 sides, about 0 sides to about 6 sides, about 0 sides to about 5 sides, about 0 sides to about 4 sides, about 0 sides to about 3 sides, about 0 sides to about 2 sides, about 10 sides to about 1000 sides, about 10 sides to about 900 sides, about 10 sides to about 800 sides, about 10 sides to about 700 sides, about 10 sides to about 600 sides, about 10 sides to about 500 sides, about 10 sides to about 400 sides, about 10 sides to about 300 sides, about 10 sides to about 200 sides, about 10 sides to about 100 sides, about 10 sides to about 90 sides, about 10 sides to about 80 sides, about 10 sides to about 70 sides, approximately 10 sides to approximately 60 sides, approximately 10 sides to approximately 50 sides, approximately 10 sides to approximately 40 sides, approximately 10 sides to approximately 30 sides, approximately 10 sides to approximately 20 sides, approximately 20 sides to approximately 1000 sides, approximately 20 sides to approximately 900 sides, approximately 20 sides to approximately 800 sides, approximately 20 sides to approximately 700 sides, approximately 20 sides to approximately 600 sides, approximately 20 sides to approximately 500 sides, approximately 20 sides to approximately 400 sides, approximately 20 sides to approximately 300 sides, approximately 20 sides to approximately 200 sides, approximately 20 sides to approximately 100 sides, approximately 20 sides to approximately 90 sides, approximately 20 sides to approximately 80 sides, approximately 20 sides to approximately 70 sides, approximately 20 sides to approximately 60 sides, approximately 20 sides to about 50 sides, about 20 sides to about 40 sides, about 20 sides to 30 sides, about 100 sides to about 900 sides, about 30 sides to about 800 sides, about 20 sides to about 600 sides, about 30 sides to about 700 sides, about 30 sides to about 600 sides, about 30 sides to about 500 sides, about 30 sides to about 400 sides, about 30 sides to about 300 sides, about 30 sides to about 200 sides, about 30 sides to about 100 sides, about 30 sides to about 90 sides, about 30 sides to about 80 sides, about 30 sides to about 70 sides, about 30 sides to about 60 sides, about 30 sides to about 50 sides, about 30 sides to about 40 sides, about 50 sides to about 1000 sidesApproximately 50 sides to approximately 900 sides, approximately 50 sides to approximately 800 sides, approximately 50 sides to approximately 700 sides, approximately 50 sides to approximately 600 sides, approximately 50 sides to approximately 500 sides, approximately 50 sides to approximately 400 sides, approximately 50 sides to approximately 300 sides, approximately 50 sides to approximately 200 sides, approximately 50 sides to approximately 100 sides, approximately 50 sides to approximately 90 sides, approximately 50 sides to approximately 80 sides, approximately 50 sides to approximately 70 sides, approximately 50 sides to approximately 60 sides, Approximately 100 sides, approximately 75 to 900 sides, approximately 75 to approximately 800 sides, approximately 75 to 700 sides, approximately 600 sides, approximately 75 to 500 sides, approximately 700 to 400 sides, approximately 100 sides to approximately 900 sides, approximately 75 to approximately 500 sides, approximately 75 to approximately 300 sides, approximately 75 to approximately 200 sides, approximately 75 to approximately 100 sides, approximately 75 to approximately 90 sides, approximately 75 to approximately 80 sides, approximately 100 to approximately 1000 sides , approximately 100 to approximately 900 sides, approximately 100 to approximately 700 sides, approximately 100 to approximately 600 sides, approximately 100 to approximately 500 sides, approximately 100 to approximately 400 sides, approximately 100 to approximately 300 sides, approximately 100 to 200 sides, approximately 150 to 1000 sides, approximately 150 to approximately 900 sides, approximately 250 sides to approximately 800 sides, approximately 250 sides to approximately 700 sides, approximately 250 sides to approximately 600 sides, approximately 250 sides It may be about 500 sides, about 250 sides to about 400 sides, about 250 sides to about 300 sides, about 500 sides to about 1000 sides, about 500 sides to about 900 sides, about 500 sides to about 800 sides, about 500 sides to about 600 sides, about 750 sides to about 1000 sides, about 750 sides to about 900 sides, about 800 sides, about 900 sides to 1000 sides, or values ​​within these ranges. Specific examples include dissolvable microneedle patches having a diameter of about 1000 sides, about 900 sides, about 800 sides, about 700 sides, about 600 sides, about 500 sides, about 400 sides, about 300 sides, about 200 sides, about 100 sides, about 90 sides, about 80 sides, about 70 sides, about 60 sides, about 50 sides, about 40 sides, about 30 sides, about 20 sides, about 10 sides, about 9 sides, about 8 sides, about 7 sides, about 6 sides, about 5 sides, about 4 sides, about 3 sides, about 2 sides, or a range between any two of these values.

[0162] In some embodiments, a method of making a dissolvable microneedle patch, wherein the dissolvable microneedle patch may have sides of equal length. In further embodiments, the dissolvable microneedle patch may have sides of unequal length. In some embodiments, the dissolvable microneedle patch is in the shape of a medical bandage. In some embodiments, the dissolvable microneedle patch is in a size range of about 0.1 square centimeters to about 1000 square centimeters, about 0.1 square centimeters to about 900 square centimeters, about 0.1 square centimeters to about 800 square centimeters, about 0.1 square centimeters to about 700 square centimeters, about 0.1 square centimeters to about 600 square centimeters, about 0.1 square centimeters to about 500 square centimeters, about 0.1 square centimeters to about 400 square centimeters, about 0.1 square centimeters to about 300 square centimeters, about 0.1 square centimeters to about 200 square centimeters, about 0.1 square centimeters to about 100 square centimeters, about 0.1 square centimeters to about 90 square centimeters, about 0.1 square centimeters to about 80 square centimeters, about 0.1 square centimeters to about 70 square centimeters, about 0.1 square centimeters to about 10 ... Square centimeters to about 60 square centimeters, about 0.1 square centimeters to about 60 square centimeters, about 100 square centimeters, 1 square centimeter to about 50 square centimeters, about 0.1 square centimeters to about 40 square centimeters, about 0.1 square centimeters to about 30 square centimeters, about 0.1 square centimeters to about 20 square centimeters, about 0.1 square centimeters to about 10 square centimeters, about 0.1 square centimeters to about 5 square centimeters, about 0.1 square centimeters to about 4 square centimeters, about 0.1 square centimeters to about 3 square centimeters, about 0.1 square centimeters to about 3,000 square centimeters, 1 square centimeter to about 2 square centimeters, about 0.1 square centimeters to about 1 square centimeter, about 0.1 square centimeters to about 0.9 square centimeters, about 0.1 square centimeters to about 0.8 square centimeters,Approximately 0.1 square centimeters to approximately 0.7 square centimeters, approximately 0.1 square centimeters to approximately 0.6 square centimeters, approximately 0.1 square centimeters to approximately 0.5 square centimeters, approximately 0.1 square centimeters to approximately 100 square centimeters, 1 square centimeter to approximately 0.4 square centimeters, approximately 0.1 square centimeters to approximately 0.3 square centimeters, approximately 0.1 square centimeters to approximately 0.2 square centimeters, approximately 0.5 square centimeters to approximately 1000 square centimeters, approximately 0.5 square centimeters to approximately 9 00 square centimeters, about 0.1 square centimeters to about 200 square centimeters, 5 square centimeters to about 900 square centimeters, about 0.5 square centimeters to about 800 square centimeters, about 0.5 square centimeters to about 700 square centimeters, about 0.5 square centimeters to about 600 square centimeters, about 0.5 square centimeters to about 1,500 square centimeters, about 0.5 square centimeters to about 1,600 square centimeters, 5 square centimeters to about 500 square centimeters, about 0.5 square centimeters 0.5 square centimeters to approximately 400 square centimeters, approximately 0.5 square centimeters to approximately 300 square centimeters, approximately 0.5 square centimeters to approximately 200 square centimeters, approximately 0.5 square centimeters to approximately 100 square centimeters, approximately 0.5 square centimeters to approximately 90 square centimeters, approximately 0.5 square centimeters to approximately 80 square centimeters, approximately 0.5 square centimeters to approximately 60 square centimeters, approximately 70 square centimeters to approximately 90 square centimeters, approximately 40 square centimeters to approximately 60 square centimeters , about 40 square centimeters to about 60 square centimeters, 5 square centimeters to about 70 square centimeters, about 0.5 square centimeters to about 60 square centimeters, about 0.5 square centimeters to about 50 square centimeters, about 0.5 square centimeters to about 40 square centimeters, about 0.5 square centimeters to about 30 square centimeters, about 0.5 square centimeters to about 20 square centimeters, about 0.5 square centimeters to about 10 square centimeters, about 0.5 square centimeters to about 5 square centimeters,Approximately 0.5 square centimeters to approximately 40 square centimeters, 5 square centimeters to approximately 4 square centimeters, approximately 0.5 square centimeters to approximately 3 square centimeters, approximately 0.5 square centimeters to approximately 2 square centimeters, approximately 0.5 square centimeters to approximately 1 square centimeter, approximately 0.5 square centimeters to approximately 0.9 square centimeters, approximately 0.5 square centimeters to approximately 0.8 square centimeters, approximately 0.5 square centimeters to approximately 0.7 square centimeters, approximately 0.5 square centimeters to approximately 0.6 square centimeters, 6 square centimeters , about 1 square centimeter to about 1000 square centimeters, about 1 square centimeter to about 900 square centimeters, about 1 square centimeter to about 800 square centimeters, about 1 square centimeter to about 700 square centimeters, about 1 square centimeter to about 600 square centimeters, about 1 square centimeter to about 500 square centimeters, about 1 square centimeter to about 400 square centimeters, about 1 square centimeter to about 300 square centimeters, about 1 square centimeter to about 200 square centimeters, about 1 square centimeter to Approximately 100 square centimeters, 1 square centimeter to approximately 90 square centimeters, approximately 1 square centimeter to approximately 80 square centimeters, approximately 1 square centimeter to approximately 70 square centimeters, approximately 1 square centimeter to approximately 60 square centimeters, approximately 1 square centimeter to approximately 50 square centimeters, approximately 1 square centimeter to approximately 40 square centimeters, approximately 1 square centimeter to approximately 30 square centimeters, approximately 1 square centimeter to approximately 20 square centimeters, approximately 1 square centimeter to approximately 10 square centimeters, approximately 1 square centimeter 1 to about 5 square centimeters, about 1 to about 4 square centimeters, about 1 to about 3 square centimeters, about 1 to about 2 square centimeters, about 10 to about 1000 square centimeters, about 10 to about 900 square centimeters, about 10 to about 800 square centimeters, about 10 to about 700 square centimeters, 10 to about 600 square centimeters, about 10 to about 500 square centimeters,Approximately 10 square centimeters to approximately 400 square centimeters, approximately 10 square centimeters to approximately 300 square centimeters, approximately 10 square centimeters to approximately 200 square centimeters, approximately 10 square centimeters to approximately 100 square centimeters, approximately 10 square centimeters to approximately 90 square centimeters, approximately 10 square centimeters to approximately 80 square centimeters, approximately 10 square centimeters to approximately 70 square centimeters, approximately 10 square centimeters to approximately 60 square centimeters, approximately 10 square centimeters to approximately 50 square centimeters, approximately 10 square centimeters Approximately 10 to approximately 40 square centimeters, approximately 10 to approximately 30 square centimeters, approximately 10 to approximately 20 square centimeters, approximately 50 to approximately 1000 square centimeters, approximately 50 to approximately 900 square centimeters, approximately 50 to approximately 800 square centimeters, approximately 50 to approximately 700 square centimeters, approximately 50 to approximately 600 square centimeters, approximately 50 to approximately 500 square centimeters, approximately 50 to approximately 400 square centimeters inches, approximately 50 square centimeters to approximately 300 square centimeters, approximately 50 square centimeters to approximately 200 square centimeters, approximately 50 square centimeters to approximately 100 square centimeters, approximately 75 square centimeters to approximately 1000 square centimeters, approximately 75 square centimeters to approximately 900 square centimeters, approximately 75 square centimeters to approximately 800 square centimeters, approximately 75 square centimeters to approximately 700 square centimeters, approximately 75 square centimeters to approximately 600 square centimeters, approximately 75 square centimeters to approximately 500 square centimeters , about 75 square centimeters to about 400 square centimeters, about 75 square centimeters to about 300 square centimeters, about 75 square centimeters to about 200 square centimeters, about 75 square centimeters to about 100 square centimeters, about 100 square centimeters to about 1000 square centimeters, about 100 square centimeters to about 900 square centimeters, about 100 square centimeters to about 800 square centimeters, about 100 square centimeters to about 700 square centimeters, about 100 square centimeters to about 600 square centimeters,Approximately 100 square centimeters to approximately 500 square centimeters, approximately 100 square centimeters to approximately 400 square centimeters, approximately 100 square centimeters to approximately 300 square centimeters, approximately 100 square centimeters to approximately 200 square centimeters, approximately 250 square centimeters to approximately 1000 square centimeters, approximately 250 square centimeters to approximately 900 square centimeters, approximately 250 square centimeters to approximately 800 square centimeters, approximately 250 square centimeters to approximately 700 square centimeters, approximately 250 square centimeters to approximately 600 square centimeters, approximately 250 square centimeters to approximately 500 square centimeters, approximately 250 square centimeters to about 400 square centimeters, about 250 square centimeters to about 300 square centimeters, about 500 square centimeters to about 1000 square centimeters, about 500 square centimeters to about 900 square centimeters, about 500 square centimeters to about 800 square centimeters, about 500 square centimeters to about 700 square centimeters, about 500 square centimeters to about 600 square centimeters, about 750 square centimeters to about 1000 square centimeters, about 750 square centimeters to about 900 square centimeters, about 750 square centimeters to about 800 square centimeters, or a range between any two of these values. Specific examples of dissolvable microneedle patches include about 1000 square centimeters, about 900 square centimeters, about 800 square centimeters, about 700 square centimeters, about 600 square centimeters, about 500 square centimeters, about 400 square centimeters, about 300 square centimeters, about 200 square centimeters, about 100 square centimeters, about 90 square centimeters, about 80 square centimeters, about 70 square centimeters, about 60 square centimeters, about 50 square centimeters, about 40 square centimeters, about 30 square centimeters, about 20 square centimeters, about 10 square centimeters, about 5 square centimeters, about 4 square centimeters, about 3 square centimeters, about 2 square centimeters, about 1 square centimeter, about 0.9 square centimeters, about 0.8 square centimeters, about 0.7 square centimeters, about 0.6 square centimeters, about 0.5 square centimeters,about 0.4 square centimeters, about 0.3 square centimeters, about 0.2 square centimeters, about 0.1 square centimeters, or a range between any two of these values.

[0163] In some embodiments, there is provided a method for manufacturing a dissolvable microneedle patch, wherein the dissolvable microneedle patch comprises a backing layer and a microneedle layer. In some embodiments, the dissolvable microneedle patch comprises a backing layer and a microneedle layer, wherein the microneedle layer is placed directly on the skin. In some embodiments, the dissolvable microneedle patch comprises a backing layer, wherein the backing layer is comprised of adhesive medical tape. In some embodiments, the dissolvable microneedle patch comprises a backing layer comprising a therapeutically active ingredient.

[0164] In some embodiments, a method for manufacturing a dissolvable microneedle patch is provided, wherein the dissolvable microneedle patch comprises a backing layer, the backing layer being a releasable substrate. In some embodiments, a dissolvable microneedle patch is provided, wherein the removable substrate is comprised of adhesive medical tape. In some embodiments, the backing layer comprises a fast-dissolving polymer. In some embodiments, a dissolvable microneedle patch is provided, wherein the removable substrate comprises a therapeutically active ingredient dispersed in the polymer. In some embodiments, a dissolvable microneedle patch is provided, wherein a plurality of microneedles are attached to a removable substrate and comprise tapered tips extending away from the removable substrate. In some embodiments, a dissolvable microneedle patch is provided, wherein the removable substrate releases at least about 90% of the microneedles from the adhesive surface within about 20 minutes after application to the skin. In some embodiments, a dissolvable microneedle patch is provided, wherein the removable substrate releases at least about 90% of the microneedles from the adhesive surface within about 5 minutes after application to the skin. In some embodiments, the dissolvable microneedle patch in which 90% of the microneedles detach from the adhesive surface within a period of about 0 to about 20 minutes, about 0 to about 15 minutes, about 0 to about 10 minutes, about 0 to about 9 minutes, about 0 to about 8 minutes, about 0 to about 7 minutes, about 0 to about 6 minutes, about 0 to about 5 minutes, or about 0 to about 4 minutes is as follows:About 0 to about 3 minutes, about 0 to about 2 minutes, about 0 to about 1 minute, about 1 to about 20 minutes, about 1 to about 15 minutes, about 1 to about 10 minutes, about 1 to about 9 minutes, about 1 to about 8 minutes, about 1 to about 7 minutes, about 1 to about 6 minutes, about 1 to about 5 minutes, about 1 to about 4 minutes, about 1 to about 3 minutes, about 1 to about 2 minutes, about 2 to about 20 minutes, about 2 to about 15 minutes, about 2 to about 10 minutes, about 2 to about 9 minutes, about 2 to about 8 minutes, about 2 to about 7 minutes, about 2 to about 6 minutes, about 2 to about 5 minutes, about 2 to about 4 minutes, about 2 to about 3 minutes, about 5 minutes ~20 minutes, approximately 5 minutes to approximately 15 minutes, approximately 5 minutes to approximately 10 minutes, approximately 5 minutes to approximately 10 minutes, approximately 5 minutes to approximately 9 minutes, approximately 5 minutes to approximately 8 minutes, approximately 5 minutes to approximately 7 minutes, approximately 5 minutes to approximately 6 minutes, approximately 10 minutes to approximately 20 minutes, approximately 10 minutes to approximately 15 minutes, approximately 15 minutes to approximately 20 minutes, approximately 0 seconds to approximately 60 seconds, approximately 0 seconds to approximately 45 seconds, approximately 0 seconds to approximately 30 seconds, approximately 0 seconds to approximately 15 seconds, approximately 0 seconds to approximately 10 minutes, approximately 0 seconds to approximately 9 seconds, approximately 0 seconds to approximately 8 seconds, approximately 0 seconds to approximately 7 seconds, approximately 0 seconds to approximately 6 seconds, approximately 0 seconds to approximately 5 seconds, approximately 0 seconds to approximately 4 seconds, approximately 0 seconds to approximately 3 seconds, approximately 0 seconds to approximately 2 seconds, 1 second to 60 seconds, 1 second to 45 seconds, 1 second to 30 seconds, 1 second to 15 seconds, 1 second to 10 seconds, 1 second to 9 seconds, 1 second to 8 seconds, 1 second to 7 seconds, 1 second to 6 seconds, 1 second to 5 seconds, 1 second to 4 seconds, 1 second to 3 seconds, 1 second to 2 seconds, 2 seconds to 60 seconds, 2 seconds to 45 seconds, 2 seconds to 30 seconds, 2 seconds to 15 seconds, 2 seconds to 10 seconds, 2 seconds to 9 seconds, 2 seconds to 8 seconds, 2 seconds to 7 seconds, 2 seconds to 6 seconds, 2 seconds to 5 seconds, 2 seconds to 4 seconds, approx. The time may be 2 seconds to about 3 seconds, about 5 seconds to about 60 seconds, about 5 seconds to about 45 seconds, about 5 seconds to about 30 seconds, about 5 seconds to about 15 seconds, about 5 seconds to about 10 seconds, about 5 seconds to about 9 seconds, about 5 seconds to about 8 seconds, about 5 seconds to about 7 seconds, about 5 seconds to about 6 seconds, about 10 seconds to about 60 seconds, about 10 seconds to about 45 seconds, about 10 seconds to about 30 seconds, about 10 seconds to about 15 seconds, about 15 seconds to about 60 seconds, about 15 seconds to about 45 seconds, about 15 seconds to about 30 seconds, about 30 seconds to about 60 seconds, about 30 seconds to about 45 seconds, about 45 seconds to about 60 seconds, or a value within these ranges. In specific examples, 90% of the microneedles are released from the adhesive surface of the dissolvable microneedle patch within about 20 minutes, about 15 minutes, about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, about 1 minute, about 60 seconds, about 45 seconds, about 30 seconds, about 15 seconds, about 10 seconds, about 9 seconds, about 8 seconds, about 7 seconds, about 6 seconds, about 5 seconds, about 4 seconds, about 3 seconds, about 2 seconds, about 1 second, or a range between any two of these values.

[0165] In some embodiments, a method for making a dissolvable microneedle patch includes a backing layer overlying the base of the tip portion such that each microneedle is separated from the other microneedles on the patch to form spaced apart entities upon removal of the substrate upon application of the patch to the skin.

[0166] In some embodiments, a method for manufacturing a dissolvable microneedle patch includes the steps of: (i) placing the dissolvable microneedle patch on a surface area of ​​the skin of a patient in need of treatment or pre-treatment testing to assess hypersensitivity reactions, general tolerability, or other adverse events; (ii) applying sufficient force to the patch composition to allow the microneedles to penetrate from the epidermis to the papillary dermis; (iii) placing multiple microneedles on the patch composition while the microneedles penetrate from the epidermis to the papillary dermis; and (iii) allowing the multiple microneedles to remain in the skin until the biodegradable polymer degrades; and (iv) removing the adhesive substrate from the patch composition, wherein step (ii) is performed by applying finger pressure, the pressure being sufficient to resist a force ranging from about 0 N to about 1,000 N. In a preferred embodiment of the present application, the...

Claims

1. A dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin, comprising: a plurality of microneedles, including microneedles having at least two different lengths; and a removable substrate; the plurality of microneedles are attached to the removable substrate; the plurality of microneedles include tapered tips extending away from the removable substrate; the plurality of microneedles comprising a biodegradable polymer and a therapeutically active ingredient dispersed in the biodegradable polymer; and A dissolvable microneedle patch, wherein the therapeutically active ingredient is selected from the group consisting of a vaccine, an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein.

2. 2. The dissolvable microneedle patch of claim 1, wherein the at least two different lengths are selected from the group consisting of a length terminating in the epidermis and a length terminating in the reticular or papillary dermis.

3. 10. The dissolvable microneedle patch of claim 1, wherein the one or more microneedle lengths can range from about 10 microns to about 1000 microns.

4. 10. The dissolvable microneedle patch of claim 1, wherein the at least two microneedles of different lengths are composed of equal amounts of biodegradable polymer.

5. 10. The dissolvable microneedle patch of claim 1, wherein the at least two different length microneedles may be of different lengths based on location on the body, age of the patient, or skin condition to be treated.

6. 10. The dissolvable microneedle patch of claim 1, wherein each of the plurality of microneedles contains approximately the same amount of a therapeutically active ingredient.

7. 10. The dissolvable microneedle patch of claim 1, wherein the plurality of microneedles each contain an unequal amount of a therapeutically active ingredient.

8. 2. The dissolvable microneedle patch of claim 1, wherein the vaccine is selected from the group consisting of measles-mumps-rubella vaccine, mumps vaccine, human papillomavirus vaccine, Bacillus Calmette-Guerin vaccine, and Mycobacterium w vaccine.

9. 2. The dissolvable microneedle patch of claim 1, wherein the immunostimulatory molecule is imiquimod.

10. 10. The dissolvable microneedle patch of claim 1, wherein the immunostimulatory protein is a Candida antigen.

11. 11. The immunostimulatory protein of claim 10, wherein the Candida antigen is substantially free of glycerin.

12. 12. The glycerin-free Candida antigen of claim 11, wherein the Candida antigen is lyophilized.

13. 2. The dissolvable microneedle patch of claim 1, wherein the immunostimulatory organism is selected from the group consisting of Propionibacterium acnes, Corynebacterium parvum, Priopiobacterium, and Mycobacterium indicus planii.

14. 2. The dissolvable microneedle patch of claim 1, wherein the immunostimulatory protein is selected from the group consisting of Candida antigen, tinea fungus antigen, tuberculin, purified protein derivative, human papillomavirus surface protein, interferon alpha, interferon beta, and interferon gamma.

15. 10. The dissolvable microneedle patch of claim 1, wherein the dissolvable microneedle patch comprises at least about 1 to about 200 microneedles per square centimeter.

16. 10. The dissolvable microneedle patch of claim 1, wherein the dissolvable microneedle patch ranges from about 0.1 to about 1000 square centimeters and can be trimmed to fit any shape necessary to accommodate any surface of human skin topology.

17. 10. The dissolvable microneedle patch of claim 1, wherein the plurality of microneedles are configured to provide sustained release of a therapeutically active ingredient to the skin.

18. 18. The sustained release microneedle of claim 17, wherein the sustained release microneedle is configured to release the therapeutically active ingredient for about 1 day to about 30 days after application of the dissolvable microneedle patch to the skin.

19. 10. The dissolvable microneedle patch of claim 1, wherein the plurality of microneedles are configured to have an immediate release of a therapeutically active ingredient into the skin.

20. 20. The immediate release microneedle of claim 19, configured to release a therapeutically active ingredient from about 0 hours to about 24 hours after application of the dissolvable microneedle patch to the skin.

21. 10. The dissolvable microneedle patch of claim 1, wherein the plurality of microneedles are configured to have both sustained and immediate release of a therapeutically active ingredient to the skin.

22. 10. The dissolvable microneedle patch of claim 1, wherein the plurality of microneedles are spatially separated within the skin such that one microneedle does not touch another microneedle.

23. 10. The dissolvable microneedle patch of claim 1, wherein the plurality of microneedles are tapered to facilitate insertion of the microneedles into the skin.

24. 2. The dissolvable microneedle patch of claim 1, wherein the tapered tip comprises from about 5% to about 99% of the total volume of the plurality of microneedles.

25. 10. The dissolvable microneedle patch of claim 1, wherein the removable substrate comprises a therapeutically active ingredient dispersed in a polymer.

26. 10. The dissolvable microneedle patch of claim 1, wherein the removable substrate comprises adhesive medical tape.

27. 10. The dissolvable microneedle patch of claim 1, wherein the microneedle patch administers a therapeutically effective amount of a Candida antigen to a subject in need thereof.

28. 10. The dissolvable microneedle patch of claim 1, wherein the therapeutically active ingredient stimulates a local immune response.

29. 1. A method of treating a skin condition, comprising: i) applying to the skin a dissolvable microneedle patch for delivering a therapeutically active ingredient to said skin, a plurality of microneedles, including microneedles having at least two different lengths; and a removable substrate; the plurality of microneedles are attached to the removable substrate; the plurality of microneedles include tapered tips extending away from the removable substrate; and the plurality of microneedles comprising a biodegradable polymer and a therapeutically active ingredient dispersed in the biodegradable polymer; and applying the dissolvable microneedle patch, wherein the active ingredient is selected from the group consisting of a vaccine, an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein; and ii) applying sufficient force to the dissolvable microneedle patch to allow the microneedles to penetrate into a location selected from the group consisting of the epidermis, the dermis, and the papillary dermis; and iii) allowing the plurality of microneedles to remain within the skin until the biodegradable polymer degrades; and iv) removing the adhesive substrate from said patch composition.

30. 30. The method of claim 29, wherein at least 90% of the plurality of microneedles detach from the removable substrate within about 20 minutes after application of the dissolvable microneedle patch.

31. 30. The method of claim 29, wherein at least 90% of the microneedles detach from the adhesive surface of the substrate upon removal of the substrate within 5 minutes.

32. 30. The method of claim 29, wherein the biodegradable polymer degrades to release a therapeutically active agent into the skin.

33. 30. The method of claim 29, wherein the biodegradable polymer degrades over a period of about 1 day to about 30 days, releasing a therapeutically active ingredient into the skin.

34. 30. The method of claim 29, wherein the biodegradable polymer degrades over a period of about 2 days to about 21 days, releasing a therapeutically active ingredient into the skin.

35. 30. The method of claim 29, wherein the sufficient force is applied to the skin with a finger.

36. 36. The method of claim 35, wherein the sufficient force is applied in the range of 0 Newtons to about 1000 Newtons.

37. 36. The method of claim 35, wherein the sufficient force applied is 10 N.

38. 30. The method of claim 29, wherein the sufficient force is applied by impact insertion with an applicator device.

39. 39. The method of claim 38, wherein the sufficient force ranges from 0N to about 1000N.

40. 39. The method of claim 38, wherein the sufficient force applied is 10 N.

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