Microneedle patches for immunostimulant drug delivery

Abstract

The present application provides a dissolvable microneedle device comprising a therapeutically active ingredient dispersed in a biodegradable polymer for delivering an immune stimulant to the skin. The present application also provides a method of treating a skin condition comprising applying to the skin a dissolvable microneedle device comprising a therapeutically active ingredient dispersed in a biodegradable polymer.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 191,564, filed May 21, 2021, and is incorporated herein by reference. [Background technology]

[0002] At first glance, transdermal drug delivery appears to be an attractive route of drug administration due to the large surface area of ​​the skin and its relative accessibility to directly apply drugs to areas affected by skin diseases. However, in reality, transdermal drug delivery is not a suitable route of administration for many therapeutically active ingredients, because the skin acts as a protective barrier that prevents these ingredients from reaching clinically relevant concentrations within the epidermis and dermis.

[0003] The ability of skin to act as a barrier for effective drug delivery is primarily due to the lipid-rich outer layer of the epidermis, called the stratum corneum. The lipids contained in the stratum corneum prevent hydrophilic molecules from passing through the skin barrier. In addition, tight junctions between cells in the epidermis (e.g., adherens junctions, desmosomes, zonula occludens) prevent substances larger than 500 kilodaltons from penetrating the skin. As a result, the large immunogenic proteins and peptides that constitute a class of cutaneous immunotherapies cannot be reliably administered to the skin with conventional formulations.

[0004] Several methods have been attempted to enhance transdermal drug delivery of large substances such as cutaneous immune stimulants. These include the addition of chemical penetration enhancers such as ethanol, propylene glycol, and hydrophobic vesicles to topical formulations, cell membrane polarization by iontophoresis, and mechanical delivery by cavitational ultrasound. Unfortunately, these methods of enhancing transdermal drug delivery have two major pitfalls: 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 are oily) or too burdensome for the patient due to the need for cumbersome equipment (e.g., cavitational ultrasound, iontophoresis).

[0005] 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, delivering drugs directly to the desired depth within the epidermis and / or dermis, where they can perform their desired function. Dissolvable microneedles, a subtype of microneedles, are composed solely of degradable polymers complexed with active ingredients. Thus, once inserted into the skin, they are completely consumed in the process of dissolution.

[0006] 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 microneedles, they have never been used to deliver cutaneous immunostimulants with the aim of generating a local immune response to treat skin diseases.

[0007] One group of skin conditions that would benefit from finely tuned administration of immune stimulants to the skin are infectious and malignant neoplasms such as viral warts, molluscum contagiosum, and non-melanoma skin cancers. These conditions cannot be adequately treated with microneedles containing immunosuppressants or chemotherapy for several reasons. Essentially, these neoplasms vary in size and shape, even between 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 they have. The reason these drug classes need to be administered with precisely sized microneedle patches is so that the drug can reach all neoplastic cells while minimizing damage to surrounding cells. Creating microneedle patches of numerous sizes, as would be required for these types of components, is impractical from a manufacturing standpoint, thus limiting the use of immunosuppressant and chemotherapy microneedles in the treatment of skin diseases. Additionally, these types of neoplasms often result in multiple skin lesions in the same patient. Treating neoplasms with microneedles composed of immunosuppressants or local chemotherapy requires the application of microneedle patches to individual neoplasms, which is burdensome from the perspective of clinical management.

[0008] One condition in particular that may benefit from fine-tuned delivery of immune stimulants to the skin is viral warts. Viral warts are an extremely common condition that affects nearly 20% of school-age children. Unfortunately, currently available wart treatments are 1) painful, 2) ineffective, 3) leave scars, 4) must be applied daily for months at a time, and / or 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 destroy the adhesion between the cells that make up the wart, and immune stimulants that are applied locally or injected into the wart. Destructive wart treatments are painful, create open wounds in the skin, and can leave permanent scars. Salicylic acid-containing products must be applied daily under occlusion and worn 24 hours a day for months at a time, limiting real-world treatment compliance and efficacy.

[0009] Cutaneous immunotherapy is a type of wart treatment in which immune stimulants are applied topically or injected into the wart to generate a local immune response that recognizes and destroys the viral infection that causes the wart. The use of immunotherapy in clinical practice is limited by issues with current formulations, such as creams and injectable solutions. Topical application of creams is burdensome and time-consuming, requiring patients to apply the cream daily for up to several months at a time. The reason that immunotherapy creams require so many applications to be effective is because penetration of topically applied immunotherapy active ingredients into the skin is limited by the stratum corneum. Injectable immune stimulants require fewer doses than topical agents because the injections bypass the stratum corneum. However, the use of injectable immune stimulants is limited by the pain associated with injections and the inability to reliably place injectable immune stimulants within the epidermis because intercellular junctions prevent fluid expansion within the epidermis. In addition, because injections of immune stimulants into warts must be performed by experienced healthcare professionals, their use requires patients to visit the clinic every 2–4 weeks for treatment. The need for frequent visits places time constraints on both patients and healthcare providers, reducing completion rates of the treatment course.

[0010] The creation of the first ever dissolvable microneedles containing cutaneous immunotherapy addresses current limitations in cutaneous immunotherapy delivery by enabling precise delivery of immune stimulants to the epidermis and dermis, where the key immune effector cells, Langerhans cells and dermal dendritic cells, reside, respectively. The present invention not only enables painless and precise delivery of cutaneous immune stimulants to the skin to treat skin diseases, but is also the only cutaneous immunotherapy formulation that allows for sustained release of immune stimulants creating controlled and ongoing immune stimulation.

[0011] The limitation of using immune stimulating antigens as therapeutic agents in microneedle patches is that glycerol is required to stabilize these proteins. However, the addition of glycerol inhibits the formation of microneedle structures. The present invention provides an alternative antigen composition that allows for proper stabilization of antigens in dissolvable microneedle patches made of biodegradable polymers. These dissolvable microneedle patches can be used to deliver therapeutically active ingredients such as antigens to patients in need. Summary of the Invention

[0012] An embodiment of the present application relates to a dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin, the dissolvable microneedle patch comprising a plurality of microneedles and a removable substrate, the plurality of microneedles being attached to the removable substrate, the plurality of microneedles comprising a tapered tip portion 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 the therapeutically active ingredient is an antigen composition comprising less than 50% glycerol.

[0013] An embodiment of the present application relates to a method of treating a skin condition comprising: i) applying a dissolvable microneedle patch to deliver a therapeutically active ingredient to the skin, the dissolvable microneedle patch comprising a plurality of microneedles and a removable substrate, the plurality of microneedles being attached to the removable substrate, the plurality of microneedles comprising a tapered tip portion 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 the therapeutically active ingredient is an antigen composition comprising less than 50% glycerol; ii) applying sufficient force to the dissolvable microneedle patch to enable the microneedles to penetrate a location selected from the group consisting of the epidermis, the dermis and the papillary dermis; iii) allowing the plurality of microneedles to remain on the skin until the biodegradable polymer degrades; and iv) removing the adhesive substrate from the patch composition. [Brief description of the drawings]

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

[0015] [Figure 1] FIG. 1 shows a top view of the microneedle patch of the present application, where if the adhesive were translucent the pyramidal needles underneath would be visible. [Diagram 2] FIG. 2 shows a side view of the microneedle patch of the present application 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 to the various layers of the skin. [Diagram 3] FIG. 3 shows a top view of the microneedle patch of the present application, where if the adhesive were translucent the cone-shaped needles underneath would be visible. [Figure 4]FIG. 4 is a scanning electron micrograph image of a microneedle patch having microneedles that are 500 microns in length. [Diagram 5] FIG. 5 is a scanning electron micrograph image of a microneedle patch having microneedles that are 800 microns in length. [Figure 6] FIG. 6 is a top view of pig skin after insertion of a microneedle patch containing a blue tissue marking dye. [Figure 7] FIG. 7 shows a cross-sectional image of pig skin after insertion of a microneedle patch containing a blue tissue marking dye. [Figure 8] FIG. 8 is a scanning electron micrograph image of a microneedle patch containing 500 micron long immediate release biodegradable polymer microneedles. [Figure 9] FIG. 9 is a scanning electron micrograph image of a microneedle patch containing 800 micron long immediate release biodegradable polymer microneedles. [Figure 10] FIG. 10 is a diagram of a microneedle patch from a side view showing 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 showing the release of Candida antigens from a 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 microneedle comprising an immediate release water soluble polymer and one or more therapeutic active ingredients at the base of the microneedle and a sustained release polymer and one or more therapeutic active ingredients at the tip of the microneedle. [Figure 13] FIG. 13 is a treatment regimen consisting of successive applications of microneedle patches containing an immediate release polymer. [Figure 14] FIG. 14 is a treatment regimen consisting of successive applications of microneedle patches containing sustained release polymers. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] The present disclosure is not limited to the specific systems, apparatus, and methods described. The terminology used herein is for the purpose of describing the particular versions or embodiments only, and is not intended to limit the scope. Such aspects of the present 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 in the disclosure, which are intended as examples of various aspects. As will be apparent to those skilled in the art, many modifications and variations can be made without departing from the spirit and scope thereof. Functionally equivalent methods and devices within the scope of the present disclosure will be apparent to those skilled in the art from the foregoing description, in addition to those recited herein. Such modifications and variations are intended to be included 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 to be understood that the present disclosure is not limited to specific methods, reagents, compounds, compositions, or biological systems. 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 indicates otherwise. 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 is to 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 "including, but not limited to."

[0019] Although various compositions, methods, and devices are described in terms "comprising" (which should be interpreted as meaning "including, but not limited to") various components or steps, the compositions, methods, and devices can also "consist essentially of" or "consist of" the various components and steps, and such terms should be interpreted as defining essentially closed groups of members.

[0020] With respect to the use of virtually any plural and / or singular term herein, one of ordinary skill in the art can translate 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 provided herein for clarity.

[0021] In general, those skilled in the art will understand 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 not limited to," etc.). Those skilled in the art will further understand that if a particular number of recitations of the introduced claims are intended, such intention will be expressly set forth in the claims, and in the absence of such recitation, no such intention exists. For example, as an aid to understanding, the following appended claims may use the introductory phrases "at least one" and "one or more" to introduce the recitations of the claims. However, the use of such phrases should not be construed to mean that the introduction of a claim repeat with the indefinite article "a" or "an" limits a particular claim that includes such an introduced claim repeat to embodiments that include only one such repeat, even if the same claim includes the introductory phrase "one or more" or "at least one" and an indefinite article such as "a" or "an" (e.g., "a" and / or "an" should be construed to mean "at least one" or "one or more"); nor should the use of definite articles used at the beginning of a claim. Moreover, even if a particular number of introduced claim repeats is explicitly recited, one of ordinary skill in the art will recognize that such recitation should be construed to mean at least the number recited (e.g., the mere recitation of "two recitations" without other modifiers means at least two recitations or two or more recitations).Furthermore, when a convention similar to "at least one of A, B, and C" is used, such configurations are generally intended in the sense that one of ordinary skill in the art would understand the convention (e.g., "a system having at least one of A, B, and C" includes, 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 a convention similar to "at least one of A, B, or C" is used, such configurations are generally intended in the sense that one of ordinary skill in the art would understand the convention (e.g., "a system having at least one of A, B, or C" includes, 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.). Those skilled in the art will further appreciate that virtually any conjunctive word and / or phrase presenting two or more alternative terms, whether in the specification, 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" is understood to include the possibilities of "A" or "B," or "A and B."

[0022] In addition, where 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 thereby also described in terms of any individual members or subgroups of members of the Markush group.

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

[0024] As will be appreciated by those of skill in the art, all ranges disclosed herein encompass all possible subranges and combinations of subranges thereof for any purpose, including in terms of providing a written description. 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, and upper third, etc. As will also be appreciated by those of skill in the art, all phrases such as "up to," "at least," etc. refer to ranges that are inclusive of the recited numbers and that can then be broken down into subranges as described above. Finally, as will be appreciated by those of skill in the art, ranges include individual members. Thus, for example, a group having 1-3 cells refers to a group having 1, 2, or 3 cells. Similarly, a group having 1-5 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, for example, due to real-world measurement or handling procedures, due to inadvertent errors in these procedures, due to differences in the manufacture, source, or purity of the composition or reagent, and the like. In general, the term "about" as used herein means greater or smaller than the stated value or range of values ​​by 1 / 10 of the stated value, e.g., ±10%. The term "about" also refers to variations that would be recognized as equivalent by one 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 also 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 numerical quantities of such values ​​that may occur but are recognized as equivalent by one of ordinary skill in the art. If the context of this disclosure indicates otherwise or is inconsistent with such an interpretation, the above interpretation can 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 less than half the interval between the preceding and succeeding values, e.g., a range extending from more than 49.5 to less than 52.5. Furthermore, expressions less than "about" a value or greater than "about" a value 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 referenced is present in an amount of not more than 10% by weight or volume of the total composition.

[0027] When a range of values ​​is listed, each intervening value between the upper and lower limits of that range, as well as other stated or intervening values ​​within that listed range, are intended to be encompassed by the disclosure. For example, if a range of 1 μm to 8 μm is listed, 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 ​​equal to or greater than 1 μm and ranges of values ​​equal to or less than 8 μm.

[0028] The terms "patient" and "subject" are interchangeable and may be taken to mean any living organism that may be treated with the compounds of the present invention. Thus, the terms "patient" and "subject" may include, but are not limited to, any non-human mammal, primate, or human. In some embodiments, the "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, the patient or subject is an adult, child, or infant. In some embodiments, the patient or subject is a human.

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

[0030] The term "tissue" refers to an association of similarly specialized cells that unite to perform a particular function.

[0031] In this disclosure, the term "disorder" means, and is used interchangeably with, the terms 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 the direct administration of a compound (also referred to as a substance of interest) or a pharma- ceutically acceptable salt or composition of a compound (substance of interest) to a subject.

[0034] The terms "treat", "treated" or "treating" as used herein 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 medical condition, improve the texture, appearance, color, feel, 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 otherwise obtain a beneficial or desired clinical result. For purposes of the present invention, beneficial or desired clinical results include, but are not limited to, reversal, reduction, or alleviation of symptoms; reduction in the extent of a condition, disorder, or disease; stabilization (i.e., not worsening) of a condition, disorder, or disease; delay in onset or slowing of progression of a condition, disorder, or disease; improvement in the condition of a condition, disorder, or disease; and remission (whether partial or total), or enhancement or amelioration, whether detectable or undetectable, of a 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 treated.

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

[0036] The term "therapeutic agent" or "therapeutic agent" or "pharmaceutical active agent" as used herein means an agent utilized to treat, combat, ameliorate, prevent or improve an undesirable condition or disease in a patient.

[0037] As used herein, the term "composition" refers to a combination or mixture of two or more different ingredients, components, 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, such as immunogenic antigens, such as Candida antigens, Trichophyton antigens, and tuberculin, immunogenic microorganisms, such as Corynebacterium parvum, Cutibacterium acnes, and Mycobacterium indicus pranii (formerly Mycobacterium w), immunogenic molecules, such as imiquimod, and immunogenic vaccines, such as human papillomavirus vaccines, measles-mumps-rubella vaccines, mumps vaccines, Bacillus Calmette-Guerin vaccines, and Mycobacterium w vaccines.

[0039] The term "antigen" as used herein refers to any substance that activates an immune response in a subject. Antigens can be vaccines, immunostimulatory proteins, immunostimulatory compounds, and immunostimulatory organisms.

[0040] The phrase "therapeutically effective" is intended to modify the amount of active ingredient (ie, a compound or derivative thereof) used to treat a disease or disorder or effect a clinical endpoint.

[0041] A "therapeutically effective amount" or "effective amount" of a compound or composition is a predetermined amount calculated to inhibit, block, or reverse the desired effect, i.e., cell activation, migration, or proliferation. The activity contemplated by the present method includes both medical and / or prophylactic treatment, as appropriate. The specific dose of the compound administered according to the present invention to obtain 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 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 chosen route of administration, and thus the above dosage ranges 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 a local concentration in tissues when administered in a physiologically acceptable excipient composition.

[0042] The term "inhibiting" includes administering a compound of the invention to prevent the onset of the symptoms, alleviate the symptoms, relieve the symptoms, slow or reduce the progression of the disease and / or its symptoms, or eliminate the disease, condition, or disorder.

[0043] As used herein, the phrase "essentially free of therapeutically active ingredients" refers to an amount of therapeutically active ingredients that would not elicit a physiological response. "Essentially free of therapeutically active ingredients" can be defined as about 10% or less of a therapeutically active ingredient.

[0044] The term "excipient" as used herein encompasses carriers and diluents, which means materials, compositions or vehicles, such as liquid or solid fillers, diluents, excipients, solvents or encapsulating materials, that are involved in carrying or transporting a pharmaceutical, cosmetic or other agent across a tissue layer, such as the stratum corneum or stratum spinosum.

[0045] As used herein, the term "glycerol" refers to either glycerol or glycerin.

[0046] The terms "topically" and "topical" as used herein refer to the application of the composition to the surface of the skin, mucosal cells, keratin and tissue. Examples of keratin are nails and hair.

[0047] As used herein, the term "skin" refers to the thin layer of tissue that naturally covers the human and animal body. Skin is made up of the epidermis and the dermis. As used herein, the stratum corneum is the outermost layer of the epidermis and the papillary dermis is the topmost layer of the dermis.

[0048] As used herein, the term "immediate release" refers to a polymer designed to release at least 75% of the therapeutically active ingredient on a time scale of about 0 to about 24 hours.

[0049] As used herein, the term "sustained release" refers to a polymer that does not release more than 75% of the therapeutically active ingredient until more than about 24 hours after application.

[0050] 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.

[0051] As used herein, the term "sufficient force" refers to the force required to apply the microneedle patch such that the microneedles penetrate the skin to the desired depth.

[0052] As used herein, the term "sensitization" refers to the administration of a therapeutic or stimulating agent to prime the immune system with the intent of obtaining a more robust response with subsequent administration.

[0053] The term "hypersensitivity" as used herein refers to an unwanted reaction produced by the normal immune system, such as allergy or autoimmunity.

[0054] Less than the full scale of the disclosure may be claimed for any reason, by reserving the right to exclude or exclude by proviso any individual member of such group, including any subrange or combination of subranges within such group, which may be claimed according to ranges or similar methods herein. Furthermore, less than the full scale of the disclosure may be claimed for any reason, by reserving the right to exclude any individual substituent, structure, or any member of the group or claimed group herein. 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 of the date of this disclosure to those skilled in the art. This disclosure applies in the event of a conflict between the cited patents, patent applications, and publications and this disclosure.

[0055] 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 is to be construed as an admission that the embodiments described in this disclosure are not entitled to antedate such disclosure by virtue of prior invention.

[0056] Dissolvable Microneedle Patch The present application relates 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 includes a tapered tip portion extending away from the removable substrate. The plurality of microneedles includes 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 immune stimulating molecule, an immune stimulating organism, and an immune stimulating protein.

[0057] In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the at least two different lengths being selected from the group consisting of a length terminating at the epidermis and a length terminating at the reticular dermis or papillary dermis. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles having 1-5 different lengths. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, 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 of equal proportion. In some embodiments, the needles of at least two different lengths may be of different proportion. In an alternative embodiment, 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 different lengths being 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 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 ... 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, 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 Chromium 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 Chron, 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, about 900 microns to about 1000 microns, or values ​​within these ranges.

[0058] 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.

[0059] In some embodiments, the dissolvable microneedle patch is composed of a biodegradable polymer with multiple microneedles of equal volume, including at least two different lengths of microneedles. In some embodiments, the dissolvable microneedle patch includes multiple microneedles, and the volume of each microneedle can remain constant, which is achieved by varying the diameter of each microneedle as needed. In some embodiments, the dissolvable microneedle patch includes multiple microneedles, with each microneedle having an unequal volume. In some embodiments, the dissolvable microneedle patch includes multiple microneedles, and the volume depends on the concentration of the particular immune stimulant used.

[0060] In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles having a tip portion. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles having a tip portion, the tip portion comprising about 5% to about 99% of the total volume of the microneedles. In some embodiments, the microneedle tip portion comprises about 20% to about 90% of the total volume of the microneedles. In some embodiments, the microneedle tip portion comprises about 50% of the total volume of the microneedles. In some embodiments, the microneedle tip portion comprises 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%, about 10% to about 99%, about 10% to about 95%, 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 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 10% to about 15%, 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 about 70%, about 15% to about 60%, about 15% to about 50%, about 15% to about 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%, about 50% to about 99%, 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 60%, 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 85%, about 70% to about 80%, about 70% to about 75%, about 80% to about 99%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to about 99%, about 90% to about 95%, or values ​​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 a range 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 plurality of microneedles comprises a different amount of the therapeutically active ingredient.

[0061] In some embodiments, a method of treating a skin condition comprising applying a dissolvable microneedle patch, wherein the skin condition is selected from the group consisting of warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, Gorlin syndrome, and alopecia areata, vitiligo.

[0062] Certain compounds disclosed herein may have useful immune stimulating activity and may be used in the treatment or prevention of diseases or conditions in which the immune system may play an active role. In some embodiments, successful delivery of immune stimulants results in classical clinical signs of inflammation, such as rashes, tumors, and fever (redness, swelling, and warmth, respectively). Thus, embodiments also relate to pharmaceutical compositions comprising one or more compounds disclosed herein together with a pharma- ceutically acceptable carrier, as well as methods of making and using the compounds and compositions. Certain embodiments relate to methods for stimulating the immune system. Other embodiments relate to methods for treating skin conditions in patients in need of such treatment, comprising administering to said 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 medicaments for the treatment of diseases or conditions ameliorated by the activation of the immune system.

[0063] In some embodiments, the method is 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 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.

[0064] In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, the therapeutically active ingredient being selected from the group consisting of a vaccine, an immunostimulating molecule, an immunostimulating organism, and an immunostimulating 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, the vaccine being 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 immunostimulating molecule, the immunostimulating molecule being imiquimod. In some embodiments, the therapeutically active ingredient is an immunostimulating organism, the immunostimulating organism being Corynebacterium parvum, Cutibacterium acnes, Propionobacterium, and / or Mycobacterium indicus planii (formerly Mycobacterium w). In some embodiments, the therapeutically active ingredient is an immunostimulatory protein, said immunostimulatory protein being selected from the group consisting of Candida antigens, Trichophyton antigens, tuberculin, purified protein derivatives (also), human papillomavirus surface proteins, interferon alpha, interferon beta, and interferon gamma.

[0065] In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, the therapeutically active ingredient being an antigen composition. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, the therapeutically active ingredient being a Candida antigen composition. In some embodiments, the antigen composition is substantially free of glycerol. In some embodiments, the Candida antigen composition is substantially free of glycerol. In some embodiments, the antigen composition is glycerol free. In some embodiments, the Candida antigen composition is glycerol free. In some embodiments, the glycerol free antigen composition is lyophilized. In some embodiments, the glycerin free Candida antigen composition is lyophilized. In some embodiments, the antigen composition comprises less than about 50% glycerol. In some embodiments, the antigen composition comprises less than about 40% glycerol. In some embodiments, the antigen composition comprises less than about 30% glycerol. In some embodiments, the antigen composition comprises less than about 20% glycerol. In some embodiments, the antigen composition comprises less than 15% glycerol. In some embodiments, the antigen composition comprises less than about 10% glycerol. In some embodiments, the antigen composition comprises less than about 5% glycerol. In some embodiments, the antigen composition comprises less than about 1% glycerol.In some embodiments, the antigen composition comprises about 0.1% to about 15% glycerol, about 0.1% to about 14% glycerol, about 0.1% to about 13% glycerol, about 0.1% to about 12% glycerol, about 0.1% to about 11% glycerol, about 0.1% to about 10% glycerol, about 0.1% to about 9% glycerol, about 0.1% to about 8% glycerol, about 0.1% to about 7% glycerol, about 0.1% to about 6% glycerol, about 0.1% to about 5% glycerol, about 0.1% to about 4% glycerol, about 0.1% to about 3% glycerol, about 0.1% to about 2% glycerol, about 0.1% to about 1% glycerol, about 0.1% to about 0.9% glycerol, about 0.1% to about 0.8% glycerol, about 0.1% to about 0.7% glycerol, about 0.1% to about 0.6% glycerol, about 0.1% to about 0.5% glycerol, about 0.1% to about 0.4% glycerol, about 0.1% to about 0.3% glycerol glycerol, about 0.1% to about 0.2% glycerol, about 0.2% to about 15% glycerol, about 0.3% to about 15% glycerol, about 0.4% to about 15% glycerol, about 0.5% to about 15% glycerol, about 0.6% to about 15% glycerol, about 0.7% to about 15% glycerol, about 0.8% to about 15% glycerol, about 0.9% to about 15% glycerol, about 1% to about 15% glycerol, about 2% to about 15% glycerol, about 3% to about 15% glycerol, about 4% to about 15% glycerol, about 5% to about 15% glycerol, about 6% to about 15% glycerol, about 7% to about 15% glycerol, about 8% to about 15% glycerol, about 9% to about 15% glycerol, about 10 ... Including 5% glycerol, about 4% to about 15% glycerol, about 5% to about 15% glycerol, about 6% to about 15% glycerol, about 7% to about 15% glycerol, about 8% to about 15% glycerol, about 9% to about 15% glycerol, about 10% to about 15% glycerol, about 11% to about 15% glycerol, about 12% to about 15% glycerol, about 13% to about 15% glycerol, about 14% to about 15% glycerol, or values ​​within these ranges.In some embodiments, the antigen composition comprises about 0.1% glycerol, about 0.2% glycerol, about 0.3% glycerol, about 0.4% glycerol, about 0.5% glycerol, about 0.6% glycerol, about 0.7% glycerol, about 0.8% glycerol, about 0.9% glycerol, about 1% glycerol, about 2% glycerol, about 3% glycerol, about 4% glycerol, about 5% glycerol, about 6% glycerol, about 7% glycerol, about 8% glycerol, about 9% glycerol, about 10% glycerol, about 20% glycerol, about 30% glycerol, about 40% glycerol, about 50% glycerol, about 60% glycerol, about 70% glycerol, about 80% glycerol, about 90% glycerol, about 100% glycerol, about 11% glycerol, about 12% glycerol, about 13% glycerol, about 14% glycerol, about 15% glycerol, about 16% glycerol, about 17% glycerol, about 18% glycerol, about 19% glycerol, about 20% glycerol, about 21% glycerol, about 22% glycerol, about 23% glycerol, about 24% glycerol, about 25% glycerol, about 26% glycerol, about 27% glycerol, about 28% glycerol, about 29% glycerol, about 30% glycerol, about 31% glycerol, about 32% glycerol, about glycerol, about 8% glycerol, about 9% glycerol, about 10% glycerol, about 11% glycerol, about 12% glycerol, about 13% glycerol, about 14% glycerol, about 15% glycerol, about 20% glycerol, about 25% glycerol, about 30% glycerol, about 35% glycerol, about 40% glycerol, about 45% glycerol, about 50% glycerol, or a range between any two of these values.

[0066] In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, said therapeutically active ingredient being dispersed throughout the polymer. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, said therapeutically active ingredient being uniformly dispersed throughout the microneedles. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, said therapeutically active ingredient being concentrated at the tip of the microneedle. In some embodiments, the plurality of microneedles comprises a microneedle that is essentially free of the therapeutically active ingredient in the half of the microneedle that is closest to the base. In some embodiments, the plurality of microneedles comprises a microneedle that is essentially free of the therapeutically active ingredient in the half of the microneedle that is closest to the base. 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.

[0067] Some embodiments disclosed herein also include pharmaceutical compositions that include, as an active ingredient, one or more of the compounds disclosed herein in combination with one or more pharma- ceutically acceptable carriers (excipients).

[0068] In some embodiments, the excipient is lactose, sucrose, glucose, mannitol, sorbitol, trehalose, fructose, galactose, dextrose, xylitol, maltitol, raffinose, dextran, maltodextrin, cyclodextrin, collagen, glycine, histidine, calcium carbonate, magnesium stearate, serum albumin (human and / or animal origin), gelatin, chitosan, deoxyribonucleic acid (DNA), hyaluronic acid, polyvinylpyrrolidone, polyvinyl alcohol, polylactic acid (PLA), polyglycolic acid (PGA), polyactive coglycolic acid (PLGA), polyethylene glycol (PEG, PEG300, PEG400, PEG600, PEG3350, PEG4000), cellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, acacia, Lecithin, Polysorbate 20, Polysorbate 80, Pluronic F-68, Sorbitan Trioleate (span85), EDTA, Hydroxypropylcellulose, Sodium Chloride, Sodium Phosphate, Ammonium Acetate, Potassium Phosphate, Sodium Citrate, Sodium Hydroxide, Sodium Carbonate, Tris Base-65, Tris Acetate, Tris HCl-65, Citrate Buffer, Talc, Silica, Fat, Methylparaben, Propylparaben, Selenium, Vitamins (A, E, C, Retinyl Palmitate, and Selenium), Amino Acids (Methionine, Cysteine, Arginine), Citric Acid, Sodium Citrate, Benzyl Alcohol, Chlorobutanol, Cresols, Phenol, Thimerosal, Acetone, Sodium Bisulfate, Ascorbyl Palmitate, Ascorbate, Castor Oil, Cottonseed Oil, Alum, Aluminum Hydroxide, Aluminum Phosphate, Calcium Hydroxyphosphate, Paraffin Oil, Squalene, Quiloxacin ... A, IL-1, IL-2, IL-12, Freund's complete adjuvant, Freund's incomplete adjuvant, killed Bordetella pertussis, Mycobacterium bovis, and toxoid. In some embodiments, the excipient may be a polymer.In some embodiments, the excipient may be a biodegradable polymer. In some embodiments, the excipient is a polymer, and the polymer is maltodextrin. In some embodiments, there is one excipient. In some embodiments, there are two excipients, and in some embodiments, there are three or more excipients. In some embodiments, the two excipients are maltodextrin and lactose, maltodextrin and sodium thiosulfate, maltodextrin and trehalose, maltodextrin and sodium citrate, maltodextrin and sorbitol, maltodextrin and arginine, maltodextrin and arginine, arginine and lactose, arginine and sodium thiosulfate, arginine and trehalose, arginine and sodium citrate, arginine and sorbitol, sorbitol and lactose, sorbitol and sodium thiosulfate, sorbitol and trehalose, sorbitol and sodium citrate, sodium citrate and lactose, sodium citrate and sodium thiosulfate, sodium citrate and trehalose, trehalose and lactose, trehalose and sodium thiosulfate, or sodium thiosulfate and lactose.

[0069] The active compound is effective over a wide range of dosages 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 being 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.

[0070] The amount of compound or composition administered to a patient will vary depending on what is administered, the purpose of administration, such as prevention or treatment, the condition of the patient, the method of administration, etc. 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 disease is selected from warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, and successful treatment of these diseases results in a one-point improvement in symptoms on any ordinal or interval rating scale, such as Physician Global Assessment or Investigator Global Assessment. In some embodiments, the disease is selected from warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucosa, and epidermodysplasia verruciformis, and successful treatment of these diseases results in about 100% disappearance of the skin lesion at the site where the patch is administered, as assessed by clinical, histopathological, or dermatoscopic evaluation, as well as by optical coherence tomography or confocal microscopy. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and epidermodysplasia verruciformis, and successful treatment of these conditions results in about 50% disappearance of the skin lesion at the site where the patch is administered, as assessed by clinical, histopathological, or dermatoscopic evaluation, as well as by optical coherence tomography or confocal microscopy.In some embodiments, successful treatment of warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, or epidermodysplasia verruciformis with a dissolving microneedle patch may include a reduction in the appearance of skin lesions in 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 Reduce by 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 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 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or by a value within these ranges. Specific examples may 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 by clinical, histopathological, or dermatoscopic evaluation, as well as by optical coherence tomography or confocal microscopy.

[0071] In some embodiments, methods of treating skin disorders, including successfully treating warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, with a dissolvable microneedle patch include reducing the width, length, or height of the skin lesion 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%, about 50% to about 65%, about 50% to about Reduce by 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 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 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or by a value within these ranges. Specific examples may include reducing 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 any two of these values, as measured by clinical, histopathological, or dermatoscopic evaluation, as well as optical coherence tomography or confocal microscopy evaluation.

[0072] In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in a one-point improvement in 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% hair growth recovery in the area where the patch is administered. In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in at least about 50% increase in hair growth in the area 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 may result in the following results at the site where the patch was administered: 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%, Hair growth is increased by 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 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 values ​​within these ranges. Specific examples include increasing hair growth, as defined by the number of hair follicles with actively growing hair shafts as seen by clinical, trichoscopic, or histopathological evaluation, 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.

[0073] In some embodiments, successful treatment of the skin condition alopecia areata with a dissolvable microneedle patch may result in an Alopecia Severity Assessment Tool (SALT) score at the site where the patch was 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%, 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 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 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or an improvement within these ranges. Specific examples can include improving Alopecia Severity Assessment Tool (SALT) score 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.

[0074] In some embodiments, each dissolvable microneedle patch contains a standardized amount of a therapeutically active ingredient.

[0075] 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 from about 1% to about 90%, from about 1% to about 85%, from about 1% to about 80%, from about 1% to about 75%, from about 1% to about 70%, from about 1% to about 65%, from about 1% to about 60%, from about 1% to about 55%, from about 1% to about 50%, from about 1% to about 45%, from about 1% to about 40%, from about 1% to about 35%, from about 1% to about 30%, from 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 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 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 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 45%, about 15% to about 40%, about 15% to about 35%, about 15% to about 30%, 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%, about 20% to about 50%, about 20% to about 45%, about 20% to about 40%, about 20% to about 35%, about 20% to about 30%, about 20% to about 25%, 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 65%, 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%, about 30% to about 90%, about 30% to about 85%, about 30% to about 80%, about 30% to about 75%, about 30% to About 70%, about 30% to about 65%, about 30% to about 60%, about 30% to about 55%, about 30% to about 50%, about 30% to about 45%, about 30% to about 40%, about 30% to about 35%, about 35% to about 90%, about 35% to about 85%, about 35% to about 80%, about 35% to about 75%, about 35% to about 70%, About 35% to about 65%, about 35% to about 60%, about 35% to about 60%, about 35% to about 55%, about 35% to about 50%, about 35% to about 45%, about 35% to about 40%, about 40% to about 90%, about 40% to about 85%, about 40% to about 80%, about 40% to about 75%, about 40% to about 70%, about 40% to About 65%, about 40% to about 60%, about 40% to about 55%, about 40% to about 50%, about 40% to about 45%, about 45% to about 90%, about 45% to about 85%, about 45% to about 80%, about 45% to about 75%, about 45% to about 70%, about 45% to about 65%, about 45% to about 60%, about 45% to about 55%, About 45% to about 50%, 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 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 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 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 90%, about 80% to about 85%, about 85% to about 90%, or an amount within these ranges. Specific examples may 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%, and about 1%. All of the above represent weight percent of the pharmaceutical composition. In some embodiments, the pharmaceutical composition is suitable for transdermal administration.

[0076] In some embodiments, the therapeutically active ingredient is in a therapeutically effective amount. In some embodiments, the therapeutically effective amount is 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 300 mg, about 1 mg to about 200 mg, about 1 mg to about 100 mg, about 10 mg to about 1000 mg, about 50 mg ~1000mg, 100mg~1000mg, 200mg~1000mg, 300mg~1000mg, 400mg~1000mg, 500mg~100 The dose may be 0 mg, about 10 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 value between the ranges disclosed above.

[0077] In some embodiments, the therapeutically effective amount may vary depending on, for example, the particular application for which the treatment is performed, 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 microneedle may vary depending on many factors, including the dosage, chemical properties (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 potency of the selected compound, the composition of excipients, and the location of administration. Effective amounts can be estimated from dose-response curves obtained from in vitro or animal model test systems.

[0078] In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising a biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising poly(lactic-co-glycolic acid) (PLGA). In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising a polymer selected from PLGA (poly(lactic-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, the microneedles comprising a single biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising two biodegradable polymers. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising a plurality of biodegradable polymers.

[0079] In some embodiments, the polymer may act as an excipient that stabilizes the therapeutically active ingredient. In some embodiments, the polymer may form the structure of the microneedle. In some embodiments, the polymer may act both as an excipient that stabilizes the therapeutically active ingredient and as a polymer that forms the structure of the microneedle.

[0080] In some embodiments, the biodegradable polymer can provide 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 includes carboxymethylcellulose, chondroitin sulfate, dextran, dextrin, polyvinylpyrrolidone, maltose, trelahose, sucrose, galactose, amylopectin, polyvinyl alcohol, and / or polyvinylpyrrolidone methacrylate. In further embodiments, the immediate release biodegradable polymer releases the therapeutically active ingredient within about 0 hours 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 on a time scale of about 0 hours to about 24 hours. In some embodiments, the immediate release biodegradable polymer releases about 100% of the therapeutically active ingredient on a time scale of about 0 hours to about 24 hours. In some embodiments, the immediate release biodegradable polymer releases 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 100%, about 90% to about 95%, about 95% to about 100%, or values ​​within these ranges of the therapeutically active ingredient on a time scale of about 0 hours to about 24 hours. Specific examples include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, about 100%, or ranges between any two of these values.

[0081] 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. 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 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 7 hours, about 1 hour to about 6 hours, about 1 hour to about 5 hours, about 1 hour ~ 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 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, about 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 0 minutes to about 4 minutes, about 0 minutes to about 3 minutes, about 0 minutes to about 5 minutes ...5 minutes, about 0 minutes to about 4 minutes, about 0 minutes to about 3 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 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 5 minutes to about 10 minutes, about 10 minutes to about 60 minutes, about 10 minutes to about 50 minutes, about 10 minutes to about 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 The therapeutically active ingredient is released within about 15 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, about 30 minutes to about 35 minutes, about 45 minutes to about 60 minutes, about 45 minutes to about 50 minutes, or a value within these ranges. Specific examples may 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.

[0082] In some embodiments, the biodegradable polymer can provide sustained release of the therapeutic active ingredient after insertion of the microneedle patch into the skin. In further embodiments, the sustained release biodegradable polymer is water soluble and includes PLGA (poly(lactic-co-glycolic acid)), polyglycolic acid, fibroin, PLA (polylactic acid), PVP (polyvinylpyrrolidone) or PCL (polycaprolactone). In further embodiments, the sustained release biodegradable polymer releases the therapeutic 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 therapeutic 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 provides a sustained release biodegradable polymer that is capable of delivering a therapeutically effective amount of glycerol to the tissue of the subject by 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% for a period of more than about 24 hours. , about 80% to about 85%, about 85% to about 100%, about 85% to about 99%, about 85% to about 95%, about 85% to about 90%, about 90% to about 100%, about 90% to about 99%, about 90% to about 95%, about 95% to about 100%, about 95% to about 99%, about 99% to about 100%, or values ​​within these ranges of the therapeutically active ingredient. Specific examples may include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, and about 100%.

[0083] In some embodiments, the sustained release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 to about 30 days. In some embodiments, the sustained release biodegradable polymer releases the therapeutically active ingredient over a period of about 2 to about 21 days. In some embodiments, the sustained release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 to about 30 days, about 1 to about 28 days, about 1 to about 26 days, about 1 to about 24 days, about 1 to about 22 days, about 1 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 days to about 22 days, about 2 days to about 21 days, about 2 days to about 14 days, about 2 days to about 7 days, about 2 days to about 6 days, about 2 days to about 5 days, about 2 days to about 4 days, about 2 days to about 3 days, about 3 days to about 30 days, about 3 days to about 28 days, about 3 days to about 26 days, about 3 days to about 24 days, about 3 days to about 22 days, about 3 days to about 21 days, about 3 days to about 14 days, about 3 days to about 7 days, about 3 days to about 6 days, about 3 days to about 5 days, about 3 days to about 4 days, about 4 days to about 30 days, about 4 days to about 28 days, about 4 days to about 26 days, about 4 days to about 24 days, about 4 days to about 22 days, about 4 days to about 21 days, about 4 days to about 14 days, about 4 days to about 7 days, about 4 days to about 6 days, about 4 days to about 5 days, about 5 days to about 30 days, about 5 days to about 28 days, about 5 days to about 26 days, about 5 days to about 24 days, about 5 days to about 22 days, about 5 days to about 21 days, about 5 days to about 14 days, about 5 days to about 7 days, about 5 days to about 6 days, about 7 days to about 30 days, about 7 days to about 28 days, about 7 days to about 2 The therapeutic activity is released for 6 days, 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 values ​​within these ranges. Specific examples may 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.

[0084] In some embodiments, the biodegradable polymer can provide 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 microneedle and a sustained release biodegradable polymer at the tip portion of the microneedle ...

[0085] In some embodiments, the dissolvable microneedle patch is applied to 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.

[0086] In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, said 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, the microneedle patch having 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 1 to about 125 microneedles per square centimeter, about 1 to about 100 microneedles per square centimeter, about 1 to about 90 microneedles per square centimeter, about 1 to about 80 microneedles per square centimeter, about 1 to about 70 microneedles per square centimeter, about 1 to about 60 microneedles per square centimeter, about 1 to about 50 microneedles per square centimeter, about 1 to about 40 microneedles per square centimeter, about 1 to about 30 microneedles per square centimeter, about 1 to about 25 microneedles per square centimeter. needles, about 1 to about 20 microneedles per square centimeter, 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 1 to about 2 ... 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 15 ... about 10 to about 150 microneedles per square centimeter, about 10 to about 125 microneedles per square centimeter, about 10 to about 100 microneedles per square centimeter, about 10 to about 90 microneedles per square centimeter, about 10 to about 80 microneedles per square centimeter, about 10 to about 70 microneedles per square centimeter, about 10 to about 60 microneedles per square centimeter, about 10 to about 50 microneedles per square centimeter, about 10 to about 60 microneedles per square centimeter, about 10 to about 70 microneedles per square centimeter, about 10 to about 80 microneedles per square centimeter, about 10 to about 90 microneedles per square centimeter, about 10 to about 10 ... about 40 microneedles, about 10 to about 30 microneedles per square centimeter, about 10 to about 25 microneedles per square centimeter, about 10 to about 20 microneedles per square centimeter, 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 microneedles, 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 60 microneedles per square centimeter, about 25 to about 50 microneedles per square centimeter, about 25 to about 40 microneedles per square centimeter, about 25 to about 30 microneedles per square centimeter,about 50 to about 200 microneedles per square centimeter, about 50 to about 175 microneedles per square centimeter, about 50 to about 150 microneedles per square centimeter, about 50 to about 125 microneedles per square centimeter, about 50 to about 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 including about 75 to about 100 microneedles per square centimeter, about 75 to about 90 microneedles per square centimeter, about 75 to about 80 microneedles per square centimeter, 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, about 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, said 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 125 microneedles per square centimeter, at least about 100 microneedles per square centimeter, at least about 90 microneedles per square centimeter, at least about 80 microneedles per square centimeter, at least about 70 microneedles per square centimeter, at least about 60 microneedles per square centimeter, at least about 50 microneedles per square centimeter, at least about 40 microneedles per square centimeter, at least about 30 microneedles per square centimeter, At least about 25 microneedles per square centimeter, at least about 20 microneedles per square centimeter, at least about 15 microneedles per square centimeter, at least about 10 microneedles per square centimeter, at least about 5 microneedles per square centimeter, at least about 4 microneedles per square centimeter, at least about 3 microneedles per square centimeter, at least about 2 microneedles per square centimeter, at least about 1 microneedle per square centimeter, or a range between any two of these values.

[0087] 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 n sides, where n ranges from about 0 sides to about 1000 sides. In some embodiments, the dissolvable microneedle patch may have 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, about 10 sides to about 60 sides, about 10 sides ~50 sides, ~10 sides~40 sides, ~10 sides~30 sides, ~10 sides~20 sides, ~20 sides~1000 sides, ~20 sides~900 sides, ~20 sides~800 sides, ~20 sides~700 sides, ~20 sides~600 sides, ~20 sides~500 sides, ~20 sides~400 sides, ~20 sides~300 sides, ~20 sides~200 sides, ~20 sides~100 sides, ~20 sides~90 sides, ~20 sides~80 sides, ~20 sides~70 sides, ~20 sides~60 sides, ~20 sides~50 sides, ~20 sides~40 sides, ~20 sides~30 sides , about 30 sides to about 1000 sides, about 30 sides to about 900 sides, about 30 sides to about 800 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 sides, about 50 sides to about 900 sides, about 50 sides to about 800 sides, about 50 sides to about 700 sides,About 50 sides to about 600 sides, about 50 sides to about 500 sides, about 50 sides to about 400 sides, about 50 sides to about 300 sides, about 50 sides to about 200 sides, about 50 sides to about 100 sides, about 50 sides to about 90 sides, about 50 sides to about 80 sides, about 50 sides to about 70 sides, about 50 sides to about 60 sides, about 75 sides to about 1000 sides, about 75 sides to about 900 sides, about 75 sides to about 800 sides, about 7 5 sides to about 700 sides, about 75 sides to about 600 sides, about 75 sides to about 500 sides, about 75 sides to about 400 sides, about 75 sides to about 300 sides, about 75 sides to about 200 sides, about 75 sides to about 100 sides, about 75 sides to about 90 sides, about 75 sides to about 80 sides, about 100 sides to about 1000 sides, about 100 sides to about 900 sides, about 100 sides to about 800 sides, about 100 sides to about 700 sides , about 100 sides to about 600 sides, about 100 sides to about 500 sides, about 100 sides to about 400 sides, about 100 sides to about 300 sides, about 100 sides to about 200 sides, about 250 sides to about 1000 sides, about 250 sides to about 900 sides, about 250 sides to about 800 sides, about 250 sides to about 700 sides, about 250 sides to about 600 sides, about 250 sides to about 500 sides, about 250 sides to about 40 0 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 700 sides, about 500 sides to about 600 sides, about 750 sides to about 1000 sides, about 750 sides to about 900 sides, about 750 sides to about 800 sides, about 900 sides to about 1000 sides, or values ​​within these ranges. Specific examples may include dissolvable microneedle patches having 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 these two values.

[0088] In further embodiments, the dissolvable microneedle patch can have sides of equal length. In further embodiments, the dissolvable microneedle patch can 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 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, about 0.1 square centimeters to about 10 ... Centimeters 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 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, about 0.1 square centimeters to about 0.6 square centimeters, about 0.1 square centimeters to about 0.5 square centimeters, about 0.1 square centimeters to about 0.4 square centimeters,About 0.1 square centimeters to about 0.3 square centimeters, about 0.1 square centimeters to about 0.2 square centimeters, about 0.5 square centimeters to about 1000 square centimeters, about 0.5 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 500 square centimeters, about 0.5 square centimeters to about 400 square centimeters 0.5 square centimeters to about 300 square centimeters, 0.5 square centimeters to about 200 square centimeters, 0.5 square centimeters to about 100 square centimeters, 0.5 square centimeters to about 90 square centimeters, 0.5 square centimeters to about 80 square centimeters, 0.5 square centimeters to about 70 square centimeters, 0.5 square centimeters to about 60 square centimeters, 0.5 square centimeters to about 50 square centimeters, 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 4 square centimeters, about 0.5 square centimeters to about 3 square centimeters, about 0.5 square centimeters to about 2 square centimeters, about 0.5 square centimeters to about 1 square centimeter, about 0.5 square centimeters to about 0.9 square centimeters 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 about 100 square centimeters, about 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 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, about 10 square centimeters to about 600 square centimeters, about 10 square centimeters to about 500 square centimeters, about 10 square centimeters to about 400 square centimeters, about 10 square centimeters to about 300 square centimeters, about 10 square centimeters to about 200 square centimeters, about 10 square centimeters to about 100 square centimeters, about 10 square centimeters to about 90 square centimeters, about 10 square centimeters to about 80 square centimeters 1000 square centimeters, about 1000 square centimeters to about 900 square centimeters, about 1000 square centimeters to about 800 square centimeters, about 1000 square centimeters to about 900 square centimeters, about 1000 square centimeters to about 10 ...About 50 square centimeters to about 700 square centimeters, about 50 square centimeters to about 600 square centimeters, about 50 square centimeters to about 500 square centimeters, about 50 square centimeters to about 400 square centimeters, 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 75cm2~800cm2, 75cm2~700cm2, 75cm2~600cm2, 75cm2~500cm2, 75cm2~400cm2, 75cm2~300cm2, 75cm2~200cm2, 75cm2~100cm2, 100cm2~1000cm2, 100cm2~2000cm2 100 to 900 square centimeters, 100 to 800 square centimeters, 100 to 700 square centimeters, 100 to 600 square centimeters, 100 to 500 square centimeters, 100 to 400 square centimeters, 100 to 300 square centimeters, 100 to 200 square centimeters, 250 to 1000 square centimeters, 250 Square centimeters to about 900 square centimeters, about 250 square centimeters to about 800 square centimeters, about 250 square centimeters to about 700 square centimeters, about 250 square centimeters to about 600 square centimeters, about 250 square centimeters to about 500 square centimeters, about 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,The size may be 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 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 30 square centimeters, about 40 square centimeters, about 50 square centimeters, about 60 square centimeters, about 70 square centimeters, about 80 square centimeters, about 90 square centimeters, about 10 ... 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 0.7 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.

[0089] 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, the microneedle layer being placed directly on the skin. In some embodiments, the dissolvable microneedle patch comprises a backing layer, the backing layer being comprised of adhesive medical tape. In some embodiments, the dissolvable microneedle patch comprises a backing layer, the backing layer comprising a therapeutically active ingredient.

[0090] In some embodiments, the dissolvable microneedle patch includes a backing layer, the backing layer being a removable substrate. In some embodiments, the dissolvable microneedle patch includes a removable substrate that includes an adhesive medical tape. In some embodiments, the backing layer includes a fast-dissolving polymer. In some embodiments, the removable substrate includes a therapeutically active ingredient dispersed in the polymer. In some embodiments, the dissolvable microneedle patch includes a plurality of microneedles attached to a removable substrate and including a tapered tip portion that extends away from the removable substrate. In some embodiments, the dissolvable microneedle patch includes a removable substrate that releases at least about 90% of the microneedles from the adhesive surface within a period of about 20 minutes after application to the skin. In some embodiments, the dissolvable microneedle patch includes a removable substrate that releases at least about 90% of the microneedles from the adhesive surface within a period of about 5 minutes after application to the skin.In some embodiments, in the dissolvable microneedle patch, 90% of the microneedles are in contact with the microneedle within about 0 minutes to about 20 minutes, about 0 minutes to about 15 minutes, about 0 minutes to about 10 minutes, about 0 minutes to about 9 minutes, about 0 minutes to about 8 minutes, about 0 minutes to about 7 minutes, about 0 minutes to about 6 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 1 minute to about 20 minutes, about 1 minute to about 15 minutes, about 1 minute to about 10 minutes, about 1 minute to about 9 minutes, about 1 minute to about 8 minutes, about 1 minute to about 7 minutes, about 1 minute to about 6 minutes, about 1 minute to about 5 minutes, about 1 minute to about 4 minutes, about 1 minute to about 3 minutes, about 1 minute ... 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 Approximately 6 minutes, approximately 2 minutes to approximately 5 minutes, approximately 2 minutes to approximately 4 minutes, approximately 2 minutes to approximately 3 minutes, approximately 5 minutes to approximately 20 minutes, approximately 5 minutes to approximately 15 minutes, approximately 5 minutes to approximately 10 minutes, approximately 5 minutes 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 seconds, approximately 0 seconds to approximately 9 seconds, approximately 0 seconds to approximately 8 seconds , about 0 seconds to about 7 seconds, about 0 seconds to about 6 seconds, about 0 seconds to about 5 seconds, about 0 seconds to about 4 seconds, about 0 seconds to about 3 seconds, about 0 seconds to about 2 seconds, about 0 seconds to about 1 second, about 1 seconds 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 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 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 about 45 seconds, about 2 seconds to about 30 seconds, about 2 seconds to about 15 seconds, about 2 seconds to about 10 seconds, about 2 seconds to about 9 seconds, about 2 seconds to about 8 seconds, about 2 seconds to about 7 seconds, about It is released from the adhesive surface within a period of 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 within a value within these ranges.In specific examples, 90% of the microneedles are released from the adhesive surface of the 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 within a range between these two values.

[0091] In some embodiments, the backing layer covers the base of the tip portion such that each microneedle is isolated from the other microneedles on the patch and forms an individual entity when the substrate is removed upon application of the patch to the skin.

[0092] In some embodiments, the dissolvable microneedle patch comprises (i) placing on a superficial area of ​​the skin of a patient in need of treatment or performing a pre-treatment test to evaluate hypersensitivity reactions, general tolerability, or other adverse events; (ii) applying a sufficient force to the patch composition to allow the microneedles to penetrate the epidermis and enter 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 backing from the patch composition, wherein the step (ii) is performed by applying pressure with a finger, and a pressure ranging from about 0 N to about 1,000 N is sufficient. In a preferred embodiment of the present disclosure, the applied pressure is about 10 N. In an alternative embodiment of the present disclosure, the step (ii) is performed by impact insertion using an applicator device, and the pressure ranging from about 0 N to about 1,000 N is sufficient. In a preferred embodiment of the present disclosure, 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 500 N, Approximately 100N, approximately 0N to 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 30 N, about 0N to about 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, Approximately 0N to approximately 3N, approximately 0N to approximately 2N, approximately 0N to approximately 1N, approximately 0N to approximately 0.9N, approximately 0N to approximately 0.8N, approximately 0N to approximately 0.7N, approximately 0N to approximately 0.6N, approximately 0N ~0.5N, 0N~0.4N, 0N~0.3N, 0N~0.2N, 0N~0.1N, 0.1N~1000N, 0.1N~9 00N, about 0.1N to about 800N, about 0.1N to about 700N, about 0.1N to about 600N, about 0.1N to about 500N, about 0.1N to about 400N, about 0.1 N ~ about 300N, about 0.1N - about 200N, about 0.1N - about 100N, about 0.1N - about 90N, about 0.1N - about 80N, about 0.1N - about 70N, about 0.1N to approximately 60N, approximately 0.1N to approximately 50N, approximately 0.1N to approximately 40N, approximately 0.1N to approximately 30N, approximately 0.1N to approximately 20N, approximately 0.1N to approximately 10N, 9N, approximately 0.1N to approximately 8N, approximately 0.1N to approximately 7N, approximately 0.1N to approximately 6N, approximately 0.1N to approximately 5N, approximately 0.1N to approximately 4N, approximately 0.1N to approximately 3N, approximately 0.1N to approximately 2N, approximately 0.1N to approximately 1N, approximately 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, approximately 0.1N to approximately 0.3N, approximately 0.1N to approximately 0.2N, about 1N to about 1000N, about 1N to about 900N, about 1N to about 800N, about 1N to about 700N, about 1N to about 600N, about 1N to about 500N, about 1N to about 400N, about 1N to about 300N, about 1N to about 200N, about 1N to about 100N, Approximately 1N to approximately 90N, approximately 1N to approximately 80N, approximately 1N to approximately 70N, approximately 1N to approximately 60N, approximately 1N to approximately 50N, approximately 1N to approximately 40N, approximately 1N to approximately 30N, approximately 1N to approximately 20N, approximately 1N to approximately 10N, approximately 1N to approximately 9N, approximately 1N to approximately 8N, approximately 1N to approximately 7N , about 1N to about 6N, about 1N to about 5N, about 1N to about 4N, about 1N to about 3N, about 1N to about 2N, about 10N to about 1000N, about 10N to about 900N, about 10N to about 800N, about 10N to about 700N, about 10N to about 600N, about 10N to about 5 00N, approximately 10N to approximately 400N, approximately 10N to approximately 300N, approximately 10N to approximately 200N, approximately 10N to approximately 100N, approximately 10N to approximately 90N, approximately 10N to approximately 80N, approximately 10N to approximately 70N, approximately 10N to approximately 60N, approximately 10N to approximately 50N, approximately 10N to approximately 4 0N, 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, 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, 100N to about 400N, about 100N to about 300N, about 100N to about 200N, about 200N to about 1000N, about 200N 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 values ​​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 0.9N, about 1N, about 2N, about 3N, about 4N, about 5N, about 6N, about 7N, about 8N, about 9N, about 10N, about 15N, about 20N, about 30N, about 40N, about 50N, about 60N, about 70N, about 80N, about 90N, about 100N, about 200N, about 300N, about 400N, about 500N, about 600N, about 700N, about 800N, about 900N, or a range between two of these values.

[0093] How to Treat a Skin Condition An embodiment of the present application relates 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 enable the microneedles to penetrate to a location selected from the group consisting of the epidermis, the dermis and the papillary dermis, removing an adhesive backing from the patch composition, and leaving the plurality of microneedles behind.

[0094] In some embodiments, the 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 1-5 different lengths. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, at least two different lengths which 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 of equal proportion. In some embodiments, the needles of at least two different lengths may be of different proportion. In an alternative embodiment, 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 different lengths being 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 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 ... 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, 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 Chromium 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 Chron, 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, about 900 microns to about 1000 microns, or values ​​within these ranges.

[0095] In some embodiments, a method of treating a skin condition comprises applying a dissolvable microneedle patch comprising a plurality of microneedles, the microneedles being 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 a tapered tip portion comprising a therapeutically active ingredient dispersed in a matrix or suspension of a biodegradable polymer.

[0096] In some embodiments, the method of treating a skin condition comprises applying a dissolvable microneedle patch in which a plurality of microneedles, including at least two different lengths, are composed of equal volumes of biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, and the volume of each microneedle can remain constant, which is 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, and the volume depends on the concentration of the particular immune stimulant used.

[0097] In some embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch comprising 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%, about 10% to about 99%, about 10% to about 95%, 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 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 10% to about 15%, 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 about 70%, about 15% to about 60%, about 15% to about 50%, about 15% to about 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%, about 50% to about 99%, 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 60%, 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 85%, about 70% to about 80%, about 70% to about 75%, about 80% to about 99%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to about 99%, about 90% to about 95%, or values ​​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 a range 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 plurality of microneedles comprises a different amount of the therapeutically active ingredient.

[0098] In some embodiments, a method of treating a skin condition comprising applying a dissolvable microneedle patch, wherein the skin condition is warts, genital condyloma, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, and alopecia areata, vitiligo.

[0099] Certain compounds disclosed herein may have useful immune stimulating activity and may be used in the treatment or prevention of diseases or conditions in which the immune system may play an active role. In some embodiments, successful delivery of immune stimulants results in classical clinical signs of inflammation, such as rashes, tumors, and fever (redness, swelling, and warmth, respectively). Thus, embodiments also relate to pharmaceutical compositions comprising one or more compounds disclosed herein together with a pharma- ceutically acceptable carrier, as well as methods of making and using the compounds and compositions. Certain embodiments relate to methods for stimulating the immune system. Other embodiments relate to methods for treating skin conditions in patients in need of such treatment, comprising administering to said 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 medicaments for the treatment of diseases or conditions ameliorated by the activation of the immune system.

[0100] In some embodiments, the method is 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 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.

[0101] In some embodiments, a method of treating a skin condition comprising a plurality of microneedles containing a therapeutically active ingredient, the therapeutically active ingredient being selected from the group consisting of a vaccine, an immunostimulating molecule, an immunostimulating organism, and an immunostimulating protein. In some embodiments, a dissolvable microneedle patch delivers a therapeutically active ingredient to stimulate a local immune response. In some embodiments, the therapeutically active ingredient is a vaccine, the vaccine being 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 immunostimulating molecule, the immunostimulating molecule being imiquimod. In some embodiments, the therapeutically active ingredient is an immunostimulating organism, the immunostimulating organism being Corynebacterium parvum, Cutibacterium acnes, Propionobacterium, and / or Mycobacterium indicus planii (formerly Mycobacterium w). In some embodiments, the therapeutically active ingredient is an immunostimulatory protein, said immunostimulatory protein being selected from the group consisting of Candida antigens, Trichophyton antigens, tuberculin, purified protein derivatives (also), human papillomavirus surface proteins, interferon alpha, interferon beta, and interferon gamma.

[0102] In some embodiments, in a method of treating a skin condition comprising applying a plurality of microneedles comprising a therapeutically active ingredient, the therapeutically active ingredient is an antigen composition. In some embodiments, in a method of treating a skin condition comprising applying a plurality of microneedles comprising a therapeutically active ingredient, the therapeutically active ingredient is a Candida antigen composition. In some embodiments, the antigen composition is substantially free of glycerol. In some embodiments, the Candida antigen composition is substantially free of glycerol. In some embodiments, the antigen composition is glycerol-free. In some embodiments, the Candida antigen composition is glycerol-free. In some embodiments, the glycerol-free antigen composition is lyophilized. In some embodiments, the glycerin-free Candida antigen composition is lyophilized. In some embodiments, the antigen composition comprises less than about 50% glycerol. In some embodiments, the antigen composition comprises less than about 40% glycerol. In some embodiments, the antigen composition comprises less than about 30% glycerol. In some embodiments, the antigen composition comprises less than about 20% glycerol. In some embodiments, the antigen composition comprises less than 15% glycerol. In some embodiments, the antigen composition comprises less than about 10% glycerol. In some embodiments, the antigen composition comprises less than about 5% glycerol, hi some embodiments, the antigen composition comprises less than about 1% glycerol.In some embodiments, the antigen composition comprises about 0.1% to about 15% glycerol, about 0.1% to about 14% glycerol, about 0.1% to about 13% glycerol, about 0.1% to about 12% glycerol, about 0.1% to about 11% glycerol, about 0.1% to about 10% glycerol, about 0.1% to about 9% glycerol, about 0.1% to about 8% glycerol, about 0.1% to about 7% glycerol, about 0.1% to about 6% glycerol, about 0.1% to about 5% glycerol, about 0.1% to about 4% glycerol, about 0.1% to about 3% glycerol, about 0.1% to about 2% glycerol, about 0.1% to about 1% glycerol, about 0.1% to about 0.9% glycerol, about 0.1% to about 0.8% glycerol, about 0.1% to about 0.7% glycerol, about 0.1% to about 0.6% glycerol, about 0.1% to about 0.5% glycerol, about 0.1% to about 0.4% glycerol, about 0.1% to about 0.3% glycerol glycerol, about 0.1% to about 0.2% glycerol, about 0.2% to about 15% glycerol, about 0.3% to about 15% glycerol, about 0.4% to about 15% glycerol, about 0.5% to about 15% glycerol, about 0.6% to about 15% glycerol, about 0.7% to about 15% glycerol, about 0.8% to about 15% glycerol, about 0.9% to about 15% glycerol, about 1% to about 15% glycerol, about 2% to about 15% glycerol, about 3% to about 15% glycerol, about 4% to about 15% glycerol, about 5% to about 15% glycerol, about 6% to about 15% glycerol, about 7% to about 15% glycerol, about 8% to about 15% glycerol, about 9% to about 15% glycerol, about 10 ... Including 5% glycerol, about 4% to about 15% glycerol, about 5% to about 15% glycerol, about 6% to about 15% glycerol, about 7% to about 15% glycerol, about 8% to about 15% glycerol, about 9% to about 15% glycerol, about 10% to about 15% glycerol, about 11% to about 15% glycerol, about 12% to about 15% glycerol, about 13% to about 15% glycerol, about 14% to about 15% glycerol, or values ​​within these ranges.In some embodiments, the antigen composition comprises about 0.1% glycerol, about 0.2% glycerol, about 0.3% glycerol, about 0.4% glycerol, about 0.5% glycerol, about 0.6% glycerol, about 0.7% glycerol, about 0.8% glycerol, about 0.9% glycerol, about 1% glycerol, about 2% glycerol, about 3% glycerol, about 4% glycerol, about 5% glycerol, about 6% glycerol, about 7% glycerol, about 8% glycerol, about 9% glycerol, about 10% glycerol, about 20% glycerol, about 30% glycerol, about 40% glycerol, about 50% glycerol, about 60% glycerol, about 70% glycerol, about 80% glycerol, about 90% glycerol, about 100% glycerol, about 11% glycerol, about 12% glycerol, about 13% glycerol, about 14% glycerol, about 15% glycerol, about 16% glycerol, about 17% glycerol, about 18% glycerol, about 19% glycerol, about 20% glycerol, about 21% glycerol, about 22% glycerol, about 23% glycerol, about 24% glycerol, about 25% glycerol, about 26% glycerol, about 27% glycerol, about 28% glycerol, about 29% glycerol, about 30% glycerol, about 31% glycerol, about 32% glycerol, about glycerol, about 8% glycerol, about 9% glycerol, about 10% glycerol, about 11% glycerol, about 12% glycerol, about 13% glycerol, about 14% glycerol, about 15% glycerol, about 20% glycerol, about 25% glycerol, about 30% glycerol, about 35% glycerol, about 40% glycerol, about 45% glycerol, about 50% glycerol, or a range between any two of these values.

[0103] In some embodiments, a method of treating a skin condition comprising a plurality of microneedles comprising a therapeutically active ingredient, the therapeutically active ingredient being dispersed throughout a polymer. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, the therapeutically active ingredient being dispersed uniformly throughout the microneedles. In some embodiments, the plurality of microneedles comprises a therapeutically active ingredient, the therapeutically active ingredient being concentrated at the tip of the microneedle. In some embodiments, the plurality of microneedles comprises a microneedle that is essentially free of the therapeutically active ingredient in the half of the microneedle closest to the base. In some embodiments, the plurality of microneedles comprises a microneedle that is essentially free of the therapeutically active ingredient in the half of the microneedle closest to the base. 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.

[0104] Some embodiments disclosed herein also include pharmaceutical compositions that include, as an active ingredient, one or more of the compounds disclosed herein in combination with one or more pharma- ceutically acceptable carriers (excipients).In some embodiments, the excipient is lactose, sucrose, glucose, mannitol, sorbitol, trehalose, fructose, galactose, dextrose, xylitol, maltitol, raffinose, dextran, maltodextrin, cyclodextrin, collagen, glycine, histidine, calcium carbonate, magnesium stearate, serum albumin (human and / or animal origin), gelatin, chitosan, deoxyribonucleic acid (DNA), hyaluronic acid, polyvinylpyrrolidone, polyvinyl alcohol, polylactic acid (PLA), polyglycolic acid (PGA), polyactive coglycolic acid (PLGA), polyethylene glycol (PEG, PEG300, PEG400, PEG600, PEG3350, PEG4000), cellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, acacia, Lecithin, Polysorbate 20, Polysorbate 80, Pluronic F-68, Sorbitan Trioleate (span85), EDTA, Hydroxypropylcellulose, Sodium Chloride, Sodium Phosphate, Ammonium Acetate, Potassium Phosphate, Sodium Citrate, Sodium Hydroxide, Sodium Carbonate, Tris Base-65, Tris Acetate, Tris HCl-65, Citrate Buffer, Talc, Silica, Fat, Methylparaben, Propylparaben, Selenium, Vitamins (A, E, C, Retinyl Palmitate, and Selenium), Amino Acids (Methionine, Cysteine, Arginine), Citric Acid, Sodium Citrate, Benzyl Alcohol, Chlorobutanol, Cresols, Phenol, Thimerosal, Acetone, Sodium Bisulfate, Ascorbyl Palmitate, Ascorbate, Castor Oil, Cottonseed Oil, Alum, Aluminum Hydroxide, Aluminum Phosphate, Calcium Hydroxyphosphate, Paraffin Oil, Squalene, Quiloxacin ... A, IL-1, IL-2, IL-12, Freund's complete adjuvant, Freund's incomplete adjuvant, killed Bordetella pertussis, Mycobacterium bovis, and toxoid. In some embodiments, the excipient may be a polymer.In some embodiments, the excipient may be a biodegradable polymer. In some embodiments, the excipient is a polymer, and the polymer is maltodextrin. In some embodiments, there is one excipient. In some embodiments, there are two excipients, and in some embodiments, there are three or more excipients. In some embodiments, the two excipients are maltodextrin and lactose, maltodextrin and sodium thiosulfate, maltodextrin and trehalose, maltodextrin and sodium citrate, maltodextrin and sorbitol, maltodextrin and arginine, maltodextrin and arginine, arginine and lactose, arginine and sodium thiosulfate, arginine and trehalose, arginine and sodium citrate, arginine and sorbitol, sorbitol and lactose, sorbitol and sodium thiosulfate, sorbitol and trehalose, sorbitol and sodium citrate, sodium citrate and lactose, sodium citrate and sodium thiosulfate, sodium citrate and trehalose, trehalose and lactose, trehalose and sodium thiosulfate, or sodium thiosulfate and lactose.

[0105] The active compound is effective over a wide range of dosages 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 being 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.

[0106] The amount of compound or composition administered to a patient will vary depending on what is administered, the purpose of administration, such as prevention or treatment, the condition of the patient, the method of administration, etc. 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 disease is selected from warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, and successful treatment of these diseases results in a one-point improvement in symptoms on any ordinal or interval rating scale, such as Physician Global Assessment or Investigator Global Assessment. In some embodiments, the disease is selected from warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucosa, and epidermodysplasia verruciformis, and successful treatment of these diseases results in about 100% disappearance of the skin lesion at the site where the patch is administered, as assessed by clinical, histopathological, or dermatoscopic evaluation, as well as by optical coherence tomography or confocal microscopy. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and epidermodysplasia verruciformis, and successful treatment of these conditions results in about 50% disappearance of the skin lesion at the site where the patch is administered, as assessed by clinical, histopathological, or dermatoscopic evaluation, as well as by optical coherence tomography or confocal microscopy.In some embodiments, successful treatment of warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, or epidermodysplasia verruciformis with a dissolving microneedle patch may include a reduction in the appearance of skin lesions in 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 Reduce by 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 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 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or by a value within these ranges. Specific examples may 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 by clinical, histopathological, or dermatoscopic evaluation, as well as by optical coherence tomography or confocal microscopy.

[0107] In some embodiments, methods of treating skin disorders, including successfully treating warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, with a dissolvable microneedle patch include reducing the width, length, or height of the skin lesion 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%, about 50% to about 65%, about 50% to about Reduce by 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 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 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or by a value within these ranges. Specific examples may include reducing 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 any two of these values, as measured by clinical, histopathological, or dermatoscopic evaluation, as well as optical coherence tomography or confocal microscopy evaluation.

[0108] In some embodiments, the method of treating the skin disease alopecia areata with a dissolvable microneedle patch, where successful treatment of the disease results in a one-point improvement in 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% hair growth recovery in the area where the patch is administered.In some embodiments, the condition is alopecia areata, and successful treatment of the condition results in at least about 50% 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, in the area where the patch is administered. In some embodiments, successful treatment of alopecia areata with a dissolvable microneedle patch may result in the following results at the site where the patch was administered: 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%, Hair growth is increased by 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 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 values ​​within these ranges. Specific examples include increasing hair growth, as defined by the number of hair follicles with actively growing hair shafts as seen by clinical, trichoscopic, or histopathological evaluation, 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.

[0109] In some embodiments, a method of treating the skin condition alopecia areata with a dissolvable microneedle patch, wherein successful treatment indicates an Alopecia Severity Assessment Tool (SALT) score at the site where the patch was 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%, about 50% to about 65%, about 50% to about 60%, about 50% to about 55%, about 60% to about 100%, The improvement is 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 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 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or a value within these ranges. Specific examples can include improving Alopecia Severity Assessment Tool (SALT) score 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.

[0110] In some embodiments, in a method of treating a skin condition with dissolvable microneedle patches, each dissolvable microneedle patch contains a standardized amount of a therapeutically active ingredient.

[0111] In some embodiments, a method of treating a skin condition with a dissolvable microneedle patch, the dissolvable microneedle may comprise from about 1% to about 90% of one or more therapeutic actives disclosed herein. In some embodiments, the dissolvable microneedle may comprise from about 50% to about 75% of one or more therapeutic actives disclosed herein. In some embodiments, the dissolvable microneedle may comprise from about 25% to about 50% of one or more therapeutic actives disclosed herein. In some embodiments, the dissolvable microneedle may comprise from about 25% to about 75% of one or more therapeutic actives disclosed herein. In some embodiments, the dissolvable microneedle may comprise from about 40% to about 60% of one or more therapeutic actives disclosed herein. In some embodiments, the dissolvable microneedle may comprise from about 60% to about 80% of one or more therapeutic actives disclosed herein. In some embodiments, the one or more therapeutically active ingredients are present in an amount of from about 1% to about 90%, from about 1% to about 85%, from about 1% to about 80%, from about 1% to about 75%, from about 1% to about 70%, from about 1% to about 65%, from about 1% to about 60%, from about 1% to about 55%, from about 1% to about 50%, from about 1% to about 45%, from about 1% to about 40%, from 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 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 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 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 45%, about 15% to about 40%, about 15% to about 35%, about 15% to about 30%, 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%, about 20% to about 50%, about 20% to about 45%, about 20% to about 40%, about 20% to about 35%, about 20% to about 30%, about 20% to about 25%, 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 65%, 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%, about 30% to About 90%, about 30% to about 85%, about 30% to about 80%, about 30% to about 75%, about 30% to about 70%, about 30% to about 65%, about 30% to about 60%, about 30% to about 55%, about 30% to about 50%, about 30% to about 45%, about 30% to about 40%, about 30% to about 35%, about 35% to about 90%, About 35% to about 85%, about 35% to about 80%, about 35% to about 75%, about 35% to about 70%, about 35% to about 65%, about 35% to about 60%, about 35% to about 60%, about 35% to about 55%, about 35% to about 50%, about 35% to about 45%, about 35% to about 40%, about 40% to about 90%, about 40% to About 85%, about 40% to about 80%, about 40% to about 75%, about 40% to about 70%, about 40% to about 65%, about 40% to about 60%, about 40% to about 55%, about 40% to about 50%, about 40% to about 45%, about 45% to about 90%, about 45% to about 85%, about 45% to about 80%, about 45% to about 75%, About 45% to about 70%, about 45% to about 65%, about 45% to about 60%, about 45% to about 55%, about 45% to about 50%, 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 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 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 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 90%, about 80% to about 85%, about 85% to about 90%, or an amount within these ranges. Specific examples may 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%, and about 1%. All of the above represent weight percent of the pharmaceutical composition. In some embodiments, the pharmaceutical composition is suitable for transdermal administration.

[0112] In some embodiments, in the method of treating a skin condition with a dissolvable microneedle patch comprising a therapeutically active ingredient, the therapeutically active ingredient is in a therapeutically effective amount. In some embodiments, the 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 300 mg, about 1 mg to about 200 mg, about 1 mg to about 100 mg, about 10 mg to about 1000 mg, about 50 mg ~1000mg, 100mg~1000mg, 200mg~1000mg, 300mg~1000mg, 400mg~1000mg, 500mg~100 The dose may be 0 mg, about 10 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 value between the ranges disclosed above.

[0113] In some embodiments, in the method of treating a skin condition with a dissolvable microneedle patch containing a therapeutically effective amount of an active ingredient, the therapeutically effective amount may vary depending on, for example, the particular application to which the treatment is applied, 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 microneedle may vary depending on many factors, including the dosage, chemical properties (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 potency of the selected compound, the composition of excipients, and the location of administration. The effective amount may be estimated from dose-response curves obtained from in vitro or animal model test systems.

[0114] In some embodiments, a method of treating a skin condition comprising applying a dissolvable microneedle patch, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising a biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising poly(lactic-co-glycolic acid) (PLGA). In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising a polymer selected from PLGA (poly(lactic-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, the microneedles comprising a single biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising two biodegradable polymers. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedles comprising a plurality of biodegradable polymers.

[0115] In some embodiments, the polymer may act as an excipient that stabilizes the therapeutically active ingredient. In some embodiments, the polymer may form the structure of the microneedle. In some embodiments, the polymer may act both as an excipient that stabilizes the therapeutically active ingredient and as a polymer that forms the structure of the microneedle.

[0116] In some embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch comprising a biodegradable polymer, the biodegradable polymer being 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, trellahorse, sucrose, galactose, amylopectin, polyvinyl alcohol, and / or polyvinylpyrrolidone methacrylate. In further embodiments, the immediate release biodegradable polymer releases the therapeutically active ingredient within about 0 hours 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 time scale of about 0 hours to about 24 hours. In some embodiments, the immediate release biodegradable polymer releases about 100% of the therapeutically active ingredient over a time scale of about 0 hours to about 24 hours. In some embodiments, the immediate release biodegradable polymer releases 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 100%, about 90% to about 95%, about 95% to about 100%, or values ​​within these ranges of the therapeutically active ingredient on a time scale of about 0 hours to about 24 hours. Specific examples include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, about 100%, or ranges between any two of these values.

[0117] 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. 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 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 7 hours, about 1 hour to about 6 hours, about 1 hour to about 5 hours, about 1 hour ~ 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 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, about 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 0 minutes to about 4 minutes, about 0 minutes to about 3 minutes, about 0 minutes to about 5 minutes ...5 minutes, about 0 minutes to about 4 minutes, about 0 minutes to about 3 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 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 5 minutes to about 10 minutes, about 10 minutes to about 60 minutes, about 10 minutes to about 50 minutes, about 10 minutes to about 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 The therapeutically active ingredient is released within about 15 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, about 30 minutes to about 35 minutes, about 45 minutes to about 60 minutes, about 45 minutes to about 50 minutes, or a value within these ranges. Specific examples may 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.

[0118] In some embodiments, the method of treating a skin condition includes applying a dissolvable microneedle patch comprising a biodegradable polymer, the biodegradable polymer being capable of providing a 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 (poly(lactic-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 until more than about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the sustained release biodegradable polymer provides a sustained release biodegradable polymer that is capable of delivering a therapeutically effective amount of glycerol to the tissue of the subject by 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% for a period of more than about 24 hours. , about 80% to about 85%, about 85% to about 100%, about 85% to about 99%, about 85% to about 95%, about 85% to about 90%, about 90% to about 100%, about 90% to about 99%, about 90% to about 95%, about 95% to about 100%, about 95% to about 99%, about 99% to about 100%, or values ​​within these ranges of the therapeutically active ingredient. Specific examples may include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, and about 100%.

[0119] In some embodiments, the sustained release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 to about 30 days. In some embodiments, the sustained release biodegradable polymer releases the therapeutically active ingredient over a period of about 2 to about 21 days. In some embodiments, the sustained release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 to about 30 days, about 1 to about 28 days, about 1 to about 26 days, about 1 to about 24 days, about 1 to about 22 days, about 1 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 days to about 22 days, about 2 days to about 21 days, about 2 days to about 14 days, about 2 days to about 7 days, about 2 days to about 6 days, about 2 days to about 5 days, about 2 days to about 4 days, about 2 days to about 3 days, about 3 days to about 30 days, about 3 days to about 28 days, about 3 days to about 26 days, about 3 days to about 24 days, about 3 days to about 22 days, about 3 days to about 21 days, about 3 days to about 14 days, about 3 days to about 7 days, about 3 days to about 6 days, about 3 days to about 5 days, about 3 days to about 4 days, about 4 days to about 30 days, about 4 days to about 28 days, about 4 days to about 26 days, about 4 days to about 24 days, about 4 days to about 22 days, about 4 days to about 21 days, about 4 days to about 14 days, about 4 days to about 7 days, about 4 days to about 6 days, about 4 days to about 5 days, about 5 days to about 30 days, about 5 days to about 28 days, about 5 days to about 26 days, about 5 days to about 24 days, about 5 days to about 22 days, about 5 days to about 21 days, about 5 days to about 14 days, about 5 days to about 7 days, about 5 days to about 6 days, about 7 days to about 30 days, about 7 days to about 28 days, about 7 days to about 2 The therapeutic activity is released for 6 days, 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 values ​​within these ranges. Specific examples may 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.

[0120] In some embodiments, a method of 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 portion of the microneedles ...

[0121] 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 in need of treatment.

[0122] In some embodiments, a method of treating a skin condition comprising applying a dissolvable microneedle patch comprises a plurality of microneedles, said plurality of 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, the microneedle patch having 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 1 to about 125 microneedles per square centimeter, about 1 to about 100 microneedles per square centimeter, about 1 to about 90 microneedles per square centimeter, about 1 to about 80 microneedles per square centimeter, about 1 to about 70 microneedles per square centimeter, about 1 to about 60 microneedles per square centimeter, about 1 to about 50 microneedles per square centimeter, about 1 to about 40 microneedles per square centimeter, about 1 to about 30 microneedles per square centimeter, about 1 to about 20 microneedles per square centimeter, about 1 to about 20 microneedles per square centimeter, about 1 to about 30 microneedles per square centimeter, about 1 to about 40 microneedles per square centimeter, about 1 to about 5 ...50 microneedles per square centimeter, about 1 to about 60 microneedles per square centimeter, about 1 to about 70 microneedles per square centimeter, about 1 to about 80 microneedles per square centimeter, about 1 to about 90 microneedles per square centimeter, about 1 to about 90 microneedles per square centimeter, about 1 to about 100 microneedles per square centimeter, about 1 to about about 1 to about 25 microneedles per square centimeter, about 1 to about 20 microneedles per square centimeter, 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 20 ... 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, about 10 to about 100 microneedles per square centimeter, about 10 to about 90 microneedles per square centimeter, about 10 to about 80 microneedles per square centimeter, about 10 to about 70 microneedles per square centimeter, about 10 to about 60 microneedles per square centimeter, ... about 50 microneedles, about 10 to about 40 microneedles per square centimeter, about 10 to about 30 microneedles per square centimeter, about 10 to about 25 microneedles per square centimeter, about 10 to about 20 microneedles per square centimeter, 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 black needles, 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 60 microneedles per square centimeter, about 25 to about 50 microneedles per square centimeter, about 25 to about 40 microneedles per square centimeter,about 25 to about 30 microneedles per square centimeter, about 50 to about 200 microneedles per square centimeter, about 50 to about 175 microneedles per square centimeter, about 50 to about 150 microneedles per square centimeter, about 50 to about 125 microneedles per square centimeter, about 50 to about 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 per square centimeter, 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 100 to 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, said 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 125 microneedles per square centimeter, at least about 100 microneedles per square centimeter, at least about 90 microneedles per square centimeter, at least about 80 microneedles per square centimeter, at least about 70 microneedles per square centimeter, at least about 60 microneedles per square centimeter, at least about 50 microneedles per square centimeter, at least about 40 microneedles per square centimeter, at least about 30 microneedles per square centimeter microneedles, at least about 25 microneedles per square centimeter, at least about 20 microneedles per square centimeter, at least about 15 microneedles per square centimeter, at least about 10 microneedles per square centimeter, at least about 5 microneedles per square centimeter, at least about 4 microneedles per square centimeter, at least about 3 microneedles per square centimeter, at least about 2 microneedles per square centimeter, at least about 1 microneedle per square centimeter, or a range between any two of these values.

[0123] 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. In some embodiments, the dissolvable microneedle patch has any number of n sides, where n ranges 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 30 sides, about 0 to about 40 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 50 sides, about 0 to about 50 sides, about 0 to about 60 sides, about 0 to about 70 sides, about 0 to about 80 sides, about 0 to about 90 sides, about 0 to about 10 ... ~10 sides, ~0 sides~9 sides, ~0 sides~8 sides, ~0 sides~7 sides, ~0 sides~6 sides, ~0 sides~5 sides, ~0 sides~4 sides, ~0 sides~3 sides, ~0 sides~2 sides, ~10 sides~1000 sides, ~10 sides~900 sides, ~10 sides~800 sides, ~10 sides~700 sides, ~10 sides~600 sides, ~10 sides~500 sides, ~10 sides~400 sides, ~10 sides~300 sides, ~10 sides~200 sides, ~10 sides~100 sides, ~10 sides~90 sides, ~10 sides~80 sides, ~10 sides~7 0 sides, about 10 sides to about 60 sides, about 10 sides to about 50 sides, about 10 sides to about 40 sides, about 10 sides to about 30 sides, about 10 sides to about 20 sides, about 20 sides to about 1000 sides, about 20 sides to about 900 sides, about 20 sides to about 800 sides, about 20 sides to about 700 sides, about 20 sides to about 600 sides, about 20 sides to about 500 sides, about 20 sides to about 400 sides, about 20 sides to about 300 sides, about 20 sides to about 200 sides, about 20 sides to about 100 sides, about 20 sides to about 90 sides, about 20 sides to about 80 sides, about 20 sides to about 70 sides, about 20 sides to about 60 sides, about 20 sides ~50 sides, ~20 sides~40 sides, ~20 sides~30 sides, ~30 sides~1000 sides, ~30 sides~900 sides, ~30 sides~800 sides, ~30 sides~700 sides, ~30 sides~600 sides, ~30 sides~500 sides, ~30 sides~400 sides, ~30 sides~300 sides, ~30 sides~200 sides, ~30 sides~100 sides, ~30 sides~90 sides, ~30 sides~80 sides, ~30 sides~70 sides, ~30 sides~60 sides, ~30 sides~50 sides, ~30 sides~40 sides, ~50 sides~1000 sides,About 50 sides to about 900 sides, about 50 sides to about 800 sides, about 50 sides to about 700 sides, about 50 sides to about 600 sides, about 50 sides to about 500 sides, about 50 sides to about 400 sides, about 50 sides to about 300 sides, about 50 sides to about 200 sides, about 50 sides to about 100 sides, about 50 sides to about 90 sides, about 50 sides to about 80 sides, about 50 sides to about 70 sides, about 50 sides to about 60 sides, about 75 sides to about 1000 sides, About 75 sides to about 900 sides, about 75 sides to about 800 sides, about 75 sides to about 700 sides, about 75 sides to about 600 sides, about 75 sides to about 500 sides, about 75 sides to about 400 sides, about 75 sides to about 300 sides, about 75 sides to about 200 sides, about 75 sides to about 100 sides, about 75 sides to about 90 sides, about 75 sides to about 80 sides, about 100 sides to about 1000 sides, about 100 sides to about 900 sides, about 100 sides to about 800 sides, about 100 sides to about 700 sides, about 100 sides to about 600 sides, about 100 sides to about 500 sides, about 100 sides to about 400 sides, about 100 sides to about 300 sides, about 100 sides to about 200 sides, about 250 sides to about 1000 sides, about 250 sides to about 900 sides, about 250 sides to about 800 sides, about 250 sides to about 700 sides, about 250 sides to about 600 sides, about 250 sides to 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 700 sides, about 500 sides to about 600 sides, about 750 sides to about 1000 sides, about 750 sides to about 900 sides, about 750 sides to about 800 sides, about 900 sides to about 1000 sides, or values ​​within these ranges. Specific examples may include dissolvable microneedle patches having 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 these two values.

[0124] In further embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch, the dissolvable microneedle patch can have sides of equal length. In further embodiments, the dissolvable microneedle patch can 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 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 ... 0.1 square centimeters to about 60 square centimeters, about 0.1 square centimeters 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 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, about 0.1 square centimeters to about 0.6 square centimeters,About 0.1 square centimeters to about 0.5 square centimeters, about 0.1 square centimeters to about 0.4 square centimeters, about 0.1 square centimeters to about 0.3 square centimeters, about 0.1 square centimeters to about 0.2 square centimeters, about 0.5 square centimeters to about 1000 square centimeters, about 0.5 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 centimeters, about 0.5 square centimeters to about 500 square centimeters, about 0.5 square centimeters to about 400 square centimeters, about 0.5 square centimeters to about 300 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 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, about 0.5 square centimeters to about 4 square centimeters, about 0.5 square centimeters to about 3 square centimeters, about 0.5 square centimeters to about 2 square centimeters torr, about 0.5 square centimeters to about 1 square centimeter, about 0.5 square centimeters to about 0.9 square centimeters, about 0.5 square centimeters to about 0.8 square centimeters, about 0.5 square centimeters to about 0.7 square centimeters, about 0.5 square centimeters to about 0.6 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 about 100 square centimeters, about 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 1 000 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, about 10 square centimeters to about 600 square centimeters, about 10 square centimeters to about 500 square centimeters, about 10 square centimeters to about 400 square centimeters, about 10 square centimeters to about 300 square centimeters, about 10 square centimeters to about 200 square centimeters, about 10 square centimeters to about 100 Square centimeters, about 10 square centimeters to about 90 square centimeters, about 10 square centimeters to about 80 square centimeters, about 10 square centimeters to about 70 square centimeters, about 10 square centimeters to about 60 square centimeters, about 10 square centimeters to about 50 square centimeters, about 10 square centimeters to about 40 square centimeters, about 10 square centimeters to about 30 square centimeters, about 10 square centimeters to about 20 square centimeters, about 50 square centimeters to about 1000 square centimeters,About 50 square centimeters to about 900 square centimeters, about 50 square centimeters to about 800 square centimeters, about 50 square centimeters to about 700 square centimeters, about 50 square centimeters to about 600 square centimeters, about 50 square centimeters to about 500 square centimeters, about 50 square centimeters to about 400 square centimeters, 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 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, about 75 square centimeters to about 200 square centimeters, about 75 square centimeters 100 sq. cm to about 1000 sq. cm, 100 sq. cm to about 900 sq. cm, 100 sq. cm to about 800 sq. cm, 100 sq. cm to about 700 sq. cm, 100 sq. cm to about 600 sq. cm, 100 sq. cm to about 500 sq. cm, 100 sq. cm to about 400 sq. cm, 100 sq. cm to about 300 sq. cm, 100 sq. cm to about 500 sq. cm, 100 sq. cm to about 600 sq. cm, 100 sq. cm to about 700 sq. cm, 100 sq. cm to about 800 sq. cm, 100 sq. cm to about 900 sq. cm, 100 sq. cm to about 10 ... 250 square centimeters to about 200 square centimeters, about 250 square centimeters to about 1000 square centimeters, about 250 square centimeters to about 900 square centimeters, about 250 square centimeters to about 800 square centimeters, about 250 square centimeters to about 700 square centimeters, about 250 square centimeters to about 600 square centimeters, about 250 square centimeters to about 500 square centimeters, about 250 square centimeters to about 400 square centimeters, about 250 square centimeters to about 300 square centimeters,The size may be 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 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 30 square centimeters, about 40 square centimeters, about 50 square centimeters, about 60 square centimeters, about 70 square centimeters, about 80 square centimeters, about 90 square centimeters, about 10 ... 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 0.7 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.

[0125] In some embodiments, a method of treating a skin condition comprises applying a dissolvable microneedle patch, the dissolvable microneedle patch comprising a backing layer and a microneedle layer, the microneedle layer being placed directly on the skin. In some embodiments, the dissolvable microneedle patch comprises a backing layer, the backing layer being comprised of adhesive medical tape. In some embodiments, the dissolvable microneedle patch comprises a backing layer, the backing layer comprising a therapeutically active ingredient.

[0126] In some embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch, the dissolvable microneedle patch including a backing layer, the backing layer being a removable substrate. In some embodiments, the dissolvable microneedle patch includes a removable substrate including an adhesive medical tape. In some embodiments, the backing layer includes a fast dissolving polymer. In some embodiments, the removable substrate includes a therapeutically active ingredient dispersed in a polymer. In some embodiments, the dissolvable microneedle patch includes a plurality of microneedles attached to a removable substrate and including a tapered tip portion extending away from the removable substrate. In some embodiments, the dissolvable microneedle patch includes a removable substrate that releases at least about 90% of the microneedles from the adhesive surface within a period of about 20 minutes after application to the skin. In some embodiments, the dissolvable microneedle patch includes a removable substrate that releases at least about 90% of the microneedles from the adhesive surface within a period of about 5 minutes after application to the skin.In some embodiments, in the dissolvable microneedle patch, 90% of the microneedles are in contact with the microneedle within about 0 minutes to about 20 minutes, about 0 minutes to about 15 minutes, about 0 minutes to about 10 minutes, about 0 minutes to about 9 minutes, about 0 minutes to about 8 minutes, about 0 minutes to about 7 minutes, about 0 minutes to about 6 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 1 minute to about 20 minutes, about 1 minute to about 15 minutes, about 1 minute to about 10 minutes, about 1 minute to about 9 minutes, about 1 minute to about 8 minutes, about 1 minute to about 7 minutes, about 1 minute to about 6 minutes, about 1 minute to about 5 minutes, about 1 minute to about 4 minutes, about 1 minute to about 3 minutes, about 1 minute ... 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 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 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 seconds, approximately 0 seconds to approximately 9 seconds, approximately 0 seconds to approximately 8 seconds , about 0 seconds to about 7 seconds, about 0 seconds to about 6 seconds, about 0 seconds to about 5 seconds, about 0 seconds to about 4 seconds, about 0 seconds to about 3 seconds, about 0 seconds to about 2 seconds, about 0 seconds to about 1 second, about 1 seconds 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 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 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 about 45 seconds, about 2 seconds to about 30 seconds, about 2 seconds to about 15 seconds, about 2 seconds to about 10 seconds, about 2 seconds to about 9 seconds, about 2 seconds to about 8 seconds, about 2 seconds to about 7 seconds, about It is released from the adhesive surface within a period of 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 within a value within these ranges.In specific examples, 90% of the microneedles are released from the adhesive surface of the 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 within a range between these two values.

[0127] In some embodiments, a method of treating a skin condition comprises applying a dissolvable microneedle patch comprising a backing layer, said backing layer covering the base of the tip portion such that each microneedle is separated from the other microneedles on the patch and forms an individual entity when the substrate is removed upon application of the patch to the skin.

[0128] In some embodiments, a method of treating a skin condition includes applying a dissolvable microneedle patch, the dissolvable microneedle patch being (i) placed on a superficial area of ​​the skin of a patient in need of treatment or performing a pre-treatment test to evaluate hypersensitivity reactions, general tolerability, or other adverse events; (ii) applying a sufficient force to the patch composition to allow 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 backing from the patch composition, the step (ii) being performed by applying pressure with a finger, the pressure being sufficient with a force ranging from about 0 N to about 1,000 N. In a preferred embodiment of the present disclosure, the applied pressure is about 10 N. In an alternative embodiment of the present disclosure, the step (ii) is performed by impact insertion using an applicator device, the pressure being sufficient with a force ranging from about 0 N to about 1,000 N. In a preferred embodiment of the present disclosure, 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 20 N, about 0 N to about 10 N, about 0 N to about 9 N, about 0 N to about 8 N, about 0 N to about 7 N, about 0 N to about 8 N, about 0 N to about 7 N, about 0 N to about 8 N, about 0 N to about 9 ... N ~ about 6N, about 0N - about 5N, about 0N - about 4N, about 0N - about 3N, about 0N - about 2N, about 0N - about 1N, about 0N - about 0.9N, about 0N - 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 0.2 N, approximately 0N to approximately 0.1N, approximately 0.1N to approximately 1000N, approximately 0.1N to approximately 900N, approximately 0.1N to approximately 800N, approximately 0.1N to approximately 700N, approximately 0.1N to about 600N, about 0.1N to about 500N, about 0.1N to about 400N, about 0.1N to about 300N, about 0.1N to about 200N, about 0.1 N to approximately 100 N, approximately 0.1 N to approximately 90 N, approximately 0.1 N to approximately 80 N, approximately 0.1 N to approximately 70 N, approximately 0.1 N to approximately 60 N, approximately 0.1 N to approximately 50 N, approximately 0.1 N to approximately 40 N, approximately 0.1 N to approximately 30 N, approximately 0.1 N to approximately 20 N, approximately 0.1 N to approximately 10 N, approximately 9 N, approximately 0.1 N to approximately 8 N, approximately 0.1 N to approximately 7 N, approximately 0.1 N to approximately 6 N, approximately 0.1 N to approximately 5 N, approximately 0.1 N to approximately 4 N, approximately 0.1 N to approximately 3 N, approximately 0.1 N to approximately 2 N, approximately 0.1 N to approximately 1 N, approximately 0.1 N to approximately 0.9 N, approximately 0.1 N to approximately 0.8 N, approximately 0.1 N to approximately 0.7 N, approximately 0.1 N to approximately 0.6 N, approximately 0.1 N to approximately 0.5 N, approximately 0.1 N to approximately 0.4 N, approximately 0.1 N to approximately 0.3 N, approximately 0.1 N to approximately 0.2N, about 1N to about 1000N, about 1N to about 900N, about 1N to about 800N, about 1N to about 700N, about 1N to about 600N, about 1N to about 500N, about 1N to about 400N, about 1N to about 300N, about 1N to about 200N, about 1N to about 100N, Approximately 1N to approximately 90N, approximately 1N to approximately 80N, approximately 1N to approximately 70N, approximately 1N to approximately 60N, approximately 1N to approximately 50N, approximately 1N to approximately 40N, approximately 1N to approximately 30N, approximately 1N to approximately 20N, approximately 1N to approximately 10N, approximately 1N to approximately 9N, approximately 1N to approximately 8N, approximately 1N to approximately 7N , about 1N to about 6N, about 1N to about 5N, about 1N to about 4N, about 1N to about 3N, about 1N to about 2N, about 10N to about 1000N, about 10N to about 900N, about 10N to about 800N, about 10N to about 700N, about 10N to about 600N, about 10N to about 5 00N, approximately 10N to approximately 400N, approximately 10N to approximately 300N, approximately 10N to approximately 200N, approximately 10N to approximately 100N, approximately 10N to approximately 90N, approximately 10N to approximately 80N, approximately 10N to approximately 70N, approximately 10N to approximately 60N, approximately 10N to approximately 50N, approximately 10N to approximately 4 0N, 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, 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, 100N to about 400N, about 100N to about 300N, about 100N to about 200N, about 200N to about 1000N, about 200N 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 values ​​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 0.9N, about 1N, about 2N, about 3N, about 4N, about 5N, about 6N, about 7N, about 8N, about 9N, about 10N, about 15N, about 20N, about 30N, about 40N, about 50N, about 60N, about 70N, about 80N, about 90N, about 100N, about 200N, about 300N, about 400N, about 500N, about 600N, about 700N, about 800N, about 900N, or a range between two of these values.

[0129] In some embodiments, the method of treating a skin condition includes applying a dissolvable microneedle patch, the dissolvable microneedle patch being (i) placed on a superficial area of ​​the skin of a patient in need of treatment or performing a pre-treatment test to evaluate hypersensitivity reactions, general tolerability, or other adverse events, and (ii) applying a sufficient force to the patch composition to allow the microneedles to penetrate the epidermis and enter the papillary dermis, the sufficient force being 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.

[0130] In some embodiments, a method of treating a skin condition comprises 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.

[0131] In some embodiments, a method of treating a skin condition comprises applying a dissolvable microneedle patch comprising an immediate release polymer, the skin condition comprising alopecia areata or vitiligo. In some embodiments, a method of applying a dissolvable microneedle patch comprising an immediate release polymer, the method comprises a medical procedure for testing for allergy or hypersensitivity to a therapeutically active agent.

[0132] An embodiment of the present disclosure relates to a method of testing for allergies in a patient in need thereof, 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 an adhesive backing from the patch composition, and allowing a plurality of the microneedles to remain on the skin until a biodegradable polymer degrades.

[0133] In some embodiments, a method of testing a patient in need thereof for hypersensitivity comprises 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 to a location selected from the group consisting of the epidermis, the dermis, and the papillary dermis; removing the adhesive backing from the patch composition; and allowing the plurality of microneedles to remain on the skin until the biodegradable polymer degrades.

[0134] In some embodiments, a method of sensitizing a patient to the required immune stimulating active ingredient comprises applying a dissolvable microneedle patch for delivering a therapeutic active ingredient to the skin; applying sufficient force to the dissolvable microneedle patch to allow the microneedles to penetrate to a location selected from the group consisting of the epidermis, dermis and papillary dermis; removing the adhesive backing from the patch composition; and allowing the plurality of microneedles to remain on the skin until the biodegradable polymer degrades.

[0135] Method for producing dissolvable microneedle patch An embodiment of the present application is a method for manufacturing a dissolvable microneedle patch for delivering a therapeutic active agent to the skin, comprising dispersing a lyophilized therapeutic active agent 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 includes microneedles of at least two different lengths, and wherein the therapeutic active agent is selected from the group consisting of a vaccine, an immunostimulating molecule, an immunostimulating organism, and an immunostimulating protein.

[0136] In some embodiments, in a method of making a dissolvable microneedle patch, the dissolvable microneedle patch comprises a plurality of microneedles including microneedles of at least two different lengths 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 1-5 different lengths. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, where 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 in equal proportions. In some embodiments, the needles of at least two different lengths may be in different proportions. In an alternative embodiment, the dissolvable microneedle patch comprises a plurality of microneedles, where the microneedles are of a single length. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, where the microneedles are of equal length. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles having at least two different lengths, such as from about 10 microns to about 1000 microns, from about 10 microns to about 900 microns, from about 10 microns to about 800 microns, from about 10 microns to about 700 microns, from about 10 microns to about 600 microns, from about 10 microns to about 500 microns, from about 10 microns to about 400 microns, from about 10 microns to about 300 microns, from about 10 microns to about 200 microns, from about 10 microns to about 100 microns, and from about 10 microns to about 200 microns. ~ 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, 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 lon, 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 to about 500 microns, about 200 to about 400 microns, about 200 to about 300 microns, about 500 to about 1000 microns, about 500 to about 900 microns, about 500 to about 800 microns, about 500 to about 700 microns, about 500 to about 600 microns, about 800 to about 1000 microns, about 800 to about 900 microns, about 900 to about 1000 microns, or values ​​within these ranges.

[0137] In some embodiments, the method of making a dissolvable microneedle patch includes a plurality of microneedles having a tapered tip portion that includes a therapeutically active ingredient dispersed in a matrix or suspension of a biodegradable polymer.

[0138] In some embodiments, a method for producing a dissolvable microneedle patch is provided, the dissolvable microneedle patch being composed of a biodegradable polymer with a plurality of microneedles of equal volume, including at least two different lengths of microneedles. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, and the volume of each microneedle may remain constant, which is 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, and the volume of each microneedle is dependent on the concentration of the particular immunostimulant used.

[0139] In some embodiments, a method of making a dissolvable microneedle patch, the dissolvable microneedle patch comprising a plurality of microneedles, the tip portions of which constitute 5-99% of the total volume of the microneedles. In some embodiments, the microneedle tip portions constitute about 20% to about 90% of the total volume of the microneedles. In some embodiments, the microneedle tip portions constitute about 50% of the total volume of the microneedles. In some embodiments, the microneedle tip portions constitute 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%, about 10% to about 99%, about 10% to about 95%, 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 60%, about 10% to about 50%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 10% to about 15%, 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 about 70%, about 15% to about 60%, about 15% to about 50%, about 15% to about 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%, about 50% to about 99%, 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 60%, 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 85%, about 70% to about 80%, about 70% to about 75%, about 80% to about 99%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 90% to about 99%, about 90% to about 95%, or values ​​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 a range 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 plurality of microneedles comprises a different amount of the therapeutically active ingredient.

[0140] 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, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, vitiligo, and alopecia areata.

[0141] In some embodiments, in the method of manufacturing a dissolvable microneedle patch, certain compounds disclosed herein may have useful immune stimulating activity and may be used in the treatment or prevention of diseases or conditions in which the immune system may play an active role. In some embodiments, successful delivery of immune stimulants results in classical clinical signs of inflammation, such as rash, tumors, and fever (redness, swelling, and warmth, respectively). Thus, embodiments also relate to pharmaceutical compositions comprising one or more compounds disclosed herein together with a pharma- ceutically acceptable carrier, as well as methods of making and using the compounds and compositions. Certain embodiments relate to methods for stimulating the immune system. Other embodiments relate to methods for treating skin conditions in patients in need of such treatment, comprising administering to said 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 medicaments for the treatment of diseases or conditions ameliorated by the activation of the immune system.

[0142] In some embodiments, the method of manufacturing a dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin. 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 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.

[0143] In some embodiments, a method of manufacturing a dissolvable microneedle patch for delivering a therapeutically active agent, wherein the therapeutically active agent is selected from the group consisting of a vaccine, an immunostimulatory molecule, an immunostimulatory organism, and an immunostimulatory protein.

[0144] In some embodiments, the therapeutically active ingredient is a vaccine, the vaccine being 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 immunostimulating molecule, the immunostimulating molecule being imiquimod. In some embodiments, the therapeutically active ingredient is an immunostimulating organism, the immunostimulating organism being Corynebacterium parvum, Cutibacterium acnes, Propionobacterium, and / or Mycobacterium indicus planii (formerly Mycobacterium w). In some embodiments, the therapeutically active ingredient is an immunostimulating protein, the immunostimulating protein being selected from the group consisting of Candida antigen, Trichophyton antigen, tuberculin, purified protein derivative (also), human papillomavirus surface protein, interferon alpha, interferon beta, and interferon gamma.

[0145] In some embodiments, in a method of manufacturing a dissolvable microneedle patch for delivering a therapeutically active ingredient, the therapeutically active ingredient is an antigen composition. In some embodiments, in a method of manufacturing a dissolvable microneedle patch for delivering a therapeutically active ingredient, the therapeutically active ingredient is a Candida antigen composition. In some embodiments, the antigen composition is substantially free of glycerol. In some embodiments, the Candida antigen composition is substantially free of glycerol. In some embodiments, the antigen composition is glycerol-free. In some embodiments, the Candida antigen composition is glycerol-free. In some embodiments, the glycerol-free antigen composition is lyophilized. In some embodiments, the glycerin-free Candida antigen composition is lyophilized. In some embodiments, the antigen composition comprises less than about 50% glycerol. In some embodiments, the antigen composition comprises less than about 40% glycerol. In some embodiments, the antigen composition comprises less than about 30% glycerol. In some embodiments, the antigen composition comprises less than about 20% glycerol. In some embodiments, the antigen composition comprises less than 15% glycerol. In some embodiments, the antigen composition comprises less than about 10% glycerol. In some embodiments, the antigen composition comprises less than about 5% glycerol, hi some embodiments, the antigen composition comprises less than about 1% glycerol.In some embodiments, the antigen composition comprises about 0.1% to about 15% glycerol, about 0.1% to about 14% glycerol, about 0.1% to about 13% glycerol, about 0.1% to about 12% glycerol, about 0.1% to about 11% glycerol, about 0.1% to about 10% glycerol, about 0.1% to about 9% glycerol, about 0.1% to about 8% glycerol, about 0.1% to about 7% glycerol, about 0.1% to about 6% glycerol, about 0.1% to about 5% glycerol, about 0.1% to about 4% glycerol, about 0.1% to about 3% glycerol, about 0.1% to about 2% glycerol, about 0.1% to about 1% glycerol, about 0.1% to about 0.9% glycerol, about 0.1% to about 0.8% glycerol, about 0.1% to about 0.7% glycerol, about 0.1% to about 0.6% glycerol, about 0.1% to about 0.5% glycerol, about 0.1% to about 0.4% glycerol, about 0.1% to about 0.3% glycerol glycerol, about 0.1% to about 0.2% glycerol, about 0.2% to about 15% glycerol, about 0.3% to about 15% glycerol, about 0.4% to about 15% glycerol, about 0.5% to about 15% glycerol, about 0.6% to about 15% glycerol, about 0.7% to about 15% glycerol, about 0.8% to about 15% glycerol, about 0.9% to about 15% glycerol, about 1% to about 15% glycerol, about 2% to about 15% glycerol, about 3% to about 15% glycerol, about 4% to about 15% glycerol, about 5% to about 15% glycerol, about 6% to about 15% glycerol, about 7% to about 15% glycerol, about 8% to about 15% glycerol, about 9% to about 15% glycerol, about 10 ... Including 5% glycerol, about 4% to about 15% glycerol, about 5% to about 15% glycerol, about 6% to about 15% glycerol, about 7% to about 15% glycerol, about 8% to about 15% glycerol, about 9% to about 15% glycerol, about 10% to about 15% glycerol, about 11% to about 15% glycerol, about 12% to about 15% glycerol, about 13% to about 15% glycerol, about 14% to about 15% glycerol, or values ​​within these ranges.In some embodiments, the antigen composition comprises about 0.1% glycerol, about 0.2% glycerol, about 0.3% glycerol, about 0.4% glycerol, about 0.5% glycerol, about 0.6% glycerol, about 0.7% glycerol, about 0.8% glycerol, about 0.9% glycerol, about 1% glycerol, about 2% glycerol, about 3% glycerol, about 4% glycerol, about 5% glycerol, about 6% glycerol, about 7% glycerol, about 8% glycerol, about 9% glycerol, about 10% glycerol, about 20% glycerol, about 30% glycerol, about 40% glycerol, about 50% glycerol, about 60% glycerol, about 70% glycerol, about 80% glycerol, about 90% glycerol, about 100% glycerol, about 11% glycerol, about 12% glycerol, about 13% glycerol, about 14% glycerol, about 15% glycerol, about 16% glycerol, about 17% glycerol, about 18% glycerol, about 19% glycerol, about 20% glycerol, about 21% glycerol, about 22% glycerol, about 23% glycerol, about 24% glycerol, about 25% glycerol, about 26% glycerol, about 27% glycerol, about 28% glycerol, about 29% glycerol, about 30% glycerol, about 31% glycerol, about 32% glycerol, about glycerol, about 8% glycerol, about 9% glycerol, about 10% glycerol, about 11% glycerol, about 12% glycerol, about 13% glycerol, about 14% glycerol, about 15% glycerol, about 20% glycerol, about 25% glycerol, about 30% glycerol, about 35% glycerol, about 40% glycerol, about 45% glycerol, about 50% glycerol, or a range between any two of these values.

[0146] Some embodiments relate to a method for making a dissolvable microneedle patch comprising an immunostimulatory compound, the method comprising the steps of: adding an immunostimulatory compound to a biodegradable polymer; pouring a composition comprising the biodegradable polymer and an immunostimulatory compound into a microneedle mold; and removing the microneedle mold after the composition comprising the biodegradable polymer and an immunostimulatory compound has solidified. In some embodiments, the immunostimulatory compound comprises glycerol. In some embodiments, the method for making a dissolvable microneedle patch comprising an immunostimulatory compound further comprises removing glycerol from the immunostimulatory compound. In some embodiments, the method for making a dissolvable microneedle patch comprising an immunostimulatory compound further comprises removing glycerol from the immunostimulatory compound, the glycerol being removed by dialysis. In some embodiments, the method for making a dissolvable microneedle patch comprising an immunostimulatory compound further comprises removing glycerol from the immunostimulatory compound, the glycerol being removed by dilution. In some embodiments, the immunostimulatory compound is lyophilized after the glycerol is removed. In some embodiments, the glycerol is removed prior to adding the immunostimulatory compound to the biodegradable polymer.

[0147] 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, a plurality of microneedles comprises a therapeutically active ingredient, wherein the therapeutically active ingredient is uniformly dispersed throughout the microneedles. In some embodiments, a 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 a microneedle in the half of the microneedle closest to the base that is essentially free of the therapeutically active ingredient. In some embodiments, the plurality of microneedles comprises a microneedle in the half of the microneedle closest to the base that 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.

[0148] Some embodiments disclosed herein also include pharmaceutical compositions that include, as an active ingredient, one or more of the compounds disclosed herein in combination with one or more pharma- ceutically acceptable carriers (excipients).

[0149] In some embodiments, the excipient is lactose, sucrose, glucose, mannitol, sorbitol, trehalose, fructose, galactose, dextrose, xylitol, maltitol, raffinose, dextran, maltodextrin, cyclodextrin, collagen, glycine, histidine, calcium carbonate, magnesium stearate, serum albumin (human and / or animal origin), gelatin, chitosan, deoxyribonucleic acid (DNA), hyaluronic acid, polyvinylpyrrolidone, polyvinyl alcohol, polylactic acid (PLA), polyglycolic acid (PGA), polyactive coglycolic acid (PLGA), polyethylene glycol (PEG, PEG300, PEG400, PEG600, PEG3350, PEG4000), cellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, acacia, Lecithin, Polysorbate 20, Polysorbate 80, Pluronic F-68, Sorbitan Trioleate (span85), EDTA, Hydroxypropylcellulose, Sodium Chloride, Sodium Phosphate, Ammonium Acetate, Potassium Phosphate, Sodium Citrate, Sodium Hydroxide, Sodium Carbonate, Tris Base-65, Tris Acetate, Tris HCl-65, Citrate Buffer, Talc, Silica, Fat, Methylparaben, Propylparaben, Selenium, Vitamins (A, E, C, Retinyl Palmitate, and Selenium), Amino Acids (Methionine, Cysteine, Arginine), Citric Acid, Sodium Citrate, Benzyl Alcohol, Chlorobutanol, Cresols, Phenol, Thimerosal, Acetone, Sodium Bisulfate, Ascorbyl Palmitate, Ascorbate, Castor Oil, Cottonseed Oil, Alum, Aluminum Hydroxide, Aluminum Phosphate, Calcium Hydroxyphosphate, Paraffin Oil, Squalene, Quiloxacin ... A, IL-1, IL-2, IL-12, Freund's complete adjuvant, Freund's incomplete adjuvant, killed Bordetella pertussis, Mycobacterium bovis, and toxoid. In some embodiments, the excipient may be a polymer.In some embodiments, the excipient may be a biodegradable polymer. In some embodiments, the excipient is a polymer, and the polymer is maltodextrin. In some embodiments, there is one excipient. In some embodiments, there are two excipients, and in some embodiments, there are three or more excipients. In some embodiments, the two excipients are maltodextrin and lactose, maltodextrin and sodium thiosulfate, maltodextrin and trehalose, maltodextrin and sodium citrate, maltodextrin and sorbitol, maltodextrin and arginine, maltodextrin and arginine, arginine and lactose, arginine and sodium thiosulfate, arginine and trehalose, arginine and sodium citrate, arginine and sorbitol, sorbitol and lactose, sorbitol and sodium thiosulfate, sorbitol and trehalose, sorbitol and sodium citrate, sodium citrate and lactose, sodium citrate and sodium thiosulfate, sodium citrate and trehalose, trehalose and lactose, trehalose and sodium thiosulfate, or sodium thiosulfate and lactose.

[0150] The active compound is effective over a wide range of dosages 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 being 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.

[0151] In some embodiments, in the method of manufacturing a dissolvable microneedle patch for delivering a therapeutic active ingredient, the amount of therapeutic active ingredient administered to a patient varies depending on what is administered, the purpose of administration, such as prevention or treatment, the condition of the patient, the method of administration, etc. 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 disease is selected from warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis, and successful treatment of these diseases results in a one-point improvement in symptoms on any ordinal or interval rating scale, such as Physician Global Assessment or Investigator Global Assessment. In some embodiments, the disease is selected from warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucosa, and epidermodysplasia verruciformis, and successful treatment of these diseases results in about 100% disappearance of the skin lesion at the site where the patch is administered, as assessed by clinical, histopathological, or dermatoscopic evaluation, as well as by optical coherence tomography or confocal microscopy. In some embodiments, the condition is selected from warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, and epidermodysplasia verruciformis, and successful treatment of these conditions results in about 50% disappearance of the skin lesion at the site where the patch is administered, as assessed by clinical, histopathological, or dermatoscopic evaluation, as well as by optical coherence tomography or confocal microscopy.In some embodiments, successful treatment of warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, or epidermodysplasia verruciformis with a dissolving microneedle patch may include a reduction in the appearance of skin lesions in 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 Reduce by 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 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 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or by a value within these ranges. Specific examples may 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 by clinical, histopathological, or dermatoscopic evaluation, as well as by optical coherence tomography or confocal microscopy.

[0152] In some embodiments, in the method of manufacturing a dissolvable microneedle patch for delivery of a therapeutically active ingredient to treat a skin condition, successful treatment of warts, condyloma acuminata, bowenoid papulosis, molluscum contagiosum, actinic keratosis, squamous cell carcinoma, basal cell carcinoma, verrucous carcinoma, epidermodysplasia verruciformis with the dissolvable microneedle patch is characterized by a reduction in width, length, or height of the skin lesion at the site where the patch was 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%, or about 50% to about 80%. , 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 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 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or a value within these ranges. Specific examples may include reducing 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 any two of these values, as measured by clinical, histopathological, or dermatoscopic evaluation, as well as optical coherence tomography or confocal microscopy evaluation.

[0153] In some embodiments, in the method of manufacturing a dissolvable microneedle patch for delivering therapeutic active ingredients for treating skin condition alopecia areata with the dissolvable microneedle patch, the successful treatment of the condition results in a one-point improvement in any ordinal or interval rating scale, such as Physician Global Assessment or Investigator Global Assessment.In some embodiments, the condition is alopecia areata, and the successful treatment of the condition results in about 100% hair growth recovery in the area where the patch is administered.In some embodiments, the condition is alopecia areata, and the successful treatment of the disease results in at least about 50% 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, in the area where the patch is administered. In some embodiments, successful treatment of alopecia areata with a dissolvable microneedle patch may result in the following results at the site where the patch was administered: 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%, Hair growth is increased by 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 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 values ​​within these ranges. Specific examples include increasing hair growth, as defined by the number of hair follicles with actively growing hair shafts as seen by clinical, trichoscopic, or histopathological evaluation, 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.

[0154] In some embodiments, a method of manufacturing a dissolvable microneedle patch for delivering a therapeutic active ingredient for treating a skin condition alopecia areata using a dissolvable microneedle patch, comprising administering to said patient a treatment that is successful and / or reduces the severity of the Alopecia Severity Assessment 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%, about 50% to about 65%, about 50% to about 60%, about 50% to about 75%, about 50% to about 70%, about 50% to about 85%, about 50% to about 80%, about 50% to about 90%, about 50% to about 90%, about 50% to about 10 ... % 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 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 80% to about 85%, about 90% to about 100%, about 90% to about 95%, or a value within these ranges. Specific examples can include improving Alopecia Severity Assessment Tool (SALT) score 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.

[0155] In some embodiments, a method of manufacturing a dissolvable microneedle patch, wherein each dissolvable microneedle patch contains a standardized amount of a therapeutically active ingredient.

[0156] In some embodiments, in the method of manufacturing a dissolvable microneedle patch, the dissolvable microneedle may comprise about 1% to about 90% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedle may comprise about 50% to about 75% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedle may comprise about 25% to about 50% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedle may comprise about 25% to about 75% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedle may comprise about 40% to about 60% of one or more therapeutically active ingredients disclosed herein. In some embodiments, the dissolvable microneedle 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 from about 1% to about 90%, from about 1% to about 85%, from about 1% to about 80%, from about 1% to about 75%, from about 1% to about 70%, from about 1% to about 65%, from about 1% to about 60%, from about 1% to about 55%, from about 1% to about 50%, from about 1% to about 45%, from about 1% to about 40%, from about 1% to about 35%, from about 1% to about 50%, from about 1% to about 55%, from about 1% to about 50%, from about 1% to about 50%, from about 1% to about 65%, from about 1% to about 60%, from about 1% to about 70%, from about 1% to about 75%, from about 1% to about 80%, from about 1% to about 85%, from about 1% to about 90%, from about 1% to about 100%, from about 1% to about 15 ... ~ 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 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 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 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 45%, about 15% to about 40%, about 15% to about 35%, about 15% to about 30%, 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%, about 20% to about 50%, about 20% to about 45%, about 20% to about 40%, about 20% to about 35%, about 20% to about 30%, about 20% to about 25%, 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 65%, 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%, about 30% to about 90%, about 30% to About 85%, about 30% to about 80%, about 30% to about 75%, about 30% to about 70%, about 30% to about 65%, about 30% to about 60%, about 30% to about 55%, about 30% to about 50%, about 30% to about 45%, about 30% to about 40%, about 30% to about 35%, about 35% to about 90%, about 35% to about 85%, About 35% to about 80%, about 35% to about 75%, about 35% to about 70%, about 35% to about 65%, about 35% to about 60%, about 35% to about 60%, about 35% to about 55%, about 35% to about 50%, about 35% to about 45%, about 35% to about 40%, about 40% to about 90%, about 40% to about 85%, about 40% to About 80%, about 40% to about 75%, about 40% to about 70%, about 40% to about 65%, about 40% to about 60%, about 40% to about 55%, about 40% to about 50%, about 40% to about 45%, about 45% to about 90%, about 45% to about 85%, about 45% to about 80%, about 45% to about 75%, about 45% to about 70%, About 45% to about 65%, about 45% to about 60%, about 45% to about 55%, about 45% to about 50%, 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 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 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 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 90%, about 80% to about 85%, about 85% to about 90%, or an amount within these ranges. Specific examples may 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%, and about 1%. All of the above represent weight percent of the pharmaceutical composition. In some embodiments, the pharmaceutical composition is suitable for transdermal administration.

[0157] In some embodiments, in the method of manufacturing a dissolvable microneedle patch for delivering a therapeutically active ingredient, the therapeutically active ingredient is in a therapeutically effective amount. In some embodiments, the therapeutically effective amount is 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 300 mg, about 1 mg to about 200 mg, about 1 mg to about 100 mg, about 10 mg to about 1000 mg, about 50 mg ~1000mg, 100mg~1000mg, 200mg~1000mg, 300mg~1000mg, 400mg~1000mg, 500mg~100 The dose may be 0 mg, about 10 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 value between the ranges disclosed above.

[0158] In some embodiments, in the method of manufacturing a dissolvable microneedle patch containing a therapeutically effective amount of an active ingredient, the therapeutically effective amount may vary depending on, for example, the particular application for which the treatment is performed, 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 microneedle may vary depending on many factors, including the dosage, chemical properties (e.g., hydrophobicity), and the type of microneedle polymer. The dosage will depend on variables such as the type and extent of progression of the disease or disorder, the overall health of the particular patient, the relative biological potency of the selected compound, the composition of excipients, and the location of administration. The effective amount may be estimated from dose-response curves obtained from in vitro or animal model test systems.

[0159] In some embodiments, a method of manufacturing a dissolvable microneedle patch comprising a plurality of needles, the plurality of microneedles comprises a biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the plurality of microneedles comprises poly(lactic-co-glycolic acid) (PLGA). In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the plurality of microneedles comprises a polymer selected from PLGA (poly(lactic-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, the plurality of microneedles comprises a single biodegradable polymer. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the plurality of microneedles comprises two biodegradable polymers. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the plurality of microneedles comprises a plurality of biodegradable polymers.

[0160] In some embodiments, the polymer may act as an excipient that stabilizes the therapeutically active ingredient. In some embodiments, the polymer may form the structure of the microneedle. In some embodiments, the polymer may act both as an excipient that stabilizes the therapeutically active ingredient and as a polymer that forms the structure of the microneedle.

[0161] In some embodiments, a method of manufacturing a dissolvable microneedle patch comprising a biodegradable polymer, the biodegradable polymer being capable of providing an 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 methacrylate. In further embodiments, the immediate release biodegradable polymer releases the therapeutically active ingredient within about 0 hours 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 time scale of about 0 hours to about 24 hours. In some embodiments, the immediate release biodegradable polymer releases about 100% of the therapeutically active ingredient over a time scale of about 0 hours to about 24 hours. In some embodiments, the immediate release biodegradable polymer releases 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 100%, about 90% to about 95%, about 95% to about 100%, or values ​​within these ranges of the therapeutically active ingredient on a time scale of about 0 hours to about 24 hours. Specific examples include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, about 100%, or ranges between any two of these values.

[0162] 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. 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 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 7 hours, about 1 hour to about 6 hours, about 1 hour to about 5 hours, about 1 hour ~ 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 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, about 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 0 minutes to about 4 minutes, about 0 minutes to about 3 minutes, about 0 minutes to about 5 minutes ...5 minutes, about 0 minutes to about 4 minutes, about 0 minutes to about 3 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 5 minutes, about 0 minutes to about 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 5 minutes to about 10 minutes, about 10 minutes to about 60 minutes, about 10 minutes to about 50 minutes, about 10 minutes to about 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 The therapeutically active ingredient is released within about 15 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, about 30 minutes to about 35 minutes, about 45 minutes to about 60 minutes, about 45 minutes to about 50 minutes, or a value within these ranges. Specific examples may 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.

[0163] In some embodiments, a method of manufacturing a dissolvable microneedle patch comprising a biodegradable polymer, said biodegradable polymer being 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 (poly(lactic-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 until more than about 24 hours after insertion of the microneedle patch into the skin. In some embodiments, the sustained release biodegradable polymer provides a sustained release biodegradable polymer that is capable of delivering a therapeutically effective amount of glycerol to the tissue of the subject by 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% for a period of more than about 24 hours. , about 80% to about 85%, about 85% to about 100%, about 85% to about 99%, about 85% to about 95%, about 85% to about 90%, about 90% to about 100%, about 90% to about 99%, about 90% to about 95%, about 95% to about 100%, about 95% to about 99%, about 99% to about 100%, or values ​​within these ranges of the therapeutically active ingredient. Specific examples may include about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, and about 100%.

[0164] In some embodiments, the sustained release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 to about 30 days. In some embodiments, the sustained release biodegradable polymer releases the therapeutically active ingredient over a period of about 2 to about 21 days. In some embodiments, the sustained release biodegradable polymer releases the therapeutically active ingredient over a period of about 1 to about 30 days, about 1 to about 28 days, about 1 to about 26 days, about 1 to about 24 days, about 1 to about 22 days, about 1 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 days to about 22 days, about 2 days to about 21 days, about 2 days to about 14 days, about 2 days to about 7 days, about 2 days to about 6 days, about 2 days to about 5 days, about 2 days to about 4 days, about 2 days to about 3 days, about 3 days to about 30 days, about 3 days to about 28 days, about 3 days to about 26 days, about 3 days to about 24 days, about 3 days to about 22 days, about 3 days to about 21 days, about 3 days to about 14 days, about 3 days to about 7 days, about 3 days to about 6 days, about 3 days to about 5 days, about 3 days to about 4 days, about 4 days to about 30 days, about 4 days to about 28 days, about 4 days to about 26 days, about 4 days to about 24 days, about 4 days to about 22 days, about 4 days to about 21 days, about 4 days to about 14 days, about 4 days to about 7 days, about 4 days to about 6 days, about 4 days to about 5 days, about 5 days to about 30 days, about 5 days to about 28 days, about 5 days to about 26 days, about 5 days to about 24 days, about 5 days to about 22 days, about 5 days to about 21 days, about 5 days to about 14 days, about 5 days to about 7 days, about 5 days to about 6 days, about 7 days to about 30 days, about 7 days to about 28 days, about 7 days to about 2 The therapeutic activity is released for 6 days, 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 values ​​within these ranges. Specific examples may 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.

[0165] In some embodiments, a method of manufacturing a dissolvable microneedle patch comprising a biodegradable polymer, said 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 portion of the microneedles ...

[0166] In some embodiments, in a method of manufacturing a dissolvable microneedle patch for treating a skin condition, the method of treating the skin condition comprises applying a dissolvable microneedle patch, the dissolvable microneedle patch being 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.

[0167] In some embodiments, a method of manufacturing a dissolvable microneedle patch comprising a plurality of microneedles, said plurality of microneedles being spatially separated within the skin such that no one microneedle touches another microneedle. In some embodiments, the dissolvable microneedle patch comprises a plurality of microneedles, the microneedle patch having 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 1 to about 125 microneedles per square centimeter, about 1 to about 100 microneedles per square centimeter, about 1 to about 90 microneedles per square centimeter, about 1 to about 80 microneedles per square centimeter, about 1 to about 70 microneedles per square centimeter, about 1 to about 60 microneedles per square centimeter, about 1 to about 50 microneedles per square centimeter, about 1 to about 40 microneedles per square centimeter, about 1 to about 30 microneedles per square centimeter, about 1 to about 20 microneedles per square centimeter, about 1 to about 20 microneedles per square centimeter, about 1 to about 30 microneedles per square centimeter, about 1 to about 40 microneedles per square centimeter, about 1 to about 5 ...50 microneedles per square centimeter, about 1 to about 60 microneedles per square centimeter, about 1 to about 70 microneedles per square centimeter, about 1 to about 80 microneedles per square centimeter, about 1 to about 90 microneedles per square centimeter, about 1 to about 90 microneedles per square centimeter, about 1 to about 100 microneedles per square centimeter, about 1 to about about 1 to about 25 microneedles per square centimeter, about 1 to about 20 microneedles per square centimeter, 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 20 ... 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, about 10 to about 100 microneedles per square centimeter, about 10 to about 90 microneedles per square centimeter, about 10 to about 80 microneedles per square centimeter, about 10 to about 70 microneedles per square centimeter, about 10 to about 60 microneedles per square centimeter, ... about 50 microneedles, about 10 to about 40 microneedles per square centimeter, about 10 to about 30 microneedles per square centimeter, about 10 to about 25 microneedles per square centimeter, about 10 to about 20 microneedles per square centimeter, 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 black needles, 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 60 microneedles per square centimeter, about 25 to about 50 microneedles per square centimeter, about 25 to about 40 microneedles per square centimeter,about 25 to about 30 microneedles per square centimeter, about 50 to about 200 microneedles per square centimeter, about 50 to about 175 microneedles per square centimeter, about 50 to about 150 microneedles per square centimeter, about 50 to about 125 microneedles per square centimeter, about 50 to about 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 per square centimeter, 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 100 to 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, said 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 125 microneedles per square centimeter, at least about 100 microneedles per square centimeter, at least about 90 microneedles per square centimeter, at least about 80 microneedles per square centimeter, at least about 70 microneedles per square centimeter, at least about 60 microneedles per square centimeter, at least about 50 microneedles per square centimeter, at least about 40 microneedles per square centimeter, at least about 30 microneedles per square centimeter microneedles, at least about 25 microneedles per square centimeter, at least about 20 microneedles per square centimeter, at least about 15 microneedles per square centimeter, at least about 10 microneedles per square centimeter, at least about 5 microneedles per square centimeter, at least about 4 microneedles per square centimeter, at least about 3 microneedles per square centimeter, at least about 2 microneedles per square centimeter, at least about 1 microneedle per square centimeter, or a range between any two of these values.

[0168] In some embodiments, a method of manufacturing a dissolvable microneedle patch, 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 n sides, where n ranges 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 1 0 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, about 10 ~60 sides, ~50 sides, ~40 sides, ~30 sides, ~10 sides, ~20 sides, ~1000 sides, ~900 sides, ~800 sides, ~700 sides, ~600 sides, ~500 sides, ~400 sides, ~300 sides, ~20 sides, ~200 sides, ~100 sides, ~90 sides, ~80 sides, ~70 sides, ~600 sides, ~500 sides, ~400 sides, ~300 sides, ~20 sides, ~100 sides, ~90 sides, ~80 sides, ~70 sides, ~60 sides, ~50 sides, ~20 sides sides to about 40 sides, about 20 sides to about 30 sides, about 30 sides to about 1000 sides, about 30 sides to about 900 sides, about 30 sides to about 800 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 sides, about 50 sides to about 900 sides,About 50 sides to about 800 sides, about 50 sides to about 700 sides, about 50 sides to about 600 sides, about 50 sides to about 500 sides, about 50 sides to about 400 sides, about 50 sides to about 300 sides, about 50 sides to about 200 sides, about 50 sides to about 100 sides, about 50 sides to about 90 sides, about 50 sides to about 80 sides, about 50 sides to about 70 sides, about 50 sides to about 60 sides, about 75 sides to about 1000 sides, about 75 sides to about 90 0 sides, about 75 sides to about 800 sides, about 75 sides to about 700 sides, about 75 sides to about 600 sides, about 75 sides to about 500 sides, about 75 sides to about 400 sides, about 75 sides to about 300 sides, about 75 sides to about 200 sides, about 75 sides to about 100 sides, about 75 sides to about 90 sides, about 75 sides to about 80 sides, about 100 sides to about 1000 sides, about 100 sides to about 900 sides, about 100 sides to about 800 sides, Approximately 100 sides to approximately 700 sides, approximately 100 sides to approximately 600 sides, approximately 100 sides to approximately 500 sides, approximately 100 sides to approximately 400 sides, approximately 100 sides to approximately 300 sides, approximately 100 sides to approximately 200 sides, approximately 250 sides to approximately 1000 sides, approximately 250 sides 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 to approximately 500 sides, approximately 25 It has 0 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 700 sides, about 500 sides to about 600 sides, about 750 sides to about 1000 sides, about 750 sides to about 900 sides, about 750 sides to about 800 sides, about 900 sides to about 1000 sides, or values ​​within these ranges. Specific examples may include dissolvable microneedle patches having 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 these two values.

[0169] In some embodiments, the method of manufacturing a dissolvable microneedle patch, the dissolvable microneedle patch can have sides of equal length. In further embodiments, the dissolvable microneedle patch can 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 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 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 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, about 0.1 square centimeters to about 0.6 square centimeters, about 0.1 square centimeters to about 0.5 square centimeters,About 0.1 square centimeters to about 0.4 square centimeters, about 0.1 square centimeters to about 0.3 square centimeters, about 0.1 square centimeters to about 0.2 square centimeters, about 0.5 square centimeters to about 1000 square centimeters, about 0.5 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 500 square centimeters centimeters, about 0.5 square centimeters to about 400 square centimeters, about 0.5 square centimeters to about 300 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 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, about 0.5 square centimeters to about 4 square centimeters, about 0.5 square centimeters to about 3 square centimeters, about 0.5 square centimeters to about 2 square centimeters, about 0.5 square centimeters to about 1 square centimeter torr, about 0.5 square centimeters to about 0.9 square centimeters, about 0.5 square centimeters to about 0.8 square centimeters, about 0.5 square centimeters to about 0.7 square centimeters, about 0.5 square centimeters to about 0.6 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 about 100 square centimeters, about 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 1000 square centimeters, about ... About 900 square centimeters, about 10 square centimeters to about 800 square centimeters, about 10 square centimeters to about 700 square centimeters, about 10 square centimeters to about 600 square centimeters, about 10 square centimeters to about 500 square centimeters, about 10 square centimeters to about 400 square centimeters, about 10 square centimeters to about 300 square centimeters, about 10 square centimeters to about 200 square centimeters, about 10 square centimeters to about 100 square centimeters, about 10 square centimeters to about 90 Square centimeters, about 10 square centimeters to about 80 square centimeters, about 10 square centimeters to about 70 square centimeters, about 10 square centimeters to about 60 square centimeters, about 10 square centimeters to about 50 square centimeters, about 10 square centimeters to about 40 square centimeters, about 10 square centimeters to about 30 square centimeters, about 10 square centimeters to about 20 square centimeters, about 50 square centimeters to about 1000 square centimeters, about 50 square centimeters to about 900 square centimeters,About 50 square centimeters to about 800 square centimeters, about 50 square centimeters to about 700 square centimeters, about 50 square centimeters to about 600 square centimeters, about 50 square centimeters to about 500 square centimeters, about 50 square centimeters to about 400 square centimeters, 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 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, about 75 square centimeters to about 200 square centimeters, about 75 square centimeters to about 100 square centimeters, about 100 square centimeters 1000 square centimeters, 100 square centimeters to 900 square centimeters, 100 square centimeters to 800 square centimeters, 100 square centimeters to 700 square centimeters, 100 square centimeters to 600 square centimeters, 100 square centimeters to 500 square centimeters, 100 square centimeters to 400 square centimeters, 100 square centimeters to 300 square centimeters, 100 square centimeters to 200 square centimeters, 250 square centimeters 250 square centimeters to about 1000 square centimeters, about 250 square centimeters to about 900 square centimeters, about 250 square centimeters to about 800 square centimeters, about 250 square centimeters to about 700 square centimeters, about 250 square centimeters to about 600 square centimeters, about 250 square centimeters to about 500 square centimeters, about 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,The size may be 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 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 c...

Claims

Claim 1 A dissolvable microneedle patch for delivering a therapeutically active ingredient to the skin, comprising a plurality of microneedles, a removable substrate, and wherein the plurality of microneedles are attached to the removable substrate, the plurality of microneedles include a tapered tip portion extending away from the removable substrate, the plurality of microneedles include a biodegradable polymer and a therapeutically active ingredient dispersed in the biodegradable polymer, and the therapeutically active ingredient is an antigen composition containing less than 50% glycerol, a dissolvable microneedle patch. Claim 2 The dissolvable microneedle patch according to claim 1, wherein the plurality of microneedles include an excipient for stabilizing the antigen composition, a dissolvable microneedle patch. Claim 3 In the dissolvable microneedle patch according to claim 2, the excipient is lactose, sucrose, glucose, mannitol, sorbitol, trehalose, fructose, galactose, dextrose, xylitol, maltitol, raffinose, dextran, maltodextrin, cyclodextrin, collagen, glycine, histidine, calcium carbonate, magnesium stearate, serum albumin (derived from human and / or animal), gelatin, chitosan, deoxyribonucleic acid (DNA), hyaluronic acid, polyvinylpyrrolidone, polyvinyl alcohol, polylactic acid (PLA), polyglycolic acid (PGA), polyactidecoglycolic acid (PLGA), polyethylene glycol (PEG, PEG300, PEG400, PEG600, PEG3350, PEG4000), cellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, acacia, lecithin, polysorbate 20, polysorbate 80, pluronic F-68, sorbitan trioleate (span85), EDTA, hydroxypropylcellulose, sodium chloride, sodium phosphate, ammonium acetate, potassium phosphate, sodium citrate, sodium hydroxide, sodium carbonate, tris base-65, tris acetate, tris HCl-65, citrate buffer, talc, silica, fat, methylparaben, propylparaben, selenium, vitamins (A, E, C, retinyl palmitate, and, selenium), amino acids (methionine, cysteine, arginine), citric acid, sodium citrate, benzyl alcohol, chlorobutanol, cresol, phenol, thimerosal, acetone, sodium bisulfate, ascorbyl palmitate, ascorbate, castor oil, cottonseed oil, alum, aluminum hydroxide, aluminum phosphate, calcium hydrogen phosphate, paraffin oil, squalene, Quil A, IL-1, IL-2, IL-12, Freund's complete adjuvant, Freund's incomplete adjuvant, killed Bordetella pertussis, bovine tuberculosis bacteria, and at least one selected from toxoids, a dissolvable microneedle patch.

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

5. The dissolvable microneedle patch according to claim 1, wherein the plurality of microneedles each contain substantially the same amount of the therapeutically active ingredient, a dissolvable microneedle patch.

6. The dissolvable microneedle patch according to claim 1, wherein the plurality of microneedles each contain unequal amounts of the therapeutically active ingredient, a dissolvable microneedle patch.

7. The dissolvable microneedle patch according to claim 1, wherein the antigen composition comprises an antigen selected from the group consisting of Candida antigen, Trichophyton antigen, tuberculin, Corynebacterium parvum, Cutibacterium acnes, and Mycobacterium indicus pranii (formerly Mycobacterium w), imiquimod, human papillomavirus vaccine, measles, mumps, and rubella vaccine, mumps vaccine, Bacillus Calmette-Guerin vaccine, and Mycobacterium w vaccine, a dissolvable microneedle patch.

8. The dissolvable microneedle patch according to claim 1, wherein the antigen composition comprises a Candida antigen, a dissolvable microneedle patch.

9. The immunostimulatory protein according to claim 8, wherein the antigen composition comprising a Candida antigen is substantially free of glycerol, an immunostimulatory protein.

10. The Candida antigen according to claim 9, wherein the antigen composition comprising a Candida antigen is lyophilized, a Candida antigen.

11. The dissolvable microneedle patch according to claim 1, wherein the antigen composition is substantially free of glycerol, a dissolvable microneedle patch.

12. The dissolvable microneedle patch according to claim 1, wherein the antigen composition contains less than about 10% glycerol, a dissolvable microneedle patch.

13. The dissolvable microneedle patch according to claim 1, wherein the plurality of microneedles are configured to have sustained release of a therapeutically active ingredient into the skin, the dissolvable microneedle patch.

14. The sustained release microneedle according to claim 13, which is configured to have release of a therapeutically active ingredient into the skin for about 1 day to about 30 days after application of the dissolvable microneedle patch, the sustained release microneedle.

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

16. The immediate release microneedle according to claim 15, which is configured to have immediate release of a therapeutically active ingredient into the skin for about 0 hours to about 24 hours after application of the dissolvable microneedle patch, the immediate release microneedle.

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

18. The dissolvable microneedle patch according to claim 1, wherein the removable substrate contains a therapeutically active ingredient dispersed in a polymer, the dissolvable microneedle patch.

19. The dissolvable microneedle patch according to claim 1, which administers a therapeutically effective amount of a Candida antigen to a subject in need thereof, the dissolvable microneedle patch.

20. The dissolvable microneedle patch according to claim 1, wherein the therapeutically active ingredient stimulates a local immune response, the dissolvable microneedle patch.

21. A dissolvable microneedle patch for use in the treatment of a skin condition, i) the dissolvable microneedle patch is applied to deliver a therapeutically active ingredient to the skin, the dissolvable microneedle patch comprising a plurality of microneedles and a removable substrate, wherein the plurality of microneedles are attached to the removable substrate, and the plurality of microneedles include a tapered tip portion extending away from the removable substrate. ​ The plurality of microneedles comprise a biodegradable polymer and a therapeutically effective ingredient dispersed in the biodegradable polymer, and, the therapeutically effective ingredient is an antigen composition containing less than 50% glycerol, ii) the microneedles are capable of penetrating to a position selected from the group consisting of the epidermis, dermis, and dermal papillary layer when sufficient force is applied to the dissolvable microneedle patch, iii) the plurality of microneedles remain in the skin until the biodegradable polymer degrades, A dissolvable microneedle patch.

22. In the dissolvable microneedle patch according to claim 21, at least 90% of the plurality of microneedles peel off from the removable substrate within about 20 minutes after application of the dissolvable microneedle patch. A dissolvable microneedle patch.

23. In the dissolvable microneedle patch according to claim 21, the biodegradable polymer degrades to release a therapeutically effective ingredient into the skin. A dissolvable microneedle patch.

24. In the dissolvable microneedle patch according to claim 21, the biodegradable polymer degrades over a period of about 1 day to about 30 days to release a therapeutically effective ingredient into the skin. A dissolvable microneedle patch.

25. A method for treating a skin condition, comprising: i) a step of applying a dissolvable microneedle patch for delivering a therapeutically effective ingredient to the skin, the dissolvable microneedle patch comprising: a plurality of microneedles and a removable substrate, wherein the plurality of microneedles are attached to the removable substrate, the plurality of microneedles include a tapered tip portion extending away from the removable substrate, the plurality of microneedles comprise a biodegradable polymer and a therapeutically effective ingredient dispersed in the biodegradable polymer, and, the therapeutically effective ingredient is an antigen composition containing less than 50% glycerol, the step of applying; ii) a step of applying sufficient force to the dissolvable microneedle patch to enable the microneedles to penetrate to a position selected from the group consisting of the epidermis, dermis, and dermal papillary layer. ​ iii) A step of leaving the plurality of microneedles on the skin until the biodegradable polymer decomposes; iv) A step of removing the adhesive substrate from the patch composition; A method comprising the above steps.

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