Composition for the treatment of skin conditions

Abstract

The present disclosure relates to the treatment of a skin condition of a subject, including hyperhidrosis, without limitation, comprising the step of applying a first composition derived from one or more sponges and a second composition comprising one or more botulinum toxins to the skin of a subject. Additionally, the present disclosure provides a composition for use in the treatment of a skin condition of a subject, including hyperhidrosis, without limitation, comprising the first composition and the second composition, wherein (a) the first composition comprises Spongilla; and (b) the second composition comprises one or more botulinum toxins. Additionally, the present disclosure provides a kit for the treatment of a skin condition of a subject, including hyperhidrosis, without limitation, comprising the first composition and the second composition, wherein the first composition comprises Spongilla and the second composition comprises one or more botulinum toxins.

Description

Technology Field

[0001] Cross-reference

[0002] The present application claims the benefit of priority from U.S. Provisional Application No. 62 / 684,699 filed June 13, 2018; U.S. Provisional Application No. 62 / 788,628 filed January 4, 2019; and U.S. Provisional Application No. 62 / 838,801 filed April 25, 2019, all of which are incorporated herein by reference in their entirety.

[0003] field

[0004] The present disclosure relates to the treatment of a skin condition in a subject, including, without limitation, hyperhidrosis, comprising the step of applying a first composition derived from one or more sponges and a second composition comprising one or more botulinum toxins to the skin of the subject. In one aspect, the composition is derived from one or more sponges. In another aspect, one or more sponges may be seawater sponges or freshwater sponges. In another aspect, one or more sponges are seawater sponges. In another aspect, the sponges are freshwater sponges. In another aspect, the composition is Polypera ( Porifera It originates from the sponge of the ) inquiry. In another aspect, the composition is to the demospongia ( Demospongiae It is derived from the sponges of the ) river. In another aspect, the composition is Spongedilla ( Spongdilla It is derived from the sponge of the neck. In another aspect, the composition is to ( Spongillidae It is derived from a sponge of ). In another aspect, the composition is Spongilla ( Spongilla It is derived from a sponge of the genus ). In another aspect, the composition is Spongilla lacustris ( Spongilla lacustris It originates from sponges of the ) species. In another aspect, the composition is Haploscraridae ( Haplosclerida It is derived from the sponge of the neck. In another aspect, the composition is Callinidea ( ChalinideaIt is derived from a sponge of ). In another aspect, the composition is Halciona ( Halciona It originates from the sponge inside.

[0005] The present disclosure describes a sponge ( Spongilla The present disclosure relates to the treatment of a skin condition in a subject, including, but not limited to, hyperhidrosis, comprising the step of applying a first composition comprising a sponge, and a second composition comprising one or more botulinum toxins. The present disclosure also relates to a product or kit for the treatment of a skin condition in a subject, including, but not limited to, hyperhidrosis, comprising a first composition comprising a sponge and a second composition comprising one or more botulinum toxins. The present disclosure also relates to a first composition comprising a sponge for use in a method for treating a skin disease or condition in a subject requiring treatment, including, but not limited to, hyperhidrosis, wherein the method comprises the step of administering to the subject an effective amount of the first composition in combination with an effective amount of the second composition, and the second composition comprises one or more botulinum toxins. Background Technology

[0006] Skin conditions in subjects, including human subjects, such as acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, post-herpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, dyshidrosis of the legs, congenital onychomycosis, hydrokeratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, and eccrine nevus can be difficult to treat. In some cases, topical treatment of these skin conditions is successful, but the proper use of topical therapy is often more complex than that of oral therapy, and adherence to topical therapy can be a particularly important issue. Insufficient subject compliance with therapeutic regimens using topical methods, the development of drug resistance, and increased costs can be causes of treatment failure. Therefore, methods to treat these skin conditions in subjects using topical products with a simple application paradigm, such as once-weekly application, will have the opportunity to demonstrate greater treatment success due to improved subject compliance.

[0007] Numerous skin conditions in subjects have been treated with the topical application of materials derived from naturally occurring sponges, such as *Sponzilla lacustris*. Some materials derived from *Sponzilla* are promoted for the treatment of certain skin conditions, such as acne vulgaris, and as cosmetics. *Sponzilla* contains organic and inorganic compounds. The total lipid content is approximately 5% of the dry sponge biomass, and the proteins consist of spongin or hardened collagen. Polysaccharides and N-acetyl-D-glucosamine (NAG) are part of chitosan and chitin, which have been reported to be important components within the skeletal fibers of *Sponzilla lacustris*, and 750 ± 1.5 µg of N-acetyl-D-glucosamine is detected per 1 mg of non-spinous skeleton. Chitin and chitosan are described as a family of linear polysaccharides composed of varying amounts of α or β (1-4) linked N-acetyl-2-amino-2-deoxy-D-glucose residues and 2-amino-2-deoxy-D-glucose residues. In α-chitin, chains are arranged in sheets or stacks, and the chains of any one sheet have the same orientation or 'sense'. In β-chitin, adjacent sheets along the c-axis have the same orientation; the sheets are parallel, whereas in α-chitin, adjacent sheets along the c-axis have opposite orientations, so they are antiparallel. Chitin can be deacetylated into chitosan and further broken down into N-acetyl-D-glucosamine (NAG) units. Chitosan preparations are classified into natural chitosan, chitosan formulations, complexes with other substances, and derivatives. Chitosan can be used to prevent or treat wound and burn infections due to its inherent antimicrobial properties as well as its ability to deliver foreign antimicrobial agents to wounds and burns. Chitosan is highly viscous and water-insoluble in diluted acidic solutions. Soluble chitosan oligosaccharides have been identified as important in suppressing LPS-induced nuclear factor kappa-light chain enhancer (NF-κB)-dependent inflammatory gene expression in activated B cells, which was associated with reduced nuclear translocation of NF-κB. Chitosan also P. Acnes ( P. acnes ) and S. Aureus ( S. aureus It has been proven to have an antimicrobial effect against ). As chitosan of different molecular weights (WM), antibacterial activity was tested with low MW (50-190 kDa), medium MW (190-310 kDa), and high MW (310-375+ kDa) chitosan. Concentrations of 2.5, 5, 10, and 20 µg / mL were tested against P. acnes, and in clinical studies, NAG reduced the number of acne lesions over an 8-week period in subjects with acne vulgaris, and high molecular weight has a much greater effect against Gram-positive bacteria P. acnes, as demonstrated by the fact that subjects tolerated it better than 10% benzoyl peroxide.

[0008] Hyperhidrosis is a disorder characterized by excessive sweating that exceeds the proportion required for thermoregulation. While many individuals may exhibit this excessive sweating in response to specific triggers (e.g., emotional stress), others may present with symptoms spontaneously. The diagnosis of hyperhidrosis is based in part on subjective measurements of how excessive sweating affects the individual's quality of life. Although the amount of sweat secreted can be measured by weight, there is no standard threshold that defines hyperhidrosis. Hyperhidrosis can be classified as localized (affecting a specific area, e.g., the palms or armpits) or generalized (affecting the entire body). Hyperhidrosis can be secondary to a wide variety of medical conditions, typically manifesting as generalized hyperhidrosis. In contrast, primary hyperhidrosis is idiopathic and generally manifests as localized sweating, most frequently occurring in the armpits (51%), soles (30%), palms (24%), and face (10%). Primary localized axillary hyperhidrosis is not uncommon. In the United States, the prevalence is estimated at 2.8% of the population, which is similar to that of psoriasis. Two-thirds of affected individuals do not seek medical treatment because conventional treatments are generally ineffective and the social embarrassment is significant. However, hyperhidrosis carries a high disease burden, primarily due to its effects on the subject's quality of life and psychosocial well-being, and can also lead to bacterial and fungal overgrowth. Although primary hyperhidrosis is idiopathic, the mechanism is believed to involve neurogenic overactivation of the eccrine glands in the affected area. This hypothesis regarding the mechanism is supported by the clinical effects confirmed by botulinum toxin type A, which significantly reduced axillary sweating over a period of 4 to 12 months by acting to disrupt sympathetic stimulation of the eccrine glands. However, the volumetric effects and skin penetration resulting from botulinum toxin treatment cause injection site pain.Given the properties of the target tissue, injection site pain is considered a major cause of lack of compliance, especially when large volumes of injection must be administered to sensitive skin areas, such as the armpit. Therefore, topical products with a simple application paradigm that enables the penetration of botulinum toxin through the stratum corneum into the dermis can exhibit greater compliance and acceptance due to improved therapeutic tolerability.

[0009] The inventors of the subject matter of the present disclosure have discovered that the main component of a material derived from Spongilla is a siliceous spicule comprising the skeletal structure of Spongilla. The inventors have discovered that the spicule penetrates the stratum corneum of the subject's skin during application and promotes the abscission of keratinocytes. The inventors of the subject matter disclosed herein have also discovered that the spicule derived from Spongilla is useful for facilitating and allowing certain therapeutic compounds and compositions to penetrate the skin of the subject to which the spicule is applied, otherwise these compounds and compositions would not be able to penetrate the subject's skin to reach their therapeutic targets and treat certain skin conditions. Among the compounds and compositions that can penetrate the skin better in the presence of a material derived from Spongilla are products containing botulinum toxin.

[0010] Products containing botulinum toxin have been proven useful in the treatment of numerous medical conditions, including those affecting the skin of subjects. For example, products containing botulinum toxin have been approved for the treatment of subjects suffering from hyperhidrosis (excessive sweating). There are also reports that the topical application of products containing botulinum toxin may be useful in the treatment of subjects suffering from acne (see, for example, U.S. Patent No. 7,226,605). However, the difficulties in using one or more products containing botulinum toxin for the topical treatment of skin conditions in subjects are well known. One of the difficulties in the topical use of botulinum toxin-containing products is Clostridium botulinum ( Clostridium botulinum It is recognized that endogenous non-toxic proteins (i.e., non-toxic hemagglutinin and non-hemagglutinin proteins) among botulinum toxin complexes obtained from bacteria reduce the ability of toxins to spread through the skin epithelium. These effects may be further exacerbated when exogenous stabilizers, such as albumin, are bound to botulinum toxin during the usual manufacturing process. Therefore, the application of a composition containing Spongilla, for example in powder form, to the skin of a subject helps facilitate the penetration of a topical product containing one or more botulinum toxins into the subject's skin, sometimes leading to the use of a new therapeutic regimen because it is difficult to treat skin conditions.

[0011] In one aspect, a method for treating a skin condition in a subject is provided, comprising the step of applying a first composition containing a sponge and a second composition containing one or more botulinum toxins to the skin of a subject.

[0012] In one aspect, a method for treating a skin condition in a subject is provided, comprising the step of applying a first composition comprising one or more sponges and a second composition comprising one or more botulinum toxins to the skin of a subject. In one aspect, the composition is derived from one or more sponges. In another aspect, one or more sponges may be saltwater sponges or freshwater sponges. In another aspect, one or more sponges are saltwater sponges. In another aspect, the sponges are freshwater sponges. In another aspect, the composition is derived from a sponge of the Polypera phylum. In another aspect, the composition is derived from a sponge of the Demospongiae phylum. In another aspect, the composition is derived from a sponge of the Spongodiala order. In another aspect, the composition is derived from a sponge of the Spongiladae genus. In another aspect, the composition is derived from a sponge of the Spongila genus. In another aspect, the composition is derived from a sponge of the Spongila lacoustris genus. In another aspect, the composition is derived from a sponge of the Haploscriladales order. In another aspect, the composition is derived from a sponge of the Callinidea genus. In another aspect, the composition is derived from a sponge of the genus Halciona.

[0013] In one aspect, a method for treating a skin condition in a subject is provided, comprising the step of applying a first composition comprising one or more sponges and a second composition comprising one or more botulinum toxins to the skin of a subject, wherein (a) the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G; (b) The skin conditions in the subject are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, one or more sponges may be seawater sponges or freshwater sponges. In another aspect, one or more sponges are seawater sponges. In another aspect, the sponge is a freshwater sponge. In another aspect, the composition is derived from a sponge of the Polypera claudication. In another aspect, the composition is derived from a sponge of the Demospongiae class. In another aspect, the composition is derived from a sponge of the Spongodiala order. In another aspect, the composition is derived from a sponge of the Spongiladae family. In another aspect, the composition is derived from a sponge of the genus Sponzilla. In another aspect, the composition is derived from a sponge of the species Sponzilla lacustris. In another aspect, the composition is derived from a sponge of the Haploscraridae order. In another aspect, the composition is derived from a sponge of the family Callinidea. In another aspect, the composition is derived from a sponge of the genus Halciona.

[0014] In one aspect, a method for treating a skin condition in a subject is provided, comprising the step of applying a first composition and a second composition to the skin of a subject, wherein (a) the first composition comprises one or more sponges; and (b) the second composition comprises one or more types of botulinum toxin selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E; (c) The skin conditions in the subject are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In other aspects, one or more sponges may be seawater sponges or freshwater sponges. In other aspects, one or more sponges are seawater sponges. In other aspects, the sponge is a freshwater sponge. In other aspects, the composition is derived from a sponge of the Polypera claudication. In another aspect, the composition is derived from a sponge of the Demospongiae class. In another aspect, the composition is derived from a sponge of the Spongodiala order. In another aspect, the composition is derived from a sponge of the Spongiladae family. In another aspect, the composition is derived from a sponge of the genus Sponzilla. In another aspect, the composition is derived from a sponge of the species Sponzilla lacustris. In another aspect, the composition is derived from a sponge of the Haploscraridae order. In another aspect, the composition is derived from a sponge of the family Callinidea. In another aspect, the composition is derived from a sponge of the genus Halciona.

[0015] In another aspect, a kit comprising a first composition and a second composition is provided, wherein (a) the first composition comprises one or more sponges; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a kit comprising a first composition and a second composition is provided, wherein (a) the first composition comprises Spongilla; and (b) the second composition comprises one or more botulinum toxins, and the kit is used for the treatment of a skin condition in a subject. In another aspect, a kit comprising a first composition and a second composition is provided, wherein (a) the first composition comprises Spongilla; and (b) the second composition comprises one or more botulinum toxins, and the kit is intended for use in the treatment of a skin condition in a subject. In another aspect, a kit as described in this specification is provided, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, post-herpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratoderma, paresthetic back pain, dyshidrosis (hyperhidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, one or more sponges may be seawater sponges or freshwater sponges. In another aspect, one or more sponges are seawater sponges. In another aspect, the sponge is a freshwater sponge. In another aspect, the composition is derived from a sponge of the Polypera phylum. In another aspect, the composition is derived from a sponge of the Demospongiae phylum. In another aspect, the composition is derived from a sponge of the Spongodiala order. In another aspect, the composition is derived from a sponge of the Spongiladae genus. In another aspect, the composition is derived from a sponge of the Sponzilla genus. In another aspect, the composition is derived from a sponge of the Sponzilla lacoustris genus.In another aspect, the composition is derived from a sponge of the Haploscraridae order. In another aspect, the composition is derived from a sponge of the Callinidea family. In another aspect, the composition is derived from a sponge of the Halciona genus.

[0016] In another aspect, a composition comprising a first composition and a second composition for use as a drug is provided, wherein (a) the first composition comprises one or more sponges; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a composition comprising a first composition and a second composition for use as a drug is provided, wherein (a) the first composition comprises Spongilla lacustris; and (b) the second composition comprises one or more botulinum toxins. In another aspect, such composition is provided for use as a drug for the treatment of skin conditions in a subject. Another aspect is that this combination is used as a drug for the treatment of a skin condition in a subject, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, dermatophytosis of the legs, congenital onychomycosis, hydrogenic keratoderma, paresthetic back pain, dyshidrosis (hyperhidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, one or more sponges may be saltwater sponges or freshwater sponges. In another aspect, one or more sponges are saltwater sponges. In another aspect, the sponge is a freshwater sponge. In another aspect, the composition is derived from a sponge of the Polypera phylum. In another aspect, the composition is derived from a sponge of the Demospongiae phylum. In another aspect, the composition is derived from a sponge of the Spongodiala order. In another aspect, the composition is derived from a sponge of the Spongilidae genus. In another aspect, the composition is derived from a sponge of the Sponzilla genus. In another aspect, the composition is derived from a sponge of the Sponzilla lacoustris genus. In another aspect, the composition is derived from a sponge of the Haploscraridae order.In another aspect, the composition is derived from a sponge of the family Callinidea. In another aspect, the composition is derived from a sponge of the genus Halciona.

[0017] In another aspect, a composition comprising a first composition and a second composition for use in the treatment of a skin condition in a subject is provided, wherein (a) the first composition comprises one or more sponges; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a combination of a first composition and a second composition for use in the treatment of a skin condition in a subject is provided, wherein (a) the first composition comprises a sponge; and (b) the second composition comprises one or more botulinum toxins. Another aspect is this composition for use in the treatment of skin conditions in a subject, wherein the skin conditions in the subject are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, post-herpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (hyperhidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, one or more sponges may be seawater sponges or freshwater sponges. In another aspect, one or more sponges are seawater sponges. In another aspect, the sponge is a freshwater sponge. In another aspect, the composition is derived from a sponge of the Polypera phylum. In another aspect, the composition is derived from a sponge of the Demospongiae phylum. In another aspect, the composition is derived from a sponge of the Spongodiala order. In another aspect, the composition is derived from a sponge of the Spongilidae genus. In another aspect, the composition is derived from a sponge of the Sponzilla genus. In another aspect, the composition is derived from a sponge of the Sponzilla lacoustris genus. In another aspect, the composition is derived from a sponge of the Haploscridarida order. In another aspect, the composition is derived from a sponge of the Callinidea genus. In another aspect, the composition is derived from a sponge of the Halciona genus.

[0018] In another aspect, a composition for preparing a drug for treating a skin condition in a subject is provided, the composition comprises a first composition and a second composition, wherein (a) the first composition comprises one or more sponges; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a composition for preparing a drug for treating a skin condition in a subject is provided, the composition comprises a first composition and a second composition, wherein (a) the first composition comprises Spongilla lacustris; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, post-herpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratoderma, paresthetic back pain, dyshidrosis (hyperhidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, one or more sponges may be seawater sponges or freshwater sponges. In another aspect, one or more sponges are seawater sponges. In another aspect, the sponge is a freshwater sponge. In another aspect, the composition is derived from a sponge of the Polypera phylum. In another aspect, the composition is derived from a sponge of the Demospongiae phylum. In another aspect, the composition is derived from a sponge of the Spongodiala order. In another aspect, the composition is derived from a sponge of the Spongilidae genus. In another aspect, the composition is derived from a sponge of the Sponzilla genus. In another aspect, the composition is derived from a sponge of the Sponzilla lacoustris genus. In another aspect, the composition is derived from a sponge of the Haploscreridae order. In another aspect, the composition is derived from a sponge of the Callinidea genus.In another aspect, the composition is derived from a sponge of the genus Halciona.

[0019] In one aspect, a method for treating a skin condition in a subject is provided, comprising the step of applying a first composition comprising a sponge and a second composition comprising one or more botulinum toxins to the skin of a subject, wherein (a) the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G; (b) Skin conditions in the subjects are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaign disease, dermatophytosis, congenital onychomycosis, hydrokeratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma.

[0020] A method for treating a skin condition in a subject is provided, comprising the step of applying a first composition and a second composition to the skin of a subject in one aspect, wherein (a) the first composition comprises a sponge powder; and (b) the second composition comprises one or more types of botulinum toxin selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E; (c) Skin conditions in the subjects are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaign disease, dermatophytosis, congenital onychomycosis, hydrokeratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma.

[0021] In another aspect, a kit comprising a first composition and a second composition is provided, wherein (a) the first composition comprises a sponge; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a kit comprising a first composition and a second composition is provided, wherein (a) the first composition comprises a sponge; and (b) the second composition comprises one or more botulinum toxins, and the kit is used for the treatment of a skin condition in a subject. In another aspect, a kit comprising a first composition and a second composition is provided, wherein (a) the first composition comprises a sponge; and (b) the second composition comprises one or more botulinum toxins, and the kit is intended for use in the treatment of a skin condition in a subject. In another aspect, a kit as described in the present specification is provided, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma.

[0022] In another aspect, a composition comprising a first composition and a second composition for use as a drug is provided, wherein (a) the first composition comprises Spongilla; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a composition comprising a first composition and a second composition for use as a drug is provided, wherein (a) the first composition comprises Spongilla lacustris; and (b) the second composition comprises one or more botulinum toxins. In another aspect, such composition is provided for use as a drug for the treatment of skin conditions in a subject. Another aspect is that this combination is used as a drug for treating skin conditions in subjects, and the skin conditions in subjects are selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, dermatophytosis of the legs, congenital onychomycosis, hydrokeratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma.

[0023] In another aspect, a composition comprising a first composition and a second composition for use in the treatment of a skin condition in a subject is provided, wherein (a) the first composition comprises Spongilla; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a combination of a first composition and a second composition for use in the treatment of a skin condition in a subject is provided, wherein (a) the first composition comprises Spongilla lacustris; and (b) the second composition comprises one or more botulinum toxins. Another aspect is this composition for use in the treatment of skin conditions in a subject, and the skin conditions in the subject are selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, dysphagia, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (hyperhidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma.

[0024] In another aspect, a composition for preparing a drug for treating a skin condition in a subject is provided, wherein (a) a first composition comprises Spongilla; and (b) a second composition comprises one or more botulinum toxins. In another aspect, a composition for preparing a drug for treating a skin condition in a subject is provided, wherein the composition comprises a first composition and a second composition, wherein (a) a first composition comprises Spongilla lacustris; and (b) a second composition comprises one or more botulinum toxins. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, post-herpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. Specific details for implementing the invention

[0025] The singular forms “one,” “one,” and “he” include plural references unless otherwise explicitly indicated in the context. For example, the term “one cell” includes one or more cells, including mixtures thereof. “A and / or B” is used herein by reference including all of the following alternatives: “A,” “B,” “A or B,” and “A and B.”

[0026] As used herein, the term “about” means within 10% plus or minus of the provided value, or in all cases including the provided value, rounded to the nearest significant figure. Where provided as a range, they include boundary values.

[0027] As used herein, the terms “applied,” “application step,” “administration,” “administration step,” and “used” refer to the delivery of the composition disclosed herein to a subject, in particular to the skin of the subject, through a route of administration including intraperitoneal, subcutaneous, intramuscular, topical, or any combination thereof. In some embodiments disclosed herein, the composition disclosed herein is administered to a subject, in particular to the skin of the subject, through topical administration.

[0028] As used herein, the term "aspect ratio" refers to the ratio between the average length of a particle and the average diameter of a particle for the particles of Spongilla described herein.

[0029] As used herein, the term "botulinum toxin" refers to a protein produced by Clostridium botulinum bacteria and related species. As used herein, the term "Type A botulinum toxin" refers to a protein known to those skilled in the art, also referred to as "BoNT / A" or "botA," and having representative UniProt reference numbers BXA1_CLOBH (strain Hall), BXA1_CLOBO, BXA2_CLOBO, or variants thereof. As used herein, the term "Type B botulinum toxin" refers to a protein known to those skilled in the art, also referred to as "BoNT / B" or "botB," and having representative UniProt reference number BXB_CLOBO, or variants thereof. As used herein, the term "Type C1 botulinum toxin" refers to a protein known to those skilled in the art, also referred to as "BoNT / C1," and having representative UniProt reference number BXC1_CLOBO, or variants thereof. As used herein, the term "Type C2 botulinum toxin" refers to a protein known to those skilled in the art as a protein designated as Type C2 botulinum toxin. As used herein, the term "Type D botulinum toxin" refers to a protein known to those skilled in the art as a protein also designated as "BoNT / D" or "botD," and refers to a protein having the representative UniProt reference number BXD_CLOBO or a variant thereof. As used herein, the term "Type E botulinum toxin" refers to a protein known to those skilled in the art as a protein also designated as "BoNT / E," and refers to a protein having the representative UniProt reference number BXE_CLOBO or a variant thereof. As used herein, the term "Type F botulinum toxin" refers to a protein known to those skilled in the art as a protein also designated as "BoNT / F" or "botF," and refers to a protein having the representative UniProt reference number BXF_CLOBO or a variant thereof.As used herein, the term “Type G botulinum toxin” means a protein known to those skilled in the art, also referred to as “BoNT / E” or “botG,” having the representative UniProt reference number BXG_CLOBO or a variant thereof. As used herein, the term “variant” means a protein having 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or any percentage of homology.

[0030] As used herein, the terms “concurrent” and “in combination with” mean the application, use, or administration of one or more compositions disclosed herein sequentially or simultaneously. This includes, for example, on a periodic basis on the same day or every other day or every other week or simultaneously or concurrently with it, or while administering another composition during at least a portion of the time during which the composition disclosed herein is applied, used, or administered, simultaneously or within minutes or hours of each other, or on the same day or every other day, or on a daily basis, or on a weekly basis, or on a weekly basis. For example, one or more compositions disclosed herein may be applied, used, or administered to a subject daily or several days per week, while applying, using, or administering additional compositions every other day or every other week or for other time periods, e.g., every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 days or more.

[0031] As used herein, the term "Avobotulinum Toxin A" refers to a type A botulinum toxin product approved by the FDA under BLA No. 125274.

[0032] term "Callinidea ( Chalinidea )" means one or more sponges of the Callinidea family.

[0033] The term "Doxybotulinum toxin A" refers to the doxybotulinum toxin A 150 kilodalton (kDa) purified type A botulinum toxin complex currently under development by Revance Therapeutics, Inc.

[0034] The term "demospongia" ( Demospongiae )" means one or more sponges in the lecture.

[0035] As used herein, the term "EB-001A" refers to a type E botulinum toxin product under development by Bonti, Inc. (Orange County, California).

[0036] As used herein, the term "EB-001T" refers to a type E botulinum toxin product under development by Bonti, Inc. (Orange County, California).

[0037] The term "halciona" as used in this specification ( Halciona )" means one or more sponges of the genus Halciona.

[0038] The term "haploskreda (as used in this specification Haplosclerida )" refers to one or more sponges of the haploscraridae order.

[0039] As used herein, the term "Incobotulinum toxin A" refers to a type A botulinum toxin product approved by the FDA under BLA No. 125360.

[0040] As used herein, the term “onabotulinum toxin A” refers to a type A botulinum toxin product approved by the United States Food and Drug Administration (“FDA”) under Biologics License Application (“BLA”) No. 103000.

[0041] As used herein, the term "Limabotulin Toxin B" refers to botulinum toxin type B approved by the FDA under BLA No. 103846.

[0042] The term "polypera" as used in this specification ( Porifera )" refers to one or more sponge members of the Polypera group.

[0043] The term "Frabotulinum Toxin A" refers to the Prabotulinum Toxin A 900 kilodalton (kDa) purified botulinum toxin complex of type A currently under development by Evolus, Inc. and Daewoong Pharmaceutical Co. Ltd.

[0044] The term "Sponzilla" as used in this specification ( Spongilla )" is without restriction, Spongilla Rakustris ( Spongilla lacustris ), S. Fragiles Lady ( S. fragilis Leidy ), and Epidatia pluviatilis ( Ephydatia fluviatilis Including ) in spongilida ( Spongillidae It refers to the genus of freshwater sponges. The term "Sponzilla lacustris" used in this specification refers to a species of freshwater sponge of the family Sponzillaidae.

[0045] As used herein, terms such as “composition comprising one or more sponges,” “powder comprising one or more sponges,” “material comprising one or more sponges,” “sponge in powder form,” etc., mean a material derived from one or more sponges that have been harvested and processed, and may include all organic and / or inorganic compounds and materials that are part of a naturally occurring sponge, or any sponge specifically grown or adapted for use in the disclosed composition, method, and / or kit, and may include all various components of the sponge after harvest, or may include only a portion of the organic and / or inorganic compounds and materials that are part of the naturally occurring sponge. In one aspect, any method or kit disclosed herein is provided, wherein the sponge material comprises all or substantially all organic and inorganic materials derived from a naturally occurring sponge. In other aspects, any method or kit disclosed herein is provided, wherein the sponge material comprises (a) only sigmoid and any material naturally associated with sigmoid, or (b) substantially purified sigmoid and any material naturally associated with sigmoid, or (c) purified sigmoid and any material naturally associated with sigmoid that is part of the composition of a naturally occurring sponge. In other aspects, any method or kit disclosed herein is provided, wherein the sponge material comprises only sigmoid and any material naturally associated with sigmoid. In other aspects, any method or kit disclosed herein is provided, wherein the sponge material comprises substantially purified sigmoid and any material naturally associated with sigmoid. In other aspects, any method or kit disclosed herein is provided, wherein the sponge material comprises purified sigmoid and any material naturally associated with sigmoid that is part of the composition of a naturally occurring sponge. These terms may be used herein in relation to materials derived from the Polypera phylum.In another aspect, the material is derived from a sponge of the Demospongiae River. In another aspect, the material is derived from a sponge of the Spongodiala order. In another aspect, the material is derived from a sponge of the Spongiladae family. In another aspect, the material is derived from a sponge of the genus Sponzilla. In another aspect, the material is derived from a sponge of the species Sponzilla lacustris. In another aspect, the material is derived from a sponge of the Haploscrieda order. In another aspect, the material is derived from a sponge of the family Callinidea. In another aspect, the material is derived from a sponge of the genus Halciona.

[0046] As used herein, terms such as “composition containing spongezilla,” “powder containing spongezilla,” “material containing spongezilla,” and “sponzilla in powder form” refer to a material containing spongezilla derived from raw spongezilla that has been harvested and processed, and may include all various components of the spongezilla after harvest, including all organic and / or inorganic compounds and materials that are part of the naturally occurring spongezilla, or may include only a portion of the organic and / or inorganic compounds and materials that are part of the naturally occurring spongezilla. In one aspect, any method or kit disclosed herein is provided, wherein the spongezilla material comprises all or substantially all organic and inorganic materials derived from naturally occurring spongezilla. In another aspect, any method or kit disclosed herein is provided, wherein the Spongilla material comprises (a) only an cuspidata and any material naturally associated with an cuspidata, or (b) substantially purified an cuspidata and any material naturally associated with an cuspidata, or (c) purified an cuspidata and any material naturally associated with an cuspidata that is part of the composition of naturally occurring Spongilla. In another aspect, any method or kit disclosed herein is provided, wherein the Spongilla material comprises only an cuspidata and any material naturally associated with an cuspidata. In another aspect, any method or kit disclosed herein is provided, wherein the Spongilla material comprises substantially purified an cuspidata and any material naturally associated with an cuspidata. In another aspect, any method or kit disclosed herein is provided, wherein the Spongilla material comprises purified an cuspidata and any material naturally associated with an cuspidata that is part of the composition of naturally occurring Spongilla.

[0047] As used herein, the term "object" has the meaning provided to this term by those skilled in the art and may mean a mammal, including a human, dog, cat, cow, or pig. In one embodiment, the object is a human. In one embodiment, the object is a dog. In one embodiment, the object is a cat. In one embodiment, the object is a cow. In one embodiment, the object is a pig.

[0048] As used herein, the term "therapeutic effective amount" means the amount of a composition or a combination of compositions applied, used, or administered to a subject who treats, alleviates, or prevents one or more symptoms of the disorder being treated to some degree.

[0049] Spongilla, including *Sponzilla lacustris*, and powders produced from Spongilla used in the methods disclosed herein may be obtained, processed, and characterized by methods known to those skilled in the art. For example, U.S. Patent No. 7,604,821 describes the harvesting, processing, and characterization of several species of Spongilla, including *Sponzilla lacustris*. The entire disclosure of U.S. Patent No. 7,604,821 is incorporated herein by reference. Sponge material may be collected using methods ordinarily known to those skilled in the art of marine microbiology. For example, sponges may be collected manually using basic underwater diving techniques, or larger colonies in deeper waters may be harvested using an Agassiz trawl (AGT) or an epibenthic sledge (EBS). Under certain environmental conditions, Spongilla colonies exist as a thin, breadcrumb-like carpet over several meters and must be collected manually using tools such as forks and nets. The collected sponge mass is dried, and after trimming off all contaminants, such as husks, stems, plants, rocks, and other impurities, it is washed to remove soil, sand, sediment, and soluble impurities. The trimmed sponge mass is weighed and dried using methods known to those skilled in the art, such as air drying and the use of dryers used for dehydrating food and pharmaceuticals. The sponge mass is dried until the residual moisture content is below a desirable value, as further disclosed herein. Residual moisture measurement may be performed using methods commonly known in the fields of food science, analytical chemistry, or pharmaceuticals. For example, 10 grams of the dried material may be placed in a body-weighted vessel and weighed. The weighed material is exposed to a heat source, such as a drying oven or heat lamp operating at an appropriate temperature, and then the sample is cooled in a drying chamber and re-weighed. Residual moisture is calculated as the percentage difference between the sample weight before drying and the weight after cooling.After drying, the sponge material may optionally be packaged in a sealed container that protects the material from light, moisture, and oxygen. The material may then be further tested for the presence of pathogens, E. coli-like organisms, and organisms representing bioburden. To reduce any pathogens, E. coli-like organisms, or other organisms representing bioburden, the material may be further heated or irradiated as disclosed herein. Next, the material may be further processed using methods known to those skilled in the art to provide a powder containing particles of a desired size. For example, the sponge material may be ground, and the final material is passed through one or more sieves of a defined size to provide a final material containing particles of a uniform or substantially uniform size. After the final processing and sizing process is completed, the dried sponge material may be packaged in a sealed moisture-proof container and stored at an appropriate temperature, such as approximately room temperature or ambient temperature.

[0050] Materials derived from sponges other than *Sponzilla lacoustris* may be manufactured according to the methods described above and known to those skilled in the art. In particular, these methods may be applied to sponges of the *Polypera* phylum. In another aspect, these methods may be applied to sponges of the *Demospongiae* phylum. In another aspect, these methods may be applied to sponges of the *Spondilla* order. In another aspect, these methods may be applied to sponges of the *Spongilidae* genus. In another aspect, these methods may be applied to sponges of the *Sponzilla* genus. In another aspect, these methods may be applied to sponges of the *Sponzilla lacoustris* genus. In another aspect, these methods may be applied to sponges of the *Haploscreridae* order. In another aspect, these methods may be applied to sponges of the *Calinidea* genus. In another aspect, these methods may be applied to sponges of the *Halciona* genus.

[0051] A method for treating a skin condition in a subject, comprising the step of applying, in one aspect, an effective amount of a first composition containing a sponge and an effective amount of a second composition containing one or more botulinum toxins to the skin of a subject requiring treatment, wherein

[0052] (a) The second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G;

[0053] (b) The skin conditions in the subject are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaign disease, dyshidrosis of the legs, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. Any method is provided in other aspects, wherein the skin conditions in the subject are hyperhidrosis, acne vulgaris, and rosacea. In one aspect, any method is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is incobotulinum toxin A.In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin of type B. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin of type B are limabotulinum toxin B. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin of type C1. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin of type C2. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin of type D. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin of type E. In another aspect, any method disclosed herein is provided, wherein one or more of the botulinum toxins of type E are EB-001A or EB-001T. In another aspect, any method disclosed herein is provided, wherein one or more of the botulinum toxins of type E are EB-001A. In another aspect, any method disclosed herein is provided, wherein one or more of the botulinum toxins of type E are EB-001T. In another aspect, any method disclosed herein is provided, wherein one or more of the botulinum toxin types are botulinum toxins of type F. In another aspect, any method disclosed herein is provided, wherein one or more of the botulinum toxin types are botulinum toxins of type G. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is selected from acne vulgaris, rosacea of ​​type 1, rosacea of ​​type 2, psoriasis, and hyperhidrosis. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is acne vulgaris.In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is type 1 rosacea. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is type 2 rosacea. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is psoriasis. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is hyperhidrosis. In another aspect, any method is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, and for at least 17 weeks It is applied at least once per week, at least once per week for at least 18 weeks, at least once per week for at least 19 weeks, at least once per week for at least 20 weeks, at least once per week for at least 21 weeks, at least once per week for at least 22 weeks, at least once per week for at least 23 weeks, and at least once per week for at least 24 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 2 weeks.In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for three weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for four weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for five weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for six weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for seven weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for eight weeks.

[0054] In one aspect, a method for treating hyperhidrosis in a subject is provided, comprising the step of applying to the skin of a subject requiring treatment an effective amount of a first composition containing a sponge and an effective amount of a second composition containing one or more botulinum toxins, wherein the second composition comprises one or more botulinum toxins selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In one aspect, any method is provided, wherein the second composition comprises one or more botulinum toxins selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type A. In another aspect, any method disclosed herein is provided, wherein botulinum toxin type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein botulinum toxin type A is onabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein botulinum toxin type A is avibotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is flabotulinum toxin A.In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type B. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxins type B are lima botulinum toxin B. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type C1. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type C2. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type D. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type E. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are EB-001A or EB-001T. In another aspect, any method disclosed herein is provided, wherein one or more of the E-type botulinum toxins are EB-001A. In another aspect, any method disclosed herein is provided, wherein one or more of the E-type botulinum toxins are EB-001T. In another aspect, any method disclosed herein is provided, wherein one or more of the botulinum toxin types are F-type botulinum toxins. In another aspect, any method disclosed herein is provided, wherein one or more of the botulinum toxin types are G-type botulinum toxins.In another aspect, any method is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, and for at least 17 weeks It is applied at least once per week, at least once per week for at least 18 weeks, at least once per week for at least 19 weeks, at least once per week for at least 20 weeks, at least once per week for at least 21 weeks, at least once per week for at least 22 weeks, at least once per week for at least 23 weeks, and at least once per week for at least 24 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 2 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 3 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 4 weeks. In another aspect, any method disclosed in this specification is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for five weeks.In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for six weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for seven weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for eight weeks.

[0055] In one aspect, a method for treating hyperhidrosis in a subject is provided, comprising the step of applying to the skin of a subject requiring treatment an effective amount of a first composition containing Spongilla and an effective amount of a second composition containing botulinum toxin of type A. In another aspect, any method disclosed herein is provided, wherein botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein botulinum toxin of type A is onabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein botulinum toxin of type A is avibotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein botulinum toxin of type A is incobotulinum toxin A. In another aspect, any method disclosed in this specification is provided, wherein type A botulinum toxin is flabotulinum toxin A.In another aspect, any method is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, and for at least 17 weeks It is applied at least once per week, at least once per week for at least 18 weeks, at least once per week for at least 19 weeks, at least once per week for at least 20 weeks, at least once per week for at least 21 weeks, at least once per week for at least 22 weeks, at least once per week for at least 23 weeks, and at least once per week for at least 24 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 2 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 3 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 4 weeks. In another aspect, any method disclosed in this specification is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for five weeks.In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for six weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for seven weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for eight weeks.

[0056] A first composition comprising a Spongilla for use in a method for treating a skin disease or pathological condition in a subject requiring treatment, wherein the method comprises the step of administering an effective amount of the first composition to a subject in combination with an effective amount of the second composition, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G, and the skin pathological condition in the subject is acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, It is selected from leg disease, congenital onychomycosis, hydrogenic keratoderma, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, this first composition is provided for use, wherein the skin pathology or condition in the subject is hyperhidrosis, acne vulgaris, and rosacea. In one aspect, this first composition is provided for use, wherein the second composition comprises one or more types of botulinum toxin selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In one aspect, such a first composition for use is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In one aspect, such a first composition for use is provided, wherein one or more botulinum toxin types are botulinum toxin type A.In one aspect, a first composition for use is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one aspect, a first composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one aspect, a first composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one aspect, a first composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one aspect, a first composition for use is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In one aspect, a first composition for use is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In one aspect, a first composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin of type B. In another aspect, any method disclosed herein is provided, wherein one or more of the type B botulinum toxins are lima botulinum toxins B. In one aspect, such a first composition for use is provided, wherein one or more of the botulinum toxin types are type C1 botulinum toxins. In one aspect, such a first composition for use is provided, wherein one or more of the botulinum toxin types are type C2 botulinum toxins. In one aspect, such a first composition for use is provided, wherein one or more of the botulinum toxin types are type D botulinum toxins. In one aspect, such a first composition for use is provided, wherein one or more of the botulinum toxin types are type E botulinum toxins. In one aspect, such a first composition for use is provided, wherein one or more of the type E botulinum toxins are EB-001A or EB-001T. In one aspect, such a first composition for use is provided, wherein one or more of the type E botulinum toxins are EB-001A. In one aspect, this first composition for use is provided, wherein one or more of the type E botulinum toxins are EB-001T.In one aspect, a first composition for use is provided, wherein one or more types of botulinum toxin are type F botulinum toxin. In one aspect, a first composition for use is provided, wherein one or more types of botulinum toxin are type G botulinum toxin. In one aspect, a first composition for use is provided, wherein the skin condition in a subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, and hyperhidrosis. In one aspect, a first composition for use is provided, wherein the skin condition in a subject is acne vulgaris. In one aspect, a first composition for use is provided, wherein the skin condition in a subject is type rosacea. In one aspect, a first composition for use is provided, wherein the skin condition in a subject is type 2 rosacea. In one aspect, a first composition for use is provided, wherein the skin condition in a subject is psoriasis. In one aspect, a first composition for use is provided, wherein the skin condition in a subject is hyperhidrosis.In one aspect, the first composition is provided for use, wherein the first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, at least It is applied at least once per week for 17 weeks, at least once per week for 18 weeks, at least once per week for 19 weeks, at least once per week for 20 weeks, at least once per week for 21 weeks, at least once per week for 22 weeks, at least once per week for 23 weeks, and at least once per week for 24 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 2 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 3 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 4 weeks. In one aspect, a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 5 weeks.In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 6 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 7 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 8 weeks.

[0057] A first composition comprising a sponge for use in a method for treating hyperhidrosis in a subject requiring treatment, wherein the method comprises the step of administering an effective amount of the first composition to the subject in combination with an effective amount of a second composition, and the second composition comprises a botulinum toxin of type A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one aspect, this first composition for use is provided, wherein the type A botulinum toxin is flabotulinum toxin A.In one aspect, the first composition is provided for use, wherein the first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, at least It is applied at least once per week for 17 weeks, at least once per week for 18 weeks, at least once per week for 19 weeks, at least once per week for 20 weeks, at least once per week for 21 weeks, at least once per week for 22 weeks, at least once per week for 23 weeks, and at least once per week for 24 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 2 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 3 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 4 weeks. In one aspect, a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 5 weeks.In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 6 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 7 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 8 weeks.

[0058] A first composition comprising a sponge for use in a method for treating hyperhidrosis in a subject requiring treatment, wherein the method comprises the step of administering an effective amount of the first composition to a subject in combination with an effective amount of the second composition, and the second composition comprises onabotulinum toxin A. In one aspect, the first composition is provided for use, wherein the first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, at least It is applied at least once a week for 17 weeks, at least once a week for 18 weeks, at least once a week for 19 weeks, at least once a week for 20 weeks, at least once a week for 21 weeks, at least once a week for 22 weeks, at least once a week for 23 weeks, and at least once a week for 24 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 2 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 3 weeks.In one aspect, a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 4 weeks. In one aspect, a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 5 weeks. In one aspect, a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 6 weeks. In one aspect, a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 7 weeks. In one aspect, a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 8 weeks.

[0059] A composition comprising Spongilla and one or more botulinum toxins for the treatment of skin conditions or diseases in subjects requiring treatment, wherein the skin conditions in the subjects are selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, dermatophytosis of the legs, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, this first composition for use is provided, wherein the skin pathology or condition in the subject is hyperhidrosis, acne vulgaris, and rosacea, and the botulinum toxin is selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G, and the skin pathology in the subject is acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrokeratosis, paresthetic backache, dyshidrosis (Hyperhidrosis), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma are selected. In other aspects, such compositions are provided for use, wherein the skin pathology or condition in the subject is hyperhidrosis, acne vulgaris, and rosacea.In one aspect, such a composition for use is provided, wherein the botulinum toxin is selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are botulinum toxin type A. In one aspect, such a composition for use is provided, wherein the botulinum toxin type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin of type B. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin of type B are limabotulinum toxin B. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin of type C1. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are C2 type botulinum toxin. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are D type botulinum toxin.In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type E. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001A or EB-001T. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001A. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001T. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type F. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type G. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is acne vulgaris. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is type 1 rosacea. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is type 2 rosacea. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is psoriasis. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is hyperhidrosis.In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, and at least once per week for at least 17 weeks. It is applied once, at least once per week for at least 18 weeks, at least once per week for at least 19 weeks, at least once per week for at least 20 weeks, at least once per week for at least 21 weeks, at least once per week for at least 22 weeks, at least once per week for at least 23 weeks, and at least once per week for at least 24 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once per week for 2 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once per week for 3 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once per week for 4 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once per week for 5 weeks. In one aspect, such a composition for use is provided, wherein the composition containing Spongilla is applied to the skin of a subject once a week for 6 weeks.In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once a week for 7 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once a week for 8 weeks.

[0060] The composition comprises Spongilla and one or more botulinum toxins for use in the treatment of hyperhidrosis in subjects requiring treatment. In one aspect, such a composition for use is provided, wherein the botulinum toxin is selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are botulinum toxin type A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin of type B. In another aspect, any method disclosed herein is provided, wherein one or more of the type B botulinum toxins are lima botulinum toxins B. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are type C1 botulinum toxins. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are type C2 botulinum toxins.In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type D. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type E. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001A or EB-001T. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001A. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001T. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type F. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type G.

[0061] The composition comprises Spongilla and one or more botulinum toxins for use in the treatment of hyperhidrosis in subjects requiring treatment. In one aspect, such a composition for use is provided, wherein the botulinum toxin is selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E.

[0062] The composition comprises Spongilla and one or more botulinum toxins of type A for use in the treatment of hyperhidrosis in subjects requiring treatment, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, such a composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one embodiment, such a composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one embodiment, such a composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one embodiment, such a composition for use is provided, wherein the botulinum toxin of type A is flabotulinum toxin A.

[0063] The composition comprises Spongilla and Onabotulinum Toxin A for use in the treatment of hyperhidrosis in subjects requiring treatment. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, and at least once per week for at least 17 weeks. It is applied at least once per week for at least 18 weeks, at least once per week for at least 19 weeks, at least once per week for at least 20 weeks, at least once per week for at least 21 weeks, at least once per week for at least 22 weeks, at least once per week for at least 23 weeks, and at least once per week for at least 24 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once per week for 2 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once per week for 3 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once per week for 4 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once per week for 5 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once a week for 6 weeks.In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once a week for 7 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject and applied to the skin of a subject once a week for 8 weeks.

[0064] A first composition comprising a sponge for use in reducing sweat secretion in a subject, wherein the method comprises the step of administering an effective amount of the first composition to a subject in combination with an effective amount of the second composition, and the second composition comprises one or more types of botulinum toxin selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, such a first composition is provided, wherein the subject experiences a reduction of more than 10% in the amount of sweat secretion measured by weight after administration of the first composition and the second composition compared to the amount of sweat secretion measured by weight of the subject before such administration. In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% in the amount of sweat secreted by weight after administration of the first composition and the second composition, compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 30% in the amount of sweat secreted by weight after administration of the first composition and the second composition, compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 40% in the amount of sweat secreted by weight after administration of the first composition and the second composition, compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, a composition for use is provided, wherein the subject experiences a reduction of more than 50% in the amount of sweat secreted measured by weight after administration of the first composition and the second composition compared to the amount of sweat secreted measured by weight of the subject before treatment.In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 60% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 70% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 80% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 90% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, a composition for use is provided, wherein the subject experiences a reduction of more than 95% in the amount of sweat secreted by weighing after the administration of the first composition and the second composition compared to the amount of sweat secreted by weighing the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject is treated once per month, twice per month, three times per month, four times per month, five times per month, six times per month, seven times per month, eight times per month, nine times per month, ten times per month, eleven times per month, twelve times per month, thirteen times per month, fourteen times per month, fifteen times per month, sixteen times per month, seventeen times per month, eighteen times per month, nineteen times per month, twenty times per month, twenty-one times per month, twenty-two times per month, twenty-two times per month, or twenty-four times per month. In another aspect, such a composition for use is provided, wherein the subject is treated twice per month.In another aspect, this composition is provided for use, wherein the subject is treated three times per month. In another aspect, this composition is provided for use, wherein the subject is treated once per week. In another aspect, this composition is provided for use, wherein the subject is at least 18 years of age. In another aspect, this composition is provided for use, wherein the subject is treated once per month, or once every two months, or once every three months, or once every four months, or once every five months, or once every six months, or once every seven months, or once every eight months, or once every nine months, or once every ten months, or once every eleven months, or once every twelve months. In another aspect, this composition is provided for use, wherein the subject is treated once per month. In another aspect, this composition is provided for use, wherein the subject is treated once every two months. In another aspect, this composition is provided for use, wherein the subject is treated once every three months. In another aspect, this composition is provided for use, wherein the subject is treated once every four months. In another aspect, this composition is provided for use, wherein the subject is treated once every five months. In another aspect, this composition is provided for use, wherein the subject is treated once every six months. In another aspect, this composition is provided for use, wherein the subject is treated once every seven months. In another aspect, this composition is provided for use, wherein the subject is treated once every eight months. In another aspect, this composition is provided for use, wherein the subject is treated once every nine months. In another aspect, this composition is provided for use, wherein the subject is treated once every ten months. In another aspect, this composition is provided for use, wherein the subject is treated once every eleven months.In another aspect, this composition is provided for use, wherein the subject is treated once every 12 months. In another aspect, this composition is provided for use, wherein the subject suffers from primary axillary hyperhidrosis.

[0065] A first composition comprising a sponge for use in reducing sweat secretion in a subject, wherein the method comprises the step of administering an effective amount of the first composition to a subject in combination with an effective amount of a second composition, wherein the second composition comprises one or more types of botulinum toxin selected from botulinum toxin of type A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one aspect, a first composition for use is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, a first composition is provided, wherein a subject experiences a reduction of more than 10% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before such administration. In another aspect, a composition for use is provided, wherein a subject experiences a reduction of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, a composition for use is provided, wherein a subject experiences a reduction of more than 30% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment.In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 40% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 50% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 60% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 70% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 80% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight before treatment. In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 90% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight before treatment. In another aspect, such compositions for use are provided, wherein the subject experiences a reduction of more than 95% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight before treatment.In another aspect, such a composition for use is provided, wherein the subject is treated once per month, twice per month, three times per month, four times per month, five times per month, six times per month, seven times per month, eight times per month, nine times per month, ten times per month, eleven times per month, twelve times per month, thirteen times per month, fourteen times per month, fifteen times per month, sixteen times per month, seventeen times per month, eighteen times per month, nineteen times per month, twenty times per month, twenty-one times per month, twenty-two times per month, twenty-two times per month, or twenty-four times per month. In another aspect, such a composition for use is provided, wherein the subject is treated twice per month. In another aspect, this composition is provided for use, wherein the subject is treated three times per month. In another aspect, this composition is provided for use, wherein the subject is treated once per week. In another aspect, this composition is provided for use, wherein the subject is at least 18 years of age. In another aspect, this composition is provided for use, wherein the subject is treated once per month, or once every two months, or once every three months, or once every four months, or once every five months, or once every six months, or once every seven months, or once every eight months, or once every nine months, or once every ten months, or once every eleven months, or once every twelve months. In another aspect, this composition is provided for use, wherein the subject is treated once per month. In another aspect, this composition is provided for use, wherein the subject is treated once every two months. In another aspect, this composition is provided for use, wherein the subject is treated once every three months. In another aspect, this composition is provided for use, wherein the subject is treated once every four months. In another aspect, this composition is provided for use, wherein the subject is treated once every five months.In another aspect, this composition is provided for use, wherein the subject is treated once every 6 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 7 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 8 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 9 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 10 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 11 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 12 months. In another aspect, this composition is provided for use, wherein the subject suffers from primary axillary hyperhidrosis.

[0066] A first composition comprising a Spongilla for use in reducing sweat secretion in a subject, wherein the method comprises the step of administering an effective amount of the first composition to a subject in combination with an effective amount of a second composition, the second composition comprising onabotulinum toxin A. In another aspect, such a first composition is provided, wherein the subject experiences a reduction of more than 10% in the amount of sweat secretion measured by weight after administration of the first composition and the second composition compared to the amount of sweat secretion measured by weight of the subject before such administration. In another aspect, such a composition is provided for use, wherein the subject experiences a reduction of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% in the amount of sweat secretion measured by weight after administration of the first composition and the second composition compared to the amount of sweat secretion measured by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 30% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 40% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 50% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 60% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment.In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 70% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 80% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 90% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject experiences a reduction of more than 95% in the amount of sweat secreted by weight after administration of the first composition and the second composition compared to the amount of sweat secreted by weight of the subject before treatment. In another aspect, such a composition for use is provided, wherein the subject is treated once per month, twice per month, three times per month, four times per month, five times per month, six times per month, seven times per month, eight times per month, nine times per month, ten times per month, eleven times per month, twelve times per month, thirteen times per month, fourteen times per month, fifteen times per month, sixteen times per month, seventeen times per month, eighteen times per month, nineteen times per month, twenty times per month, twenty-one times per month, twenty-two times per month, twenty-two times per month, or twenty-four times per month. In another aspect, such a composition for use is provided, wherein the subject is treated twice per month. In another aspect, this composition is provided for use, wherein the subject is treated three times per month. In another aspect, this composition is provided for use, wherein the subject is treated once per week.In another aspect, this composition is provided for use, wherein the subject is at least 18 years of age. In another aspect, this composition is provided for use, wherein the subject is treated once per month, or once every 2 months, or once every 3 months, or once every 4 months, or once every 5 months, or once every 6 months, or once every 7 months, or once every 8 months, or once every 9 months, or once every 10 months, or once every 11 months, or once every 12 months. In another aspect, this composition is provided for use, wherein the subject is treated once per month. In another aspect, this composition is provided for use, wherein the subject is treated once every 2 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 3 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 4 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 5 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 6 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 7 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 8 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 9 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 10 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 11 months. In another aspect, this composition is provided for use, wherein the subject is treated once every 12 months. In another aspect, this composition is provided for use, wherein the subject suffers from primary axillary hyperhidrosis.

[0067] A first composition comprising a sponge for use in a method for treating hyperhidrosis in a subject requiring treatment, wherein the method comprises the step of administering an effective amount of the first composition to the subject in combination with an effective amount of a second composition, and the second composition comprises a botulinum toxin of type A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one aspect, such a first composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one aspect, this first composition for use is provided, wherein the type A botulinum toxin is flabotulinum toxin A.In one aspect, the first composition is provided for use, wherein the first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, at least It is applied at least once per week for 17 weeks, at least once per week for 18 weeks, at least once per week for 19 weeks, at least once per week for 20 weeks, at least once per week for 21 weeks, at least once per week for 22 weeks, at least once per week for 23 weeks, and at least once per week for 24 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 2 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 3 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 4 weeks. In one aspect, a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 5 weeks.In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 6 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 7 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once a week for 8 weeks.

[0068] A first composition comprising a sponge for use in a method for treating hyperhidrosis in a subject requiring treatment, wherein the method comprises the step of administering an effective amount of the first composition to a subject in combination with an effective amount of the second composition, and the second composition comprises onabotulinum toxin A. In one aspect, the first composition is provided for use, wherein the first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, and at least once per week for at least 17 weeks. It is applied once, at least once per week for at least 18 weeks, at least once per week for at least 19 weeks, at least once per week for at least 20 weeks, at least once per week for at least 21 weeks, at least once per week for at least 22 weeks, at least once per week for at least 23 weeks, and at least once per week for at least 24 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 2 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 3 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 4 weeks.In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 5 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 6 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 7 weeks. In one aspect, such a first composition for use is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 8 weeks.

[0069] The composition comprises Spongilla and one or more botulinum toxins for the treatment of skin conditions or diseases in subjects requiring treatment, wherein the skin conditions in the subjects are selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, dermatophytosis of the legs, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (hyperhidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, this first composition for use is provided, wherein the skin pathology or condition in the subject is hyperhidrosis, acne vulgaris, and rosacea, and the botulinum toxin is selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G, and the skin pathology in the subject is acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrokeratosis, paresthetic backache, dyshidrosis (Hyperhidrosis), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma are selected. The composition is provided for use in other aspects, wherein the skin pathology or condition in the subject is hyperhidrosis, acne vulgaris, and rosacea.In one aspect, such a composition for use is provided, wherein the botulinum toxin is selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are botulinum toxin type A. In one aspect, such a composition for use is provided, wherein the botulinum toxin type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin of type B. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin of type B are limabotulinum toxin B. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin of type C1. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are C2 type botulinum toxin. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are D type botulinum toxin.In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type E. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001A or EB-001T. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001A. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001T. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type F. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type G. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is acne vulgaris. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is type 1 rosacea. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is type 2 rosacea. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is psoriasis. In one aspect, such a composition for use is provided, wherein the skin condition in the subject is hyperhidrosis.In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, and at least once per week for at least 17 weeks. It is applied once, at least once per week for at least 18 weeks, at least once per week for at least 19 weeks, at least once per week for at least 20 weeks, at least once per week for at least 21 weeks, at least once per week for at least 22 weeks, at least once per week for at least 23 weeks, and at least once per week for at least 24 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once per week for 2 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once per week for 3 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once per week for 4 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once per week for 5 weeks. In one aspect, such a composition for use is provided, wherein the composition containing Spongilla is applied to the skin of a subject once a week for 6 weeks.In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once a week for 7 weeks. In one aspect, such a composition for use is provided, wherein the composition is applied to the skin of a subject once a week for 8 weeks.

[0070] The composition comprises Spongilla and one or more botulinum toxins for use in the treatment of hyperhidrosis in subjects requiring treatment. In one aspect, such a composition for use is provided, wherein the botulinum toxin is selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are botulinum toxin type A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one aspect, such a composition for use is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin of type B. In another aspect, any method disclosed herein is provided, wherein one or more of the type B botulinum toxins are lima botulinum toxins B. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are type C1 botulinum toxins. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are type C2 botulinum toxins.In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type D. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type E. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001A or EB-001T. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001A. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin type E are EB-001T. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type F. In one aspect, such a composition for use is provided, wherein one or more types of botulinum toxin are botulinum toxin type G.

[0071] The composition comprises a sponge and one or more botulinum toxins for use in the treatment of hyperhidrosis in subjects requiring treatment. In one aspect, such a composition for use is provided, wherein the botulinum toxin is selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In one aspect, such a composition for use is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E.

[0072] A composition comprising a Spongilla and one or more botulinum toxins of type A for use in the treatment of hyperhidrosis in subjects requiring treatment, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, such a composition for use is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In one embodiment, such a composition for use is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In one embodiment, such a composition for use is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In one embodiment, such a composition for use is provided, wherein the botulinum toxin of type A is flabotulinum toxin A.

[0073] The composition comprises Spongilla and Onabotulinum Toxin A for use in the treatment of hyperhidrosis in subjects requiring treatment. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, and at least once per week for at least 17 weeks. It is applied at least once per week for at least 18 weeks, at least once per week for at least 19 weeks, at least once per week for at least 20 weeks, at least once per week for at least 21 weeks, at least once per week for at least 22 weeks, at least once per week for at least 23 weeks, and at least once per week for at least 24 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once per week for 2 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once per week for 3 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once per week for 4 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once per week for 5 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once a week for 6 weeks.In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once a week for 7 weeks. In another aspect, such a composition is provided, wherein the composition is applied to the skin of a subject once a week for 8 weeks.

[0074] A method for treating hyperhidrosis in a subject is provided, comprising the step of applying an effective amount of a first composition containing a sponge and an effective amount of a second composition containing onabotulinum toxin A to the skin of a subject requiring treatment in one aspect. In another aspect, any method is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, and for at least 17 weeks It is applied at least once per week, at least once per week for at least 18 weeks, at least once per week for at least 19 weeks, at least once per week for at least 20 weeks, at least once per week for at least 21 weeks, at least once per week for at least 22 weeks, at least once per week for at least 23 weeks, and at least once per week for at least 24 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 2 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 3 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 4 weeks.In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 5 weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 6 weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 7 weeks. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 8 weeks.

[0075] In another aspect, any disclosed method is provided herein, wherein the method comprises the step of applying an effective amount of a first composition comprising a sponge and an effective amount of a second composition comprising one or more botulinum toxins to the skin of a subject requiring treatment.

[0076] In one aspect, a method for treating a skin condition in a subject is provided, comprising the step of applying a first composition comprising a sponge and a second composition comprising one or more botulinum toxins to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin of type B. In another aspect, any method disclosed in this specification is provided, wherein one or more of the type B botulinum toxins are lima botulinum toxins B.In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are C1 type botulinum toxin. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are C2 type botulinum toxin. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are D type botulinum toxin. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are E type botulinum toxin. In another aspect, any method disclosed herein is provided, wherein one or more E type botulinum toxins are EB-001A or EB-001T. In another aspect, any method disclosed herein is provided, wherein one or more E type botulinum toxins are EB-001A. In another aspect, any method disclosed herein is provided, wherein one or more E type botulinum toxins are EB-001T. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type F. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type G. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is acne vulgaris. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is rosacea type 1. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is rosacea type 2. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is psoriasis.In another aspect, any method disclosed in this specification is provided, wherein the skin condition in the subject is hyperhidrosis.

[0077] In another aspect, a composition comprising a first composition and a second composition for use as a drug is provided, wherein (a) the first composition comprises Spongilla; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a composition comprising a first composition and a second composition for use as a drug is provided, wherein (a) the first composition comprises Spongilla lacustris; and (b) the second composition comprises one or more botulinum toxins. In another aspect, such composition is provided for use as a drug for the treatment of skin conditions in a subject. Another aspect is that this combination is used as a drug for treating skin conditions in a subject, wherein the skin conditions in the subject are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids, and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, dermatophytosis of the legs, congenital onychomycosis, hydrokeratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, and eccrine nevus. In another aspect, any composition disclosed herein is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, any composition disclosed herein is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In another aspect, any composition disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type A.In another aspect, any composition disclosed herein is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In another aspect, any composition disclosed herein is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In another aspect, any composition disclosed herein is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In another aspect, any composition disclosed herein is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In another aspect, any composition disclosed herein is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, any composition disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type B. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin type B are lima botulinum toxin B. In another aspect, any composition disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type C1. In another aspect, any composition disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type C2. In another aspect, any composition disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type D. In another aspect, any composition disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type E. In another aspect, any composition disclosed herein is provided, wherein one or more types of botulinum toxin are EB-001A or EB-001T. In another aspect, any composition disclosed herein is provided, wherein one or more of the type E botulinum toxins are EB-001A. In another aspect, any composition disclosed herein is provided, wherein one or more of the type E botulinum toxins are EB-001T.In another aspect, any composition disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type F. In another aspect, any composition disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type G. In another aspect, any composition disclosed herein is provided, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In another aspect, any composition disclosed herein is provided, wherein the skin condition in the subject is acne vulgaris. In another aspect, any composition disclosed herein is provided, wherein the skin condition in the subject is rosacea type 1. In another aspect, any composition disclosed herein is provided, wherein the skin condition in the subject is rosacea type 2. In another aspect, any composition disclosed herein is provided, wherein the skin condition in the subject is psoriasis. In another aspect, any composition disclosed herein is provided, wherein the skin condition in the subject is hyperhidrosis. In another aspect, any composition disclosed herein is provided, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is type 1 rosacea. In another aspect, any composition disclosed herein is provided, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001, and the skin condition in the subject is type 2 rosacea. In another aspect, any composition disclosed in this specification is provided, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001, and the skin condition in the subject is psoriasis.In another aspect, any composition disclosed herein is provided, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is hyperhidrosis. In another aspect, any composition disclosed herein is provided, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is type 1 rosacea. In another aspect, any composition disclosed herein is provided, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is type 2 rosacea. In another aspect, any composition disclosed herein is provided, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is psoriasis. In another aspect, any composition disclosed in this specification is provided, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is hyperhidrosis.

[0078] In another aspect, a composition comprising a first composition and a second composition for use in the treatment of a skin condition in a subject, wherein (a) the first composition comprises Spongilla; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a combination of a first composition and a second composition for use in the treatment of a skin condition in a subject, wherein (a) the first composition comprises Spongilla lacustris; and (b) the second composition comprises one or more botulinum toxins. In another aspect, this composition is provided for use in the treatment of skin conditions in a subject, wherein the skin conditions in the subject are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, this composition is provided for use in the treatment of skin conditions in a subject, wherein the skin conditions in the subject are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, dysphagia, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma.In another aspect, as such a composition for use in the treatment of skin conditions in a subject, wherein the second composition comprises one or more types of botulinum toxin selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, as such a composition for use in the treatment of skin conditions in a subject, wherein one or more types of botulinum toxin are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In another aspect, as such a composition for use in the treatment of skin conditions in a subject, wherein one or more types of botulinum toxin are botulinum toxin type A. In another aspect, as such a composition for use in the treatment of skin conditions in a subject, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In another aspect, as such a composition for use in the treatment of skin conditions in a subject, wherein the botulinum toxin of type A is onabotulinum toxin A. In another aspect, as such a composition for use in the treatment of skin conditions in a subject, wherein the botulinum toxin of type A is avibotulinum toxin A. In another aspect, as such a composition for use in the treatment of skin conditions in a subject, wherein the botulinum toxin of type A is incobotulinum toxin A. In another aspect, as such a composition for use in the treatment of skin conditions in a subject, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, as a composition for use in the treatment of skin conditions in a subject, wherein the botulinum toxin of type A is doxybotulinum toxin A. In another aspect, as a composition for use in the treatment of skin conditions in a subject, wherein one or more types of botulinum toxin are botulinum toxin of type B.In another aspect, any method disclosed herein is provided, wherein one or more of the type B botulinum toxins are lima botulinum toxins B. In another aspect, as a composition for use in the treatment of skin conditions in a subject, wherein one or more botulinum toxin types are type C1 botulinum toxins. In another aspect, as a composition for use in the treatment of skin conditions in a subject, wherein one or more botulinum toxin types are type C2 botulinum toxins. In another aspect, as a composition for use in the treatment of skin conditions in a subject, wherein one or more botulinum toxin types are type D botulinum toxins. In another aspect, as a composition for use in the treatment of skin conditions in a subject, wherein one or more botulinum toxin types are type E botulinum toxins. In another aspect, as a composition for use in the treatment of skin conditions in a subject, wherein one or more of the type E botulinum toxins are EB-001A or EB-001T. In another aspect, as this composition for use in the treatment of a skin condition in a subject, wherein one or more of the botulinum toxin type E is EB-001A. In another aspect, as this composition for use in the treatment of a skin condition in a subject, wherein one or more of the botulinum toxin type E is EB-001T. In another aspect, as this composition for use in the treatment of a skin condition in a subject, wherein one or more of the botulinum toxin type is botulinum toxin type F. In another aspect, as this composition for use in the treatment of a skin condition in a subject, wherein one or more of the botulinum toxin type is botulinum toxin type G. In another aspect, as this composition for use in the treatment of a skin condition in a subject, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In another aspect, as this composition for use in the treatment of a skin condition in a subject, wherein the skin condition in the subject is acne vulgaris.In another aspect, any composition disclosed herein is provided, wherein the skin condition in the subject is type 1 rosacea. In another aspect, such a composition is provided for use in the treatment of a skin condition in the subject, wherein the skin condition in the subject is type 2 rosacea. In another aspect, such a composition is provided for use in the treatment of a skin condition in the subject, wherein the skin condition in the subject is psoriasis. In another aspect, such a composition is provided for use in the treatment of a skin condition in the subject, wherein the skin condition in the subject is hyperhidrosis. In another aspect, such a composition is provided for use in the treatment of a skin condition in the subject, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is type 1 rosacea. In another aspect, as such a composition for use in the treatment of a skin condition in a subject, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is type 2 rosacea. In another aspect, as such a composition for use in the treatment of a skin condition in a subject, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is psoriasis. In another aspect, as such a composition for use in the treatment of a skin condition in a subject, wherein the second composition is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is hyperhidrosis. In another aspect, as such a composition for use in the treatment of a skin condition in a subject, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is type 1 rosacea.In another aspect, this composition is for use in the treatment of a skin condition in a subject, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is type 2 rosacea. In another aspect, this composition is for use in the treatment of a skin condition in a subject, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is psoriasis. In another aspect, this composition is for use in the treatment of a skin condition in a subject, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is hyperhidrosis.

[0079] In another aspect, a composition for preparing a drug for treating a skin condition in a subject is provided, wherein the composition comprises a first composition and a second composition, (a) the first composition comprises Spongilla; and (b) the second composition comprises one or more botulinum toxins. In another aspect, a composition for preparing a drug for treating a skin condition in a subject is provided, wherein the composition comprises a first composition and a second composition, (a) the first composition comprises Spongilla lacustris; and (b) the second composition comprises one or more botulinum toxins. A composition for manufacturing a drug for treating a skin condition in a subject, wherein the skin condition in the subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, suppurative hidradenitis, Raynaud's phenomenon, post-herpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma.In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the second composition comprises one or more types of botulinum toxin selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more types of botulinum toxin are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more types of botulinum toxin are botulinum toxin type A. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the botulinum toxin of type A is onabotulinum toxin A.In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the botulinum toxin of type A is daxibotulinum toxin A. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more types of botulinum toxin are botulinum toxin of type B. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin of type B are limabotulinum toxin B. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more types of botulinum toxin are C1 type botulinum toxin. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more types of botulinum toxin are C2 type botulinum toxin. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more types of botulinum toxin are D type botulinum toxin. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more types of botulinum toxin are E type botulinum toxin. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more types of E type botulinum toxin are EB-001A or EB-001T. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more of the E-type botulinum toxins are EB-001A.In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more of the E-type botulinum toxins are EB-001T. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more of the botulinum toxin types are F-type botulinum toxins. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein one or more of the botulinum toxin types are G-type botulinum toxins. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, and hyperhidrosis. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is acne vulgaris. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is type 1 rosacea. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is type 2 rosacea. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is psoriasis. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the skin condition in the subject is hyperhidrosis. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is type 1 rosacea.In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is type 2 rosacea. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the second composition is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is psoriasis. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the second composition is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is hyperhidrosis. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is type 1 rosacea. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is type 2 rosacea. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the second composition is onabotulinum toxin A and the skin condition in the subject is psoriasis. In another aspect, a composition for manufacturing a drug for treating a skin condition in a subject is provided, wherein the second composition is onabotulinum toxin A and the skin condition in the subject is hyperhidrosis.

[0080] In another aspect, a method for treating hyperhidrosis in a subject is provided, comprising the step of applying a first composition comprising a sponge and a second composition comprising one or more botulinum toxins to the skin of a subject. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein botulinum toxin type A is onabotulinum toxin A. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences at least a 1-grade improvement in the HDSS score after treatment compared to the subject's HDSS score before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences at least a 2-grade improvement in the HDSS score after treatment compared to the subject's HDSS score before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences at least a 3-grade improvement in the HDSS score after treatment compared to the subject's HDSS score before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 10% in the sweat secretion measured by weight after treatment compared to the sweat secretion measured by weight of the subject before treatment.In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% in the amount of sweat secreted by weight after treatment compared to the amount of sweat secreted by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 30% in the amount of sweat secreted by weight after treatment compared to the amount of sweat secreted by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 40% in the amount of sweat secreted by weight after treatment compared to the amount of sweat secreted by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 50% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 60% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 70% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 80% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment.In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 90% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 95% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once per month, twice per month, three times per month, four times per month, five times per month, six times per month, seven times per month, eight times per month, nine times per month, ten times per month, eleven times per month, twelve times per month, thirteen times per month, fourteen times per month, fifteen times per month, sixteen times per month, seventeen times per month, eighteen times per month, nineteen times per month, twenty times per month, twenty-one times per month, twenty-two times per month, twenty-two times per month, or twenty-four times per month. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated twice per month. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated three times per month. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once per week. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is at least 18 years of age.In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once per month, or once every two months, or once every three months, or once every four months, or once every five months, or once every six months, or once every seven months, or once every eight months, or once every nine months, or once every ten months, or once every eleven months, or once every twelve months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once per month. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every two months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every three months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every four months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every five months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every six months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every seven months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every eight months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every nine months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every ten months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every 11 months.In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every 12 months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject suffers from primary axillary hyperhidrosis.

[0081] In another aspect, a method for treating hyperhidrosis in a subject is provided, comprising the step of applying a first composition comprising a sponge and a second composition comprising one or more botulinum toxins to the skin of a subject. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein botulinum toxin type A is onabotulinum toxin A. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences at least a 4-point improvement from the baseline in the weekly average Axillary Sweating Daily Diary (ASDD) Item 2 score compared to the subject's ASDD score before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences at least a 4-point improvement from the baseline in the weekly average Axillary Sweating Daily Diary (ASDD) Item 2 score at 4 weeks after treatment compared to the subject's ASDD score before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences at least a 2-grade improvement in the ASDD score after treatment compared to the subject's ASDD score before treatment.In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences at least a 3-grade improvement in the ASDD score after treatment compared to the subject's ASDD score before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 10% in the sweat secretion measured by weight after treatment compared to the sweat secretion measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% in the sweat secretion measured by weight after treatment compared to the sweat secretion measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 30% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight of the subject before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 40% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight of the subject before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 50% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight of the subject before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 60% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight of the subject before treatment.In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 70% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 80% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 90% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject experiences a reduction of more than 95% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once per month, twice per month, three times per month, four times per month, five times per month, six times per month, seven times per month, eight times per month, nine times per month, ten times per month, eleven times per month, twelve times per month, thirteen times per month, fourteen times per month, fifteen times per month, sixteen times per month, seventeen times per month, eighteen times per month, nineteen times per month, twenty times per month, twenty-one times per month, twenty-two times per month, twenty-two times per month, or twenty-four times per month. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated twice per month. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated three times per month.In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once per week. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is at least 18 years of age. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once per month, or once every two months, or once every three months, or once every four months, or once every five months, or once every six months, or once every seven months, or once every eight months, or once every nine months, or once every ten months, or once every eleven months, or once every twelve months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once per month. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every two months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every three months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every four months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every five months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every six months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every seven months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every eight months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every nine months.In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every 10 months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every 11 months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject is treated once every 12 months. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the subject suffers from primary axillary hyperhidrosis.

[0082] Any method, composition, composition for use, and kit disclosed herein in other aspects are provided, wherein the percentage of treated subjects having a gravimetric sweat secretion of ≤ 50 mg per armpit at 4 weeks after application of a composition comprising Spongilla and a composition comprising one or more botulinum toxins is about 10% of the subjects, about 15% of the subjects, about 20% of the subjects, about 25% of the subjects, about 30% of the subjects, about 35% of the subjects, about 40% of the subjects, about 45% of the subjects, about 50% of the subjects, about 55% of the subjects, about 60% of the subjects, about 65% of the subjects, about 70% of the subjects, about 75% of the subjects, about 80% of the subjects, about 85% of the subjects, about 90% of the subjects, about 95% of the subjects, or about 99% of the subjects. In another aspect, any method, composition, composition for use, and kit are provided, wherein the second composition comprises one or more types of botulinum toxin selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, any method, composition, composition for use, and kit are provided, wherein the second composition comprises one or more types of botulinum toxin selected from botulinum toxin type A. In another aspect, any method, composition, composition for use, and kit are provided, wherein botulinum toxin type A is onabotulinum toxin A.In other aspects, any method, composition, composition for use, and kit are provided, wherein the subject is treated once per month, twice per month, three times per month, four times per month, five times per month, six times per month, seven times per month, eight times per month, nine times per month, ten times per month, eleven times per month, twelve times per month, thirteen times per month, fourteen times per month, fifteen times per month, sixteen times per month, seventeen times per month, eighteen times per month, nineteen times per month, twenty times per month, twenty-one times per month, twenty-two times per month, twenty-two times per month, or twenty-four times per month. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated twice per month. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated three times per month. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated once per week. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is at least 18 years of age. In other aspects, any method, composition, composition for use, and kit are provided, wherein the subject is treated once per month, or once every two months, or once every three months, or once every four months, or once every five months, or once every six months, or once every seven months, or once every eight months, or once every nine months, or once every ten months, or once every eleven months, or once every twelve months. In other aspects, any method, composition, composition for use, and kit are provided, wherein the subject is treated once per month. In other aspects, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every two months. In other aspects, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every three months.In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is administered once every 4 months. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every 5 months. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every 6 months. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every 7 months. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every 8 months. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every 9 months. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every 10 months. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every 11 months. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject is treated once every 12 months. In another aspect, any method, composition, composition for use, and kit are provided, wherein the subject suffers from primary axillary hyperhidrosis.

[0083] In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the first composition comprises about 0.25 grams to about 10 grams of Spongilla. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the composition comprises Spongilla and a hydrogen peroxide solution. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the hydrogen peroxide solution comprises about 3% hydrogen peroxide. In another aspect, any method disclosed herein for treating hyperhidrosis is provided, wherein the first composition comprises about 2 grams of Spongilla and about 6 mL of 3% hydrogen peroxide or about 6 mL of saline solution.

[0084] In another aspect, any method disclosed herein is provided, wherein the first composition comprises Spongilla in powder form. The material comprising Spongilla may be prepared in the form of a powder having substantially uniform particles by using techniques known to those skilled in the art, such as grinding and sieving. In another aspect, any method disclosed herein is provided, wherein Spongilla is in the form of a powder comprising substantially uniform particles. In another aspect, any method disclosed herein is provided, wherein at least about 50% of the particles comprising Spongilla powder pass through a US 70-mesh screen. In another aspect, any method disclosed herein is provided, wherein at least about 60%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90%, or about 95%, or about 96%, or about 97%, or about 98%, or about 99% of the particles comprising Spongilla powder pass through a US 70-mesh screen. In another aspect, any method disclosed herein is provided, wherein about 95%, or about 96%, or about 97%, or about 98%, or about 99% or more of the particles containing Spongilla powder pass through a US 70-mesh screen. In another aspect, any method disclosed herein is provided, wherein about 95% or more of the particles containing Spongilla powder pass through a US 70-mesh screen. In another aspect, any method disclosed herein is provided, wherein about 96% or more of the particles containing Spongilla powder pass through a US 70-mesh screen. In another aspect, any method disclosed herein is provided, wherein about 97% or more of the particles containing Spongilla powder pass through a US 70-mesh screen. In another aspect, any method disclosed herein is provided, wherein about 98% or more of the particles containing Spongilla powder pass through a US 70-mesh screen.In another aspect, any method disclosed herein is provided, wherein about 99% of the particles comprising Spongilla powder are passed through a US 70-mesh screen. Spongilla particles may be produced or manufactured from harvested Spongilla material through procedures known to those skilled in the art, such as determining an appropriate harvesting period, removing foreign matter, drying, milling and grinding using equipment known to those skilled in the art.

[0085] In another aspect, any method disclosed in this specification is provided, wherein particles comprising spongilla powder have an average length of about 50 μm to about 500 μm. In another aspect, any method disclosed herein is provided, wherein the particles comprising spongezilla powder are about 50 µm to about 400 µm, or about 50 µm to about 350 µm, or about 50 µm to about 300 µm, or about 50 µm to about 250 µm, or about 50 µm to about 200 µm, or about 75 µm to about 500 µm, or about 75 µm to about 450 µm, or about 80 µm to about 450 µm, or about 80 µm to about 400 µm, or about 85 µm to about 450 µm, or about 85 µm to about 400 µm, or about 90 µm to about 450 µm, or about 90 µm to about 400 µm, or about 90 µm to about 350 µm, or About 100 µm to about 450 µm, or about 100 µm to about 400 µm, or about 100 µm to about 350 µm, or about 100 µm to about 300 µm, or about 100 µm to about 250 µm, or about 100 µm to about 200 µm, or about 150 µm to about 500 µm, or about 150 µm to about 450 µm, or about 150 µm to about 400 µm, or about 150 µm to about 350 µm, or about 150 µm to about 350 µm, or about 150 µm to about 300 µm, or about 150 µm to about 250 µm, or about 150 µm to about 200 µm, or about 175 µm to It has an average length of about 450 µm, or about 175 µm to about 400 µm, or about 175 µm to about 350 µm, or about 175 µm to about 300 µm, or about 175 µm to about 250 µm, or about 175 µm to about 200 µm.In another aspect, any method disclosed herein is provided, wherein particles comprising Spongilla powder have an average length of about 50 µm, or about 75 µm, or about 80 µm, or about 85 µm, or about 90 µm, or about 100 µm, or about 125 µm, or about 150 µm, or about 175 µm, or about 200 µm, or about 225 µm, or about 250 µm, or about 300 µm, or about 350 µm, or about 400 µm, or about 450 µm, or about 500 µm. In another aspect, any method disclosed herein is provided, wherein particles comprising Spongilla powder have an average length of about 200 µm. Particles containing spongezilla powder may be produced or manufactured from spongezilla material harvested by procedures known to those skilled in the art, such as milling and grinding using equipment known to those skilled in the art. The average length of particles containing spongezilla powder may be measured using analytical methods known to those skilled in the art, such as scanning electron microscopy (SEM) and sieve analysis. Sieve analysis may also be used to determine the particle size distribution of particles containing spongezilla powder.

[0086] In another aspect, any method disclosed herein is provided, wherein particles comprising Spongilla powder have an average diameter of about 5 μm to about 50 μm. In another aspect, any method disclosed herein is provided, wherein particles comprising Spongilla powder have an average diameter of about 5 μm to about 45 μm, or about 5 μm to about 40 μm, about 5 μm to about 35 μm, about 5 μm to about 30 μm, about 5 μm to about 25 μm, about 5 μm to about 20 μm, about 10 μm to about 50 μm, about 10 μm to about 45 μm, about 10 μm to about 40 μm, about 10 μm to about 35 μm, about 10 μm to about 30 μm, about 10 μm to about 25 μm, or about 10 μm to about 20 μm. In another aspect, any method disclosed herein is provided, wherein particles comprising Spongilla powder have an average diameter of about 5 µm, or about 10 µm, or about 15 µm, or about 20 µm, or about 25 µm, or about 30 µm, or about 35 µm, or about 40 µm, or about 45 µm, or about 50 µm. Particles comprising Spongilla powder may be produced or manufactured from harvested Spongilla material through procedures known to those skilled in the art, such as milling and grinding using equipment known to those skilled in the art. The average diameter of particles comprising Spongilla powder may be measured using analytical methods known to those skilled in the art, such as scanning electron microscopy (SEM) and sieve analysis. Sieve analysis may also be used to determine the particle size distribution of particles comprising Spongilla powder.

[0087] In another aspect, any method disclosed in this specification is provided, wherein particles comprising spongilla powder have an aspect ratio of about 1 to about 100. In another aspect, any method disclosed herein is provided, wherein particles comprising spongezilla powder are about 1 to about 75, or about 1 to about 50, or about 1 to about 25, or about 1 to about 20, or about 1 to about 15, or about 5 to about 100, or about 5 to about 75, or about 5 to about 50, or about 5 to about 40, or about 5 to about 35, or about 5 to about 30, or about 5 to about 25, or about 5 to about 20, or about 5 to about 15, or about 7 to about 50, or about 7 to about 45, or about 7 to about 40, or about 7 to about 35, or about 7 to about 30, or about 7 to about 25, or about 10 to about 50, or about 10 to about 45, or about It has an aspect ratio of 10 to about 40, or about 10 to about 35, or about 10 to about 30, or about 10 to about 25, about 10 to about 20, or about 10 to about 15. Any method disclosed herein in another aspect is provided, wherein particles comprising spongezilla powder have an aspect ratio of about 5, or about 6, or about 7, or about 8, or about 9, or about 10, or about 11, or about 12, or about 13, or about 14, or about 15, or about 16, or about 17, or about 18, or about 19, or about 20, or about 21, or about 22, or about 23, or about 24, or about 25, or about 26, or about 27, or about 28, or about 29, or about 30, or about 35, or about 40, or about 45, or about 50, or about 75, or about 100.Particles containing spongezilla powder may be produced or manufactured from harvested spongezilla material through procedures known to those skilled in the art, such as milling and grinding using equipment known to those skilled in the art. The aspect ratio of particles containing spongezilla powder may be measured using analytical methods known to those skilled in the art, such as scanning electron microscopy (SEM) and sieve analysis. Sieve analysis may also be used to determine the particle size distribution of particles containing spongezilla powder.

[0088] A material containing Spongilla may be processed and dried using techniques known to those skilled in the art, for example, by using a drying oven, in order to provide a material having a desirable residual moisture content. Any method disclosed herein in another aspect is provided, wherein the first composition containing Spongilla has a residual moisture content of about 20% or less. Any method disclosed herein in another aspect is provided, wherein the first composition has a residual moisture content of about 15% or less, or about 10% or less, or about 9% or less, or about 8% or less, or about 7% or less, or about 6% or less, or about 5% or less, or about 4% or less, or about 3% or less, or about 2% or less, or 1% or less. Any method disclosed herein in another aspect is provided, wherein the first composition has a residual moisture content of about 5% or less. Any method disclosed herein in another aspect is provided, wherein the first composition has a residual moisture content of about 4% or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a residual moisture content of about 3% or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a residual moisture content of about 2% or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a residual moisture content of about 1% or less. The moisture content of the Spongilla material can be reduced by heating the raw Spongilla material using equipment known to the art, such as by outdoor drying, or by using a conventional oven dryer or vacuum dryer. For example, the raw Spongilla material can be placed on a tray and heated in a drying oven at a temperature in the range of about 30°C to about 200°C, for example down to about 70°C, for a period of time required to reduce the residual moisture content to a desirable level.The level of residual moisture in the material is the United States Pharmacopoeia method (USP). <731> (Drying Loss) and USP <921> It can be measured using methods known to those skilled in the art, such as those described in (determination of water).

[0089] Materials containing Spongilla, for example through heat treatment or the use of irradiation, for example, gamma ray irradiation, the microbial contamination (bioburden) of the material before packaging and use, such as aerobic and anaerobic microorganisms, yeasts and molds, E. coli-type bacteria, Salmonella ( Salmonella ), Pseudomonas aeruginosa ( pseudomonas aeruginosa ), and Staphilococcus aureus ( Staphylococcus aureus In order to reduce ), it can be processed.

[0090] In another aspect, any method disclosed herein is provided, wherein the first composition is about 25 x 10 4 It has a combined aerobic and anaerobic microbial content of colony-forming units (CFU / g) or less per gram. In another aspect, any method disclosed herein provides, wherein the first composition is about 10 x 10 4 CFU / g or less, or about 5 x 10 4 CFU / g or less, or about 1 x 10⁻⁶ 4 CFU / g or less, or about 5 x 10 3 CFU / g or less, or about 1 x 10⁻⁶ 3CFU / g or less, or about 10,000 CFU / g or less, or about 7,500 CFU / g or less, or about 5,000 CFU / g or less, or about 2,500 CFU / g or less, or about 2,000 CFU / g or less, or about 1,500 CFU / g or less, or about 1,000 CFU / g or less, or about 750 CFU / g or less, or about 500 CFU / g or less, or about 250 CFU / g or less, or about 200 CFU / g or less, or about 150 CFU / g or less, or about 100 CFU / g or less, or about 75 CFU / g or less, or about 50 CFU / g or less, or about 25 CFU / g or less, or about 15 CFU / g or less, or about 10 CFU / g or less, or about 5 CFU / g or less, or about 1 It has a combined aerobic and anaerobic microbial content of CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 1,000 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 750 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 500 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 250 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 200 CFU / g or less. In another aspect, any method disclosed in this specification is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 150 CFU / g or less.In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 100 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 75 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 50 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 25 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 20 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 10 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined aerobic and anaerobic microbial content of about 1 CFU / g or less. The combined aerobic and anaerobic microbial content of the Spongilla material may be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material with heat in the form of steam or dry heat, chemical treatment in the form of exposure to ethylene oxide gas, or treatment with ionizing radiation for a sufficient amount of time to reduce the microbial content to a desirable level. The combined aerobic and anaerobic microbial content of the Spongilla material is United States Pharmacopoeia method USP <61> It can be measured by methods known to those skilled in the art, such as as described in (microbiological count test).

[0091] In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is approximately 25 x 10 4It has a combined yeast and mold content of colony-forming units (CFU / g) or less per gram. In another aspect, any method disclosed herein is provided, wherein the first composition is about 5 x 10 4 CFU / g or less, or about 1 x 10⁻⁶ 4 CFU / g or less, or about 5 x 10 3 CFU / g or less, or about 1 x 10⁻⁶ 3CFU / g or less, or about 10,000 CFU / g or less, or about 7,500 CFU / g or less, or about 5,000 CFU / g or less, or about 2,500 CFU / g or less, or about 2,000 CFU / g or less, or about 1,500 CFU / g or less, or about 1,000 CFU / g or less, or about 750 CFU / g or less, or about 500 CFU / g or less, or about 250 CFU / g or less, or about 200 CFU / g or less, or about 150 CFU / g or less, or about 100 CFU / g or less, or about 75 CFU / g or less, or about 50 CFU / g or less, or about 25 CFU / g or less, or about 15 CFU / g or less, or about 10 CFU / g or less, or about 5 CFU / g or less, or about 1 It has a combined yeast and mold content of CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and mold content of about 1,000 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and mold content of about 750 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and mold content of about 500 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and mold content of about 250 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and mold content of about 200 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and mold content of about 150 CFU / g or less. In another aspect, any method disclosed in this specification is provided, wherein the first composition has a combined yeast and mold content of about 100 CFU / g or less.In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and fungus content of about 75 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and fungus content of about 50 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and fungus content of about 25 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and fungus content of about 20 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and fungus content of about 10 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a combined yeast and fungus content of about 1 CFU / g or less. The combined yeast and fungal content of Spongilla materials may be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material with heat in the form of steam or dry heat, chemical treatment in the form of exposure to ethylene oxide gas, or treatment with ionizing radiation for a sufficient amount of time to reduce the microbial content to a desirable level. The combined yeast and fungal content of Spongilla materials is based on the United States Pharmacopoeia method USP. <61> It can be measured through methods known to those skilled in the art, such as those described in (microbiological count test).

[0092] In another aspect, any method disclosed herein is provided, wherein the amount of E. coli-type bacteria in the first composition is about 25 x 10 4 It is less than or equal to colony-forming units per gram (CFU / g). In another aspect, any method disclosed herein is provided, wherein the amount of E. coli-type bacteria in the first composition is about 5 x 10 4CFU / g or less, or about 1 x 10⁻⁶ 4 CFU / g or less, or about 5 x 10 3 CFU / g or less, or about 1 x 10⁻⁶ 3CFU / g or less, or about 10,000 CFU / g or less, or about 7,500 CFU / g or less, or about 5,000 CFU / g or less, or about 2,500 CFU / g or less, or about 2,000 CFU / g or less, or about 1,500 CFU / g or less, or about 1,000 CFU / g or less, or about 750 CFU / g or less, or about 500 CFU / g or less, or about 250 CFU / g or less, or about 200 CFU / g or less, or about 150 CFU / g or less, or about 100 CFU / g or less, or about 75 CFU / g or less, or about 50 CFU / g or less, or about 25 CFU / g or less, or about 15 CFU / g or less, or about 10 CFU / g or less, or about 5 CFU / g or less, or about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 1,000 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 750 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 500 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 250 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 200 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 150 CFU / g or less. In another aspect, any method disclosed in this specification is provided, wherein the first composition has an E. coli-type bacterial content of about 100 CFU / g or less.In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 75 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 50 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 25 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 20 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 10 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has an E. coli-like bacterial content of about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has no detectable E. coli-like bacterial content. The E. coli-type bacterial content of Spongilla materials may be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material with heat in the form of steam or dry heat, chemical treatment in the form of exposure to ethylene oxide gas, or treatment with ionizing radiation for a sufficient amount of time to reduce the microbial content to a desirable level. The E. coli-type bacterial content of Spongilla materials is United States Pharmacopoeia method USP <62> It can be measured by methods known to those skilled in the art, such as as described in (specific microorganism test).

[0093] In another aspect, any method disclosed herein is provided, wherein the amount of Salmonella in the first composition is about 25 x 10 4It is less than or equal to colony-forming units per gram (CFU / g). In another aspect, any method disclosed herein is provided, wherein the amount of Salmonella in the first composition is about 5 x 10 4 CFU / g or less, or about 1 x 10⁻⁶ 4 CFU / g or less, or about 5 x 10 3 CFU / g or less, or about 1 x 10⁻⁶ 3CFU / g or less, or about 10,000 CFU / g or less, or about 7,500 CFU / g or less, or about 5,000 CFU / g or less, or about 2,500 CFU / g or less, or about 2,000 CFU / g or less, or about 1,500 CFU / g or less, or about 1,000 CFU / g or less, or about 750 CFU / g or less, or about 500 CFU / g or less, or about 250 CFU / g or less, or about 200 CFU / g or less, or about 150 CFU / g or less, or about 100 CFU / g or less, or about 75 CFU / g or less, or about 50 CFU / g or less, or about 25 CFU / g or less, or about 15 CFU / g or less, or about 10 CFU / g or less, or about 5 CFU / g or less, or about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 1,000 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 750 CFU / g. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 500 CFU / g. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 250 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 200 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 150 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 100 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 75 CFU / g or less.In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 50 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 25 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 20 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 10 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Salmonella content of about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has no detectable Salmonella content. The Salmonella content of Spongilla materials can be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material with heat in the form of steam or dry heat, chemical treatment in the form of exposure to ethylene oxide gas, or treatment with ionizing radiation for a sufficient amount of time to reduce the microbial content to a desirable level. The Salmonella content of Spongilla materials is based on the United States Pharmacopoeia method (USP). <62> It can be measured by methods known to those skilled in the art, such as as described in (specific microorganism test).

[0094] In another aspect, any method disclosed herein is provided, wherein the amount of Pseudomonas aeruginosa bacteria in the first composition is about 25 x 10 4 It is less than or equal to colony-forming units per gram (CFU / g). In another aspect, any method disclosed herein is provided, wherein the amount of Pseudomonas aeruginosa bacteria in the first composition is about 5 x 10 4 CFU / g or less, or about 1 x 10⁻⁶ 4 CFU / g or less, or about 5 x 10 3CFU / g or less, or about 1 x 10⁻⁶ 3CFU / g or less, or about 10,000 CFU / g or less, or about 7,500 CFU / g or less, or about 5,000 CFU / g or less, or about 2,500 CFU / g or less, or about 2,000 CFU / g or less, or about 1,500 CFU / g or less, or about 1,000 CFU / g or less, or about 750 CFU / g or less, or about 500 CFU / g or less, or about 250 CFU / g or less, or about 200 CFU / g or less, or about 150 CFU / g or less, or about 100 CFU / g or less, or about 75 CFU / g or less, or about 50 CFU / g or less, or about 25 CFU / g or less, or about 15 CFU / g or less, or about 10 CFU / g or less, or about 5 CFU / g or less, or about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterium content of about 1,000 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterium content of about 750 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterium content of about 500 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterium content of about 250 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterium content of about 200 CFU / g or less. In another aspect, any method disclosed in this specification is provided, wherein the first composition has a content of about 150 CFU / g or less of Pseudomonas aeruginosa bacteria.In another aspect, any method disclosed herein is provided, wherein the first composition has a content of Pseudomonas aeruginosa bacteria of about 100 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a content of Pseudomonas aeruginosa bacteria of about 75 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a content of Pseudomonas aeruginosa bacteria of about 50 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a content of Pseudomonas aeruginosa bacteria of about 25 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a content of Pseudomonas aeruginosa bacteria of about 20 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 10 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition does not have a detectable Pseudomonas aeruginosa bacterial content. The Pseudomonas aeruginosa bacterial content of the Spongilla material may be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material with heat in the form of steam or dry heat, chemical treatment in the form of exposure to ethylene oxide gas, or treatment with ionizing radiation for an amount of time sufficient to reduce the microbial content to a desirable level. The Pseudomonas aeruginosa bacterial content of the Spongilla material is United States Pharmacopoeia method USP <62> It can be measured by methods known to those skilled in the art, such as as described in (specific microorganism test).

[0095] In another aspect, any method disclosed herein is provided, wherein the amount of Staphylococcus aureus bacteria in the first composition is about 25 x 10 4 It is less than or equal to colony-forming units per gram (CFU / g). In another aspect, any method disclosed herein is provided, wherein the amount of Staphylococcus aureus bacteria in the first composition is about 5 x 10⁶ 4 CFU / g or less, or about 1 x 10⁻⁶ 4 CFU / g or less, or about 5 x 10 3 CFU / g or less, or about 1 x 10⁻⁶ 3CFU / g or less, or about 10,000 CFU / g or less, or about 7,500 CFU / g or less, or about 5,000 CFU / g or less, or about 2,500 CFU / g or less, or about 2,000 CFU / g or less, or about 1,500 CFU / g or less, or about 1,000 CFU / g or less, or about 750 CFU / g or less, or about 500 CFU / g or less, or about 250 CFU / g or less, or about 200 CFU / g or less, or about 150 CFU / g or less, or about 100 CFU / g or less, or about 75 CFU / g or less, or about 50 CFU / g or less, or about 25 CFU / g or less, or about 15 CFU / g or less, or about 10 CFU / g or less, or about 5 CFU / g or less, or about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 1,000 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 750 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 500 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 250 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 200 CFU / g or less. In another aspect, any method disclosed in this specification is provided, wherein the first composition has a Staphylococcus aureus bacteria content of about 150 CFU / g or less.In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 100 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 75 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 50 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 25 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 20 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 10 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition has a Staphylococcus aureus bacterial content of about 1 CFU / g or less. In another aspect, any method disclosed herein is provided, wherein the first composition does not have a detectable Staphylococcus aureus bacterial content. The Staphylococcus aureus bacterial content of the Spongilla material may be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material with heat in the form of steam or dry heat, chemical treatment in the form of exposure to ethylene oxide gas, or treatment with ionizing radiation for an amount of time sufficient to reduce the microbial content to a desirable level. The Staphylococcus aureus bacterial content of the Spongilla material is the United States Pharmacopoeia method USP <62> It can be measured through methods known to those skilled in the art, such as those described in (specific microorganism test).

[0096] In another aspect, any method disclosed herein is provided, wherein the first composition is packaged before use. In another aspect, any method disclosed herein is provided, wherein the first composition is prepared by heating to at least about 70°C before packaging to reduce microbial contamination. In another aspect, any method disclosed herein is provided, wherein the first composition is prepared by heating to at least about 50°C, or at least about 60°C, or at least about 75°C, or at least about 80°C, or at least about 85°C, or at least about 90°C, or at least about 100°C, or at least about 110°C, or at least about 115°C, or at least about 120°C, or at least about 125°C, or at least about 130°C, or at least about 135°C, or at least about 140°C, or at least about 150°C, or at least about 160°C, or at least about 170°C, or at least about 180°C, or at least about 190°C, or at least about 200°C before packaging.

[0097] In another aspect, any method disclosed in this specification is provided, wherein the first composition comprising Spongilla is heated to at least about 70°C for at least about 5 minutes before packaging. In another aspect, any method disclosed herein is provided, wherein the first composition is heated to at least about 70°C for at least about 10 minutes, or at least about 15 minutes, or at least about 20 minutes, or at least about 25 minutes, or at least about 30 minutes, or at least about 35 minutes, or at least about 40 minutes, or at least about 45 minutes, or at least about 50 minutes, or at least about 55 minutes, or at least about 60 minutes, or at least about 75 minutes, or at least about 90 minutes, or at least about 120 minutes, or at least about 180 minutes, or at least about 4 hours, or at least about 5 hours, or at least about 6 hours, or at least about 7 hours, or at least about 8 hours, or at least about 9 hours, or at least about 10 hours, or at least about 11 hours, or at least about 12 hours, or at least about 24 hours.

[0098] In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is prepared by treating it with ionizing radiation, such as gamma radiation, before or after packaging. For example, gamma irradiation may be performed on raw Spongilla material before grinding to reduce particle size, after grinding to reduce particle size, on material packaged in bulk, and / or on material after packaging in unit-dose containers. The material may be treated with ionizing radiation, such as gamma radiation, using methods and equipment known to those skilled in the art, such as a gamma irradiator or an electron beam irradiator. In another aspect, any method disclosed herein is provided, wherein a first composition is prepared by treating it with ionizing radiation, such as gamma radiation, to deliver an absorbed radiation dose of about 1 kGy to about 50 kGy before packaging.In another aspect, any method disclosed herein is provided, wherein the first composition is about 1 kGy to about 45 kGy, or about 1 kGy to about 40 kGy, about 1 kGy to about 35 kGy, about 1 kGy to about 30 kGy, or about 1 kGy to about 25 kGy, or about 5 kGy to about 50 kGy, or about 5 kGy to about 45 kGy, or about 5 kGy to about 40 kGy, or about 5 kGy to about 35 kGy, or about 5 kGy to about 30 kGy, or about 5 kGy to about 25 kGy, or about 10 kGy to about 50 kGy, or about 10 kGy to about 45 kGy, or about 10 kGy to about 40 kGy, or about 10 kGy to about 40 kGy, or about 10 It is manufactured by treating with ionizing radiation, such as gamma radiation, to deliver an absorbed radiation dose of kGy to about 35 kGy, or about 10 kGy to about 30 kGy, or about 10 kGy to about 25 kGy, or about 15 kGy to about 50 kGy, or about 15 kGy to about 45 kGy, or about 15 kGy to about 40 kGy, or about 15 kGy to about 35 kGy, or about 15 kGy to about 30 kGy, or about 15 kGy to about 25 kGy.In another aspect, any method disclosed herein is provided, wherein the first composition is about 1 kGy, or about 5 kGy, or about 10 kGy, 11 kGy, or about 12 kGy, or about 13 kGy, or about 14 kGy, or about 15 kGy, or about 16 kGy, or about 17 kGy, or about 18 kGy, or about 19 kGy, or about 20 kGy, or about 21 kGy, or about 22 kGy, or about 23 kGy, or about 24 kGy, or about 25 kGy, or about 26 kGy, or about 27 kGy, or about 28 kGy, or about 29 kGy, or about 30 kGy, or about 31 kGy, or about 32 kGy, or about 33 kGy, It is manufactured by treating with ionizing radiation, such as gamma radiation, to deliver an absorbed radiation dose of about 34 kGy, or about 35 kGy, or about 36 kGy, or about 37 kGy, or about 38 kGy, or about 39 kGy, or about 40 kGy, or about 41 kGy, or about 42 kGy, or about 43 kGy, or about 44 kGy, or about 45 kGy, or about 46 kGy, or about 47 kGy, or about 48 kGy, or about 49 kGy, or about 50 kGy.

[0099] In another aspect, any method disclosed herein is provided, wherein the first composition is applied to the skin of a subject in the form of a paste. In another aspect, any method disclosed herein is provided, wherein the paste further comprises water or saline solution. In another aspect, any method disclosed herein is provided, wherein the paste is prepared by mixing a composition comprising Spongilla and an aqueous solution comprising hydrogen peroxide. In another aspect, any method disclosed herein is provided, wherein hydrogen peroxide is about 0.1% w / w to about 50% w / w, or about 0.1% w / w to about 45% w / w, or about 0.1% w / w to about 40% w / w, or about 0.1% w / w to about 35% w / w, or about 0.1% w / w to about 30% w / w, or about 0.1% w / w to about 25% w / w, or about 0.1% w / w to about 20% w / w, or about 0.1% w / w to about 15% w / w, or about 0.1% w / w to about 10% w / w, or about 0.1% w / w to about 9% w / w, or about 0.1% w / w to about 8% w / w, or about 0.1% w / w Up to about 7% w / w, or about 0.1% w / w to about 6% w / w, or about 0.1% w / w to about 5% w / w, or about 0.1% w / w to about 4% w / w, or about 0.1% w / w to about 3% w / w, or about 0.1% w / w to about 2% w / w, or about 0.1% w / w to about 1% w / w, or about 0.5% w / w to about 45% w / w, or about 1% w / w to about 45% w / w, or about 1% w / w to about 40% w / w, or about 1% w / w to about 35% w / w, or about 1% w / w to about 30% w / w, or about 1% w / w to about 25% w / w, or about 1% w / w to about 20% w / w, or about 1% w / w to about 15% w / w, or about 1% w / w to about 10% w / w, or about 1% w / w to about 9% w / w, or about 1% w / w to about 8% w / w, or about 1% w / w to about 7% w / w, or about 1% w / w to about 6% w / w, or about 1% w / w to about 5% w / w, or About 1% w / w to about 4% w / w, or about 1% w / w to about 3% w / w, or about 1% w / w to about 2% w / w, or about 2% w / w to about 45% w / w, or about 2% w / w to about 40% w / w, or about 2% w / w to about 35% w / w, or about 2% w / w to about 30% w / w, or about 2% w / w to about 25% w / w, or about 2% w / w to about 20% w / w, or about 2% w / w to about 15% w / w, or about 2% w / w to about 10% w / w, or about 2% w / w to about 9% w / w, or about 2% w / w to about 8% w / w, or about 1% w / w to about 7% w / w, or The concentration is about 2% w / w to about 6% w / w, or about 2% w / w to about 5% w / w, or about 2% w / w to about 4% w / w, or about 2% w / w to about 3% w / w. In another aspect, any method disclosed herein is provided, wherein hydrogen peroxide is about 0.1% w / w, or about 0.The concentration is 5% w / w, or about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 6% w / w, or about 7% w / w, or about 8% w / w, or about 9% w / w, or about 10% w / w, or about 15% w / w, or about 20% w / w, or about 25% w / w, or about 30% w / w, or about 35% w / w, or about 40% w / w, or about 45% w / w, or about 50% w / w. Any method disclosed herein in another aspect is provided, wherein the hydrogen peroxide is at a concentration of about 3% w / w. An aqueous hydrogen peroxide solution that may be useful for treating skin conditions in objects as disclosed in this specification may be commercially available or prepared by methods known to those skilled in the art.

[0100] In another aspect, any method disclosed herein is provided, wherein the first composition and / or the second composition may be used in combination with a gel or cream, and the gel or cream may or may not further comprise hydrogen peroxide. In another aspect, any method disclosed herein is provided, wherein the first composition and / or the second composition may be used in combination with a gel or cream, and the gel or cream does not further comprise hydrogen peroxide. In another aspect, any method disclosed herein is provided, wherein the first composition and / or the second composition may be used in combination with a gel or cream, and the gel or cream further comprises hydrogen peroxide. Such gel or cream is generally commercially available and may contain about 0.5% w / w to about 50% w / w hydrogen peroxide. For example, a gel containing about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 6% w / w, or about 7% w / w, or about 8% w / w, or about 9% w / w, or about 10% w / w, or about 15% w / w, or about 20% w / w, or about 25% w / w, or about 30% w / w, or about 40% w / w, or about 45% w / w, or about 50% w / w of hydrogen peroxide may be used in combination with the first composition and the second composition in any of the methods disclosed herein.

[0101] In another aspect, any method disclosed herein is provided, wherein the method further comprises the step of applying a third composition to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the third composition comprises hydrogen peroxide. In another aspect, any method disclosed herein is provided, wherein the hydrogen peroxide has a w / w concentration of about 3%. In another aspect, any method disclosed herein is provided, wherein hydrogen peroxide is about 0.1% w / w to about 50% w / w, or about 0.1% w / w to about 45% w / w, or about 0.1% w / w to about 40% w / w, or about 0.1% w / w to about 35% w / w, or about 0.1% w / w to about 30% w / w, or about 0.1% w / w to about 25% w / w, or about 0.1% w / w to about 20% w / w, or about 0.1% w / w to about 15% w / w, or about 0.1% w / w to about 10% w / w, or about 0.1% w / w to about 9% w / w, or about 0.1% w / w to about 8% w / w, or about 0.1% w / w Up to about 7% w / w, or about 0.1% w / w to about 6% w / w, or about 0.1% w / w to about 5% w / w, or about 0.1% w / w to about 4% w / w, or about 0.1% w / w to about 3% w / w, or about 0.1% w / w to about 2% w / w, or about 0.1% w / w to about 1% w / w, or about 0.5% w / w to about 45% w / w, or about 1% w / w to about 45% w / w, or about 1% w / w to about 40% w / w, or about 1% w / w to about 35% w / w, or about 1% w / w to about 30% w / w, or about 1% w / w to about 25% w / w, or about 1% w / w to about 20% w / w, or about 1% w / w to about 15% w / w, or about 1% w / w to about 10% w / w, or about 1% w / w to about 9% w / w, or about 1% w / w to about 8% w / w, or about 1% w / w to about 7% w / w, or about 1% w / w to about 6% w / w, or about 1% w / w to about 5% w / w, or About 1% w / w to about 4% w / w, or about 1% w / w to about 3% w / w, or about 1% w / w to about 2% w / w, or about 2% w / w to about 45% w / w, or about 2% w / w to about 40% w / w, or about 2% w / w to about 35% w / w, or about 2% w / w to about 30% w / w, or about 2% w / w to about 25% w / w, or about 2% w / w to about 20% w / w, or about 2% w / w to about 15% w / w, or about 2% w / w to about 10% w / w, or about 2% w / w to about 9% w / w, or about 2% w / w to about 8% w / w, or about 1% w / w to about 7% w / w, or The w / w concentration is about 2% w / w to about 6% w / w, or about 2% w / w to about 5% w / w, or about 2% w / w to about 4% w / w, or about 2% w / w to about 3% w / w. In another aspect, any method disclosed herein is provided, wherein hydrogen peroxide is about 0.1% w / w, or about 0.The concentration is 5% w / w, or about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 6% w / w, or about 7% w / w, or about 8% w / w, or about 9% w / w, or about 10% w / w, or about 15% w / w, or about 20% w / w, or about 25% w / w, or about 30% w / w, or about 35% w / w, or about 40% w / w, or about 45% w / w, or about 50% w / w. Any method disclosed herein in another aspect is provided, wherein the hydrogen peroxide is at a concentration of about 3% w / w. An aqueous hydrogen peroxide solution that may be useful for treating skin conditions in objects as disclosed in this specification may be commercially available or prepared by methods known to those skilled in the art.

[0102] In another aspect, any method disclosed in this specification is provided, wherein Spongilla is Spongilla Lacustris.

[0103] The presence of botulinum toxin in vivo can be determined by measuring the presence of proteolytic cleavage products derived from various SNARE proteins (Soluble NSF (N-ethylmaleimide-sensitive factor) Attachment Protein) Receptors. It is known to those skilled in the art that botulinum toxin targets one or more of three SNARE proteins, VAMP (vesicle-associated membrane protein, also known as synaptobrevin), SNAP-25 (synaptosomal-associated protein 25), and syntaxin (STX). BoNT / B cleaves the Q76 (P1 site)-F77 (P1' site) peptide bonds of VAMP-2 (human numbering from here on), BoNT / D and / DC cleave the K59-L60 bond, BoNT / F1 cleaves the Q58-K59 bond, and BoNT / G cleaves the A81-A82 bond. BoNT / F5 and BoNT / FA (also known as BoNT / H) hydrolyze the L54-E55 bond of VAMP-2, and BoNT / X cleaves R66-A67. BoNT / A cleaves the Q197-R198 bond at the C-terminus of SNAP-25, whereas BoNT / E hydrolyzes the R180-I181 peptide bond. BoNT / C cleaves SNAP-25 (in R198-A199), STX-1A (in K253-A254), and STX-1B (in K252-A253). For example, the in vivo presence of BoNT / A can be determined by measuring the presence of SNAP25 cleavage products using an appropriate assay, such as an ELISA assay using one or more monoclonal antibodies.For example, the in vivo presence of onabotulinum toxin A can be determined using one or more mAbs, such as the anti-SNAP-25 monoclonal antibody 4F3-2C1 (available from MyBioSource, Inc. (San Diego, California, United States of America)) and / or the anti-SNAP-25 biotinylated antibody MBS423684 (available from MyBioSource, Inc. (San Diego, California, United States of America)).

[0104] In another aspect, any method disclosed herein is provided, wherein a second composition comprising one or more botulinum toxins is applied topically to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the second composition is applied to the skin of a subject in the form of a solution. In another aspect, any method disclosed herein is provided, wherein a second composition comprising one or more botulinum toxins is applied to the skin of a subject in the form of an aqueous solution. A solution of botulinum toxin comprising an aqueous solution may be prepared by a method known to those skilled in the art. For example, a botulinum toxin product may be available in the form of a vacuum-dried or freeze-dried solid packaged in a vial containing suitable excipients, such as human albumin, sodium chloride, sucrose, and sodium succinate. The vacuum-dried or freeze-dried material may be prepared for use according to the method disclosed herein by reconstituting with a suitable diluent, e.g., preservative-free 0.9% sodium chloride injection USP, slowly injecting the diluent into a vial and mixing the diluent with the vacuum-dried material while rotating the vial. Alternatively, a first aliquot of a suitable diluent, e.g., preservative-free 0.9% sodium chloride injection USP, may be injected into a container containing the vacuum-dried material and mixed to provide a first solution. A second aliquot of a suitable diluent, e.g., preservative-free 0.9% sodium chloride injection USP, may be placed in a syringe, followed by the addition of a predetermined amount of the reconstituted toxin solution, and then the two aliquots may be mixed in the syringe to provide a final solution having a desired concentration of toxin. Generally, the date and time of reconstitution must be recorded, and the reconstituted material must generally be used within 24 hours of reconstitution. Any reconstituted material must be stored under appropriate conditions, such as at a temperature of about 2°C to 8°C, after reconstitution and before use. Generally, the reconstituted material must be clear, colorless, glassy, ​​or particulate before use.Alternatively, the toxin product is available as a pre-formed solution of a predetermined concentration. The toxin solution may be applied topically to the skin of a subject by drawing an appropriate amount of the reconstituted solution from a container, such as a vial, via a syringe, and applying the reconstituted solution to the skin of the subject by an appropriate method, such as a cotton swab or a brush.

[0105] In another aspect, any method disclosed herein is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are selected from botulinum toxin type A and botulinum toxin type B. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type A. In another aspect, any method disclosed herein is provided, wherein botulinum toxin type A is selected from onabotulinum toxin A, avibotulinum toxin A, and incobotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is onabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is avibotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is incobotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin of type B. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are limabotulinum toxin B. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin of type C1. In another aspect, any method disclosed in this specification is provided, wherein one or more types of botulinum toxin are C2 type botulinum toxin.In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type D. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type E. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxins of type E are EB-001A or EB-001T. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxins of type E are EB-001A. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxins of type E are EB-001A. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxins of type E are EB-001T. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type F. In another aspect, any method disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type G.

[0106] In another aspect, any method disclosed in this specification is provided, wherein the number of potency units of a second composition comprising one or more botulinum toxins applied to the skin of a subject is about 1 to about 400 potency units.In another aspect, any method disclosed herein is provided, wherein the number of potency units of a second composition comprising one or more botulinum toxins applied to the skin of a subject is about 10 units to about 400 units, or about 10 units to about 375 units, or about 10 units to about 350 units, or about 10 units to about 325 units, or about 10 units to about 300 units, or about 10 units to about 275 units, or about 10 units to about 250 units, or about 10 units to about 225 units, or about 10 units to about 200 units, or about 10 units to about 175 units, or about 10 units to about 150 units, or about 10 units to about 125 units, or about 10 units to about 100 units, or about 10 units to about 75 units, or about 10 units to about 50 units, or about 10 units to about 40 units, or about 10 units to about 35 units, or about 10 units to about 30 units, or about 10 units to about 25 units, or about 5 units to about 75 units, or about 5 units to 50 units, or about 5 units to about 45 units, or about 5 units to about 40 units, or about 5 units to about 35 units, or about 5 units to about 30 units, or about 5 units to about 25 units, or about 5 units to about 20 units, or about 5 units to about 15 units, or about 5 units to about 10 units, or about 15 units to about 100 units, or about 20 units to about 100 units, or about 25 units to about 100 units, or about 35 units to about 100 units, or about 40 units to about 100 units, or about 50 units to It is about 100 units, or about 60 units to about 100 units, or about 70 units to about 100 units, or about 80 units to about 100 units, or about 90 units to about 100 units.Any method disclosed herein in another aspect is provided, wherein the number of potency units of a second composition comprising one or more botulinum toxins applied to the skin of a subject is about 1 unit, or about 2 units, or about 3 units, or about 4 units, or about 5 units, or about 6 units, or about 7 units, or about 8 units, or about 9 units, or about 10 units, or about 11 units, or about 12 units, or about 13 units, or about 14 units, or about 15 units, or about 20 units, or about 25 units, or about 30 units, or about 35 units, or about 40 units, or about 45 units, or about 50 units, or about 60 units, or about 70 units, or about 80 units, or about 90 units, or about 100 units. The number of potency units of a composition comprising at least one botulinum toxin that can be used according to the methods and kits disclosed herein may be determined by a person skilled in the art. The potency of an individual botulinum toxin composition may be determined by a method known to a person skilled in the art (e.g., see Fernandez-Salas et al., PLOS ONE, vol. 7, pp. e49516 (2012)), e.g., a suitable cell-based assay, mouse LD. 50 (mLD 50) use of bioassays, localized muscle paralysis (abdominal apoptosis) (e.g., see [Sesardic et al., Pharmacol. Toxicol., vol. 78, pp. 283 to 288 (1996)]), finger abduction score assay (e.g., [Aoki et al., Toxicon., vol. 39, pp. 1815–1820 (2001)]), rat or mouse phrenic diaphragm (e.g., [Goschel et al., Exp Neurol., vol. 147, pp. 96–102 (1997)]), rat intercostal muscle strip assay (e.g., [Huber et al., Altern Lab Anim., vol. 36, pp. 141–152 (2008)]), and [Rasetti-Escargucil et al., It can be determined by [refer to Toxicon., vol. 53, pp. 503-511 (2009)].

[0107] In another aspect, any method disclosed herein is provided, wherein the amount of a first composition comprising Spongilla applied to the skin of a subject is about 0.5 grams to about 50 grams. In one aspect, any method disclosed herein is provided, wherein the amount of the first composition is measured as dry weight. In another aspect, any method disclosed herein is provided, wherein the amount of a first composition comprising Spongilla applied to the skin of a subject is about 0.5 grams to about 40 grams, or about 0.5 grams to about 35 grams, or about 0.5 grams to about 30 grams, or about 0.5 grams to about 25 grams, or about 0.5 grams to about 20 grams, or about 0.5 grams to about 15 grams, or about 0.5 grams to about 10 grams, or about 0.75 grams to about 20 grams, or about 0.75 grams to about 15 grams, or about 0.75 grams to about 10 grams, or about 1 gram to about 20 grams, or about 1 gram to about 15 grams, or about 1 gram to about 10 grams, or about 1 gram to about 9 grams. It is gram, or about 1 gram to about 8 grams, or about 1 gram to about 7 grams, or about 1 gram to about 6 grams, or about 1 gram to about 5 grams, or about 1 gram to about 4 grams, or about 1 gram to about 3 grams, or about 1 gram to 2 grams. In other aspects, any method disclosed herein is provided, wherein, as disclosed above, the amount of Spongilla applied to the skin is each measured as dry weight.

[0108] In another aspect, any method disclosed herein is provided, wherein the amount of a first composition comprising Spongilla applied to the skin of a subject is, in each case, measured as dry weight, about 0.5 grams, or about 0.75 grams, or about 1 gram, or about 1.25 grams, or about 1.5 grams, or about 1.75 grams, or about 2 grams, or about 2.25 grams, or about 2.5 grams, or about 2.75 grams, or about 3 grams, or about 3.25 grams, or about 3.5 grams, or about 3.75 grams, or about 4 grams, or about 4.25 grams, or about 4.5 grams, or about 4.75 grams, or about 5 grams, or about 5.25 grams, or about 5.5 grams, or about 5.75 grams, or about 6 grams, or about 6.25 grams, or about 6.5 grams, or about 7 grams, or about 7.25 grams, or about 7.5 grams, or about 7.75 grams, or about 8 grams, or about 8.25 grams, or about 8.5 grams, or about 8.75 grams, or about 9 grams, or about 9.25 grams, or about 9.5 grams, or about 9.75 grams, or about 10 grams, or about 11 grams, or about 12 grams, or about 13 grams, or about 14 grams, or about 15 grams, or about 16 grams, or about 17 grams, or about 18 grams, or about 19 grams, or about 20 grams, or about 25 grams, or about 35 grams, or about 40 grams, or about 45 grams, or It is about 50 grams, or about 75 grams, or about 100 grams, or about 250 grams, or about 500 grams, or about 750 grams, or about 1000 grams.

[0109] In another aspect, any method disclosed herein is provided, wherein the first composition is applied to the skin of a subject before the second composition is applied to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the first composition is applied to the skin of a subject and is allowed to dry on the skin of a subject before the application of the second composition to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the first composition is applied to the skin of a subject in the form of an aqueous paste, wherein the aqueous component may be water or saline solution. In another aspect, any method disclosed herein is provided, wherein the aqueous paste further comprises hydrogen peroxide. In another aspect, any method disclosed herein is provided, wherein an aqueous solution of hydrogen peroxide is applied to the face of a subject after the application of the first composition to the skin of a subject and before the application of the second composition to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the first composition further comprises hydrogen peroxide. In another aspect, any method disclosed herein is provided, wherein the hydrogen peroxide is an aqueous solution. In another aspect, any method disclosed herein is provided, wherein the aqueous solution comprises hydrogen peroxide at a w / w concentration of about 3%. In another aspect, any method disclosed herein is provided, wherein the second composition is allowed to dry on the skin of the subject after application.

[0110] In another aspect, any method disclosed herein is provided, wherein the second composition is applied to the skin of a subject before the first composition is applied to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the second composition is allowed to dry on the skin of a subject before the first composition is applied to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the first composition is applied to the skin of a subject in the form of an aqueous paste, wherein the aqueous portion may be derived from water or brine. In another aspect, any method disclosed herein is provided, wherein the aqueous paste further comprises hydrogen peroxide. In another aspect, any method disclosed herein is provided, wherein an aqueous solution of hydrogen peroxide is applied to the face of a subject after the application of the first composition to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the hydrogen peroxide is an aqueous solution. In another aspect, any method disclosed herein is provided, wherein the aqueous solution comprises hydrogen peroxide at a concentration of about 3% w / w. In another aspect, any method disclosed in this specification is provided, wherein the first composition is allowed to dry on the skin of a subject.

[0111] In another aspect, any method disclosed herein is provided, wherein the first composition and the second composition are mixed together and the final mixture is applied to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the first composition is mixed with an aqueous solution of hydrogen peroxide before being mixed with the second composition. In another aspect, any method disclosed herein is provided, wherein the mixture of the first composition and the second composition is further mixed with an aqueous solution of hydrogen peroxide before being applied to the skin of a subject. In another aspect, any method disclosed herein is provided, wherein the aqueous solution contains hydrogen peroxide at a w / w concentration of about 3%. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla and the second composition comprising one or more botulinum toxins are applied to the skin of a subject once per week.

[0112] In another aspect, any method disclosed in this specification is provided, wherein the subject applies a second composition comprising one or more botulinum toxins to the skin no more than once every four weeks.

[0113] In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least one week. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject at least twice per week for at least one week, at least three times per week for at least one week, at least four times per week for at least one week, at least five times per week for at least one week, at least six times per week for at least one week, or at least seven times per week for at least one week.

[0114] In another aspect, any method disclosed in this specification is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject at least once per week for at least 2 weeks, at least once per week for at least 3 weeks, at least once per week for at least 4 weeks, at least once per week for at least 5 weeks, at least once per week for at least 6 weeks, at least once per week for at least 7 weeks, at least once per week for at least 8 weeks, at least once per week for at least 9 weeks, at least once per week for at least 10 weeks, at least once per week for at least 11 weeks, at least once per week for at least 12 weeks, at least once per week for at least 13 weeks, at least once per week for at least 14 weeks, at least once per week for at least 15 weeks, at least once per week for at least 16 weeks, at least It is applied at least once per week for 17 weeks, at least once per week for 18 weeks, at least once per week for 19 weeks, at least once per week for 20 weeks, at least once per week for 21 weeks, at least once per week for 22 weeks, at least once per week for 23 weeks, and at least once per week for 24 weeks. In another aspect, any method disclosed herein is provided, wherein the first composition comprising Spongilla is applied to the skin of a subject once per week for 6 weeks.

[0115] In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 24 weeks, and a second composition comprising one or more botulinum toxins is applied to the skin of a subject only during the first week of treatment. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 20 weeks, and a second composition comprising one or more botulinum toxins is applied to the skin of a subject only during the first week of treatment. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 16 weeks, and a second composition comprising one or more botulinum toxins is applied to the skin of a subject only during the first week of treatment. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 12 weeks, and a second composition comprising one or more botulinum toxins is applied to the skin of a subject only during the first week of treatment. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 8 weeks, and a second composition comprising one or more botulinum toxins is applied to the skin of a subject only during the first week of treatment. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for 6 weeks, and a second composition comprising one or more botulinum toxins is applied to the skin of a subject only during the first week of treatment.In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of a subject once per week for four weeks, and a second composition comprising one or more botulinum toxins is applied to the skin of a subject only during the first week of treatment.

[0116] In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins is applied to the skin of a subject on at least one of the face, back, and chest of the subject. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins is applied to the skin of a subject on the face of the subject. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins is applied to the skin of a subject on the back of the subject. In another aspect, any method disclosed herein is provided, wherein a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins is applied to the skin of a subject on the chest of the subject.

[0117] In another aspect, any method disclosed herein is provided, wherein the skin of a subject is cleansed using a non-comedogenic cleanser, water, or a combination of a non-comedogenic cleanser and water after the application of a first composition comprising Spongilla. In another aspect, any method disclosed herein is provided, wherein the skin of a subject is cleansed using a non-comedogenic cleanser, water, or a combination of a non-comedogenic cleanser and water after the application of a second composition comprising one or more botulinum toxins to the skin of a subject. The non-comedogenic cleanser is formulated so as not to cause pore blockage on the skin of a subject to which such cleanser is applied.

[0118] In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, leg disease, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (hyperhidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is acne vulgaris. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is type 1 rosacea. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is type 2 rosacea. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is psoriasis. In another aspect, any method disclosed herein is provided, wherein the skin condition in the subject is hyperhidrosis.

[0119] Acne vulgaris is a common chronic skin condition involving blockage and / or inflammation of the pilosebaceous unit (hair follicles and their associated sebaceous glands). Acne can exist as non-inflammatory lesions, inflammatory lesions, or a mixture of both, and generally affects the face, as well as the back and chest. The efficacy of a therapeutic regimen in subjects with acne vulgaris can be measured by methods known to those skilled in the art, such as the measurement of lesion counts on the subject's face and a comprehensive evaluation by the researcher, as identified below:

[0120]

[0121] Rosacea is well known as a chronic skin disorder of the central facial bulges (cheeks, chin, nose, and central forehead), often characterized by periods of remission and exacerbation. Based on current knowledge, it is considered a syndrome or typology that includes various combinations of skin signs such as flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and rhinophyma. In most cases, some rather than all of these signs appear in any given subject. Type 1 rosacea, or erythematotelangiectatic rosacea, is primarily characterized by flushing and persistent central facial erythema. The presence of telangiectasia is common but not essential in the diagnosis of its subtypes. Central facial edema, tingling and burning sensations, and coarseness or scaling may also be reported. A history of flushing alone is common among subjects presenting with erythematotelangiectatic rosacea. The efficacy of the treatment regimen in subjects with type 1 rosacea can be measured by the use of methods known to those skilled in the art, such as the clinical erythema evaluation (CEA), the 5-point grading scale for facial erythema severity, and the subject self-assessment (SSA) indicated below:

[0122]

[0123]

[0124] Type 2 rosacea (papulopustular) is characterized by persistent central facial erythema distributed in the center of the face, consisting of transient papules or pustules, or both. However, papules and pustules may also occur around pores (i.e., they may occur in the perioral, nasal, or periorbital areas). The papulopustular subtype resembles acne vulgaris except for the absence of comedones. Rosacea and acne can occur concurrently, and such subjects may have comedones as well as papules and pustules of rosacea. Burning and stinging sensations may be reported by subjects with papulopustular rosacea. This subtype is often identified after or in combination with the first subtype, including the presence of telangiectasia. Telangiectasia may be obscured by persistent erythema, papules, or pustules and tends to become more visible after successful treatment of these masking components. The efficacy of the treatment regimen in subjects with type 2 rosacea can be measured through methods known to those skilled in the art, for example, through the measurement of the total lesions on the skin area of ​​the treated subject and the investigator's comprehensive evaluation indicated below:

[0125]

[0126] Psoriasis is a skin condition that accelerates the life cycle of skin cells. This causes cells to accumulate rapidly on the surface of the skin. The excess skin cells form itchy and sometimes painful scales and red patches. Symptoms that may be exhibited by subjects with psoriasis include red patches of skin covered with thick, silvery scales, small patches of desquamation (usually seen in children), dry, cracked skin that may bleed, itching, burning or stinging, thickened, pitted, or furrowed nails, and swollen and stiff joints. The efficacy of a treatment regimen in subjects with psoriasis can be measured through methods known to those skilled in the art, such as the use of the Psoriasis Area and Severity Index (PASI). The use of PASI involves dividing the subject's body into four parts (head (H) (10% of human skin); arms (A) (20%); trunk (T) (30%); legs (L) (40%)). Each of these areas is scored individually, and the four scores are combined to form a final PASI. For each part, the percentage of the skin area involved is estimated and then converted to a grade from 0 to 6 as shown in the table below. Within each area, severity is estimated based on three clinical signs: erythema (redness), induration (thickness), and peeling (skin peeling). Severity parameters are measured on a scale from 0 to 4, ranging from 0 to maximum. Next, the sum of all three severity parameters is calculated for each part of the skin, multiplied by the area score for that area, and multiplied by the weight of the individual part (0.1 for the head, 0.2 for the arms, 0.3 for the body, and 0.4 for the legs).

[0127]

[0128] Hyperhidrosis is a condition generally characterized by abnormally increased sweating that exceeds what is necessary for thermoregulation. While primarily a physical burden, hyperhidrosis can impair quality of life from psychological, emotional, and social perspectives. The efficacy of therapeutic regimens in subjects with hyperhidrosis may be measured by methods known to those skilled in the art, such as the use of the Hyperhidrosis Disease Severity Scale (HDSS), a 4-point scale designed to assess the severity of primary axillary hyperhidrosis in daily clinical practice or clinical research. The HDSS may be administered by an interviewer or self-completed by the subject. The HDSS assesses subject severity based on the degree of excessive sweating-related impairment in daily activities. Subjects rate their severity as follows: 1 = My axillary sweating is not noticeable and does not interfere with my daily activities at all; 2 = My axillary sweating is tolerable and occasionally interferes with my daily activities; 3 = My underarm sweating is barely bearable and frequently interferes with my daily activities; or 4 = My underarm sweating is unbearable and always interferes with my daily activities.

[0129] The efficacy of a therapeutic regimen in subjects with hyperhidrosis may also be measured through the use of the Axillary Sweating Daily Diary (ASDD), Item 2, and / or the Axillary Sweating Daily Diary-Children (ASDD-C), which are validated patient-reported outcome measures for assessing the severity of axillary hyperhidrosis sweating. ADSS Item 2 asks subjects to rate their axillary sweating during the last 24-hour period at its worst using a 10-point scale, where 0 indicates "no sweating at all" and 10 indicates "worst possible sweating." [Glaser et. al., J. Am. Acad. Dermatol Refer to Supplementary Drawing 1 for the description of ASDD, including Item 2 of [., 2018], and ASDD-C.

[0130] Alopecia areata is an autoimmune skin disease that causes hair loss on the scalp, face, and sometimes other areas of the body. In fact, it affects as many as 6.8 million people in the United States. The efficacy of a treatment regimen in subjects with alopecia areata can be measured by methods known to those skilled in the art, such as the count of scattered hairs on the subject's pillow and the use of a fixed count of hairs.

[0131] Androgenetic alopecia is a genetically determined disorder characterized by a gradual transition from terminal hair to intermediate hair, and finally to vellus hair. It is an extremely common disease affecting both men and women. Subjects suffering from androgenetic alopecia generally exhibit symptoms such as the onset of gradual hair loss, increased hair shedding, and a transition in the affected area from large, thick, colored terminal hair to thinner, shorter intermediate hair, and finally to short, sparse, colorless vellus hair; the final result may be a total area of ​​hair loss; this area varies from subject to subject and is generally most prominent on the crown. The efficacy of a treatment regimen in subjects with androgenetic alopecia can be measured by methods known to those skilled in the art, such as the count of scattered hairs on the subject's pillow and the count of fixed hairs.

[0132] A keloid is a raised, reddish nodule that develops at a site of injury. After a wound occurs on the skin, both skin cells and connective tissue cells (fibroblasts) begin to proliferate to repair the damage. A scar consists of cartilage-like fibers, or 'connective tissue,' deposited in the skin by fibroblasts that keep the wound closed. In the case of a keloid, fibroblasts continue to proliferate even after the wound has filled. Consequently, the keloid protrudes above the surface of the skin, forming a massive pile of scar tissue. While keloids can form on any part of the body, they tend to form particularly on the upper chest, shoulders, and upper back. Symptoms include skin discoloration, itching, redness, and uncommon sensations and pain. People of darker skin tones appear to be more prone to forming keloids. Men and women are equally affected. Although keloids are considered benign tumors, they are primarily a cosmetic nuisance and never become malignant. Surgery for keloids generally stimulates the formation of more tissue; it can be said that for many individuals with keloids, there is no available treatment. Hypertrophic scars appear similar and are more common than keloids, but they generally do not grow as large as keloids, can gradually fade over time, and occur in all racial groups.The efficacy of the treatment regimen in subjects with keloids and / or hypertrophic scars may be measured by methods known to those skilled in the art, such as the use of the Vancouver Scar Scale (VSS), Manchester Scar Scale (MSS), Subject and Observer Scar Assessment Scale (POSAS), Visual Analog Scale (VAS), and Stony Brook Scar Evaluation Scale (SBSES).

[0133] Hidradenitis suppurativa tends to occur in areas where normal pimples do not appear, and is a condition that generally begins as pimple-like bumps on the skin, most commonly in the armpits and groin. If hidradenitis suppurativa worsens, the pimple-like bumps may grow deep into the skin, become painful, and rupture. When the deep bumps heal, scars may form, and in some subjects, tunnel-like ducts may develop beneath their skin, leading to scar formation and thickening. If thick scars form in the armpits, it may be difficult to move the arms. Thick scars in the groin area may make walking difficult. The efficacy of the treatment in subjects suffering from hidradenitis suppurativa can be measured through methods known to those skilled in the art, such as visual measurement of the number of lesions on the affected area of ​​the subject's skin.

[0134] Raynaud's phenomenon is a type of vascular disorder most commonly characterized by a change in finger color from pale blue to red after exposure to cold. The cause of Raynaud's phenomenon is unknown, but it is suspected that nerve sensitivity to cold and abnormal nerve control of blood vessel diameter are involved. The symptoms of Raynaud's phenomenon depend on the severity, frequency, and duration of vasospasms. The efficacy of therapeutic regimens in subjects suffering from Raynaud's phenomenon can be measured through methods known in the field, such as digital pulp temperature measurement, photographic analysis of the affected area, and visual analog scales for pain in the affected area.

[0135] Postherpetic neuralgia is generally considered a complication of shingles caused by the varicella-zoster virus. Postherpetic neuralgia affects nerve fibers and the skin, resulting in burning pain that persists for a long time even after the rash and blisters of shingles have disappeared. The signs and symptoms of postherpetic neuralgia are generally confined to the skin area of ​​the subject where the shingles outbreak first occurred. The signs and symptoms of postherpetic neuralgia may include pain that persists for more than three months after the shingles rash has healed and sensitivity to light contact has subsided, as well as itching and tingling in the affected area. The efficacy of a treatment regimen for a subject suffering from postherpetic neuralgia can be measured by methods known to those skilled in the art, such as the use of a visual analog scale for pain in the affected area.

[0136] Heri-Heri disease (familial benign pemphigus) is a genetic disorder characterized by the manifestation of skin rashes and blisters, resulting in the formation of blisters on the skin, typically in skin folds, and often over large areas of the body. Painful blisters rupture, sometimes become infected and peel off, and sometimes new blisters form on the peeled skin in seemingly infinite cycles of manifestation. The cause of the disease is a half-deficiency of the enzyme ATP2C1, which codes for the protein hSPCA1. A mutation in one copy of the gene causes only half of this essential protein to be produced, and because skin cells do not adhere properly due to malformations of intracellular desmosomes, it results in acanthosis, blisters, and rashes. The efficacy of a therapeutic regimen in subjects suffering from Heri-Heri disease can be measured through methods known to those skilled in the art, such as measuring the total number of lesions in the subject, where a decrease in the total number of lesions indicates that the therapeutic regimen has a benign effect.

[0137] Linear IgA bullous dermatitis (LABD) is a rare subepidermal bullous disease caused by an autoimmune reaction to basement membrane proteins, such as the plaques clear and the lamina propria. Basement membranes help stabilize the skin by anchoring the epidermis to the dermis. When IgA antibodies target these proteins, the basement membranes become destabilized, leading to the formation of taut substances. In most cases of LABD, the cause is unknown or idiopathic. Furthermore, more than half of all childhood cases tend to relapse during an average course of two to four years. Adults may have a more delayed course, and LABD has been identified in individuals with internal malignancies, infections, and other autoimmune diseases, such as rheumatoid arthritis or dermatomyositis. Other cases of LABD are often drug-induced by vancomycin, and in some cases, the condition may develop early after the first dose of vancomycin. The efficacy of a therapeutic agent in a subject suffering from LABD can be measured by methods known to those skilled in the art, such as the measurement of the total number of lesions in the subject, where a decrease in the total number of lesions indicates that the therapeutic agent has a positive effect.

[0138] Epidermolysis bullosa (EBS) is a chronic vesicular disease characterized by the formation of intraepidermal vesicles and milia on the hands, elbows, or knees from birth to infancy, following minimal trauma. It is a genetic disorder caused by dominant-negative mutations in the Keratin 5 (KRT5) or Keratin 14 (KRT14) genes. Based on its clinical signs, EBS is subdivided into generalized (Koebner), focal (Weber-Cockayne), and herpetic type 1 (Dowling-Meara). The focal form of EBS is the mildest subtype, involving the easy onset of vesicles on the palms and soles following minimal mechanical trauma. Molecular genetic studies of EBS indicate the presence of mutations in KRT5 and KRT14 due to scaffolding on hemidesmosomes within keratinocytes located in the basal layer near the dermal-epidermal junction. Mutations in each subtype of EBS vary in location and severity2,3. The efficacy of a treatment in subjects suffering from EBS can be measured by methods known to those skilled in the art, such as measuring the total number of lesions in subjects, where a decrease in the total number of lesions indicates that the treatment has a positive effect.

[0139] Dermatosis is a skin condition characterized by wart-like lesions on the body. The lesions are generally yellowish in color, difficult to touch, slightly oily, and may emit a strong odor. The most common sites for lesions are the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ears. Mucosal membranes can also be affected, with lesions appearing on the roof of the mouth (palate), tongue, inside the cheeks, gums, and throat. Other features of dermatosis include nail abnormalities such as red and white streaks on the fingernails and toenails with an irregular texture, and small pitted marks on the palms and soles. The wart-like lesion features of dermatosis generally appear in late childhood to early adulthood. The severity of the disease varies over time, and affected individuals experience sharp relapses alternating with periods of having few lesions. The appearance of lesions is influenced by environmental factors. Most people with leg disease will experience more abrasions during the summer months when they are exposed to heat and humidity. UV rays; minor injuries or friction, such as rubbing or abrasions; and the intake of certain medications can also lead to an increase in abrasions. The efficacy of a treatment regimen in subjects suffering from leg disease can be measured through methods known to those skilled in the art, such as the measurement of the total number of lesions and the measurement of lesion size in subjects, where a decrease in the total number of lesions indicates that the treatment regimen has a positive effect.

[0140] Congenital onychomycosis is a condition that primarily affects the nails and skin. Signs and symptoms of this condition generally become apparent within the first few months of an individual's life. Almost all individuals with congenital onychomycosis exhibit hypertrophic onychomycosis, characterized by thickened and abnormally formed fingernails and toenails. Many affected children also develop very painful blisters and calluses on the soles of their feet, which are less common on the palms. This condition is also known as palmoplantar keratoderma. Severe blisters and calluses on the feet can make walking painful or impossible. Congenital onychomycosis may present several additional features that vary depending on the affected individual. These features include thick, white patches on the tongue and inside the cheeks (oral leukorrhea); lumps called follicular keratosis occurring around hair follicles on the elbows, knees, and waist; and cysts on the armpits, groin, back, or scalp. and includes excessive sweating on the palms and soles (palmar-plantar hyperhidrosis). Some affected individuals also develop extensive cysts called multiple sebaceous cysts, which are filled with an oily substance called sebum that normally smooths the skin and hair. Some infants with congenital onychomycosis have fetal or birth teeth, which are teeth present at birth or in early infancy. Rarely, congenital onychomycosis can affect the vocal box (larynx), potentially causing hoarseness or breathing problems. The efficacy of a therapeutic regimen in subjects suffering from congenital onychomycosis can be measured through methods known to those skilled in the art, such as counting the total number of substances and measuring the size of the substances in the affected area on the subject.

[0141] Hydrogenic keratosis (AK) is a skin disorder also known as acquired hydrogenic palmoplantar keratosis, transient reactive translucent papular acrokeratosis, hydrogenic folds of the palms, or hydrogenic syringe acrokeratosis. The main features of this disorder are edema, white papules, pruritus, burning sensation, and painful skin folds on the palms and soles following contact with water. While prolonged water exposure and water temperature influence the rate and intensity of lesion development, the pathogenesis of AK is not fully understood. The efficacy of a therapeutic regimen in subjects suffering from AK can be measured through methods known to those skilled in the art, such as the total number of lesions in the subject, visual analog pain scores, and visual analog pruritus scores.

[0142] Paresthetic back pain is a sensory neuropathic syndrome of the skin of the middle back, classically described as a unilateral subscapular area. It is primarily a localized pruritus and paresthesia syndrome, and generally involves transient itching or pain on a small area of ​​the middle back, which is an easily accessible skin area. The correlation between corresponding degenerative changes in the spine and the location of paresthetic back pain suggests that while spinal nerve impingement may be a contributing cause, the subject may also have other pathological conditions that make them vulnerable to peripheral neuropathy, such as nerve damage. The efficacy of a therapeutic regimen in subjects suffering from paresthetic back pain can be measured by methods known to those skilled in the art, such as the measurement of the total number of lesions in the subject, visual analog pain scores, and visual analog pruritus scores.

[0143] Dyshidrotic eczema (hypochondriac eczema) is a skin condition in which very small, fluid-filled blisters appear on the palms of the subject's hands, the sides of the fingers, and the soles of the feet. Blisters caused by abnormal sweating can cause severe itching, and when dry, may cause scaling on the subject's skin. Typically, blisters sometimes recur on the subject's skin before previous blisters have completely healed. The efficacy of a treatment regimen in subjects suffering from dyshidrotic eczema can be measured by methods known to those skilled in the art, such as the observation of signs and symptoms of the eczema, visual analog pain scores, and visual analog pruritus scores.

[0144] Chromhidrosis is a pathological condition characterized by the secretion of colored sweat and is caused by the deposition of lipofuscin in the sweat glands. It generally affects the apocrine glands of the face and armpits. The efficacy of a therapeutic regimen in subjects suffering from chromhidrosis can be measured through methods known to those skilled in the art, such as observing signs of sweat and the odor of sweat in the affected subjects.

[0145] Bromhidrosis, also known as bromhidrosis, is a pathological condition of abnormal or unpleasant body odor determined generally by apocrine gland secretion, although other sources may play a role. Sweat glands are classified into two types: apocrine and eccrine, and some crossover exists in some subjects. The efficacy of a therapeutic regimen in subjects suffering from bromhidrosis can be measured through methods known to those skilled in the art, such as observing the odor of sweat in the affected subjects.

[0146] Eccrine nevus is a condition that may be present at birth or in early childhood. It is more often associated with focal hyperhidrosis, but unassociated cases have also been reported. It is generally characterized by an increase in the number or size of eccrine glands that are histologically and structurally normal. The efficacy of a treatment in subjects suffering from eccrine nevus can be measured by methods known to those skilled in the art, such as the use of the Hyperhidrosis Disease Severity Scale (HDSS) and the measurement of the number of sweating episodes per month in the affected subjects.

[0147] Facial wrinkles are a pathological condition of a subject associated with moderate to severe glabellar wrinkles associated with corrugator muscle and / or nasal muscle, moderate to severe lateral canthoplasty wrinkles associated with periorbital muscle activity, and / or moderate to severe forehead wrinkles associated with frontal muscle activity. The efficacy of a therapeutic regimen in subjects with facial wrinkles can be measured by methods known to those skilled in the art, including the 4-point facial wrinkle scale (FWS; 0=none, 1=mild, 2=moderate, 3=severe).

[0148] Atrophic acne scars can occur in subjects suffering from acne. The efficacy of a treatment regimen in subjects suffering from atrophic acne scars can be measured through methods known to those skilled in the art, including self-assessment of clinical acne-related scars (SCARS) and the Facial Acne Scar Quality of Life (FASQoL) tool.

[0149] In another aspect, a method for treating a skin condition in a subject is provided, comprising the step of applying a first composition comprising a sponge and a second composition comprising one or more botulinum toxins to the skin of a subject, wherein (a) the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G; (b) The skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloid, and hypertrophic scar, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaigne disease, dermatophytosis of the legs, congenital onychomycosis, hydrogenic keratoderma, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. Another embodiment is a method, wherein one or more botulinum toxin types are selected from botulinum toxin type A and botulinum toxin type B. Another embodiment is a method, wherein one or more botulinum toxin types are botulinum toxin type A. Another embodiment is a method, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. Another embodiment is a method, wherein the botulinum toxin of type A is onabotulinum toxin A. Another embodiment is a method, wherein the botulinum toxin of type A is avibotulinum toxin A. Another embodiment is a method, wherein the botulinum toxin of type A is incobotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is daxibotulinum toxin A.Another embodiment is a method, wherein one or more types of botulinum toxin are botulinum toxin type B. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin type B are limabotulinum toxin B. Another embodiment is a method, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are botulinum toxin type E. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin are EB-001A or EB-001T. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin type E are EB-001A. In another aspect, any method disclosed herein is provided, wherein one or more types of botulinum toxin type E are EB-001T. Another embodiment is a method, wherein the skin condition in the subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, and hyperhidrosis. Another embodiment is a method, wherein the skin condition in the subject is acne vulgaris. Another embodiment is a method, wherein the skin condition in the subject is type rosacea. Another embodiment is a method, wherein the skin condition in the subject is type 2 rosacea. Another embodiment is a method, wherein the skin condition in the subject is psoriasis. Another embodiment is a method, wherein the skin condition in the subject is hyperhidrosis. Another embodiment is a method, wherein the spongilla is Spongilla lacustris. Another embodiment is a method, wherein the second composition comprising one or more botulinum toxins is applied topically to the skin of the subject. Another embodiment is a method, wherein the second composition comprising one or more botulinum toxins is in the form of an aqueous solution. Another embodiment is a method in which the second composition is applied to the skin of a subject in the form of a solution.Another embodiment is a method, wherein the second composition is in the form of an aqueous solution. Another embodiment is a method, wherein the amount of the first composition containing Spongilla applied to the skin of a subject is about 0.5 grams to about 50 grams, measured by dry weight. Another embodiment is a method, wherein the first composition is applied to the skin of a subject in the form of a paste. Another embodiment is a method, wherein the paste further comprises water or a brine. Another embodiment is a method, wherein the paste is prepared by mixing a powder containing Spongilla and an aqueous solution containing hydrogen peroxide. Another embodiment is a method, wherein the aqueous solution contains hydrogen peroxide at a w / w concentration of about 3%. Another embodiment is a method, wherein the first composition is applied to the skin of a subject before the second composition is applied to the skin of a subject. Another embodiment is a method, wherein the first composition is applied to the skin of a subject and left to dry on the skin of a subject before the second composition is applied to the skin of a subject. Another embodiment is a method in which the first composition is applied to the skin of a subject in the form of an aqueous paste, wherein the aqueous portion is derived from water or brine. Another embodiment is a method in which the aqueous paste further comprises hydrogen peroxide. Another embodiment is a method in which an aqueous solution of hydrogen peroxide is applied to the face of a subject after the application of the first composition to the skin of a subject and before the application of the second composition to the skin of a subject. Another embodiment is a method in which the first composition further comprises hydrogen peroxide. Another embodiment is a method in which the hydrogen peroxide is an aqueous solution. Another embodiment is a method in which the aqueous solution comprises hydrogen peroxide at a w / w concentration of about 3%. Another embodiment is a method in which the second composition is left to dry on the skin of a subject after application to the skin of a subject. Another embodiment is a method in which the second composition is applied to the skin of a subject before the first composition is applied to the skin of a subject.Another embodiment is a method, wherein the second composition is left to dry on the skin of the subject before the first composition is applied to the skin of the subject. Another embodiment is a method, wherein the first composition is applied to the skin of the subject in the form of an aqueous paste, and the aqueous portion is derived from water or brine. Another embodiment is a method, wherein the aqueous paste further comprises hydrogen peroxide. Another embodiment is a method, wherein an aqueous solution of hydrogen peroxide is applied to the face of the subject after the application of the first composition to the skin of the subject. Another embodiment is a method, wherein the hydrogen peroxide is an aqueous solution. Another embodiment is a method, wherein the aqueous solution comprises hydrogen peroxide at a w / w concentration of about 3%. Another embodiment is a method, wherein the first composition is left to dry on the skin of the subject. Another embodiment is a method, wherein the first composition and the second composition are mixed together, and the final mixture is applied to the skin of the subject. Another embodiment is a method, wherein the first composition is mixed with an aqueous solution of hydrogen peroxide before being mixed with the second composition. Another embodiment is a method in which a mixture of the first composition and the second composition is further mixed with an aqueous solution of hydrogen peroxide before application to the skin of a subject. Another embodiment is a method in which the aqueous solution contains hydrogen peroxide at a w / w concentration of about 3%. Another embodiment is a method in which the first composition and the second composition are applied to the skin of a subject once per week. Another embodiment is a method in which the second composition is applied to the skin of a subject no more than once every four weeks. Another embodiment is a method in which the first composition is applied to the skin of a subject at least once per week for at least one week. Another embodiment is a method in which the first composition is applied to the skin of a subject once per week for six weeks. Another embodiment is a method in which the first composition and the second composition are applied to the skin of a subject on at least one of the face, back, and chest of a subject.Another embodiment is a method in which the first composition and the second composition are applied to the skin of the subject on the face of the subject. Another embodiment is a method in which the first composition and the second composition are applied to the skin of the subject on the back of the subject. Another embodiment is a method in which the first composition and the second composition are applied to the skin of the subject on the chest of the subject.

[0150] In one aspect, a method for treating a skin condition in a subject is provided, comprising the step of applying a first composition and a second composition to the skin of a subject, wherein (a) the first composition comprises a sponge powder; and (b) the second composition comprises one or more types of botulinum toxin selected from botulinum toxin type A and botulinum toxin type B; (c) The skin conditions in the subject are selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, androgenetic alopecia, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Heri-Heri disease, IgA bullous dermatitis, simple bullous epidermolysis, Weber-Cockaign disease, dysphagia, congenital onychomycosis, hydrogenic keratosis, paresthetic back pain, dyshidrosis (dyshidrotic eczema), chromhidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melasma. Another embodiment is a method, wherein one or more types of botulinum toxin are botulinum toxin type A. Another embodiment is a method, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avibotulinum toxin A, incobotulinum toxin A, flabotulinum toxin A, and daxibotulinum toxin A. Another embodiment is a method, wherein the botulinum toxin of type A is onabotulinum toxin A. Another embodiment is a method, wherein the botulinum toxin of type A is avibotulinum toxin A. Another embodiment is a method, wherein the botulinum toxin of type A is incobotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is flabotulinum toxin A. In another aspect, any method disclosed herein is provided, wherein the botulinum toxin of type A is daxibotulinum toxin A. Another embodiment ...

Claims

Claim 1 A pharmaceutical composition comprising a first topical composition and a second topical composition for use in the treatment of hyperhidrosis in a subject, wherein (a) the first topical composition comprises a sponge; (b) the second topical composition comprises one or more botulinum toxins; and the treatment comprises applying the first topical composition and the second topical composition to the skin of the subject. Claim 2 A pharmaceutical composition according to claim 1, wherein the second topical composition comprises one or more types of botulinum toxin selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. Claim 3 A pharmaceutical composition according to paragraph 2, wherein the second topical composition comprises one or more types of botulinum toxin selected from type A botulinum toxin. Claim 4 In paragraph 3, the pharmaceutical composition wherein the type A botulinum toxin is onabotulinum toxin A. Claim 5 A pharmaceutical composition according to claim 1, wherein the subject experiences at least a 2-grade improvement in the HDSS score after treatment compared to the subject's HDSS score before treatment. Claim 6 A pharmaceutical composition according to claim 1, wherein the subject experiences a decrease of more than 10% in the amount of sweat secreted measured by weight after treatment compared to the amount of sweat secreted measured by weight before treatment. Claim 7 A pharmaceutical composition according to claim 1, wherein the subject experiences at least a 4-point improvement from the reference value of the weekly average ASDD Item 2 score compared to the subject's Axillary Sweating Daily Diary (ASDD) score prior to treatment. Claim 8 A pharmaceutical composition according to claim 1, wherein the subject is treated once per month, or once every two months, or once every three months, or once every four months, or once every five months, or once every six months, or once every seven months, or once every eight months, or once every nine months, or once every ten months, or once every eleven months, or once every twelve months. Claim 9 In claim 1, the subject is a pharmaceutical composition that is treated once per week. Claim 10 A pharmaceutical composition according to claim 1, wherein the subject suffers from primary axillary hyperhidrosis. Claim 11 A pharmaceutical composition according to claim 1, wherein the first topical composition comprises 0.225 grams to 11 grams of Spongilla. Claim 12 A pharmaceutical composition according to claim 1, wherein the first topical composition comprises 1.8 to 2.2 grams of Spongilla and 5.4 to 6.6 mL of 3% hydrogen peroxide or 5.4 to 6.6 mL of saline solution. Claim 13 A kit for use in treating a subject having hyperhidrosis, comprising a first topical composition and a second topical composition, wherein (a) the first topical composition comprises a sponge; (b) the second topical composition comprises one or more botulinum toxins; and the treatment comprises applying the first topical composition and the second topical composition to the skin of the subject. Claim 14 A kit according to claim 13, wherein the second topical composition comprises one or more types of botulinum toxin selected from botulinum toxin type A, botulinum toxin type B, botulinum toxin type C1, botulinum toxin type C2, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F, and botulinum toxin type G. Claim 15 In paragraph 13, the botulinum toxin is kit, which is onabotulinum toxin A. Claim 16 A pharmaceutical composition according to claim 1, wherein the sponge is Spongilla lacustris. Claim 17 In Paragraph 13, Spongilla is Kit, who is Spongilla Rakustris. Claim 18 A pharmaceutical composition according to claim 1, wherein the spongilla comprises particles having an average length of 200 μm to 350 μm and an average diameter of 5 μm to 20 μm. Claim 19 In claim 13, the Spongilla is a kit comprising particles having an average length of 200 μm to 350 μm and an average diameter of 5 μm to 20 μm. Claim 20 delete

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