Compositions for the treatment of skin conditions

Abstract

To provide methods of treating hyperhidrosis, and to provide compositions and kits for use in the treatment.SOLUTION: The present disclosure relates to the treatment of a skin condition in a subject, including but not limited to hyperhidrosis, comprising the step for applying to the skin of the subject a first composition derived from one or more sponges, and a second composition comprising one or more botulinum toxins. Also provided are compositions for use in the treatment of a skin condition in the subject, comprising a first composition and a second composition, (a) the first composition comprising Spongilla; and (b) the second composition comprising one or more botulinum toxins. Also provided are kits for the treatment of a skin condition in the subject, comprising a first composition and a second composition, the first composition comprising Spongilla, and the second composition comprising one or more botulinum toxins.SELECTED DRAWING: None

Description

【Technical Field】 【0001】 Cross-reference 【0001】This application claims the benefit of priority of U.S. Provisional Application No. 62 / 684,699, filed on June 13, 2018, U.S. Provisional Application No. 62 / 788,628, filed on January 4, 2019, and U.S. Provisional Application No. 62 / 838,801, filed on April 25, 2019. All of these are hereby incorporated by reference in their entirety. 【0002】 【0002】The present disclosure relates to the treatment of skin conditions in a subject, including but not limited to hyperhidrosis, comprising the step of applying to the skin of the subject a first composition derived from one or more sponges and a second composition comprising one or more botulinum toxins. In one aspect, the composition is derived from one or more sponges. In another aspect, the one or more sponges may be marine sponges or freshwater sponges. In another aspect, the one or more sponges are marine sponges. In another aspect, the sponge is a freshwater sponge. In another aspect, the composition is derived from a sponge of the phylum Porifera. In another aspect, the composition is derived from a sponge of the class Demospongiae. In another aspect, the composition is derived from a sponge of the order Spongillida. In another aspect, the composition is derived from a sponge of the family Spongillidae. In another aspect, the composition is derived from a sponge of the genus Spongilla. In another aspect, the composition is derived from a sponge of the species Spongilla lacustris. In another aspect, the composition is derived from a sponge of the order Haplosclerida. In another aspect, the composition is derived from a sponge of the family Clionaidae. In another aspect, the composition is derived from a sponge of the genus Mycale. 【0003】

[0003] The Disclosure relates to the treatment of a skin condition in a subject, including but not limited to hyperhidrosis, comprising the step of applying to the skin of the subject a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins. The 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 Spongilla and a second composition comprising one or more botulinum toxins. The Disclosure also relates to a first composition comprising Spongilla for use in a method for treating a skin disease or condition in a subject requiring treatment of a skin disease or condition, including but not limited to hyperhidrosis, the method comprising the step of administering to the subject an effective amount of the first composition in combination with an effective amount of the second composition comprising one or more botulinum toxins. [Background technology] 【0004】

[0004] Skin conditions in subjects including human subjects, including acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockane type epidermolysis bullosa Simplex Weber-Cockane, Darier's disease, pachyonchia congenita, aquagenic keratoderma, notalgia paresthetic, dyshidrotic eczema, chromohidrosis and bromhidrosis, and eccrine nevi, can be difficult to treat. While topical treatment of these skin conditions is successful in some cases, the proper use of topical therapies is often more complex than that of oral therapies, and adherence can be a particularly significant problem with topical treatments. Poor adherence to treatment regimens using topical therapies, the development of drug resistance, and increased costs can contribute to treatment failure. Therefore, methods of treating these skin conditions in subjects using topical products with a simpler dosage paradigm (e.g., applied once a week) offer an opportunity to demonstrate greater treatment success through improved subject adherence. 【0005】

[0005] Several skin conditions in the subject have been treated by topical application of materials derived from naturally occurring sponges, such as Spongilla lacustris. Several materials derived from Spongilla are recommended for the treatment of certain skin conditions, such as acne vulgaris, and as cosmetics. Spongilla contains organic and inorganic compounds. The total lipid content is about 5% of the biomass of the dried sponge, and the proteins consist of spongy tissue or hardened collagen. Polysaccharides and N-acetyl-D-glucosamine (NAG) are part of chitin and chitosan, which have been reported to be important components in the skeletal fibers of Spongilla lacustris, with 750 ± 1.5 μg of N-acetyl-D-glucosamine detected per 1 mg of the skeleton excluding the spicule. Chitin and chitosan are described as a family of linear polysaccharides consisting of varying amounts of α or β(1-4) bonded N-acetyl-2-amino-2-deoxy-D-glucose residues and 2-amino-2-deoxy-D-glucose residues. In α-chitin, the chains are arranged in sheets or layers, and within any one sheet, the chains have the same direction or "sense." In β-chitin, adjacent sheets along the c-axis have the same direction and the sheets are parallel, while in α-chitin, adjacent sheets along the c-axis have opposite directions and the sheets are antiparallel. Chitin can be deacetylated to chitosan and further broken down into N-acetyl-D-glucosamine (NAG) units. Chitosan preparations are classified into natural chitosan, chitosan formulations containing other substances, complexes, and derivatives. Chitosan can be used to prevent or treat wound and burn infections not only due to its endogenous antibacterial properties but also by its ability to deliver exogenous antibacterial agents to wounds and burns. Chitosan is water-soluble and becomes highly viscous in diluted acidic solutions. Soluble chitosan oligosaccharides were found to help suppress LPS-induced nuclear factor kappa light chain enhancer in activated B cell (NF-κB)-dependent inflammatory gene expression, which was associated with reduced nuclear translocation of NF-κB. Chitosan has also been shown to have antibacterial effects against Propionibacterium acnes and Staphylococcus aureus.Chitosan of different molecular weights (MW) was tested for antimicrobial activity (low MW (50-190 kDa), medium MW (190-310 kDa), and high MW (310-375+ kDa) chitosan). Clinical trials showed that NAG rapidly reduced the number of acne lesions over 8 weeks in subjects with acne vulgaris and was better tolerated than 10% benzoyl peroxide by these subjects. Higher molecular weights were used to show greater efficacy against the Gram-positive bacterium Propionibacterium acnes, and concentrations of 2.5, 5, 10, and 20 μg / mL were tested against Propionibacterium acnes. 【0006】

[0006] Hyperhidrosis is a disorder characterized by excessive sweating that is disproportionate to thermoregulatory requirements. Many individuals may exhibit this excessive sweating in response to specific triggers (e.g., mental stress), while others may present spontaneously. Diagnosis of hyperhidrosis is partly based on subjective measures that assess how excessive sweating affects the individual's quality of life. The amount of sweat produced can be measured by gravimetric analysis, but there is no standardized threshold for defining hyperhidrosis. Hyperhidrosis can be classified as either focal (affecting a specific area such as the palms or armpits) or generalized (affecting the entire body). Hyperhidrosis can be secondary to a wide variety of other conditions and usually presents as generalized hyperhidrosis. Primary hyperhidrosis, on the other hand, is idiopathic and commonly presents as focal sweating, most frequently occurring in the armpits (51%), soles of the feet (30%), palms (24%), and face (10%). Primary focal axillary hyperhidrosis is not uncommon. The prevalence in the United States is estimated at 2.8% of the population, comparable to that of psoriasis. Conventional treatments are generally ineffective, and due to the significant social embarrassment associated with the condition, two-thirds of those affected do not seek treatment. Furthermore, hyperhidrosis carries a heavy burden not only due to its impact on quality of life and psychosocial health, but also potentially leading to bacterial and fungal overgrowth. Primary hyperhidrosis is idiopathic, but the mechanism is thought to be neurogenic hyperactivity of eccrine glands in the affected area. The hypothesis for this mechanism is type A Supported by the clinical effects observed with botulinum toxin. Botulinum toxin type A is used in ecru. It works by interfering with sympathetic nerve stimulation of the glands, resulting in a significant reduction in axillary sweating. The effects last for 12 months. However, the skin penetration and volumetric effects from botulinum toxin treatment cause injection site pain. Given the nature of the target tissue, injection site pain is considered a major cause of lack of compliance, especially when numerous injections must be administered to sensitive skin areas such as the armpits. Therefore, topical products with a simpler administration paradigm that allow botulinum toxin to penetrate through the stratum corneum into the dermis may gain greater compliance and adoption by improving the tolerability of the treatment. 【0007】

[0007] The inventors of the subject matter disclosed herein have found that a key component of the material derived from Spongilla is siliceous bone needles containing the skeletal structure of Spongilla. The inventors have found that the bone needles penetrate the stratum corneum of the target skin during application and promote the shedding of keratinocytes. The inventors of the subject matter disclosed herein have also found that the bone needles derived from Spongilla are useful in facilitating and enabling the penetration of certain therapeutic compounds and compositions into the target skin to which the bone needles are applied. Otherwise, the compounds and compositions would not be able to penetrate the target skin to reach their therapeutic targets and treat certain skin conditions. Compounds and compositions that can penetrate the skin better in the presence of the material derived from Spongilla are, among other things, products containing botulinum toxin. 【0008】

[0008] Products containing botulinum toxin have been shown to be useful in treating several medical conditions, including those affecting the skin of the subject. For example, products containing botulinum toxin have been approved for the treatment of subjects suffering from hyperhidrosis (excessive sweating). Topical application of products containing botulinum toxin may also be useful in the treatment of subjects suffering from acne (see, for example, U.S. Patent No. 7,226,605). However, the problems with using one or more products containing botulinum toxin for the topical treatment of skin conditions in subjects are well known. One problem with the topical use of botulinum toxin-containing products is the recognition that endogenous non-toxic proteins (i.e., non-toxic hemagglutinin proteins and non-hemagglutinin proteins) in the botulinum toxin complex obtained from Clostridium botulinum reduce the ability of the toxin to diffuse through the skin epithelium. These effects may be further exacerbated if exogenous stabilizers such as albumin bind to the botulinum toxin during conventional manufacturing processes. Therefore, applying a composition containing Spongilla, for example in powder form, to the target skin may help facilitate the penetration of one or more topical application products containing botulinum toxins into the target skin, potentially leading to the use of new treatment regimens when skin conditions are difficult to treat. [Overview of the project] 【0009】

[0009] In one embodiment, a method is provided for treating a skin condition in a subject, the method comprising the steps of applying to the skin of the subject a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins. 【0010】

[0010] In one embodiment, a method is provided for treating a skin condition in a subject, comprising the step of applying to the skin of the subject a first composition comprising one or more sponges and a second composition comprising one or more botulinum toxins. In one embodiment, the composition is derived from one or more sponges. In another embodiment, one or more sponges may be marine sponges or freshwater sponges. In another embodiment, one or more sponges are marine sponges. In another embodiment, the sponges are freshwater sponges. In another embodiment, the composition is derived from sponges of the phylum Porifera. In another embodiment, the composition is derived from sponges of the class Polypodium. In another embodiment, the composition is derived from sponges of the order Polypodium. In another embodiment, the composition is derived from sponges of the family Polypodium. In another embodiment, the composition is derived from sponges of the genus Spongilla. In another embodiment, the composition is derived from sponges of the species Spongilla lacustris. In another embodiment, the composition is derived from sponges of the order Polypodium. In another embodiment, the composition is derived from a sponge of the family Eucomnaidae. In yet another embodiment, the composition is derived from a sponge of the genus Eucomna. 【0011】

[0011] In one embodiment, a method for treating a skin condition in a subject, comprising the steps of applying to the skin of a subject a first composition comprising one or more sponges and a second composition comprising one or more botulinum toxins, wherein (a) the second composition comprises one or more botulinum toxin types selected from 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 botulinum toxin and type G botulinum toxin (b) A method is provided in which the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, one or more sponges may be marine sponges or freshwater sponges. In another embodiment, one or more sponges may be marine sponges. In another embodiment, the sponges may be freshwater sponges. In another embodiment, the composition may be derived from sponges of the phylum Spongia. In another embodiment, the composition is derived from sponges of the class Polypodium. In another embodiment, the composition is derived from sponges of the order Polypodium. In another embodiment, the composition is derived from sponges of the family Polypodium. In another embodiment, the composition is derived from sponges of the genus Spongilla. In another embodiment, the composition is derived from sponges of the species Spongilla lacustris. In another embodiment, the composition is derived from sponges of the order Polypodium. In another embodiment, the composition is derived from sponges of the family Polypodium. In another embodiment, the composition is derived from sponges of the genus Polypodium. 【0012】

[0012] In one embodiment, a method for treating a skin condition in a subject, comprising the steps of applying a first composition and a second composition to the skin of the subject, wherein (a) the first composition comprises one or more sponges, (b) the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E, and (c) the skin condition in the subject is acne vulgaris A method is provided to select from the following: type 1 rosacea acne, type 2 rosacea acne, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrohpic acne scars, and melanosis. In another embodiment, one or more sponges may be marine sponges or freshwater sponges. In another embodiment, one or more sponges may be marine sponges. In another embodiment, the sponges may be freshwater sponges. In another embodiment, the composition may be derived from sponges of the phylum Spongia. In another embodiment, the composition is derived from sponges of the class Spongila. In another embodiment, the composition is derived from sponges of the order Spongiformes. In another embodiment, the composition is derived from sponges of the family Spongidae. In another embodiment, the composition is derived from sponges of the genus Spongilla. In another embodiment, the composition is derived from Spongilla In another embodiment, the composition is derived from sponges of the species Lacustris. In yet another embodiment, the composition is derived from sponges of the order Monospongiformes. In yet another embodiment, the composition is derived from sponges of the family Pleurospongiidae. In yet another embodiment, the composition is derived from sponges of the genus Pleurospongi. 【0013】

[0013] In another embodiment, a kit is provided comprising 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 embodiment, a kit is provided comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins, for use in the treatment of a skin condition in a subject. In another embodiment, a kit comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins, for use in the treatment of a skin condition in a subject A kit for this purpose is provided. In another embodiment, a kit is provided which the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, onychomycosis, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, one or more sponges may be marine sponges or freshwater sponges. In another embodiment, one or more sponges are marine sponges. In another embodiment, the sponges are freshwater sponges. In another embodiment, the composition is derived from a sponge of the phylum Porifera. In another embodiment, the composition is derived from a sponge of the class Polypodium. In another embodiment, the composition is derived from a sponge of the order Polypodium. In another embodiment, the composition is derived from a sponge of the family Polypodium. In another embodiment, the composition is derived from a sponge of the genus Spongilla. In another embodiment, the composition is derived from a sponge of the species Spongilla lacustris. In another embodiment, the composition is derived from a sponge of the order Polypodium. In another embodiment, the composition is derived from a sponge of the family Polypodium. In another embodiment, the composition is derived from a sponge of the genus Polypodium. 【0014】

[0014] In another embodiment, a composition comprising a first composition and a second composition for use as a pharmaceutical 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 embodiment, a composition comprising a first composition and a second composition for use as a pharmaceutical is provided, wherein (a) the first composition comprises Spongilla lacustris, and (b) the second composition comprises one or more botulinum toxins. In another embodiment, such a composition for use as a pharmaceutical for the treatment of a skin condition in a subject is provided. In another embodiment, such a combination is provided for use as a medicament 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, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, one or more sponges may be marine sponges or freshwater sponges. In another embodiment, one or more sponges are marine sponges. In another embodiment, the sponges are freshwater sponges. In another embodiment, the composition is derived from a sponge of the phylum Porifera. In another embodiment, the composition is derived from a sponge of the class Polypodium. In another embodiment, the composition is derived from a sponge of the order Polypodium. In another embodiment, the composition is derived from a sponge of the family Polypodium. In another embodiment, the composition is derived from a sponge of the genus Spongilla. In another embodiment, the composition is derived from a sponge of the species Spongilla lacustris. In another embodiment, the composition is derived from a sponge of the order Polypodium. In another embodiment, the composition is derived from a sponge of the family Polypodium. In another embodiment, the composition is derived from a sponge of the genus Polypodium. 【0015】

[0015] In another embodiment, 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 embodiment, a combination comprising a first composition and a second composition is provided for use in the treatment of a skin condition in a subject, wherein (a) the first composition comprises a sponge, and (b) the second composition comprises one or more botulinum toxins. In another embodiment, such a composition for use in the treatment of a skin condition in a subject, wherein the skin condition in the subject is acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne syndrome. Such combinations are provided, selected from epidermolysis bullosa simplex, Darier's disease, onychomycosis, aqueous keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, one or more sponges may be marine sponges or freshwater sponges. In another embodiment, one or more sponges are marine sponges. In another embodiment, the sponge is a freshwater sponge. In another embodiment, the composition is derived from a sponge of the phylum Spongiformes. In another embodiment, the composition is derived from a sponge of the class Polypongia. In another embodiment, the composition is derived from a sponge of the order Polypongiformes. In another embodiment, the composition is derived from a sponge of the family Polypongiaceae. In another embodiment, the composition is derived from a sponge of the genus Spongilla. In another embodiment, the composition is derived from a sponge of the species Spongilla lacustris. In another embodiment, the composition is derived from a sponge of the order Polypongiformes. In another embodiment, the composition is derived from a sponge of the family Eucomnaidae. In yet another embodiment, the composition is derived from a sponge of the genus Eucomna. 【0016】

[0016] In another embodiment, a composition for manufacturing a medicament for the treatment of a skin condition in a subject is provided, comprising 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 embodiment, a composition for manufacturing a medicament for the treatment of a skin condition in a subject is provided, comprising 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 embodiment, a composition is provided for manufacturing a medicament 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, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, one or more sponges may be marine sponges or freshwater sponges. In another embodiment, one or more sponges are marine sponges. In another embodiment, the sponges are freshwater sponges. In another embodiment, the composition is derived from a sponge of the phylum Porifera. In another embodiment, the composition is derived from a sponge of the class Polypodium. In another embodiment, the composition is derived from a sponge of the order Polypodium. In another embodiment, the composition is derived from a sponge of the family Polypodium. In another embodiment, the composition is derived from a sponge of the genus Spongilla. In another embodiment, the composition is derived from a sponge of the species Spongilla lacustris. In another embodiment, the composition is derived from a sponge of the order Polypodium. In another embodiment, the composition is derived from a sponge of the family Polypodium. In another embodiment, the composition is derived from a sponge of the genus Polypodium. 【0017】

[0017] In one embodiment, a method for treating a skin condition in a subject, comprising the step of applying to the skin of a subject a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins, 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) A method is provided in which the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melanosis. 【0018】

[0018] In one embodiment, the first composition and the second composition are applied to the target skin. A method for treating a skin condition in a subject, including a TEP, comprising: (a) a first composition comprising Spongilla powder; (b) a second composition comprising one or more botulinum toxin types selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E; and (c) a skin condition in the subject being acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata. Methods are provided for a selection of conditions including: male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. 【0019】

[0019] In another embodiment, a kit is provided comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins. In another embodiment, a kit is provided comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins, for use in treating a skin condition in a subject. In another embodiment, a kit is provided comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins, for use in treating a skin condition in a subject. In another embodiment, a kit is provided according to this specification in which the skin condition of the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. 【0020】

[0020] In another embodiment, a composition is provided for use as a pharmaceutical, comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins. In another embodiment, a composition is provided for use as a pharmaceutical, comprising 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 embodiment, such a composition is provided for use as a pharmaceutical for the treatment of a skin condition in a subject. In another embodiment, such combinations are provided for use as pharmaceuticals 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, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. 【0021】

[0021] In another embodiment, 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 embodiment, a combination 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 lacustris, and (b) the second composition comprises one or more botulinum toxins. In another embodiment, such a composition for use in the treatment of a skin condition in a subject is provided, wherein the skin condition in the subject is acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids, and hypertrophic scars. Such compositions are provided, selected from hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. 【0022】

[0022] In another embodiment, a composition is provided for manufacturing a medicament for the treatment of a skin condition in a subject, comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins. In another embodiment, a composition is provided for manufacturing a medicament 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, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, onychomycosis, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melanosis. [Modes for carrying out the invention] 【0023】

[0023] The singular forms “a,” “an,” and “the” encompass multiple references unless the context clearly indicates otherwise. For example, the term “a cell” encompasses one or more cells, including mixtures thereof. “A and / or B” is used herein to encompass all of the options “A,” “B,” “A or B,” and “A and B.” 【0024】

[0024] As used herein, the term “about” means in all cases within plus or minus 10% of the indicated value, including the indicated value, or rounded to the nearest significant figure. Where a range is indicated, the range includes the boundary values. 【0025】

[0025] As used herein, the terms “apply,” “administer,” “give,” and “use” mean the delivery of the compositions disclosed herein to a subject, in particular to the skin of the subject, by a route of administration including, but not limited to, intraperitoneal, subcutaneous, intramuscular, topical, or any combination thereof. In some embodiments disclosed herein, the compositions disclosed herein are administered to a subject, in particular to the skin of the subject, by topical administration. 【0026】

[0026] As used herein, the term “aspect ratio” means, with respect to the Spongilla particles described herein, the ratio of the average length of the particle to the average diameter of the particle. 【0027】

[0027] As used herein, the term “botulinum toxin” means the protein produced by the bacterium Clostridium botulinum and related species. As used herein, the term “type A botulinum toxin” means the protein known to those skilled in the art as also known as “BoNT / A” or “botA,” with representative examples being UniProt reference numbers BXA1_CLOBH (Hall strain), BXA1_CLOBO, BXA2_CLOBO, or their variants. As used herein, the term “type B botulinum toxin” means the protein also known as “BoNT / B” or “botB.” The term "C1 botulinum toxin" means a protein known to those skilled in the art as a protein, with UniProt reference number BXB_CLOBO or its variants being representative. As used herein, the term "C1 botulinum toxin" means a protein known to those skilled in the art as a protein also known as "BoNT / C1," with UniProt reference number BXC1_CLOBO or its variants being representative. As used herein, the term "C2 botulinum toxin" means a protein known to those skilled in the art as a protein also known as C2 botulinum toxin. As used herein, the term "D botulinum toxin" means a protein known to those skilled in the art as a protein also known as "BoNT / D" or "botD," with UniProt reference number BXD_CLOBO or its variants being representative. As used herein, the term "E botulinum toxin" means a protein known to those skilled in the art as a protein also known as "BoNT / E," with UniProt reference number BXE_CLOBO or its variants being representative. As used herein, the term “botulinum toxin type F” means the protein known to those skilled in the art as also known as “BoNT / F” or “botF,” with UniProt reference number BXF_CLOBO or its variants being representative. As used herein, the term “botulinum toxin type G” means the protein known to those skilled in the art as also known as “BoNT / E” or “botG,” with UniProt reference number BXG_CLOBO or its variants being representative. As used herein, the term “variant” means a protein having homology of 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, or any percentage in between. 【0028】

[0028] As used herein, the terms “combination” and “in combination” mean the sequential or simultaneous application, use, or administration of one or more of the compositions disclosed herein. This includes administering the compositions disclosed herein simultaneously, within minutes or hours of each other, on the same day, or on alternating days, or using them on a daily basis, on multiple days a week, or on a weekly basis, for example, on the same day, or on alternating days or weeks, or periodically during periods of simultaneous or parallel use, or while administering another composition at least at one point in time between the application, use, or administration of the compositions disclosed herein. For example, one or more of the compositions disclosed herein may be applied, used, or administered to a subject daily or several days a week, with additional compositions being applied, used, or administered on a daily, weekly, or other interval, for example, every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more days. 【0029】

[0029] As used herein, the term “Avobotulinum toxin A” means the botulinum toxin type A product approved by the FDA under BLA number 125274. 【0030】 As used herein, the term "Chalinidea" means one or more species of sponge belonging to the family Chalinidea.

[0030] 【0031】 The term "Daxibotulinum toxin A" refers to the 150 kilodalton (kDa) purified type A botulinum toxin complex currently under development by Revance Therapeutics, Inc.

[0031] 【0032】 The term "Demospongiae" refers to one or more species of sponge belonging to the class Demospongiae. 【0033】As used herein, the term "EB-001A" means the botulinum toxin type E product developed by Bonti, Inc. in Orange County, California.

[0032] 【0034】 As used herein, the term "EB-001T" refers to the botulinum toxin type E product developed by Bonti, Inc. in Orange County, California.

[0033] 【0035】 As used herein, the term "Halciona" means one or more species of sponge belonging to the genus Halciona. 【0036】 As used herein, the term "Haplosclerida" means one or more species of sponge in the order Haplosclerida.

[0034] 【0037】 As used herein, the term “incobotulinum toxin A” means the botulinum toxin type A product approved by the FDA under BLA number 125360. 【0038】 As used herein, the term “onabotulinum toxin A” means the botulinum toxin type A product approved by the U.S. Food and Drug Administration ("FDA") under Biologics License Application ("BLA") number 103000.

[0035] 【0039】 As used herein, the term “limabotulinum toxin B” means the botulinum toxin type B product approved by the FDA under BLA number 103846. 【0040】 As used herein, the term "Porifera" means one or more members of the phylum Porifera.

[0036] 【0041】 The term "Plabotulinum Toxin A" refers to the 900 kilodalton (kDa) purified type A botulinum toxin complex currently under development by Evolus, Inc. and Daewoong Pharmaceutical Co. Ltd.

[0037] 【0042】 As used herein, the term “Spongilla” means the genus of freshwater sponges in the family Spongillidae, including, but not limited to, Spongilla lacustris, S. fragilis Leidy, and Ephydatia fluviatilis. As used herein, the term “Spongilla lacustris” means the species of freshwater sponge in the family Spongillidae.

[0038] 【0043】The terms “composition comprising one or more sponges,” “powder comprising one or more sponges,” “material comprising one or more sponges,” and “sponge in powder form” are, as used herein, meant material derived from one or more sponges that have been harvested and processed, and may include all various components of a post-harvested sponge, including all organic and / or inorganic compounds and materials that are part of a naturally occurring sponge or any sponge that has been specifically grown or adapted for use in the disclosed compositions, methods, and / or kits, or may include only a portion of the organic and / or inorganic compounds and materials that are part of a naturally occurring sponge. In one embodiment, any method or kit disclosed herein is provided in which the sponge material comprises all or substantially all organic and inorganic materials derived from a naturally occurring sponge. In another embodiment, a method or kit disclosed herein is provided in which the sponge material comprises (a) any material naturally associated with bone fragments alone or (b) any material naturally associated with substantially purified bone fragments or (c) any material naturally associated with purified bone fragments that is a component of a naturally occurring sponge. Any method or kit disclosed herein is provided. These terms may be used herein in reference to materials derived from the phylum Porifera. In another embodiment, the material is derived from sponges of the class Demospongiae. In another embodiment, the material is derived from sponges of the order Spongdillae. In another embodiment, the material is derived from sponges of the family Spongillidae. In another embodiment, the material is derived from sponges of the genus Spongilla. In another embodiment, the material is derived from sponges of the species Spongilla lacustris. In another embodiment, the material is derived from sponges of the order Haploscleridae. In another embodiment, the material is derived from sponges of the family Chalinidea. In another embodiment, the material is derived from sponges of the genus Halciona.

[0039] 【0044】The terms “Composition containing Spongilla,” “Powder containing Spongilla,” “Material containing Spongilla,” and “Spongilla in powder form,” as used herein, mean Spongilla-containing material derived from harvested and processed raw Spongilla, which may include all the various components of post-harvested Spongilla, including all the organic and / or inorganic compounds and materials that are part of naturally occurring Spongilla, or it may include only a portion of the organic and / or inorganic compounds and materials that are part of naturally occurring Spongilla. In one embodiment, any method or kit disclosed herein is provided in which the Spongilla material includes all or substantially all of the organic and inorganic materials derived from naturally occurring Spongilla. In another embodiment, any method or kit disclosed herein is provided in which the Spongilla material includes (a) only the bone fragments and any material naturally associated with the bone fragments, or (b) substantially purified bone fragments and any material naturally associated with the bone fragments, or (c) purified bone fragments and any material naturally associated with the bone fragments that are component parts of naturally occurring Spongilla. In another embodiment, any method or kit disclosed herein is provided in which the Spongilla material comprises either bone fragments or materials naturally associated with bone fragments. In another embodiment, any method or kit disclosed herein is provided in which the Spongilla material comprises substantially purified bone fragments and materials naturally associated with bone fragments. In another embodiment, any method or kit disclosed herein is provided in which the Spongilla material comprises purified bone fragments and materials naturally associated with bone fragments, which are naturally occurring component parts of Spongilla.

[0040] 【0045】As used herein, the term “Subject” has the meaning assigned to the term by those skilled in the art and may mean mammals, including humans, dogs, cats, cattle, or pigs. In one embodiment, the subject is a human. In one embodiment, the subject is a dog. In one embodiment, the subject is a cat. In one embodiment, the subject is a cat. In one embodiment, the subject is a pig.

[0041] 【0046】 As used herein, the term “therapeutic dose” means the amount of a composition or combination of compositions applied to, used or administered to a subject that treats, alleviates or prevents, to some extent, one or more symptoms of the disorder being treated.

[0042] 【0047】 Spongilla, including Spongilla lacustris, and powders prepared from Spongilla, used in the methods disclosed herein, can 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 Spongilla species, including Spongilla lacustris. The disclosure of U.S. Patent No. 7,604,821 is incorporated herein by reference in its entirety. Sponge material can be collected using methods generally known to those skilled in the art in the field of marine biology. For example, sponges can be collected manually using basic diving techniques. In shallow or deeper waters, larger colonies are harvested using an agathias roll (AGT) or an epibenthic sledge (EBS). Under certain environmental conditions, Spongilla colonies exist in thin, shell-like spreads several meters wide and must be collected manually using tools such as forks and nets. The collected sponge masses are dried to remove coarse impurities such as shells, stalks, plants, stones, and other contaminants, and then washed to remove mud, sand, silt, and soluble impurities. The cleaned sponge masses are weighed and dried using methods known to those skilled in the art, such as air drying or using a dryer used for dehydrating food and pharmaceuticals. The sponge masses are dried until the residual moisture content is less than the desired value as further disclosed herein. Residual moisture measurement can be performed using methods generally known in the fields of food science, analytical chemistry, or pharmaceuticals. For example, 10 grams of dry material can be placed on a weighing boat with a tare weight and then weighed. The weighed material is then exposed to a heat source such as a drying oven or heat lamp operated at an appropriate temperature, and then the sample is cooled in a desiccated chamber and weighed again. The residual moisture content is calculated as the percentage difference between the sample weight before drying and the weight after cooling. After drying, the sponge material can be packaged in a sealed container that protects the material from light, moisture, and oxygen, if necessary. The material can then be further tested for the presence of pathogens, E. coli-type organisms, and organisms that form bioburden. Further heating or irradiation of the material as disclosed herein can reduce the presence of pathogens, E. coli-type organisms, or other organisms that form bioburden. The material can then be further processed using methods known to those skilled in the art to obtain a powder containing particles of a desired size. For example, the sponge material can be pulverized and the resulting material can be passed through one or more sieves of a predetermined size to ensure that the resulting material contains particles of uniform or substantially uniform size. After the final processing and particle separation steps are completed, the dried sponge material can be packaged in an airtight, moisture-proof container and stored at a suitable temperature, such as room temperature or ambient temperature.

[0043] 【0048】 Materials derived from sponges other than Spongilla lacustris may be prepared according to the methods described above and methods known to those skilled in the art. In particular, such methods can be applied to sponges of the phylum Porifera. In another embodiment, such methods can be applied to sponges of the class Demospongiae. In another embodiment, such methods can be applied to sponges of the order Spongdilla. In another embodiment, such methods can be applied to sponges of the family Spongillidae. In another embodiment, such methods can be applied to sponges of the genus Spongilla. In another embodiment, such methods can be applied to sponges of the species Spongilla lacustris. In another embodiment, such methods can be applied to sponges of the order Haplosclerida. In another embodiment, such methods can be applied to sponges of the family Chalinidea. In another embodiment, such methods can be applied to sponges of the genus Halciona.

[0044] 【0049】 In one embodiment, a method for treating a skin condition in a subject, comprising the steps of applying to the skin of the subject requiring treatment an effective amount of a first composition containing Spongilla and an effective amount of a second composition containing one or more botulinum toxins, (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 include acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, and dorsal paresthesia. Methods are provided for a selection of conditions including dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, a method is provided in which the skin condition in the subject is hyperhidrosis, acne vulgaris, and rosacea. In one embodiment, a method is provided in which 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 embodiment, a method is provided in which one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are botulinum toxin type A. In another embodiment, any method disclosed herein is provided in which botulinum toxin type A is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In another embodiment, any method disclosed herein is provided in which botulinum toxin type A is onabotulinum toxin A. In another embodiment, any method disclosed herein is provided in which botulinum toxin type A is avobotulinum toxin A. In another embodiment, any method disclosed herein is provided in which botulinum toxin type A is incobotulinum toxin A. In another embodiment, any method disclosed herein is provided in which botulinum toxin type A is prabotulinum toxin A. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are botulinum toxin type B. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are lima botulinum toxin B. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are botulinum toxin type C1. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are botulinum toxin type C2.In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type D botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type E botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type E botulinum toxins are EB-001A or EB-001T. In another embodiment, any method disclosed herein is provided in which one or more type E botulinum toxins are EB-001A. In another embodiment, any method disclosed herein is provided in which one or more type E botulinum toxins are EB-001T. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type F botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type G botulinum toxin. In another embodiment, any method disclosed herein is provided in which the skin condition of the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In another embodiment, any method disclosed herein is provided in which the skin condition of the subject is acne vulgaris. In another embodiment, any method disclosed herein is provided in which the skin condition of the subject is rosacea type 1. In another embodiment, any method disclosed herein is provided in which the skin condition of the subject is rosacea type 2. In another embodiment, any method disclosed herein is provided in which the skin condition of the subject is psoriasis. In another embodiment, any method disclosed herein is provided in which the skin condition of the subject is hyperhidrosis.In another embodiment, the first composition comprising Spongilla is consumed at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, and at least. A method is provided in which the product is applied to the target skin at least once a week over 11 weeks, at least once a week over 12 weeks, at least once a week over 13 weeks, at least once a week over 14 weeks, at least once a week over 15 weeks, at least once a week over 16 weeks, at least once a week over 17 weeks, at least once a week over 18 weeks, at least once a week over 19 weeks, at least once a week over 20 weeks, at least once a week over 21 weeks, at least once a week over 22 weeks, at least once a week over 23 weeks, and at least once a week over 24 weeks. In another embodiment, a method is provided in which the first composition comprising Spongilla is applied to the target skin at least once a week over 2 weeks, as disclosed herein. In another embodiment, a method is provided in which a first composition containing Spongilla is applied to the target skin once a week for three weeks. In another embodiment, a method is provided in which a first composition containing Spongilla is applied to the target skin once a week for four weeks. In another embodiment, a method is provided in which a first composition containing Spongilla is applied to the target skin once a week for five weeks. In another embodiment, a method is provided in which a first composition containing Spongilla is applied to the target skin once a week for six weeks. In another embodiment, a method is provided in which a first composition containing Spongilla is applied to the target skin once a week for seven weeks. In another embodiment, a method is provided in which a first composition containing Spongilla is applied to the target skin once a week for eight weeks.

[0045] 【0050】In one embodiment, a method for treating hyperhidrosis in a subject is provided, comprising the step of applying to the skin of the subject in need of the treatment an effective amount of a first composition containing Spongilla and an effective amount of a second composition containing one or more botulinum toxins, 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 one embodiment, a method is provided in which 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 embodiment, a method is provided in which one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In yet another embodiment, a method is provided in which one or more botulinum toxin types are botulinum toxin type A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is onabotulinum toxin A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is avobotulinum toxin A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is incobotulinum toxin A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is prabotulinum toxin A. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type B botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are limabotulinum toxin B.In another embodiment, any method disclosed herein is proposed in which one or more botulinum toxin types are C1 botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are C2 botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are D botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are E botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more E botulinum toxins are EB-001A or EB-001T. In another embodiment, any method disclosed herein is provided in which one or more E botulinum toxins are EB-001A. In another embodiment, any method disclosed herein is provided in which one or more E botulinum toxins are EB-001T. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type F botulinum toxin. In yet another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type G botulinum toxin.In another embodiment, the first composition containing Spongilla is used at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, and less than once a week for at least thirteen weeks. In another embodiment, any method is provided in which the first composition comprising Spongilla is applied to the skin of the subject at least once a week, at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In yet another embodiment, any method is provided in which the first composition comprising Spongilla is applied to the skin of the subject at least once a week for 2 weeks. In yet another embodiment, any method is provided in which the first composition comprising Spongilla is applied to the skin of the subject at least once a week for 3 weeks. In another embodiment, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of the subject once a week for four weeks. In yet another embodiment, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of the subject once a week for five weeks.In another embodiment, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the target skin once a week for six weeks. In another embodiment, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the target skin once a week for seven weeks. In yet another embodiment, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the target skin once a week for eight weeks.

[0046] 【0051】 In one embodiment, a method for hyperhidrosis in a subject is provided, comprising the step of applying to the skin of the subject in need of the treatment an effective amount of a first composition containing Spongilla and an effective amount of a second composition containing botulinum toxin type A. In another embodiment, any method disclosed herein is provided, wherein the botulinum toxin type A is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In yet another embodiment, any method disclosed herein is provided, wherein the botulinum toxin type A is onabotulinum toxin A. In one embodiment, any method disclosed herein is provided in which the type A botulinum toxin is avobotulinum toxin A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is incobotulinum toxin A. In yet another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is prabotulinum toxin A. In yet another embodiment, a first composition comprising Spongilla is used at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, and at least once a week for at least thirteen weeks. In another embodiment, any method is provided in which the first composition comprising Spongilla is applied to the skin of the subject at least once a week, at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In yet another embodiment, any method is provided in which the first composition comprising Spongilla is applied to the skin of the subject at least once a week for 2 weeks. In yet another embodiment, any method is provided in which the first composition comprising Spongilla is applied to the skin of the subject at least once a week for 3 weeks.In another embodiment, a method is provided in which a first composition comprising Spongilla is applied to the target skin once a week for four weeks, as disclosed herein. In another embodiment, a method is provided in which a first composition comprising Spongilla is applied to the target skin once a week for five weeks, as disclosed herein. In another embodiment, a method is provided in which a first composition comprising Spongilla is applied to the target skin once a week for six weeks, as disclosed herein. In another embodiment, a method is provided in which a first composition comprising Spongilla is applied to the target skin once a week for seven weeks, as disclosed herein. In another embodiment, a method is provided in which a first composition comprising Spongilla is applied to the target skin once a week for eight weeks, as disclosed herein.

[0047] 【0052】A first composition comprising Spongilla for use in a method of treating a skin disease or condition in a subject requiring it, the method comprising administering to the subject an effective amount of the first composition in combination with an effective amount of a second composition, the second composition comprising one or more botulinum toxins selected from 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 botulinum toxin, and type G botulinum toxin The toxin type is included, and the skin condition in the subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, such a first composition is provided for use when the skin condition or condition in the subject is hyperhidrosis, acne vulgaris, and rosacea. In one embodiment, the second composition is 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 G A first composition is provided for use comprising one or more botulinum toxin types selected from type A botulinum toxins. In one embodiment, a first composition is provided for use in which one or more botulinum toxin types are selected from type A botulinum toxin, type B botulinum toxin, and type E botulinum toxin. In one embodiment, a first composition is provided for use in which one or more botulinum toxin types are type A botulinum toxin. In one embodiment, a first composition is provided for use in which type A botulinum toxin is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, a first composition is provided for use in which type A botulinum toxin is onabotulinum toxin A. In one embodiment, a first such composition is provided for use in which the type A botulinum toxin is avobotulinum toxin A. In one embodiment, a first such composition is provided for use in which the type A botulinum toxin is incobotulinum toxin A. In one embodiment, a first such composition is provided for use in which the type A botulinum toxin is prabotulinum toxin A. In one embodiment, a first such composition is provided for use in which one or more botulinum toxin types are type B botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are limabotulinum toxin B. In one embodiment, a first such composition is provided for use in which one or more botulinum toxin types are type C1 botulinum toxin. In one embodiment, a first composition is provided for use in which one or more botulinum toxin types are C2 botulinum toxin. In one embodiment, a first composition is provided for use in which one or more botulinum toxin types are D botulinum toxin. In one embodiment, a first composition is provided for use in which one or more botulinum toxin types are E botulinum toxin. In one embodiment, a first composition is provided for use in which one or more E botulinum toxins are EB-001A or EB-001T.In one embodiment, such a first composition is provided for use in which one or more type E botulinum toxins are EB-001A. In one embodiment, such a first composition is provided for use in which one or more type E botulinum toxins are EB-001T. In one embodiment, such a first composition is provided for use in which one or more botulinum toxin types are type F botulinum toxins. In one embodiment, such a first composition is provided for use in which one or more botulinum toxin types are type G botulinum toxins. In one embodiment, such a first composition is provided for use in which the skin condition in the subject is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, and hyperhidrosis. In one embodiment, such a first composition is provided for use in which the skin condition in the subject is acne vulgaris. In one embodiment, such a first composition is provided for use in a subject whose skin condition is type 1 rosacea acne. In one embodiment, such a first composition is provided for use in a subject whose skin condition is type 2 rosacea acne. In one embodiment, such a first composition is provided for use in a subject whose skin condition is psoriasis. In one embodiment, such a first composition is provided for use in a subject whose skin condition is hyperhidrosis.In one embodiment, a first composition containing Spongilla is consumed at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, at least once a week for at least thirteen weeks, at least once a week for at least fourteen weeks, at least once a week for at least fifteen weeks, at least once a week for at least sixteen weeks, at least once a week for at least seventeen weeks, at least once a week for at least eighteen weeks, and at least once a week for at least nineteen weeks. A first composition is provided for use in which the first composition is applied to the skin of a subject at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the skin of a subject at least once a week for 2 weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the skin of a subject at least once a week for 3 weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the skin of a subject at least once a week for 4 weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the skin of a subject at least once a week for 5 weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of six weeks. In another embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of seven weeks. In yet another embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of eight weeks.

[0048] 【0053】A method comprising administering to a subject an effective amount of a first composition in combination with an effective amount of a second composition, wherein the second composition comprises botulinum toxin type A, and is a first composition comprising Spongilla for use in a method for treating hyperhidrosis in a subject requiring it. In one embodiment, such a first composition is provided for use in which botulinum toxin type A is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, such a first composition is provided for use in which botulinum toxin type A is onabotulinum toxin A. In one embodiment, such a first composition is provided for use in which botulinum toxin type A is avobotulinum toxin A. In one embodiment, such a first composition is provided for use in which botulinum toxin type A is incobotulinum toxin A. In one embodiment, a first composition is provided for use in which the type A botulinum toxin is plabotulinum toxin A.In one embodiment, the first composition containing Spongilla is used at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, and at least once a week for at least thirteen weeks. A first composition is provided for use in which the first composition is applied to the skin of a subject at least once, at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In one embodiment, a first composition comprising Spongilla is provided for use in which the first composition is applied to the skin of a subject at least once a week for 2 weeks. In one embodiment, a first composition comprising Spongilla is provided for use in which the first composition is applied to the skin of a subject at least once a week for 3 weeks. In one embodiment, Spongilla. A first composition is provided for use in which a first composition containing lla is applied once a week to the skin of a subject over a period of four weeks. In one embodiment, a first composition is provided for use in which a first composition containing Spongilla is applied once a week to the skin of a subject over a period of five weeks. In one embodiment, a first composition is provided for use in which a first composition containing Spongilla is applied once a week to the skin of a subject over a period of six weeks. In one embodiment, a first composition is provided for use in which a first composition containing Spongilla is applied once a week to the skin of a subject over a period of seven weeks. In one embodiment, a first composition is provided for use in which a first composition containing Spongilla is applied once a week to the skin of a subject over a period of eight weeks.

[0049] 【0054】The method comprises administering to a subject an effective amount of a first composition in combination with an effective amount of a second composition, wherein the second composition comprises onabotulinum toxin A, and the first composition comprises Spongilla for use in a method of treating hyperhidrosis in a subject requiring it. In one embodiment, the first composition comprising Spongilla is administered at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, and at least once a week for at least thirteen weeks. A first composition is provided for use in which the first composition is applied to the skin of a subject at least once, at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In one embodiment, a first composition is provided for use in which the first composition comprising Spongilla is applied to the skin of a subject at least once a week for 2 weeks. In one embodiment, a first composition is provided for use in which the first composition comprising Spongilla is applied to the skin of a subject at least once a week for 3 weeks. In one embodiment, a first composition comprising Spongilla is provided for use in which the first composition is applied once a week to the skin of a subject over a period of four weeks.In one embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of five weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of six weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of seven weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of eight weeks.

[0050] 【0055】 A composition comprising Spongilla and one or more botulinum toxins for treating a skin condition or disease in a subject where it is needed, wherein the skin condition in the subject is acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type simple epidermal disease A composition selected from bullous diseases, Darier's disease, congenital onychoplasty, aqueous keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, the skin condition or state in the subject is hyperhidrosis, acne vulgaris, and rosacea, 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 condition in the subject is acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, and alopecia areata. Such a first composition is provided for use selected from among male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, such a composition is provided for use when the skin condition or state in the subject is hyperhidrosis, acne vulgaris, and rosacea. In one embodiment, such a composition is provided for use in which the botulinum toxin is selected from 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 botulinum toxin, and type G botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are selected from type A botulinum toxin, type B botulinum toxin, and type E botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type A botulinum toxin. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is onabotulinum toxin A.In one embodiment, such a composition is provided for use in which the type A botulinum toxin is avobotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is incobotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is prabotulinum toxin A. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type B botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are limabotulinum toxin B. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type C1 botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type C2 botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type D botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type E botulinum toxin. In one embodiment, such a composition is provided for use in which one or more type E botulinum toxins are EB-001A or EB-001T. In one embodiment, such a composition is provided for use in which one or more type E botulinum toxins are EB-001A. In one embodiment, such a composition is provided for use in which one or more type E botulinum toxins are EB-001T. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type F botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type G botulinum toxin. In one embodiment, such a composition is provided for use in which the skin condition of the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In one embodiment, such a composition is provided for use in which the skin condition of the subject is acne vulgaris. In one embodiment, such a composition is provided for use in which the skin condition of the subject is rosacea type 1.In one embodiment, such a composition is provided for use when the skin condition of the subject is type 2 rosacea acne. In another embodiment, such a composition is provided for use when the skin condition of the subject is psoriasis. Such compositions are provided. In one embodiment, such compositions are provided for use in which the skin condition in the subject is hyperhidrosis. In one embodiment, the composition is used at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, at least once a week for at least thirteen weeks, and at least once a week for at least thirteen weeks. Such a composition is provided for use in which the composition is applied to the skin of a subject at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In one embodiment, such a composition is provided for use in which the composition is applied to the skin of a subject at least once a week for 2 weeks. In one embodiment, such a composition is provided for use in which the composition is applied to the skin of a subject at least once a week for 3 weeks. In one embodiment, such a composition is provided for use in which the composition is applied to the skin of a subject at least once a week for 4 weeks. In one embodiment, such a composition is provided for use in which the composition is applied once a week to the skin of a subject over a period of five weeks. In another embodiment, such a composition is provided for use in which the composition comprising Spongilla is applied once a week to the skin of a subject over a period of six weeks.In one embodiment, such a composition is provided for use in which the composition is applied once a week to the skin of a subject over a period of seven weeks. In another embodiment, such a composition is provided for use in which the composition is applied once a week to the skin of a subject over a period of eight weeks.

[0051] 【0056】 A composition comprising Spongilla and one or more botulinum toxins for use in the treatment of hyperhidrosis in subjects requiring it. In one embodiment, such a composition is provided for use in which 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 embodiment, such a composition is provided for use in which one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are botulinum toxin type A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is onabotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is avobotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is incobotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is prabotulinum toxin A. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type B botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are lima botulinum toxin B. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type C1 botulinum toxin. In one embodiment, one or more Such compositions are provided for use in which the botulinum toxin type is C2 botulinum toxin. In one embodiment, such compositions are provided for use in which one or more botulinum toxin types are D botulinum toxin. In one embodiment, such compositions are provided for use in which one or more botulinum toxin types are E botulinum toxin. In one embodiment, such compositions are provided for use in which one or more E botulinum toxins are EB-001A or EB-001T. In one embodiment, such compositions are provided for use in which one or more E botulinum toxins are EB-001A. In one embodiment, such compositions are provided for use in which one or more E botulinum toxins are EB-001T. In one embodiment, such compositions are provided for use in which one or more botulinum toxin types are F botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are G-type botulinum toxins.

[0052] 【0057】 A composition comprising Spongilla and one or more botulinum toxins for use in the treatment of hyperhidrosis in subjects requiring it. In one embodiment, such a composition is provided for use in which the botulinum toxin is selected from 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 botulinum toxin, and type G botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are selected from type A botulinum toxin, type B botulinum toxin, and type E botulinum toxin.

[0053] 【0058】A composition comprising Spongilla and one or more botulinum toxins of type A, for use in the treatment of hyperhidrosis in subjects requiring it, wherein the botulinum toxin of type A is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, such a composition is provided for use in which the botulinum toxin of type A is onabotulinum toxin A. In one embodiment, such a composition is provided for use in which the botulinum toxin of type A is avobotulinum toxin A. In one embodiment, such a composition is provided for use in which the botulinum toxin of type A is incobotulinum toxin A. In one embodiment, such a composition is provided for use in which the botulinum toxin of type A is prabotulinum toxin A.

[0054] 【0059】A composition comprising Spongilla and onabotulinum toxin A for use in the treatment of hyperhidrosis in subjects requiring it. In another embodiment, the composition is administered at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, and at least once a week for at least thirteen weeks. A composition is provided which is applied to the skin of a subject at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In another embodiment, a composition is provided which is applied to the skin of a subject at least once a week for 2 weeks. In another embodiment, a composition is provided which is applied to the skin of a subject once a week over a period of three weeks. In another embodiment, a composition is provided which is applied to the skin of a subject once a week over a period of four weeks. In another embodiment, a composition is provided which is applied to the skin of a subject once a week over a period of five weeks. In another embodiment, a composition is provided which is applied to the skin of a subject once a week over a period of six weeks. In another embodiment, a composition is provided which is applied to the skin of a subject once a week over a period of seven weeks. In another embodiment, a composition is provided which is applied to the skin of a subject once a week over a period of eight weeks.

[0055] 【0060】The method comprises administering to a subject an effective amount of a first composition in combination with an effective amount of a 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 first composition comprising Spongilla for use in reducing sweat production in a subject. In another embodiment, a first composition is provided such that the subject experiences a reduction in gravimetric sweat production of more than 10% after administration of the first and second compositions compared to the gravimetric sweat production of the subject prior to such administration. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% after administration of the first and second compositions compared to the gravimetric sweat production of the subject before treatment. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 30% after administration of the first and second compositions compared to the gravimetric sweat production of the subject before treatment. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 40% after administration of the first and second compositions compared to the gravimetric sweat production of the subject before treatment. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 50% after administration of the first and second compositions compared to the gravimetric sweat production of the subject before treatment. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 60% compared to the subject's gravimetric sweat production before treatment after administration of the first and second compositions. In yet another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 70% compared to the subject's gravimetric sweat production before treatment after administration of the first and second compositions.In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 80% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 90% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In yet another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 95% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which the subject is treated once, twice, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, eighteen, or twenty-four times per month. In another embodiment, such compositions are provided for use in which the subject is treated twice per month. In another embodiment, such compositions are provided for use in which the subject is treated three times per month. In another embodiment, such compositions are provided for use in which the subject is treated once per week. In another embodiment, such a composition is provided for use in subjects aged 18 years or older. In another embodiment, the subject is for use for one month. Such compositions are provided for use in which the subject is treated 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 embodiment, such compositions are provided for use in which the subject is treated once every 1 month. In another embodiment, such compositions are provided for use in which the subject is treated once every 2 months. In another embodiment, such compositions are provided for use in which the subject is treated once every 3 months. In another embodiment, such compositions are provided for use in which the subject is treated once every 4 months. In another embodiment, such compositions are provided for use in which the subject is treated once every 5 months. In another embodiment, such compositions are provided for use in which the subject is treated once every 6 months. In another embodiment, such compositions are provided for use in which the subject is treated once every 7 months. In another embodiment, such a composition is provided for use in which the subject is treated once every eight months. In another embodiment, such a composition is provided for use in which the subject is treated once every nine months. In another embodiment, such a composition is provided for use in which the subject is treated once every ten months. In another embodiment, such a composition is provided for use in which the subject is treated once every eleven months. In another embodiment, such a composition is provided for use in which the subject is treated once every twelve months. In another embodiment, such a composition is provided for use in which the subject suffers from primary axillary hyperhidrosis.

[0056] 【0061】A method comprising administering to a subject an effective amount of a first composition in combination with an effective amount of a second composition, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A, the first composition comprising Spongilla for use in reducing sweat production in a subject. In one embodiment, such a first composition is provided for use in which the botulinum toxin type A is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, such a first composition is provided for use in which the botulinum toxin type A is onabotulinum toxin A. In one embodiment, such a first composition is provided for use in which the botulinum toxin type A is avobotulinum toxin A. In one embodiment, a first such composition is provided for use in which the botulinum toxin type A is incobotulinum toxin A. In another embodiment, a first such composition is provided for use in which the botulinum toxin type A is prabotulinum toxin A. In yet another embodiment, a first such composition is provided in which a subject experiences a reduction in gravimetric sweat production of more than 10% after administration of the first and second compositions compared to the gravimetric sweat production of the subject prior to such administration. In yet another embodiment, a first such composition is provided in which a subject experiences a reduction in gravimetric sweat production of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% after administration of the first and second compositions compared to the gravimetric sweat production of the subject prior to treatment. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 30% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 40% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In yet another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 50% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions.In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 60% compared to the subject's gravimetric sweat production before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 70% compared to the subject's gravimetric sweat production before treatment after administration of the first and second compositions. In another embodiment. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 80% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In yet another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 90% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In yet another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 95% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which the subject is treated once, twice, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, eighteen, or twenty-four times per month. In another embodiment, such compositions are provided for use in which the subject is treated twice per month. In another embodiment, such compositions are provided for use in which the subject is treated three times per month. In another embodiment, such compositions are provided for use in which the subject is treated once per week. In another embodiment, such a composition is provided for use in subjects aged 18 years or older. In another embodiment, such a composition is provided for use in which the subject is treated once a 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 embodiment, such a composition is provided for use in which the subject is treated once a month. In another embodiment, such a composition is provided for use in which the subject is treated once every two months. In another embodiment, such a composition is provided for use in which the subject is treated once every three months.In another embodiment, such a composition is provided for use in which the subject is treated once every four months. In another embodiment, such a composition is provided for use in which the subject is treated once every five months. In another embodiment, such a composition is provided for use in which the subject is treated once every six months. In another embodiment, such a composition is provided for use in which the subject is treated once every seven months. In another embodiment, such a composition is provided for use in which the subject is treated once every eight months. In another embodiment, such a composition is provided for use in which the subject is treated once every nine months. In another embodiment, such a composition is provided for use in which the subject is treated once every ten months. In another embodiment, such a composition is provided for use in which the subject is treated once every eleven months. In another embodiment, such a composition is provided for use in which the subject is treated once every twelve months. In another embodiment, such a composition is provided for use in which the subject suffers from primary axillary hyperhidrosis.

[0057] 【0062】A method is provided for use in reducing sweat production in a subject, comprising administering an effective amount of a first composition to a subject in combination with an effective amount of a second composition, wherein the second composition comprises Spongilla, the first composition for use in reducing sweat production in a subject, comprising onabotulinum toxin A. In another embodiment, such a first composition is provided, in which a subject experiences a reduction in gravimetric sweat production of more than 10% after administration of the first and second compositions compared to the gravimetric sweat production of the subject prior to such administration. In another embodiment, such a composition is provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% after administration of the first and second compositions compared to the gravimetric sweat production of the subject prior to treatment. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 30% compared to the subject's gravimetric sweat production before treatment after administration of the first and second compositions. In another embodiment, a subject experiences a reduction in gravimetric sweat production of more than 40% compared to the subject's gravimetric sweat production before treatment after administration of the first and second compositions. Such compositions are provided for use in which a reduction in quantity is experienced. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 50% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 60% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 70% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 80% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 90% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In yet another embodiment, such compositions are provided for use in which a subject experiences a reduction in gravimetric sweat production of more than 95% compared to the gravimetric sweat production of the subject before treatment after administration of the first and second compositions. In another embodiment, such compositions are provided for use in which the subject is treated once, twice, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, eighteen, or twenty-four times per month. In another embodiment, such compositions are provided for use in which the subject is treated twice per month. In another embodiment, such compositions are provided for use in which the subject is treated three times per month. In another embodiment, such compositions are provided for use in which the subject is treated once per week.In another embodiment, such a composition is provided for use in subjects aged 18 years or older. In another embodiment, such a composition is provided for use in which the subject is treated once a 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 embodiment, such a composition is provided for use in which the subject is treated once a month. In another embodiment, such a composition is provided for use in which the subject is treated once every two months. In another embodiment, such a composition is provided for use in which the subject is treated once every three months. In another embodiment, such a composition is provided for use in which the subject is treated once every four months. In another embodiment, such a composition is provided for use in which the subject is treated once every five months. In another embodiment, such a composition is provided for use in which the subject is treated once every six months. In another embodiment, such a composition is provided for use in which the subject is treated once every seven months. In another embodiment, such a composition is provided for use in which the subject is treated once every eight months. In another embodiment, such a composition is provided for use in which the subject is treated once every nine months. In another embodiment, such a composition is provided for use in which the subject is treated once every ten months. In another embodiment, such a composition is provided for use in which the subject is treated once every eleven months. In another embodiment, such a composition is provided for use in which the subject is treated once every twelve months. In another embodiment, such a composition is provided for use in which the subject suffers from primary axillary hyperhidrosis.

[0058] 【0063】The method comprises administering to a subject an effective amount of a first composition in combination with an effective amount of a second composition, wherein the second composition comprises Spongilla for use in a method of treating hyperhidrosis in a subject requiring it. In one embodiment, the botulinum toxin type A is derived from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. Such a first composition is provided for a selected use. In one embodiment, such a first composition is provided for a use in which the type A botulinum toxin is onabotulinum toxin A. In one embodiment, such a first composition is provided for a use in which the type A botulinum toxin is avobotulinum toxin A. In one embodiment, such a first composition is provided for a use in which the type A botulinum toxin is incobotulinum toxin A. In one embodiment, such a first composition is provided for a use in which the type A botulinum toxin is prabotulinum toxin A. In one embodiment, the first composition containing Spongilla is used at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, and at least once a week for at least thirteen weeks. A first composition is provided for use in which the composition is applied to the skin of a subject at least once, at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In one embodiment, a first composition is provided for use in which the first composition comprising Spongilla is applied to the skin of a subject at least once a week for 2 weeks.In one embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the target skin once a week over a period of three weeks. In another embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the target skin once a week over a period of four weeks. In another embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the target skin once a week over a period of five weeks. In another embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the target skin once a week over a period of six weeks. In yet another embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the target skin once a week over a period of seven weeks. In yet another embodiment, a first composition containing Spongilla is provided for use in which the first composition is applied to the target skin once a week over a period of eight weeks.

[0059] 【0064】The method comprises administering to a subject an effective amount of a first composition in combination with an effective amount of a second composition, wherein the second composition comprises onabotulinum toxin A, and the first composition comprises Spongilla for use in a method of treating hyperhidrosis in a subject requiring it. In one embodiment, the first composition containing Spongilla is used at least once a week for at least two weeks, at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, at least once a week for at least thirteen weeks, at least once a week for at least fourteen weeks, at least once a week for at least fifteen weeks, at least once a week for at least sixteen weeks, and at least once a week for at least seventeen weeks. A first composition is provided for use in which the first composition is applied to the skin of a target at least once a week, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In one embodiment, a first composition is provided for use in which the first composition containing Spongilla is applied to the skin of a target at least once a week for 2 weeks. In one embodiment, a first composition is provided for use in which the first composition containing Spongilla is applied to the skin of a target at least once a week for 3 weeks. In one embodiment, a first composition is provided for use in which the first composition containing Spongilla is applied to the skin of a target at least once a week for 4 weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of five weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of six weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of seven weeks. In one embodiment, a first composition containing Spongilla is provided for use in which the composition is applied to the skin of a subject once a week over a period of eight weeks.

[0060] 【0065】A composition comprising Spongilla and one or more botulinum toxins for treating a skin condition or disease in a subject in need thereof, wherein the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, onychomycosis, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, the skin condition or state in the subject is hyperhidrosis, acne vulgaris, and rosacea, 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 condition in the subject is acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, and alopecia areata. Such a first composition is provided for use selected from among male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, such a composition is provided for use when the skin condition or state in the subject is hyperhidrosis, acne vulgaris, and rosacea. In one embodiment, such a composition is provided for use in which the botulinum toxin is selected from 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 botulinum toxin, and type G botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are selected from type A botulinum toxin, type B botulinum toxin, and type E botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type A botulinum toxin.In one embodiment, such a composition is provided for use in which botulinum toxin type A is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, such a composition is provided for use in which botulinum toxin type A is onabotulinum toxin A. In one embodiment, such a composition is provided for use in which botulinum toxin type A is avobotulinum toxin A. Provided. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is incobotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is prabotulinum toxin A. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type B botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are limabotulinum toxin B. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type C1 botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type C2 botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type D botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type E botulinum toxin. In one embodiment, such a composition is provided for use in which one or more type E botulinum toxins are EB-001A or EB-001T. In one embodiment, such a composition is provided for use in which one or more type E botulinum toxins are EB-001A. In one embodiment, such a composition is provided for use in which one or more type E botulinum toxins are EB-001T. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type F botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type G botulinum toxin. In one embodiment, such a composition is provided for use in which the skin condition of the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In one embodiment, such a composition is provided for use in which the skin condition of the subject is acne vulgaris. In one embodiment, such a composition is provided for use in which the skin condition of the subject is rosacea type 1. In one embodiment, such a composition is provided for use in which the skin condition of the subject is rosacea type 2.In one embodiment, such a composition is provided for use in which the skin condition of the subject is psoriasis. In one embodiment, such a composition is provided for use in which the skin condition of the subject is hyperhidrosis. In one embodiment, the composition is provided to be used at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, at least once a week for at least thirteen weeks, and at least once a week. Such a composition is provided for use in which the composition is applied to the skin of a subject at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In one embodiment, such a composition is provided for use in which the composition is applied to the skin of a subject at least once a week for 2 weeks. In one embodiment, such a composition is provided for use in which the composition is applied to the skin of a subject at least once a week for 3 weeks. In one embodiment, such a composition is provided for use in which the composition is applied to the skin of a subject at least once a week for 4 weeks. In one embodiment, such a composition is provided for use in which the composition is applied once a week to the skin of a subject over a period of five weeks.In one embodiment, a composition comprising Spongilla is provided for use in which the composition is applied once a week to the skin of a subject over a period of six weeks. In another embodiment, the composition is applied once a week over a period of seven weeks. Such compositions are provided for use applied to the skin of a subject. In one embodiment, such compositions are provided for use applied to the skin of a subject once a week for eight weeks.

[0061] 【0066】A composition comprising Spongilla and one or more botulinum toxins for use in the treatment of hyperhidrosis in subjects requiring it. In one embodiment, such a composition is provided for use in which 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 embodiment, such a composition is provided for use in which one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are botulinum toxin type A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is onabotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is avobotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is incobotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is prabotulinum toxin A. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type B botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are lima botulinum toxin B. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type C1 botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type C2 botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type D botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are type E botulinum toxin.In one embodiment, such a composition is provided for use in which one or more E-type botulinum toxins are EB-001A or EB-001T. In one embodiment, such a composition is provided for use in which one or more E-type botulinum toxins are EB-001A. In one embodiment, such a composition is provided for use in which one or more E-type botulinum toxins are EB-001T. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are F-type botulinum toxins. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are G-type botulinum toxins.

[0062] 【0067】 A composition comprising Spongilla and one or more botulinum toxins for use in the treatment of hyperhidrosis in subjects requiring it. In one embodiment, such a composition is provided for use in which the botulinum toxin is selected from 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 botulinum toxin, and type G botulinum toxin. In one embodiment, such a composition is provided for use in which one or more botulinum toxin types are selected from type A botulinum toxin, type B botulinum toxin, and type E botulinum toxin.

[0063] 【0068】 Botulinum toxin type A is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A for use in the treatment of hyperhidrosis in subjects requiring it, Spongil A composition comprising la and one or more type A botulinum toxins. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is onabotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is avobotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is incobotulinum toxin A. In one embodiment, such a composition is provided for use in which the type A botulinum toxin is prabotulinum toxin A.

[0064] 【0069】A composition comprising Spongilla and onabotulinum toxin A for use in the treatment of hyperhidrosis in subjects requiring it. In another embodiment, the composition is administered at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, at least once a week for at least eleven weeks, at least once a week for at least twelve weeks, and at least once a week for at least thirteen weeks. A composition is provided which is applied to the skin of the subject at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In another embodiment, a composition is provided which is applied to the skin of the subject once a week for 2 weeks. In another embodiment, a composition is provided which is applied to the skin of the subject once a week for 3 weeks. In another embodiment, a composition is provided which is applied to the skin of the subject once a week for 4 weeks. In another embodiment, a composition is provided which is applied to the skin of the subject once a week for 5 weeks. In another embodiment, a composition is provided which is applied to the skin of a subject once a week for a period of six weeks. In yet another embodiment, a composition is provided which is applied to the skin of a subject once a week for a period of seven weeks.In another embodiment, a composition is provided which is applied to the skin of a subject once a week for eight weeks.

[0065] 【0070】 In one embodiment, a method for hyperhidrosis in a subject is provided, comprising the step of applying to the skin of the subject in need an effective amount of a first composition containing Spongilla and an effective amount of a second composition containing onabotulinum toxin A. In another embodiment, the first composition containing Spongilla is applied at least once a week for at least two weeks, at least once a week for at least three weeks, at least once a week for at least four weeks, at least once a week for at least five weeks, at least once a week for at least six weeks, at least once a week for at least seven weeks, at least once a week for at least eight weeks, at least once a week for at least nine weeks, at least once a week for at least ten weeks, and at least once a week for at least eleven weeks. At least once a week, at least once a week for at least 12 weeks, at least once a week for at least 13 weeks, at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least A method is provided in which the composition is applied to the target skin at least once a week over 22 weeks, at least once a week over 23 weeks, and at least once a week over 24 weeks. In another embodiment, a method is provided in which the first composition comprising Spongilla is applied to the target skin at least once a week over 2 weeks. In another embodiment, a method is provided in which the first composition comprising Spongilla is applied to the target skin at least once a week over 3 weeks. In another embodiment, a method is provided in which the first composition comprising Spongilla is applied to the target skin at least once a week over 4 weeks. In another embodiment, a method is provided in which the first composition comprising Spongilla is applied to the target skin at least once a week over 5 weeks. In another embodiment, a method is provided in which the first composition comprising Spongilla is applied to the target skin at least once a week over 6 weeks. In another embodiment, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of the subject once a week for seven weeks. In yet another embodiment, any method disclosed herein is provided, wherein a first composition comprising Spongilla is applied to the skin of the subject once a week for eight weeks.

[0066] 【0071】 In another embodiment, any method disclosed herein is provided, comprising the step of applying to the skin of a subject requiring such application an effective amount of a first composition containing Spongilla and an effective amount of a second composition containing one or more botulinum toxins.

[0067] 【0072】In one embodiment, a method is provided for treating a skin condition in a subject, comprising the step of applying to the skin of the subject a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins. In another embodiment, 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 embodiment, any method disclosed herein is provided, wherein the one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In yet another embodiment, any method disclosed herein is provided, wherein the one or more botulinum toxin types is botulinum toxin type A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is onabotulinum toxin A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is avobotulinum toxin A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is incobotulinum toxin A. In another embodiment, any method disclosed herein is provided in which the type A botulinum toxin is prabotulinum toxin A. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type B botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are lima botulinum toxin B. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type C1 botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type C2 botulinum toxin.In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type D botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type E botulinum toxin. In yet another embodiment, any method disclosed herein is provided in which one or more type E botulinum toxins are EB-001A or EB-001T. A method is provided in which one or more E-type botulinum toxins are EB-001A. A method is provided in which one or more E-type botulinum toxins are EB-001T. A method is provided in which one or more botulinum toxin types are F-type botulinum toxins. A method is provided in which one or more botulinum toxin types are G-type botulinum toxins. A method is provided in which the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. A method is provided in which the skin condition in the subject is acne vulgaris. A method is provided in which the skin condition in the subject is rosacea type 1. In another embodiment, any of the methods disclosed herein is provided, wherein the skin condition of the subject is rosacea type 2. In another embodiment, any of the methods disclosed herein is provided, wherein the skin condition of the subject is psoriasis. In another embodiment, any of the methods disclosed herein is provided, wherein the skin condition of the subject is hyperhidrosis.

[0068] 【0073】In another embodiment, a composition is provided for use as a pharmaceutical, comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins. In another embodiment, a composition is provided for use as a pharmaceutical, comprising 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 embodiment, such a composition is provided for use as a pharmaceutical for treating a skin condition in a subject. In another embodiment, such combinations are provided for use as a pharmacopoeia for treating a skin condition in a subject, where the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, and eccrine nevus. In another embodiment, 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 embodiment, 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 yet another embodiment, any composition disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type A. In another embodiment, any composition disclosed herein is provided in which the botulinum toxin type A is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A. In yet another embodiment, any composition disclosed herein is provided in which the botulinum toxin type A is onabotulinum toxin A.In another embodiment, any composition disclosed herein is provided in which the type A botulinum toxin is avobotulinum toxin A. In another embodiment, any composition disclosed herein is provided in which the type A botulinum toxin is incobotulinum toxin A. In another embodiment, any composition disclosed herein is provided in which the type A botulinum toxin is prabotulinum toxin A. In another embodiment, any composition disclosed herein is provided in which one or more botulinum toxin types are type B botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are limabotulinum toxin B. In another embodiment, any composition disclosed herein is provided in which one or more botulinum toxin types are type C1 botulinum toxin. In another embodiment. In another embodiment, any composition disclosed herein is provided, wherein one or more botulinum toxin types are C2 botulinum toxin. In yet another embodiment, any composition disclosed herein is provided, wherein one or more botulinum toxin types are D botulinum toxin. In yet another embodiment, any composition disclosed herein is provided, wherein one or more botulinum toxin types are E botulinum toxin. In yet another embodiment, any composition disclosed herein is provided, wherein one or more E botulinum toxins are EB-001A or EB-001T. In yet another embodiment, any composition disclosed herein is provided, wherein one or more E botulinum toxins are EB-001A. In yet another embodiment, any composition disclosed herein is provided, wherein one or more E botulinum toxins are EB-001T. In another embodiment, any composition disclosed herein is provided, wherein one or more botulinum toxin types are type F botulinum toxin. In another embodiment, any composition disclosed herein is provided, wherein one or more botulinum toxin types are type G botulinum toxin. In another embodiment, 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 embodiment, any composition disclosed herein is provided, wherein the skin condition in the subject is acne vulgaris. In another embodiment, any composition disclosed herein is provided, wherein the skin condition in the subject is rosacea type 1. In another embodiment, any composition disclosed herein is provided, wherein the skin condition in the subject is rosacea type 2. In another embodiment, any composition disclosed herein is provided, wherein the skin condition in the subject is psoriasis. In another embodiment, any composition disclosed herein is provided, wherein the skin condition in the subject is hyperhidrosis. In another embodiment, the second composition is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, EB-001A, and EB-001T, and any of the compositions disclosed herein is provided, wherein the skin condition in the subject is type 1 rosacea acne.In another embodiment, any of the compositions disclosed herein is provided, wherein the second composition is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, EB-001A, and EB-001, and the skin condition in the subject is type 2 rosacea acne. In another embodiment, any of the compositions disclosed herein is provided, wherein the second composition is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, EB-001A, and EB-001, and the skin condition in the subject is psoriasis. In another embodiment, any of the compositions disclosed herein is provided, wherein the second composition is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is hyperhidrosis. In another embodiment, any of the compositions disclosed herein is provided, wherein the second composition is onabotulinum toxin A and the skin condition in the subject is type 1 rosacea acne. In another embodiment, any of the compositions disclosed herein is provided, wherein the second composition is onabotulinum toxin A and the skin condition in the subject is type 2 rosacea acne. In yet another embodiment, any of the compositions disclosed herein is provided, wherein the second composition is onabotulinum toxin A and the skin condition in the subject is psoriasis. In another embodiment, any of the compositions disclosed herein is provided, wherein the second composition is onabotulinum toxin A, and the skin condition in the subject is hyperhidrosis.

[0069] 【0074】 In another embodiment, a composition is provided for use in the treatment of a skin condition in a subject, comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins. In another embodiment, a combination comprising a first composition and a second composition is provided for use in the treatment of a skin condition in a subject, wherein (a) the first composition comprises Spongilla (b) A combination is provided in which the second composition comprises lacustris and one or more botulinum toxins. In another embodiment, the skin condition in the subject is acne vulgaris, Such compositions are provided for use in the treatment of skin conditions in subjects selected from rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, such compositions are provided for use in the treatment of a skin condition in a subject, where the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, 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 embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In yet another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein one or more botulinum toxin types are botulinum toxin type A. In another embodiment, such compositions are provided for use in the treatment of skin conditions in a subject, wherein the type A botulinum toxin is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A.In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein the botulinum toxin type A is onabotulinum toxin A. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein the botulinum toxin type A is avobotulinum toxin A. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein the botulinum toxin type A is incobotulinum toxin A. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein the botulinum toxin type A is prabotulinum toxin A. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein the botulinum toxin type A is daxibotulinum toxin A. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein one or more botulinum toxin types are botulinum toxin type B. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are lima botulinum toxin B. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, in which one or more botulinum toxin types are type C1 botulinum toxin. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, in which one or more botulinum toxin types are type C2 botulinum toxin. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, in which one or more botulinum toxin types are type D botulinum toxin. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, in which one or more botulinum toxin types are type E botulinum toxin. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, in which one or more type E botulinum toxins are EB-001A or EB-001T. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein one or more types of botulinum toxin E are EB-001A.In another embodiment, a composition is provided for use in the treatment of a skin condition in a subject, wherein one or more types of botulinum toxin E are EB-001T. In yet another embodiment, one or more. In another embodiment, such compositions are provided for use in the treatment of a skin condition in a subject, wherein one or more botulinum toxin types are type F botulinum toxin. In yet another embodiment, such compositions are provided for use in the treatment of a skin condition in a subject, wherein one or more botulinum toxin types are type G botulinum toxin. In yet another embodiment, such compositions are provided 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 yet another embodiment, such compositions are provided for use in the treatment of a skin condition in a subject, wherein the skin condition in the subject is acne vulgaris. In yet another embodiment, any of the compositions disclosed herein is provided, wherein the skin condition in the subject is rosacea type 1. In yet another embodiment, such compositions are provided for use in the treatment of a skin condition in a subject, wherein the skin condition in the subject is rosacea type 2. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein the skin condition in the subject is psoriasis. In another embodiment, such a composition is provided for use in the treatment of a skin condition in a subject, wherein the skin condition in the subject is hyperhidrosis. In another embodiment, such a composition is provided 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, prabotulinum toxin A, EB-001A, and EB-001T, wherein the skin condition in the subject is rosacea acne type 1. In another embodiment, such a composition is provided 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, prabotulinum toxin A, EB-001A, and EB-001T, wherein the skin condition in the subject is rosacea acne type 2. In another embodiment, a second composition is provided which is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, EB-001A, and EB-001T, and is for use in the treatment of a skin condition in a subject, wherein the skin condition in the subject is psoriasis.In another embodiment, a composition is provided 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, prabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is hyperhidrosis. In another embodiment, a composition is provided 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 acne. In another embodiment, a composition is provided 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 acne. In yet another embodiment, a composition is provided 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 embodiment, a composition is provided 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.

[0070] 【0075】In another embodiment, a composition is provided for manufacturing a medicament for the treatment of a skin condition in a subject, comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla, and (b) the second composition comprises one or more botulinum toxins. To manufacture pharmaceuticals for the treatment of skin conditions in subjects selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. A composition for the purpose of treating a skin condition in a subject is provided. In another embodiment, a composition is provided for the manufacture of a medicament for the treatment of a skin condition in a subject, selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, a composition is provided for manufacturing a medicament for the treatment of a skin condition in a subject, selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevus, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, 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 embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein one or more botulinum toxin types are selected from botulinum toxin type A, botulinum toxin type B, and botulinum toxin type E. In yet another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein one or more botulinum toxin types are botulinum toxin type A. In another embodiment, a composition is provided for producing a pharmaceutical for the treatment of a skin condition in a subject, wherein the type A botulinum toxin is selected from onabotulinum toxin A, avobotulinum toxin A, incobotulinum toxin A, prabotulinum toxin A, and daxibotulinum toxin A.In another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein the botulinum toxin type A is onabotulinum toxin A. In another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein the botulinum toxin type A is avobotulinum toxin A. In another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein the botulinum toxin type A is incobotulinum toxin A. In another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein the botulinum toxin type A is prabotulinum toxin A. In another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein the botulinum toxin type A is daxibotulinum toxin A. In another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein one or more botulinum toxin types are botulinum toxin type B. In another embodiment, any method disclosed herein is provided, wherein one or more type B botulinum toxins are lima botulinum toxin B. In another embodiment, a composition for producing a pharmaceutical for the treatment of a skin condition in a subject is provided, wherein one or more botulinum toxin types are type C1 botulinum toxin. In another embodiment, a composition for producing a pharmaceutical for the treatment of a skin condition in a subject is provided, wherein one or more botulinum toxin types are type C2 botulinum toxin. In another embodiment, a composition for producing a pharmaceutical for the treatment of a skin condition in a subject is provided, wherein one or more botulinum toxin types are type D botulinum toxin. In another embodiment, a composition for producing a pharmaceutical for the treatment of a skin condition in a subject is provided, wherein one or more botulinum toxin types are type E botulinum toxin. In another embodiment, a composition for producing a pharmaceutical for the treatment of a skin condition in a subject is provided, wherein one or more type E botulinum toxins are EB-001A or EB-001T. In another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein one or more type E botulinum toxins are EB-001A.In another embodiment, a composition is provided for manufacturing a pharmaceutical for the treatment of a skin condition in a subject, wherein one or more type E botulinum toxins are EB-001T. A composition is provided for manufacturing a pharmacopoeia for the treatment of a skin condition in a subject, wherein the botulinum toxin type is type F botulinum toxin. In another embodiment, a composition is provided for manufacturing a pharmacopoeia for the treatment of a skin condition in a subject, wherein one or more botulinum toxin types are type G botulinum toxin. In another embodiment, a composition is provided for manufacturing a pharmacopoeia 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, and hyperhidrosis. In another embodiment, a composition is provided for manufacturing a pharmacopoeia for the treatment of a skin condition in a subject, wherein the skin condition in the subject is acne vulgaris. In another embodiment, a composition is provided for manufacturing a pharmacopoeia for the treatment of a skin condition in a subject, wherein the skin condition in the subject is type 1 rosacea. In another embodiment, a composition is provided for manufacturing a pharmacopoeia for the treatment of a skin condition in a subject, wherein the skin condition in the subject is type 2 rosacea. In another embodiment, a composition is provided for manufacturing a pharmacopoeia for the treatment of a skin condition in a subject, wherein the skin condition in the subject is psoriasis. In another embodiment, a composition is provided for manufacturing a pharmacopoeia for the treatment of a skin condition in a subject, wherein the skin condition in the subject is hyperhidrosis. In another embodiment, a composition is provided for manufacturing a pharmacopoeia for 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, prabotulinum toxin A, EB-001A, and EB-001T, wherein the skin condition in the subject is type 1 rosacea acne. In another embodiment, a composition is provided for manufacturing a pharmacopoeia for 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, prabotulinum toxin A, EB-001A, and EB-001T, wherein the skin condition in the subject is type 2 rosacea acne. In another embodiment, a composition is provided for manufacturing a medicament for 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, prabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is psoriasis.In another embodiment, a composition is provided for manufacturing a pharmacopoeci for 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, prabotulinum toxin A, EB-001A, and EB-001T, and the skin condition in the subject is hyperhidrosis. In another embodiment, a composition is provided for manufacturing a pharmacopoeci for 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 acne. In another embodiment, a composition is provided for manufacturing a pharmacopoeci for 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 acne. In yet another embodiment, a composition is provided for manufacturing a pharmacopoeci for 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 embodiment, a composition is provided for producing a medicament for 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.

[0071] 【0076】 In another embodiment, a method for treating hyperhidrosis in a subject is provided, comprising the step of applying to the skin of the subject a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins. In another embodiment, any method for treating hyperhidrosis 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 embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A. In another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein botulinum toxin type A is onabotulinum toxin A. In another embodiment, a hyperhidrosis treatment in which the subject experiences an improvement of at least one level in their HDSS score after the treatment compared to their HDSS score before the treatment.A method for treating hyperhidrosis is provided as disclosed herein. In another embodiment, a method for treating hyperhidrosis is provided in which a subject experiences an improvement of at least two levels in its HDSS score after treatment compared to the subject's HDSS score before treatment. In another embodiment, a method for treating hyperhidrosis is provided in which a subject experiences an improvement of at least three levels in its HDSS score after treatment compared to the subject's HDSS score before treatment. In another embodiment, a method for treating hyperhidrosis is provided in which a subject experiences a decrease in its weight-measured sweat production of more than 10% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, a method for treating hyperhidrosis is provided in which a subject experiences a decrease in its weight-measured sweat production of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 30% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 40% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 50% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 60% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 70% after treatment compared to the subject's weight-measured sweat production before treatment.In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 80% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 90% after treatment compared to the subject's weight-measured sweat production before treatment. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 95% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once, twice, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, eighteen, or twenty-four times per month. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated twice per month. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated three times per month. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once a week. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is 18 years of age or older. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once a 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 embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once a month.In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every two months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every three months. In yet another embodiment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every four months. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every five months. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every six months. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every seven months. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every eight months. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every nine months. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every ten months. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every eleven months. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every twelve months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is suffering from primary axillary hyperhidrosis.

[0072] 【0077】In another embodiment, a method for treating hyperhidrosis in a subject is provided, comprising the step of applying to the skin of the subject a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins. In another embodiment, any method for treating hyperhidrosis 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 embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A. In another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein botulinum toxin type A is onabotulinum toxin A. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences an improvement of at least 4 points from baseline in the Axillary Sweating Daily Diary (ASDD) Item 2 score compared to the subject's ASDD score before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences an improvement of at least 4 points from baseline in the Axillary Sweating Daily Diary (ASDD) Item 2 score at 4 weeks post-treatment compared to the subject's ASDD score before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences an improvement of at least two levels in the ASDD score after treatment compared to the subject's ASDD score before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences an improvement of at least three levels in the ASDD score after treatment compared to the subject's ASDD score before treatment. In another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 10% after the treatment compared to the subject's weight-measured sweat production before the treatment.In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 30% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 40% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 50% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 60% after treatment compared to the subject's weight-measured sweat production before treatment. In yet another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 70% after treatment compared to the subject's weight-measured sweat production before treatment. In yet another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 80% after treatment compared to the subject's weight-measured sweat production before treatment. In yet another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 90% after treatment compared to the subject's weight-measured sweat production before treatment. In yet another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject experiences a reduction in weight-measured sweat production of more than 95% after treatment compared to the subject's weight-measured sweat production before treatment. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once, twice, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, eighteen, or twenty-four times per month. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated twice per month. In yet another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated three times per month. In another embodiment, any of the methods disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once a week. In yet another embodiment, any of the methods disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is 18 years of age or older.In another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject is treated once a 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 embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject is treated once a month. In another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject is treated once every two months. In another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject is treated once every three months. In another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject is treated once every four months. In another embodiment, any method for treating hyperhidrosis disclosed herein is provided, wherein the subject is treated once every five months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every six months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every seven months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every eight months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every nine months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every ten months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every eleven months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject is treated once every twelve months. In another embodiment, any method disclosed herein for the treatment of hyperhidrosis is provided, wherein the subject suffers from primary axillary hyperhidrosis.

[0073] 【0078】In another embodiment, the amount of percutaneous sweat production per axilla at 4 weeks after application of the composition containing Spongilla and the composition containing one or more botulinum toxins is 50 mg or less, the percentage of treated subjects is approximately 10% of the subjects, approximately 15% of the subjects, Any method, composition, composition for use, and kit disclosed herein is provided, wherein the target is approximately 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% of the target. In another embodiment, any method, composition, composition for use, and kit 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 embodiment, a method, composition, composition for use, and kit are provided, wherein the second composition comprises one or more botulinum toxin types selected from botulinum toxin type A. In yet another embodiment, a method, composition, composition for use, and kit are provided, wherein the botulinum toxin type A is onabotulinum toxin A. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once, twice, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, eighteen, or twenty-four times per month. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated twice per month. In yet another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated three times per month. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once a week. In yet another embodiment, a method, composition, composition for use, and kit are provided in which the subject is 18 years of age or younger.In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once a 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 embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once a month. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every two months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every three months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every four months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every five months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every six months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every seven months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every eight months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every nine months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every ten months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every eleven months. In another embodiment, a method, composition, composition for use, and kit are provided in which the subject is treated once every twelve months. In another embodiment, a method, composition, composition for use, and kit are provided for a subject suffering from primary axillary hyperhidrosis.

[0074] 【0079】In another embodiment, the first composition contains about 0.25 grams to about 10 grams of Spong A method for treating hyperhidrosis is provided, comprising Spongilla. In another embodiment, a method for treating hyperhidrosis is provided, wherein the composition comprises Spongilla and a hydrogen peroxide solution. In yet another embodiment, a method for treating hyperhidrosis is provided, wherein the hydrogen peroxide solution comprises about 3% hydrogen peroxide. In yet another embodiment, a method 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.

[0075] 【0080】In another embodiment, any method disclosed herein is provided in which the first composition comprises Spongilla in powder form. The Spongilla-containing material may be prepared in powder form in which the particles are substantially the same size by using techniques known to those skilled in the art, such as gliding or sieving. In another embodiment, any method disclosed herein is provided in which Spongilla is in powder form comprising particles of substantially uniform size. In another embodiment, any method disclosed herein is provided in which about 50% or more of the particles constituting the Spongilla powder pass through a US70 mesh screen. In another embodiment, any method disclosed herein is provided in which 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% or more of the particles constituting the Spongilla powder pass through a US70 mesh screen. In another embodiment, any method disclosed herein is provided in which about 95%, or about 96%, or about 97%, or about 98%, or about 99% or more of the particles constituting the Spongilla powder pass through a US70 mesh screen. In another embodiment, any method disclosed herein is provided in which about 95% or more of the particles constituting the Spongilla powder pass through a US70 mesh screen. In another embodiment, any method disclosed herein is provided in which about 96% or more of the particles constituting the Spongilla powder pass through a US70 mesh screen. In another embodiment, any method disclosed herein is provided in which about 97% or more of the particles constituting the Spongilla powder pass through a US70 mesh screen. In another embodiment, any method disclosed herein is provided in which about 98% or more of the particles constituting the Spongilla powder pass through a US70 mesh screen. In another embodiment, any method disclosed herein is provided in which about 99% or more of the particles constituting the Spongilla powder pass through a US70 mesh screen.Spongilla particles may be manufactured or produced from Spongilla material harvested using equipment known to those skilled in the art, by procedures known to those skilled in the art, such as determining the appropriate harvest time, removing foreign materials, drying, grinding, and gliding.

[0076] 【0081】 In another embodiment, any method disclosed herein is provided in which the particles constituting the Spongilla powder have an average length of about 50 μm to about 500 μm. In another embodiment, the particles constituting the Spongilla powder have an average length of 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 400 μm. Approximately 350 μm, or approximately 100 μm to approximately 450 μm, or approximately 100 μm to approximately 400 μm, or approximately 100 μm to approximately 350 μm, or approximately 100 μm to approximately 300 μm, or approximately 100 μm to approximately 250 μm, or approximately 100 μm to approximately 200 μm, or approximately 150 μm to approximately 500 μm, or approximately 150 μm to approximately 450 μm, or approximately 150 μm to approximately 400 μm, or approximately 150 μm to approximately 350 μm, or approximately 150 μm to approximately 350 μm, or approximately 150 μm to approximately 300 μm, or approximately 150 μm to approximately 250 μm, or approximately 150 μm to approximately 200 Any method disclosed herein is provided, having an average length of μm, or about 175 μm to 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 embodiment, any method disclosed herein is provided in which the particles constituting the 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 embodiment, any method disclosed herein is provided in which the particles constituting the Spongilla powder have an average length of about 200 μm. The particles constituting the Spongilla powder may be manufactured or produced from Spongilla material harvested by procedures known to those skilled in the art, such as grinding or gliding, using equipment known to those skilled in the art. The average length of the particles constituting Spongilla powder can be measured using analytical methods known to those skilled in the art, such as scanning electron microscopy (SEM) or sieve analysis. Sieve analysis can also be used to determine the particle size distribution of the particles constituting Spongilla powder.

[0077] 【0082】In another embodiment, any method disclosed herein is provided in which the particles constituting the Spongilla powder have an average diameter of about 5 μm to about 50 μm. In yet another embodiment, any method disclosed herein is provided in which the particles constituting the 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 embodiment, any method disclosed herein is provided in which the particles constituting the 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. The particles constituting the Spongilla powder may be manufactured or produced from Spongilla material harvested by procedures known to those skilled in the art, such as grinding or gliding, using equipment known to those skilled in the art. The average diameter of the particles constituting the Spongilla powder can be measured using analytical methods known to those skilled in the art, such as scanning electron microscopy (SEM) or sieve analysis. Sieve analysis can also be used to determine the particle size distribution of the particles constituting the Spongilla powder.

[0078] 【0083】In another embodiment, any method disclosed herein is provided in which the particles constituting the Spongilla powder have an aspect ratio of about 1 to about 100. In another embodiment, the particles constituting the Spongilla powder have an aspect ratio of 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 5 A method is provided disclosed herein in which the particles constituting the Spongilla powder have an aspect ratio of approximately 0, 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 10 to about 40, or about 10 to about 35, or about 10 to about 30, or about 10 to about 25, or about 10 to about 20, or about 10 to about 15. In another embodiment, the particles constituting the Spongilla powder have an aspect ratio of approximately 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 Any method disclosed herein is provided, having an aspect ratio of approximately 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 75, or 100. The particles constituting the Spongilla powder may be manufactured or produced from Spongilla material harvested by procedures known to those skilled in the art, such as grinding or gliding, using equipment known to those skilled in the art. The aspect ratio of the particles constituting the Spongilla powder can be measured using analytical methods known to those skilled in the art, such as scanning electron microscopy (SEM) or sieve analysis. Sieve analysis can also be used to determine the particle size distribution of the particles constituting the Spongilla powder.

[0079] 【0084】A material containing Spongilla can be processed and dried using techniques known to those skilled in the art, such as the use of a drying oven, to obtain a material having a desired residual moisture content. In another embodiment, any method disclosed herein is provided in which a first composition containing Spongilla has a residual moisture content of about 20% or less. In another embodiment, any method disclosed herein is provided in which a 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. In another embodiment, any method disclosed herein is provided in which a first composition has a residual moisture content of about 5% or less. In another embodiment, any method disclosed herein is provided in which a first composition has a residual moisture content of about 4% or less. In another embodiment, any method disclosed herein is provided in which a first composition has a residual moisture content of about 3% or less. In another embodiment, any method disclosed herein is provided in which the first composition has a residual water content of about 2% or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has a residual water content of about 1% or less. The water content of Spongilla material can be reduced by heating the raw Spongilla material using methods known to those skilled in the art, such as by sun drying or by using a conventional oven dryer or vacuum dryer, using equipment known to those skilled in the art. For example, the raw Spongilla material can be placed in a tray and heated in a drying oven at a temperature in the range of about 30°C to about 200°C, for example, up to about 70°C, for the time necessary to reduce the residual water content to the desired level. The level of residual moisture in the material is determined by the United States Pharmacopeia (USP) method. <731> (Loss on Drying) and USP <921> It can be measured using methods known to those skilled in the art, such as those described in (Water Determination).

[0080] 【0085】Materials containing Spongilla may be treated before packaging and use, for example, by heat treatment or irradiation, such as gamma irradiation, to reduce the bioburden of the material, including aerobic and anaerobic microorganisms, yeasts and molds, E. coli-type bacteria, Salmonella, pseudomonas aeruginosa, and Staphylococcus aureus.

[0081] 【0086】 In another embodiment, the first composition is approximately 25 × 10 per gram. 4 A method disclosed herein is provided which has a total aerobic and anaerobic microbial content of less than or equal to colony-forming units (CFU / g). In another embodiment, the first composition is about 10 × 10 4 CFU / g or less, or approximately 5 x 10 4 Less than CFU / g, or approximately 1 × 10⁻⁶ 4 CFU / g or less, or approximately 5 x 10 3 Less than CFU / g, or approximately 1 × 10⁻⁶ 3 Less than or equal to 10,000 CFU / g, or less than or equal to 7,500 CFU / g, or less than or equal to 5,000 CFU / g, or less than or equal to 2,500 CFU / g, or less than or equal to 2,000 CFU / g, or less than or equal to 1,500 CFU / g, or less than or equal to 1,000 CFU / g, A method disclosed herein is provided in which the total aerobic and anaerobic microbial content is approximately 750 CFU / g or less, or approximately 500 CFU / g or less, or approximately 250 CFU / g or less, or approximately 200 CFU / g or less, or approximately 150 CFU / g or less, or approximately 100 CFU / g or less, or approximately 75 CFU / g or less, or approximately 50 CFU / g or less, or approximately 25 CFU / g or less, or approximately 15 CFU / g or less, or approximately 10 CFU / g or less, or approximately 5 CFU / g or less, or approximately 1 CFU / g or less. In another embodiment, a method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of approximately 1,000 CFU / g or less. In another embodiment, a method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of approximately 750 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of about 500 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of about 250 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of about 200 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of about 150 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of about 100 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of about 75 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of about 50 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has a total aerobic and anaerobic microbial content of about 25 CFU / g or less.In another aspect, any of the methods disclosed herein is provided, wherein the first composition has an aerobic and anaerobic total microbial content of about 20 CFU / g or less. In another aspect, any of the methods disclosed herein is provided, wherein the first composition has an aerobic and anaerobic total microbial content of about 10 CFU / g or less. In another aspect, any of the methods disclosed herein is provided, wherein the first composition has an aerobic and anaerobic total microbial content of about 1 CFU / g or less. The aerobic and anaerobic total microbial content of the Spongilla material can be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material by heat in the form of steam or dry heat for a time sufficient to reduce the microbial content to the desired level, or chemical treatment in the form of exposure to ethylene oxide gas or treatment by ionizing radiation. The aerobic and anaerobic total microbial content of the Spongilla material can be measured by methods known to those skilled in the art, such as those described in the United States Pharmacopeia USP method <61> (Microbial Enumeration Tests). 【0082】 【0087】 In another aspect, any of the methods disclosed herein is provided, wherein the first composition containing Spongilla has a total yeast and mold content of about 25×10 4 colony forming units (CFU / g) or less per gram. In another aspect, the first composition has about 5×10 4 CFU / g or less, or about 1×10 4 CFU / g or less, or about 5×10 3 CFU / g or less, or about 1×10 3Less than or approximately 10,000 CFU / g or less, or approximately 7,500 CFU / g or less, or approximately 5,000 CFU / g or less, or approximately 2,500 CFU / g or less, or approximately 2,000 CFU / g or less, or approximately 1,500 CFU / g or less, or approximately 1,000 CFU / g or less, or approximately 750 CFU / g or less, or approximately 500 CFU / g or less, or approximately 250 CFU / g or less, or approximately 200 CFU / g or less, or approximately 150 CFU / g or less, or approximately 100 CFU / g or less, or approximately 75 CFU / g or less, or approximately 50 CFU / g or less, or approximately 25 CFU / g or less, or approximately 15 CFU / g or less, or approximately 10 CFU / g or less, or approximately 5 CFU / g or less, In another embodiment, any method disclosed herein is provided, having a total yeast and mold content of approximately 1 CFU / g or less. In yet another embodiment, any method disclosed herein is provided, wherein the first composition has a total yeast and mold content of approximately 1,000 CFU / g or less. In yet another embodiment, any method disclosed herein is provided, wherein the first composition has a total yeast and mold content of approximately 750 CFU / g or less. In yet another embodiment, any method disclosed herein is provided, wherein the first composition has a total yeast and mold content of approximately 500 CFU / g or less. In yet another embodiment, any method disclosed herein is provided, wherein the first composition has a total yeast and mold content of approximately 250 CFU / g or less. In yet another embodiment, any method disclosed herein is provided, wherein the first composition has a total yeast and mold content of approximately 200 CFU / g or less. In yet another embodiment, any method disclosed herein is provided, wherein the first composition has a total yeast and mold content of approximately 150 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total yeast and mold content of about 100 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total yeast and mold content of about 75 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total yeast and mold content of about 50 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total yeast and mold content of about 25 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total yeast and mold content of about 20 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total yeast and mold content of about 10 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a total yeast and mold content of about 1 CFU / g or less.The total yeast and mold content of Spongilla material can be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material by heat in the form of steam or dry heat, or 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 desired level. The total yeast and mold content of Spongilla material is determined by the United States Pharmacopeia (USP) method. <61> It can be measured by methods known to those skilled in the art, such as those described in (Microbial Enumeration Tests).

[0083] 【0088】 In another embodiment, the amount of E. coli-type bacteria in the first composition is approximately 25 × 10⁶ per gram. 4 Any method disclosed herein is provided, wherein the amount of colony-forming units (CFU / g) is less than or equal to the amount of colony-forming units (CFU / g). In another embodiment, the amount of Escherichia coli-type bacteria in the first composition is about 5 × 10⁻⁶ 4 Less than CFU / g, or approximately 1 × 10⁻⁶ 4 CFU / g or less, or approximately 5 x 10 3 Less than CFU / g, or approximately 1 × 10⁻⁶ 3Any method disclosed herein is provided, which is less than or equal to CFU / g, 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 embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 1,000 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 750 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 500 CFU / g or less. In another embodiment, In another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 250 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 200 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 150 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 100 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 75 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 50 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 25 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 20 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 10 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 1 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has an E. coli content of about 1 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a detectable E. coli content of zero. The E. coli content of Spongilla material can be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material by heat in the form of steam or dry heat for a sufficient amount of time to reduce the microbial content to a desired level, or chemical treatment in the form of exposure to ethylene oxide gas or treatment with ionizing radiation. The E. coli content of Spongilla material is determined according to the United States Pharmacopeia (USP) method. <62> It can be measured by methods known to those skilled in the art, such as those described in (Tests for Specified Microorganisms).

[0084] 【0089】 In another embodiment, the amount of Salmonella in the first composition is approximately 25 × 10 per gram. 4 Any method disclosed herein is provided, wherein the amount of Salmonella in the first composition is less than or equal to the colony-forming units (CFU / g). In another embodiment, the amount of Salmonella in the first composition is about 5 × 10 4 Less than CFU / g, or approximately 1 × 10⁻⁶ 4 CFU / g or less, or approximately 5 x 10 3 Less than CFU / g, or approximately 1 × 10⁻⁶ 3Any method disclosed herein is provided, which is less than or equal to CFU / g, 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 embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 1,000 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 750 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 500 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 250 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 200 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 150 CFU / g or less. In another embodiment, the first composition In another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 100 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 75 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 50 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 25 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 20 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 10 CFU / g or less. In yet another embodiment, any method disclosed herein is provided in which the first composition has a Salmonella content of about 1 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a detectable Salmonella content of zero. The Salmonella content of Spongilla material can be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material by heat in the form of steam or dry heat for a time sufficient to reduce the microbial content to a desired level, or chemical treatment in the form of exposure to ethylene oxide gas or treatment with ionizing radiation. The Salmonella content of Spongilla material is determined by the United States Pharmacopeia (USP) method. <62> It can be measured by methods known to those skilled in the art, such as those described in (Tests for Specified Microorganisms).

[0085] 【0090】 In another embodiment, the amount of Pseudomonas aeruginosa bacteria in the first composition is approximately 25 × 10⁶ per gram. 4Any method disclosed herein is provided, wherein the amount of colony-forming units (CFU / g) is less than or equal to the amount of Pseudomonas aeruginosa bacteria in the first composition is about 5 × 10⁻⁶. 4 Less than CFU / g, or approximately 1 × 10⁻⁶ 4 CFU / g or less, or approximately 5 x 10 3 Less than CFU / g, or approximately 1 × 10⁻⁶ 3Any method disclosed herein is provided, which is less than or equal to CFU / g, 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 embodiment, any method disclosed herein is provided in which the first composition has a Pseudomonas aeruginosa bacterial content of about 1,000 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Pseudomonas aeruginosa bacterial content of about 750 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Pseudomonas aeruginosa bacterial content of about 500 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Pseudomonas aeruginosa bacterial content of about 250 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Pseudomonas aeruginosa bacterial content of about 200 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Pseudomonas aeruginosa bacterial content of about 150 CFU / g or less. In another embodiment, the first composition has a Pseudomonas aeruginosa bacterial content of about 100 CFU / g or less. One of the methods disclosed herein is provided. In another embodiment, one of the methods disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 75 CFU / g or less. In another embodiment, one of the methods disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 50 CFU / g or less. In another embodiment, one of the methods disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 25 CFU / g or less. In another embodiment, one of the methods disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 20 CFU / g or less. In another embodiment, one of the methods disclosed herein is provided, wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 10 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Pseudomonas aeruginosa bacterial content of about 1 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a detectable Pseudomonas aeruginosa bacterial content of zero. The Pseudomonas aeruginosa bacterial content of Spongilla material can be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material by heat in the form of steam or dry heat for a time sufficient to reduce the microbial content to a desired level, or chemical treatment in the form of exposure to ethylene oxide gas or treatment with ionizing radiation. The Aeruginosa bacterial content is determined by the United States Pharmacopeia (USP) method. <62> It can be measured by methods known to those skilled in the art, such as those described in (Tests for Specified Microorganisms).

[0086] 【0091】In another embodiment, the amount of Staphylococcus aureus bacteria in the first composition is approximately 25 × 10⁶ per gram. 4 Any method disclosed herein is provided, wherein the amount of colony-forming units (CFU / g) is less than or equal to the amount of Staphylococcus aureus bacteria in the first composition is about 5 × 10⁻⁶. 4 Less than CFU / g, or approximately 1 × 10⁻⁶ 4 CFU / g or less, or approximately 5 x 10 3 Less than CFU / g, or approximately 1 × 10⁻⁶ 3Any method disclosed herein is provided, which is less than or equal to CFU / g, 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 embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 1,000 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 750 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 500 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 250 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 200 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 150 CFU / g or less. A method is provided. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 100 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 75 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 50 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 25 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 20 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 10 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a Staphylococcus aureus bacterial content of about 1 CFU / g or less. In another embodiment, any method disclosed herein is provided in which the first composition has a detectable Staphylococcus aureus bacterial content of zero. The Staphylococcus aureus bacterial content of Spongilla material can be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material by heat in the form of steam or dry heat for a time sufficient to reduce the microbial content to a desired level, or chemical treatment in the form of exposure to ethylene oxide gas or treatment with ionizing radiation. The Staphylococcus aureus bacterial content of Spongilla material is determined by the United States Pharmacopeia (USP) method. <62> It can be measured by methods known to those skilled in the art, such as those described in (Tests for Specified Microorganisms).

[0087] 【0092】 In another embodiment, any method disclosed herein is provided in which the first composition is packaged before use. In another embodiment, any method disclosed herein is provided in which the first composition is prepared by heating to at least about 70°C before packaging in order to reduce bioburden. In another embodiment, any method disclosed herein is provided in which 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.

[0088] 【0093】 In another embodiment, any method disclosed herein is provided in which the first composition comprising Spongilla is heated to at least about 70°C for at least about 5 minutes before being packaged. In another embodiment, the first composition is heated 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 before being packaged. A method is provided which involves heating to at least about 70°C, as disclosed herein.

[0089] 【0094】In another embodiment, any method disclosed herein is provided in which a first composition comprising Spongilla is prepared by treating it with ionizing radiation, such as gamma rays, before or after packaging. For example, gamma irradiation may be performed on raw Spongilla material before and after gliding for particle size reduction, on bulk-packaged material, and / or on material after packaging into unit-dose containers. The material may be treated with ionizing radiation, such as gamma rays, using methods and equipment known to those skilled in the art, such as gamma ray irradiation devices or electron beam irradiation devices. In another embodiment, any method disclosed herein is provided in which a first composition is prepared by treating it with ionizing radiation, such as gamma rays, before packaging to deliver an absorbed radiation dose between about 1 kGy and about 50 kGy. In another embodiment, the material is treated with ionizing radiation such as gamma rays, in the range of approximately 1 kGy to approximately 45 kGy, or approximately 1 kGy to approximately 40 kGy, approximately 1 kGy to approximately 35 kGy, approximately 1 kGy to approximately 30 kGy, or approximately 1 kGy to approximately 25 kGy, or approximately 5 kGy to approximately 50 kGy, or approximately 5 kGy to approximately 45 kGy, or approximately 5 kGy to approximately 40 kGy, or approximately 5 kGy to approximately 35 kGy, or approximately 5 kGy to approximately 30 kGy, or approximately 5 kGy to approximately 25 kGy, or approximately 10 kGy to approximately 50 kGy, or approximately 10 kGy to approximately 45 kGy Any method disclosed herein is provided for preparing a first composition by delivering an absorbed radiation dose in the range of Gy, or between approximately 10 kGy and approximately 40 kGy, or between approximately 10 kGy and approximately 35 kGy, or between approximately 10 kGy and approximately 30 kGy, or between approximately 10 kGy and approximately 25 kGy, or between approximately 15 kGy and approximately 50 kGy, or between approximately 15 kGy and approximately 45 kGy, or between approximately 15 kGy and approximately 40 kGy, or between approximately 15 kGy and approximately 35 kGy, or between approximately 15 kGy and approximately 30 kGy, or between approximately 15 kGy and approximately 25 kGy.In another embodiment, the substance is treated with ionizing radiation such as gamma rays to approximately 1 kGy, or approximately 5 kGy, or approximately 10 kGy, 11 kGy, or approximately 12 kGy, or approximately 13 kGy, or approximately 14 kGy, or approximately 15 kGy, or approximately 16 kGy, or approximately 17 kGy, or approximately 18 kGy, or approximately 19 kGy, or approximately 20 kGy, or approximately 21 kGy, or approximately 22 kGy, or approximately 23 kGy, or approximately 24 kGy, or approximately 25 kGy, or approximately 26 kGy, or approximately 27 kGy, or approximately 28 kGy, or approximately 29 kGy, or approximately 30 kGy, or A method is provided herein, any of which involves preparing a first composition by delivering an absorbed radiation dose of approximately 31 kGy, or approximately 32 kGy, or approximately 33 kGy, or approximately 34 kGy, or approximately 35 kGy, or approximately 36 kGy, or approximately 37 kGy, or approximately 38 kGy, or approximately 39 kGy, or approximately 40 kGy, or approximately 41 kGy, or approximately 42 kGy, or approximately 43 kGy, or approximately 44 kGy, or approximately 45 kGy, or approximately 46 kGy, or approximately 47 kGy, or approximately 48 kGy, or approximately 49 kGy, or approximately 50 kGy.

[0090] 【0095】 In another embodiment, any method disclosed herein is provided in which the first composition is applied to the skin of the subject in the form of a plaster. In another embodiment, any method disclosed herein is provided in which the plaster further comprises water or saline solution. In yet another embodiment, any method disclosed herein is provided in which the plaster is prepared by mixing the composition comprising Spongilla with an aqueous solution comprising hydrogen peroxide. In another embodiment, hydrogen peroxide is present in concentrations of approximately 0.1% w / w to approximately 50% w / w, or approximately 0.1% w / w to approximately 45% w / w, or approximately 0.1% w / w to approximately 40% w / w, or approximately 0.1% w / w to approximately 35% w / w, or approximately 0.1% w / w to approximately 30% w / w, or approximately 0.1% w / w to approximately 25% w / w, or approximately 0.1% w / w to approximately 20% w / w, or approximately 0.1% w / w to approximately 15% w / w, or approximately 0.1% w / w to approximately 10% w / w, or approximately 0.1% w / w to approximately 9% w / w, or approximately 0.1% w / w to approximately 8% w / w, or approximately 0.1% w / w to approximately 7% w / w, or approximately 0.1% w / w to approximately 6% w / w, or approximately 0.1% w / w to approximately 5% w / w, or approximately 0.1% w / w to approximately 4% w / w, or approximately 0.1% w / w to approximately 3% w / w, or approximately 0.1% w / w to approximately 2% w / w, or approximately 0.1% w / w to approximately 1% w / w, or approximately 0.5% w / w to approximately 45% w / w, or approximately 1% w / w to approximately 45% w / w, or approximately 1% w / w to approximately 40% w / w, or approximately 1% w / w~approximately 35% w / w, or approximately 1% w / w~approximately 30% w / w, or approximately 1% w / w~approximately 25% w / w, or approximately 1% w / w~approximately 20% w / w, or approximately 1% w / w~approximately 15% w / w, or approximately 1% w / w~approximately 10% w / w, or approximately 1% w / w~approximately 9% w / w, or approximately 1% w / w~approximately 8% w / w, or approximately 1% w / w~approximately 7% w / w, or approximately 1% w / w~approximately 6% w / w, or approximately 1% w / w~approximately 5% w / w, or approximately 1% w / w~approximately 4% w / w, or approximately 1% w / w~approximately 3% w / w, or approximately 1% w / w~approximately 2% w / w, or approximately 2% w / w~approximately 45% w / w, or approximately 2% w / w~approximately 40% w / w, or approximately 2% w / w~approximately 35% w / w, or approximately 2% w / w~approximately 30% w / w, or approximately 2% w / w~approximately 25% w / w, or approximately 2% w / w~approximately 20% w / w, or approximately 2% w / Any method disclosed herein is provided, having concentrations of w to approximately 15% w / w, or approximately 2% w / w to approximately 10% w / w, or approximately 2% w / w to approximately 9% w / w, or approximately 2% w / w to approximately 8% w / w, or approximately 1% w / w to approximately 7% w / w, or approximately 2% w / w to approximately 6% w / w, or approximately 2% w / w to approximately 5% w / w, or approximately 2% w / w to approximately 4% w / w, or approximately 2% w / w to approximately 3% w / w. In another embodiment, any method disclosed herein is provided in which hydrogen peroxide is present at a concentration of about 0.1% w / w, or about 0.5% 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.In another embodiment, any of the methods disclosed herein is provided, wherein the hydrogen peroxide is present at a concentration of about 3% w / w. Aqueous solutions of hydrogen peroxide that may be useful in treating skin conditions in subjects as disclosed herein are commercially available or can be prepared by methods known to those skilled in the art.

[0091] 【0096】 In another embodiment, any method disclosed herein is provided in which the first composition and / or the second composition may be used in combination with a gel or cream that may or may not further contain hydrogen peroxide. In another embodiment, any method disclosed herein is provided in which the first composition and / or the second composition may be used in combination with a gel or cream that may not further contain hydrogen peroxide. In another embodiment, any method disclosed herein is provided in which the first composition and / or the second composition may be used in combination with a gel or cream that may further contain hydrogen peroxide. Such gels or creams are generally available commercially and may contain about 0.5% w / w to about 50% w / w of 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, may be used in combination with the first and second compositions in any of the methods disclosed herein.

[0092] 【0097】In another embodiment, any method disclosed herein is provided, further comprising the step of applying the third composition to the skin of interest. In another embodiment, any method disclosed herein is provided, wherein the third composition comprises hydrogen peroxide. In another embodiment, any method disclosed herein is provided, wherein the hydrogen peroxide is at a concentration of about 3% w / w. In another embodiment, the hydrogen peroxide is at a concentration of about 0.1% w / w to about 50% w / w, or about 0.1% w / w. / w~approximately 45% w / w, or approximately 0.1% w / w~approximately 40% w / w, or approximately 0.1% w / w~approximately 35% w / w, or approximately 0.1% w / w~approximately 30% w / w, or approximately 0.1% w / w~approximately 25% w / w, or approximately 0.1% w / w~approximately 20% w / w, or approximately 0.1% w / w~approximately 15% w / w, or approximately 0.1% w / w~approximately 10% w / w, or approximately 0.1% w / w~approximately 9% w / w, or approximately 0.1% w / w~approximately 8% w / w, or approximately 0.1% w / w~approximately 7% w / w, or approximately 0.1% w / w~approximately 6% w / w, also This ranges from approximately 0.1% w / w to approximately 5% w / w, or approximately 0.1% w / w to approximately 4% w / w, or approximately 0.1% w / w to approximately 3% w / w, or approximately 0.1% w / w to approximately 2% w / w, or approximately 0.1% w / w to approximately 1% w / w, or approximately 0.5% w / w to approximately 45% w / w, or approximately 1% w / w to approximately 45% w / w, or approximately 1% w / w to approximately 40% w / w, or approximately 1% w / w to approximately 35% w / w, or approximately 1% w / w to approximately 30% w / w, or approximately 1% w / w to approximately 25% w / w, or approximately 1% w / w to approximately 20% w / w, or approximately 1% w / w ~15% w / w, or approximately 1% w / w to approximately 10% w / w, or approximately 1% w / w to approximately 9% w / w, or approximately 1% w / w to approximately 8% w / w, or approximately 1% w / w to approximately 7% w / w, or approximately 1% w / w to approximately 6% w / w, or approximately 1% w / w to approximately 5% w / w, or approximately 1% w / w to approximately 4% w / w, or approximately 1% w / w to approximately 3% w / w, or approximately 1% w / w to approximately 2% w / w, or approximately 2% w / w to approximately 45% w / w, or approximately 2% w / w to approximately 40% w / w, or approximately 2% w / w to approximately 35% w / w, or approximately 2% w / w to approximately 3% Any method disclosed herein is provided, having a w / w concentration of 0% 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 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 embodiment, any method disclosed herein is provided in which hydrogen peroxide is present at a concentration of about 0.1% w / w, or about 0.5% 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. In another embodiment, any method disclosed herein is provided in which hydrogen peroxide is present at a concentration of about 3% w / w. Aqueous solutions of hydrogen peroxide that may be useful in treating skin conditions in subjects as disclosed herein are commercially available or can be prepared by methods known to those skilled in the art.

[0093] 【0098】 In another embodiment, any method disclosed herein is provided in which Spongilla is Spongilla lacustris. 【0099】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) attached protein receptors). It is known to those skilled in the art that botulinum toxin targets one or more of three SNARE (soluble NSF attached protein receptor) proteins: VAMP (vesicle-binding membrane protein also known as synaptobrevin), SNAP-25 (synaptosome-associated protein 25), and syntaxin (STX). BoNT / B cleaves the Q76 (P1 site)-F77 (P1' site) peptide bond (hereinafter numbered in humans) of VAMP-2, 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, BoNT / X cleaves R66-A67. BoNT / A cleaves the Q197-R198 bond at the C-terminus of SNAP-25, while BoNT / E hydrolyzes the R180-I181 peptide bond. BoNT / C cleaves SNAP-25 (R STX-1A is cleaved (in 198-A199), STX-1A (in K253-A254), and STX-1B (in K252-A253). The presence of BoNT / A in vivo can be revealed by measuring the presence of SNAP25 cleavage products using, for example, an appropriate assay, e.g., an ELISA assay utilizing one or more monoclonal antibodies. The presence of onabotulinum toxin A in vivo can be revealed using, for example, one or more mAbs, e.g., anti-SNAP-25 monoclonal antibody 4F3-2C1 (available from MyBioSource, Inc., San Diego, California, USA) and / or anti-SNAP-25 biotin-labeled antibody MBS423684 (available from MyBioSource, Inc., San Diego, California, USA).

[0094] 【0100】In another embodiment, a second composition comprising one or more botulinum toxins is used as the target. A method of topical application to the skin is provided as disclosed herein. In another embodiment, a method of application of the second composition to the skin in question is provided as disclosed herein. In yet another embodiment, a method of application of the second composition to the skin in question as an aqueous solution is provided as disclosed herein. A solution of botulinum toxin, including an aqueous solution, can be prepared by methods known to those skilled in the art. For example, botulinum toxin products may be available in the form of vacuum-dried or lyophilized solids packaged in vials containing suitable excipients such as human albumin, sodium chloride, sucrose, and sodium succinate. The vacuum-dried or lyophilized material may also be prepared for use according to the method disclosed herein by reconstitution, which involves slowly injecting a suitable diluent, such as preservative-free 0.9% sodium chloride injection USP, into a vial and rotating the vial to mix the diluent and the vacuum-dried material. Alternatively, a first fixed volume of a suitable diluent, such as preservative-free 0.9% sodium chloride injection USP, may be injected into a container containing the vacuum-dried material and mixed to form the first solution. A second fixed volume of a suitable diluent, such as preservative-free 0.9% sodium chloride injection USP, may be withdrawn into a syringe, followed by the withdrawal of a given amount of the reconstituted toxin solution. Subsequently, the two fixed volumes in the syringe may be mixed to obtain a solution with the desired concentration of toxin. In general, the date and time of reconstitution should be recorded, and the reconstituted material should generally be used within 24 hours of reconstitution. Any reconstituted material should be stored under appropriate conditions, such as at a temperature of approximately 2°C to 8°C, both after reconstitution and before use. In general, the reconstituted material should be clear, colorless, and free or granular before use. Alternatively, the toxin product may be available as a pre-produced solution of a given concentration. The toxin solution can be applied topically to the target skin by withdrawing an appropriate amount of the reconstituted solution from a vial or other container using a syringe, and then applying the reconstituted solution to the target skin using an appropriate method such as a cotton swab or brush.

[0095] 【0101】 In another embodiment, the second composition comprises botulinum toxin type A, botulinum toxin type B, A method disclosed herein is provided, comprising one or more botulinum toxin types selected from C1 botulinum toxin, C2 botulinum toxin, D botulinum toxin, E botulinum toxin, F botulinum toxin, and G botulinum toxin. In another embodiment, a method disclosed herein is provided, wherein one or more botulinum toxin types are selected from A botulinum toxin and B botulinum toxin. In another embodiment, a method disclosed herein is provided, wherein one or more botulinum toxin types is A botulinum toxin. In another embodiment, a method disclosed herein is provided, wherein A botulinum toxin is selected from onabotulinum toxin A, avobotulinum toxin A, and incobotulinum toxin A. In another embodiment, a method disclosed herein is provided, wherein A botulinum toxin is onabotulinum toxin A. In another embodiment, botulinum toxin type A is abobotulinum toxin A, as disclosed herein. A method is provided. In another embodiment, any method disclosed herein is provided in which type A botulinum toxin is parcobotulinum toxin A. In another embodiment, any method disclosed herein is provided in which type A botulinum toxin is plabotulinum toxin A. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type B botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type B botulinum toxins are limabotulinum toxin B. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type C1 botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type C2 botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type D botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type E botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more type E botulinum toxins are EB-001A or EB-001T. In another embodiment, any method disclosed herein is provided in which one or more type E botulinum toxins are EB-001A. In another embodiment, any method disclosed herein is provided in which one or more type E botulinum toxins are EB-001T. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type F botulinum toxin. In another embodiment, any method disclosed herein is provided in which one or more botulinum toxin types are type G botulinum toxin.

[0096] 【0102】 In another embodiment, the method includes one or more botulinum toxins applied to the skin in question. A method is provided herein, wherein the number of effective units of the second composition is about 1 to about 400 effective units. In another embodiment, the number of potency units of a second composition containing one or more botulinum toxins applied to the target skin is approximately 10 to approximately 400 units, or approximately 10 to approximately 375 units, or approximately 10 to approximately 350 units, or approximately 10 to approximately 325 units, or approximately 10 to approximately 300 units, or approximately 10 to approximately 275 units, or approximately 10 to approximately 250 units, or approximately 10 to approximately 225 units, or approximately 10 to approximately 200 units, or approximately 10 to approximately 175 units, or approximately 10 to approximately 150 units, or approximately 10 to approximately 125 units, or approximately 10 to approximately 100 units, or approximately 10 to approximately 75 units, or approximately 10 to approximately 50 units, or approximately 10 to approximately 40 units, or approximately 10 to approximately 35 units, or approximately 10 to approximately 30 units, or approximately 10 Any method disclosed herein is provided, where the units are approximately 25 units, or approximately 5 to 75 units, or approximately 5 to 50 units, or approximately 5 to 45 units, or approximately 5 to 40 units, or approximately 5 to 35 units, or approximately 5 to 30 units, or approximately 5 to 25 units, or approximately 5 to 20 units, or approximately 5 to 15 units, or approximately 5 to 10 units, or approximately 15 to 100 units, or approximately 20 to 100 units, or approximately 25 to 100 units, or approximately 35 to 100 units, or approximately 40 to 100 units, or approximately 50 to 100 units, or approximately 60 to 100 units, or approximately 70 to 100 units, or approximately 80 to 100 units, or approximately 90 to 100 units.In another embodiment, 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 target skin 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. At least one botulinum toxin that can be used according to the method and kit disclosed herein. The number of potency units of a composition containing botulinum toxin can be determined by those skilled in the art. The potency of individual botulinum toxin compositions can be determined by methods known to those skilled in the art, such as appropriate cell-based assays (see, for example, Fernandez-Salas et al., PLOS ONE, Vol. 7, e49516 (2012)), and mouse LD 50 (mLD 50 ) may be determined by the use of bioassays, including focal muscle paralysis (abdominal apoptosis) (see, e.g., Sesardic et al., Pharmacol. Toxicol., Vol. 78, pp. 283-288 (1996)), finger abduction score assay (see, e.g., Aoki et al., Toxicon., Vol. 39, pp. 1815-1820 (2001)), rat or mouse phrenic nerve diaphragm (see, e.g., Goschel et al., Exp Neurol., Vol. 147, pp. 96-102 (1997)), rat intercostal striae assay (see, e.g., Huber et al., Altern Lab Anim., Vol. 36, pp. 141-152 (2008) and Rasetti-Escargucil et al., Toxicon., Vol. 53, pp. 503-511 (2009)).

[0097] 【0103】 In another embodiment, a first composition comprising Spongilla applied to the skin in question. A method is provided disclosed herein in which the amount of the substance is about 0.5 grams to about 50 grams. In one embodiment, a method is provided disclosed herein in which the amount of the first composition is measured as dry weight. In another embodiment, the amount of the first composition containing Spongilla applied to the skin of the 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. Any method disclosed herein is provided, where the amount is 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, 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 about 2 grams. In another embodiment, any method disclosed herein is provided, where the amount of Spongilla applied to the skin, such as those disclosed above, is measured as dry weight, each.

[0098] 【0104】 In another embodiment, the subject is applied to the skin, measured in each case as dry weight. The amount of the first composition containing Spongilla is approximately 0.5 grams, or approximately 0.75 grams, or approximately 1 gram, or approximately 1.25 grams, or approximately 1.5 grams, or approximately 1.75 grams, or approximately 2 grams, or approximately 2.25 grams, or approximately 2.5 grams, or approximately 2.75 grams, or approximately 3 grams, or approximately 3.25 grams, or approximately 3.5 grams, or approximately 3.75 grams, or approximately 4 grams, or approximately 4.25 grams, or approximately 4.5 grams, or approximately 4.75 grams, or approximately 5 grams, or approximately 5.25 grams, or approximately 5.5 grams, or approximately 5.75 grams, or approximately 6 grams, or approximately 6.25 grams, or approximately 6.5 grams, or approximately 7 grams, or approximately 7.25 grams, or approximately 7.5 grams, or approximately 7.75 grams. Alternatively, any of the methods disclosed herein is provided, which are approximately 8 grams, or approximately 8.25 grams, or approximately 8.5 grams, or approximately 8.75 grams, or approximately 9 grams, or approximately 9.25 grams, or approximately 9.5 grams, or approximately 9.75 grams, or approximately 10 grams, or approximately 11 grams, or approximately 12 grams, or approximately 13 grams, or approximately 14 grams, or approximately 15 grams, or approximately 16 grams, or approximately 17 grams, or approximately 18 grams, or approximately 19 grams, or approximately 20 grams, or approximately 25 grams, or approximately 35 grams, or approximately 40 grams, or approximately 45 grams, or approximately 50 grams, or approximately 75 grams, or approximately 100 grams, or approximately 250 grams, or approximately 500 grams, or approximately 750 grams, or approximately 1000 grams.

[0099] 【0105】 In another embodiment, the first composition is applied to the skin before the second composition is applied to the skin in question. A method of applying to the target skin is provided as disclosed herein. In another embodiment, a method of applying to the target skin is provided as disclosed herein, wherein the first composition is applied to the target skin and dried on the target skin before the second composition is applied to the target skin. In another embodiment, a method of applying to the target skin is provided as disclosed herein, wherein the first composition is applied to the target skin in the form of an aqueous plaster, and the aqueous component may be water or saline. In another embodiment, a method of applying to the target skin is provided as disclosed herein, wherein the aqueous plaster further comprises hydrogen peroxide. In another embodiment, a method of applying to the target face is provided as disclosed herein, after the first composition has been applied to the target skin and before the second composition is applied to the target skin. In another embodiment, a method of applying to the target skin is provided as disclosed herein, wherein the first composition further comprises hydrogen peroxide. In another embodiment, a method of applying to the target face is provided as disclosed herein, wherein the hydrogen peroxide is an aqueous solution. In another embodiment, a method of applying to the target face is provided as disclosed herein, wherein the aqueous solution contains hydrogen peroxide at a concentration of about 3% w / w. In another embodiment, any method disclosed herein is provided in which the second composition is applied to the skin in question and then dried on the skin in question.

[0100] 【0106】 In another embodiment, before the first composition is applied to the skin in question, the second composition is A method of application to the target skin is provided as disclosed herein. In another embodiment, a method of application to the target skin is provided as disclosed herein, wherein the second composition is dried on the target skin before the first composition is applied to the target skin. In another embodiment, a method of application to the target skin is provided as disclosed herein, wherein the first composition is applied to the target skin in the form of an aqueous paste, and the aqueous portion may be derived from water or saline. In another embodiment, a method of application to the target skin is provided as disclosed herein, wherein the aqueous paste further comprises hydrogen peroxide. In another embodiment, a method of application to the target face is provided as disclosed herein, after the first composition has been applied to the target skin. In another embodiment, a method of application to the target face is provided as disclosed herein, wherein the hydrogen peroxide is an aqueous solution. In another embodiment, a method of application to the target face is provided as disclosed herein, wherein the aqueous solution comprises hydrogen peroxide at a concentration of about 3% w / w. In another embodiment, a method of application to the target skin is provided as disclosed herein, wherein the first composition is dried on the target skin.

[0101] 【0107】 In another embodiment, the first composition and the second composition are mixed together to obtain a mixture One of the methods disclosed herein is provided for applying the composition to the skin of the subject. In another embodiment, one of the methods disclosed herein is provided in which the first composition is mixed with an aqueous solution of hydrogen peroxide before mixing with the second composition. In another embodiment, one of the methods disclosed herein is provided in which a mixture of the first and second compositions is further mixed with an aqueous solution of hydrogen peroxide before application to the skin of the subject. In another embodiment, one of the methods disclosed herein is provided in which the aqueous solution contains hydrogen peroxide at a concentration of about 3% w / w. In another embodiment, one of the methods disclosed herein is provided in which the first composition containing Spongilla and the second composition containing one or more botulinum toxins are applied to the skin of the subject once a week.

[0102] 【0108】 In another embodiment, the subject is a second composition comprising one or more botulinum toxins. A method is provided which involves applying the substance to the skin no more than once every four weeks, as disclosed herein.

[0103] 【0109】 In another embodiment, the first composition containing Spongilla lasts for at least one week A method is provided which involves applying the product to the skin in question at least once a week over a period of time. In another embodiment, the first composition comprising Spongilla is applied at least twice a week over a period of time the time of time of the time of time of the time of time of the time of time of the time of time of the time of time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of the time of A method is provided which involves applying the product to the skin in question three times a week, at least four times a week over at least one week, at least five times a week over at least one week, at least six times a week over at least one week, or at least seven times a week over at least one week, as disclosed herein.

[0104] 【0110】 In another embodiment, the first composition containing Spongilla lasts for at least two weeks. A method is provided which involves applying the first composition containing Spongilla to the skin at least once a week over a period of at least two weeks, at least once a week over a period of at least three weeks, at least once a week over a period of at least four weeks, at least once a week over a period of at least five weeks, at least once a week over a period of at least six weeks, at least once a week over a period of at least seven weeks, at least once a week over a period of at least eight weeks, at least once a week over a period of at least nine weeks, at least once a week over a period of at least ten weeks, at least once a week over a period of at least eleven weeks, at least once a week over a period of at least twelve weeks, and at least once a week over a period of at least thirteen weeks. A method is provided which involves applying the product to the skin in question once, at least once a week for at least 14 weeks, at least once a week for at least 15 weeks, at least once a week for at least 16 weeks, at least once a week for at least 17 weeks, at least once a week for at least 18 weeks, at least once a week for at least 19 weeks, at least once a week for at least 20 weeks, at least once a week for at least 21 weeks, at least once a week for at least 22 weeks, at least once a week for at least 23 weeks, and at least once a week for at least 24 weeks. In another embodiment, a method is provided which involves applying a first composition comprising Spongilla to the skin in question once a week for 6 weeks.

[0105] 【0111】 In another embodiment, a first composition containing Spongilla is used over a period of 24 weeks. A method is provided herein in which a second composition containing one or more botulinum toxins is applied to the target skin once a week, and is applied to the target skin only during the first week of treatment. In another embodiment, a method is provided herein in which a first composition containing Spongilla is applied to the target skin once a week for 20 weeks, and a second composition containing one or more botulinum toxins is applied to the target skin only during the first week of treatment. In another embodiment, a method is provided herein in which a first composition containing Spongilla is applied to the target skin once a week for 16 weeks, and a second composition containing one or more botulinum toxins is applied to the target skin only during the first week of treatment. In another embodiment, a method is provided herein in which a first composition containing Spongilla is applied to the target skin once a week for 12 weeks, and a second composition containing one or more botulinum toxins is applied to the target skin only during the first week of treatment. In another embodiment, any method disclosed herein is provided, wherein a first composition containing Spongilla is applied to the target skin once a week for eight weeks, and a second composition containing one or more botulinum toxins is applied to the target skin only during the first week of treatment. In another embodiment, any method disclosed herein is provided, wherein a first composition containing Spongilla is applied to the target skin once a week for six weeks, and a second composition containing one or more botulinum toxins is applied to the target skin only during the first week of treatment. In yet another embodiment, any method disclosed herein is provided, wherein a first composition containing Spongilla is applied to the target skin once a week for four weeks, and a second composition containing one or more botulinum toxins is applied to the target skin only during the first week of treatment.

[0106] 【0112】 In another embodiment, a first composition comprising Spongilla and one or more A method is provided herein in which a second composition comprising botulinum toxin is applied to the skin of a subject on at least one of the subject's face, back, and chest. In another embodiment, a method is provided herein in which 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 subject's face. In another embodiment, a method is provided herein in which 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 subject's back. In another embodiment, a method is provided herein in which 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 subject's chest.

[0107] 【0113】 In another embodiment, after applying the first composition containing Spongilla, the skin of the subject A method is provided herein in which the skin is cleansed using a non-comedone-forming cleanser, water, or a combination of a non-comedone-forming cleanser and water. In another embodiment, a method is provided herein in which the skin is cleansed using a non-comedone-forming cleanser, water, or a combination of a non-comedone-forming cleanser and water after applying a second composition comprising one or more botulinum toxins to the skin in question. The non-comedone-forming cleanser is formulated so as not to clog pores in the skin to which such a cleanser is applied.

[0108] 【0114】 In another embodiment, the skin condition of the subject is acne vulgaris, type 1 rosacea, type 2 A method is provided which is selected from rosacea, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplakia, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, a method is provided which is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, and hyperhidrosis in the subject. In yet another embodiment, a method is provided which is selected from acne vulgaris, type 1 rosacea, type 2 rosacea, psoriasis, and hyperhidrosis in the subject. In another embodiment, any of the methods disclosed herein is provided, wherein the skin condition of the subject is type 1 rosacea acne. In another embodiment, any of the methods disclosed herein is provided, wherein the skin condition of the subject is type 2 rosacea acne. In another embodiment, any of the methods disclosed herein is provided, wherein the skin condition of the subject is psoriasis. In another embodiment, any of the methods disclosed herein is provided, wherein the skin condition of the subject is hyperhidrosis.

[0109] 【0115】 Acne vulgaris is caused by the obstruction of the hair follicle sebaceous gland unit (hair follicle and its associated sebaceous gland) and Acne is a common chronic skin disease involving eczema and / or inflammation. Acne is most common on the face, but can also affect the back and chest, and may exist as non-inflammatory lesions, inflammatory lesions, or a combination of both. The effectiveness of a treatment regimen in a subject with acne vulgaris can be measured by methods known to those skilled in the art, such as measurement of the number of lesions and a physician's comprehensive assessment of the subject's face, as described below.

[0110] [Table 1]

[0111] 【0116】 Rosacea is a chronic skin condition that primarily affects the convex areas of the central face (cheeks, chin, nose, and forehead). It is clearly distinguishable as a skin disorder and is often characterized by remission and relapse. Based on current knowledge, rosacea is considered a syndrome or type 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. Acne rosacea type 1, or erythematous telangiectasia, is primarily characterized by flushing and persistent erythema in the center of the face. The appearance of telangiectasia is common but not essential for the diagnosis of this subtype. Edema in the center of the face, tingling and burning sensations, as well as roughness or scalyness, may also be reported. Among subjects presenting with erythematous telangiectasia, a history of flushing alone is common. The effectiveness of treatment regimens in subjects with type 1 rosacea acne can be measured by methods known to those skilled in the art, such as the Clinician Erythema Assessment (CEA), a five-level grading scale for facial erythema severity, and the Subject Self-Assessment (SSA), as described below.

[0112] 【0117】

[0113] [Table 2]

[0114] 【0118】

[0115] [Table 3]

[0116] 【0119】 Type 2 rosacea (papulopustular) is characterized by transient papules distributed in the center of the face or It is characterized by persistent erythema in the center of the face, accompanied by pustules or both. However, papules and pustules may also occur around orifices (i.e., around the mouth, nose, or eyes). The papular-pustular subtype resembles acne vulgaris, except that comedones are absent. Rosacea and acne may occur simultaneously, and such individuals may have comedones in addition to the papules and pustules of rosacea. Burning and tingling sensations may also be reported by individuals with papular-pustular rosacea. This subtype is often observed after or in combination with subtype 1, which includes the presence of telangiectasias. Telangiectasias can be obscured by persistent erythema, papules, or pustules, and tend to become more visible after these concealing components have been successfully treated. The effectiveness of a treatment regimen in subjects with type 2 rosacea acne can be measured by methods known to those skilled in the art, such as the total number of lesions in the skin area of ​​the subject receiving treatment, and by a comprehensive physician assessment as described below.

[0117] 【0120】

[0118] [Table 4]

[0119] 【0121】 Psoriasis is a skin condition in which the life cycle of skin cells is accelerated. It rapidly accumulates on the surface of the skin. The excess skin cells form itchy, sometimes painful, scaly, and red patches. Symptoms that a person with psoriasis may exhibit include red patches of skin covered with thick, silvery-white scales, scaly patches (common in children), dry and cracked skin that may bleed, itch, burn, or sting, thickened, indented, or wavy nails, and swollen and stiff joints. The effectiveness of a treatment regimen in a person with psoriasis can be measured by methods known to those skilled in the art, for example, by using the Psoriasis Area and Severity Index (PASI). The use of PASI involves dividing the subject's body into four sections: head (H) (10% of human skin), arms (A) (20%), trunk (T) (30%), and legs (L) (40%). Each of these areas is scored in itself, and then the four scores are combined to arrive at the final PASI. For each section, the percentage of the skin area of ​​the lesion is estimated and then converted to a grade of 0-6 as shown in the table below. Within each area, the severity is estimated by three clinical signs: erythema (redness), induration (thickness), and desquamation (scaling). Severity parameters are measured on a scale of 0-4 from zero to the maximum. Then, the sum of all these severity parameters is calculated for each skin section, multiplied by the area score for that section, and then multiplied by the weight of each section (0.1 for the head, 0.2 for the arms, 0.3 for the torso, and 0.4 for the legs).

[0120] 【0122】

[0121] [Table 5]

[0122] 【0123】 Hyperhidrosis is generally an abnormal increase in sweating that exceeds the amount necessary for regulating body temperature. This condition is characterized by excessive sweating. While hyperhidrosis is primarily a physical burden, it can also reduce the quality of life from psychological, emotional, and social perspectives. The effectiveness of treatment regimens in subjects with hyperhidrosis can be measured by methods known to those skilled in the art, for example, by using the Hyperhidrosis Severity Scale (HDSS), a four-point scale designed to assess the severity of primary axillary hyperhidrosis in routine clinical practice or clinical research. The HDSS may be administered by an interviewer or self-completed by the subject. The HDSS assesses the severity of a subject based on the degree of impairment of daily activities associated with excessive sweating. Subjects grade their severity as follows: 1 = I don't mind underarm sweating at all, and it doesn't interfere with my daily activities at all; 2 = I can tolerate underarm sweating, but it occasionally interferes with my daily activities; 3 = I can hardly tolerate underarm sweating, and it frequently interferes with my daily activities; or 4 = I cannot tolerate underarm sweating, and it constantly interferes with my daily activities.

[0123] 【0124】 The effectiveness of treatment regimens in subjects with hyperhidrosis depends on the severity of axillary hyperhidrosis. Effective patient-reported outcome measures for evaluating this may be the use of the Axillary Sweating Daily Diary (ASDD) Item 2 and / or the Axillary Sweating Daily Diary-Children (ASDD-C). ADSS Item 2 asks subjects to rate their worst axillary sweating in the preceding 24 hours, using a 10-point scale where a score of zero (0) corresponds to "no sweating at all" and a score of 10 corresponds to "worst possible sweating." For the content of ASDD and ASDD-C, including Item 2, see Glaser et al., J.Am.Acad.Dermatol., 2018, Supplemental Figure 1.

[0124] 【0125】 Alopecia areata causes hair loss on the scalp, face, and sometimes other areas of the body. It is an autoimmune skin disease. In fact, as many as 6.8 million people in the United States suffer from alopecia areata. The effectiveness of treatment regimens in subjects with alopecia areata is known to those skilled in the art. This can be measured, for example, by using fixed hair counting and non-fixed hair counting on the pillow in question.

[0125] 【0126】 Male pattern baldness is a condition in which terminal hairs gradually transform into intermediate hairs, and eventually into vellus hairs. It is a genetically determined disorder characterized by the following: Androgenetic alopecia is a very common disease affecting both men and women. Individuals with androgenetic alopecia generally exhibit symptoms such as a gradual onset of hair loss, increased shedding, and a progression of affected areas from abundant, thick, pigmented terminal hairs to thinner, shorter intermediate hairs, and finally to short, weak, unpigmented vellus hairs, which may result in complete baldness, but the extent of the affected area varies from person to person and is usually most pronounced on the crown of the head. The effectiveness of treatment regimens in individuals with androgenetic alopecia can be measured by methods known to those skilled in the art, for example, by using fixed hair counting and non-fixed hair counting on the subject's pillow.

[0126] 【0127】 A keloid is a raised, reddish nodule that forms on the site of an injury. After a wound occurs, both skin cells and connective tissue cells (fibroblasts) increase to begin repairing the damage. Scars are composed of "connective tissue," which is cartilage-like fibers deposited in the skin by fibroblasts to keep the wound closed. Fibroblasts continue to increase even after the wound has closed, resulting in keloids. Therefore, keloids protrude above the surface of the skin, forming large raised bumps of scar tissue. Keloids can develop on any part of the body, although the upper chest, shoulders, and upper back are particularly prone to keloid formation. Symptoms include skin discoloration, itching, redness, unusual sensations, and pain. People with darker skin tones appear to be more prone to keloid formation. Men and women are equally susceptible. Keloids are considered benign tumors, but are primarily undesirable for cosmetic reasons and never become malignant. Surgery for keloids typically stimulates the formation of more scar tissue, and therefore, many subjects with keloids may be told that there are no available treatments. Hypertrophic scars generally do not grow as large as keloids, may disappear over time, occur in all racial groups, but appear like keloids and are more common. The effectiveness of treatment regimens in subjects with keloids and / or hypertrophic scars is assessed by methods known to those skilled in the art, for example, using the Vancouver Scar Scale (VSS), Manchester Scar Scale (MSS), and Subject and Observer Scar Assessment Scales. It can be measured using the Scar Assessment Scale (POSAS), Visual Analog Scale (VAS), and Stony Brook Scar Evaluation Scale (SBSES).

[0127] 【0128】 Hidradenitis suppurativa is a disease that usually begins as acne-like bumps on the skin. Acne tends to occur in areas where nodules do not appear, most commonly in the armpits and groin. If hidradenitis suppurativa worsens, the acne-like bumps may grow deeper into the skin, become painful, and may even rupture. When deep bumps heal, scarring may occur, and in some individuals, a tunnel-like pathway for scar formation may develop beneath the skin, which may become thicker. Thick scarring in the armpits may make it difficult to move the arm. Thick scarring in the groin area may make walking difficult. The effectiveness of a treatment regimen in individuals suffering from hidradenitis suppurativa can be measured by methods known to those skilled in the art, for example, by visually counting the number of lesions in the affected area of ​​the skin of the individual.

[0128] 【0129】 Raynaud's phenomenon is most commonly observed after exposure to cold, where the skin changes from pale to blue and then to red. Raynaud's phenomenon is a type of vascular disease characterized by discoloration of the fingers. The cause of Raynaud's phenomenon is unknown, although it is suspected to involve abnormal nerve control of vascular diameter and abnormal nerve sensitivity to cold. The symptoms of Raynaud's phenomenon vary depending on the severity, frequency, and duration of vasospasm. The effectiveness of a treatment regimen in a patient suffering from Raynaud's phenomenon can be measured by methods known to those skilled in the art, such as measuring fingertip temperature, photographic evaluation of the affected area, and a visual analog scale for pain in the affected area.

[0129] 【0130】 Postherpetic neuralgia is generally caused by the varicella (herpes zoster) virus. It is considered a complication of herpes zoster. Postherpetic neuralgia affects nerve fibers and skin, causing a burning pain that persists long after the herpes zoster rash and blisters have disappeared. The signs and symptoms of postherpetic neuralgia are generally limited to the area of ​​the subject's skin where the herpes zoster outbreak first occurred. The signs and symptoms of postherpetic neuralgia may include pain lasting three months or longer after the herpes zoster rash has healed, sensitivity to light touch, and itching and numbness in the affected area. The effectiveness of a treatment regimen in a subject suffering from postherpetic neuralgia can be measured by a method known to those skilled in the art, namely, the use of a visual analog scale for pain in the affected area.

[0130] 【0131】 Hailey-Hailey disease (familial benign pemphigus) is a genetic condition that causes the formation of blisters on the skin. Hailey-Hailey disease is a sexual disorder characterized by a surge in skin lesions and blisters, usually in the folds of skin but often over a wide area of ​​the body. Painful blisters rupture, sometimes become infected, and become raw, with new blisters forming on the raw skin in what sometimes seems like an endless cycle of surges. The cause of the disease is haploinsufficiency of the ATP2C1 enzyme that codes for the hSPCA1 protein. A mutation in one copy of the gene results in only half of this necessary protein being produced, causing skin cells to fail to properly adhere to each other due to abnormal formation of intercellular adhesion plaques, leading to acantholysis, blistering, and skin lesions. The effectiveness of treatment regimens in subjects with Hailey-Hailey disease can be measured by methods known to those skilled in the art, for example, by counting the total number of lesions in the subjects, and a reduction in the total number of lesions indicates that the treatment regimen has a positive effect.

[0131] 【0132】 Linear IgA bullous dermatosis (LABD) is characterized by the stratum lucidum and stratum compacta. LABD is a rare subepidermal blistering disorder caused by an autoimmune reaction against basement membrane proteins such as IgA densa. The basement membrane anchors the epidermis to the dermis and promotes skin stabilization. When IgA antibodies target these proteins, the basement membrane becomes unstable, resulting in the formation of firm blisters. In most cases of LABD, the cause is unknown or idiopathic. Furthermore, more than half of all childhood cases tend to remit within an average of 2 to 4 years. In adults, the course can be longer, and LABD has been shown to occur in individuals with underlying malignancies, infections, and other autoimmune diseases such as rheumatoid arthritis and dermatomyositis. Other cases of LABD are drug-induced, often due to vancomycin, and in some cases, the subject may develop a rash shortly after the first dose of vancomycin. The effectiveness of a treatment regimen in subjects suffering from LABD can be measured by methods known to those skilled in the art, for example, by counting the total number of lesions in the subjects, and a reduction in the total number of lesions indicates that the treatment regimen has a positive effect.

[0132] 【0133】 Epidermolysis bullosa (EBS) is a condition that presents with odor on the hands, elbows, or knees from birth through childhood. EBS is a chronic vesicular disorder characterized by the formation of intraepidermal vesicles and milia with minimal trauma. EBS is a genetic disorder caused by dominant-negative mutations in either the keratin 5 (KRT5) or keratin 14 (KRT14) gene. Based on its clinical manifestations, EBS is subdivided into systemic (Koebner), localized (Weber-Cockayne), and herpetiform (Dowling-Meara) type 1. Localized EBS is the mildest subtype, characterized by the easy formation of vesicles on the palms and soles of the feet with minimal mechanical trauma. Molecular genetic studies of EBS suggest that mutations in KRT5 and KRT14, which contribute to the hemiadhesive plaque structure in keratinocytes located in the basal layer near the dermal-epidermal junction, are present. Mutations in each subtype of EBS vary in location and severity.2,3 The effectiveness of a treatment regimen in subjects affected by EBS can be measured by methods known to those skilled in the art, for example, by counting the total number of lesions in the subjects, and a reduction in the total number of lesions indicates that the treatment regimen has a positive effect.

[0133] 【0134】 Darier's disease is a skin condition characterized by wart-like spots on the body. The spots are yellow. The spots are typically polished in color, hard to the touch, slightly greasy, and may emit a strong odor. The most common sites of the spots are the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ears. Mucous membranes can also be affected, with spots appearing on the roof of the mouth (palate), tongue, inside of the cheeks, gums, and throat. Other features of Darier's disease include nail abnormalities, such as red and white streaks on bumpy nails, as well as small holes on the palms of the hands and soles of the feet. The characteristic wart-like spots of Darier's disease usually appear in late childhood or early adulthood. The severity of the disease varies over time, with patients experiencing sudden relapses alternating with periods of only a few spots. The appearance of the spots is influenced by environmental factors. Most people with Darier's disease develop more spots during the summer months when they are exposed to heat and humidity. UV light, minor injuries or friction such as abrasions or scratches, and the ingestion of certain drugs can also cause an increase in spots. The effectiveness of a treatment regimen in subjects with Darier's disease can be measured by methods known to those skilled in the art, such as counting the total number of lesions and measuring the size of the lesions in the subject, and a reduction in the total number of lesions indicates that the treatment regimen has a positive effect.

[0134] 【0135】 Congenital onychoplasty is a condition that primarily affects the nails and skin. The signs and symptoms of this condition usually become apparent within the first few months of the subject's life. Almost all individuals with congenital onychomycosis have hypertrophic onychomycosis, in which the fingernails and toenails are thickened and abnormally shaped. Many pediatric patients also develop very painful blisters and calluses on the soles of their feet, and less often on their palms. This condition is known as palmoplantar keratosis. Severe blisters and calluses on the feet can make walking painful or difficult. Congenital onychomycosis may have several additional features that vary among affected individuals. These features include thickened white patches on the tongue and inside of the cheeks (oral leukokeratosis); follicular keratosis, which are bumps that occur around hair follicles on the elbows, knees, and torso; cysts on the axillae, groin, back, or scalp; and excessive sweating on the palms and soles of the feet (palmoplantar hyperhidrosis). Some affected individuals also develop extensive cysts called sebaceous cysts, which are typically filled with an oily substance called sebum that smooths the skin and hair. Some infants with congenital onychomycosis have prenatal teeth or natal teeth, which are teeth present at birth or in early childhood. Rarely, congenital onychomycosis can affect the larynx, potentially leading to hoarseness or breathing problems. The effectiveness of a treatment regimen in subjects with congenital onychomycosis can be measured by methods known to those skilled in the art, such as counting the total number of blisters on the affected area of ​​the subject and measuring the size of the blisters.

[0135] 【0136】Aquatic keratoderma (AK), also known as acquired aquagenic palmoplantar keratoderma, transient reactive papulotranslucent acrokeratoderma, aquagenic wrinkling of the palms, or aquagenic syringeal acrokeratoderma, is a skin disorder. The main features of this disorder are edema of the palms / plantars, whitish papules, itchiness, burning, and painful wrinkles of the skin following contact with water. Prolonged water exposure and water temperature influence the rate and severity of lesion development. However, the etiology of AK is largely unknown. The effectiveness of treatment regimens in subjects with AK is assessed by counting the total number of lesions in the subjects, visual analog pain scores, and visual It can be measured by methods known to those skilled in the art, such as analog pruritus scores.

[0136] 【0137】 Back paresthesia is a sensory neuropathic syndrome of the mid-back skin, classically described as being located below the unilateral scapula. Back paresthesia is primarily a localized itchy and paresthesia syndrome, sometimes presenting with occasional itching or pain in small compartments of the mid-back, areas of skin that are normally easily accessible. The correlation between localized back paresthesia and corresponding spinal degenerative changes suggests that spinal nerve impingement may be a contributing factor, but also that subjects may have other conditions that predispose them to peripheral neuropathy, such as nerve damage. The effectiveness of treatment regimens in subjects with back paresthesia can be measured by methods known to those skilled in the art, such as counting the total number of lesions, visual analog pain scores, and visual analog pruritus scores.

[0137] 【0138】Dyshidrotic eczema is a skin condition characterized by the appearance of very small, fluid-filled blisters on the palms of the hands, sides of the fingers, and soles of the feet. The blisters that occur in dyshidrosis can cause intense itching and, when dry, can make the skin appear scaly. The blisters typically recur, sometimes before the skin has completely healed from previous blisters. The effectiveness of a treatment regimen in a person suffering from dyshidrotic eczema can be measured by methods known to those skilled in the art, such as observation of the signs and symptoms of the eczema, a visual analog pain score, and a visual analog pruritus score.

[0138] 【0139】 Phenohitrosis is a condition characterized by the secretion of colored sweat, resulting from the deposition of lipofuscin in the sweat glands. Phenohitrosis usually affects the apocrine glands, primarily in the face and armpits. The effectiveness of treatment regimens in subjects suffering from phenohitrosis can be measured by methods known to those skilled in the art, such as observation of sweat signs and odor in the affected subjects.

[0139] 【0140】 Odorosis, also known as axillary osmidrosis, is a condition of abnormal or unpleasant body odor largely determined by apocrine gland secretion, although other sources may play a role. Sweat glands are divided into two types: apocrine and eccrine, and some cross-pollination is observed in certain individuals. The effectiveness of treatment regimens in individuals suffering from odorosis can be measured by methods known to those skilled in the art, such as observation of the odor of sweat in the affected individuals.

[0140] 【0141】 Eccrine nevi are conditions that can be present at birth or at a young age. They are often accompanied by localized hyperhidrosis, but cases without localized hyperhidrosis have also been reported. Eccrine nevi are usually histologically characterized by an increase in the number or size of structurally normal eccrine glands. The effectiveness of treatment regimens in subjects with eccrine nevi can be measured by methods known to those skilled in the art, such as the use of the Hyperhidrosis Severity Scale (HDSS) and the measurement of the number of sweat episodes per month in affected subjects.

[0141] 【0142】 Facial wrinkles are a condition in subjects characterized by moderate to severe glabellar lines associated with corrugator supercilii and / or procerus muscle activity, moderate to severe lateral canthal lines associated with orbicularis oculi muscle activity, and / or moderate to severe forehead lines associated with frontalis muscle activity. The effectiveness of treatment regimens 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).

[0142] 【0143】 Atrophic acne scars can occur in individuals with acne. The effectiveness of treatment regimens in individuals with atrophic acne scars is assessed by self-assessment of clinical acne-related scars. It can be measured by methods known to those skilled in the art, including the (SCARS) and Facial Acne Scar Quality of Life (FASQoL) tools.

[0143] 【0144】In another embodiment, a method for treating a skin condition in a subject, comprising the steps of applying to the skin of a subject a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins, 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, and (b) A method is provided in which the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, hyperhidrosis, alopecia areata, male pattern baldness, keloids and hypertrophic scars, hidradenitis suppurativa, Raynaud's phenomenon, postherpetic neuralgia, Hailey-Hailey disease, IgA bullous dermatosis, Weber-Cockayne type epidermolysis bullosa, Darier's disease, congenital onychoplasty, aquatic keratosis, dorsal paresthesia, dyshidrotic eczema, chromohidrosis and bromhidrosis, eccrine nevi, facial wrinkles, atrophic acne scars, and melanosis. In another embodiment, a method is provided in which one or more botulinum toxin types are selected from botulinum toxin type A and botulinum toxin type B. In yet another embodiment, a method is provided in which one or more botulinum toxin types are botulinum toxin type A. In another embodiment, a method is provided in which the botulinum toxin type A is selected from onabotulinumtoxin A, abobotulinumtoxin A, incobotulinumtoxin A, prabotulinumtoxin A, and daxibotulinumtoxin A. In another embodiment, a method is provided in which the botulinum toxin type A is onabotulinumtoxin A. In another embodiment, a method is provided in which the botulinum toxin type A is abobotulinumtoxin A. In another embodiment, a method is provided in which the botulinum toxin type A is incobotulinumtoxin A. In yet another aspect, any of the methods disclosed herein is provided in which the botulinum toxin type A is prabotulinumtoxin A.In another embodiment, any of the methods disclosed herein is provided, wherein the type A botulinum toxin is daxibotulinum toxin A. In another embodiment, a method is provided, wherein one or more botulinum toxin types are botulinum toxin type B. In another embodiment, any of the methods disclosed herein is provided, wherein one or more type B botulinum toxins are rimabotulinum toxin B. In another embodiment, a method 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 embodiment, any of the methods disclosed herein is provided, wherein one or more botulinum toxin types are botulinum toxin type E. In another embodiment, any of the methods disclosed herein is provided, wherein one or more type E botulinum toxins are EB-001A or EB-001T. In another embodiment, any of the methods disclosed herein is provided, wherein one or more type E botulinum toxins are EB-001A. In another embodiment, any of the methods disclosed herein is provided, wherein one or more type E botulinum toxins are EB-001T. In another embodiment, a method is provided in which the skin condition in the subject is selected from acne vulgaris, rosacea type 1, rosacea type 2, psoriasis, and hyperhidrosis. In another embodiment, a method is provided in which the skin condition in the subject is acne vulgaris. In another embodiment, a method is provided in which the skin condition in the subject is rosacea type 1. In another embodiment, a method is provided in which the skin condition in the subject is rosacea type 2. In another embodiment, a method is provided in which the skin condition in the subject is psoriasis. In another embodiment, a method is provided in which the skin condition in the subject is hyperhidrosis. In another embodiment, a method is provided in which Spongilla is Spongilla lacustris. In another embodiment, a second method comprising one or more botulinum toxins. A method is provided for topically applying the composition to the skin of a target. In another embodiment, a method is provided in which the second composition, comprising one or more botulinum toxins, is in the form of an aqueous solution. In another embodiment, a method is provided in which the second composition is applied to the skin of a target in the form of a solution. In another embodiment, a method is provided in which the second composition is in the form of an aqueous solution. In another embodiment, a method is provided in which the amount of the first composition containing Spongilla applied to the skin of a target is about 0.5 grams to about 50 grams, measured as dry weight. In another embodiment, a method is provided in which the first composition is applied to the skin of a target in the form of a paste. In another embodiment, a method is provided in which the paste further comprises water or saline solution. In another embodiment, a method is provided in which the paste is prepared by mixing a powder containing Spongilla and an aqueous solution containing hydrogen peroxide. In another embodiment, a method is provided in which the aqueous solution contains hydrogen peroxide at a concentration of about 3% w / w. In another embodiment, a method is provided in which the first composition is applied to the skin of a target before the second composition is applied to the skin of a target. In another embodiment, a method is provided in which the first composition is applied to the skin of a target and may be dried on the skin of a target before the second composition is applied to the skin of a target. In another embodiment, a method is provided in which the first composition is applied to the target skin in the form of an aqueous paste, the aqueous portion of which is derived from water or saline solution. In another embodiment, a method is provided in which the aqueous paste further comprises hydrogen peroxide. In another embodiment, a method is provided in which an aqueous solution of hydrogen peroxide is applied to the target face after the application of the first composition to the target skin and before the application of the second composition to the target skin. In another embodiment, a method is provided in which the first composition further comprises hydrogen peroxide. In another embodiment, a method is provided in which the hydrogen peroxide is an aqueous solution. In another embodiment, a method is provided in which the aqueous solution comprises hydrogen peroxide at a concentration of about 3% w / w. In another embodiment, a method is provided in which the second composition may be dried on the target skin after application to the target skin. In another embodiment, a method is provided in which the second composition is applied to the target skin before the first composition is applied to the target skin.In another embodiment, a method is provided in which the...

Claims

[Claim 1] A combination for use in the treatment of acne in a subject, comprising a first composition comprising Spongilla and a second composition comprising one or more botulinum toxins, wherein the treatment comprises applying the first composition and the second composition to the skin of the subject. [Claim 2] The combination according to claim 1, 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. [Claim 3] The combination according to claim 2, wherein the second composition comprises one or more botulinum toxin types selected from type A botulinum toxins. [Claim 4] The combination according to claim 3, wherein the type A botulinum toxin is onabotulinum toxin A. [Claim 5] A kit for use in treating an object having acne, comprising a first composition and a second composition, (a) The first composition comprises Spongilla, (b) The second composition comprises one or more botulinum toxins, The kit, wherein the procedure includes applying a first composition and a second composition to the skin of a target. [Claim 6] The kit according to claim 5, 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. [Claim 7] The kit according to claim 5, wherein the botulinum toxin is onabotulinum toxin A.

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