Compositions for treatment of conditions by dermal fillers

Abstract

To provide compositions and methods for cosmetic, reparative and restorative dermatological treatment of a subject.SOLUTION: The present disclosure relates to treatment of diseases or conditions in a subject, including skin conditions or diseases. The treatment comprises applying to the skin of the subject a first composition comprising Spongilla and a second composition comprising an effective amount of one or more dermal fillers. The dermal fillers are selected from a chemical compound, a mixture of chemical compounds, a biological macromolecule, or an extract made from biological materials. Further provided are such methods in which the one or more dermal fillers are selected from a group consisting of commercially available dermal fillers.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] Cross - referenced applications

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 877,680, filed Jul. 23, 2019, which is hereby incorporated by reference in its entirety.

[0002]

[0002] This disclosure relates to cosmetic, restorative, and recovery-promoting dermatological treatments for a subject, the treatment comprising applying to the subject's skin a first composition comprising Spongilla and a second composition comprising one or more dermal filler compositions comprising hyaluronic acid, calcium hydroxylapatite, polyalkylimide, polymethylmethacrylate, collagen, polymethylmethacrylate microspheres (PMMA), polylactic acid, polycaprolactone, carboxymethyl cellulose, polymers and / or copolymers of poly-L-lactic acid, and crosslinking reagents. This disclosure also relates to a product or kit for cosmetic, restorative, and recovery-promoting dermatological treatment of a subject's skin, the product or kit comprising a second composition comprising Spongilla and one or more dermal filler compositions. This disclosure relates to treatment of a condition in a subject, including a skin condition, the treatment comprising applying to the subject's skin a first composition comprising Spongilla and a second composition comprising one or more dermal filler compositions. This disclosure also relates to a method for delivering a dermal filler into the skin of a subject, including the dermis, the method comprising applying to the subject's skin a first composition comprising Spongilla and a second composition comprising an effective amount of a dermal filler. This disclosure also relates to a method for delivering an effective amount of a dermal filler to the intradermal compartment, such as the dermis, of a subject's skin by applying to the subject's skin a first composition comprising Spongilla and a second composition comprising an effective amount of one or more dermal fillers. This disclosure also relates to a method for promoting skin penetration of a topically applied dermal filler composition, the method comprising applying a first composition comprising Spongilla to the subject's skin, and subsequently applying a second composition to the subject's skin, the second composition comprising an effective amount of the dermal filler composition, the dermal filler composition comprising hyaluronic acid, calcium hydroxylapatite, polyalkylimide, polymethylmethacrylate, collagen, polymethylmethacrylate microspheres (PMMA), polylactic acid, polycaprolactone, carboxymethyl cellulose, polymers and / or copolymers of poly-L-lactic acid, and crosslinking reagents.Furthermore, the second composition comprises an effective amount of a topical skin filler composition comprising glycerin, a collagen-derived peptide, alguronic acid, a low molecular weight hyaluronic acid polymer, sodium acetylated hyaluronate, glycolic acid, lactic acid, L-lactic acid, amino acids, NIA-114™, acetylated peptides, Activen™ XEP-18, and / or Erasa™ XEP-30.

Background Art

[0003]

[0003] Skin fillers are mainly known for cosmetic use. However, skin fillers can be used for medical purposes including the treatment of facial adipose tissue atrophy caused by the human immunodeficiency virus. Although the popularity of skin fillers for dermatological uses is prominent, little progress has been made in developing methods for delivering these compounds to the target area of the patient. The high molecular weight hydrophilic polymers that make up most commercially available skin fillers do not penetrate beyond the uppermost layer of the skin. Thus, most skin fillers are delivered by needle injection to reach the desired subcutaneous depth and location. Conventional needle delivery has drawbacks including causing anxiety in patients who fear needles, pain at the injection site, and injection site reactions to high concentrations of skin filler (bolus injection). Accordingly, there is a need for an improved method of treating or preventing a skin condition or skin disease and / or delivering a cosmetic topical agent in a subject using one or more skin fillers, where the one or more skin fillers are topically applied to the subject's skin, avoiding the drawbacks of needle injection that can result in unwanted side effects or adverse events, and allowing an effective amount of the one or more skin fillers to penetrate the subject's skin, such that an effective amount of the one or more skin fillers is delivered to the desired site of action, such as the subject's dermis. In these methods, one or more skin fillers are topically applied to the subject's skin, avoiding the drawbacks of needle injection that can result in unwanted side effects or adverse events, and allowing an effective amount of the one or more skin fillers to penetrate the subject's skin, such that an effective amount of the one or more skin fillers is delivered to the desired site of action, such as the subject's dermis.

Summary of the Invention

Problems to be Solved by the Invention

[0004]

[0004] The inventors of the subject matter disclosed herein have discovered that an important component of the material derived from Spongilla is the siliceous spicules that make up the skeletal structure of Spongilla. The inventors have found that the spicules penetrate the stratum corneum and the entire dermis of the skin of the subject upon application, facilitating the penetration of topically applied skin fillers, such as polymers, copolymers, and hydrogels composed of their cross-linked forms, into the skin of the subject, e.g., the dermis, and enabling or enhancing the delivery of an effective amount of the skin filler to the site of action necessary to effectively treat a skin disease or condition in the subject. The inventors of the subject matter disclosed herein have also discovered that the spicules derived from Spongilla are useful in facilitating and enabling the penetration of certain therapeutic compounds and compositions into the skin of the subject to which they are applied. These compounds and compositions would not ordinarily be expected to penetrate the skin of the subject to reach the target and treat a particular skin condition. Compounds and compositions whose penetration into the skin can be improved in the presence of the material derived from Spongilla include products containing one or more chemical compounds, mixtures of chemical compounds, one or more biopolymers, or extracts made from biological materials. The inventors of the subject matter disclosed herein have discovered that the material containing Spongilla used herein may include all of the organic and / or inorganic compounds and substances that are part of the naturally occurring Spongilla, or may include only a portion of the organic and / or inorganic compounds and substances that are part of the naturally occurring Spongilla.

Means for Solving the Problems

[0005]

[0005] In one aspect, a composition is provided herein that includes a first composition containing Spongilla and a second composition containing a skin filler.

[0006] In one aspect, provided herein is a method for administering a dermal filler to a subject's skin, comprising applying to the subject's skin a first composition comprising Spongilla and a second composition comprising an effective amount of a dermal filler.

[0006]

[0007] In one aspect, provided herein are methods for treating or preventing a skin condition or skin disease in a subject. These methods comprise administering, to the intradermal compartment of the subject's skin, a first composition comprising Spongilla in a therapeutically effective amount or a prophylactically effective amount and a second composition comprising a therapeutically effective amount of a dermal filler. These methods comprise applying the first composition and the second composition to the subject's skin.

[0007]

[0008] In one aspect, provided herein are methods for promoting the skin penetration of a topically applied dermal filler composition into a subject's skin. These methods comprise applying a first composition comprising Spongilla to the skin and subsequently applying a second composition comprising an effective amount of a dermal filler.

[0008]

[0009] In one aspect, provided herein is a kit comprising a first composition comprising Spongilla and a second composition comprising one or more dermal fillers in an amount effective to treat a skin condition in a subject.

Brief Description of the Drawings

[0009]

Figure 1

[0010] It is a figure showing the enlarged surface of a typical Spongilla composition.

Mode for Carrying Out the Invention

[0010]

[0011] The singular forms "a", "an", and "the" , unless otherwise indicated in the context, includes a plurality of indicated objects. For example, the term "cell" includes one or more cells, including mixtures thereof. "A and / or B" is used herein to include all of the following options: "A", "B", "A or B", and "A and B".

[0011]

[0012] As used herein, the term "about" means within plus or minus 10% from the provided value, or rounding up or down to the nearest significant digit, and in all cases includes the provided value. When ranges are provided, those ranges include the boundary values.

[0012]

[0012]

[0013] As used herein, the terms "applied", "applying", "administering", "administer", and "used" mean the delivery of the compositions disclosed herein to a subject, particularly to the skin of the subject, by an administration route 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, particularly to the skin of the subject, by topical administration.

[0013]

[0014] As used herein, the term "aspect ratio" means, for the Spongilla particles described herein, the ratio of the average length of the particles to the average diameter of the particles.

[0014]

[0014]

[0015] As used herein, the terms "combination" and "in combination with" means sequential or simultaneous application, use, or administration of one or more of the compositions disclosed herein. This includes administering, using, or applying the compositions disclosed herein simultaneously, or within minutes or hours of each other, or on the same day, or on alternate days, or using the compositions disclosed herein, for example, daily, or on multiple days per week, or weekly, during a period that is concurrent with or parallel to, or during at least a portion of the period during which the compositions disclosed herein are applied, used, or administered, another composition on the same day, or on alternate days or weeks, or periodically. For example, one or more of the compositions disclosed herein can be applied, used, or administered to a subject daily or on multiple days per week concurrently with an additional composition being applied, used, or administered to the subject on alternate days or weeks or other time periods, for example, every day, every other day, every third day, every fourth day, every fifth day, every sixth day, every seventh day, every eighth day, every ninth day, every tenth day, every eleventh day, every twelfth day, every thirteenth day, every fourteenth day, or every greater number of days.

[0015]

[0016] The term "Spongilla", as used herein, means, but is not limited to, the genus of freshwater sponges of the family Spongillidae, including Spongilla lacustris, S. fragilis Leidy, and Ephydatia fluviatilis. The term "Spongilla lacustris", as used herein, means a species of sponge belonging to the family Spongillidae of freshwater sponges. Figure 1 shows a scanning electron microscope photograph of the structure of Spongillidae.

[0016]

[0016]

[0017] "Compositions containing Spongilla", "powders containing Spongilla", As used herein, terms such as "materials containing Spongilla" and "Spongilla in powder form" mean materials containing Spongilla derived from raw Spongilla, which raw Spongilla has been harvested and processed and may include all of the various components of the Spongilla after harvesting, including all organic and / or inorganic compounds and substances that are a part of the naturally occurring Spongilla, or may include only a portion of the organic and / or inorganic compounds and substances that are a part of the naturally occurring Spongilla. In one aspect, there is provided any of the methods or kits disclosed herein, wherein the Spongilla material contains all or substantially all of the organic and inorganic substances derived from the naturally occurring Spongilla. In another aspect, there is provided any of the methods or kits disclosed herein, wherein the Spongilla material contains (a) the bone pieces themselves and any substances naturally associated with the bone pieces, or (b) substantially purified bone pieces and any substances naturally associated with the bone pieces, or (c) purified bone pieces and any substances naturally associated with the bone pieces that are components of the naturally occurring Spongilla. In another aspect, there is provided any of the methods or kits disclosed herein, wherein the Spongilla material contains the bone pieces themselves and any substances naturally associated with the bone pieces. In another aspect, there is provided any of the methods or kits disclosed herein, wherein the Spongilla material contains substantially purified bone pieces and any substances naturally associated with the bone pieces. In another aspect, there is provided any of the methods or kits disclosed herein, wherein the Spongilla material contains purified bone pieces and any substances naturally associated with the bone pieces that are components of the naturally occurring Spongilla.

[0017]

[0018] As used herein, the term "therapeutically effective amount" means an amount of a composition or combination of compositions that, when applied, used, or administered to a subject, is believed to treat, reduce, or prevent to some extent one or more of the symptoms of the disorder being treated. ​ Composition

[0019] In one aspect, a composition comprising a first composition and a second composition, wherein the first composition comprises Spongilla and the second composition comprises one or more dermal fillers is provided.

[0018]

[0020] In a plurality of embodiments, the first composition comprises Spongilla. In a plurality of embodiments, Spongilla is Spongilla lacustris.

[0021] The Spongilla including Spongilla lacustris and powders prepared from Spongilla utilized in the methods, uses, compositions for use as medicaments, kits, and dermal fillers disclosed herein may be obtained, processed, and It is dried until the content becomes less than the desired value further disclosed herein. The measurement of residual moisture can be carried out using methods generally known in the technical fields of food science, analytical chemistry, or pharmacy. For example, 10 grams of the dried material may be placed on a tared weighing boat and then weighed. Next, the weighed material is exposed to a heat source such as a dryer or a heating lamp operated at an appropriate temperature. Thereafter, the sample is cooled in a drying chamber and reweighed. The residual moisture is calculated as the percentage difference between the weight of the sample before drying and the weight after cooling. After drying, the sponge material may be placed in a sealed container that protects the material from light, moisture, and oxygen as necessary. These materials may then be further tested for the presence of organisms indicating pathogens, coliforms, and bioburden. These materials may be further heated or irradiated as disclosed herein to reduce any pathogens, coliforms, or other organisms indicating bioburden. These materials may then be further processed using methods known to those skilled in the art to provide a powder containing particles of a desired size. For example, the sponge material may be milled, and the resulting material passes through one or more sieves of a predetermined size to provide a resulting substance containing particles of a uniform size or a substantially uniform size. After the final processing and classification steps are completed, the dried sponge material may be placed in an airtight moisture-proof container and stored at an appropriate temperature, such as room temperature or ambient temperature.

[0019]

[0022] In a plurality of embodiments, Spongilla exists in the form of a powder. In a plurality of embodiments, the powder comprises particles having a substantially uniform size. In a plurality of embodiments, the powder comprises particles having a substantially uniform size.

[0023] In another aspect, a first composition comprises Spongilla in powder form. Provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed in the present application. A material containing Spongilla may be prepared in a powdered form having particles of substantially the same size using techniques known to those skilled in the art, such as grinding and sieving. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed in the present application, wherein Spongilla is present in the form of a powder containing particles of substantially uniform size. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed in the present application, wherein at least about 50% of the particles containing Spongilla powder pass through a US 70 mesh screen. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed in the present application, wherein 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 containing Spongilla powder pass through a US 70 mesh screen. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed in the present application, wherein about 95%, or about 96%, or about 97%, or about 98%, or about 99% or more of the particles containing Spongilla powder pass through a US 70 mesh screen. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed in the present application, wherein at least about 95% of the particles containing Spongilla powder pass through a US 70 mesh screen. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed in the present application, wherein at least about 96% of the particles containing Spongilla powder pass through a US 70 mesh screen. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed in the present application, wherein at least about 97% of the particles containing Spongilla powder pass through a US 70 mesh screen.In another aspect, provided is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein at least about 98% of the particles comprising Spongilla powder pass through a US 70 mesh screen. In another aspect, at least about 99% of the particles comprising Spongilla powder pass through a US 70 mesh screen, and provided is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein. The particles of Spongilla may be produced or manufactured from the harvested Spongilla material by procedures known to those skilled in the art, such as determination of an appropriate harvesting period, removal of foreign substances, drying, grinding, and milling using equipment known to those skilled in the art.

[0020]

[0024] In another aspect, the particles comprising Spongilla powder are from about 50 μm to about 500 μ Provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein having an average length of m. In another aspect, particles comprising Spongilla powder have an average length of from about 50 μm to about 400 μm, or from about 50 μm to about 350 μm, or from about 50 μm to about 300 μm, or from about 50 μm to about 250 μm, or from about 50 μm to about 200 μm, or from about 75 μm to about 500 μm, or from about 75 μm to about 450 μm, or from about 80 μm to about 450 μm, or from about 80 μm to about 400 μm, or from about 85 μm to about 450 μm, or from about 85 μm to about 400 μm, or from about 90 μm to about 450 μm, or from about 90 μm to about 400 μm, or from about 90 μm to about 350 μm, or from about 100 μm to about 450 μm, or from about 100 μm to about 400 μm, or from about 100 μm to about 350 μm, or from about 100 μm to about 300 μm, or from about 100 μm to about 250 μm, or from about 100 μm to about 200 μm, or from about 150 μm to about 500 μm, or from about 100 μm to about 450 mm, or from about 150 μm to about 400 μm, or from about 150 μm to about 350 μm, or from about 150 μm to about 350 μm, or from about 150 μm to about 300 μm, or from about 150 μm to about 250 mm, or from about 150 μm to about 200 μm, or from about 175 μm to about 450 μm, or from about 175 μm to about 400 μm, or from about 175 μm to about 350 μm, or from about 175 μm to about 300 mm, or from about 175 μm to about 250 μm, or from about 175 μm to about 200 μm, and provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein. In another aspect, particles comprising Spongilla powder have an average length of about 50 μm, or about 75 μm, or about 80 μm, or about 85 μm, or about 90 μm, or about 100 μm, or about 125 μm, or about 150 μm, or about 175 μm, or about 200 μm, or about 225 μm, or about 250 μm, or about 300 μm, or about 350 μm, or about 400 μm, or about 450 μm, or about 500 μm, and provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein.In another aspect, provided is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the particles comprising Spongilla powder have an average length of about 200 μm. The particles comprising Spongilla powder may be manufactured or produced from the harvested Spongilla material by procedures known to those skilled in the art, such as grinding and milling using equipment known to those skilled in the art. The average length of the particles comprising Spongilla powder may be measured using analytical methods known to those skilled in the art, such as, for example, scanning electron microscopy (SEM) and sieve analysis. Sieve analysis may also be used to determine the particle size distribution of the particles comprising Spongilla powder.

[0021]

[0025] In another aspect, provided is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the particles comprising Spongilla powder have an average diameter of from about 5 μm to about 50 μm. In another aspect, provided is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the particles comprising Spongilla powder have an average diameter of from about 5 μm to about 45 μm, or from about 5 μm to about 40 μm, from about 5 μm to about 35 μm, from about 5 μm to about 30 μm, from about 5 μm to about 25 μm, from about 5 μm to about 20 μm, from about 10 μm to about 45 μm, from about 10 μm to about 40 μm, from about 10 μm to about 35 μm, from about 10 μm to about 30 μm, from about 10 μm to about 25 μm, from about 10 μm to about 20 mm, and from about 10 μm to about 15 μm. In another aspect, the particles comprising Spongilla powder have an average diameter of about 5 μm, or about 10 μm, or about 15 μm, or Provided is any of the methods, compositions for use as medicaments, pharmaceutical products, and kits disclosed herein, having an average diameter of about 20 μm, or about 25 μm, or about 30 μm, or about 35 μm, or about 40 μm, or about 45 μm, or about 50 μm. Particles containing Spongilla powder may be manufactured or produced from the Spongilla material taken by procedures known to those skilled in the art, such as grinding and attrition using equipment known to those skilled in the art. The average diameter of the particles containing Spongilla powder may be measured using analytical methods known to those skilled in the art, such as scanning electron microscopy (SEM) and sieve analysis. Also, sieve analysis may be used to determine the particle size distribution of the particles containing Spongilla powder.

[0022]

[0026] In another aspect, the particles containing Spongilla powder have an aspect ratio of about 1 to about 100 Provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed herein, having an aspect ratio. In another aspect, provided is any one of a method, a composition for use as a medicament, a drug product, and a kit, as disclosed herein, wherein the particles comprising Spongilla powder have an aspect ratio of from about 1 to about 75, or from about 1 to about 50, or from about 1 to about 25, or from about 1 to about 20, or from about 1 to about 15, or from about 5 to about 100, or from about 5 to about 75, or from about 5 to about 50, or from about 5 to about 40, or from about 5 to about 35, or from about 5 to about 30, or from about 5 to about 25, or from about 5 to about 20, or from about 5 to about 15, or from about 7 to about 50, or from about 7 to about 45, or from about 7 to about 40, or from about 7 to about 35, or from about 7 to about 30, or from about 7 to about 25, or from about 10 to about 50, or from about 10 to about 45, or from about 10 to about 40, or from about 10 to about 35, or from about 10 to about 30, or from about 10 to about 25, or from about 10 to about 15. In another aspect, provided is any one of a method, a composition for use as a medicament, a drug product, and a kit, as disclosed herein, wherein the particles comprising Spongilla powder have an aspect ratio of about 5, or about 6, or about 7, or about 8, or about 9, or about 10, or about 11, or about 12, or about 13, or about 14, or about 15, or about 16, or about 17, or about 18, or about 19, or about 20, or about 21, or about 22, or about 23, or about 24, or about 25, or about 26, or about 27, or about 28, or about 29, or about 30, or about 35, or about 40, or about 45, or about 50, or about 75, or about 100. The particles comprising Spongilla powder may be manufactured or produced from Spongilla material obtained by procedures known to those skilled in the art, such as grinding and milling using equipment known to those skilled in the art. The aspect ratio of the particles comprising Spongilla powder may be measured using analytical methods known to those skilled in the art, such as, for example, scanning electron microscopy (SEM) and sieve analysis. Also, sieve analysis may be used to determine the particle size distribution of the particles comprising Spongilla powder.

[0023]

[0027] Materials containing Spongilla may be processed and dried using techniques known to those skilled in the art, such as the use of a dryer, to provide a substance having a desirable residual moisture content. In another aspect, a first composition containing Spongilla is provided, which has a residual moisture content of about 20% or less, and is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein. In another aspect, a first composition is provided, which 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, and is any of the methods, compositions for use as a medicament, pharmaceutical products, and kits disclosed herein. In another aspect, a first composition is provided, which has a residual moisture content of about 5% or less, and is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein. In another aspect, a first composition is provided, which has a residual moisture content of about 4% or less, and is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein. In another aspect, a first composition has a residual of about 3% or less ​Provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit disclosed herein, having a residual water content. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit disclosed herein, wherein a first composition has a residual water content of about 2% or less. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit disclosed herein, wherein a first composition has a residual water content of about 1% or less. The water content of the Spongilla material can be reduced by heating the raw Spongilla material using methods known to those skilled in the art, for example, by drying in the field using equipment known to those skilled in the art, or by using a conventional oven dryer or vacuum dryer. For example, the raw Spongilla material can be placed in a tray and heated in a dryer for a period necessary to reduce the residual water content to a desired level in a temperature range from about 30 °C to about 200 °C, for example, up to about 70 °C. The level of residual water in the material can be measured using methods known to those skilled in the art, such as those described in the United States Pharmacopeia methods USP<731> (Loss on Drying) and USP<921> (Determination of Moisture).

[0024]

[0028] Materials containing Spongilla may, prior to packaging and use, be treated, for example, by the use of heat treatment or radiation, for example gamma irradiation, to reduce the bioburden of the material, for example aerobic and anaerobic microorganisms, yeasts and molds, Escherichia coli type bacteria, Salmonella, Pseudomonas aeruginosa, and Staphylococcus aureus. Materials containing Spongilla may, after packaging, be treated, for example, by the use of heat treatment or radiation, for example gamma radiation.

[0025]

[0025]

[0029] In another aspect, the total content of aerobic and anaerobic microorganisms in a first composition is about 25×10 4Either the methods and / or kits disclosed herein are provided, which are below colony forming units / gram (CFU / g). In another aspect, the total content of aerobic and anaerobic microorganisms in the first composition is about 10×10 4 CFU / g, or 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 3Provided is any of the methods and / or kits disclosed herein that are less than 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 aspect, provided is any of the methods and / or kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 1,000 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 750 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 500 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 250 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 200 CFU / g or less. In another aspect, the first composition has about 150 CFU Provided is either a method and / or a kit disclosed herein having a total content of aerobic and anaerobic microorganisms of 100 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 100 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 75 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 50 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 25 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 20 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 10 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 1 CFU / g or less. The total content of aerobic and anaerobic microorganisms that the Spongilla material has may be reduced by physical or chemical methods and / or kits 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 by ionizing radiation for a time sufficient to reduce the microorganism content to a desired level. The total content of aerobic and anaerobic microorganisms that the Spongilla material has may be measured using methods known to those skilled in the art, such as those described in the method USP<61> (Microbial Enumeration Tests) of the United States Pharmacopeia.

[0026]

[0030] In another aspect, the total content of yeast and mold in the first composition containing Spongilla is about 25×10 4 colony forming units / gram (CFU / g) or less, and any of the methods and / or kits disclosed herein are provided. In another aspect, the total content of yeast and mold in the first composition is 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 3Provided are any of the methods and / or kits disclosed herein that are less than 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 aspect, provided are any of the methods and / or kits disclosed herein, wherein the first composition has a total content of yeast and mold of about 1,000 CFU / g or less. In another aspect, provided are any of the methods and / or kits disclosed herein, wherein the first composition has a total content of yeast and mold of about 750 CFU / g or less. In another aspect, provided are any of the methods and / or kits disclosed herein, wherein the first composition has a total content of yeast and mold of about 500 CFU / g or less. In another aspect, provided are any of the methods and / or kits disclosed herein, wherein the first composition has a total content of yeast and mold of about 250 CFU / g or less. In another aspect, provided are any of the methods and / or kits disclosed herein, wherein the first composition has a total content of yeast and mold of about 200 CFU / g or less. In another aspect, the first composition has a total content of yeast and mold of about 150 CFU / g or less of Provided is either a method and / or a kit disclosed herein having a total content of yeast and mold. In another aspect, provided is either a method and / or a kit disclosed herein, wherein a first composition has a total content of yeast and mold of about 100 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein a first composition has a total content of yeast and mold of about 75 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein a first composition has a total content of yeast and mold of about 50 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein a first composition has a total content of yeast and mold of about 25 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein a first composition has a total content of yeast and mold of about 20 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein a first composition has a total content of yeast and mold of about 10 CFU / g or less. In another aspect, provided is either a method and / or a kit disclosed herein, wherein a first composition has a total content of yeast and mold of about 1 CFU / g or less. The total content of yeast and mold in the Spongilla material may be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material 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 time sufficient to reduce the microbial content to a desired level. The total content of yeast and mold in the Spongilla material may be measured using methods known to those skilled in the art, such as those described in the United States Pharmacopeia method USP <61> (Microbial Enumeration Tests).

[0027]

[0031] In another aspect, the amount of Salmonella in the first composition is about 25×10 4Either the method and / or kit disclosed herein is provided, which is below colony forming unit / gram (CFU / g). In another aspect, the amount of Salmonella in the first composition is 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 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, any of the methods and / or kits disclosed herein are provided. In another aspect, any of the methods and / or kits disclosed herein are provided, wherein the Salmonella content of the first composition is about 1,000 CFU / g or less. In another aspect, any of the methods and / or kits disclosed herein are provided, wherein the Salmonella content of the first composition is about 750 CFU / g or less. In another aspect, any of the methods and / or kits disclosed herein are provided, wherein the Salmonella content of the first composition is about 500 CFU / g or less. In another aspect, any of the methods and / or kits disclosed herein are provided, wherein the Salmonella content of the first composition is about 250 CFU / g or less. In another aspect, any of the methods and / or kits disclosed herein are provided, wherein the Salmonella content of the first composition is about 200 CFU / g or less. In another aspect, any of the methods and / or kits disclosed herein are provided, wherein the Salmonella content of the first composition is about 150 CFU / g or less. In another aspect, the Salmonella content of the first composition is 、Either the method and / or kit disclosed herein is provided, wherein the Salmonella content is about 100 CFU / g or less. In another aspect, either the method and / or kit disclosed herein is provided, wherein the Salmonella content of the first composition is about 75 CFU / g or less. In another aspect, either the method and / or kit disclosed herein is provided, wherein the Salmonella content of the first composition is about 50 CFU / g or less. In another aspect, either the method and / or kit disclosed herein is provided, wherein the Salmonella content of the first composition is about 25 CFU / g or less. In another aspect, either the method and / or kit disclosed herein is provided, wherein the Salmonella content of the first composition is about 20 CFU / g or less. In another aspect, either the method and / or kit disclosed herein is provided, wherein the Salmonella content of the first composition is about 10 CFU / g or less. In another aspect, either the method and / or kit disclosed herein is provided, wherein the Salmonella content of the first composition is about 1 CFU / g or less. In another aspect, either the method and / or kit disclosed herein is provided, wherein the Salmonella content of the first composition is not detectable. The Salmonella content of the Spongilla material may be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material 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 time sufficient to reduce the microbial content to a desired level. The Salmonella content of the Spongilla material may be measured using methods known to those skilled in the art, such as those described in the United States Pharmacopeia method USP <62> (Tests for Specified Microorganisms).

[0028]

[0032] In another aspect, the amount of Escherichia coli-type bacteria in the first composition is about 25×10 4 colony Either the method and / or kit disclosed herein is provided, which is less than or equal to 4 CFU / g, or about 5×10 4 CFU / g or less, or about 1×10 3 CFU / g or less, or about 5×10 3Provided is any of the methods and / or kits disclosed herein that is less than 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 aspect, provided is any of the methods and / or kits disclosed herein, wherein the Escherichia coli-type bacteria content of the first composition is about 1,000 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Escherichia coli-type bacteria content of the first composition is about 750 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Escherichia coli-type bacteria content of the first composition is about 500 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Escherichia coli-type bacteria content of the first composition is about 250 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Escherichia coli-type bacteria content of the first composition is about 200 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Escherichia coli-type bacteria content of the first composition is about 150 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Escherichia coli-type bacteria content of the first composition is about 100 CFU / g or less, and / or the methods and / or kits disclosed herein Either a method or a kit is provided. In another aspect, either a method or a kit disclosed herein is provided, wherein the Escherichia coli - type bacteria content of the first composition is about 75 CFU / g or less. In another aspect, either a method or a kit disclosed herein is provided, wherein the Escherichia coli - type bacteria content of the first composition is about 50 CFU / g or less. In another aspect, either a method or a kit disclosed herein is provided, wherein the Escherichia coli - type bacteria content of the first composition is about 25 CFU / g or less. In another aspect, either a method or a kit disclosed herein is provided, wherein the Escherichia coli - type bacteria content of the first composition is about 20 CFU / g or less. In another aspect, either a method or a kit disclosed herein is provided, wherein the Escherichia coli - type bacteria content of the first composition is about 10 CFU / g or less. In another aspect, either a method or a kit disclosed herein is provided, wherein the Escherichia coli - type bacteria content of the first composition is about 1 CFU / g or less. In another aspect, either a method or a kit disclosed herein is provided, wherein the Escherichia coli - type bacteria content of the first composition is not detectable. The Escherichia coli - type bacteria content of the Spongilla material may be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material 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 time sufficient to reduce the microbial content to a desired level. The Escherichia coli - type bacteria content of the Spongilla material may be measured using methods known to those skilled in the art, such as those described in the United States Pharmacopeia method USP <62> (Tests for Specified Microorganisms).

[0029]

[0033] In another aspect, the amount of Pseudomonas aeruginosa bacteria in the first composition is about 25×10 4Either the method and / or kit disclosed herein is provided, which is below colony forming units / gram (CFU / g). In another aspect, the amount of Pseudomonas aeruginosa bacteria in the first composition is 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 3Provided are any of the methods and / or kits disclosed herein that are less than 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 aspect, provided are any of the methods and / or kits disclosed herein wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 1,000 CFU / g or less. In another aspect, provided are any of the methods and / or kits disclosed herein wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 750 CFU / g or less. In another aspect, provided are any of the methods and / or kits disclosed herein wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 500 CFU / g or less. In another aspect, provided are any of the methods and / or kits disclosed herein wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 250 CFU / g or less. In another aspect, provided are any of the methods and / or kits disclosed herein wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 200 CFU / g or less. In another aspect, provided are any of the methods and / or kits disclosed herein wherein the first composition has a Pseudomonas aeruginosa bacterial content of about 150 CFU / g or less In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Pseudomonas aeruginosa bacterial content of the first composition is about 100 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Pseudomonas aeruginosa bacterial content of the first composition is about 75 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Pseudomonas aeruginosa bacterial content of the first composition is about 50 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Pseudomonas aeruginosa bacterial content of the first composition is about 25 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Pseudomonas aeruginosa bacterial content of the first composition is about 20 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Pseudomonas aeruginosa bacterial content of the first composition is about 10 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Pseudomonas aeruginosa bacterial content of the first composition is about 1 CFU / g or less. In another aspect, provided is any of the methods and / or kits disclosed herein, wherein the Pseudomonas aeruginosa bacterial content of the first composition is not detectable. The Pseudomonas aeruginosa bacterial content of the Spongilla material may be reduced by physical or chemical methods known to those skilled in the art, such as physical treatment of the material 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 time sufficient to reduce the microbial content to a desired level.The Pseudomonas aeruginosa bacterial content of the Spongilla material may be measured using methods known to those skilled in the art, such as those described in the United States Pharmacopeia method USP <62> (Microbial Tests for Specified Microorganisms).

[0030]

[0034] In another aspect, provided is any one of the methods and / or kits disclosed herein, wherein the amount of Staphylococcus aureus bacteria in the first composition is about 25 × 10 4 colony forming units / gram (CFU / g) or less. In another aspect, provided is any one of the methods and / or kits disclosed herein, wherein the amount of Staphylococcus aureus bacteria in the first composition is 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 3 CFU / g or less, or about 10,000 CFU / g or less, or about 7,500 CFU / g or less, or about 5,000 CFU / g or less, or about 2,500 CFU / g or less, or about 2,000 CFU / g or less, or about 1,500 CFU / g or less, or about 1,000 CFU / g or less, or about 750 CFU / g or less, or about 500 CFU / g or less, or about 250 CFU / g or less, or about 200 CFU / g or less, or about 150 CFU / g or less, or about 100 CFU / g or less, or about 75 CFU / g or less, or about 50 CFU / g or less, or about 25 CFU / g or less, or about 15 CFU / g or less, or about 10 CFU / g or less, or about 5 CFU / g or less, or about 1 CFU / g or less. In another aspect, the first composition has Staphylococcus Either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content is about 1,000 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 750 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 500 CFU / g or less. In another aspect, the Staphylococcus aureus bacterial content of the first composition is about 250 CFU / g or less Either a method and / or a kit disclosed herein is provided. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 200 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 150 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 100 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 75 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 50 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 25 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 20 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 10 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 1 CFU / g or less. In another aspect, either a method and / or a kit disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is not detectable.The Staphylococcus aureus bacterial content of the Spongilla material may be reduced by physical or chemical methods known to those skilled in the art, such as, for example, physical treatment of the material with 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 time sufficient to reduce the microbial content to a desired level. The Staphylococcus aureus bacterial content of the Spongilla material may be reduced by physical or chemical methods known to those skilled in the art, such as, for example, physical treatment of the material with 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 time sufficient to reduce the microbial content to a desired level. <62> (Specific Microbial Testing) may be measured using methods known to those skilled in the art.

[0031]

[0035] In another embodiment, the presently disclosed subject matter provides a method for the preparation of a pharmaceutical composition comprising the steps of: In another aspect, there is provided any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the first composition is prepared by heating to at least about 70° C. before packaging to reduce bioburden. In another aspect, there is provided any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the first composition is prepared by heating to at least about 50° C., or at least about 60° C., or at least about 75° C., or at least about 80° C., or at least about 85° C., or at least about 90° C., or at least about 100° C., or at least about 110° C., or at least about 115° C., or at least about 120° C., or at least about 125° C., or at least about 130° C., or at least about 135° C., or at least about 140° C., or at least about 150° C., or at least about 160° C., or at least about 170° C., or at least about 180° C., or at least about 190° C., or at least about 200° C. prior to packaging.

[0032]

[0036] In another embodiment, the first composition comprising Spongilla is slightly diluted before being packaged. Provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed herein, that is heated to at least about 70° C. for at least about 5 minutes. In another aspect, a first composition is heated to at least about 70° C. for at least about 10 minutes, or at least about 15 minutes, or at least about 20 minutes, or at least about 25 minutes, or at least about 30 minutes, or at least about 35 minutes, or at least about 40 minutes, or at least about 45 minutes, or at least about 50 minutes, or at least about 55 minutes, or at least about 60 minutes, or at least about 75 minutes, or at least about 90 minutes, or at least about 120 minutes, or at least about 180 minutes, or at least about 4 hours, or at least about 5 hours, or at least about 6 hours, or at least about 7 hours, or at least about 8 hours, or at least about 9 hours, or at least about 10 hours, or at least about 11 hours, or at least about 12 hours, or at least about 24 hours, before being packaged. Provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed herein, that is heated to at least about 70° C.

[0033]

[0037] In another aspect, a first composition comprising Spongilla is before or Provided is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, which are prepared by treating, after packaging, with ionizing radiation such as gamma radiation. For example, gamma irradiation may be performed on the raw Spongilla material before milling to reduce the particle size, the material after milling to reduce the particle size, the packaged material together, and / or the material after packaging in a unit dose container. These materials may be treated with ionizing radiation such as gamma radiation using methods and equipment known to those skilled in the art, such as a gamma irradiation device or an electron beam irradiation device. In another aspect, provided is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition is prepared by treating, prior to being packaged, with ionizing radiation such as gamma radiation to deliver an absorbed radiation dose between about 1 kGy and about 50 kGy. In another aspect, provided is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition is treated with ionizing radiation such as gamma radiation to deliver an absorbed radiation dose between about 1 kGy and about 45 kGy, or between about 1 kGy and about 40 kGy, between about 1 kGy and about 35 kGy, between about 1 kGy and about 30 kGy, or between about 1 kGy and about 25 kGy, or between about 5 kGy and about 50 kGy, or between about 5 kGy and about 45 kGy, or between about 5 kGy and about 40 kGy, or between about 5 kGy and about 35 kGy, or between about 5 kGy and about 30 kGy, or between about 5 kGy and about 25 kGy, or between about 10 kGy and about 50 kGy, or between about 10 kGy and about 45 kGy, or between about 10 kGy and about 40 kGy, or between about 10 kGy and about 35 kGy, or between about 10 kGy and about 30 kGy, or between about 10 kGy and about 25 kGy, or between about 15 kGy and about 50 kGy, or between about 15 kGy and about 45 kGy, or between about 15 kGy and about 40 kGy, or between about 15 kGy and about 35 kGy, or between about 15 kGy and about 30 kGy, or between about 15 kGy and about 25 kGy.In another aspect, the first composition is about 1 kGy, or about 5 kGy, or about 10 kGy, 11 kGy, or about 12 kGy, or about 13 kGy, or about 14 kGy, or about 15 kGy, or about 16 kGy, or about 17 kGy, or about 18 kGy, or about 19 kGy, or about 20 kGy, or about 21 kGy, or about 22 kGy, or about 23 kGy, or about 24 kGy, or about 25 kGy, or about 26 kGy, or about 27 kGy, or about 28 kGy, or about 29 kGy, or about 30 kGy, or about 31 kGy, or about 32 kGy, or about 33 kGy, or about 34 kGy, or about 35 kGy, or about 36 kGy, or about 37 kGy, or about 38 kGy, or about 39 kGy, or about 40 kGy, or about 41 kGy, or about 42 kGy, or about 43 kGy, or about 44 kGy, or about 45 kGy, or about 46 kGy, or about 47 kGy, or about 48 kGy, or about 49 kGy, or. Any of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein are provided, which are prepared by treating with ionizing radiation such as gamma radiation to deliver an absorbed radiation dose of about 50 kGy.

[0034]

[0038] In another aspect, Spongilla contains Spongilla lacustri Any of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein are provided.

[0035]

[0039] In another aspect, a first composition containing Spongilla applied to the skin of a subject Provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit disclosed herein, wherein the amount of the substance is from about 0.5 grams to about 50 grams. In one aspect, provided is any one of the methods disclosed herein, wherein the amount of the first composition is measured as dry weight. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit disclosed herein, wherein the amount of the first composition comprising Spongilla applied to the skin of a subject is from about 0.5 grams to about 40 grams, or from about 0.5 grams to about 35 grams, or from about 0.5 grams to about 30 grams, or from about 0.5 grams to about 25 grams, or from about 0.5 grams to about 20 grams, or from about 0.5 grams to about 15 grams, or from about 0.5 grams to about 10 grams, or from about 0.75 grams to about 20 grams, or from about 0.75 grams to about 15 grams, or from about 0.75 grams to about 10 grams, or from about 1 gram to about 20 grams, or from about 1 gram to about 15 grams, or from about 1 gram to about 10 grams, or from about 1 gram to about 9 grams, or from about 1 gram to about 8 grams, or from about 1 gram to about 7 grams, or from about 1 gram to about 6 grams, or from about 1 gram to about 5 grams, or from about 1 gram to about 4 grams, or from about 1 gram to about 3 grams, or from about 1 gram to 2 grams. In another aspect, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit disclosed herein, wherein the amount of Spongilla applied to the skin, such as that disclosed above, is measured as dry weight respectively.

[0036]

[0040] In another aspect, the first composition comprising Spongilla applied to the skin of a subject The amount of the substance is about 0.5 grams, or about 0.75 grams, or about 1 gram, or about 1.25 grams, or about 1.5 grams, or about 1.75 grams, or about 2 grams, or about 2.25 grams, or about 2.5 grams, or about 2.75 grams, or about 3 grams, or about 3.25 grams, or about 3.5 grams, or about 3.75 grams, or about 4 grams, or about 4.25 grams, or about 4.5 grams, or about 4.75 grams, or about 5 grams, or about 5.25 grams, or about 5.5 grams, or about 5.75 grams, or about 6 grams, or about 6.25 grams, or about 6.5 grams, or about 7 grams, or about 7.25 grams, or about 7.5 grams, or about 7.75 grams, or about 8 grams, or about 8.25 grams, or about 8.5 grams, or about 8.75 grams, or about 9 grams, or about 9.25 grams, or about 9.5 grams, or about 9.75 grams, or about 10 grams, or about 11 grams, or about 12 grams, or about 13 grams, or about 14 grams, or about 15 grams, or about 16 grams, or about 17 grams, or about 18 grams, or about 19 grams, or about 20 grams, or about 25 grams, or about 35 grams, or about 40 grams, or about 45 grams, or about 50 grams, or about 75 grams, or about 100 grams, or about 250 grams, or about 500 grams, or about 750 grams, or about 1000 grams, and in each case is measured as dry weight, and any of the methods, compositions for use as a medicament, dermal filler products, and kits disclosed herein are provided.

[0037]

[0041] In another aspect, the first composition is applied to the skin of the subject in the form of a paste. The methods, compositions for use as a medicament, pharmaceutical products, and Either a kit is provided. In another aspect, either a method, a composition for use as a medicament, a pharmaceutical product, and a kit as disclosed herein is provided, wherein the paste further comprises water or saline. In another aspect, either a method, a composition for use as a medicament, a pharmaceutical product, and a kit as disclosed herein is provided, wherein the paste is prepared by mixing a composition containing Spongilla and an aqueous solution containing hydrogen peroxide.In another aspect, hydrogen peroxide is present at a concentration of from about 0.1 wt% to about 50 wt%, or from about 0.1 wt% to about 45 wt%, or from about 0.1 wt% to about 40 wt%, or from about 0.1 wt% to about 35 wt%, or from about 0.1 wt% to about 30 wt%, or from about 0.1 wt% to about 25 wt%, or from about 0.1 wt% to about 20 wt%, or from about 0.1 wt% to about 15 wt%, or from about 0.1 wt% to about 10 wt%, or from about 0.1 wt% to about 9 wt%, or from about 0.1 wt% to about 8 wt%, or from about 0.1 wt% to about 8 wt%, or from about 0.1 wt% to about 7 wt%, or from about 0.1 wt% to about 6 wt%, or from about 0.1 wt% to about 5 wt%, or from about 0.1 wt% to about 4 wt%, or from about 0.1 wt% to about 3 wt%, or from about 0.1 wt% to about 2 wt%, or from about 0.1 wt% to about 1 wt%, or from about 0.5 wt% to about 45 wt%, or from about 1 wt% to about 45 wt%, or from about 1 wt% to about 40 wt%, or from about 1 wt% to about 35 wt%, or from about 1 wt% to about 30 wt%, or from about 1 wt% to about 25 wt%, or from about 1 wt% to about 20 wt%, or from about 1 wt% to about 15 wt%, or from about 1 wt% to about 10 wt%, or from about 1 wt% to about 9 wt%, or from about 1 wt% to about 8 wt%, or from about 1 wt% to about 8 wt%, or from about 1 wt% to about 7 wt%, or from about 1 wt% to about 6 wt%, or from about 1 wt% to about 5 wt%, or from about 1 wt% to about 4 wt%, or from about 1 wt% to about 3 wt%, or from about 1 wt% to about 2 wt%, or from about 2 wt% to about 45 wt%, or from about 2 wt% to about 40 wt%, or from about 2 wt% to about 35 wt%, or from about 2 wt% to about 30 wt%, or from about 2 wt% to about 25 wt%, or from about 2 wt% to about 20 wt%, or from about 2 wt% to about 15 wt%, or from about 2 wt% to about 10 wt%, or from about 2 wt% to about 9 wt%, or from about 2 wt% to about 8 wt%, or from about 1 wt% to about 7 wt%, or from about 2 wt% to about 6 wt%, or from about 2 wt% to about 5 wt%, or from about 2 wt% to about 4 wt%, or from about 2 wt% to about 3 wt%, and any of the methods, compositions for use as a medicament, pharmaceutical products, and kits disclosed herein are provided.In another aspect, provided is any of the methods, compositions for use as a medicament, pharmaceutical products, and kits disclosed herein, wherein hydrogen peroxide is present at a concentration of about 0.1 wt%, or about 0.5 wt%, or about 1 wt%, or about 2 wt%, or about 3 wt%, or about 4 wt%, or about 5 wt%, or about 6 wt%, or about 7 wt%, or about 8 wt%, or about 9 wt%, or about 10 wt%, or about 15 wt%, or about 20 wt%, or about 25 wt%, or about 30 wt%, or about 35 wt%, or about 40 wt%, or about 45 wt%, or about 50 wt%. In another aspect, provided is any of the methods, compositions for use as a medicament, pharmaceutical products, and kits disclosed herein, wherein hydrogen peroxide is present at a concentration of about 3 wt%. An aqueous hydrogen peroxide solution that may be useful for treating skin conditions in a subject as disclosed herein may be commercially available or prepared by methods known to those skilled in the art.

[0038]

[0042] In another aspect, the first composition and / or the second composition may be used in combination with a gel or cream, and the gel or cream may or may not further contain hydrogen peroxide. Provided is any of the methods, compositions for use as a medicament, pharmaceutical products, and kits disclosed herein. In another aspect, the first composition and / or the second composition may be used in combination with a gel or cream that does not further contain hydrogen peroxide. Provided is any of the methods, compositions for use as a medicament, pharmaceutical products, and kits disclosed herein. In another aspect, the first composition and / or the second composition may be used in combination with a gel or cream that further contains hydrogen peroxide. As disclosed herein A method, a composition for use as a medicament, a pharmaceutical product, and a kit are provided. Such gels or creams are generally commercially available and may contain from about 0.5% to about 50% by weight hydrogen peroxide. For example, a gel containing about 1%, or about 2%, or about 3%, or about 4%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10%, or about 15%, or about 20%, or about 25%, or about 30%, or about 40%, or about 45%, or about 50% by weight hydrogen peroxide may be used in any of the methods disclosed herein in combination with the first composition and the second composition.

[0039]

[0043] In a plurality of embodiments, the composition includes one or more skin fillers. In a plurality of embodiments, the skin filler is selected from a chemical compound, a mixture of chemical compounds, a biopolymer, or an extract made from a biological material. In a plurality of embodiments, one or more skin fillers are chemical compounds. In a plurality of embodiments, one or more skin fillers are biopolymers. In a plurality of embodiments, one or more skin fillers are extracts made from biological materials.

[0040]

[0044] In a plurality of embodiments, the skin filler is hyaluronic acid, calcium hydroxyl It includes apatite, polyalkylimide, polymethyl methacrylate, collagen, polymethyl methacrylate microspheres (PMMA), polylactic acid, polycaprolactone, carboxymethyl cellulose, polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of poly-L-lactic acid. In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of hyaluronic acid. In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of calcium hydroxylapatite. In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of polyalkylimide. In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of polymethyl methacrylate. In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of collagen. In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of polymethyl methacrylate microspheres (PMMA). In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of polylactic acid. In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of polycaprolactone. In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of carboxymethyl cellulose. In multiple embodiments, the dermal filler includes polymers, copolymers, crosslinked polymers, and / or crosslinked copolymers of poly-L-lactic acid.

[0041]

[0045] In multiple embodiments, the dermal filler is glycerin, a peptide derived from collagen , including alguronic acid, low molecular weight hyaluronic acid polymer, sodium acetylated hyaluronate, glycolic acid, lactic acid, L-lactic acid, amino acids, NIA-114™, acetylated peptides, Activen™ XEP-18, and / or Erasa™ XEP-30, a topical skin filler. In a plurality of embodiments, the skin filler includes glycerin. In a plurality of embodiments, the skin filler includes collagen-derived peptides. In a plurality of embodiments, the skin filler includes alguronic acid. In a plurality of embodiments, the skin filler includes a low molecular weight hyaluronic acid polymer. In a plurality of embodiments, the skin filler includes sodium acetylated hyaluronate. In a plurality of embodiments, the skin filler includes glycolic acid. In a plurality of embodiments, the skin filler includes lactic acid. In a plurality of embodiments, the skin filler includes L-lactic acid. In a plurality of embodiments, the skin filler includes amino acids. In a plurality of embodiments, the skin filler includes NIA-114™. In a plurality of embodiments, the skin filler includes acetylated peptides. In a plurality of embodiments, the skin filler includes Activen™ XEP-18. In a plurality of embodiments, the skin filler includes Erasa™ XEP-30.

[0042]

[0046] In a plurality of embodiments, the first composition includes Spongilla, and the second composition The article contains an effective amount of a dermal filler selected from one or more commercially available dermal fillers for treating skin diseases or skin conditions in a subject. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Restylane®. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Restylane® Lyft (Perlane®-L). In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Restylane® Refyne. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Restylane® Defyne. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Restylane® Silk. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Belotero® Hydro. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Belotero® Soft. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Belotero® Balance. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Captique™. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Esthelis™. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Fortelis™. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Modelis™. In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Elevess® (Hydrelle®). In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Hylaform® (Hylan B Gel). In a plurality of embodiments, the first composition contains Spongilla, and the second composition contains Puragen™.In multiple embodiments, the first composition comprises Spongilla and the second composition comprises Prevelle® Silk. In multiple embodiments, the first composition comprises Spongilla and the second composition comprises Radiesse®. In multiple embodiments, the first composition comprises Spongilla and the second composition comprises Radiesse®(+). In multiple embodiments, the first composition comprises Spongilla and the second composition comprises Aquamid®. In multiple embodiments, the first composition comprises Spongilla and the second composition comprises Sculptura®. In multiple embodiments, the first composition comprises Spongilla and the second composition comprises Bellafill®. In multiple embodiments, the first composition comprises Spongilla and the second composition comprises Juvaderm®.

[0043]

[0047] In multiple embodiments, the second composition comprises deoxycholic acid. Deoxycholic acid is also known as cholanic acid and 3a,12a-dihydroxy-5β-cholan-24-oic acid.

[0044]

[0048] In multiple embodiments, provided herein is a first composition comprising Spongilla and a second composition comprising an effective amount of one or more dermal fillers effective to treat a disease or condition in a subject, including a skin condition or a skin disease. In multiple embodiments, provided herein is a kit comprising a first composition comprising Spongilla and a second composition comprising an effective amount of one or more dermal fillers effective to treat a condition in a subject, including a skin condition. In multiple embodiments, provided herein is a product comprising a first composition and a second composition, wherein the first composition comprises Spongilla, and the second composition comprises an effective amount of one or more dermal fillers effective to treat a skin disease or a skin condition in a subject, and the second composition is present in the form of a solution, an aqueous solution, a powder, or a hydrogel.

[0045] ​​​

[0049] In another embodiment, the disease or condition comprising a skin disease or condition is a human immune system disorder. Any of the dermal filler compositions or kits disclosed herein are provided for treating lipoatrophy, facial wrinkles, grooves, hollows, augmentation of existing face, body, or limb structures, improvement of nose function, and / or cheek augmentation due to immunodeficiency virus infection or acne scarring. In another aspect, any of the dermal filler compositions or kits disclosed herein are provided for treating the disease or condition selected from correction of fine, moderate, and / or severe wrinkles or grooves of the skin in the areas of the face, lips, nose, under-eye area, eyebrows, head, chin, neck, ears, earlobes, décolleté, elbows, hands, feet, and knees. In another aspect, any of the dermal filler compositions or kits disclosed herein are provided for treating the disease or condition selected from correction and / or modification of the shape of certain areas of the areas of the face, lips, nose, under-eye area, eyebrows, head, chin, neck, ears, earlobes, décolleté, elbows, hands, feet, and knees. In another aspect, there is provided any of the dermal filler compositions or kits disclosed herein, wherein the disease or condition, including the skin disease or condition, is improvement of the moderate to severe convex or hypertrophied appearance associated with submental adipose tissue or fat.

[0046]

[0050] In another embodiment, the disease or condition, including a skin disease or condition, is characterized by an increase in lip volume. Provided is any of the skin filler compositions or kits disclosed herein, selected from correcting strong perioral wrinkles, moderate to severe facial grooves and wrinkles, such as nasolabial folds, moderate to severe facial wrinkles, such as smile lines or marionette lines, midfacial contour deficiencies due to aging, lack of three-dimensionality, the dorsum of the hand to be corrected for lack of three-dimensionality, glabellar wrinkles, correction of facial depressions caused by injury or due to aging, perioral wrinkles, commissures of the lips, crow's feet, forehead wrinkles, soft tissue contour deficiencies, acne scars, moderate to severe stretchable facial acne scars on the cheeks, reduction of three-dimensionality due to aging, facial adipose tissue atrophy or lipoatrophy in HIV+ patients, and improvement of moderate to severe convex or hypertrophic appearance or enlargement related to the adipose tissue or fat under the chin. In another embodiment, provided is any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is lip enhancement. In another embodiment, provided is any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is perioral wrinkles. In another embodiment, provided is any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is moderate to severe facial grooves and wrinkles, such as nasolabial folds. In another embodiment, provided is any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is moderate to severe facial wrinkles, such as smile lines or marionette lines. In another embodiment, provided is any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is midfacial contour deficiencies due to aging. In another embodiment, provided is any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is the dorsum of the hand to be corrected for lack of three-dimensionality. In another embodiment, provided is any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is glabellar wrinkles. In another embodiment, provided is any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is correction of facial depressions caused by injury or due to aging. In another embodiment, provided is any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is perioral wrinkles.In another embodiment, there is provided any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is lip commissure. In another embodiment, there is provided any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is crow's feet. In another embodiment, there is provided any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is forehead wrinkles. In another embodiment, the disease or condition is a soft tissue contour defect, as disclosed herein. In another embodiment, there is provided any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is acne scar. In another embodiment, there is provided any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is moderate to severe stretchable facial acne scars on the cheeks. In another embodiment, there is provided any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is loss of three-dimensionality due to aging. In another embodiment, there is provided any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is facial adipose tissue atrophy or lipoatrophy in HIV+ patients. In another embodiment, there is provided any of the pharmaceutical products or kits disclosed herein, wherein the disease or condition is improvement of a moderate to severe convex or hypertrophic appearance related to the adipose tissue or fat under the chin.

[0047]

[0051] In another embodiment, one or more dermal fillers are chemical compounds, chemical compounds Provided are any of the skin filler compositions or kits disclosed herein, selected from mixtures, biopolymers, or extracts made from biological materials. In another aspect, provided is any of the skin filler compositions or kits disclosed herein, wherein the one or more skin fillers are biopolymers. In another aspect, provided is any of the skin filler compositions or kits disclosed herein, wherein the one or more skin fillers are chemical compounds. In another aspect, provided is any of the skin filler compositions or kits disclosed herein, wherein the one or more skin fillers are mixtures of chemical compounds. In another aspect, provided is any of the skin filler compositions or kits disclosed herein, wherein the one or more skin fillers are biopolymers. In another aspect, provided is any of the skin filler compositions or kits disclosed herein, wherein the one or more skin fillers are extracts made from biological materials. Method

[0052] In one aspect, a method for treating or preventing one or more skin conditions or skin diseases in a subject is provided herein, comprising delivering a therapeutically effective or prophylactically effective amount of a skin filler to the intradermal compartment of the subject's skin by applying to the subject's skin a first composition comprising Spongilla and a second composition comprising a therapeutically effective amount of one or or more skin fillers.

[0048]

[0053] In a plurality of embodiments, the disease or condition is adipose tissue atrophy, facial wrinkles, grooves, depressions is selected from enhancement of an existing facial, body, or limb structure, or improvement of nasal function. In multiple embodiments, the disease or condition is adipose tissue atrophy. In multiple embodiments, the adipose tissue atrophy is due to human immunodeficiency virus infection or acne scarring. In multiple embodiments, the disease or condition is facial wrinkles. In multiple embodiments, the disease or condition is grooves in the facial skin. In multiple embodiments, the disease or condition is skin grooves. In multiple embodiments, the disease or condition is treated by enhancement of an existing facial structure. In multiple embodiments, the disease or condition is treated by enhancement of an existing body structure. In multiple embodiments, the disease or condition is treated by enhancement of an existing limb structure. In multiple embodiments, the disease or condition is treated by improving nasal function.

[0049]

[0054] In another embodiment, the disease or condition is selected from enhancement of the lips, perioral wrinkles, moderate to severe facial grooves and wrinkles, such as nasolabial folds, moderate to severe facial wrinkles, such as smile lines or marionette lines, correction of central facial contour deficiency due to aging, dorsum of the hand where three-dimensionality should be corrected, glabellar wrinkles, correction of facial depressions due to injury or aging, perioral wrinkles, commissure of the lips, crow's feet wrinkles, forehead wrinkles, soft tissue contour deficiency, acne scars, moderate to severe stretchable facial acne scars on the cheeks, loss of three-dimensionality due to aging, facial adipose tissue atrophy or lipoatrophy in HIV+ patients, improvement of moderate to severe convex or hypertrophic appearance or hypertrophy related to adipose tissue or fat under the chin. In another embodiment, the disease or condition is lip enhancement. Another In an embodiment, the disease or condition is perioral wrinkles. In another embodiment, the disease or condition is moderate to severe facial grooves and wrinkles, such as nasolabial folds. In another embodiment, the disease or condition is moderate to severe facial wrinkles, such as smile lines or marionette lines. In another embodiment, the disease or condition is loss of central facial contour due to aging. In another embodiment, the disease or condition is the dorsum of the hand where lack of three-dimensionality should be corrected. In another embodiment, the disease or condition is glabellar wrinkles. In another embodiment, the disease or condition is correction of facial depressions caused by injury or due to aging. In another embodiment, the disease or condition is perioral wrinkles. In another embodiment, the disease or condition is commissure of the lips. In another embodiment, the disease or condition is crow's feet. In another embodiment, the disease or condition is forehead wrinkles. In another embodiment, the disease or condition is soft tissue contour deficiency. In another embodiment, the disease or condition is acne scars. In another embodiment, the disease or condition is moderate to severe stretchable facial acne scars on the cheeks. In another embodiment, the disease or condition is loss of three-dimensionality due to aging. In another embodiment, the disease or condition is facial adipose tissue atrophy or lipoatrophy in HIV+ patients. In another embodiment, the disease or condition is improvement of moderate to severe convex or hypertrophic appearance related to adipose tissue or fat under the chin.

[0050]

[0055] Facial adipose tissue atrophy is a decrease in fatty or adipose tissue under the skin. Facial fat Adipose tissue atrophy may be directly caused by some antiretroviral drugs, including those used in the treatment of human immunodeficiency virus (HIV). Facial adipose tissue atrophy may also be caused by HIV infection, genetic nature, having high levels of triglycerides, and / or the natural aging process. The effectiveness of treatment regimens in subjects suffering from facial adipose tissue atrophy can be measured by methods known to those skilled in the art, including using a 4-point scale evaluation system. In this system, grade 1 is characterized by fat loss in a small local area, grade 2 involves a larger area than the small local area of grade 1 being affected (usually including the jaw or the corners of the mouth), grade 3 is a larger area than grade 2, including darkening within the area, and grade 4 indicates severe lipoatrophy with muscle and / or bone protrusions.

[0051]

[0056] Acne scarring can occur in subjects suffering from acne. The effectiveness of treatment regimens in subjects suffering from acne scarring can be measured by methods known to those skilled in the art, including the Self-assessment of Clinical Acne-Related Scars (SCARS) tool and the Facial Acne Scar Quality of Life (FASQoL) tool.

[0052]

[0057] Facial wrinkles are a condition in a subject related to moderate to severe glabellar wrinkles associated with the activity of the corrugator supercilii and / or procerus muscles, moderate to severe lateral canthal wrinkles associated with the activity of the orbicularis oculi muscle, and / or moderate to severe forehead wrinkles associated with the activity of the frontalis muscle. 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).

[0053]

[0053]

[0058] Submental hypertrophy is excess fatty or adipose tissue under the skin in the area of ​​the lower jaw. It is an aesthetic condition. Excessive subcutaneous adipose tissue under the mandibular area creates a moderate to severe convex condition commonly known as a "double chin". The efficacy of the treatment regimen in subjects with submental hypertrophy was measured using a 5-point rating scale, with 0=none, 1=minimal, 2=moderate, 3=severe, and 4=extreme. Further evaluation of the treatment regimen efficacy was performed by using magnetic resonance imaging of the submental volume before and after treatment.

[0054]

[0059] Global Aesthetic Improvement Scale (Global Aesthetic Improvement Scale) Treatment of wrinkles or facial lines with spongilla and dermal fillers as assessed by the Generalized Aesthetic Improvement Scale (GAIS) scale rating. The 5-point GAIS scale for aesthetic improvement has five levels: very much improved, very much improved, improved, no change, and worsening. Data measured by standardized photographic documentation.

[0055]

[0060] Merz Aesthetic Scale (MA Treatment with Spongilla and Dermal Fillers for Deformities of the Face or Neck, including those with Loss of Three-Dimensional Shape, as assessed by a 5-point MAS scale ranging from 0 (no sagging), 1 (mild sagging), 2 (moderate sagging), 3 (severe sagging), and 4 (very severe sagging). The 5-point Merz scale is also applied to wrinkles, ranging from 0 (no wrinkles), 1 (mild wrinkles), 2 (moderate wrinkles), 3 (severe wrinkles), and 4 (very severe wrinkles). Data measured by standardized photographic documentation.

[0056]

[0061] In one embodiment, a first composition comprising Spongilla is applied to the skin of a subject. , followed by the step of applying a second composition comprising an effective amount of a skin filler, a method for promoting skin penetration of a topically applied skin filler composition in the skin of a subject is provided herein.

[0057]

[0062] In a plurality of embodiments, the first composition comprises Spongilla as described above. comprises.

[0063] In a plurality of embodiments, the second composition comprises a skin filler as described above.

[0058]

[0064] In a plurality of embodiments, the second composition comprises deoxycholic acid as described above. contains.

[0065] In a plurality of embodiments, the step of administering comprises applying the first composition to the skin of the subject in the form of a paste. In a plurality of embodiments, the paste comprises water, saline, or hydrogen peroxide. In a plurality of embodiments, the paste is prepared by mixing a powder comprising Spongilla with water, saline, or hydrogen peroxide.

[0059]

[0066] In a plurality of embodiments, the step of administering comprises applying the first composition to the skin of the subject in the form of a gel. In a plurality of embodiments, the gel comprises water, saline, or hydrogen peroxide. In a plurality of embodiments, the gel comprises Spongilla and water, saline, or hydrogen peroxide.

[0060]

[0067] In a plurality of embodiments, the step of applying the first composition is a part of the skin of the subject. ​​It includes rubbing in a paste or gel agent every minute. In a plurality of embodiments, this part is selected from a part of the face, lips, nose, area under the eyes, eyebrows, head, chin, neck, ears, earlobes, décolletage, elbows, hands, feet, and knees. In a plurality of embodiments, this part is a part of the face. In a plurality of embodiments, this part is a part of the lips. In a plurality of embodiments, this part is a part of the nose. In a plurality of embodiments, this part is a part of the area under the eyes. In a plurality of embodiments, this part is a part of the eyebrows. In a plurality of embodiments, this part is a part of the head. In a plurality of embodiments, this part is a part of the chin. In a plurality of embodiments, this part is a part of the neck. In a plurality of embodiments, this part is a part of the ears. In a plurality of embodiments, this part is a part of the earlobes. In a plurality of embodiments, this part is a part of the décolletage. In a plurality of embodiments, this part is a part of the elbows. In a plurality of embodiments, this part is a part of the hands. In a plurality of embodiments, this part is a part of the feet. In a plurality of embodiments, this part is a part of the knees.

[0061]

[0068] In another embodiment, before the second composition is applied to the skin of the subject, the first composition Provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed herein, wherein a substance is applied to the skin of a subject. In another embodiment, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed herein, wherein a first composition is applied to the skin of a subject before a second composition is applied to the same area of the skin of the subject. In another embodiment, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed herein, wherein a first composition is applied to the skin of a subject and dried on the skin of the subject before a second composition is applied to the skin of the subject. In another embodiment, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed herein, wherein the first composition is applied to the skin of the subject in the form of an aqueous paste, wherein the aqueous component may be water, saline, or hydrogen peroxide. In another embodiment, provided is any one of a method, a composition for use as a medicament, a dermal filler, and a kit, as disclosed herein, wherein the first composition is applied to the skin of the subject in the form of a gel, wherein the aqueous component may be water, saline, or hydrogen peroxide.

[0062]

[0069] In another aspect, the first composition is applied to the skin of the subject in the form of an aqueous paste , provided herein is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the aqueous portion may be derived from water or saline. In another aspect, provided herein is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the aqueous paste further comprises hydrogen peroxide. In another aspect, provided herein is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein an aqueous solution of hydrogen peroxide is applied to the subject's skin after the first composition has been applied to the subject's skin. In another aspect, provided herein is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the hydrogen peroxide is an aqueous solution. In another aspect, provided herein is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the aqueous solution comprises hydrogen peroxide at a concentration of about 3% by weight. In another aspect, provided herein is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the first composition is dried on the subject's skin.

[0063]

[0070] In another embodiment, provided herein is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein the subject applies a second composition comprising a dermal filler to the skin no more than once every three months.

[0064]

[0071] In another aspect, the first composition comprising Spongilla is administered at least Any of the methods disclosed herein is provided that is applied to the skin of a subject at least once for at least one week. In another aspect, a first composition comprising Spongilla is provided that is applied to the skin of a subject at least twice a week for at least one week, at least three times a week for at least one week, at least four times a week for at least one week, at least five times a week for at least one week, at least six times a week for at least one week, or at least seven times a week for at least one week, any of the methods disclosed herein.

[0065]

[0072] In another embodiment, a first composition comprising Spongilla is provided that is applied to the skin of a subject at least once a week for at least two weeks, any of the methods, compositions for use as a medicament, skin fillers, and kits disclosed herein. In another aspect, a first composition comprising Spongilla is provided that is applied to the skin of a subject at least once a week for at least three weeks, at least once a week for at least four weeks, at least Also, at least once for at least 5 weeks, at least once a week for at least 6 weeks, at least once a week for at least 7 weeks, at least once a week for at least 8 weeks, at least once a week for at least 9 weeks, at least once a week for at least 10 weeks, at least once a week for at least 11 weeks, 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 once a week for at least 22 weeks, at least once a week for at least 23 weeks, at least once a week for at least 24 weeks, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, which are applied to the skin of interest.

[0066]

[0073] In another embodiment, a first composition comprising Spongilla is once a week A second composition containing one or more dermal fillers is applied to the skin of a subject for 24 weeks, and is applied to the skin of the subject only during the first week of treatment. Any of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein are provided. In another aspect, a first composition containing Spongilla is applied to the skin of a subject once a week for 20 weeks, and a second composition containing one or more dermal fillers is applied to the skin of the subject only during the first week of treatment. Any of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein are provided. In another aspect, a first composition containing Spongilla is applied to the skin of a subject once a week for 16 weeks, and a second composition containing one or more dermal fillers is applied to the skin of the subject only during the first week of treatment. Any of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein are provided. In another aspect, a first composition containing Spongilla is applied to the skin of a subject once a week for 12 weeks, and a second composition containing one or more dermal fillers is applied to the skin of the subject only during the first week of treatment. Any of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein are provided. In another aspect, a first composition containing Spongilla is applied to the skin of a subject once a week for 8 weeks, and a second composition containing one or more dermal fillers is applied to the skin of the subject only during the first week of treatment. Any of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein are provided. In another aspect, a first composition containing Spongilla is applied to the skin of a subject once a week for 6 weeks, and a second composition containing one or more dermal fillers is applied to the skin of the subject only during the first week of treatment. Any of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein are provided.In another aspect, a first composition comprising Spongilla is applied to the skin of a subject once a week for four weeks, and a second composition comprising one or more dermal fillers is applied to the skin of the subject only during the first week of treatment. Provided is any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein.

[0067]

[0074] In another embodiment, a first composition comprising Spongilla and one or more dermal fillers are applied to the skin of the subject once a week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, once every eleven weeks, once every twelve weeks, once every thirteen weeks, once every fourteen weeks, once every fifteen weeks, once every sixteen weeks, once every seventeen weeks, once every eighteen weeks, once every nineteen weeks, once every twenty weeks, once every twenty - one weeks, once every twenty - two weeks, once every twenty - three weeks, once every twenty - four weeks, once every nine months, once every twelve months, once every fifteen months, once every eighteen months Provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, which are applied to the skin of interest once every time, once every 21 months, or once every 24 months. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest in combination once every 3 months, once every 6 months, once every 9 months, once every 12 months, once every 15 months, once every 18 months, once every 21 months, or once every 24 months. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest in combination once a week. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest in combination once every two weeks. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest in combination once every three weeks. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest in combination once every four weeks. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest in combination once every five weeks.In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every six weeks. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every seven weeks. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every eight weeks. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every nine weeks. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every ten weeks. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every eleven weeks. In another embodiment, provided is any one of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein, wherein a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every twelve weeks.In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are used for 13 weeks. Provided is any one of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein, which are applied to the skin of interest once every time in combination. In another embodiment, provided is any one of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest once every 14 weeks in combination. In another embodiment, provided is any one of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest once every 15 weeks in combination. In another embodiment, provided is any one of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest once every 16 weeks in combination. In another embodiment, provided is any one of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest once every 17 weeks in combination. In another embodiment, provided is any one of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest once every 18 weeks in combination. In another embodiment, provided is any one of the methods, compositions for use as medicaments, dermal fillers, and kits disclosed herein, wherein a first composition containing Spongilla and a second composition containing one or more dermal fillers are applied to the skin of interest once every 19 weeks in combination.In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the subject's skin in combination once every 20 weeks, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided. In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the subject's skin in combination once every 21 weeks, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided. In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the subject's skin in combination once every 22 weeks, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided. In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the subject's skin in combination once every 23 weeks, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided. In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the subject's skin in combination once every 24 weeks, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided. In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the subject's skin in combination once every 9 months, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided. In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the subject's skin in combination once every 12 months, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided.In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every 15 months, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided. Another embodiment. In an embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every 18 months, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided. In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every 21 months, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided. In another embodiment, a first composition comprising Spongilla and a second composition comprising one or more dermal fillers are applied to the skin of a subject in combination once every 24 months, and any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided.

[0068]

[0075] In another embodiment, any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided, where the skin of the subject is washed with a non-comedogenic cleanser, water, or a combination of a non-comedogenic cleanser and water following application of the first composition comprising Spongilla. In another embodiment, any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided, where the skin of the subject is washed with a non-comedogenic cleanser, water, or a combination of a non-comedogenic cleanser and water following application of the second composition comprising one or more dermal fillers to the skin of the subject. The non-comedogenic cleanser is prepared such that it does not cause blocked pores in the skin to which such cleanser is applied. for use as a medicament, dermal fillers, and kits disclosed herein are provided, where the skin of the subject is washed with a non-comedogenic cleanser, water, or a combination of a non-comedogenic cleanser and water following application of the first composition comprising Spongilla. In another embodiment, any of the methods, compositions for use as a medicament, dermal fillers, and kits disclosed herein are provided, where the skin of the subject is washed with a non-comedogenic cleanser, water, or a combination of a non-comedogenic cleanser and water following application of the second composition comprising one or more dermal fillers to the skin of the subject. The non-comedogenic cleanser is prepared such that it does not cause blocked pores in the skin to which such cleanser is applied.

[0069]

[0076] In another aspect, the methods disclosed herein include Any of the compositions, pharmaceutical products and kits are provided, wherein the subject is a human.

[0077] Treatment with the compositions of the embodiments recited herein above is Contraindicated for patients with sensitivity to any / all of the compositions containing ngilla, dermal fillers, preservative agents and / or reconstitution agents. Patients may have allergies, active infections, glabellar necrosis, allergies to lidocaine, allergies or sensitivities to any dermal filler ingredients, allergies or sensitivities to Spongilla, allergies or sensitivities to any anaerobic or aerobic bacterial proteins or molecules, or may be pregnant or nursing. Kit

[0078] In another embodiment, a kit is provided that includes a first composition and a second composition, Here, the first composition comprises Spongilla and the second composition comprises one or more dermal fillers. In another embodiment, provided is any of the kits described herein further comprising instructions for handling the first and second compositions in the treatment of a subject having a skin disorder condition. In another embodiment, provided is any of the kits described herein, wherein the first composition comprises Spongilla in powder form. In another embodiment, provided is any of the kits described herein, wherein Spongilla is in powder form comprising particles of substantially uniform size. In an embodiment, the second composition comprises one or more dermal fillers. In another embodiment, provided is any of the kits described herein, wherein the dermal filler is selected from a chemical compound, a mixture of chemical compounds, an extract made from a biopolymer or a biomaterial. In another embodiment, provided is any of the kits described herein, wherein the one or more dermal fillers are chemical compounds. In another embodiment, provided is any of the kits described herein, wherein the one or more dermal fillers are biopolymers. In another embodiment, provided is any of the kits described herein, wherein the one or more dermal fillers are extracts made from biomaterials.

[0070]

[0079] In another aspect, a kit comprising a first composition, a second composition and a third composition is provided, wherein the first composition comprises Spongilla, the second composition comprises one or more dermal fillers, and the third composition comprises a reagent for the reconstitution of Spongilla. In another embodiment, provided is any of the kits described herein further comprising instructions for handling the first, second, and third compositions in the treatment of a subject having a skin disorder condition. In another embodiment, provided is any of the kits described herein, wherein the first composition comprises Spongilla in powder form. In another embodiment, provided is any of the kits described herein, wherein Spongilla is in powder form comprising particles of substantially uniform size. In an embodiment, the second composition comprises one or more dermal fillers. In another embodiment, provided is any of the kits described herein, wherein the dermal filler is selected from chemical compounds, mixtures of chemical compounds, biopolymers, or extracts made from biological materials. In another embodiment, provided is any of the kits described herein, wherein the one or more dermal fillers are chemical compounds. In another embodiment, provided is any of the kits described herein, wherein the one or more dermal fillers are biopolymers. In another embodiment, provided is any of the kits described herein, wherein the one or more dermal fillers are extracts made from biological materials. In another embodiment, provided is any of the kits described herein, wherein the one or more reconstitution reagents are saline or buffered saline. In another embodiment, provided is any of the kits described herein, wherein the one or more reconstitution reagents are hydrogels.

[0071]

[0080] In another aspect, a kit comprising a first composition, a second composition, and a third composition is provided, wherein the first composition comprises Spongilla, the second composition comprises one or more skin fillers, and the third composition comprises a preservative reagent. In another embodiment, provided is any of the kits described herein further comprising instructions for handling the first, second, and third compositions in the treatment of a subject having a skin disorder condition. In another embodiment, provided is any of the kits described herein, wherein the first composition comprises Spongilla in powder form. In another embodiment, provided is any of the kits described herein, wherein Spongilla is in powder form comprising particles of substantially uniform size. In an embodiment, the second composition comprises one or more skin fillers. In another embodiment, provided is any of the kits described herein, wherein the skin filler is selected from a chemical compound, a mixture of chemical compounds, an extract made from a biopolymer or a biomaterial. In another embodiment, provided is any of the kits described herein, wherein the one or more skin fillers are chemical compounds. In another embodiment, provided is any of the kits described herein, wherein the one or more skin fillers are biopolymers. In another embodiment, provided is any of the kits described herein, wherein the one or more skin fillers are extracts made from biomaterials. In another embodiment, provided is any of the kits described herein, wherein the one or more preservative reagents are hydrogen peroxide solutions. In another embodiment, provided is any of the kits described herein, wherein the one or more preservative reagents are hydrogels containing hydrogen peroxide. In another embodiment, provided is any of the kits described herein, wherein the one or more preservative reagents are non-comedogenic cleansers. In another embodiment, provided is any of the kits described herein, wherein the one or more preservative reagents are solutions of isopropyl alcohol.In another embodiment, any of the kits described herein are provided, where the one or more antiseptic reagents include, but are not limited to, any acceptable skin antiseptic commonly used in surgery, including chlorhexidine, chlorhexidine gluconate, iodine, hexachlorophene, benzalkonium chloride, and any reconstitutions thereof.

[0072]

[0081] In another aspect, the first composition, the second composition, the third composition, and the fourth composition A kit is provided that includes an article, where the first composition includes Spongilla, the second composition includes one or more skin fillers, the third composition includes a reagent for the reconstitution of Spongilla, and the fourth composition includes a preservative reagent. In another embodiment, provided is any of the kits described herein that further includes instructions for handling the first, second, third, and fourth compositions in the treatment of a subject having a skin disorder condition. In another embodiment, provided is any of the kits described herein where the first composition includes Spongilla in powder form. In another embodiment, provided is any of the kits described herein where Spongilla is in powder form comprising particles of substantially uniform size. In an embodiment, the second composition includes one or more skin fillers. In another embodiment, provided is any of the kits described herein where the skin filler is selected from a chemical compound, a mixture of chemical compounds, a biopolymer, or an extract made from a biological material. In another embodiment, provided is any of the kits described herein where one or more skin fillers are chemical compounds. In another embodiment, provided is any of the kits described herein where one or more skin fillers are biopolymers. In another embodiment, provided is any of the kits described herein where one or more skin fillers are extracts made from biological materials. In another embodiment, provided is any of the kits described herein where one or more reconstitution reagents are saline or buffered saline. In another embodiment, provided is any of the kits described herein where one or more reconstitution reagents are hydrogels. In another embodiment, provided is any of the kits described herein where one or more preservative reagents are hydrogen peroxide solutions. In another embodiment, provided is any of the kits described herein where one or more preservative reagents are hydrogels containing hydrogen peroxide. In another embodiment, provided is any of the kits described herein where one or more preservative reagents are non-comedogenic cleansers.In another embodiment, any of the kits described herein is provided, wherein one or more of the antiseptic reagents is a solution of isopropyl alcohol. In another embodiment, any of the kits described herein is provided, wherein one or more of the antiseptic reagents is any acceptable skin antiseptic commonly used in surgery, including but not limited to chlorhexidine, chlorhexidine gluconate, iodine, hexachlorophene, benzalkonium.

[0073]

[0082] In another embodiment, any of the kits described herein is provided, wherein more than 50% of the particles comprising Spongilla powder pass through a US 7 0 mesh screen.

[0074]

[0083] In another embodiment, any of the kits described herein is provided, wherein about 50% or more of the particles comprising Spongilla powder pass through a US 70 mesh screen. Another embodiment is a method in which about 60% or more, or about 70% or more, or about 75% or more, or about 80% or more, or about 85% or more, or about 90% or more, or about 95% or more, or about 96% or more, or about 97% or more, or about 98% or more, or about 99% or more of the particles comprising Spongilla powder pass through a US 70 mesh screen. In another embodiment, any of the kits disclosed herein is provided, wherein about 95% or more, or about 96% or more, or 97% or more, or about 98% or more, or about 99% or more of the particles comprising Spongilla powder pass through a US 70 mesh screen. In another embodiment, any of the kits disclosed herein is provided, wherein about 95% or more of the particles comprising Spongilla powder pass through a US 70 mesh screen. In another embodiment, about 96% or more of the particles comprising Spongilla powder pass through a US Any of the kits disclosed herein that pass through a 70-mesh screen are provided. In another embodiment, any of the kits disclosed herein are provided, wherein at least about 97% of the particles comprising Spongilla powder pass through a US 70-mesh screen. In another embodiment, any of the kits disclosed herein are provided, wherein at least about 98% of the particles comprising Spongilla powder pass through a US 70-mesh screen. In another embodiment, any of the kits disclosed herein are provided, wherein at least about 99% of the particles comprising Spongilla powder pass through a US 70-mesh screen.

[0075]

[0084] In another embodiment, the particles comprising Spongilla powder are from about 50 μm to about 5 Any of the kits disclosed herein having an average length of 00 μm is provided. In another embodiment, particles comprising 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 350 μm, or about 100 μm to about 450 μm, or about 100 μm to about 400 μm, or about 100 μm to about 350 μm, or about 100 μm to about 300 μm, or about 100 μm to about 250 μm, or about 100 μm to about 200 μm, or about 150 μm to about 500 μm, or about 100 μm to about 450 μm, or about 150 μm to about 400 μm, or about 150 μm to about 350 μm, or about 150 μm to about 350 μm, or about 150 μm to about 300 μm, or about 150 μm to about 250 μm, or about 150 μm to about 200 μm, or about 175 μm to 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, and any of the kits disclosed herein is provided. In another embodiment, particles comprising Spongilla powder have an average length of about 50 μm, or about 75 μm, or about 80 μm, or about 85 μm, or about 90 μm, or about 100 μm, or about 125 μm, or about 150 μm, or about 175 μm, or about 200 μm, or about 225 μm, or about 250 μm, or about 300 μm, or about 350 μm, or about 400 μm, or about 450 μm, or about 500 μm, and any of the kits disclosed herein is provided. In another embodiment, particles comprising Spongilla powder have an average length of about 200 μm, and any of the kits disclosed herein is provided.

[0076]

[0085] In another embodiment, any of the kits disclosed herein are provided, wherein the particles comprising Spongilla powder have an average diameter of from about 5 μm to about 50 μm. In another embodiment, any of the kits disclosed herein are provided, wherein the particles comprising Spongilla powder have an average diameter of from about 5 μm to about 45 μm, or from about 5 μm to about 40 μm, from about 5 μm to about 35 μm, from about 5 μm to about 30 μm, from about 5 μm to about 25 μm, from about 5 μm to about 20 μm, from about 10 μm to about 45 μm, from about 10 μm to about 40 μm, from about 10 μm to about 35 μm, from about 10 μm to about 30 μm, from about 10 μm to about 25 μm, from about 10 μm to about 20 μm. In another embodiment, any of the kits disclosed herein are provided, wherein the particles comprising Spongilla powder have an average diameter of about 5 μm, or about 10 μm, or about 15 μm, or about 20 μm, or about 25 μm, or about 30 μm, or about 35 μm, or about 40 μm, or about 45 μm, or about 50 μm.

[0077]

[0086] In another embodiment, any of the kits disclosed herein are provided, wherein the particles comprising Spongilla powder have an embodiment ratio of from about 1 to about 100. In another embodiment, any of the kits disclosed herein are provided, wherein the particles comprising Spongilla powder have an embodiment ratio of from about 1 to about 75, or from about 1 to about 5 Any of the kits disclosed herein having an embodiment ratio of 0, or from about 1 to about 25, or from about 1 to about 20, or from about 1 to about 15, or from about 5 to about 100, or from about 5 to about 75, or from about 5 to about 50, or from about 5 to about 40, or from about 5 to about 35, or from about 5 to about 30, or from about 5 to about 25, or from about 5 to about 20, or from about 5 to about 15, or from about 7 to about 50, or from about 7 to about 45, or from about 7 to about 40, or from about 7 to about 35, or from about 7 to about 30, or from about 7 to about 25, or from about 10 to about 50, or from about 10 to about 45, or from about 10 to about 40, or from about 10 to about 35, or from about 10 to about 30, or from about 10 to about 25, or from about 10 to about 15 are provided. In another embodiment, any of the kits disclosed herein having an embodiment ratio of particles comprising Spongilla powder of about 5, or about 6, or about 7, or about 8, or about 9, or about 10, or about 11, or about 12, or about 13, or about 14, or about 15, or about 16, or about 17, or about 18, or about 19, or about 20, or about 21, or about 22, or about 23, or about 24, or about 25, or about 26, or about 27, or about 28, or about 29, or about 30, or about 35, or about 40, or about 45, or about 50, or about 75, or about 100 are provided.

[0078]

[0087] In another embodiment, the first composition has a residual moisture content of about 20% or less. Any of the kits disclosed herein is provided. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition has a residual moisture content of about 15% or less, or about 10% or less, or about 9% or less, or about 8% or less, or about 7% or less, or about 6% or less, or about 5% or less, or about 4% or less, or about 3% or less, or about 2%, or 1% or less. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition has a residual moisture content of about 5% or less. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition has a residual moisture content of about 4% or less. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition has a residual moisture content of about 3% or less. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition has a residual moisture content of about 2% or less. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition has a residual moisture content of about 1% or less.

[0079]

[0088] In another embodiment, the first composition has a total content of aerobic and anaerobic microorganisms of about 25×10 4 colony forming units / gram (CFU / g) or less. Any of the kits disclosed herein is provided, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 10×10 4 CFU / g or less, or 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 3Provided is any of the kits disclosed herein having a total content of aerobic and anaerobic microorganisms of less than CFU / g, or less than about 10,000 CFU / g, or less than about 7,500 CFU / g, or less than about 5,000 CFU / g, or less than about 2,500 CFU / g, or less than about 2,000 CFU / g, or less than about 1,500 CFU / g, or less than about 1,000 CFU / g, or less than about 750 CFU / g, or less than about 500 CFU / g, or less than about 250 CFU / g, or less than about 200 CFU / g, or less than about 150 CFU / g, or less than about 100 CFU / g, or less than about 75 CFU / g, or less than about 50 CFU / g, or less than about 25 CFU / g, or less than about 15 CFU / g, or less than about 10 CFU / g, or less than about 5 CFU / g, or less than about 1 CFU / g. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of less than about 1,000 CFU / g. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of less than about 750 CFU / g. In another embodiment, the first composition has a total content of aerobic and anaerobic micro Provided is any of the kits disclosed herein having a total biological content. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 250 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 200 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 150 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 100 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 75 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 50 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 25 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 20 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 10 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total content of aerobic and anaerobic microorganisms of about 1 CFU / g or less.

[0080]

[0089] In another embodiment, the first composition is about 25×10 4 colony forming units / gram Any of the kits disclosed herein having a total yeast and mold content of less than about 5×10 4 CFU / g, or less than about 1×10 4 CFU / g, or less than about 5×10 3 CFU / g, or less than about 1×10 3Provided is any of the kits disclosed herein having a total yeast and mold content of less than 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, provided is any of the kits disclosed herein, wherein the first composition has a total yeast and mold content of about 1,000 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total yeast and mold content of about 750 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total yeast and mold content of about 500 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total yeast and mold content of about 250 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total yeast and mold content of about 200 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total yeast and mold content of about 150 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total yeast and mold content of about 100 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein, wherein the first composition has a total yeast and mold content of about 75 CFU / g or less, disclosed herein One of the kits is provided. In another embodiment, one of the kits disclosed herein is provided, wherein the first composition has a total yeast and mold content of about 50 CFU / g or less. In another embodiment, one of the kits disclosed herein is provided, wherein the first composition has a total yeast and mold content of about 25 CFU / g or less. In another embodiment, one of the kits disclosed herein is provided, wherein the first composition has a total yeast and mold content of about 20 CFU / g or less. In another embodiment, one of the kits disclosed herein is provided, wherein the first composition has a total yeast and mold content of about 10 CFU / g or less. In another embodiment, one of the kits disclosed herein is provided, wherein the first composition has a total yeast and mold content of about 1 CFU / g or less.

[0081]

[0090] In another embodiment, one of the kits disclosed herein is provided, wherein the content of Escherichia coli-type bacteria in the first composition is about 25×10 4 colony forming units per gram (CFU / g) or less. In another embodiment, the content of Escherichia coli-type bacteria in the first composition is 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 3Provided is any of the kits disclosed herein that is less than CFU / g, or less than about 10,000 CFU / g, or less than about 7,500 CFU / g, or less than about 5,000 CFU / g, or less than about 2,500 CFU / g, or less than about 2,000 CFU / g, or less than about 1,500 CFU / g, or less than about 1,000 CFU / g, or less than about 750 CFU / g, or less than about 500 CFU / g, or less than about 250 CFU / g, or less than about 200 CFU / g, or less than about 150 CFU / g, or less than about 100 CFU / g, or less than about 75 CFU / g, or less than about 50 CFU / g, or less than about 25 CFU / g, or less than about 15 CFU / g, or less than about 10 CFU / g, or less than about 5 CFU / g, or less than about 1 CFU / g. In another embodiment, provided is any of the kits disclosed herein that the content of Escherichia coli-type bacteria in the first composition is less than about 1,000 CFU / g. In another embodiment, provided is any of the kits disclosed herein that the content of Escherichia coli-type bacteria in the first composition is less than about 750 CFU / g. In another embodiment, provided is any of the kits disclosed herein that the content of Escherichia coli-type bacteria in the first composition is less than about 500 CFU / g. In another embodiment, provided is any of the kits disclosed herein that the content of Escherichia coli-type bacteria in the first composition is less than about 250 CFU / g. In another embodiment, provided is any of the kits disclosed herein that the content of Escherichia coli-type bacteria in the first composition is less than about 200 CFU / g. In another embodiment, provided is any of the kits disclosed herein that the content of Escherichia coli-type bacteria in the first composition is less than about 150 CFU / g. In another embodiment, provided is any of the kits disclosed herein that the content of Escherichia coli-type bacteria in the first composition is less than about 100 CFU / g. In another embodiment, provided is any of the kits disclosed herein that the content of Escherichia coli-type bacteria in the first composition is less than about 75 CFU / g. In another embodiment, provided is any of the kits disclosed herein that the content of Escherichia coli-type bacteria in the first composition is less than about 50 CFU / g.In another embodiment, any of the kits disclosed herein is provided, wherein the content of Escherichia coli-type bacteria in the first composition is about 25 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the content of Escherichia coli-type bacteria in the first composition is about 20 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the content of Escherichia coli-type bacteria in the first composition is about 10 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the content of Escherichia coli-type bacteria in the first composition is about 1 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition does not have a detectable content of Escherichia coli-type bacteria.

[0082]

[0091] In another embodiment, the content of Salmonella in the first composition is about 25 ×10 4 colony forming units per gram (CFU / g) or less, and any of the kits disclosed herein is provided. In another embodiment, the content of Salmonella in the first composition is 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 3Provided is any of the kits disclosed herein that is less than 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, provided is any of the kits disclosed herein wherein the Salmonella content of the first composition is about 1,000 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein wherein the Salmonella content of the first composition is about 750 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein wherein the Salmonella content of the first composition is about 500 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein wherein the Salmonella content of the first composition is about 250 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein wherein the Salmonella content of the first composition is about 200 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein wherein the Salmonella content of the first composition is about 150 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein wherein the Salmonella content of the first composition is about 100 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein wherein the Salmonella content of the first composition is about 75 CFU / g or less.In another embodiment, any of the kits disclosed herein is provided, wherein the Salmonella content of the first composition is about 50 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the Salmonella content of the first composition is about 25 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the Salmonella content of the first composition is about 20 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the Salmonella content of the first composition is about 10 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the Salmonella content of the first composition is about 1 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition has no detectable content of Salmonella.

[0083]

[0092] In another embodiment, the content of Pseudomonas aeruginosa bacteria in the first composition is about 25×10 4 colony forming units / gram (CFU / g) or less, and any of the kits disclosed herein is provided. In another embodiment, the content of Pseudomonas aeruginosa bacteria in the first composition is 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 3 CFU / g or less, or about 10,000 CFU / g or less, or about 7,500 CFU / g or less, or about 5,000 CFU / g or less, or about 2,500 CFU / g or less, or about 2,000 CFU / g or less, or about 1,500 CFU / g or less, or about 1,000 CFU / g or less, or about 750 CFU / g or less, or Provided is any of the kits disclosed herein that is at 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, provided is any of the kits disclosed herein in which the content of Pseudomonas aeruginosa bacteria in the first composition is about 1,000 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein in which the content of Pseudomonas aeruginosa bacteria in the first composition is about 750 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein in which the content of Pseudomonas aeruginosa bacteria in the first composition is about 500 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein in which the content of Pseudomonas aeruginosa bacteria in the first composition is about 250 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein in which the content of Pseudomonas aeruginosa bacteria in the first composition is about 200 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein in which the content of Pseudomonas aeruginosa bacteria in the first composition is about 150 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein in which the content of Pseudomonas aeruginosa bacteria in the first composition is about 100 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein in which the content of Pseudomonas aeruginosa bacteria in the first composition is about 75 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein in which the content of Pseudomonas aeruginosa bacteria in the first composition is about 50 CFU / g or less.In another embodiment, any of the kits disclosed herein is provided, wherein the content of Pseudomonas aeruginosa bacteria in the first composition is about 25 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the content of Pseudomonas aeruginosa bacteria in the first composition is about 20 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the content of Pseudomonas aeruginosa bacteria in the first composition is about 10 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the content of Pseudomonas aeruginosa bacteria in the first composition is about 1 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition has no detectable content of Pseudomonas aeruginosa bacteria.

[0084]

[0093] In another embodiment, the content of Staphylococcus aure us bacteria in the first composition is about 25×10 4 colony forming units / gram (CFU / g) or less, and any of the kits disclosed herein is provided. In another embodiment, the content of Staphylococcus aureus bacteria in the first composition is 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 3CFU / g or less, or about 10,000 CFU / g or less, or about 7,500 CFU / g or less, or about 5,000 CFU / g or less, or about 2,500 CFU / g or less, or about 2,000 CFU / g or less, or about 1,500 CFU / g or less, or about 1,000 CFU / g or less, or about 750 CFU / g or less, or about 500 CFU / g or less, or about 250 CFU / g or less, or about 200 CFU / g or less, or about 150 CFU / g or less, or about 100 CFU / g or less, or about 75 CFU / g or less, or about 50 CFU / g or less, or about 25 CFU / g or less, or about 15 CFU / g or less, or about 10 CFU / g or less, or about 5 CFU / g or less, or about 1 CF Provided is any of the kits disclosed herein that is below U / g. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 1,000 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 750 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 500 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 250 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 200 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 150 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 100 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 75 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 50 CFU / g or less. In another embodiment, provided is any of the kits disclosed herein where the Staphylococcus aureus bacterial content of the first composition is about 25 CFU / g or less.In another embodiment, any of the kits disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 20 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the Staphylococcus aureus bacterial content of the first composition is about 10 CFU / g or less. In another embodiment, the Staphylococcus. any of the kits disclosed herein is provided, wherein the aureus bacterial content of the first composition is about 1 CFU / g or less. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition has no detectable content of Staphylococcus aureus bacteria.

[0085]

[0094] In another embodiment, any of the kits disclosed herein is provided, wherein the first composition is packaged prior to use. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition is prepared by heating to at least about 70°C prior to packaging. In another embodiment, any of the kits disclosed herein is provided, wherein the first composition is prepared by heating to at least about 50°C, or at least about 60°C, or at least about 75°C, or at least about 80°C, or at least about 85°C, or at least about 90°C, or at least about 100°C, or at least about 110°C, or at least about 115°C, or at least about 120°C, or at least about 125°C, or at least about 130°C, or at least about 135°C, or at least about 140°C, or at least about 150°C, or at least about 160°C, or at least about 170°C, or at least about 180°C, or at least about 190°C, or at least about 200°C prior to packaging.

[0086]

[0095] In another embodiment, the first composition is heated to at least about 70°C prior to packaging. Provided is any of the kits disclosed herein that are prepared by heating for at least about 5 minutes. In another embodiment, the first composition, before being packaged, is heated to at least about 70° C. for at least about 10 minutes, or at least about 15 minutes, or at least about 20 minutes, or at least about 25 minutes, or at least about 30 minutes, or at least about 35 minutes, or at least about 40 minutes, or at least about 45 minutes, or at least about 50 minutes, or at least about 55 minutes, or at least about 60 minutes, or at least about 75 minutes, or at least about 90 minutes, or at least about 120 minutes, or at least about 180 minutes, or at least about 4 hours, or at least about 5 hours, or at least about 6 hours, or at least about 7 hours, or at least about 8 hours, or at least about 9 hours, or at least about 10 hours, or at least about 11 hours, or at least about 12 hours, or at least about 24 hours, and provided is any of the kits disclosed herein.

[0087]

[0096] In another embodiment, the first composition, before or after being packaged, is Any of the kits disclosed herein that are prepared by treatment with ionizing radiation, such as gamma radiation, are provided. For example, gamma irradiation can be performed on the untreated Spongilla material, after grinding to reduce particle size, before grinding to reduce particle size, on the material packaged in bulk, and / or on the material after packaging into unit dose containers. Materials containing the kits disclosed herein can be treated with ionizing radiation, such as gamma rays, using methods and equipment known to those skilled in the art, such as gamma irradiation devices or electron beam irradiation devices. In another embodiment, any of the kits disclosed herein are provided, wherein the first composition is prepared by treatment with ionizing radiation, such as gamma rays, that delivers a radiation dose absorbed between about 1 kGy and about 50 kGy prior to packaging. In another embodiment, the first composition is prepared by treatment with ionizing radiation, such as gamma rays, that delivers a radiation dose absorbed between about 1 kGy and about 45 kGy, or between about 1 kGy and about 40 kGy, between about 1 kGy and about 35 kGy, between about 1 kGy and about 30 kGy, or between about 1 kGy and about 25 kGy, or between about 5 kGy and about 50 kGy, or between about 5 kGy and about 45 kGy, or between about 5 kGy and about 40 kGy, or between about 5 kGy and about 35 kGy, or between about 5 kGy and about 30 kGy, or between about 5 kGy and about 25 kGy, or between about 10 kGy and about 50 kGy, or between about 10 kGy and about 45 kGy, or between about 10 kGy and about 40 kGy, or between about 10 kGy and about 35 kGy, or between about 10 kGy and about 30 kGy, or between about 10 kGy and about 25 kGy, or between about 15 kGy and about 50 kGy, or between about 15 kGy and about 45 kGy, or between about 15 kGy and about 40 kGy, or between about 15 kGy and about 35 kGy, or between about 15 kGy and about 30 kGy, or between about 15 kGy and about 25 kGy.In another embodiment, any of the kits disclosed herein are provided, which are prepared by treatment with ionizing radiation, such as gamma rays, that delivers a radiation dose absorbed at about 1 kGy, or about 5 kGy, or about 10 kGy, 11 kGy, or about 12 kGy, or about 13 kGy, or about 14 kGy, or about 15 kGy, or about 16 kGy, or about 17 kGy, or about 18 kGy, or about 19 kGy, or about 20 kGy, or about 21 kGy, or about 22 kGy, or about 23 kGy, or about 24 kGy, or about 25 kGy, or about 26 kGy, or about 27 kGy, or about 28 kGy, or about 29 kGy, or about 30 kGy, or about 31 kGy, or about 32 kGy, or about 33 kGy, or about 34 kGy, or about 35 kGy, or about 36 kGy, or about 37 kGy, or about 38 kGy, or about 39 kGy, or about 40 kGy, or about 41 kGy, or about 42 kGy, or about 43 kGy, or about 44 kGy, or about 45 kGy, or about 46 kGy, or about 47 kGy, or about 48 kGy, or about 49 kGy, or about 50 kGy.

[0088]

[0097] In another embodiment, any of the kits disclosed herein are provided, wherein the first composition further comprises an aqueous solution of hydrogen peroxide. In another embodiment, hydrogen peroxide is present in an amount of from about 0.1 wt% to about 50 wt%, or from about 0.1 wt% to about 45 wt%, or about 0.1 Any of the kits disclosed herein is provided at a concentration of from about 0.1 wt% to about 40 wt%, or from about 0.1 wt% to about 35 wt%, or from about 0.1 wt% to about 30 wt%, or from about 0.1 wt% to about 25 wt%, or from about 0.1 wt% to about 20 wt%, or from about 0.1 wt% to about 15 wt%, or from about 0.1 wt% to about 10 wt%, or from about 0.1 wt% to about 9 wt%, or from about 0.1 wt% to about 8 wt%, or from about 0.1 wt% to about 8 wt%, or from about 0.1 wt% to about 7 wt%, or from about 0.1 wt% to about 6 wt%, or from about 0.1 wt% to about 5 wt%, or from about 0.1 wt% to about 4 wt%, or from about 0.1 wt% to about 3 wt%, or from about 0.1 wt% to about 2 wt%, or from about 0.1 wt% to about 1 wt%, or from about 0.5 wt% to about 45 wt%, or from about 1 wt% to about 45 wt%, or from about 1 wt% to about 40 wt%, or from about 1 wt% to about 35 wt%, or from about 1 wt% to about 30 wt%, or from about 1 wt% to about 25 wt%, or from about 1 wt% to about 20 wt%, or from about 1 wt% to about 15 wt%, or from about 1 wt% to about 10 wt%, or from about 1 wt% to about 9 wt%, or from about 1 wt% to about 8 wt%, or from about 1 wt% to about 8 wt%, or from about 1 wt% to about 7 wt%, or from about 1 wt% to about 6 wt%, or from about 1 wt% to about 5 wt%, or from about 1 wt% to about 4 wt%, or from about 1 wt% to about 3 wt%, or from about 1 wt% to about 2 wt%, or from about 2 wt% to about 45 wt%, or from about 2 wt% to about 40 wt%, or from about 2 wt% to about 35 wt%, or from about 2 wt% to about 30 wt%, or from about 2 wt% to about 25 wt%, or from about 2 wt% to about 20 wt%, or from about 2 wt% to about 15 wt%, or from about 2 wt% to about 10 wt%, or from about 2 wt% to about 9 wt%, or from about 2 wt% to about 8 wt%, or from about 1 wt% to about 7 wt%, or from about 2 wt% to about 6 wt%, or from about 2 wt% to about 5 wt%, or from about 2 wt% to about 4 wt%, or from about 2 wt% to about 3 wt%.In another embodiment, any of the kits disclosed herein is provided wherein hydrogen peroxide is at a concentration of about 0.1 wt%, or about 0.5 wt%, or about 1 wt%, or about 2 wt%, or about 3 wt%, or about 4 wt%, or about 5 wt%, or about 6 wt%, or about 7 wt%, or about 8 wt%, or about 9 wt%, or about 10 wt%, or about 15 wt%, or about 20 wt%, or about 25 wt%, or about 30 wt%, or about 35 wt%, or about 40 wt%, or about 45 wt%, or about 50 wt%. In another embodiment, any of the methods disclosed herein is provided wherein hydrogen peroxide is at a concentration of about 3 wt%. As disclosed herein, an aqueous hydrogen peroxide solution that may be useful in treating the skin condition of a subject may be a commercially available product or may be prepared by methods known to those skilled in the art.

[0089]

[0098] In another embodiment, any of the kits disclosed herein is provided that further includes a gel or cream containing hydrogen peroxide. Such gels or creams are generally commercially available and may contain from about 0.5 wt% to about 50 wt% hydrogen peroxide. For example, a gel containing about 1 wt%, or about 2 wt%, or about 3 wt%, or about 4 wt%, or about 6 wt%, or about 7 wt%, or about 8 wt%, or about 9 wt%, or about 10 wt%, or about 15 wt%, or about 20 wt%, or about 25 wt%, or about 30 wt%, or about 40 wt%, or about 45 wt%, or about 50 wt% hydrogen peroxide can be combined with the first and second compositions and used in any of the methods and kits disclosed herein.

[0090]

[0090]

[0099] In another embodiment, any of the kits disclosed herein is provided wherein Spongilla is Spongilla lacus tris. tris. [000100]The compositions disclosed herein, such as the first composition containing Spongilla, may further comprise one or more conventional pharmaceutical carriers or excipients. Suitable pharmaceutical carriers and excipients include inert diluents, binders (such as starch), fillers (such as sugars including colloidal silicon dioxide, lactose, sucrose, mannitol or sorbitol, cellulose preparations such as corn starch, wheat starch, rice starch, potato starch, gelatin, gums, methylcellulose, hydroxypropylmethylcell ulose, carboxymethylcellulose, or polyvinylpyrrolidone (PVP)), bulking agents, lubricants (such as magnesium stearate, sodium dodecyl sulfate and talc), coloring agents or dyes, and, optionally, emulsifying or suspending agents in combination with a diluent such as water, saline, ethanol, propylene glycol, glycerin or combinations thereof.

[0091] [000101]In another embodiment, provided is any of the kits disclosed herein that further comprises a dermal filler comprising hyaluronic acid, calcium hydroxylapatite, polyalkylimide, polymethylmethacrylate, collagen, polymethylmethacrylate microspheres (PMMA), polylactic acid, polycaprolactone, carboxymethylcellulose, polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of poly-L-lactic acid. In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of hyaluronic acid. In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of calcium hydroxyapatite. In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of polyalkylimide. In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of polymethylmethacrylate. In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of collagen. In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of polymethylmethacrylate microspheres (PMMA). In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of polylactic acid. In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of polycaprolactone. In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of carboxymethylcellulose. In an embodiment, the dermal filler comprises polymers, copolymers, crosslinked polymers and / or crosslinked copolymers of poly-L-lactic acid.

[0092] [000102]In another embodiment, any of the kits disclosed herein further comprises a topical skin filler comprising glycerin, a collagen-derived peptide, alguronic acid, a low molecular weight hyaluronic acid polymer, sodium acetylated hyaluronate, glycolic acid, lactic acid, L-lactic acid, an amino acid, NIA-114™, an acetylated peptide, Activen™ XEP-18, and / or Erasa™ XEP-30. In embodiments, the skin filler comprises glycerin. In embodiments, the skin filler comprises a collagen-derived peptide. In embodiments, the skin filler comprises alguronic acid. In embodiments, the skin filler comprises a low molecular weight hyaluronic acid polymer. In embodiments, the skin filler comprises sodium acetylated hyaluronate. In embodiments, the skin filler comprises glycolic acid. In embodiments, the skin filler comprises lactic acid. In embodiments, the skin filler comprises L-lactic acid. In embodiments, the skin filler comprises an amino acid. In embodiments, the skin filler comprises NIA-114™. In embodiments, the skin filler comprises an acetylated peptide. In embodiments, the skin filler comprises Activen™ XEP-18. In embodiments, the skin filler comprises Erasa™ XEP-30.

[0093] [000103]In another embodiment, any of the kits disclosed herein further comprises a composition comprising deoxycholic acid. [000104]The compositions disclosed herein may be in unit dosage forms suitable for accurate single administration. In another embodiment, the unit dosage form of the first composition and / or the second composition is for 2 administrations, 3 administrations, 4 administrations, 5 administrations, 6 administrations, 7 administrations, 8 administrations, 9 administrations, 10 administrations, 11 administrations, 12 administrations, 13 administrations, 14 administrations, 15 administrations, 16 administrations, 17 administrations, 18 administrations, 19 administrations Provided is either a method or a kit disclosed herein that is suitable for administration, 20 administrations, 21 administrations, 22 administrations, 23 administrations, 24 administrations, 25 administrations, 26 administrations, 27 administrations, 28 administrations, 29 administrations, 30 administrations, administration for 2 months, administration for 3 months, administration for 4 months, administration for 5 months, administration for 6 months, administration for 7 months, administration for 8 months, administration for 9 months, administration for 10 months, administration for 11 months, or administration for 12 months.

[0094] [000105] It will be appreciated that the actual dosage of the compositions disclosed herein can vary depending on the composition used, the mode of administration, and the specific site of the subject being treated and the skin condition being treated. One of ordinary skill in the art, considering the experimental data for a given composition and using conventional dosage determination tests, can confirm the optimal dosage for a given combination of conditions. This amount varies depending on various factors, such as, but not limited to, the characteristics of the compositions and formulations disclosed herein (including their activity, pharmacokinetics, pharmacodynamics, and bioavailability), the physiological state of the subject or cells being treated (age, gender, type and stage of disease, general health status, response to a given dosage, and type of drug), the nature of the pharmaceutically acceptable carrier in the formulation or mg / kg of the carrier, and the route of administration. Further, the effective amount or therapeutically effective amount can vary depending on whether one or more of the compositions and formulations disclosed herein are administered alone or in combination with other dermal fillers, other therapeutic agents (if any), or other therapies or modalities (if any). One of ordinary skill in the clinical and pharmaceutical arts can determine the effective amount or therapeutically effective amount by routine testing, i.e., by monitoring the response of the cells or subject to the administration of one or more of the compositions and formulations disclosed herein and adjusting the dosage accordingly.

[0095] [000106]The dosage regimens using the first composition and the second composition can be adjusted to provide an optimal desired response. As used herein, "unit dosage form" means physically discrete units suitable as unit dosages for the subject to be treated, each unit containing a predetermined quantity of the composition disclosed herein calculated to obtain the desired therapeutic effect in relation to the required pharmaceutical carrier. In the case of the compositions disclosed herein in unit dosage form, the specifications thereof describe (a) the characteristics of the composition and the specific therapeutic or prophylactic effect obtained, and (b) the inherent technical limitations in mixing such compositions for the treatment of a specific condition of the subject, and are directly dependent thereon.

[0096] [000107]Thus, those skilled in the art will recognize that, based on the disclosure provided herein, the dosages and dosing regimens for using the compositions disclosed herein can be adjusted according to methods well known in the medical field. That is, the maximum allowable dose can be readily determined, and an effective amount that provides a detectable therapeutic benefit to the subject can also be determined, as can the time requirements for administering each agent to provide a detectable therapeutic benefit to the subject. Accordingly, specific dosages and dosing schedules are exemplified herein, but these examples are in no way intended to limit the dosages and dosing schedules that can be provided to a subject in practicing the methods of the present disclosure.

[0097] [000108]It should be noted that dosage values may vary depending on the type and severity of the condition to be alleviated and may include a single or multiple dosages. For any particular subject, the specific dosage regimen should be adjusted at any time according to the individual needs and the professional judgment of the person administering or supervising the administration of the composition, and it should be further understood that the dosage ranges described herein are merely exemplary and are not intended to limit the scope or practice of the claimed composition. For example, the dosage can be adjusted based on pharmacokinetic or pharmacodynamic parameters, which can include clinical effects such as toxic effects and / or laboratory values. The embodiments disclosed herein The regimen is intended to include dose escalation within the patient, which is determined by those skilled in the art. Determining the appropriate dosage and regimen for administration of the chemotherapeutic agent is well known in the art, and those skilled in the art will understand, based on the teachings disclosed herein, that it is encompassed by the present invention.

[0098] [000109]In some embodiments, the composition can be used in combination with one or more additional compositions useful in treating the above-described skin conditions of the subject. When using combination therapy, the one or more additional compositions may be administered sequentially or simultaneously with respect to the first composition and / or the second composition disclosed herein. In some embodiments, the additional composition is administered to the subject before, at the same time as, or after the administration of the first composition and / or the second composition disclosed herein. In some embodiments, the additional composition is administered to the subject before the administration of the first composition and / or the second composition disclosed herein. In some embodiments, the additional composition is administered to the subject at the same time as the administration of the first composition and / or the second composition disclosed herein. In some embodiments, the additional composition is administered to the subject after the administration of the first composition and / or the second composition disclosed herein. Additional compositions that can be used according to any of the methods disclosed herein include, but are not limited to, sodium cromolyn (also known as sodium cromoglycate), topical alpha agonists (including, but not limited to, oxymetazoline hydrochloride, clonidine hydrochloride, apraclonidine hydrochloride, and brimonidine tartrate), topical antibiotics (including, but not limited to, tetracyclines [tetracycline, doxycycline, minocycline, sarecycline], clindamycin, and erythromycin), benzoyl peroxide, salicylic acid, azelaic acid, retinoids, topical anticholinergics (including, but not limited to, oxybutynin, glycopyrrolate, and propantheline), topical prostaglandin analogs (including, but not limited to, latanoprost, bimatoprost, travoprost, and tafluprost), and topical hydroquinone, or a combination of fluocinonide acetonide, hydroquinone, and tretinoin (commercially available as Tri-Luma® cream).

[0099] [000110]As will be understood by those skilled in the art, for all purposes, all ranges disclosed herein include any and all available sub-ranges and combinations of those sub-ranges. Any recited range can be fully described as the same range divided into at least two equal parts, three equal parts, four equal parts, five equal parts, ten equal parts, etc., and it can be readily understood that they are practicable. As a non-limiting example, each range discussed herein can be easily divided into a lower third, a middle third, and an upper third. Also, as will be understood by those skilled in the art, all terms such as "up to", "at least", "more than", "less than", etc. include the recited number and refer to ranges that can be subsequently divided into sub-ranges as described above. Finally, as will be understood by those skilled in the art, a range includes each member individually. Thus, for example, a group having 1 to 3 articles refers to a group having 1, 2, or 3 articles. Similarly, a group having 1 to 5 articles refers to a group having 1, 2, 3, 4, or 5 articles, etc.

[0100] [000111]Headings, for example, (a), (b), (i), etc. are provided solely to facilitate reading of the specification and claims. The use of headings in the specification or claims does not require that steps or elements be performed in alphabetical or numerical order or in the order in which they are presented.

[0101] [000112]The preparations and examples of many embodiments disclosed herein are for illustrative purposes only and are not limiting. All starting materials are either commercially available or described in the literature. All temperatures are reported in °C.

Examples

[0102] [000113] Example 1 Use of Spongilla and hyaluronic acid for the treatment of moderate to severe facial wrinkles and grooves, such as nasolabial folds.

[0103] [000114]Subjects 21 years of age or older with moderate to severe facial wrinkles and grooves, such as the nasolabial fold on a 5-point wrinkle severity rating scale (WSRS), are treated as follows. [000115]Week 1: Cleanse the subject's skin with a mild, hypoallergenic cleanser (e.g., Cetaphil®), and dry. Remove a pre-filled syringe containing hyaluronic acid from the refrigerator and let stand at room temperature (30 minutes) with the needle cap on. Add 6 mL of 3% hydrogen peroxide USP to 2 grams of Spongilla powder and stir the mixture until all the powder is mixed into the hydrogen peroxide solution. Rub the Spongilla mixture into the affected skin areas of the subject, taking care to avoid the mucous membranes (e.g., eyes, mouth, and nostrils), and allow the Spongilla composition to dry in the applied area. Next, remove the Spongilla composition using a non-hypoallergenic wipe or water with a cleanser added. Apply a composition containing 20 mg of hyaluronic acid to the subject's skin where Spongilla was applied, taking care to avoid the mucous membranes (e.g., eyes, mouth, and nostrils), and rub the hyaluronic acid into the subject's skin. The hyaluronic acid composition can remain on the application area while providing comfort to the subject. After 15 minutes, wash the application area with a hypoallergenic wipe or water with a hypoallergenic cleanser added. Repeat the above procedure once every 6 months after the first application.

[0104] [000116]Thereafter, subjects report improvement in facial wrinkles and grooves, such as a ≥1-point improvement in WSRS in the nasolabial fold, and when subjects are asked to rate the level of improvement shown in the nasolabial fold, the percentage who remember some improvement (improved, considerably improved, and very much improved) on day 14 is 100%. Subjects may receive a touch-up treatment 30 days after the first treatment using the above procedure.

[0105] [000117] Example 2 Use of Spongilla and hyaluronic acid for the treatment of moderately to severely atrophic, distensible facial acne scars.

[0106] [000118]Treat subjects 21 years of age and older with moderately to severely atrophic, distensible facial acne scars on the cheeks according to the following regimen using a 4-point acne scar rating scale (ACRS).

[0107] [000119]Week 1: Cleanse the subject's skin with a mild, hypoallergenic cleanser (e.g., Cetaphil®) and dry. Remove a pre-filled syringe containing non-resorbable polymethylmethacrylate microspheres (30 - 50 microns in diameter) suspended in an aqueous carrier gel composed of 3.5% bovine collagen (PMMA-collagen) from its packaging without attaching a needle. Add 6 mL of 3% hydrogen peroxide USP to 2 grams of Spongilla powder and stir the mixture until all the powder is mixed into the hydrogen peroxide solution. Rub the Spongilla mixture into the areas of the subject's affected skin, taking care to avoid mucous membranes (e.g., eyes, mouth, and nostrils), and allow the Spongilla composition to dry in the applied area. Next, remove the Spongilla composition using a non-hypoallergenic wipe or water with a hypoallergenic cleanser added. Apply the composition containing PMMA collagen to the skin of the subject where Spongilla was applied, taking care to avoid mucous membranes (e.g., eyes, mouth, and nostrils), and rub the PMMA collagen into the subject's skin. The PMMA collagen composition should be able to remain on the applied area while providing comfort to the subject. After 15 minutes, wash the applied area with a hypoallergenic wipe or water with a hypoallergenic cleanser added. Repeat the above procedure once every 6 months after the first application. Thereafter, the subject will, based on blinded evaluation, notice an improvement of 2 points or more in the atrophic, distensible facial acne scars on the cheeks in more than 50% of the treated scars at 6 months.

[0108] [000120]Thereafter, the subject will, based on blinded evaluation, notice an improvement of 2 points or more in the atrophic, distensible facial acne scars on the cheeks in more than 50% of the treated scars at 6 months. [000121]The subject may receive a touch-up treatment 30 days after the first treatment using the above procedure.

Claims

1. (a) a first composition comprising Spongilla; and (b) a second composition comprising a dermal filler A composition comprising:

2. 2. The composition of claim 1, wherein the Spongilla is present in powder form.

3. The composition of claim 2 , wherein the powder comprises particles that are substantially uniform in size.

4. 4. The composition of claim 2 or 3, wherein 50% or more of the particles comprising the Spongilla flour pass through a US 70 mesh screen.

5. 5. The composition of any one of claims 2 to 4, wherein the particles comprising Spongilla powder have an average length of about 50 μm to about 500 μm.

6. 6. The composition of any one of claims 2 to 5, wherein the particles comprising Spongilla powder have an average diameter of about 5 μm to about 50 μm.

7. 7. The composition of claim 2, wherein the particles comprising Spongilla powder have an aspect ratio of about 1-100.

8. 8. The composition of claim 1, wherein the first composition has a residual moisture content of about 10% or less.

9. 9. The composition of any one of claims 1 to 8, wherein the amount of the first composition comprising Spongilla is from about 0.5 grams to about 50 grams.

10. The composition of claim 1 , wherein the first composition is applied to the skin of the subject in the form of a paste or gel.

11. The composition of claim 10, wherein the paste further comprises water or saline or hydrogen peroxide.

12. 12. The composition of claim 10 or 11, wherein the paste is prepared by mixing a powder containing Spongilla with water or saline or hydrogen peroxide.

13. The composition of claim 1 , wherein the first composition is packaged prior to use.

14. 14. The composition of claim 13, wherein the first composition is prepared by heating to at least about 70°C before being packaged.

15. 15. The composition of claim 14, wherein the first composition is heated to at least about 70°C for at least about 5 minutes before being packaged.

16. 14. The composition of claim 13, wherein the first composition is prepared by treating with gamma radiation or heat before being packaged.

17. The first composition is prepared by treating it with gamma radiation or heat after it is packaged. The composition of claim 13.

18. 18. The composition of any one of claims 1 to 17, wherein the Spongilla is Spongilla lacustris.

19. 19. The composition of any one of claims 1 to 18, wherein the dermal filler comprises one or more of hyaluronic acid, calcium hydroxylapatite, polyalkylimide, polymethylmethacrylate, collagen, polymethylmethacrylate microspheres (PMMA), polylactic acid, polycaprolactone, carboxymethylcellulose, a polymer or copolymer of poly-L-lactic acid, and a cross-linking agent.

20. 20. The composition of any one of claims 1 to 19, wherein the dermal filler is a topical dermal filler comprising glycerin, collagen-derived peptides, arguronic acid, low molecular weight hyaluronic acid polymers, acetylated sodium hyaluronate, glycolic acid, lactic acid, L-lactic acid, amino acids, NIA-114™, acetyl peptides, Activen™ XEP-18, and / or Erasa™ XEP-30.

21. The dermal filler may be selected from the group consisting of Restylane®, Restylane® Lyft (Perlane®-L), Restylane® Refyne, Restylane® Defyne, and / or Restylane® Silk, Captique™, Belotero® Hydro, Belotero® Soft, Belotero® Balance, and / or Belotero® Balance, Esthelis (Trademark).

20. The composition of any one of claims 1 to 19, selected from the group consisting of Fortelis™, Modelis™, Elevess® (Hydrelle®), Hylaform® (Hylan B Gel), Puragen™, Prevelle® Silk, Radiesse® (+), Radiesse®, Aquamid®, Sculptra® Aesthetic, Bellafill®, and Juvaderm®.

22. 22. The composition of any one of claims 1 to 21, wherein the second composition comprises deoxycholic acid.

23. 23. The composition of any one of claims 1 to 22, wherein the second composition is present in the form of a solution, an aqueous solution, a powder, or a hydrogel.

24. 1. A method for administering a dermal filler into the skin of a subject, comprising applying to the skin of the subject a first composition comprising Spongilla and a second composition comprising an effective amount of a dermal filler.

25. 25. The method of claim 24, wherein the Spongilla is present in powder form.

26. 26. The method of claim 25, wherein the powder comprises particles that are substantially uniform in size.

27. 27. The method of any one of claims 24 to 26, wherein greater than or equal to 50% of the particles comprising the Spongilla flour pass through a US 70 mesh screen.

28. 27. The method of any one of claims 24 to 26, wherein the particles comprising Spongilla powder have an average length of about 50 μm to about 500 μm.

29. 27. The method of any one of claims 24 to 26, wherein the particles comprising Spongilla powder have an average diameter of about 5 μm to about 50 μm.

30. 30. The method of any one of claims 24 to 29, wherein the particles comprising Spongilla powder have an aspect ratio of about 1-100.

31. 31. The method of any one of claims 24 to 30, wherein the first composition has a residual moisture content of about 10% or less.

32. 32. The method of any one of claims 24 to 31, wherein the amount of the first composition comprising Spongilla is from about 0.5 grams to about 50 grams.

33. 33. The method of any one of claims 24 to 32, wherein the first composition is applied to the subject's skin in the form of a paste or gel.

34. 34. The method of claim 33, wherein the paste further comprises water or saline or hydrogen peroxide.

35. 35. The method of claim 24 or 34, wherein the paste is prepared by mixing a powder containing Spongilla with water or saline or hydrogen peroxide.

36. 36. The method of any one of claims 33 to 35, wherein the step of applying the first composition comprises rubbing a paste onto a portion of the subject's skin.

37. 37. The method of any one of claims 24 to 36, wherein the dermal filler comprises one or more of hyaluronic acid, calcium hydroxylapatite, polyalkylimide, polymethylmethacrylate, collagen, polymethylmethacrylate microspheres (PMMA), polylactic acid, polycaprolactone, carboxymethylcellulose, a polymer or copolymer of poly-L-lactic acid, and a cross-linking agent.

38. The dermal filler may be selected from the group consisting of Restylane®, Restylane® Lyft (Perlane®-L), Restylane® Refyne, Restylane® Defyne, and / or Restylane® Silk, Captique™, Belotero® Hydro, Belotero® Soft, Belotero® Balance, and / or Belotero® Balance, Esthelis (Trademark).

36. The method of any one of claims 24 to 35, wherein the therapeutic agent is selected from the group consisting of Fortelis™, Modelis™, Elevess® (Hydrelle®), Hylaform® (Hylan B Gel), Puragen™, Prevelle® Silk, Radiesse® (+), Radiesse®, Aquamid®, Sculptra® Aesthetic, Bellafill®, and Juvaderm®.

39. 1. A method for treating or preventing a skin condition or disease in a subject, comprising: administering a therapeutically or prophylactically effective amount of a first composition comprising Spongilla and a second composition comprising a therapeutically effective amount of a dermal filler to an intradermal compartment of the subject's skin by applying the first composition and the second composition to the subject's skin.

40. 40. The method of claim 39, wherein the skin condition or disease is a skin abnormality.

41. 41. The method of claim 40, wherein the skin abnormality is due to an underlying medical condition.

42. 42. The method of claim 41, wherein the underlying medical condition is lipoatrophy.

43. 42. The method of claim 41, wherein the lipoatrophy is due to HIV or scarring.

44. 42. The method of claim 41, wherein the skin abnormality is wrinkles.

45. 42. The method of claim 41, wherein the skin abnormality is a skin groove.

46. 46. ​​The method of claim 45, wherein the grooves include fine wrinkles in the areas of the face, lips, nose, under-eye area, eyebrows, head, chin, neck, ears, earlobes, décolleté, elbows, hands, feet, and / or knees.

47. 46. ​​The method of claim 45, wherein the grooves include moderate wrinkles of skin in the areas of the face, lips, nose, under-eye area, eyebrows, head, chin, neck, ears, earlobes, décolleté, elbows, hands, feet, and knees.

48. 46. ​​The method of claim 45, wherein the grooves include severe wrinkles or grooves in the skin in the areas of the face, lips, nose, under-eye area, eyebrows, head, chin, neck, ears, earlobes, décolleté, elbows, hands, feet, and knees.

49. 40. The method of claim 39, wherein the skin abnormality is a skin dimple.

50. 50. The method of any one of claims 39 to 49, wherein the skin condition is treated by augmentation of an existing body part.

51. 51. The method of any one of claims 39 to 50, wherein the skin condition is treated by improving nasal function.

52. 52. The method of any one of claims 39 to 51, wherein the intradermal compartment of the subject's skin includes portions of the following areas: face, lips, nose, area under the eyes, eyebrows, head, chin, neck, ears, earlobes, décolleté, elbows, hands, feet, and knees, and administration of the first composition and the second composition modifies, enhances, and / or corrects the areas to which the compositions are applied.

53. 53. The method of any one of claims 39 to 52, wherein the Spongilla is present in the form of a powder.

54. 54. The method of claim 53, wherein the powder comprises particles that are substantially uniform in size.

55. 55. The method of any one of claims 52-54, wherein greater than 50% of the particles comprising the Spongilla flour pass through a US 70 mesh screen.

56. 55. The method of any one of claims 52 to 54, wherein the particles comprising Spongilla powder have an average length of about 50 μm to about 500 μm.

57. 55. The method of any one of claims 52 to 54, wherein the particles comprising Spongilla powder have an average diameter of about 5 μm to about 50 μm.

58. 55. The method of any one of claims 52 to 54, wherein the particles comprising Spongilla powder have an aspect ratio of about 1-100.

59. 59. The method of any one of claims 39 to 58, wherein the first composition has a residual moisture content of about 10% or less.

60. 60. The method of any one of claims 39 to 59, wherein the amount of the first composition comprising Spongilla is from about 0.5 grams to about 50 grams.

61. 61. The method of any one of claims 39 to 60, wherein the first composition is applied to the subject's skin in the form of a paste.

62. 62. The method of claim 61, wherein the paste further comprises water or saline or hydrogen peroxide.

63. 63. The method of claim 61 or 62, wherein the paste is prepared by mixing a powder containing Spongilla with water or saline or hydrogen peroxide.

64. 64. The method of any one of claims 39 to 63, wherein the step of applying the first composition comprises rubbing a paste onto a portion of the subject's skin.

65. 65. The method of any one of claims 39 to 64, wherein the dermal filler comprises one or more of hyaluronic acid, calcium hydroxylapatite, polyalkylimide, polymethylmethacrylate, collagen, polymethylmethacrylate microspheres (PMMA), polylactic acid, polycaprolactone, carboxymethylcellulose, a polymer or copolymer of poly-L-lactic acid, and a cross-linking agent.

66. 66. The method of any one of claims 39 to 65, wherein the dermal filler is a topical dermal filler comprising glycerin, collagen-derived peptides, arguronic acid, low molecular weight hyaluronic acid polymers, acetylated sodium hyaluronate, glycolic acid, lactic acid, L-lactic acid, amino acids, NIA-114™, acetyl peptides, Activen™ XEP-18, and / or Erasa™ XEP-30.

67. The dermal filler may be selected from the group consisting of Restylane®, Restylane® Lyft (Perlane®-L), Restylane® Refyne, Restylane® Defyne, and / or Restylane® Silk, Captique™, Belotero® Hydro, Belotero® Soft, Belotero® Balance, and / or Belotero® Balance, Esthelis (Trademark).

66. The method of any one of claims 39 to 65, wherein the therapeutic agent is selected from the group consisting of Fortelis™, Modelis™, Elevess® (Hydrelle®), Hylaform® (Hylan B Gel), Puragen™, Prevelle® Silk, Radiesse® (+), Radiesse®, Aquamid®, Sculptra® Aesthetic, Bellafill®, and Juvaderm®.

68. 68. The method of any one of claims 39 to 67, wherein the second composition comprises deoxycholic acid.

69. 1. A method for enhancing dermal penetration of a topically applied dermal filler composition in the skin of a subject, comprising the steps of applying to the skin a first composition comprising Spongilla, followed by applying a second composition comprising an effective amount of a dermal filler.

70. 70. The method of claim 69, wherein the Spongilla is in the form of a powder.

71. 71. The method of claim 70, wherein the powder comprises particles that are substantially uniform in size.

72. 72. The method of any one of claims 69-71, wherein 50% or more of the particles comprising Spongilla flour pass through a U70 mesh screen.

73. 73. The method of any one of claims 69 to 72, wherein the particles comprising Spongilla powder have an average length of about 50 μm to about 500 μm.

74. 74. The method of any one of claims 69 to 73, wherein the particles comprising Spongilla powder have an average diameter of about 5 μm to about 50 μm.

75. 75. The method of any one of claims 69 to 74, wherein the particles comprising Spongilla powder have an aspect ratio of about 1-100.

76. 76. The method of any one of claims 69 to 75, wherein the first composition has a residual moisture content of about 10% or less.

77. 77. The method of any one of claims 69 to 76, wherein the amount of the first composition comprising Spongilla is from about 0.5 grams to about 50 grams.

78. 78. The method of any one of claims 69 to 77, wherein the first composition is applied to the skin of the subject in the form of a paste.

79. 80. The method of claim 78, wherein the paste further comprises water or saline or hydrogen peroxide.

80. 80. The method of claim 78 or 79, wherein the paste is prepared by mixing a powder containing Spongilla with water or saline or hydrogen peroxide.

81. 78. The method of any one of claims 66 to 77, wherein the step of applying the first composition comprises rubbing a paste onto a portion of the subject's skin.

82. 82. The method of any one of claims 69 to 81, wherein the dermal filler comprises one or more of hyaluronic acid, calcium hydroxylapatite, polyalkylimide, polymethylmethacrylate, collagen, polymethylmethacrylate microspheres (PMMA), polylactic acid, polycaprolactone, carboxymethylcellulose, a polymer or copolymer of poly-L-lactic acid, and a cross-linking agent.

83. 83. The method of any one of claims 69 to 82, wherein the dermal filler is a topical dermal filler comprising glycerin, collagen-derived peptides, arguronic acid, low molecular weight hyaluronic acid polymers, acetylated sodium hyaluronate, glycolic acid, lactic acid, L-lactic acid, amino acids, NIA-114™, acetyl peptides, Activen™ XEP-18, and / or Erasa™ XEP-30.

84. 84. The method of any one of claims 69 to 83, wherein the second composition comprises deoxycholic acid.

85. 85. The method of any one of claims 24 to 84, wherein the first composition is applied to the skin of the subject before the second composition is applied to the skin of the subject.

86. 86. The method of claim 85, wherein the first composition is applied to the skin of the subject and allowed to dry on the skin of the subject before the second composition is applied to the skin of the subject.

87. 87. The method of claim 81 or 86, wherein the first composition is washed from the subject's skin before the second composition is applied to the subject's skin.

88. 70. The method of any one of claims 24, 39, or 69, wherein the first composition and the second composition are mixed and the resulting mixture is applied to the skin of a subject.

89. 89. The method of any one of claims 24 to 88, wherein the first composition and the second composition are applied to the skin of the subject no more than once every three months.

90. 90. The method of any one of claims 24 to 89, wherein the first composition comprising Spongilla is applied to the skin of the subject at least once a week for at least one week.

91. 92. The method of any one of claims 23-91, wherein the skin of the subject is washed using a non-comedogenic cleanser, water, or a combination of a non-comedogenic cleanser and water following application of the first composition comprising Spongilla.

92. 92. The method of any one of claims 24 to 91, wherein the subject's skin is washed using a non-comedogenic cleanser, water, or a combination of a non-comedogenic cleanser and water following application of the second composition to the subject's skin.

93. 93. The method of any one of claims 24 to 92, wherein the second composition is in the form of a hydrogel.

94. 1. A kit comprising: (a) a first composition comprising Spongilla; and (b) a second composition comprising one or more dermal fillers in an amount effective to treat a skin condition in a subject.

95. 95. A kit comprising the kit of claim 94 and a reconstitution reagent.

96. 95. A kit comprising the kit of claim 94 and an antiseptic reagent.

97. 95. A kit comprising the kit of claim 94 and a reconstitution reagent and a preservation reagent.

98. 98. The kit of any one of claims 94 to 97, further comprising instructions for use.

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