Compositions and methods for the treatment of skin diseases and conditions, including eczema.

Abstract

This specification discloses therapeutic compositions comprising bacteriophages and colloidal oatmeal, as well as methods for using these compositions to treat skin diseases and conditions, including eczema.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 493,834, filed April 3, 2023, which is incorporated herein by reference in its entirety.

[0002] Sequence List The sequence listing is submitted accompanying this application as an XML file named "177601.00023.xml", created on April 1, 2024, and having a size of 250,800 bytes. The sequence listing is submitted electronically with this application and is incorporated herein by reference in its entirety.

[0003] field The field of the present invention relates to therapeutic compositions comprising bacteriophages and colloidal oatmeal, and to methods of using these compositions for the treatment of skin diseases and conditions, including eczema. [Background technology]

[0004] Eczema is a common skin condition characterized by redness, itchy skin, and small blisters, also known in the art as rashes, eczemas, or dermatitis. There is no cure for eczema, but there are numerous treatments, ranging from special diets to emollients and immunosuppressive ointments, such as corticosteroid ointments. Corticosteroids, such as hydrocortisone or clobetasol propionate (topical, oral, or intradermal), usually provide improvement, but they can also have side effects. Long-term use of topical corticosteroids is thought to increase the risk of side effects, the most common of which is thinning and weakening of the skin (atrophy). Therefore, when used on the face or other delicate skin, low-strength steroids should be used or applied infrequently. In addition, high-strength steroids used over large areas or in occlusion may be absorbed into the body, causing suppression of the hypothalamic-pituitary-adrenal axis (HPA axis suppression).

[0005] Due to impaired skin barrier function in atopic dermatitis, an increase in skin infections by bacteria or fungi, such as Staphylococcus aureus, may occur. In more severe cases, dermatologists may also prescribe conventional antibiotics, such as penicillin, streptomycin, and chloramphenicol, either topically or orally. Antibiotics prevent infections that can arise from impaired skin barrier function, such as cracked skin. Colonization or infection with S. aureus is the most common cause of increased eczema severity. The effectiveness of antibiotic treatment varies from person to person. Known disadvantages of conventional antibiotics include specificity, i.e., the killing of non-pathogenic and / or beneficial bacteria, and the risk of developing resistance, which can be caused not only by target bacterial cells but also by other pathogenic bacteria. Furthermore, conventional systemic antibiotic treatment may interact with other medications, including oral contraceptives. Certain antibiotics cannot be used in combination with alcohol. Therefore, there is a need for improved treatment of eczema. [Overview of the project] [Problems that the invention aims to solve]

[0006] (Summary) This specification discloses compositions, kits, and methods for the prevention and treatment of skin diseases and disorders, such as, but not limited to, eczema. [Means for solving the problem]

[0007] In some embodiments, the compositions disclosed herein are formulated for topical administration and comprise a bacteriophage and colloidal oatmeal. In some embodiments, the bacteriophage comprises a Staphylococcus bacteriophage. In some embodiments, the bacteriophage comprises or comprises one or more Staphylococcus aureus (S. aureus) bacteriophages. In some embodiments, the S. aureus bacteriophage comprises or comprises one or more of SEQ ID NOs: 1 (MESA-01), 44 (MESA-05), 45 (MESA-11), and / or 46 (SaGU1).

[0008] In some embodiments, the composition further comprises one or more additional activators. Examples, but not limited to, include ceramides, hyaluronic acid, glycerin, petrolatum, niacinamide, enzymes, and / or probiotic bacteria.

[0009] In some embodiments, the composition includes, but is not limited to, one or more enzymes such as bacterial cell wall-degrading enzymes, endolysin, and / or anti-aging enzymes.

[0010] In some embodiments, the compositions disclosed herein consist of one or more S. aureus bacteriophages and colloidal oatmeal. The bacteriophages are free in the composition and are not bound to a solid support such as beads. In some embodiments, the phages (pages) are encapsulated or occluded in a suspension in a culture medium.

[0011] In some embodiments, the S. aureus bacteriophage includes or comprises SEQ ID NO: 1, SEQ ID NO: 44, SEQ ID NO: 45 and / or SEQ ID NO: 46. In some embodiments, the S. aureus bacteriophage includes a sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one of SEQ ID NOs: 1, 44, 45, and / or 46.

[0012] In some embodiments, the bacteriophage contains a nucleic acid sequence that is at least 90% identical to one or more of SEQ ID NOs: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 45 and / or 46. In some embodiments, the bacteriophage contains a nucleic acid encoding a polypeptide that is at least 90% identical to one or more of SEQ ID NOs: 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41 and / or 43.

[0013] Similarly, this specification discloses methods for treating skin diseases or disorders, such as eczema, in subjects requiring treatment of such conditions. In some embodiments, the method involves topically administering a composition of any embodiment described above to an area of ​​skin of a subject having a skin disease or disorder, such as eczema. In some embodiments, the administration includes once daily, twice daily, three times daily, or four times daily. In some embodiments, the composition is administered for one week, two weeks, three weeks, or longer. In some embodiments, the treatment reduces one or more of the following eczema symptoms: itchy skin, dry skin, redness, and swelling in the area of ​​skin of the subject to which the composition is administered. In some embodiments, the reduction of one or more eczema symptoms occurs faster in the treated subject than in a control subject (e.g., a subject not treated with a composition described herein, e.g., comprising one or more S. aureus bacteriophages).

[0014] For example, in some embodiments, the treated subject shows improvement 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% faster than an equivalent control subject. In some embodiments, the treated subject shows improvement of at least approximately 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or greater, in at least one symptom compared to an equivalent control subject over the same period of time.

[0015] In some embodiments, the eczema is selected from contact eczema, allergic contact eczema, seborrheic dermatitis, nummular eczema, neurodermatitis, stasis dermatitis, and dyshidrotic eczema. In some embodiments, the eczema includes atopic eczema.

[0016] In some embodiments, the subject being treated is a human being.

[0017] Non-limiting embodiments of the system, method, and kit can be described here by reference to the accompanying drawings. [Brief explanation of the drawing]

[0018] [Figure 1a] This is an annotated schematic diagram of an exemplary full-length bacteriophage DNA sequence (SEQ ID NO: 1). The 21 segments are as follows: SEQ ID NOs: 2 (CDS0 virtual protein), 4 (CDS1 virtual protein), 6 (CDS2 major head protein), 8 (CDS3 upper collar connector), 10 (CDS4 adapter Ad4), 12 (CDS5 minor tail protein). The proteins are shown together with 14 (CDS6 endolysin), 16 (CDS7 tail protein), 18 (CDS8 tail protein), 20 (CDS9 phorin), 22 (CDS10 virtual protein), 24 (CDS11 DNA polymerase), 26 (CDS12 terminase), 28 (CDS13 virtual protein), 30 (CDS14 virtual protein), 32 (CDS15 virtual protein), 34 (CDS16 virtual protein), 36 (CDS17 virtual protein), 38 (CDS18 virtual protein), 40 (CDS19 virtual protein), and 42 (CDS20 virtual protein). These sequence segments can be transcribed and translated into representative polypeptides, respectively, of sequence numbers 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, and 43. [Figure 1b]This is an annotated schematic diagram of an exemplary full-length bacteriophage DNA sequence (SEQ ID NO: 1). The 21 segments are as follows: SEQ ID NOs: 2 (CDS0 virtual protein), 4 (CDS1 virtual protein), 6 (CDS2 major head protein), 8 (CDS3 upper collar connector), 10 (CDS4 adapter Ad4), 12 (CDS5 minor tail protein). The proteins are shown together with 14 (CDS6 endolysin), 16 (CDS7 tail protein), 18 (CDS8 tail protein), 20 (CDS9 phorin), 22 (CDS10 virtual protein), 24 (CDS11 DNA polymerase), 26 (CDS12 terminase), 28 (CDS13 virtual protein), 30 (CDS14 virtual protein), 32 (CDS15 virtual protein), 34 (CDS16 virtual protein), 36 (CDS17 virtual protein), 38 (CDS18 virtual protein), 40 (CDS19 virtual protein), and 42 (CDS20 virtual protein). These sequence segments can be transcribed and translated into representative polypeptides, respectively, of sequence numbers 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, and 43. [Figure 1c]This is an annotated schematic diagram of an exemplary full-length bacteriophage DNA sequence (SEQ ID NO: 1). The 21 segments are as follows: SEQ ID NOs: 2 (CDS0 virtual protein), 4 (CDS1 virtual protein), 6 (CDS2 major head protein), 8 (CDS3 upper collar connector), 10 (CDS4 adapter Ad4), 12 (CDS5 minor tail protein). The proteins are shown together with 14 (CDS6 endolysin), 16 (CDS7 tail protein), 18 (CDS8 tail protein), 20 (CDS9 phorin), 22 (CDS10 virtual protein), 24 (CDS11 DNA polymerase), 26 (CDS12 terminase), 28 (CDS13 virtual protein), 30 (CDS14 virtual protein), 32 (CDS15 virtual protein), 34 (CDS16 virtual protein), 36 (CDS17 virtual protein), 38 (CDS18 virtual protein), 40 (CDS19 virtual protein), and 42 (CDS20 virtual protein). These sequence segments can be transcribed and translated into representative polypeptides, respectively, of sequence numbers 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, and 43. [Figure 2] This graph shows that S. aureus bacteriophage is even more stable in the presence of 1% colloidal oatmeal (CO). S. aureus bacteriophage was incubated at 30°C for 48 hours with and without 1% CO. Without CO: 0.53 x 10⁹ pfu / mL; with 1% CO: 1.4 x 10⁹ pfu / mL. Therefore, 1% CO imparts 2.64 x (264%) higher stability to S. aureus bacteriophage. [Figure 3]This graph shows that the number of viable S. aureus bacteria was low in the presence of 1% colloidal oatmeal. Bacteriophage killing of S. aureus bacteria was measured with and without 1% CO. Lower viable numbers of S. aureus bacteria indicate better sterilization. The number of S. aureus viable numbers was lower in the presence of 1% CO. CO-free: 1.23 x 10¹⁰ cfu / mL, 1% CO-included: 0.73 x 10¹⁰ cfu / mL. Therefore, CO enhances bacteriophage killing of S. aureus bacteria. [Modes for carrying out the invention]

[0019] This specification discloses compositions and methods for treating skin diseases or conditions, including, but not limited to, eczema. The disclosed compositions comprise bacteriophages and colloidal oatmeal, and in some embodiments, such compositions are administered topically to subjects suffering from, for example, a skin disease or condition such as eczema.

[0020] In some embodiments, the treatment method is not limited to, but is a method for preventing, delaying and / or treating skin diseases or conditions such as eczema, acne, rosacea, comedones, impetigo, boils, furuncles, cellulitis folliculitis, hidradenitis suppurativa, psoriasis, carbuncles, scaled skin syndrome, and abscesses. Preferably, the treatment method is a method for preventing, delaying, treating and / or treating eczema such as atopic dermatitis, allergic contact dermatitis, contact dermatitis, dyshidrotic dermatitis, neurodermatitis, nummular eczema, seborrheic dermatitis, stasis dermatitis, and preferably atopic dermatitis. In some embodiments, the treatment method is a topical treatment for eczema.

[0021] To aid in understanding the present invention, several terms are defined throughout the specification.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Any methods and materials similar to or equivalent to those described herein may be used in the execution or testing of the claims, and exemplary methods and materials are described herein.

[0023] Furthermore, referring to an element with the indefinite article "a" or "an" does not rule out the possibility of more than one element unless the content explicitly requires that there be one or only one element. Therefore, the indefinite article "a" or "an" usually means "at least one."

[0024] The term "approximately" means a statistically meaningful range of one or more values, such as concentration, length, molecule, pH, time frame, temperature, pressure, or volume, that are stated. Such values ​​or ranges may be within one order of magnitude of a given value or range, typically within 20%, more typically within 10%, and even more typically within 5%. The acceptable variation encompassed by "approximately" depends on the specific system under study.

[0025] The terms "comprising," "possessing," "including," and "containing" shall be interpreted as open-ended terms (i.e., meaning "including, but not limited to, these items") unless otherwise specified.

[0026] The descriptions of value ranges in this specification are intended merely as a simple way to refer to each individual value within the range, and unless otherwise specified, each individual value, including the endpoints of the defined range boundaries, is incorporated herein in the same way as if it were individually listed herein.

[0027] "Nucleic acids" refer to nucleotides (e.g., deoxyribonucleotides or ribonucleotides) in single-stranded, double-stranded, or multi-stranded forms, and their polymers or complements. The terms "polynucleotide," "oligonucleotide," and "oligo" refer to linear sequences of nucleotides in their usual, common sense. Oligonucleotides are typically about 5, 6, 7, 8, 9, 10, 12, 15, 25, 30, 40, or 50 nucleotides in length, or longer, up to about 100 nucleotides. Polynucleotides are polymers of any length, including longer lengths such as 200, 300, 500, 1000, 2000, 3000, 5000, 7000, 10000, 20000, 30000, 40000, etc. Polynucleotides and oligonucleotides generally contain phosphorodiester bonds, but in some cases include nucleic acid analogs that may have alternative skeletons, including, for example, phosphoramidate, phosphorothioate, phosphorodithioate, or O-methylphosphoramidite bonds (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, Oxford University Press), and peptide nucleic acid skeletons and bonds. Other analog nucleic acids include those with positive backbones, nonionic backbones, and non-ribose backbones, including those described in U.S. Patents 5,235,033 and 5,034,506 and Chapters 6 and 7, ASC Symposium Series 580, Carbohydrate Modifications in Antisense Research, Sanghui & Cook, eds. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acid. Modification of the ribose-phosphate skeleton may be performed for various reasons, such as to improve the stability and half-life of such molecules under physiological conditions, or for use as probes in biochips. Mixtures of naturally occurring nucleic acids and analogs may be prepared; alternatively, mixtures of different nucleic acid analogs, as well as mixtures of naturally occurring nucleic acids and analogs, may be prepared.

[0028] The term "bp," in its usual sense, refers to the number of base pairs.

[0029] The "percentage of sequence identity" is determined by comparing two optimally aligned sequences across a comparison window, where some of the polynucleotide or polypeptide sequences in the comparison window may contain additions or deletions (i.e., gaps) compared to a reference sequence (which does not contain additions or deletions) for optimal alignment of the two sequences. In embodiments, the percentage is calculated by determining the number of positions in which identical nucleic acid bases or amino acid residues occur in both sequences to obtain the number of matched positions, dividing the number of matched positions by the total number of positions in the comparison window, and multiplying the result by 100 to obtain the percentage of sequence identity.

[0030] In the context of two or more nucleic acid or polypeptide sequences, the term “identical” or percentage “identical” means two or more sequences or subsequences that are identical, or have a specific percentage of identical amino acid residues or nucleotides (i.e., 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or greater identity) across a specific region, e.g., the entire nucleic acid or polypeptide sequence or an individual part or domain of the nucleic acid or polypeptide, when compared and aligned for the greatest match across the comparison window, or when designated as such. Thereafter, such sequences are referred to as “substantially identical.” This definition also refers to the complement of a test sequence. In embodiments, identity exists over regions of approximately or at least approximately 20, 50, 100, 1000, 2500, 5000, 7500, 10000, 15000, 20000, 25000, or 30000 amino acids or nucleotides in length, or approximately less than approximately, or at least approximately 31000, 32000, 33000, 34000, or 35000 amino acids or nucleotides in length. Optionally, identity exists over regions of at least approximately 10 to approximately 100, approximately 20 to approximately 75, or approximately 30 to approximately 50 amino acids or nucleotides in length. Optionally, identity exists over regions of at least approximately 50 amino acids in length, or more preferably over regions of 100 to 500 or 1000 or more amino acids in length. This specification includes phages comprising nucleic acids (e.g., a genome or a portion thereof) having sequences substantially identical to any of SEQ ID NOs: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 45 and / or 46. Non-limiting examples of phages provided herein include genomes having sequences substantially identical to SEQ ID NOs: 1, 44, 45 and / or 46.In addition or alternatively, the Specified herein includes phages comprising polynucleotides encoding polypeptides having sequences substantially identical to any of SEQ ID NOs: 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, and 43.

[0031] For sequence comparison, typically one sequence serves as a reference sequence against which the test sequence is compared. When using a sequence comparison algorithm, the test and reference sequences are input into a computer, sub-sequence coordinates are specified as needed, and sequence algorithm program parameters are specified. Preferably, initialization program parameters may be used, or alternative parameters may be specified. The sequence comparison algorithm then calculates the sequence identity percentage for the test sequence by comparing it to the reference sequence based on the program parameters.

[0032] As used herein, a “comparison window” includes referring to any one segment of a number of proximity positions that, after two sequences have been optimally aligned, are compared to the same number of proximity positions of the reference sequence. In embodiments, the comparison window includes approximately or at least approximately 20, 50, 100, 1000, 2500, 5000, 7500, 10000, 15000, 20000, 25000, or 30000 proximity positions, less than approximately, or at least approximately 31000, 32000, 33000, 34000, or 35000 proximity positions. In embodiments, the comparison window is the entire length of the reference sequence, such as a bacteriophage genome sequence. Methods for aligning sequences for comparison are known in the art. In the embodiments, optimal alignment of sequences for comparison may be performed, for example, by the local phase alignment algorithm of Smith & Waterman, Adv.Appl.Math.2:482 (1981), by the phase alignment algorithm of Needleman & Wunsch, J.Mol.Biol.48:443 (1970), by the similarity search method of Pearson & Lipman, Proc.Nat'l.Acad.Sci.USA 85:2444 (1988), by computerized execution of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by manual alignment and visual inspection (see, for example, Current Protocols in Molecular Biology (Ausubel et al., eds. 1995 supplement)).

[0033] Examples of optimal algorithms for determining sequence identity and sequence similarity percentages are the BLAST and BLAST2.0 algorithms, described in Altschul et al., Nuc. Acids Res. 25:3389-3402 (1977) and Altschul et al., J. Mol. Biol. 215:403-410 (1990), respectively. As will be understood by those skilled in the art, software for performing BLAST analysis is publicly available through the National Center for Biotechnology Information (NCBI) website. In embodiments, BLAST and BLAST2.0 are used with the parameters described herein to determine the sequence identity percentages of nucleic acids and proteins.

[0034] The terms “polypeptide,” “peptide,” and “protein” are used interchangeably herein to refer to polymers of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residues are artificial chemical mimics of corresponding naturally occurring amino acids, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers.

[0035] The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimes that function in a similar manner to naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code and later modified amino acids, such as hydroxyproline, γ-carboxyglutamic acid, and O-phosphoserine. Amino acid analogs refer to compounds that have the same basic chemical structure as naturally occurring amino acids, i.e., carbon atoms bonded to hydrogen, carboxyl groups, amino groups, and R groups, such as homoserine, norleucine, methionine sulfoxide, and methionine methisulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide skeletons, but retain the same basic chemical structure as naturally occurring amino acids. Amino acid mimes refer to chemical compounds that have a structure different from the general chemical structure of amino acids, but that function in a similar manner to naturally occurring amino acids.

[0036] Amino acids may be referred herein by their commonly known three-letter codes or by the single-letter codes recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Similarly, nucleotides may be referred by their commonly accepted single-letter codes.

[0037] The term "conservatively modified variant" applies to both amino acid sequences and nucleic acid sequences. With respect to a specific nucleic acid sequence, a conservatively modified variant refers to a nucleic acid that codes for the same or essentially the same amino acid sequence, or, if the nucleic acid does not code for an amino acid sequence, for an essentially identical sequence. Due to the degenerate nature of the genetic code, a number of functionally identical nucleic acids code for any given protein. For example, the codons GCA, GCC, GCG, and GCU all code for the amino acid alanine. Therefore, at all positions where alanine is specified by the codon, the codon can be changed to any of the corresponding codons listed without altering the coded polypeptide. Such nucleic acid variations are "silent variations," which are a molecular species of a conservatively modified variation. All nucleic acid sequences in this specification that code for a polypeptide also describe all possible silent variations of the nucleic acid. Those skilled in the art will recognize that each codon in a nucleic acid (with the exception of AUG, which is usually the sole codon for methionine, and TGG, which is usually the sole codon for tryptophan) can be modified to result in a functionally identical molecule. Therefore, each silent variation of the nucleic acid encoding the polypeptide is latent in each sequence described for the expression product, but not in the actual probe sequence.

[0038] Those skilled in the art with respect to amino acid sequences will recognize that individual substitutions to a peptide, polypeptide, or protein sequence that alter a single amino acid are "conservatively modified variants" if the alteration results in an amino acid substitution using a chemically similar amino acid. Tables of conservative substitutions resulting in functionally similar amino acids are known in the art. Such conservatively modified variants are added to, and not excluded from, polymorphic variants, interspecific homologs, and alleles.

[0039] The following eight groups each contain amino acids that are conserved substitutions with each other: 1) alanine (A), glycine (G); 2) aspartic acid (D), glutamic acid (E); 3) asparagine (N), glutamine (Q); 4) arginine (R), lysine (K); 5) isoleucine (I), leucine (L), methionine (M), valine (V); 6) phenylalanine (F), tyrosine (Y), tryptophan (W); 7) serine (S), threonine (T); and 8) cysteine ​​(C), methionine (M) (see, for example, Creighton, Proteins (1984)).

[0040] As used herein, “Staphylococcus aureus (S. aureus) bacteriophage” is a bacteriophage that infects, replicates within, and kills S. aureus cells. In some embodiments, the S. aureus bacteriophage is a lytic S. aureus bacteriophage. In embodiments, the S. aureus bacteriophage can lyse S. aureus bacteria but cannot lyse any bacteria other than S. aureus. In embodiments, the S. aureus bacteriophage cannot maintain lysogenicity in bacteria. In embodiments, the use of a bacteriophage that can lyse S. aureus but cannot maintain lysogenicity has the advantage that the bacteriophage cannot enter a dormant state within the bacteria but will still lyse the bacteria, thereby killing them. In embodiments, S. aureus bacteriophage lacks the ability to express at least one gene necessary for maintaining lysogenicity. The term “lacking the ability to express at least one gene necessary for maintaining lysogenicity” is intended to indicate that S. aureus bacteriophage lacks the ability to produce a fully functional protein product necessary for maintaining lysogenicity, for example, as a result of one or more point mutations or deletions of all or part of the genome. In embodiments, S. aureus bacteriophage has a genome lacking all or part of at least one gene necessary for maintaining lysogenicity (for example, artificially or naturally, for example, a strain is or is derived from a strain lacking all or part of at least one gene necessary for maintaining lysogenicity). In embodiments, S. aureus bacteriophages may contain modifications (e.g., mutations, insertions, or deletions) in non-coding regions of the genome that may still affect the phage's ability to retain lysogenicity, such as deletions in genomic integration sites (e.g., a / att / sites) or repressor binding sites. In embodiments, S. aureus bacteriophages are naturally occurring and isolated, which has the additional advantage that artificial mutations do not need to be introduced into the bacteriophage.In embodiments, S. aureus bacteriophage can lyse multiple strains of S. aureus bacteria. In embodiments, S. aureus bacteriophage can lyse at least about 5, 10, 15, 20, 25, 30 or more strains of S. aureus bacteria. Non-limiting examples of S. aureus bacteriophage include, non-limitingly, those described in References 1-9, which are disclosed herein and incorporated herein by reference in their entirety.

[0041] In some embodiments, the S. aureus bacteriophage has a genome with sequence identity of at least approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 95%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, and 99.9% identity with SEQ ID NO: 1, SEQ ID NO: 44, SEQ ID NO: 45, or SEQ ID NO: 46, or a genome consisting of the sequences of SEQ ID NO: 1, SEQ ID NO: 44, SEQ ID NO: 45, or SEQ ID NO: 46. In some embodiments, the S. aureus bacteriophage has a genome that includes the sequence of SEQ ID NO: 1, SEQ ID NO: 44, SEQ ID NO: 45, or SEQ ID NO: 46. In some embodiments, the genome of the S. aureus bacteriophage has no insertions or deletions compared to SEQ ID NO: 1, SEQ ID NO: 44, SEQ ID NO: 45, or SEQ ID NO: 46. In this embodiment, the genome of S. aureus bacteriophage has no insertions or deletions and only conserved substitutions compared to SEQ ID NO: 1, SEQ ID NO: 44, SEQ ID NO: 45, or SEQ ID NO: 46.

[0042] Additional, non-limiting examples of S. aureus bacteriophages known in the art are provided in References 5 and 11-13, which are incorporated herein by reference in their entirety, and include, but are not limited to, the following bacteriophages (GenBank / NCBI accession numbers in parentheses): vB_SauM-A (number MN539736), vB_SauM-C (number MN539737), vB_SauM-D (number MN539738), JD007 (number JX878671), MCE-2024 (number KJ888149), phiIPLA-RODI (number KP02 7446), SaGU1 (number LC574321), Stau2 (number NC_030933), IME-SA1 (number NC_047729), PT1028 (number AY954948), 66 (number AY954949), 44AHJD (number NC_004678), P68 (number NC_004679), 187 (number AY954950), 69 (number AY954951), 53 (number AY954952), 85 (number AY954953), 2638A (number AY954954), 77 (number AY508486), 42e (number AY954955), 3A (number AY954956), 47 (number AY954957), 37 (number AY954958), EW (number AY954959), 96 (number AY954960), ROSA (number AY954961), 71 (number AY954962), 55 (number AY954963), 29 (number AY954964), 52A (number AY954965), 88 (number AY954966), 92 (number AY954967), X2 (number AY954968), K (number AY176327), G1 (number AY954969), Twort (number AY954970), PG-2021_1 (number MZ417323), PG-2021_3, PG-2021_4 (number MZ417338), PG-2021_7, PG-2021_8 (number MZ417350), PG-2021_9 (number MZ417354), PG-2021_10 (number M Z417315), PG-2021_11, PG-2021_12 (number MZ417316), PG-2021_13, PG-2021_14 (number MZ417317), PG-2021_15 (number MZ417318), PG-2021_16 (number MZ417319),PG-2021_17 (No. MZ417320), PG-2021_18 (No. MZ417321), PG-2021_22 (No. MZ417 324), PG-2021_23 (No. MZ417325), PG-2021_24, PG-2021_27 (No. MZ417326), PG -2021_28, PG-2021_33 (number MZ417330), PG-2021_34, PG-2021_37, PG-2021_38 (No. MZ417332), PG-2021_39, PG-2021_40 (No. MZ417333), PG-2021_42, PG-2021 Includes _43 (number MZ417335), PG-2021_45, PG-2021_47 (number MZ417337), PG-2021_48, PG-2021_49, PG-2021_50, PG-2021_51, PG-2021_52, PG-2021_53, PG-2021_63, PG-2021_64 (number MZ417340), PG-2021_68 (number MZ417342), PG-2021_78, PG-2021_84 (number MZ417345), PG-2021_86 (number MZ417346), and PG-2021_87 (number MZ417347). In embodiments, the S. aureus bacteriophage has a genome having sequence identity of at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 95%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, and 99.9% identity to one of the phages referenced above. The terms "phage" and "bacteriophage" are used interchangeably herein.

[0043] Staphylococcus aureus (S. aureus) is a Gram-positive, spherical bacterium that is a common member of the body's microbiome and is often found on the skin. While typically symbiotic, it can also be pathogenic, causing skin infections and / or exacerbating diseases and conditions affecting the skin. S. aureus strains are well known in the art, and a non-limiting example of a known exemplary S. aureus bacterial strain, UAMS-1, is described in Reference 10, which is incorporated herein by reference in its entirety.

[0044] When used with bacteria or bacteriophages, the term “isolated” means (1) isolated from at least some of the components that accompanied the initial production (whether in nature or in an experimental setting), and / or (2) produced, prepared, purified and / or manufactured by human hands using artificial culture conditions, such as (but not limited to) growth in plates and / or fermenters. Isolated bacteria include those cultured bacteria, even if such culture is not a single culture. In embodiments, isolated bacteria are bacteria cultured as a single culture (e.g., on plates or in a liquid culture such as in a fermenter). Isolated bacteria and bacteriophages can be isolated from at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 96%, about 97%, about 99%, or more (by weight) of the other components they originally accompanied. In embodiments, isolated bacteria are pure (by weight) more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99%. In embodiments, the isolated bacteriophage is pure (for example, by weight) more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99%. In embodiments, the composition provided herein comprises one or more isolated bacteriophages. In embodiments, the composition provided herein comprises one isolated bacteriophage. In embodiments, the administered bacteriophage is one isolated bacteriophage. In embodiments, the composition provided herein comprises one or more isolated bacteria. In embodiments, the composition provided herein comprises one isolated bacteria. In embodiments, the administered bacteria is one isolated bacteria.

[0045] The bacteriophages disclosed herein (e.g., S. aureus bacteriophage) are activators. In some embodiments, the bacteriophage activator consists of a bacteriophage (i.e., a bacteriophage alone, e.g., not bound to a solid support; a bacteriophage free in solution). In other embodiments, the bacteriophage activator may include or consist of a bacteriophage bound to another component, such as beads or other molecules. In yet another embodiment, the bacteriophage activator may include both a free bacteriophage and a bacteriophage bound to another molecule, such as a solid support. In some embodiments, the phage may be encapsulated or occluded in a suspension; such phage may be free or bound to a solid support.

[0046] A “control” sample or value refers to a sample that serves as a standard, usually a well-known standard, for comparison with the test sample. For example, a test sample may be taken under test conditions, e.g., in the presence of a test compound (e.g., an enzyme) or phage, and may be compared to a sample taken under well-known conditions, e.g., in the absence of the test compound, phage, or bacteria (negative control), or in the presence of a well-known compound, phage, or bacteria (positive control). A control may also represent an average value collected from multiple tests or results. Those skilled in the art will recognize that controls can be designed for the evaluation of multiple parameters. For example, controls may be designed to compare therapeutic effects based on pharmacological data (e.g., half-life, degradation of its biofilm or components, or lysis of bacterial cells, or symptoms such as disease, condition, or infection) or therapeutic measurements (e.g., comparison of side effects). Those skilled in the art will understand which controls are useful in a given situation and which data can be analyzed based on comparison with control values. Controls are also useful for determining the significance of data. For example, if the value for a given parameter varies widely in the controls, the variation in the test sample may not be considered significant. Controls may include, for example, subjects or groups who have the same disease, symptoms, or condition as the study subjects or study population, but who are receiving a placebo, some treatment, or no treatment.

[0047] The term “disease” refers to any deviation from normal health in a mammal, including the presence of disease symptoms and the state in which a deviation (e.g., dysbiosis, infection, gene mutation, gene deletion, etc.) has occurred but symptoms have not yet manifested. In embodiments, the disease is eczema. In embodiments, the disease includes dysbiosis of the skin. In embodiments, the methods, compositions, systems, phages and probiotic bacteria provided herein are suitable for use in subjects that are members of mammals, including, but not limited to, vertebrates, primates (such as humans), livestock, working animals and domestic pets (e.g., companion animals). In embodiments, the subject is a human subject. As used herein, “symptoms” of a disease include, but are not limited to, any clinical or experimental findings associated with the disease that can be felt or observed by the subject.

[0048] As used herein, the term “cutaneous dysbiosis” means a difference in the skin microbiota compared to a healthy or general population. In embodiments, dysbiosis is on the surface of the skin, within the skin (e.g., within a cutaneous area or within a layer of skin cells), within glands and / or within pores of the skin. In embodiments, dysbiosis is in sweat and / or sebum. In embodiments, skin is the face (e.g., the forehead, one or more cheeks, nose or chin of the subject). In embodiments, skin is any location on the body, including but not limited to the shoulders, chest, arms, elbows, legs and back. In embodiments, cutaneous dysbiosis includes changes in the diversity of symbiotic microbiota compared to a healthy or general population, and may include a decrease in beneficial microorganisms and / or an increase in pathogenic symbiotic organisms (pathogenic or potentially pathogenic microorganisms) and / or a decrease in overall symbiotic species diversity. Numerous factors, including hormonal changes, infrequent washing, use of cosmetics, use of antibiotics, psychological and physical stress, radiation, and dietary changes, can cause dysbiosis.

[0049] As used herein, “eczema” is a general term for many types of skin inflammation, also known as dermatitis. The most common form of eczema is atopic eczema or dermatitis (many practitioners use the terms eczema and dermatitis interchangeably). However, there are many other diverse forms of eczema, including, among others, contact eczema, allergic contact eczema, seborrheic dermatitis, nummular eczema, neurodermatitis, stasis dermatitis, and dyshidrotic eczema.

[0050] Atopic dermatitis is a chronic skin disease characterized by itchy, inflamed skin and is the most common cause of eczema. The condition tends to appear and disappear in response to exposure to triggers or causative factors. Factors that may cause atopic dermatitis (allergens) include environmental factors such as mold, pollen, or pollutants; contact with irritants such as soap, surfactants, nickel (found in jewelry), or perfumes; food allergies; or other allergies. Approximately two-thirds of those who develop the condition develop it by the age of one. When the disease begins in infancy, it is sometimes called infantile eczema.

[0051] Contact dermatitis is a local reaction involving redness, itching, and burning in the area where the skin has come into contact with an allergen (an allergen that has sensitized an individual) or a common irritant such as an acid, detergent, or other chemical. Other examples of contact dermatitis include reactions to laundry surfactants, soaps, nickel (found in jewelry), cosmetics, fabrics, clothing, and perfumes. Because individuals have come into contact with a vast number of substances, it can be difficult to determine the trigger for contact dermatitis. Sometimes the condition is called allergic contact dermatitis (i.e., allergic contact dermatitis) when the trigger is an allergen, and irritant contact dermatitis (i.e., irritant contact dermatitis) when the trigger is an irritant. Skin reactions to poison ivy, oak, and / or sumac are examples of allergic contact dermatitis. People with a history of allergies are at higher risk of developing contact dermatitis.

[0052] Seborrheic dermatitis (also known as seborrheic eczema) is a form of skin inflammation of unknown cause. Signs and symptoms of seborrheic dermatitis include yellowish, oily, scaly patches of skin on the scalp, face, and sometimes other parts of the body. Dandruff and "cradles" in infants are examples of seborrheic dermatitis. Seborrheic dermatitis often causes inflammation of the face, particularly on the folds of the cheeks and / or nose. Seborrheic dermatitis is not always itchy. The condition tends to run in families. Emotional stress, oily skin, infrequent hair washing, and weather conditions can all increase the risk of developing seborrheic dermatitis. One type of seborrheic dermatitis is also common in people with AIDS.

[0053] Nummular eczema (i.e., nummular dermatitis) is characterized by coin-shaped patches of irritated skin (most commonly on the arms, back, buttocks, and lower legs) that are scaly, scalding, and sometimes very itchy. This form of eczema is relatively rare and most frequently occurs in older men. Nummular eczema is usually a chronic condition. A history or family history of atopic dermatitis, asthma, or allergies increases the risk of developing the condition.

[0054] Neurodermatitis, also known as focal neurodermatitis, is a chronic skin inflammation that begins with localized itching (e.g., an insect bite) and develops through a scratch-itch cycle, where scratching leads to increased irritation. Women are more prone to neurodermatitis than men, and the condition is most common in people aged 20-50 years. This form of eczema presents as scaly patches on the skin of the scalp, lower legs, wrists, or forearms. Over time, the skin may thicken and become leathery. Stress can worsen the symptoms of neurodermatitis.

[0055] Stasis dermatitis is a skin irritation of the lower legs commonly associated with circulatory disorders, also known as venous insufficiency, where the function of the valves in the veins is impaired. Stasis dermatitis affects approximately 6-7% of the population over 50 years of age and almost without exception occurs in middle-aged and elderly individuals. The risk of developing stasis dermatitis increases with age. Symptoms include itching and / or red to brown discoloration of the skin on one or both legs. As the condition progresses, vesicular formation and exudative skin lesions may occur, often seen with other forms of eczema, and ulcers may develop in the affected area. Chronic circulatory disorders result in fluid retention or increased edema in the legs. Stasis dermatitis is also called varicose vein eczema.

[0056] Dyshidrotic eczema (i.e., dyshidrotic dermatitis) is an irritation of the skin of the palms of the hands and soles of the feet, characterized by itchy, burning, clear, deep blisters. The cause of dyshidrotic eczema is unknown. Dyshidrotic eczema is also known as vesicular palmoplantar dermatitis, dyshidrosis, or dyshidrotic eczema. This form of eczema occurs in up to 20% of people with hand eczema and is more common in the warmer climates of spring and summer.

[0057] Eczema can occur in people of all races and affect people of all ages, but the condition is most common in infants and young children, with about 85% developing symptoms before the age of five. Typically, eczema resolves permanently by the age of three in only about half of affected infants and young children. In others, the condition tends to recur throughout life. People with eczema have a family history of the condition or a family history of other allergic conditions such as asthma and / or seasonal rhinitis. It is estimated that about 20% of children and about 1% to 5% of adults have eczema. This means that in the United States alone, more than 15 million people exhibit symptoms of the disease, and more than 32 million people have eczema. Current statistics suggest that the number of people affected by eczema has tripled in the last 30 years, and that one-fifth of children are affected. There is currently no known cure for eczema, and it is generally accepted from a medical standpoint that symptoms can persist for a person's lifetime.

[0058] While eczema is not thought to be contagious, it is believed to be at least partially hereditary. Therefore, it is not uncommon to find other family members affected.

[0059] Skin conditions such as eczema can be painful and distressing. Eczema symptoms generally involve unbearable itching, and those affected typically suffer from sleep deprivation, often described as "sleeping in an ant's nest." In a very large number of cases, children and infants with congenital eczema have been reported to have significant developmental delays in speech and growth.

[0060] A normal skin barrier is thick, and in the stratum corneum, corneodesmosomes are intact. The outermost binding layer breaks, releasing unwanted cells, and the outermost layer of dead skin cells sloughs off, barely detectable. However, in atopic eczema or dermatitis and other dry skin disorders, the skin barrier is typically thinner than normal, impairing the skin's protective and regulatory abilities. When the skin barrier is compromised, cracks appear, allowing allergens and infectious pathogens such as dust mites and bacteria to penetrate the skin, leading to the worsening of skin disorders.

[0061] Current treatment for eczema involves applying moisturizer 4-6 times a day. Healthcare professionals may prescribe topical hydrocortisone, but this treatment is usually discontinued after 7 days, and its use in children under 2 years of age or on irritated or damaged skin is considered dangerous. Eczema is irritated and damaged skin, and those affected are often under 2 years of age. In any case, it is well known that topical steroids do not cure eczema, and they are often applied for several years, which can lead to persistent thinning of the skin, striae, cataracts (if used near the eyes), and Cushing's syndrome.

[0062] Topical immunosuppressants (topical calcineurin inhibitors) are sometimes prescribed to reduce eczema symptoms. However, such products do not provide a cure, and doctors are hesitant to prescribe immunosuppressants due to proven side effects. In particular, in 2006, the U.S. Food and Drug Administration warned on product packaging that "a small number of malignancies (skin cancer and lymphoma) have been reported in patients using topical calcineurin inhibitors."

[0063] Typically, more than half of eczema sufferers exhibit salicylic acid sensitivity, meaning their condition worsens after consuming salicylic acid-containing foods (found in many healthy foods, fruits and vegetables, sauces and juices). Susceptibility to salicylic acid (and several other chemicals) reduces people's quality of life, and long-term adherence to a low-salicylic acid diet can be restrictive and may lead to nutritional deficiencies. It is also well known that eczema sufferers have elevated blood histamine levels, along with a reduced ability to detoxify these histamines.

[0064] Therefore, this composition and method address these drawbacks and provide unexpected, rapid, and long-lasting relief of eczema symptoms.

[0065] The term “diagnosis” refers to the relative likelihood that a subject has a given metabolic disorder. Symptoms and diagnostic criteria are summarized herein. Similarly, the term “prognosis” refers to the relative likelihood that a particular future outcome may occur in a subject. For example, in the context of this invention, prognosis may refer to the likelihood that an individual will develop eczema. Prognosis may also refer to the likelihood of the severity of the disease (e.g., the importance of symptoms, the rate of functional decline, etc.). The terms are not intended to be absolute, as would be understood by any person skilled in the art in the field of medical diagnosis.

[0066] "Pharmacologically acceptable excipients" and "pharmaceutically acceptable carriers" refer to substances that can be included in the composition of the present invention without causing significant harmful toxicological effects to the patient, while assisting in the administration and absorption of the activator to the subject. Non-limiting examples of pharmacoagulable excipients include water, NaCl, physiological saline, Ringer's lactate, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, saline solutions (e.g., Ringer's solution), alcohols, oils, gelatin, carbohydrates, such as lactose, amylose or starch, fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidone, and colorants. Such preparations may be sterilized and, if desired, may be mixed with adjuvants such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts to affect osmotic pressure, buffers, colorants, and / or aromatics that do not react adversely with bacteriophages, probiotic bacteria, and / or the compounds of the present invention. Those skilled in the art will recognize that other pharmaceutically acceptable excipients are also useful in the present invention.

[0067] Additional components that may be added to the therapeutic compositions of the present disclosure, including colloidal oatmeal and bacteriophages, include, but are not limited to, enzymes, ceramides, hyaluronic acid, glycerin, petrolatum, and niacinamide.

[0068] As used herein, “colloidal oatmeal” refers to finely powdered and heat-treated oatmeal, such as boiled oatmeal (e.g., Avena sativa), which has been used to extract colloidal materials. Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) in accordance with the “Over-The-Counter Final Monograph for Skin Protectant Drug Products,” published in June 2003. Its preparation is also standardized by the United States Pharmacopeia and is publicly known in the art. Colloidal oatmeal contains a wide variety of functional molecules, such as starch and beta-glucans that contribute to protective and moisturizing functions, various types of phenols that confer antioxidant and anti-inflammatory functions, and saponins that contribute to cleansing functions. Colloidal oatmeal also has the ability to act as a pH buffer and can help regulate the pH of the skin to provide symptom relief and potentially optimize the stability and activity of S. aureus phage. Therefore, its numerous functional properties make colloidal oatmeal a cleanser, humectant, buffer, and soothing and protective anti-inflammatory agent. Examples of colloidal raw materials (brands) available include, but are not limited to, Aquaphor, Cetaphil, Cerave, Exederm, and Eczema Honey.

[0069] "Patient" or "subject in need" refers to a living member of the animal kingdom that is suffering from or susceptible to the disorder described. In embodiments, the subject is a member of a species that includes individuals naturally affected by the disease. In embodiments, the subject is a mammal. Non-limiting examples of mammals include rodents (e.g., mice and rats), primates (e.g., lemurs, bush babies, monkeys, apes and humans), rabbits, dogs (e.g., companion dogs, service dogs or working dogs, e.g., police dogs, military dogs, racing dogs or show dogs), horses (e.g., racehorses and working horses), cats (e.g., domestic cats), livestock (e.g., pigs, cattle, donkeys, mules, bison, goats, camels and sheep), and deer. In embodiments, the subject is a human. Therefore, the method is applicable to both human treatment and veterinary applications.

[0070] The terms "subject," "patient," and "individual" are not intended to be restrictive and can be used interchangeably in general. That is, an individual described as a "patient" may not necessarily have a given disease and may simply be seeking medical advice.

[0071] As used herein, the abbreviation "sp." for species means at least one species of the indicated genus (e.g., 1, 2, 3, 4, 5 or more species). The abbreviation "spp." for species means two or more species of the indicated genus (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10 or more species). In embodiments, the methods and compositions provided herein include a single species within one indicated genus or multiple indicated genuses, or two or more species (e.g., more than two) within one indicated genus or multiple indicated genuses. In embodiments, 1, 2, 3, 4, 5 or more, or all or the indicated species are isolated. In embodiments, the indicated species are administered together. In embodiments, each indicated species is present in a single composition containing the respective species. In this embodiment, each species is administered simultaneously, for example, within approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 30 or 60 seconds or minutes, between each other, between 1-5, 1-10, 1-30, 1-60 or 5-15 seconds.

[0072] As used herein, “to treat” a condition, disease, or disorder, or symptoms associated with a condition, disease, or disorder, or such “treatment” refers to a method for obtaining beneficial or desirable outcomes, including clinical outcomes. Beneficial or desirable clinical outcomes include, but are not limited to, the reduction or recovery of one or more symptoms or conditions, whether partial or whole; a decrease in the severity of a condition, disorder, or disorder; stabilization of the condition, disorder, or disorder; prevention of the development of a condition, disorder, or disorder; prevention of the spread of a condition, disorder, or disorder; slowing or delaying the progression of a condition, disorder, or disorder; delaying or delaying the onset of a condition, disorder, or disorder; recovery or mitigation of the condition, disorder, or disorder; and remission. “To treat” may also mean inhibiting the progression of a condition, disorder, or disorder, temporarily slowing the progression of a condition, disorder, or disorder, but in some cases also includes permanently halting the progression of a condition, disorder, or disorder.

[0073] As used herein, the terms “treatment” and “prevention” are not intended to be complete. In embodiments, treatment may refer to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% reduction in the severity of an established disease, condition, or symptoms of a disease or condition. In embodiments, a method for treating a disease is considered a treatment if there is a 10% reduction in one or more symptoms of the disease in the subject compared to a control. Thus, the reduction may be 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or any percentage reduction between 10% and 100% compared to natural or control levels. It is understood that treatment does not necessarily mean a cure or complete disappearance of a disease, condition, or symptoms of a disease or condition. In embodiments, criteria for reduction, mitigation, or suppression include changes of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more compared to a control level, and such terms may include, but do not necessarily include, complete elimination. Treatment may refer to any delay in onset, recovery of symptoms, improvement of the appearance of the patient's skin, etc. The effect of treatment may be compared to an untreated individual or a pool of individuals, or the same patient at different points in time before or during treatment. In embodiments, the severity of the disease is reduced to, for example, at least 10% compared to an individual before administration or an untreated control individual. In some embodiments, the severity of the disease is reduced to at least 25%, 50%, 75%, 80%, or 90%, or in some cases, is no longer detectable by standard diagnostic techniques. In embodiments, the treatment is effective in reducing at least one symptom of eczema. In the embodiments, the treatment is effective in reducing the level of one or more symptoms such as itching, burning, stinging skin, redness or skin rash, flaking skin, sleep disturbance due to skin discomfort, rough bumpy skin, skin discoloration, exudation, and crusting, although this is not limited to these.Therefore, the treated subjects show a greater reduction in symptoms over the same period of time as the corresponding control subjects (e.g., subjects with eczema who received treatment including bacteriophage alone or colloidal oatmeal alone or a placebo, or who did not receive treatment), and / or show a faster reduction in symptoms compared to the corresponding control subjects.

[0074] In embodiments, the compositions of this disclosure are administered to subjects suffering from eczema in a “therapeutic dose.” The effective dose for this use may depend on the severity of the disease and the patient’s overall health condition. Single or multiple doses of the compositions may be administered according to the dosage and frequency required and tolerated by the patient, and / or determined by a physician or other healthcare professional.

[0075] The terms "effective dose," "effective dosage," and "therapeutic effective dose" refer to the amount of drug sufficient to restore the impairment described herein. For example, for a given parameter, a therapeutic effective dose represents an increase or decrease of at least 5%, 10%, 15%, 20%, 25%, 40%, 50%, 60%, 75%, 80%, 90%, or at least 100%. Therapeutic effectiveness can also be expressed as a "times" increase or decrease. For example, a therapeutic effective dose may have an effect of at least 1.2 times, 1.5 times, 2 times, 5 times, or more than that of the control.

[0076] Compositions containing bacteriophages and combination therapy In one embodiment, the Specified Information Provides a composition comprising, essentially, at least one S. aureus bacteriophage, colloidal oatmeal, and optionally one or more pharmaceutically acceptable carriers and / or optionally one or more additional activators, components, or constituents. The S. aureus bacteriophage is free in the composition and is not bound to another molecule or solid support such as beads.

[0077] In one embodiment, the Specified Information provides a composition comprising at least one S. aureus bacteriophage and colloidal oatmeal, and optionally one or more additional activators.

[0078] In one embodiment, the Specified herein provides a composition comprising an activator consisting of at least one S. aureus bacteriophage and colloidal oatmeal.

[0079] In one embodiment, a composition is provided herein comprising at least one S. aureus bacteriophage, colloidal oatmeal, and one or more additional activators, wherein the one or more additional activators include ceramide, hyaluronic acid, glycerin, petrolatum, niacinamide, enzymes, probiotic bacteria, aloe, mineral oil, humectants, lanolin, antihistamines, alpha hydroxy acids (e.g., glycolic acid), and optionally pharmaceutically acceptable carriers or excipients.

[0080] In one embodiment, a composition comprising at least one S. aureus bacteriophage and colloidal oatmeal is provided herein, wherein the composition does not contain probiotic bacteria.

[0081] In embodiments, at least one additional activator includes ceramide. In embodiments, ceramide is present at a concentration of 2.5% to 10% (weight / volume). In embodiments, ceramide is present at a concentration of less than 2.5% but higher than approximately 0.1%, 0.5%, 1%, 1.5%, or 2% (weight / volume). In embodiments, ceramide is present at a concentration of 2.5% to 10%, for example, approximately 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% (weight / volume). In embodiments, ceramide is present at a concentration of less than 2.5% but higher than approximately 0.1%, 0.5%, 1%, 1.5%, or 2% (weight / volume).

[0082] In embodiments, at least one additional activator includes hyaluronic acid. In embodiments, hyaluronic acid is present at a concentration of 0.5% to 2% (weight / volume). In embodiments, hyaluronic acid is present at a concentration of less than 0.5% but higher than about 0.1% (weight / volume). In embodiments, hyaluronic acid is present at a concentration of 0.5% to 2%, for example, about 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, or 2% (weight / volume). In embodiments, hyaluronic acid is present at a concentration of less than 0.5% but higher than about 0.1% (weight / volume).

[0083] In embodiments, at least one additional activator includes petrolatum. In embodiments, petrolatum is present at a concentration of 3% to 10% (weight / volume). In embodiments, petrolatum is present at a concentration of less than 3% but higher than about 0.1%, 0.5%, 1%, 1.5%, 2%, or 2.5% (weight / volume). In embodiments, petrolatum is present at a concentration of 3% to 10%, for example, about 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% (weight / volume). In embodiments, petrolatum is present at a concentration of less than 3% but higher than about 0.1%, 0.5%, 1%, 1.5%, 2%, or 2.5% (weight / volume).

[0084] In embodiments, at least one additional activator comprises glycerin. In embodiments, glycerin is present in concentrations of 2% or 3% to 8% (weight / volume), (e.g., about 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, or 8%) (weight / volume).

[0085] In embodiments, at least one additional activator comprises niacinamide. In embodiments, niacinamide is present at concentrations of 2% to 8% (weight / volume) (e.g., about 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, or 8%) (weight / volume).

[0086] In an embodiment, the S. aureus bacteriophage is about 1×10 5 , 1×10 6 , 2×10 6 , 3×10 6 , 4×10 6 , 5×10 6 , 6×10 6 , 7×10 6 , 8×10 6 , 9×10 6 , 1×10 7 , 2×10 7 , 3×10 7 , 4×10 7 , 5×10 7 , 6×10 7 , 7×10 7 , 8×10 7 , 9×10 7 , 1×10 8 , 2×10 8 , 3×10 8 , 4×10 8 , 5×10 8 , 6×10 8 , 7×10 8 , 8×108, 9×10 8 , 1×10 9 , 2×10 9 , 3×10 9 , 4×10 9 , 5×10 9 , 6×10 9 , 7×10 9 , 8×10 9 , 9×10 9 , 1×10 10 , 2×10 10 , 3×10 10 , 4×10 10 , 5×10 10 , 6×10 10 , 7×10 10 , 8×10 10 , 9×10 10 Or it is present in an amount of about 1×10 11 plaque forming units (pfu). In an embodiment, the S. aureus bacteriophage is about 1×10 6 ~1×10 11 pfu. In an embodiment, the S. aureus bacteriophage is about 1×106 ~1×10 8 、 about 1×10 8 ~1×10 9 、 about 1×10 9 ~1×10 10 、 about 1×10 9 ~1×10 11 or about 1×10 10 ~1×1011 pfu are present in an amount. In some embodiments, the amount of S. aureus bacteriophage is provided or described as a concentration (e.g., pfu per mL (pfu / mL)).

[0087] In embodiments, the probiotic bacteria are present in the composition. In some embodiments, the probiotic bacteria are about 1×10 5 、 1×10 6 、 2×10 6 、 3×10 6 、 4×10 6 、 5×10 6 、 6×10 6 、 7×10 6 、 8×10 6 、 9×10 6 、 1×10 7 、 2×10 7 、 3×10 7 、 4×10 7 、 5×10 7 、 6×10<00​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​10 , 2×10 10 , 3×10 10 , 4×10 10 , 5×10 10 , 6×10 10 , 7×10 10 , 8×10 10 , 9×10 10 or 1×10 11 present in the amount of colony forming units (cfu). In embodiments, the probiotic bacteria are about 1×10 6 ~ 1×10 11 present in the amount of cfu. In embodiments, the probiotic bacteria are about 1×10 6 ~ 1×10 8 , about 1×10 8 ~ 1×10 9 , about 1×10 9 ~ 1×10 10 , about 1×10 9 ~ 1×10 11 or about 1×10 10 ~ 1×10 11 present in the amount of cfu. In some embodiments, the amount of probiotic bacteria is provided or described as a concentration (e.g., cfu per mL (cfu / mL)).

[0088] By way of example and not limitation, the probiotic bacteria can be one or more of the following: Staphylococcus epidermidis, Staphylococcus aureus 502A, Staphylococcus hominis, and Roseomonas mucosa.

[0089] In one embodiment, a composition comprising S. aureus bacteriophage, colloidal oatmeal, and an enzyme is provided herein. In some embodiments, the enzyme includes endolysin, SH3 domain-containing protein, CHAP domain-containing protein, lysine, taillysine, and / or anti-inflammatory cytokines. Enzymes such as endolysin may be provided by the phage itself and / or added externally. Exemplary, non-limiting enzymes are known in the Art, for example, GenBank AHB79986.1 (Presumed endolysin of Staphylococcus phage K); NCBI reference sequence: YP_009780264.1 (SH3 domain-containing protein of Staphylococcus phage ISP); NCBI reference sequence: YP_009780266.1 (CHAP domain-containing protein of Staphylococcus phage ISP); NCBI reference sequence: YP_008873573.1 (Presumed endolysin of Staphylococcus phage Sb1); NCBI reference sequence: YP_007002194.1 (Staphylococcus phage G15) The putative lysine is shown in the following NCBI reference sequences:UP_009275797.1(Tail lysine of Staphylococcus phage Stau2);NCBI reference sequence:YP_009275798.1(Tail lysine of Staphylococcus phage Stau2);NCBI reference sequence:YP_009275799.1(Putative tail lysine of Staphylococcus phage Stau2);NCBI reference sequence:YP_009275801.1. These publicly available NCBI and GenBank sequence registrations are incorporated herein by reference in their entirety.

[0090] In one embodiment, the Specified Information Provides a composition comprising essentially one or more thereof, comprising at least one S. aureus bacteriophage and at least one additional activator comprising an enzyme (e.g., as described above), wherein each of the at least one S. aureus bacteriophage and the enzyme comprises at least one additional activator, each of which is in a composition further comprising a pharmaceutically acceptable carrier.

[0091] In one embodiment, a combination of S. aureus bacteriophage, colloidal oatmeal, and an enzyme (for example, as described above) is provided herein.

[0092] In the embodiments, the composition or combination contains a S. aureus biofilm-degrading enzyme. In the embodiments, the enzyme is glycosidase, protease, DNAse, or restriction endonuclease. In the embodiments, the enzyme is glycosidase. In the embodiments, the glycosidase is glycoside hydrolase. In the embodiments, the enzyme catalyzes the hydrolysis of a linear polymer of N-acetyl-D-glucosamine. In the embodiments, the enzyme is β-hexosaminidase. In the embodiments, the enzyme hydrolyzes the β-1,6-glycosidic bond of the acetylglucosamine polymer. In the embodiments, the enzyme is DNAse I, restriction endonuclease, papain, bromelain, trypsin, proteinase K, subtilisin, serrathiopeptidase, dispersin, alginate lyase, amylase, or cellulase. In the embodiments, the enzyme is dispersin B. In this embodiment, the enzyme is a protease, and the protease is proteinase K or subtilisin.

[0093] Additionally or alternatively, in some embodiments, the composition or combination comprises a bacterial cell wall-degrading enzyme. In some embodiments, the cell wall-degrading enzyme comprises bacterial endolysin. In some embodiments, the endolysin is specific to Staphylococcus, and non-limiting examples include: GenBank AHB79986.1 (Prosecutor endolysin of Staphylococcus phage K); NCBI reference sequence: YP_009780264.1 (SH3 domain-containing protein of Staphylococcus phage ISP); NCBI reference sequence: YP_009780266.1 (CHAP domain-containing protein of Staphylococcus phage ISP); NCBI reference sequence: YP_008873573.1 (Prosecutor endolysin of Staphylococcus phage Sb1); NCBI reference sequence: YP_00700 Contains one or more of the following: 2194.1 (presumed lysine of Staphylococcus phage G15); NCBI reference sequence: UP_009275797.1 (tail lysine of Staphylococcus phage Stau2); NCBI reference sequence: YP_009275798.1 (tail lysine of Staphylococcus phage Stau2); NCBI reference sequence: YP_009275799.1 (presumed tail lysine of Staphylococcus phage Stau2); NCBI reference sequence: YP_009275801.1.

[0094] In additional or alternative embodiments, the composition or combination comprises an anti-aging enzyme. In embodiments, the anti-aging enzyme is superoxide dismutase or peroxidase.

[0095] In this embodiment, S. aureus bacteriophage has a linear double-stranded DNA genome.

[0096] In this embodiment, S. aureus bacteriophage is a bacteriophage, belonging to the caudoviruses order.

[0097] In this embodiment, the bacteriophage is a wild-type bacteriophage. In this embodiment, the bacteriophage has a genome containing a nucleotide sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9% identical to the genome sequence of wild-type S. aureus bacteriophage. Non-limiting examples of currently useful S. aureus bacteriophages include SEQ ID NO: 1, SEQ ID NO: 44, SEQ ID NO: 45, and / or SEQ ID NO: 46.

[0098] A therapeutic composition disclosed herein comprising colloidal oatmeal, a bacteriophage, and optionally one or more additional activators, such as endolysin. For example, but not limited to, the following formulations: in one or a combination of an aqueous phase, an organic phase, an oil-in-water emulsion, an oil-in-water emulsion, a biphasic phase-separation form, or one of the above formulations, the phage or other component is encapsulated or occluded in a suspension in a culture medium. 3 ~10 12 A therapeutic composition containing phages together with 1% colloidal oatmeal at a concentration between pfu / mL.

[0099] The combination of bacteriophage and colloidal oatmeal exhibits a synergistic effect in treating dysbiosis of the target skin (e.g., eczema). That is, as demonstrated in the examples, the combination shows a greater therapeutic effect (i.e., relief from and / or reduction of symptoms) than each component alone, i.e., bacteriophage alone or colloidal oatmeal alone.

[0100] For example, and not limited to, combinations of colloidal oatmeal and bacteriophages increase bacterial killing. In addition, combinations of colloidal oatmeal and bacteriophages provide at least one of the following unexpected effects: increased phage penetration into the target skin and increased phage retention in the target skin, thereby increasing the phage contact time with target bacteria. The increased phage contact time allows for increased destruction of target bacteria and faster treatment / recovery from eczema than provided by prior art compositions and methods, or by treatment with phage alone, or by treatment with colloidal oatmeal alone. That is, while the well-known benefits of colloidal oatmeal (e.g., soothing, moisturizing, providing a barrier against further infection, anti-inflammatory properties) contribute to symptom relief, rather than simply relivering symptoms, it allows for more opportunities for phages to lyse target cells and treat dysbiosis.

[0101] For example, but not limited to, it is expected that at least one symptom of eczema in the treated subject will show a statistically relevant reduction or a reduction at a statistically relevant earlier time compared to the eczema symptoms of an equivalent control subject (e.g., a subject treated with placebo or with phage alone or colloidal oatmeal alone). For example, subjects treated with the compositions and methods disclosed herein will show at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or more improvement in symptoms at the same time as an equivalent control subject. Additionally or alternatively in some embodiments, subjects treated with the compositions and methods disclosed herein will show improvement in at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% less time than an equivalent control subject.

[0102] In some embodiments, subjects diagnosed with, suffering from, or suspected of having a cutaneous dysbiosis such as eczema are treated with a composition of the present technology, namely a composition comprising a bacteriophage and colloidal oatmeal. The composition is applied topically to the skin of the subject. In some embodiments, the composition is applied to at least the affected area of ​​the skin of the subject (e.g., the area showing eczema), and in some embodiments, the composition is applied to the skin surrounding the affected area.

[0103] In some embodiments, the composition is administered once, twice, three, four, five, or six times daily, or as needed. In some embodiments, the composition is applied over a period of one week, two weeks, three weeks, one month, two months, three, four, five, six, seven, eight, nine, ten, eleven months, or more than one year. In some embodiments, the composition is applied daily as needed until the symptoms of skin dysbiosis (e.g., eczema) are reduced or eliminated. It is predicted that subjects treated with the compositions of this technology will show a faster reduction in symptoms of skin dysbiosis (e.g., eczema) than equivalent subjects not treated with the disclosed compositions.

[0104] Furthermore, all methods described herein may be carried out in any preferred order, unless otherwise indicated herein and unless clearly contradicted by the context. Any and all examples or illustrative words provided herein (e.g., "etc.") are intended solely to further illustrate the invention and do not limit the scope of the invention unless specifically claimed. Words in the specification should not be construed as indicating that any unclaimed element is essential to the practice of the invention.

[0105] Preferred embodiments of the present invention are described herein, including the best modes well known to the inventors for carrying out the invention. Variations of these preferred embodiments will become apparent to those skilled in the art by reading the foregoing description. The inventors expect those skilled in the art to use such variations as appropriate, and the inventors intend that the invention may be carried out in ways other than those specifically described herein. Accordingly, the invention includes, to the extent permitted by applicable law, all modifications and equivalents of the subject matter enumerated in the claims appended herein. Furthermore, any combination of all possible variations of the elements described above is encompassed by the invention unless otherwise stated herein and unless it is clearly inconsistent with the context. [Examples]

[0106] The following examples are illustrative and should not be construed as limiting the scope of the claimed subject matter.

[0107] Example 1: Higher stability: The phages can be stored for an even longer period in the presence of colloidal oatmeal (CO).

[0108] S. aureus phage MESA-11 (SEQ ID NO: 45) was prepared in either PBS or PBS + 1% colloidal oatmeal (CO). Each preparation was incubated in sets of three at 30C for 48 hours, and the phage concentration was determined by titer assay and compared to the initial concentration at t=0. Despite starting at the same concentration, 1% CO was found to confer higher stability (2.64x, 264%) than phage in PBS alone.

[0109] Temperature: In the first experiment, the stability of S. aureus bacteriophage preparations with and without CO was tested by incubation at room temperature and at increased temperatures. Under one or more of these conditions, the presence of colloidal oatmeal is expected to extend the stability of S. aureus bacteriophage.

[0110] pH: In the second experiment, S. aureus bacteriophage preparations with or without CO were incubated in buffers of various pH values. Due to the acidic buffering capacity of colloidal oatmeal, S. aureus bacteriophage were expected to show better survival at alkaline pH (as found in eczematous skin).

[0111] Example 2: Phage protection: CO extends the presence or activity of phages in the skin.

[0112] Several topical formulations (A-F) are prepared and evaluated as follows: A: Phage containing 1% CO in the aqueous phase formulation B: Phage containing 1% CO in organic phase formulations C: Phage containing 1% CO in oil-in-water emulsion formulations D: Phage containing 1% CO in an oil-water emulsion formulation E: Phage containing 1% CO in discontinuous aqueous and organic phase formulations F: Phages containing 1% CO in formulations in which phages are encapsulated or occluded within the suspension.

[0113] S. aureus bacteriophage preparations A-F, prepared with or without CO, were applied to the skin of human subjects. After a certain period of time, the applied area was wiped off, and the viable phages were quantified using a phage titer assay. Colloidal oatmeal is expected to have a positive effect on the survival of S. aureus bacteriophages on the skin.

[0114] Example 3: CO enhances phage entry into the skin.

[0115] Preparations A-F of S. aureus bacteriophage, prepared with or without CO, were applied to the skin of human subjects. After complete absorption, the applied area was subjected to tape stripping to isolate layers of the stratum corneum. Each tape strip was titrated to quantify S. aureus bacteriophage within continuous layers of the stratum corneum. The persistence of S. aureus bacteriophage in deeper layers of the stratum corneum in the colloidal oatmeal-containing preparations demonstrated that the colloidal oatmeal-containing preparations are expected to exhibit deeper penetration into the skin.

[0116] Example 4: CO enhances bacterial killing.

[0117] S. aureus phage (MESA-11 SEQ ID NO: 45) was added to log-phase cultures of S. aureus strain UAMS-01 in BHI broth in or without 1% CO. Three cultures were incubated aerobically at 37°C. After 24 hours of incubation, the viability of S. aureus bacteria was measured by seeding serial dilutions onto BHI agar plates. After overnight incubation at 37°C, S. aureus viability was calculated by counting colonies in the relevant dilutions and multiplying by the dilution factor and the inverse fraction of the seeded 1 mL. On average, the viability of S. aureus in the presence of 1% CO was 59% of the comparable viability in the absence of CO (0.73 x 10⁻¹⁰, respectively). 10 pfu / mL vs 1.23 x 10 10 It was found that (pfu / mL)

[0118] S. aureus bacteriophage preparations A-F, prepared with or without CO, were incubated with S. aureus host bacteria. The efficiency of killing S. aureus bacteria was evaluated and compared by determining the growth dynamics, phage proliferation, and host cell viability of each preparation. The presence of colloidal oatmeal is expected to enhance bacterial killing by S. aureus bacteriophages.

[0119] Example 5: CO soothes the skin with phage application.

[0120] S. aureus bacteriophage preparations A-F, prepared with or without CO, are applied to irritated or inflamed skin. After repeated application, the affected area is evaluated to quantify inflammation. The presence of colloidal oatmeal is expected to reduce inflammation more effectively than S. aureus bacteriophage alone.

[0121] In treating irritated or inflamed skin, such as eczematous skin, a combination of S. aureus bacteriophage and colloidal oatmeal is expected to achieve a synergistic effect that exceeds the additive effect (i.e., the combined effect of the bacteriophage and colloidal oatmeal is greater than the combined effect of the bacteriophage and colloidal oatmeal when each drug is used separately). The effectiveness of the treatment is measured by evaluating the patient's skin for a reduction in pain, itching, elevation, exudation, discoloration, and overall discomfort.

[0122] References

[0123] [Table 1] TIFF2026513336000003.tif214167

Claims

1. a) Bacteriophage viruses, and b) Colloidal oatmeal A composition formulated for topical administration, containing the following:

2. The composition according to claim 1, wherein the bacteriophage virus comprises Staphylococcus bacteriophage.

3. The composition according to claim 2, wherein the bacteriophage virus comprises Staphylococcus aureus (S. aureus) bacteriophage.

4. The composition according to claim 3, wherein S. aureus bacteriophage comprises SEQ ID NO: 1, SEQ ID NO: 44, SEQ ID NO: 45 and / or SEQ ID NO:

46.

5. The composition according to claim 1, further comprising one or more additional activators.

6. The composition according to claim 5, wherein one or more additional activators include ceramide, hyaluronic acid, glycerin, petrolatum, niacinamide, enzymes, and probiotic bacteria.

7. The composition according to claim 6, wherein the enzyme comprises a bacterial cell wall-degrading enzyme.

8. The composition according to claim 6, wherein the enzyme comprises endolysin.

9. The composition according to claim 6, wherein the enzyme comprises an anti-aging enzyme.

10. The composition according to claim 1, comprising one or more S. aureus bacteriophages and colloidal oatmeal.

11. A method for treating eczema in a subject requiring treatment for eczema, comprising topically administering the composition according to claim 1 to a region of the subject's skin including eczema.

12. The method according to claim 11, wherein the administration includes administration once a day, twice a day, three times a day, or four times a day.

13. The method according to claim 12, wherein the composition is administered for one week, two weeks, three weeks or longer.

14. The method according to claim 11, comprising treating one or more of the following eczematous symptoms: itchy skin, dry skin, redness, and swelling in an area of ​​skin to which the composition is administered.

15. The method according to claim 14, wherein the reduction of one or more eczematous symptoms occurs more quickly than in the control group.

16. The method according to claim 15, wherein the treated subject shows improvement 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% faster than an equivalent control subject.

17. The method according to claim 14, wherein the treated subject shows improvement of at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or greater in at least one symptom compared to an equivalent control subject, over the same period of time.

18. The method according to claim 11, wherein the eczema is selected from contact eczema, allergic contact eczema, seborrheic dermatitis, nummular eczema, neurodermatitis, stasis dermatitis, and dyshidrotic eczema.

19. The method according to claim 11, wherein the eczema includes atopic eczema.

20. The method according to claim 11, wherein the subject is a human.

21. The composition according to claim 1, wherein the bacteriophage contains a nucleic acid sequence that is at least 90% identical to one or more of SEQ ID NOs: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 45 and / or 46.

22. The composition according to claim 1, wherein the bacteriophage comprises a nucleic acid encoding a polypeptide that is at least 90% identical to one or more of SEQ ID NOs: 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, and 43.

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