Rifamycin composition for treating sarcopenia

Abstract

The present disclosure relates to a composition comprising Rifamycin SV and its use in the treatment of sarcopenia. More particularly, the present disclosure describes a pharmaceutical composition comprising Rifamycin SV for treating sarcopenia in subjects with a chronic disease.

Description

RIFAMYCIN COMPOSITION FOR TREATING SARCOPENIACROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 583,745, filed September 19. 2023 and U.S. Provisional Patent Application No. 63 / 589,236, filed October 10, 2023, each of which is incorporated by reference herein in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0002] This invention was made with government support under a Cooperative Research and Development Agreement (CRADA) between the U.S. Department of Veterans Affairs and Cosmo Technologies Ltd., “A Double-blind Randomized Controlled Trial of Rifamycin in Minimal Hepatic Encephalopathy”, entered into May 6, 2019 (GCLAWS# 30233, Agreement No. 2019-0254). This invention is a CRADA subject invention and the government has certain rights in the invention.BACKGROUND

[0003] Cirrhosis and associated cognitive impairment due to minimal hepatic encephalopathy (MHE) have major challenges with daily function and poor clinical outcomes, such as the development of overt HE (OHE). The pathogenesis of MHE and OHE are related to an altered gut-liver-brain axis and medications focused on gut microbiome have successfully been used in MHE. However, there is not a current standard of care for MHE therapy and treatment is usually on a case-by-case basis. There is an alteration of gut microbial composition and function (bile acid changes, endotoxemia and gut metabolic products) in cirrhosis, which worsens with disease progression with MHE and OHE. Current treatments for OHE are mostly focused on the gut, including lactulose and rifaximin. However, despite extracting a major toll on disease progression, there is no current guideline to treat MHE. Prior studies using lactulose and rifaximin have been performed in this setting with improvement in brain function, brain MR1 changes and microbial function. However, these are still not standard of care.

[0004] Rifamycin SV MMX® 200 mg is a gut-specific antibiotic with a long track record of safety that has been FDA approved for the treatment of traveler’s diarrhea. Unlike rifaximin, rifamycin-SV MMX mostly affects the colon, where the bacterial load is much larger than in the other parts of the GI tract. The impact of rifamycin on MHE has not been studied to date.BRIEF SUMMARY

[0005] The present disclosure relates to a composition comprising Rifamycin SV (also referred to as rifamycin herein) and its use in the treatment of sarcopenia. More particularly, thepresent disclosure describes a pharmaceutical composition comprising Rifamycin SV for treating sarcopenia in subjects with a chronic disease.

[0006] The publications and other materials used herein to illuminate the background or provide additional details respecting the practice, are incorporated by reference, and for convenience are respectively grouped in the Bibliography.

[0007] The present disclosure relates to a composition comprising rifamycin SV (also referred to as rifamycin herein) or pharmaceutically acceptable salts thereof and its use in the treatment of sarcopenia. Also disclosed are methods of treatment of sarcopenia by administering an effective amount of Rifamycin SV or pharmaceutically acceptable salts thereof to a subject in need thereof.

[0008] The present disclosure further relates to a method of treatment of sarcopenia by administering a composition comprising Rifamycin SV or pharmaceutically acceptable salts thereof to a subject in need thereof, wherein the subject has a chronic disease. The present disclosure further relates to use of pharmaceutical compositions as disclosed herein comprising Rifamycin SV in the manufacture of a medicament for treating sarcopenia. The present disclosure further relates to use of pharmaceutical compositions as disclosed herein comprising Rifamycin SV or pharmaceutically acceptable salts thereof in the manufacture of a medicament for treating sarcopenia in a subject with a chronic disease. The present disclosure describes the use of Rifamycin SV or pharmaceutically acceptable salts thereof for treating, ameliorating, reducing the severity of, inducing, maintaining the remission of, and / or slowing the progression of sarcopenia. For example, disclosure herein are methods of ameliorating one or more symptoms of Sarcopenia. Further, the present disclosure describes the use of Rifamycin SV or pharmaceutically acceptable salts thereof for treating, ameliorating, reducing the severity’ of, inducing, maintaining the remission of, and / or slowing the progression of sarcopenia in a subject with a chronic disease. More particularly, the present disclosure describes a composition comprising Rifamycin SV or pharmaceutically acceptable salts thereof for treating, ameliorating, reducing the severity of. inducing, maintaining the remission of, and / or slowing the progression of sarcopenia. Further, the present disclosure describes a composition comprising Rifamycin SV or pharmaceutically acceptable salts thereof for treating, ameliorating, reducing the severity’ of, inducing, maintaining the remission of, and / or slowing the progression of sarcopenia in a subject with a chronic disease.

[0009] In one aspect, the invention relates to a pharmaceutical composition comprising Rifamycin SV or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers and / or excipients for use in a method of treating sarcopenia.

[0010] The disclosed methods of treating sarcopenia may involve administering about 200 mg, or about 400 mg, or about 600 mg, or about 800 mg, or about 1,000 mg, or about 1,200 mg, or about 1,400 mg, or about 1,600 mg or about 1,800 mg or about 2,000 mg, or about 2,200 mg or about 2,400 mg rifamycin SV or a pharmaceutically acceptable salt thereof to a patient in need thereof. For example, the method may involve administration of a pharmaceutical composition comprising about 200 mg Rifamycin SV or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some aspects, the disclosed methods may involve administration of a pharmaceutical composition comprising about 600 mg Rifamycin SV or a pharmaceutically acceptable salt thereof to a patient in need thereof. In some aspects, the disclosed methods of treating sarcopenia may involve administering one or more units of the pharmaceutical composition comprising about 200 mg Rifamycin SV or a pharmaceutically acceptable salt thereof to achieve the therapeutically effective amount. In some aspects, the disclosed methods of treating sarcopenia may involve administering one or more units of the pharmaceutical composition comprising about 600 mg Rifamycin SV or a pharmaceutically acceptable salt thereof to achieve the therapeutically effective amount.

[0011] In some aspects, the methods may include administering a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof may comprise about 200 mg rifamycin SV or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers and / or excipients. In some aspects, the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof may comprise about 600 mg rifamycin SV or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers and / or excipients.

[0012] In some aspects, the pharmaceutical composition is an oral dosage form i.e. the pharmaceutical composition is suitable for oral administration. The oral dosage form may be a capsule, or a tablet, or a minitablet. Preferably, the oral dosage form is a tablet.

[0013] In some aspects, the pharmaceutical composition further comprises one or more of a lipophilic substance, a hydrophilic substance and an amphiphilic substance. Preferably, the pharmaceutical composition comprises at least one lipophilic substance, at least one hydrophilic substance and at least one amphiphilic substance. Preferably, the pharmaceutical composition comprises a system for controlled release which is characterized by the presence of a first, amphiphilic matrix, in which the active ingredient is incorporated and which is in turn dispersed in a second, lipophilic, matrix. The form so obtained is again in turn dispersed in a third, hydrophilic, matrix before producing the final oral pharmaceutical form.

[0014] In some aspects, the lipophilic matrix of the compositions disclosed herein isrepresented by substances having a melting point lower than 90° C, such as, for example, unsaturated or hydrogenated alcohols (such as cetyl alcohol, stearic alcohol, myristyl alcohol, lauryl alcohol, or oleyl alcohol) or fatty7acids, salts, esters thereof (such as such as palmitic, stearic, myristic, lauric, laurylic or oleic acid); fatty acids mono-, di- or triglycerides or polyethoxylated derivatives thereof, such as stearin; waxes, such as beeswax or carnauba wax; ceramides; cholesterol derivatives or mixtures thereof. Stearic acid, or one of its salts (such as, for example, magnesium stearate), is the preferred at least one lipophilic compound. The lipophilic compound may be an ester of a hydrogenated fatty alcohol. The lipophilic compound may be sodium stearyl fumarate.

[0015] The hydrophilic matrix may comprise substances such as cellulose derivatives, such as hydroxyalkylcelluloses, alkylcelluloses, carboxyalkydcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives of anionic or cationic nature, such as, for example, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives. The hydrophilic matrix may be represented by generally cross-linked or linear polymeric or copolymeric substances, which are known as hydrogels, that is to say, i.e. substances which when passing from the dry state to the hydrated one, undergo the so-called "molecular relaxation," namely a remarkable increase in mass and weight following the coordination of a large number of water molecules by the polar groups present in their polymeric chains. In particular, the at least one hydrophilic may be selected from cellulose derivatives and their esters and / or salts, such as hydroxy alkylcelluloses (for example hydroxypropylcellulose, hydroxypropylmethylcellulose or sodium hydroxypropylmethylcellulose), alkylcelluloses, carboxyalkylcelluloses (such as sodium carboxymethylcellulose); polyvinyl alcohols; carboxyvinyl derivatives; polysaccharides, such as dextrins, pectins, starches and derivatives thereof; natural or synthetic gums; alginic acid; polyalcohols such as xylitol, maltitol or mannitol.

[0016] In some aspects, the pharmaceutical composition may further comprise at least one other excipient such as for example antioxidants, chelating agents, preservatives, antimicrobial agents, surfactants, co-surfactants, lipophilic compounds, purified water, organic salts, inorganic salts, buffers agents or mixtures thereof. Suitably, the pharmaceutical composition further comprises at least one antioxidant and a least one preservative.

[0017] In some aspects, the amphiphilic matrix may be represented by substances selected, for example, from phospholipids, ceramides, sphingomyelins, lecithins, alkyl block copolymers, salts of sulphated alkyl acids, polyoxyethylenated alkyl, derivatives of sorbitan and the like, while the hydrophilic matrix is represented by generally cross-linked or linear polymeric orcopolymeric substances, which are known as hydrogels, that is to say, substances capable of increasing their mass and their weight, owing to the polar groups present in the main or side polymer chains, when they come into contact with molecules of w ater. In some aspects, the amphiphilic matrix may comprise substances selected from polar lipids of type I or II (lecithin, phosphatidylcholine, phosphatidylethanolamine), ceramides, glycol alkyl ethers such as diethylene glycol monomethyl ether (Transcutol®), natural or synthetic gums, polyoxy ethylenated sorbitan monooleate, sodium laur l sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers. Lecithin is the preferred at least one amphiphilic compound in the composition.

[0018] In some aspects, the matrices are dispersed in one another in succession together with the active ingredient, thus bringing about the formation of a homogeneous structure responsible for the site-specificity7of release.

[0019] In some aspects, the pharmaceutical compositions disclosed herein may also contain at least one physiologically acceptable excipient, for example bioadhesive excipients such as chitosans, polyacry lamides, natural or synthetic gums, acrylic acid polymers and copolymers.

[0020] In some aspects, the pharmaceutical compositions disclosed herein can further comprise a gastro-resistant coating. In some aspects, the oral pharmaceutical compositions of the invention may be covered with a gastro-resistant coating (film), which may contain polymethacrylates, acrylic and / or methacrylic acids polymers or copolymers or cellulose derivatives, such as cellulose acetophthalate. Preferably, the gastro-protective coating contains polymethacry lates including but not limited to compounds known commercially as Eudragit SI 00 (methacrylic acid-methyl methacrylate copolymer) 1 :2, Eudragit LI 00 (methacrylic acid- methyl methacrylate 1: 1 copolymer) and / or Eudragit L30 D55 (methylacrylic acid-ethylacrylate 1 : 1 copolymer). In some aspects, the gastro-protective coating may contain methacrylic acid- methyl methacrylate 1:1 copolymer (Eudragit LI 00). In some aspects, the gastro-protective coating may contain methylacrylic acid-ethylacrylate 1 : 1 copolymer (Eudragit L30 D55). Suitably, the gastro-resistant coating (film) may contain methacrylic acid-methyl methacrylate 1 :2 copolymer (Eudragit SI 00). In some aspects, the gastro-protective containg contains a mixture of methacrylic acid-methyl methacrylate 1: 1 copolymer (Eudragit LI 00) and methacrylic acid-methyl methacrylate 1:2 copolymer (Eudragit S100). In some aspects, the gastro-resistant coating (film) may further comprise one or more of talc, tri ethylcitrate, titanium dioxide, and one or more compounds imparting a color to the oral pharmaceutical composition.

[0021] Disclosed are uses of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof as described herein for treating, ameliorating, reducingthe severity of, slowing the progression of, inducing the remission of, or maintaining the remission of sarcopenia. Disclosed are uses of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof as described herein for treating, ameliorating, reducing the severity of, slowing the progression of, inducing the remission of, or maintaining the remission of sarcopenia associated with a chronic disease.

[0022] Disclosed are methods of treating, ameliorating, reducing the severity of, slowing the progression of, inducing the remission of, or maintaining the remission of sarcopenia, said method comprising administering the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof as described herein to a patient in need thereof. Disclosed are methods of treating, ameliorating, reducing the severity of, slowing the progression of, inducing the remission of, or maintaining the remission of sarcopenia, said method comprising administering the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof as described herein to a patient in need thereof, said patient having a chronic disease.

[0023] Disclosed are methods of treating, ameliorating, reducing the severity of, slowing the progression of, inducing the remission of, or maintaining the remission of sarcopenia, said method comprising administering the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof as described herein to a patient in need thereof, said patient having a chronic disease. Suitably, the chronic disease is selected from hepatic cirrhosis, hepatic encephalopathy, cancer cachexia, renal failure, congestive heart failure, or end-stage lung disease. Preferably, the chronic disease is hepatic cirrhosis and / or hepatic encephalopathy .

[0024] In some aspects, pharmaceutical compositions disclosed herein can be orally administered to a human patient.

[0025] In some aspects, disclosed are uses of a pharmaceutical composition comprising Rifamycin SV or pharmaceutically acceptable salts thereof as described herein in the manufacture of a medicament for the treatment of sarcopenia. In some aspects, disclosed are uses of a pharmaceutical composition compnsing Rifamycin SV or pharmaceutically acceptable salts thereof as described herein in the manufacture of a medicament for the treatment of sarcopenia associated with a chronic disease.

[0026] In some aspects, disclosed are uses of a pharmaceutical composition comprising Rifamycin SV or pharmaceutically acceptable salts thereof as described herein in the manufacture of a medicament for the treatment of sarcopenia in a patient with a chronic disease. In some aspects the chronic disease is selected from hepatic cirrhosis, hepatic encephalopathy, cancer cachexia, renal failure, congestive heart failure, or end-stage lung disease. In someaspects the chronic disease is hepatic cirrhosis and / or hepatic encephalopathy.

[0027] Additional advantages of the disclosed method and compositions w ill be set forth in part in the description which follows, and in part will be understood from the description, or may be learned by practice of the disclosed method and compositions. The advantages of the disclosed method and compositions will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary7and explanatory7only and are not restrictive of the invention as claimed.BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the disclosed method and compositions and together with the description, serve to explain the principles of the disclosed method and compositions.

[0029] FIGS. 1 A-B show the study design flow-chart and an example of a flow-chart template per CONSORT guidelines, respectively.

[0030] FIGS. 2A-D show7Stool Microbiota Comparisons between Rifamycin baseline versus Study end and Rifamycin Versus Placebo End. FIG. 2A) Linear discriminant function effect size comparison between rifamycin end versus baseline, linear discriminant function effect size comparison between rifamycin and placebo end (FIG. 2B), individual plots of CDR and delta within the rifamycin group comparing baseline to end (day 30). FIG. 2C) Rifamycin Baseline (oval on the right) vs End (oval on the left) PERMANOVA F-value 2.529, p=0.014). FIG. 2D) Placebo End (large oval on left) vs Rifamycin End (smaller oval within the placebo) PERMANOVA F-value 3.349, p=0.003).

[0031] FIG. 3 shows Stool Microbiota Comparisons showing lower alpha Diversity and Cirrhosis Dysbiosis Ratio after Rifamycin versus placebo.

[0032] FIGS. 4A-D show the change in dry lean mass (FIG. 4A), the change in handgrip (FIG. 4B), change in ammonia (FIG. 4C) and change in stool butyrate (FIG. 4D).

[0033] FIGS. 5A-5D show s a summary of the results of the study as per Example 1. FIG. 5 A shows changes between and within the group at baseline and study end; FIG. 5B shows the differences in change from baseline to study end in both groups; FIG. 5C shows placebo end vs RiVM end purple points in the oval show separate clustering; FIG. 5D shows RiVM baseline vs RiVM end, blue points in the oval show separate clustering.DETAILED DESCRIPTION

[0034] The disclosed method and compositions may be understood more readily byreference to the following detailed description of particular embodiments and the Example included therein and to the Figures and their previous and following description.

[0035] It is to be understood that the disclosed method and compositions are not limited to specific synthetic methods, specific analytical techniques, or to particular reagents unless otherwise specified, and. as such, may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0036] Disclosed are materials, compositions, and components that can be used for, can be used in conjunction with, can be used in preparation for, or are products of the disclosed method and compositions. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a peptide is disclosed and discussed and a number of modifications that can be made to a number of molecules including the amino acids are discussed, each and every combination and permutation of the peptide and the modifications that are possible are specifically contemplated unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited, each is individually and collectively contemplated. Thus, is this example, each of the combinations A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. Likewise, any subset or combination of these is also specifically contemplated and disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. This concept applies to all aspects of this application including, but not limited to. steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods, and that each such combination is specifically contemplated and should be considered disclosed.A. Definitions

[0037] It is understood that the disclosed method and compositions are not limited to the particular methodology, protocols, and reagents described as these may vary. It is also to beunderstood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.

[0038] It is understood that the disclosed method and compositions are not limited to the particular methodology, protocols, and reagents described as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.

[0039] It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, reference to "a subject" includes a plurality of such subjects, reference to "the subject” is a reference to one or more subjects and equivalents thereof known to those skilled in the art, and so forth.

[0040] The word “or” as used herein means any one member of a particular list and also includes any combination of members of that list. The term “and / or” means anyone of the items, any combination of the items, or all the items with which this term is associated.

[0041] As used herein, the term "therapeutically effective amount" means an amount of a therapeutic, prophylactic, and / or diagnostic agent that is sufficient, when administered to a subject suffering from or susceptible to a disease, disorder, and / or condition, to treat, alleviate, ameliorate, relieve, alleviate symptoms of, prevent, delay onset of, inhibit progression of, reduce severity of, and / or reduce incidence of the disease, disorder, and / or condition. In this case, the therapeutically effective amount of Rifamycin SV is the amount of Rifamycin SV required to treat, ameliorate, reduce the severity of, slow the progression of, induce the remission of, or maintain the remission of sarcopenia when administered to a patient in need thereof. Optionally, the patient in need thereof may have a chronic disease.

[0042] As used herein, the term "treating" refers to partially or completely alleviating, ameliorating, relieving, delaying onset of. inhibiting progression of, reducing severity of, and / or reducing incidence of one or more symptoms or features of a particular disease, disorder, and / or condition. Treatment may be administered to a subject who does not exhibit signs of a disease, disorder, and / or condition and / or to a subject who exhibits only early signs of a disease, disorder, and / or condition for the purpose of decreasing the risk of developing pathology associated with the disease, disorder, and / or condition.

[0043] As used herein, “sample” is meant to mean an animal; a tissue or organ from an animal; a cell (either within a subject, taken directly from a subject, or a cell maintained inculture or from a cultured cell line); a cell lysate (or lysate fraction) or cell extract; or a solution containing one or more molecules derived from a cell or cellular material (e.g. a polypeptide or nucleic acid), which is assayed as described herein. A sample may also be any body fluid or excretion (for example, but not limited to, blood, urine, stool, saliva, tears, bile) that contains cells or cell components.

[0044] As used herein, “subject’’ refers to the target of administration, e g. an animal. Thus, the subject of the disclosed methods can be a vertebrate, such as a mammal. For example, the subject can be a human. The term does not denote a particular age or sex. Subject can be used interchangeably with “individual” or “patient”.

[0045] Ranges may be expressed herein as from "about" one particular value, and / or to "about" another particular value. When such a range is expressed, also specifically contemplated and considered disclosed is the range from the one particular value and / or to the other particular value unless the context specifically indicates otherwise. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another, specifically contemplated embodiment that should be considered disclosed unless the context specifically indicates otherwise. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint unless the context specifically indicates otherwise. Finally, it should be understood that all of the individual values and sub-ranges of values contained within an explicitly disclosed range are also specifically contemplated and should be considered disclosed unless the context specifically indicates otherwise. The foregoing applies regardless of whether in particular cases some or all of these embodiments are explicitly disclosed.

[0046] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed method and compositions belong. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present method and compositions, the particularly useful methods, devices, and materials are as described. Publications cited herein, and the material for which they are cited, are hereby specifically incorporated by reference. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention. No admission is made that any reference constitutes prior art. The discussion of references states what their authors assert, and applicants reserve the right to challenge the accuracy and pertinency of the cited documents. It will be clearly understood that, although a number of publications are referred to herein, such reference does not constitute an admission that any of these documents forms part of thecommon general knowledge in the art.

[0047] Throughout the description and claims of this specification, the word '‘comprise” and variations of the word, such as “comprising” and “comprises,” means “including but not limited to,” and is not intended to exclude, for example, other additives, components, integers or steps. In particular, in methods stated as comprising one or more steps or operations it is specifically contemplated that each step comprises what is listed (unless that step includes a limiting term such as “consisting of’), meaning that each step is not intended to exclude, for example, other additives, components, integers or steps that are not listed in the step. The terms “consist essentially of’, “consisting essentially of’ are to be construed as a semi-closed terms, meaning that no other ingredients which materially affects the basic and novel characteristics (and optionally physiologically acceptable excipients and / or adjuvants) of the invention are included.

[0048] References in the specification to “one embodiment”, “an embodiment”, “one aspect”, '‘an aspect” and similar indicate that the described embodiment or aspect may include a particular aspect, feature, structure or characteristic. Moreover, such phrases may, but do not necessarily, refer to the same embodiment or aspect referred to in other portions of the specification. Further, when a particular aspect, feature, structure or characteristic is described in connection with an embodiment or aspect, it is within knowledge of a person skilled in the art to affect or connect said aspect, feature, structure or characteristic with other embodiment or aspect, whether or not explicitly described. The singular forms “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, a reference to “a compound” includes a plurality' of such compounds. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for the use of exclusive terminology, such as “solely”, “only”, and the like, in connection with the recitation of claims elements or use of a “negative” limitation.

[0049] The term “placebo” is intended to mean the pharmaceutical composition without the active agent. Thus, in its simplest usage, the “placebo” comprises the excipients or carriers suitable for the formulation of the pharmaceutical composition, without incorporating the active substance.

[0050] A person skilled in the art will recognize that, for any and all purposes, particularly in terms of providing a written description, all ranges recited herein also encompass any and all possible sub-ranges and combinations of sub-ranges thereof, as well as the individual values making up the range, particularly integer values. A recited range includes each specific value, integer, decimal, or identity7within the range.

[0051] A person skilled in the art will recognize that where members are grouped together ina common manner, such as in a Markush group, the invention encompasses not only the entire group listed as a whole, but each member of the group individually and all possible subgroups of the main group. Additionally, for all purposes, the invention encompasses not only the main group, but also the main group absent one or more of the group members. The invention therefore envisages the explicit exclusion of anyone or more of members of a recited group. Accordingly, provisos may apply to any of the disclosed categories or embodiments whereby anyone or more of the recited elements, species, or embodiments, may be excluded from such categories or embodiments, for example, as used in an explicit negative limitation.

[0052] The term “alleviating” refers to relieving the symptoms and / or manifestations of inflammatory and / or degenerative diseases of the gastrointestinal tract.

[0053] The term “reducing” refers to decreasing the extent of the damage caused by inflammatory and / or degenerative diseases of the gastrointestinal tract or to decreasing clinical signs or symptoms associated with such damage.

[0054] “Rifamycin SV” refers to Rifamycin, defined to the CAS N° 6998-60-3. Rifamycin SV sodium or Rifamycin sodium salt refers to the sodium salt of rifamycin SV defined to the CAS N° 14897-39-3.

[0055] The term “long-lasting” means that the formulation remains in the site of action for the time necessary to exert the therapeutic effect.

[0056] The expression "600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof herein refers to an amount of 600 mg of rifamycin SV as dry substance (anhydrous) or to 600 mg of a pharmaceutically salt of rifamycin SV as dry substance, including, but not limited to, an amount of 600 mg of the sodium salt of rifamycin SV, or to an amount of a pharmaceutically acceptable salt of rifamycin SV which is equivalent to 600 mg of rifamycin SV as dry substance (anhydrous). In one aspect, 600 mg of the sodium salt of rifamycin SV as dry substance are equivalent to 582 mg of rifamycin SV as dry substance. In one aspect, 600 mg of the sodium salt of rifamycin SV are equivalent to 582 mg of rifamycin SV and 18 mg of sodium ions. In another aspect, 600 mg of rifamycin SV as dry substance are equivalent to 618 mg of the sodium salt of rifamycin SV. In further another aspect, 618 mg of the sodium salt of rifamycin SV are equivalent to 600 mg of rifamycin SV and 18 mg of sodium ions.

[0057] The terms "approximately" and "about" as used herein refers to the range of the experimental error, which may occur in a measurement, such as for example. 10%. 5%, 2.5%, 2% or 1% error. For example, about 200 mg may be 200 mg ±10%, or 200 mg ±5%, or 200 mg ±2.5%, or 200 mg ±2% or 200 ± 1%. For example, about 200 mg is a range from 180 mg to 220 mg, or from 190 mg to 210 mg, or from 195 mg to 205 mg, or from 196 mg to 204 mg, or from199 mg to 201 mg. Similarly, about 400 mg may be 400 mg ±10%, or 400 mg ±5%, or 400 mg ±2.5%, or 400 mg ±2% or 400 ± 1%. For example, about 400 mg is a range from 360 mg to 440 mg, or from 380 mg to 420 mg, or from 390 mg to 410 mg, or from 392 mg to 408 mg, or from 396 mg to 404 mg. Similarly, about 600 mg may be may be 600 mg ±10%, or 600 mg ±5%. or 600 mg ±2.5%, or 600 mg ±2% or 600 ± 1%. For example, about 600 mg is a range from 540 mg to 660 mg, or from 570 mg to 630 mg, or from 585 mg to 615 mg, or from 588 mg to 612 mg, or from 594 mg to 606 mg.

[0058] The term "MELD" as used herein stands for Model for End stage Liver Disease, also known as Mayo End stage Liver Disease, is a scoring system utilized for staging the hepatic disease at the terminal stage. A description of the score is provided in specialized scientific literature, for example Hepatology7, vol. 45, n. 3, March 2007, pp. 797-805.

[0059] The term “Child Score'’ as used herein refer to the Child-Pugh score (or the Child- Turcotte-Pugh (CTP) score or Child Criteria), a scoring system used to assess the prognosis of the chronic liver disease, mainly cirrhosis. A description of the score is provided in specialized scientific literature, for example Alimentary Pharmacology & Therapeutics. 22 (11-12): 1079- 89.

[0060] The acronym “AST’" as used herein refers to Aspartate transaminase or aspartate aminotransferase.

[0061] The acronym “ALT” as used herein refers to Alanine transaminase or alanine aminotransferase.

[0062] The acronym “CHF” as used herein refers to congestive heart failure. The acronym “EF” refers to ejection fraction.

[0063] The acronym “COPD” as used herein refers to Chronic obstructive pulmonary disease.

[0064] The acronym “PHES” as used herein refers to Psychometric Hepatic Encephalopathy Score. A description of the score is provided in specialized scientific literature, for example Journal of Clinical Medicine 2023 Jan; 12(2): 519.

[0065] The acronym “PO” stands for “Per os”, and means by oral administration.

[0066] The acronym “HRQOL” stands for Health-Related Quality7of Life.

[0067] The acronym “AE” stands for “adverse event” and the acronym “SAE” stands for serious adverse event.

[0068] The acronym “MRI” stands for Magnetic Resonance Imaging.

[0069] The acronym “SCFA” stands for Short Chain Fatty7Acid. Exemplary7short chain fatty7acids comprise, but are not limited to: acetate acid and salts thereof (acetates); propionic acidand salts thereof (propionates); butyric acid and salts thereof (butyrates); isobutyric acid and salts thereof (isobutyrates); valeric acid and salts thereof (valerates); isovaleric acid and salts thereof (isovalerates); 2-methylbutyric acid and salts thereof (2 -methylbutyrates); hexanoic acid and salts thereof (hexanoate); and the like.B. Pharmaceutical Compositions

[0070] Disclosed are pharmaceutical compositions that can be used in the methods disclosed herein. Disclosed are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients. In some aspects, the one or more carriers and / or excipients can be referred to as a pharmaceutically acceptable carrier. Examples of pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof also include the compositions shown in Tables 1 -3 disclosed herein.

[0071] In some aspects, the pharmaceutical composition has a multi -matrix structure comprising an amphiphilic matrix in which the rifamycin SV is incorporated; a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which the amphiphilic matrix is dispersed; and a hydrophilic matrix.

[0072] Disclosed are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in the treatment of sarcopenia.

[0073] In some aspects, the pharmaceutical composition can be one or more of those described herein. In some aspects, the pharmaceutical composition has a multi-matrix structure comprising an amphiphilic matrix in which the rifamycin SV is incorporated; a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which is dispersed; and a hydrophilic matrix.

[0074] In some aspects, the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II. lecithins, alkyl block copolymers, salts of sulphated alkyl acids, polyoxy ethylenated alkyl derivatives of sorbitan, glycol alkyl ethers, natural or synthetic gums, sodium laury l sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers. In some aspects, an amphiphilic substance can be present in an amount ranging from 0.001 - 0.0500 % w / w, or 0.005 - 0.050 % w / w. or 0.005 - 0.030 % w / w of the weight of the composition.

[0075] In some aspects, the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty' acids, salts, or esters thereof; fatty' acids mono-, di- or triglycerides or polyethoxylated derivatives thereof; waxes: ceramides;cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof. In some aspects, a lipophilic substance can be present in an amount ranging from 0.01 - 0.050 % w / w, or 0.01 - 0.035 % w / w, or 0.015 - 0.025 % w / w of the weight of the composition.

[0076] In some aspects, the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol. In some aspects, a hydrophilic substance can be present in an amount ranging from 0.05 - 0.50 % w / w, or 0.1 - 0.5 % w / w, or 0.1 - 0.3 % w / w of the weight of the composition.

[0077] In some aspects, the pharmaceutical composition may comprise an amphiphilic matrix comprising lecithin, a lipophilic matrix comprising stearic acid, and a hydrophilic matrix comprising sodium carboxymethylcellulose. In some aspects, the pharmaceutical composition may comprise an amphiphilic matrix comprising lecithin, a lipophilic matrix comprising Glycery l Distearate, and a hydrophilic matrix Ammonio Methacrylate Copolymer (Type B).

[0078] In some aspects, the pharmaceutical composition further comprises a gastro-resistant (or enteric) coating. In some aspects, the pharmaceutical composition may comprise a gastro- resistant coating which dissolves at a pH of about 5, or about 5.5, or about 6.0, or about 6.2, or about 6.4, or about 6.6, or about 6.8, or about 7.0, or about 7. 1 or about 7.2. In some aspects, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH of about 6.4. In another preferred embodiment, the pharmaceutical composition comprises a gastro- resistant coating which dissolves at a pH of about 6.8. In further another preferred embodiment, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH about 7.0. In further another preferred embodiment, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH about 7.2. In some aspects, a gastro-resistant coating can comprise shellac, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose phthalate, or hydroxypropylmethylcellulose acetate succinate. In other aspects, the gastro-resistant coating (film) covering the tablet core can contain a polymethacrylate, acrylic and / or methacrylic acids polymers or copolymers, or a cellulose derivative, such as cellulose acetophthalate. . Optionally, the gastro-protective coating comprises methacrylic acid / methyl methacrylate (1 :1) copolymer (e.g., commercially known as EUDRAGIT L). Optionally, the gastro-resistant coating comprises methacrylic acid / methylmethacrylate (1 :2) copolymer (e.g., commercially known as EUDRAGIT S). Optionally, the gastro-protective coating comprises methacrylic acid-ethylacrylate (1: 1) copolymer (e.g., commercially known as EUDRAGIT L30 D55). Optionally, the gastro-protective coating comprises polymethacrylate copolymers including, but not limited, to compounds known commercially as EUDRAGIT S (methacrylic acid-methyl methacrylate copolymer 1:2). EUDRAGIT L (methacrylic acid- methyl methacrylate 1 : 1 copolymer) and / or EUDRAGIT L30 D55 (methacry lic acid-ethylacry late 1: 1 copolymer), and / or mixtures thereof. The gastro resistant coating can comprise a methacrylic acid -(meth)acrylate copolymer. In some embodiments, the gastro resistant coating comprises methacrylic acid / methyl methacrylate copolymer.

[0079] The gastro-resistant coating can comprise methacrylic acid / methyl methacrylate (1 :1) copolymer (EUDRAGIT L), or methacry lic acid / methyl methacry late (1:2) copoly mer (EUDRAGIT S).

[0080] Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacry late (1 : 1) copolymer (EUDRAGIT L).

[0081] Optionally, the gastro-resistant coating comprises methacry lic acid / methyl methacrylate (1 :2) copolymer (EUDRAGIT S).

[0082] In some embodiments, the gastro-resistant coating comprises a mixture of methacrylic acid / methyl methacrylate (1 : 1 ) copolymer and of methacrylic acid / methyl methacry late (1 :2) copolymer. Optionally, the mixture comprises a weight ratio of from 0.5: 1 to 3: 1 of methacry lic acid / methyl methacry late (1 : 1) copolymer to methacry lic acid / methyl methacrylate (1 :2). Optionally, the mixture comprises a weight ratio of from 1 : 1 to 3: 1 of methacrylic acid / methyl methacrylate (1: 1) copolymer to methacrylic acid / methyl methacrylate (1:2). In some embodiments, the mixture comprises a w eight ratio of about 2: 1 of methacrylic acid / methyl methacry late (1 :1) copolymer to methacry lic acid / methyl methacry late (1:2). Optionally, the gastro-resistant coating of the unit dose starts breaking or dissolving at or above a pH of 5, optionally, at or about a pH of 6, at or above a pH of 6.5. or at a pH of 6.8.

[0083] In some embodiments, the active substance is released from the tablet core at pH of at least 5, such as 5.1, or 5.2, or 5.3, or 5.4, or 5.5, or 5.6, or 5.7, or 5.8, or 5.9, or 6, or 6.1, or 6.2, or 6.3, or 6.4, or 6.5. or 6.6, or 6.7, or 6.8. or 6.9, or 7, or 7.1. or 7.2, or 7.3, or 7.4. or 7.5. In some embodiments, the active substance is released from the tablet core at pH in the range from about 6.5 to about 7.5, optionally, at a pH in the range of from about 6.8 to about 7. According to a certain aspect, the active substance is released from the tablet core at pH of 6.8. According to another aspect, the active substance is released from the tablet core at pH of 7. According to afurther aspect, the active substance is released from the tablet core at pH of 7.2.

[0084] In some aspects, the pharmaceutical composition comprises a tablet core and coating covering the core. In some aspects, the coating can be a gastro-resistant coating, a delayed released coating, an extended release coating.

[0085] In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal portion of the intestine, i.e. in the small intestine. In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the distal part of the small intestine, of example in the ileum. In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal part of the colon, for example in the caecum.

[0086] In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV. or a pharmaceutically acceptable salt thereof, starts in the proximal portion of the intestine, i.e. in the small intestine (duodenumjejunum and ileum) and may optionally continue throughout the large intestine. In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the distal part of the small intestine, of example in the ileum and may optionally continue throughout the large intestine. In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal part of the colon, for example in the caecum and may optionally continue throughout the large intestine.

[0087] In some aspects, the pharmaceutical composition is suitable for any know n administration, particularly those described herein. In some aspects, the pharmaceutical composition is suitable for oral administration. In other aspects, the pharmaceutical composition is suitable for rectal administration. In further aspects, the pharmaceutical composition is suitable for parenteral administration, including intravenous, intramuscular or subcutaneous injection. In a preferred aspect, the pharmaceutical composition is suitable for oral administration.

[0088] Disclosed herein are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in the treatment of sarcopenia, wherein the pharmaceutical composition has a multi-matrix structure comprising: a) an amphiphilic matrix in which the rifamycin SV is incorporated; b) a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a)is dispersed; and c) a hydrophilic matrix; wherein the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II, lecithins, alkyd block copolymers, salts of sulphated alkyl acids, poly oxy ethylenated alkyl derivatives of sorbitan, glycol alkyl ethers, natural or synthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers; wherein the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty7acids, salts, or esters thereof; fatty7acids mono-, di- or triglycerides or poly ethoxylated derivatives thereof; waxes; ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof; wherein the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol; wherein the pharmaceutical composition further comprises a gastro-resistant coating; wherein the pharmaceutical composition comprises a tablet core and coating covering the core; and wherein the pharmaceutical composition is suitable for oral administration.

[0089] In some aspects, the pharmaceutical composition may comprise about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition may comprise about 400 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition may comprise about 600 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition may comprise about 800 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition may comprise about 1,000 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition may comprise about 1.100 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition may comprise about 1,200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

[0090] In some aspects, the pharmaceutical composition may comprise about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition may comprise about 600 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

[0091] In some aspects, the compositions disclosed herein can further comprise apharmaceutically acceptable carrier. By '‘pharmaceutically acceptable” is meant a material or carrier that would be selected to minimize any degradation of the active ingredient and to minimize any adverse side effects in the subject, as would be well known to one of skill in the art.

[0092] Preparations of parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic / aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like. Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like.

[0093] The disclosed rifamycin SV or a pharmaceutically acceptable salt thereof can be formulated and / or administered in or with a pharmaceutically acceptable carrier. As used herein, the term “pharmaceutically acceptable carrier” can refer to a sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. These compositions can also contain adjuvants such as preservatives, w etting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid and the like. It can also be desirable to include isotonic agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents, such as aluminum monostearate and gelatin, which delay absorption. Injectable depot forms are made by forming microencapsulated matrices of the drug in biodegradable polymers such as polylactidepolyglycolide, poly(orthoesters) and poly(anhydrides). Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Depot injectable formulations are also prepared by entrapping the drug in liposomesor microemulsions that are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. Suitable inert carriers can include sugars such as lactose. Desirably, at least 95% by weight of the particles of the active ingredient have an effective particle size in the range of 0.01 to 10 micrometers.

[0094] In some aspects, the compositions disclosed herein can comprise lipids such as liposomes, such as cationic liposomes (e.g., DOTMA, DOPE, DC-cholesterol) or anionic liposomes. Liposomes can further comprise proteins to facilitate targeting a particular cell, if desired. Administration of a composition comprising a peptide and a cationic liposome can be administered to the blood, to a target organ, or inhaled into the respiratory tract to target cells of the respiratory tract. For example, a composition comprising a peptide or nucleic acid sequence described herein and a cationic liposome can be administered to a subject's lung cells. Regarding liposomes, see. e.g., Brigham et al. Am. J. Resp. Cell. Mol. Biol. 1:95 100 (1989); Feigner et al. Proc. Natl. Acad. Sci USA 84:7413 7417 (1987); U.S. Patent No. 4,897,355. Furthermore, the compound can be administered as a component of a microcapsule that can be targeted to specific cell types, such as macrophages, or where the diffusion of the compound or delivery of the compound from the microcapsule is designed for a specific rate or dosage.

[0095] In some aspects, disclosed are pharmaceutical compositions comprising any of the disclosed rifamycin SV described herein, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier, buffer, or diluent. In some aspects, the delivery vehicle is a liposome, a microcapsule, or a nanoparticle. In a still further aspect, the delivery vehicle is PEG-ylated.

[0096] In the methods described herein, delivery of the compositions to cells can be via a variety of mechanisms. As defined above, disclosed herein are compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof described herein and can also include a earner such as a pharmaceutically acceptable carrier. For example, disclosed are pharmaceutical compositions, comprising rifamycin SV or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In some aspects, disclosed are pharmaceutical compositions comprising the disclosed rifamycin SV or a pharmaceutically acceptable salt thereof. That is, a pharmaceutical composition can be provided comprising a therapeutically effective amount of at least one disclosed rifamycin SV or a pharmaceutically acceptable salt thereof or at least one product of a disclosed method and a pharmaceutically acceptable carrier.

[0097] In some aspects, the disclosed pharmaceutical compositions can comprise thedisclosed rifamycin SV (including pharmaceutically acceptable salt(s) thereof) as an active ingredient, a pharmaceutically acceptable carrier, and, optionally, other therapeutic ingredients or adjuvants. The instant compositions include those suitable for nasal, oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The pharmaceutical compositions can be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy.

[0098] In practice, the rifamycin SV described herein, or pharmaceutically acceptable salts thereof, can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier can take a wide variety7of forms depending on the form of preparation desired for administration, e.g., oral or parenteral (including intravenous). Thus, the pharmaceutical compositions of the present invention can be presented as discrete units suitable for oral administration such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient. Further, the compositions can be presented as a powder, as granules, as a solution, as a suspension in an aqueous liquid, as a non-aqueous liquid, as an oil-in-water emulsion or as a water-in-oil liquid emulsion. In addition to the common dosage forms set out above, the compounds of the invention, and / or pharmaceutically acceptable salt(s) thereof, can also be administered by controlled release means and / or delivery7devices. The compositions can be prepared by any of the methods of pharmacy. In general, such methods include a step of bringing into association the active ingredient with the carrier that constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both. The product can then be conveniently shaped into the desired presentation.

[0099] The pharmaceutical carrier employed can be, for example, a solid, liquid, or gas. Examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid. Examples of liquid carriers are sugar syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen. Other examples of carriers include dimyristoylphosphatidyl choline (DMPC), phosphate buffered saline or a multivesicular liposome. For example, PG:PC:Cholesterol:peptide or PC:peptide can be used as carriers in this invention. Other suitable pharmaceutically acceptable carriers and their formulations are described in Remington: The Science and Practice of Pharmacy (19th ed.) ed. A.R. Gennaro, Mack Publishing Company, Easton, PA 1995. Typically, an appropriateamount of pharmaceutically-acceptable salt is used in the formulation to render the formulation isotonic. Other examples of the pharmaceutically-acceptable carrier include, but are not limited to, saline, Ringer’s solution and dextrose solution. The pH of the solution can be from about 5 to about 8, or from about 7 to about 7.5. Further carriers include sustained release preparations such as semi-permeable matrices of solid hydrophobic polymers containing the composition, which matrices are in the form of shaped articles, e.g., films, stents (which are implanted in vessels during an angioplasty procedure), liposomes or microparticles. It will be apparent to those persons skilled in the art that certain carriers may be more preferable depending upon, for instance, the route of administration and concentration of composition being administered. These most typically would be standard carriers for administration of drugs to humans, including solutions such as sterile water, saline, and buffered solutions at physiological pH.

[0100] In order to enhance the solubility and / or the stability of the active substance in pharmaceutical compositions, it can be advantageous to employ a-. (3- or y-cyclodextrins or their derivatives, in particular hydroxyalkyl substituted cyclodextrins, e.g. 2-hydroxypropyl-(3- cyclodextrin or sulfobutyl-P-cyclodextrin. Also, co-solvents such as alcohols may improve the solubility and / or the stability of the compounds according to the invention in pharmaceutical compositions.

[0101] Pharmaceutical compositions can also include carriers, thickeners, diluents, buffers, preservatives and the like, as long as the intended activity of the active substance of the invention is not compromised. Pharmaceutical compositions may also include one or more active ingredients (in addition to the composition of the invention) such as antimicrobial agents, anti-inflammatory agents, anesthetics, and the like. The pharmaceutical composition may be administered in a number of ways depending on whether local or systemic treatment is desired, and on the area to be treated.

[0102] Because of the ease in administration, oral administration can be used, and tablets and capsules represent the most advantageous oral dosage unit forms in which case solid pharmaceutical carriers are obviously employed. In preparing the compositions for oral dosage form, any convenient pharmaceutical media can be employed. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like can be used to form oral liquid preparations such as suspensions, elixirs and solutions; while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like can be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solid pharmaceutical carriers are employed. Optionally, tablets can be coated bystandard aqueous or nonaqueous techniques.

[0103] Compositions for oral administration can include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, or tablets. Thickeners, flavorings, diluents, emulsifiers, dispersing aids, or binders may be desirable. Some of the compositions may potentially be administered as a pharmaceutically acceptable acid- or base- addition salt, formed by reaction with inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid, or by reaction with an inorganic base such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, and organic bases such as mon-, di-, trialkyl and aryl amines and substituted ethanolamines.

[0104] A tablet containing the compositions of the present invention can be prepared by compression or molding, optionally with one or more accessory ingredients or adjuvants. Compressed tablets can be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent. Molded tablets can be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent.

[0105] The pharmaceutical compositions of the present invention comprise a disclosed rifamycin SV or pharmaceutically acceptable salts thereof as an active ingredient, a pharmaceutically acceptable carrier, and optionally one or more additional therapeutic agents or adjuvants. The instant compositions include compositions suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The pharmaceutical compositions can be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy.

[0106] Preparations of parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic / aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like. Preservatives and other additives may also be present such as,for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like.

[0107] Pharmaceutical compositions of the present invention suitable for injectable use include sterile aqueous solutions or dispersions. Furthermore, the compositions can be in the form of sterile powders for the extemporaneous preparation of such sterile injectable solutions or dispersions. Typically, the final injectable form should be sterile and should be effectively fluid for easy syringability. The pharmaceutical compositions should be stable under the conditions of manufacture and storage; thus, preferably should be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof.

[0108] Injectable solutions, for example, can be prepared in which the carrier comprises saline solution, glucose solution or a mixture of saline and glucose solution. Injectable suspensions may also be prepared in which case appropriate liquid carriers, suspending agents and the like may be employed. Also included are solid form preparations that are intended to be converted, shortly before use, to liquid form preparations.

[0109] Preparations of parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic / aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer’s dextrose), and the like. Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like.

[0110] In some aspects, the pharmaceutical compositions disclosed herein can be in a form suitable for rectal administration wherein the carrier is a solid. It is preferable that the mixture forms unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art. The suppositories can be conveniently formed by first admixing the composition with the softened or melted carrier(s) followed by chilling and shaping in molds.

[0111] In addition to the aforementioned carrier ingredients, the pharmaceutical formulations described herein can include, as appropriate, one or more additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface-active agents, thickeners, lubricants, preservatives (including anti-oxidants) and the like. Furthermore, other adjuvants can be included to render the formulation isotonic with the blood of the intended recipient.Compositions containing rifamycin SV or a pharmaceutically acceptable salt thereof, can also be prepared in powder or liquid concentrate form.

[0112] The exact dosage and frequency of administration depends on the particular condition being treated and the severity of the condition being treated; various factors specific to the medical history of the subject to whom the dosage is administered such as the age; weight, sex, extent of disorder and general physical condition of the particular subject, as well as other medication the individual may be taking; as is well know n to those skilled in the art. Furthermore, it is evident that said effective daily amount may be low ered or increased depending on the response of the treated subject and / or depending on the evaluation of the physician prescribing the compositions.

[0113] Depending on the mode of administration, the pharmaceutical composition w ill comprise from 0.05 to 99 % by weight, preferably from 0.1 to 70 % by weight, more preferably from 0. 1 to 50 % by weight of the active ingredient, and, from 1 to 99.95 % by weight, preferably from 30 to 99.9 % by weight, more preferably from 50 to 99.9 % by weight of a pharmaceutically acceptable carrier, all percentages being based on the total weight of the composition.C. Methods

[0114] Disclosed are methods comprising administering a therapeutically effective amount of a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients to a subject in need thereof.1. Treating Sarcopenia

[0115] Disclosed are methods of treating a subject having sarcopenia comprising administering a therapeutically effective amount of a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients to the subject. Also disclosed are methods of ameliorating a symptom of sarcopenia in a subject having sarcopenia comprising administering a therapeutically effective amount of a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients to the subject. Symptoms of sarcopenia can include, but are not limited to loss of stamina, difficulty in performing daily activities, slow walking, poor balance, muscle atrophy, , loss of balance, falls leading to fractures and being bedridden, and muscle loss. Sarcopenia can also lead to further development of hepatic encephalopathy.

[0116] Disclosed are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in thetreatment of sarcopenia. Disclosed are pharmaceutical compositions compnsing rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in ameliorating a symptom of sarcopenia. i. Pharmaceutical composition

[0117] In some aspects, the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof can be one or more of those described herein. In some aspects, the pharmaceutical composition has a multi-matrix structure comprising an amphiphilic matrix in which the rifamycin SV is incorporated; a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a) is dispersed; and a hydrophilic matrix.

[0118] In some aspects, the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II, lecithins, alkyl block copolymers, salts of sulphated alkyl acids, polyoxy ethylenated alkyl derivatives of sorbitan. glycol alkyl ethers, natural or synthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers. In some aspects, an amphiphilic substance can be present in an amount ranging from 0.001 - 0.0500 % w / w, or 0.005 - 0.050 % w / w, or 0.005 - 0.030 % w / w of the weight of the composition.

[0119] In some aspects, the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty7acids, salts, or esters thereof; fatty7acids mono-, di- or triglycerides or polyethoxylated derivatives thereof; waxes; ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof. In some aspects, a lipophilic substance can be present in an amount ranging from 0.01 - 0.050 % w / w, or 0.01 - 0.035 % w / w, or 0.015 - 0.025 % w / w of the weight of the composition.

[0120] In some aspects, the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide denvatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol. In some aspects, a hydrophilic substance can be present in an amount ranging from 0.05 - 0.50 % w / w, or 0. 1 - 0.5 % w / w. or 0. 1 - 0.3 % w / w of the weight of the composition.

[0121] In some aspects, the pharmaceutical composition may comprise an amphiphilic matrix comprising lecithin, a lipophilic matrix comprising stearic acid, and a hydrophilic matrixcomprising sodium carboxymethylcellulose. In some aspects, the pharmaceutical composition may comprise an amphiphilic matrix comprising lecithin, a lipophilic matrix comprising Glyceryl Distearate, and a hydrophilic matrix Ammonio Methacrylate Copolymer (Type B).

[0122] In some aspects, the pharmaceutical composition further comprises a gastro-resistant (or enteric) coating. In some aspects, the pharmaceutical composition may comprise a gastro- resistant coating which dissolves at a pH of about 5, or about 5.5, or about 6.0, or about 6.2, or about 6.4, or about 6.6, or about 6.8, or about 7.0, or about 7.1 or about 7.2. In some aspects, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH of about 6.4. In another preferred embodiment, the pharmaceutical composition comprises a gastro- resistant coating which dissolves at a pH of about 6.8. In further another preferred embodiment, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH about 7.2. In some aspects, a gastro-resistan coating can comprise shellac, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose phthalate, or hydroxypropylmethylcellulose acetate succinate. In other aspects, the gastro-resistant coating (film) covering the tablet core can contain a polymethacrylate, acrylic and / or methacrylic acids polymers or copolymers, or a cellulose derivative, such as cellulose acetophthalate. . Optionally, the gastro-protective coating comprises methacrylic acid / methyl methacrylate (1 :1) copolymer (e.g.. commercially known as EUDRAGIT L). Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacrylate (1 :2) copolymer (e.g., commercially known as EUDRAGIT S). Optionally, the gastro-protective coating comprises methacrylic acid- ethylacrylate (1 : 1) copolymer (e.g., commercially known as EUDRAGIT L30 D55). Optionally, the gastro-protective coating comprises polymethacrylate copolymers including, but not limited, to compounds known commercially as EUDRAGIT S (methacrylic acid-methyl methacrylate copolymer 1 :2), EUDRAGIT L (methacrylic acid- methyl methacrylate 1: 1 copolymer) and / or EUDRAGIT L30 D55 (methacrylic acid-ethylacrylate 1: 1 copolymer), and / or mixtures thereof. The gastro resistant coating can comprise a methacrylic acid -(meth)acrylate copolymer. In some embodiments, the gastro resistant coating comprises methacrylic acid / methyl methaciy late copolymer.

[0123] The gastro-resistant coating can comprise methacrylic acid / methyl methacrylate (1 :1) copolymer (EUDRAGIT L), or methacry lic acid / methyl methacry late (1:2) copolymer (EUDRAGIT S).

[0124] Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methaciy late (1 : 1) copolymer (EUDRAGIT L).

[0125] Optionally, the gastro-resistant coating comprises methacrylic acid / methylTlmethacrylate (1 :2) copolymer (EUDRAGIT S).

[0126] In some embodiments, the gastro-resistant coating comprises a mixture of methacry lic acid / methyl methacry late (1: 1) copolymer and of methacry lic acid / methyl methacrylate (1 :2) copolymer. Optionally, the mixture comprises a weight ratio of from 0.5: 1 to 3: 1 of methacrylic acid / methyl methacrylate (1 : 1) copolymer to methacrylic acid / methyl methacrylate (1 :2). Optionally, the mixture comprises a weight ratio of from 1 : 1 to 3: 1 of methacry lic acid / methyl methacrylate (1 : 1) copolymer to methacrylic acid / methyl methacrylate (1:2). In some embodiments, the mixture comprises a weight ratio of about 2: 1 of methacry lic acid / methyl methacrylate (1 : 1) copolymer to methacrylic acid / methyl methacrylate (1:2). Optionally, the gastro-resistant coating of the unit dose starts breaking or dissolving at or above a pH of 5, optionally, at or about a pH of 6, at or above a pH of 6.5, or at a pH of 6.8.

[0206] In some embodiments, the active substance is released from the tablet core at pH of at least 5, such as 5.1, or 5.2, or 5.3, or 5.4, or 5.5. or 5.6, or 5.7, or 5.8. or 5.9, or 6, or 6.1. or 6.2, or 6.3. or 6.4, or 6.5. or 6.6. or 6.7, or 6.8. or 6.9. or 7, or 7.1. or 7.2. or 7.3, or 7.4. or 7.5. In some embodiments, the active substance is released from the tablet core at pH in the range from about 6.5 to about 7.5, optionally, at a pH in the range of from about 6.8 to about 7. According to a certain aspect, the active substance is released from the tablet core at pH of 6.8. According to another aspect, the active substance is released from the tablet core at pH of 7. According to a further aspect, the active substance is released from the tablet core at pH of 7.2.

[0127] In some aspects, the pharmaceutical composition comprises a tablet core and coating covering the core. In some aspects, the coating can be a gastro-resistant coating, a delayed released coating, an extended release coating.

[0128] In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal portion of the intestine, i.e. in the small intestine. In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV. or a pharmaceutically acceptable salt thereof, starts in the distal part of the small intestine, of example in the ileum. In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal part of the colon, for example in the caecum.

[0129] In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal portion of the intestine, i.e. in the small intestine (duodenumjejunum and ileum) and may optionally continue throughout the large intestine. In some aspects, the pharmaceuticalcomposition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the distal part of the small intestine, of example in the ileum and may optionally continue throughout the large intestine. In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal part of the colon, for example in the caecum and may optionally continue throughout the large intestine.

[0130] In some aspects, the pharmaceutical composition is suitable for any known administration, particularly those described herein. In some aspects, the pharmaceutical composition is suitable for oral administration. In other aspects, the pharmaceutical composition is suitable for rectal administration. In further aspects, the pharmaceutical composition is suitable for parenteral administration, including intravenous, intramuscular or subcutaneous inj ection. In a preferred aspect, the pharmaceutical composition is suitable for oral administration.

[0131] Disclosed herein are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in the treatment of sarcopenia, wherein the pharmaceutical composition has a multi-matrix structure comprising :a) an amphiphilic matrix in which the rifamycin SV is incorporated; b) a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a) is dispersed; and c) a hydrophilic matrix; wherein the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II. lecithins, alkyl block copolymers, salts of sulphated alkyl acids, poly oxy ethylenated alkyl derivatives of sorbitan. glycol alkyl ethers, natural or synthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers; wherein the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hy drogenated alcohols or fatty7acids, salts, or esters thereof; fatty7acids mono-, di- or triglycerides or poly ethoxylated derivatives thereof; waxes; ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof; wherein the hydrophilic matrix compnses a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol; wherein the pharmaceutical composition further comprises a gastro-resistant coating; wherein the pharmaceutical composition comprisesa tablet core and coating covering the core; and wherein the pharmaceutical composition is suitable for oral administration. Disclosed herein are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in ameliorating a symptom of sarcopenia. wherein the pharmaceutical composition has a multi-matrix structure comprising :a) an amphiphilic matrix in which the rifamycin SV is incorporated; b) a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a) is dispersed; and c) a hydrophilic matrix; wherein the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II, lecithins, alkyl block copolymers, salts of sulphated alkyl acids, polyoxyethylenated alkyl derivatives of sorbitan, glycol alkyl ethers, natural or synthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers; wherein the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty acids, salts, or esters thereof; fatty acids mono-, di- or triglycerides or polyethoxylated derivatives thereof; waxes; ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof; wherein the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol; wherein the pharmaceutical composition further comprises a gastro-resistant coating; wherein the pharmaceutical composition comprises a tablet core and coating covering the core; and wherein the pharmaceutical composition is suitable for oral administration.

[0132] The pharmaceutical composition used in the methods of treating a subject having sarcopenia or ameliorating a symptom of sarcopenia in a subject having sarcopenia disclosed herein may comprise about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. The pharmaceutical composition may comprise about 400 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. The pharmaceutical composition may comprise about 600 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. The pharmaceutical composition may comprise about 800 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. The pharmaceutical composition may comprise about 1,000 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. The pharmaceutical composition may comprise about1,100 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. The pharmaceutical composition may comprise about 1,200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

[0133] In some aspects, the pharmaceutical composition used in the methods of treating a subject having sarcopenia or ameliorating a symptom of sarcopenia in a subject having sarcopenia disclosed herein may comprise about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In another aspect, the pharmaceutical composition may comprise about 600 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

[0134] The pharmaceutical composition for use in the treatment of sarcopenia or ameliorating a symptom of sarcopenia, may comprise the step of administering about 200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subj ect in need thereof. The pharmaceutical composition for use in the treatment of sarcopenia, may comprise the step of administering about 400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in the treatment of sarcopenia or ameliorating a symptom of sarcopenia, may comprise the step of administering about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in the treatment of sarcopenia or ameliorating a symptom of sarcopenia. may comprise the step of administering about 800 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in the treatment of sarcopenia or ameliorating a symptom of sarcopenia, may comprise the step of administering about 1,000 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in the treatment of sarcopenia or ameliorating a symptom of sarcopenia, may comprise the step of administering about 1,200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in the treatment of sarcopenia or ameliorating a symptom of sarcopenia, may comprise the step of administering about 1,400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in the treatment of sarcopenia or ameliorating a symptom of sarcopenia, may comprise the step of administering about 1,600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in the treatment of sarcopenia or ameliorating a symptom of sarcopenia, may comprise the step of administering about 1,800 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. This may be achieved by administering a single dosage form that delivers about 200 mg of rifamycin SV or apharmaceutically acceptable salt thereof or by administering multiple dosage forms in order to deliver an overall dose of about 200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. This may be achieved by administering a single dosage form that delivers about 400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof or by administering multiple dosage forms in order to deliver an overall dose of about 400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. Preferably, this may be achieved by administering a single dosage form that delivers about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof or by administering multiple dosage forms in order to deliver an overall dose of about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. Advantageously, patient compliance is increased if a single dosage form such as an oral pharmaceutical composition in the form of a solid dosage form comprising about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. ii. Treatment

[0135] In some aspects, the methods of treatment of sarcopenia or ameliorating a symptom of sarcopenia may comprise administering the pharmaceutical composition to the subject in need thereof once daily. In some aspects, the methods of treatment of sarcopenia or ameliorating a symptom of sarcopeniamay comprise administering the pharmaceutical composition to the subject in need thereof twice daily. In some aspects, the methods of treatment of sarcopenia or ameliorating a symptom of sarcopeniamay comprise administering the pharmaceutical composition to the subject in need thereof thrice daily. In some aspects, the methods of treatment of sarcopenia or ameliorating a symptom of sarcopeniamay comprise administering the pharmaceutical composition to the subject in need thereof four times a day.

[0136] In some aspects, the methods of treatment of sarcopenia or ameliorating a symptom of sarcopenia may comprise administering the pharmaceutical composition to the subject in need thereof for 15 days, or 30 days, or 45 days, or 2 months, or 3 months, or 4 months, or 5 months, or 6 months. In some aspects, the methods of treatment of sarcopenia or ameliorating a symptom of sarcopenia may comprise administering the pharmaceutical composition to the subject in need thereof for at least 30 days.

[0137] Thus, an example of the methods of treatment of sarcopenia or ameliorating a symptom of sarcopenia comprises administering the pharmaceutical composition to the subject in need thereof twice daily for 30 days. iii. Subject population

[0138] In some aspects, the methods of treatment of sarcopenia or ameliorating a symptom of sarcopenia comprise administering the pharmaceutical composition to a subject, wherein thesubject has a chronic disease. In some aspects, the chronic disease is selected from the group comprising: hepatic cirrhosis, hepatic encephalopathy, cancer cachexia, renal failure, congestive heart failure, and end-stage lung disease. In some aspects, the chronic disease is hepatic cirrhosis and / or hepatic encephalopathy.

[0139] In some aspects, the subject has been diagnosed with sarcopenia prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0140] In some aspects, the subject has been diagnosed with minimal hepatic encephalopathy prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0141] In some aspects, the subject has been diagnosed with cirrhosis prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0142] In some aspects, the subject has been diagnosed with associated cognitive impairment prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0143] In some aspects, the subject does not have diarrhea prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0144] In some aspects, the subject has been previously treated with lactulose or rifaximin.2. Improving Muscle Mass

[0145] Disclosed are methods of improving muscle mass in a subject comprising administering a therapeutically effective amount of a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients to the subject.

[0146] Disclosed are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in improving muscle mass in a subject. i. Pharmaceutical composition

[0147] In some aspects, the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof can be one or more of those described herein. In some aspects, the pharmaceutical composition has a multi-matrix structure comprising an amphiphilic matrix in which the rifamycin SV is incorporated; a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a) is dispersed; and ahydrophilic matrix.

[0148] In some aspects, the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II, lecithins, alkyl block copolymers, salts of sulphated alkyl acids, polyoxyethylenated alkyl derivatives of sorbitan. glycol alkyl ethers, natural or synthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers. In some aspects, an amphiphilic substance can be present in an amount ranging from 0.001 - 0.0500 % w / w, or 0.005 - 0.050 % w / w, or 0.005 - 0.030 % w / w of the weight of the composition.

[0149] In some aspects, the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty acids, salts, or esters thereof; fatty acids mono-, di- or triglycerides or polyethoxylated derivatives thereof; waxes; ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof. In some aspects, a lipophilic substance can be present in an amount ranging from 0.01 - 0.050 % w / w, or 0.01 - 0.035 % w / w, or 0.015 - 0.025 % w / w of the weight of the composition.

[0150] In some aspects, the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol. In some aspects, a hydrophilic substance can be present in an amount ranging from 0.05 - 0.50 % w / w, or 0. 1 - 0.5 % w / w. or 0. 1 - 0.3 % w / w of the weight of the composition.

[0151] In some aspects, the pharmaceutical composition may comprise an amphiphilic matrix comprising lecithin, a lipophilic matrix comprising stearic acid, and a hydrophilic matrix comprising sodium carboxymethylcellulose. In some aspects, the pharmaceutical composition may comprise an amphiphilic matrix comprising lecithin, a lipophilic matrix comprising Glyceryl Distearate, and a hydrophilic matrix Ammonio Methacrylate Copolymer (Type B).

[0152] In some aspects, the pharmaceutical composition further comprises a gastro-resistant (or enteric) coating. In some aspects, the pharmaceutical composition may comprise a gastro- resistant coating which dissolves at a pH of about 5, or about 5.5. or about 6.0, or about 6.2, or about 6.4, or about 6.6, or about 6.8, or about 7.0, or about 7.1 or about 7.2. In some aspects, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH of about 6.4. In another preferred embodiment, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH of about 6.8. In further another preferred embodiment, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH about 7.2. In some aspects, a gastro-resistant coating can comprise shellac, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose phthalate, or hydroxypropylmethylcellulose acetate succinate.

[0153] In other aspects, the gastro-resistant coating (film) covering the tablet core can contain a polymethacrylate, acry lic and / or methacry lic acids polymers or copolymers, or a cellulose derivative, such as cellulose acetophthalate. . Optionally, the gastro-protective coating comprises methacrylic acid / methyl methacrylate (1 : 1) copolymer (e.g., commercially known as EUDRAGIT L). Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacry late (1 :2) copolymer (e.g., commercially known as EUDRAGIT S). Optionally, the gastro-protective coating comprises methacrylic acid-ethylacrylate (1: 1) copolymer (e.g., commercially known as EUDRAGIT L30 D55). Optionally, the gastro-protective coating comprises polymethacrylate copolymers including, but not limited, to compounds known commercially as EUDRAGIT S (methacrylic acid-methyl methacrylate copolymer 1:2), EUDRAGIT L (methacry lic acid- methyl methacry late 1 :1 copolymer) and / or EUDRAGIT L30 D55 (methacrylic acid-ethylacrylate 1: 1 copolymer), and / or mixtures thereof. The gastro resistant coating can comprise a methacrylic acid -(meth)acrylale copolymer. In some embodiments, the gastro resistant coating comprises methacrylic acid / methyl methacry late copolymer.

[0154] The gastro-resistant coating can comprise methacrylic acid / methyl methacry late (1 :1) copolymer (EUDRAGIT L). or methacrylic acid / methyl methacry late (1:2) copolymer (EUDRAGIT S).

[0155] Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacrylate (1 : 1) copolymer (EUDRAGIT L).

[0156] Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacrylate (1 :2) copolymer (EUDRAGIT S).

[0157] In some embodiments, the gastro-resistant coating comprises a mixture of methacry lic acid / methyl methacry late (1: 1) copolymer and of methacry lic acid / methyl methacrylate (1 :2) copolymer. Optionally, the mixture comprises a w eight ratio of from 0.5: 1 to 3: 1 of methacrylic acid / methyl methacrylate (1 : 1) copolymer to melhacrvlic acid / methyl methacrylate (1 :2). Optionally, the mixture comprises a weight ratio of from 1 : 1 to 3: 1 of methacry lic acid / methyl methacrylate (1: 1) copolymer to methacrylic acid / methyl methacrylate (1:2). In some embodiments, the mixture comprises a weight ratio of about 2: 1 of methacry licacid / methyl methacrylate (1 : 1) copolymer to methacrylic acid / methyl methacrylate (1:2). Optionally, the gastro-resistant coating of the unit dose starts breaking or dissolving at or above a pH of 5, optionally, at or about a pH of 6, at or above a pH of 6.5, or at a pH of 6.8.

[0206] In some embodiments, the active substance is released from the tablet core at pH of at least 5, such as 5.1, or 5.2, or 5.3, or 5.4, or 5.5. or 5.6, or 5.7, or 5.8. or 5.9, or 6, or 6.1. or 6.2, or 6.3, or 6.4, or 6.5, or 6.6, or 6.7, or 6.8, or 6.9, or 7, or 7.1 , or 7.2, or 7.3, or 7.4, or 7.5. In some embodiments, the active substance is released from the tablet core at pH in the range from about 6.5 to about 7.5, optionally, at a pH in the range of from about 6.8 to about 7. According to a certain aspect, the active substance is released from the tablet core at pH of 6.8. According to another aspect, the active substance is released from the tablet core at pH of 7. According to a further aspect, the active substance is released from the tablet core at pH of 7.2.

[0158] In some aspects, the pharmaceutical composition comprises a tablet core and coating covering the core. In some aspects, the coating can be a gastro-resistant coating, a delayed released coating, an extended release coating.

[0159] In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal portion of the intestine, i.e. in the small intestine. In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV. or a pharmaceutically acceptable salt thereof, starts in the distal part of the small intestine, of example in the ileum. In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal part of the colon, for example in the caecum.

[0160] In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal portion of the intestine, i.e. in the small intestine (duodenumjejunum and ileum) and may optionally continue throughout the large intestine. In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the distal part of the small intestine, of example in the ileum and may optionally continue throughout the large intestine. In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal part of the colon, for example in the caecum and may optionally continue throughout the large intestine.

[0161] In some aspects, the pharmaceutical composition is suitable for any known administration, particularly those described herein. In some aspects, the pharmaceuticalcomposition is suitable for oral administration. In other aspects, the pharmaceutical composition is suitable for rectal administration. In further aspects, the pharmaceutical composition is suitable for parenteral administration, including intravenous, intramuscular or subcutaneous injection. In a preferred aspect, the pharmaceutical composition is suitable for oral administration.

[0162] Disclosed herein are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in the treatment of sarcopenia, wherein the pharmaceutical composition has a multi-matrix structure comprising :a) an amphiphilic matrix in which the rifamycin SV is incorporated; b) a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a) is dispersed; and c) a hydrophilic matrix; wherein the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II. lecithins, alkyl block copolymers, salts of sulphated alkyl acids, poly oxy ethylenated alkyl derivatives of sorbitan. glycol alkyl ethers, natural or synthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers; wherein the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty acids, salts, or esters thereof; fatty acids mono-, di- or triglycerides or polyethoxylated derivatives thereof; waxes; ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof; wherein the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol; wherein the pharmaceutical composition further comprises a gastro-resistant coating; wherein the pharmaceutical composition comprises a tablet core and coating covering the core; and wherein the pharmaceutical composition is suitable for oral administration.

[0163] In some aspects, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 400 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 600 mg rifamycin SV, or a pharmaceutically acceptable saltthereof. In some aspects, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 800 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 1,000 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 1 , 100 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 1,200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

[0164] In some aspects, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In another aspect, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 400 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In another aspect, the pharmaceutical composition used in the methods of improving muscle mass may comprise about 600 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

[0165] The pharmaceutical composition for use in improving muscle mass in a subject, may comprise the step of administering about 200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in the improving muscle mass in a subject, may comprise the step of administering about 400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in improving muscle mass in a subject, may comprise the step of administering about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in improving muscle mass in a subject, may comprise the step of administering about 800 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in improving muscle mass in a subject, may comprise the step of administering about 1,000 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in improving muscle mass in a subject, may comprise the step of administering about 1,200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in improving muscle mass in a subject, may comprise the step of administering about 1,400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in improving muscle mass in asubject, may comprise the step of administering about 1,600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in improving muscle mass in a subject, may comprise the step of administering about 1,800 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. This may be achieved by administering a single dosage form that delivers about 200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof or by administering multiple dosage forms in order to deliver an overall dose of about 200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. This may be achieved by administering a single dosage form that delivers about 400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof or by administering multiple dosage forms in order to deliver an overall dose of about 400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. Preferably, this may be achieved by administering a single dosage form that delivers about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof or by administering multiple dosage forms in order to deliver an overall dose of about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. Advantageously, patient compliance is increased if a single dosage form such as an oral pharmaceutical composition in the form of a solid dosage form comprising about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. ii. Treatment

[0166] In some aspects, the methods of improving muscle mass in a subjectmay comprise administering the pharmaceutical composition to the subject in need thereof once daily. In some aspects, the methods of improving muscle mass in a subj ect may comprise administering the pharmaceutical composition to the subject in need thereof twice daily. In some aspects, the methods of improving muscle mass in a subject may comprise administering the pharmaceutical composition to the subject in need thereof thrice daily. In some aspects, the methods of improving muscle mass in a subject may comprise administering the pharmaceutical composition to the subject in need thereof four times a day.

[0167] In some aspects, the methods of improving muscle mass in a subjectmay comprise administering the pharmaceutical composition to the subject in need thereof for 15 days, or 30 days, or 45 days, or 2 months, or 3 months, or 4 months, or 5 months, or 6 months. In some aspects, the methods of improving muscle mass in a subj ectmay comprise administering the pharmaceutical composition to the subject in need thereof for at least 30 days.

[0168] Thus, an example of the methods of improving muscle mass in a subjectcomprises administering the pharmaceutical composition to the subject in need thereof twice daily for 30 days.iii. Subject population

[0169] In some aspects, the methods of improving muscle mass in a subject comprise administering the pharmaceutical composition to a subject, wherein the subject has a chronic disease. In some aspects, the chronic disease is selected from the group comprising: hepatic cirrhosis, hepatic encephalopathy, cancer cachexia, renal failure, congestive heart failure, and end-stage lung disease. In some aspects, the chronic disease is hepatic cirrhosis and / or hepatic encephalopathy.

[0170] In some aspects, the subject has been diagnosed with sarcopenia prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0171] In some aspects, the subject has been diagnosed with minimal hepatic encephalopathy prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0172] In some aspects, the subject has been diagnosed with cirrhosis prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0173] In some aspects, the subject has been diagnosed with associated cognitive impairment prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0174] In some aspects, the subject does not have diarrhea prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0175] In some aspects, the subject has been previously treated with lactulose or rifaximin.3. Treating Cirrhosis

[0176] Disclosed are methods of treating a subject having cirrhosis comprising administering a therapeutically effective amount of a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients to the subject.

[0177] Disclosed are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in the treatment of cirrhosis. i. Pharmaceutical composition

[0178] In some some aspects, the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof can be one or more of those described herein. In someaspects, the pharmaceutical composition has a multi-matrix structure comprising an amphiphilic matrix in which the rifamycin SV is incorporated; a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a) is dispersed; and a hydrophilic matrix.

[0179] In some aspects, the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of ty pe I or IT, lecithins, alkyl block copolymers, salts of sulphated alkyl acids, polyoxy ethylenated alkyl derivatives of sorbitan. glycol alkyl ethers, natural or synthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers. In some aspects, an amphiphilic substance can be present in an amount ranging from 0.001 - 0.0500 % w / w, or 0.005 - 0.050 % w / w, or 0.005 - 0.030 % w / w of the weight of the composition.

[0180] In some aspects, the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty acids, salts, or esters thereof; fatty acids mono-, di- or triglycerides or polyethoxylated derivatives thereof; waxes: ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof. In some aspects, a lipophilic substance can be present in an amount ranging from 0.01 - 0.050 % w / w, or 0.01 - 0.035 % w / w, or 0.015 - 0.025 % w / w of the weight of the composition.

[0181] In some aspects, the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol. In some aspects, a hydrophilic substance can be present in an amount ranging from 0.05 - 0.50 % w / w, or 0.1 - 0.5 % w / w, or 0. 1 - 0.3 % w / w of the weight of the composition.

[0182] In some aspects, the pharmaceutical composition may comprise an amphiphilic matrix comprising lecithin, a lipophilic matrix comprising stearic acid, and a hydrophilic matrix comprising sodium carboxymethylcellulose. In some aspects, the pharmaceutical composition may comprise an amphiphilic matrix comprising lecithin, a lipophilic matrix comprising Glyceryl Distearate, and a hydrophilic matrix Ammonio Methacrylate Copolymer (Type B).

[0183] In some aspects, the pharmaceutical composition further comprises a gastro-resistant (or enteric) coating. In some aspects, the pharmaceutical composition may comprise a gastro- resistant coating which dissolves at a pH of about 5, or about 5.5, or about 6.0, or about 6.2, orabout 6.4, or about 6.6, or about 6.8, or about 7.0, or about 7.1 or about 7.2. In some aspects, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH of about 6.4. In another preferred embodiment, the pharmaceutical composition comprises a gastro- resistant coating which dissolves at a pH of about 6.8. In further another preferred embodiment, the pharmaceutical composition comprises a gastro-resistant coating which dissolves at a pH about 7.2. In some aspects, a gastro-resistan coating can comprise shellac, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose phthalate, or hydroxypropylmethylcellulose acetate succinate. In other aspects, the gastro-resistant coating (film) covering the tablet core can contain a polymethacrylate, acrylic and / or methacrylic acids polymers or copolymers, or a cellulose derivative, such as cellulose acetophthalate. . Optionally, the gastro-protective coating comprises methacrylic acid / methyl methacrylate (1 :1) copolymer (e.g., commercially known as EUDRAGIT L). Optionally , the gastro-resistant coating comprises methacrylic acid / methyl methacrylate (1:2) copolymer (e.g., commercially known as EUDRAGIT S). Optionally, the gastro-protective coating comprises methacrylic acid- ethylacry late (1 : 1) copolymer (e.g., commercially known as EUDRAGIT L30 D55). Optionally, the gastro-protective coating comprises polymethacrylate copolymers including, but not limited, to compounds known commercially as EUDRAGIT S (methacrylic acid-methyl methacrylate copolymer 1 :2), EUDRAGIT L (methacrylic acid- methyl methacrylate 1: 1 copolymer) and / or EUDRAGIT L30 D55 (methacrylic acid-ethyl acrylate 1 : 1 copolymer), and / or mixtures thereof. The gastro resistant coating can comprise a methacrylic acid -(meth)acrylate copolymer. In some embodiments, the gastro resistant coating comprises methacrylic acid / methyl methacrylate copolymer.

[0184] The gastro-resistant coating can comprise methacrylic acid / methyl methacrylate (1 : 1) copolymer (EUDRAGIT L), or methacrylic acid / methyl methacrylate (1:2) copolymer (EUDRAGIT S).

[0185] Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacrylate (1 : 1) copolymer (EUDRAGIT L).

[0186] Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacry late (1 :2) copolymer (EUDRAGIT S).

[0187] In some embodiments, the gastro-resistant coating comprises a mixture of methacrylic acid / methyl methacrylate (1: 1) copolymer and of methacrylic acid / methyl methacrylate (1 :2) copolymer. Optionally, the mixture comprises a weight ratio of from 0.5: 1 to 3: 1 of methacrylic acid / methyl methacrylate (1 : 1) copolymer to methacry lic acid / methyl methacrylate (1 :2). Optionally, the mixture comprises a weight ratio of from 1 : 1 to 3: 1 ofmethacrylic acid / methyl methacrylate (1 : 1) copolymer to methacrylic acid / methyl methacrylate (1:2). In some embodiments, the mixture comprises a weight ratio of about 2: 1 of methacrylic acid / methyl methacrylate (1 :1) copolymer to methacrylic acid / methyl methacrylate (1:2).

[0188] Optionally, the gastro-resistant coating of the unit dose starts breaking or dissolving at or above a pH of 5, optionally, at or about a pH of 6, at or above a pH of 6.5, or at a pH of 6.8.

[0206] In some embodiments, the active substance is released from the tablet core at pH of at least 5, such as 5.1, or 5.2, or 5.3, or 5.4, or 5.5, or 5.6, or 5.7, or 5.8, or 5.9, or 6, or 6.1, or 6.2, or 6.3, or 6.4, or 6.5, or 6.6, or 6.7, or 6.8, or 6.9, or 7, or 7.1, or 7.2, or 7.3, or 7.4, or 7.5. In some embodiments, the active substance is released from the tablet core at pH in the range from about 6.5 to about 7.5, optionally, at a pH in the range of from about 6.8 to about 7. According to a certain aspect, the active substance is released from the tablet core at pH of 6.8. According to another aspect, the active substance is released from the tablet core at pH of 7. According to a further aspect, the active substance is released from the tablet core at pH of 7.2.

[0189] In some aspects, the pharmaceutical composition comprises a tablet core and coating covering the core. In some aspects, the coating can be a gastro-resistant coating, a delayed released coating, an extended release coating. In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal portion of the intestine, i.e. in the small intestine. In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the distal part of the small intestine, of example in the ileum. In some aspects, the pharmaceutical composition may be formulated for delayed release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal part of the colon, for example in the caecum.

[0190] In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamy cin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal portion of the intestine, i.e. in the small intestine (duodenumjejunum and ileum) and may optionally continue throughout the large intestine. In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the distal part of the small intestine, of example in the ileum and may optionally continue throughout the large intestine. In some aspects, the pharmaceutical composition may be formulated for extended release as release of the rifamycin SV, or a pharmaceutically acceptable salt thereof, starts in the proximal part of the colon, for example in the caecum and may optionally continue throughout the large intestine.

[0191] In some aspects, the pharmaceutical composition is suitable for any knownadministration, particularly those described herein. In some aspects, the pharmaceutical composition is suitable for oral administration. In other aspects, the pharmaceutical composition is suitable for rectal administration. In further aspects, the pharmaceutical composition is suitable for parenteral administration, including intravenous, intramuscular or subcutaneous injection. In a preferred aspect, the pharmaceutical composition is suitable for oral administration.

[0192] Disclosed herein are pharmaceutical compositions comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in the treatment of sarcopenia, wherein the pharmaceutical composition has a multi-matrix structure comprising :a) an amphiphilic matrix in which the rifamycin SV is incorporated; b) a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a) is dispersed; and c) a hydrophilic matrix; wherein the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II. lecithins, alkyl block copolymers, salts of sulphated alkyl acids, polyoxy ethylenated alkyl derivatives of sorbitan, glycol alkyl ethers, natural or synthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers; wherein the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty acids, salts, or esters thereof; fatty acids mono-, di- or triglycerides or polyethoxylated derivatives thereof; waxes; ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof; wherein the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol; wherein the pharmaceutical composition further comprises a gastro-resistant coating; wherein the pharmaceutical composition comprises a tablet core and coating covering the core; and wherein the pharmaceutical composition is suitable for oral administration.

[0193] In some aspects, the pharmaceutical composition used in the methods of treating a subject having cirrhosis may comprise about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of treating a subject having cirrhosis may comprise about 400 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition usedin the methods of treating a subject having cirrhosis may comprise about 600 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of treating a subject having cirrhosis may comprise about 800 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of treating a subject having cirrhosis may comprise about 1 ,000 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of treating a subject having cirrhosis may comprise about 1,100 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of treating a subject having cirrhosis may comprise about 1,200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

[0194] In some aspects, the pharmaceutical composition used in the methods of treating a subject having cirrhosis may comprise about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition used in the methods of treating a subject having cirrhosis may comprise about 600 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

[0195] The pharmaceutical composition for use in treating a subject having cirrhosis, may comprise the step of administering about 200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in treating a subject having cirrhosis, may comprise the step of administering about 400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subj ect in need thereof. The pharmaceutical composition for use in treating a subject having cirrhosis, may comprise the step of administering about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in treating a subject having cirrhosis, may comprise the step of administering about 800 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in treating a subject having cirrhosis, may comprise the step of administering about 1,000 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in treating a subject having cirrhosis, may comprise the step of administering about 1 ,200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in treating a subject having cirrhosis, may comprise the step of administering about 1,400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in the treating a subject havingcirrhosis, may comprise the step of administering about 1,600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. The pharmaceutical composition for use in treating a subject having cirrhosis, may comprise the step of administering about 1,800 mg of rifamycin SV or a pharmaceutically acceptable salt thereof to a subject in need thereof. This may be achieved by administering a single dosage form that delivers about 200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof or by administering multiple dosage forms in order to deliver an overall dose of about 200 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. This may be achieved by administering a single dosage form that delivers about 400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof or by administering multiple dosage forms in order to deliver an overall dose of about 400 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. Preferably, this may be achieved by administering a single dosage form that delivers about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof or by administering multiple dosage forms in order to deliver an overall dose of about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. Advantageously, patient compliance is increased if a single dosage form such as an oral pharmaceutical composition in the form of a solid dosage form comprising about 600 mg of rifamycin SV or a pharmaceutically acceptable salt thereof. ii. Treatment

[0196] In some aspects, the methods of treating a subject having cirrhosis may comprise administering the pharmaceutical composition to the subject in need thereof once daily. In some aspects, the methods of treating a subject having cirrhosis may comprise administering the pharmaceutical composition to the subject in need thereof twice daily. In some aspects, the methods of treating a subject having cirrhosis may comprise administering the pharmaceutical composition to the subject in need thereof thrice daily. In some aspects, the methods of treating a subject having cirrhosis may comprise administering the pharmaceutical composition to the subject in need thereof four times a day.

[0197] In some aspects, the methods of treating a subject having cirrhosismay comprise administering the pharmaceutical composition to the subject in need thereof for 15 days, or 30 days, or 45 days, or 2 months, or 3 months, or 4 months, or 5 months, or 6 months. In some aspects, the treatment may comprise administering the pharmaceutical composition to the subject in need thereof for at least 30 days.

[0198] Thus, an example of the treatment comprises administering the pharmaceutical composition to the subject in need thereof twice daily for 30 days.iii. Subject population

[0199] In some aspects, the methods of treating a subject having cirrhosiscomprise administering the pharmaceutical composition to a subject, wherein the subject has a chronic disease. In some aspects, the chronic disease is selected from the group comprising: hepatic cirrhosis, hepatic encephalopathy, cancer cachexia, renal failure, congestive heart failure, and end-stage lung disease. In some aspects, the chronic disease is hepatic cirrhosis and / or hepatic encephalopathy.

[0200] In some aspects, the subject has been diagnosed with sarcopenia prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0201] In some aspects, the subject has been diagnosed with minimal hepatic encephalopathy prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0202] In some aspects, the subject has been diagnosed with cirrhosis prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0203] In some aspects, the subject has been diagnosed with associated cognitive impairment prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0204] In some aspects, the subject does not have diarrhea prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

[0205] In some aspects, the subject has been previously treated with lactulose or rifaximin.D. Combination Therapy

[0206] In one aspect of the disclosed methods, the pharmaceutical compositions can be administered alone or in combination with one or more additional therapeutic agents. The additional therapeutic agents are selected based on the disease or symptom to be treated. A description of the various classes of suitable pharmacological agents and drugs may be found in Goodman and Gilman, The Pharmacological Basis of Therapeutics, (11th Ed., McGraw-Hill Publishing Co.) (2005). For example, the disclosed methods can be a combination therapy with a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and androgen derivatives, bile acid analogues, lactulose, beta-blockers, other antibiotics, fecal microbiota transplant, or diuretics.E. KitsThe compositions and materials described above as well as other materials can be packaged together in any suitable combination as a kit useful for performing, or aiding in the performance of, the disclosed method. It is useful if the kit components in a given kit are designed and adapted for use together in the disclosed method.ExamplesA. Example 11. Introduction

[0207] Minimal hepatic encephalopathy (MHE) is associated with poor outcomes but treatment strategies are limited. Rifamycin SV MMX (RiVM) is a novel rifamycin SV composition comprising the antibiotic formulated in a delayed and / or extended release formulation, to provide an optimal release and concentration of the active substance in the colon. Aim: Evaluate impact of RiVM on microbiome, safety & gut-brain axis in an RCT.

[0208] Rifamycin SV MMX (RIVM) is thought to be safe and favorably alter gut microbiota composition and function in patients with minimal hepatic encephalopathy compared to placebo in a randomized, double-blind, placebo-controlled, clinical trial. The aims were to determine the safety and tolerability7of RIVM in patients with cirrhosis and MHE, and the primary outcome was change in stool cirrhosis dysbiosis ratio (CDR) and microbiome composition. Secondary outcomes included safety and tolerability, impact on cognitive testing, microbial functionality, stool calprotectin, patient-reported outcomes, sarcopenia, and changes in salivary microbiota.

[0209] An exemplary7Rifamycin SV MMX composition comprising 600 mg rifamycin SV is disclosed in the following table:Table 1(1) As anhydrous substance (dried), being equivalent to about 702 mg of rifamycin SV sodium salt in hydrate form considering a mean water content of about 14.5%(2) Mannitol amount is adjusted to compensate for rifamycin SV sodium amount correction based on water content.(3) Purified water and ethanol are essentially removed during manufacturing process.

[0210] Rifamycin SV (sodium salt), ascorbic acid, lecithin, stearic acid and a portion of magnesium stearate were mixed in a suitable container till homogeneity of dispersion was obtained. Then mannitol, sodium carboxymethyl cellulose and silica were added and the mixture was mixed again; the addition of magnesium stearate was completed, and the powder was compressed into a rotating tableting machine to obtain the tablet cores. These tablet cores were then coated in coating pan equipment with Eudragit LI 00, triethylcitrate, talc, titanium dioxide and red ferric dioxide using ethanol as solvent to apply the gastro-resistant coating layer. The tablets were then polished by adding some polyethylene glycol 6000 in a water solution.

[0211] Another sample composition of the invention i.e. a representative Rifamycin SV MMX composition comprising 600 mg rifamycin SV is provided below: Table 2(1) As anhydrous substance (dried), being equivalent to about 702 mg of rifamycin SV sodium salt in hydrate form considering a mean water content of about 14.5%(2) Mannitol amount is adjusted to compensate for rifamycin SV sodium amount correction based on water content.(3) Purified water and ethanol are essentially removed during manufacturing process.

[0212] Rifamycin SV (sodium salt), ascorbic acid, lecithin, stearic acid and a portion of magnesium stearate were mixed in a suitable container till homogeneity of dispersion was obtained. Then mannitol, sodium carboxy methyl cellulose and silica were added and the mixture was mixed again; the addition of magnesium stearate was completed, and the powder was compressed into a rotating tableting machine to obtain the tablet cores. These tablet cores were then coated in a coating pan equipment with a (1 : 1) mixture of Eudragit S 100 and Eudragit LI 00, tri ethylcitrate, talc, titanium dioxide and red ferric dioxide using ethanol as solvent to apply the gastro-resistant coating layer. The tablets were then polished by adding some polyethylene glycol 6000 in a water solution.

[0213] A further example composition according to the present invention i.e. a representative Rifamycin SV MMX composition comprising 200 mg rifamycin SV for use in treating sarcopenia is described in the following table:Table 3Tablet961(1) On anhydrous basis; the quantity is adjusted based on the water content and purity of Rifamycin Sodium.(2) Adjusted based on the water content and purity' of Rifamycin Sodium.(3) Alcohol (Ethanol) and purified water used during the film coating and polishing steps are essentially removed during the manufacturing process.

[0214] As the above formulation comprises 200 mg rifamycin SV, three tablets may be administered to achieve a dose of about 600 mg rifamycin SV.2. Methods

[0215] This was a randomized, double-blind, placebo-controlled clinical trial in patients with cirrhosis over 30 days of treatment and 7 days off of therapy. The trial was carried out under FDA Investigational New Drug authorization. i. Subject population:

[0216] The subject population consisted of patients with cirrhosis between 18-75 years who were able to consent who had cognitive impairment on PHES or EncephalApp Stroop. Cirrhosis was diagnosed by liver biopsy, or imaging characteristics of a nodular liver with varices, varices on endoscopy or platelet count <150,000 and AST / ALT>1 in a patient with chronic liver disease. Patients were required to have stable liver function between 2-12 weeks prior to enrolment and those of reproductive age group had to be on reliable birth control. Patients were excluded if they had unclear diagnosis of cirrhosis, prior / current overt HE, rifaximin or lactulose therapy, unstable liver-associated enzy mes, recent (<3 months) alcohol / illicit drug use, advanced liver disease (Child score >8, MELD>20, Na<125), antibiotic use within 6 weeks, psychoactive drug use apart from long-standing opioids or stable antidepressant use, recent (<1 month) infections, post-transplant status, allergic reactions to rifamycin, rifampin or rifaximin derivatives, end-stage organ failures (CHF with EF<25%, Endstage renal disease on dialysis, COPD on home oxygen), <3 month of statin therapy if on a statin, and those who are unlikely to survive or remain without liver transplant for 6 weeks, or can adhere to the trial activities. ii. Overall study flow:

[0217] Once potential subjects were consented, screening activities, which included MMSE. cognitive testing (PHES, EncephalApp Stroop) for all and urine pregnancy test for women of reproductive age group, were performed. Patients with MMSE<25, normal performance compared to US-based norms on EncephalApp and PHES, and those who were pregnant w ere excluded. The remainder were eligible for randomization and the remaining study activities perFIG. 1A. iii. Randomization:

[0218] Subjects were randomized 1 : 1 to receive Rifamycin-SV MMX 600 mg PO twice daily (1,200 mg daily in total) or Placebo for 30 days with 7 days off drug follow-up using sealed envelopes stored in the investigational pharmacy. Only the investigational pharmacist was aware of the randomization scheme. iv. Safety assessment:

[0219] Physical examinations, history taking and routine safety laboratory examinations along with creatine phosphokinase (CPK) were performed during each visit. Adverse events were thoroughly investigated and infections, new complications of cirrhosis (overt HE, variceal bleeding, admissions for liver-related conditions) and any hospitalization were thoroughly investigated. v. Outcomes:

[0220] The primary outcome was change in Cirrhosis Dysbiosis Ratio (CDR) calculated as [Lachnospiraceae + Ruminococcaceae + Clostridium Cluster XIV + Veillonellaceae / Enterobacteriaceae + Bacteroidaceae] in stool. Secondary outcomes were (a) overall microbiota composition in stool and saliva (b) microbiota function (Bile acids and SCFA in stool and metabolomics from serum and urine), (c) stool calprotectin, (d) Cognitive function: PHES, EncephalApp Stroop, (e) HRQOL (Sickness Impact Profile) and Sleep (PSQI) and (!) Safety assessment with changes in MELD score and AE / SAEs. Exploratory outcomes were related to sarcopenia with handgrip strength and InBody assessment and Brain MR spectroscopy in a subset of patients who agreed and did not have contraindications to perform MRI. vi. Sample processing and storage:

[0221] Blood was sent for routine testing (MELD score, safety) and serum was stored for metabolomics. bile acid profile, systemic inflammation and endotoxemia assessment. Urine was collected mid-stream for metabolomics and stored at -80 degrees till metabolomics was performed. Spontaneously passed stool was collected using ParaPak kits and split into aliquots, for microbiota composition and bile acid analysis. Saliva was collected after an oral rinse with normal saline in the presence of the coordinator. This rinse was discarded, and saliva collected after that was flash-frozen for microbiome analysis. vii. Safety blood work:

[0222] Serum basic metabolic panel, liver function panel, complete blood count withdifferential, serum albumin, venous ammonia, INR and CPK can be checked at each visit. viii. Cognitive function:

[0223] Cognitive function is tested using the validated Psychometric hepatic encephalopathy score and EncephalApp Stroop. Impaired performance on either of these compared to US-based norms were considered MHE. ix. HRQOL:

[0224] The Sickness Impact Profile, a validated 136 questions HRQOL scale which has 12 dimensions and yields an overall score, a physical score and a psychosocial score along with Pittsburgh Sleep Quality Index (PSQI), was administered. x. Inflammation and endotoxemia:

[0225] Serum endotoxin binding protein and inflammatory cytokines (IL-6, TNF-a, IL- 1(3) band stool calprotectin were analyzed using published ELISA techniques. xi. Sarcopenia assessment:

[0226] Functional sarcopenia was assessed using handgrip strength through the Jamar Hand Dynamometer. The distribution of fat and muscle to assess structure was performed using the InBody machine (Cerritos. CA). xii. Microbiota analysis:

[0227] 16S rRNA was used to interrogate and characterize gut microbiome composition as per prior studies in stool and saliva and CDR was calculated [16, 17], Functionality' of the microbiota was assessed using SCFA and BA analysis of the stool using published techniques. Untargeted metabolites in serum and urine were performed using LC / MS techniques

[0018] at Metabolon Inc (Morrisville NC). xiii. Brain MRI analysis:

[0228] In a subset of those who are willing and able to do it, brain MRS were analyzed for changes in creatine ratios of myoinositol, choline, Glx and GABA using the validated LC model [19-21], xiv. Sample size:

[0229] In a prior study' pre and post development of HE, there was a significant change in CDR from 1.20 to 0.42; with an SD of 0.7 in these patients with an alpha of 0.8 will require at least 14 patients per group. xv. Statistical analysis:

[0230] Repeated measures ANOVA will be performed between groups to analyse changes in the primary outcome and secondary outcomes. Delta change in cognition, HRQOL and routine lab work (ammonia, MELD s) between groups will be compared and correlated with changes in specialized markers (inflammation) between groups.3. Results

[0231] 138 patients were considered, of whom 56 met eligibility criteria. The rest had either prior / current overt HE (n=27), unwilling to participate (n=25), had an unclear diagnosis of cirrhosis (n=19), or had recent alcohol or illicit drug use (n=l 1). Of the 56 patients who were consented and screened, 18 were screen failures due to normal performance on cognitive tests. The remaining 30 were randomized 1 : 1 into rifamycin or placebo (Figure IB). Patients in the rifamycin group w ere similar to the placebo group in terms of age, gender, etiology of cirrhosis and years of education (Table 4). MELD-Na at enrollment and other liver disease severity indices apart from ammonia were similar across groups (table 4). Ammonia levels were significantly higher in the Rifamycin groups as compared to placebo.Table 4: Baseline comparisonsi. Clinical course:

[0232] Of the 15 randomized to rifamycin, none had SAEs and 10 did not have any AEs.One person noted increased flatulence that occurred the first day, which did not require stopping the drug, another noted higher stool frequency at day 30, another noted diarrhea and fatigue and a fall on the first day, and one additional person had positional dizziness, which was self-limited. Finally, one person developed a self-limited non-productive cough that did not require antibiotics at day 4. None of these required study drug to be stopped. Of the 15 patients randomized to placebo, 10 did not develop AEs / SAEs. One developed an unrelated SAE (admission for non-cardiac chest pain), one developed abdominal bloating 5 days after the study initiation, one person complained of diarrhea 5 days after randomization, one developed jaw and neck pain 10 days post-initiation, one developed shoulder pain, and one had an elevated CPK noted at day 30 which normalized at the day 37 visit. All these episodes were self-limited and did not result in discontinuation or intermption of the study drug.

[0233] No significant changes in liver chemistry, MELD score, CPK, or safety labs were seen between or within groups.

[0234] At baseline, ammonia levels were higher in the rifamycin group. There was a significant reduction in venous ammonia within the rifamycin group compared to their baseline and to placebo. Delta ammonia was also higher in rifamycin versus placebo, and this effect was also seen in repeated measures analysis (FIG. 4). ii. Microbiome structure changes; a. Stool Microbiome:(A) CDR change:

[0235] After rifamycin, there was a reduction in Lachnospiraceae and Ruminococcaceae, increase in Bacteroidaceae and relatively similar Veillonellaceae and Enterobacteriaceae. This led to a reduction in CDR compared to baseline in rifamycin and compared to post-placebo. CDR pre- vs post-placebo remained statistically similar (Figure 2A-B).(B) Diversity:

[0236] At baseline, no differences in alpha diversity were seen between groups but at the end of rifamycin therapy, there was a significant reduction in alpha-diversity compared to baseline and to post-placebo. No change in alpha-diversity metrics were seen pre / post placebo. Similarly, there was a significant separation on PERMANOVA for analysis of beta-diversityafter nfamycin compared to the baseline and versus post-placebo, but no changes before / after placebo therapy. On LEfSe, there was a significantly increased Bifidobacterium and Coprobacillus but a reduction in Streptococcus and several genera belonging to Lachnospiraceae and Ruminococcaceae after rifamycin compared to baseline (FIG. 2). When placebo and rifamycin end values were compared, Bacteroides, Coprobacillus, Butyriciococcus, Clostridium XlVa, and Escherichia / Shigella were higher and several members of Ruminococcaceae and Lachnospiraceae as well as Streptococcus, Bamesiella, Holdemania, and Allprevotella were lower post-rifamycin compared to placebo. b. Salivary microbiota:

[0237] No changes in alpha / beta-di versity or LEfSe were seen within or between groups. c. Microbial function (Metabolomics, SCFA and Bile acids):(A)Stool SCFA:

[0238] Acetate, propionate, butyrate, isobutyrate, isovalerate, valerate were higher after rifamycin compared to baseline (Table 5 and FIG 4). No changes in hexanoate or branched chain SCFAs were seen. No changes were seen within and between placebo and rifamycin group (Table 5).(B) Bile acids:

[0239] On metabolomics in serum and urine, there was a significant increase in 7-alpha dehydoxylated secondary' BAs but higher concentrations of other secondary' Bas such as hyocholate and ursodeoxycholic acid (UDCA) after rifamycin compared to placebo and baseline. In stool on quantitative LC / MS, similar patterns were observed with secondary BAs (Table 5). Serum C4 levels, which indicate overall bile acid production yvere unchanged between / within groups.

[0240] Other changes seen in metabolomics are shown in supplementary tables but as mentioned above, major changes yvere related to bile acids and there were some changes in androgenic steroids. Sulfated forms of androgens, which are largely inactive, decreased post rifaximin vs baseline and post-placebo.Table 5: Microbial Structure and Function assaysBold font indicates significant difference. iii. Patient-reported outcomes, sarcopenia, and handgrip:

[0241] No change in overall or psychological SIP was seen but physical aspects of SIP significantly improved in the rifamycin group versus baseline (Table 6). There was a significant increase in lean body mass by the InBody machine in rifamycin group compared to their baseline but not in the placebo group. No other changes in InBody measurements, i.e., water mass, fat mass etc. were seen between / within groups. There was also an improvement in handgrip in the rifamycin group but not placebo compared to baseline.

[0242] Delta (change in pre vs post) within groups was significantly higher in the rifamycin group for improvement in physical SIP, dry lean mass, and handgrip strength (Table 7, Figure 4).Table 6: Changes between and within group at baseline and study-end (*: p<0.05 within groups, tp<0.05 between groups baseline fp<0.05 between groups end of study). Bold font indicates significant difference.iii. Cognitive testing:

[0243] No significant differences were found in PHES total score or individual componentsapart from a significant improvement (reduction) in serial dotting test (Table 6). Similarly, no significant change within the EncephalApp Stroop parameters were seen between or within groups (Table 7). Interestingly serial dotting is a test that mostly evaluates psychomotor speed.Table 7: Differences in change from baseline to study end in both groupsB. Example 2

[0244] Sarcopenia and altered muscle function are major problems in patients with cirrhosis and chronic liver diseases. While prior animal and cross-sectional studies have shown changes in gut microbial composition in cirrhosis that links with this outcome, human studies are lacking. Benefiting the gut to improve muscle and physical health in cirrhosis has not been shown in human disease in the past. Using a gut-based antibiotic, rifamycin SV MMX, there was a significant improvement over baseline for (1) dry lean mass (2) serial dotting test, which relies heavily on muscle function (3) handgrip and (4) physical aspect of the Sickness Impact Profile in those randomized to rifamycin but not placebo. These findings show changes in the structure and function of physical function and muscle mass in these patients, which is novel. These changes have not been found in other drugs that were tested such as rifaximin, fecal microbiota transplant or albumin.

[0245] Rifamycin SV MMX compositions could be used to beneficially improve muscle mass, relieve sarcopenia. and improve physical function in cirrhosis and other chronic diseases. These can include but are not limited to cancer cachexia, chronic renal failure, congestive heart failure, end-stage lung disease etc. Other diseases could be focused on muscle disorders and wasting in patients who need rehabilitation.

[0246] Cirrhosis of the liver involves scarring and can lead to multiple complications partly due to problems in the microbes present in the gut. This is associated with poor muscle structure and function, which in turn links with falls and brain problems. Rifamycin SV MMX is an antibiotic that remains mostly in the bowls and can impact these microbes. A 30-day trial of patients with cirrhosis was conducted, half of whom were given rifamycin and half an inactive placebo and were blinded to what treatment they were started. There was an improvement in lean mass only in the rifamycin group. In addition, this w as found to be linked with improvement in handgrip in the rifamycin group as well as improvement in a brain function test that evaluates muscle function. Finally, patients who were given rifamycin also felt better compared to the baseline from a physical function perspective. These to changes were linked in gut microbes and their function. Changing the gut microbiome using rifamycin can improve lean mass and muscle function in cirrhosis.C. Example 31. Background:

[0247] Minimal hepatic encephalopathy (MHE) is associated with poor outcomes but treatment strategies are limited. Rifamycin SV MMX (RiVM) is a novel rifampicin derivative which is a non-absorbable antibiotic with maximal impact in the colon.

[0248] Aim: Evaluate impact of RiVM on microbiome, safety and gut-brain axis in an RCT.

[0249] Methods: A phase 2 placebo-controlled double-blind RCT under FDA IND. Cirrhosis outputs were randomized with MHE (PHES or Stroop) 1 : 1 into RiVM or placebo 600 mg BID (1200 mg) BID for 30 days with 7 day post-drug f / u. There were 4 visits; baseline, day 7, 15 and 30. Primary outcome was stool microbial change (cirrhosis dysbiosis ratio CDR. high=good) in rifamycin vs placebo through 16SrRNA sequencing from baseline to day 30 (end). CDR is the ratio of Lachnospiraceae + Ruminococcaceae + Veillonellciceae to Enterbacteriaceae + Bacteroidaceae . Secondary outcomes were gut-brain (cognition, serum ammonia, optional brain MR spectroscopy, MRS), inflammatory (stool calprotectin), PROs (SIP: total, physical, psychosocial, high=worse) and handgrip strength. Comparisons between / within gps and delta (A Post minus Pre) values were compared.2. Results:

[0250] 58 patients were screened; 8 had overt HE, 11 screen failed due to no MHE on testing. 9 were not interested. Ultimately 30 pts were enrolled (15 / gp), who completed the study without any safety concerns, including the post-drug visit with good adherence. Groups were largely equivalent on baseline but ammonia and SIP scores were higher in RiVM vs placebo (Table 6). 7 RiVM and 11 placebo-assigned pts agreed and were eligible for the optional brain MRS.

[0251] Microbiota: CDR decreased in RiVM pts due to J. Lachnospiraceae + Ruminococcaceae^ although Bacteroidaceae 'f . There was (a-diversity and significant (3- diversity change with clustering of post-RiVM vs pre and post-RiVM vs post-placebo (Fig D / E).

[0252] Labs: No change in MELD-Na but ammonia and calprotectin decreased in RiVM vs baseline and A ammonia was higher in RiVM (Table 6; Figure 5B); no change in placebo.

[0253] Cognition and Brain MRS: Although serial dotting, which tests for psychomotor speed improved in RiVM, no other changes were seen within / b etween gps. Brain Glutathione f with RiVM and decreased in placebo (p=0.03) on brain MRS but remaining metabolites (choline, myoinositol, glutamate / glutamine) remained similar. PROs: APhysical SIP and handgrip were higher indicating improved strength and better physical QOL with RiVM vs placebo.

[0254] Conclusion: In this phase 2 double-blind placebo-controlled RCT of rifamycin SV MMX in patients with cirrhosis and MHE, no safety concerns were found. RiVM Rx resulted in lowered gut microbial a-diversity and cirrhosis dysbiosis ratio. RiVM therapy was associated with reduction in blood ammonia and improved physical function and handgrip. There was also a reduction in brain oxidative stress with RiVM but no change in cognitive testing. RiCM, withpredominant colonic action, may have important gut-brain axis modulatory impact in cirrhosis and MHE.

[0255] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the method and compositions described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

CLAIMSWe claim:

1. A pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients for use in the treatment of sarcopenia.

2. The pharmaceutical composition for use according to claim 1, having a multi -matrix structure comprising: a. an amphiphilic matrix in which the rifamycin SV is incorporated; b. a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a) is dispersed; and c. a hydrophilic matrix.

3. The pharmaceutical composition for use according to claim 2. wherein the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II, lecithins, alkyl block copolymers, salts of sulphated alkyl acids, polyoxyethylenated alkyl derivatives of sorbitan, glycol alkyl ethers, natural or synthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers.

4. The pharmaceutical composition for use according to claim 2 or 3, wherein the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty acids, salts, or esters thereof; fatty acids mono-, di- or triglycerides or polyethoxylated derivatives thereof; waxes; ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof.

5. The pharmaceutical composition for use according to any one of claims 2 to 4, wherein the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol.

6. The pharmaceutical composition for use according to any preceding claim, wherein the composition further comprises a gastro-resistant coating.

7. The pharmaceutical composition for use according to any preceding claim, wherein the composition comprises a tablet core and coating covering the core.

8. The pharmaceutical composition for use according to any of the preceding claims, wherein the composition is suitable for oral administration.

9. The pharmaceutical composition for use according to any of the preceding claims, wherein the composition comprises at least about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

10. The pharmaceutical composition for use according to any of the preceding claims, wherein the composition comprises about 600 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

11. The pharmaceutical composition for use in the treatment of sarcopenia, wherein the treatment comprises administering about 600 mg of rifamycin SC or a pharmaceutically acceptable salt thereof to a subject in need thereof.

12. The pharmaceutical composition for use according to any preceding claim wherein the subject has a chronic disease.

13. The pharmaceutical composition for use according to claim 11, wherein the chronic disease is selected from the group comprising: hepatic cirrhosis, hepatic encephalopathy, cancer cachexia, renal failure, congestive heart failure, and end-stage lung disease.

14. The pharmaceutical composition according to any preceding claim 11 or 12, wherein the chronic disease is hepatic cirrhosis and / or hepatic encephalopathy.

15. The pharmaceutical composition according to any preceding claim, wherein the treatment comprises administering said composition to the subject in need thereof twice daily.

16. The pharmaceutical composition according to claim 14, wherein the treatment comprises administering said composition to the subject in need thereof twice daily for 30 days.

17. The pharmaceutical composition according to any preceding claims, wherein the treatment comprises administering the composition to the subject in need thereof for at least 30 days.

18. A method of improving muscle mass in a subject comprising administering a therapeutically effective amount of a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients to the subject.

19. A method of treating a subject having cirrhosis comprising administering a therapeutically effective amount of a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients to the subject.

20. A method of treating a subject having sarcopenia comprising administering a therapeutically effective amount of a pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients to the subject.

21. The method of any of claims 18-220, wherein the pharmaceutical composition has a multi-matrix structure comprising: a. an amphiphilic matrix in which the rifamycin SV is incorporated; b. a lipophilic matrix which is formed by substances having a melting point of less than 90° C and in which a) is dispersed; and c. a hydrophilic matrix.

22. The method of claim 20, wherein the amphiphilic matrix comprises a substance selected from the group comprising: phospholipids, ceramides, sphingomyelins, polar lipids of type I or II, lecithins, alkyl block copolymers, salts of sulphated alky l acids, polyoxyethylenated alkyl derivatives of sorbitan, glycol alkyl ethers, natural orsynthetic gums, sodium lauryl sulphate, sodium dioctyl sulphosuccinate and / or ethylene and / or propylene block copolymers.

23. The method of any of claims 20-22, wherein the lipophilic matrix comprises a substance selected from the group comprising: unsaturated or hydrogenated alcohols or fatty acids, salts, or esters thereof; fatty acids mono-, di- or triglycerides or polyethoxylated derivatives thereof; waxes; ceramides; cholesterol derivatives or mixtures thereof; stearic acid or a salt thereof.

24. The method of any of claims 20-23, wherein the hydrophilic matrix comprises a substance selected from the group comprising: cellulose derivatives and their esters and / or salts, hydroxyalkylcelluloses, alkylcelluloses, carboxyalkylcelluloses and their salts or derivatives, polyvinyl alcohols, carboxyvinyl derivatives, polysaccharide derivatives, dextrins, pectins, starches and derivatives thereof, polysaccharides of anionic or cationic nature, hyduronic acid, glucuronic acid, or glucosamines, pectins and / or their derivatives, natural or synthetic gums; alginic acid; polyalcohols, xylitol, maltitol or mannitol.

25. The method of any of claims 18-24, wherein the composition further comprises a gastro-resistant coating.

26. The method of any of claims 18-25, wherein the composition comprises a tablet core and coating covering the core.

27. The method of any of claims 18-26, wherein the composition is suitable for oral administration.

28. The method of any of claims 18-27, wherein the composition comprises at least about 200 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

29. The method of any of claims 18-28, wherein the composition comprises about 600 mg rifamycin SV, or a pharmaceutically acceptable salt thereof.

30. The method of claim 220, wherein the treatment comprises administering about 600 mg of rifamycin SC or a pharmaceutically acceptable salt thereof to a subject in need thereof.

31. The method of any of claims 18-29, wherein the subject has a chronic disease.

32. The method of claim 31, wherein the chronic disease is selected from the group comprising: hepatic cirrhosis, hepatic encephalopathy, cancer cachexia, renal failure, congestive heart failure, and end-stage lung disease.

33. The method of claim 31 or 32, wherein the chronic disease is hepatic cirrhosis and / or hepatic encephalopathy.

34. The method of any of claims 18-33, wherein the treatment comprises administering said composition to the subject in need thereof twice daily.

35. The method of any of claims 18-34, wherein the treatment comprises administering said composition to the subject in need thereof twice daily for 30 days.

36. The method of any of claims 18-35, wherein the treatment comprises administering the composition to the subject in need thereof for at least 30 days.

37. The method of any of the preceding claims, wherein the subject has been diagnosed with sarcopenia pnor to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

38. The method of any of the preceding claims, wherein the subject has been diagnosed with minimal hepatic encephalopathy prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

39. The method of any of the preceding claims, wherein the subject has been diagnosed with cirrhosis prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

40. The method of any of the preceding claims, wherein the subject has been diagnosed with associated cognitive impairment prior to administration of the pharmaceutical composition comprising rifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

41. The method of any of the preceding claims, wherein the subject does not have diarrhea prior to administration of the pharmaceutical composition comprisingrifamycin SV or a pharmaceutically acceptable salt thereof and one or more carriers and / or excipients.

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