WO2022061123A1 - Formes posologiques solides à profils de désintégration améliorés - Google Patents

Formes posologiques solides à profils de désintégration améliorés Download PDF

Info

Publication number
WO2022061123A1
WO2022061123A1 PCT/US2021/050886 US2021050886W WO2022061123A1 WO 2022061123 A1 WO2022061123 A1 WO 2022061123A1 US 2021050886 W US2021050886 W US 2021050886W WO 2022061123 A1 WO2022061123 A1 WO 2022061123A1
Authority
WO
WIPO (PCT)
Prior art keywords
solid dosage
dosage form
total
mass
pharmaceutical composition
Prior art date
Application number
PCT/US2021/050886
Other languages
English (en)
Inventor
Syed Altaf
Jiannan LU
Original Assignee
Evelo Biosciences, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Evelo Biosciences, Inc. filed Critical Evelo Biosciences, Inc.
Publication of WO2022061123A1 publication Critical patent/WO2022061123A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders

Definitions

  • the formulation of the solid dosage form of a pharmaceutical product can have a significant impact on the bioavailability of its active pharmaceutical ingredients.
  • a disintegration agent can be included in the solid dosage form.
  • the effectiveness of any particular disintegration agent to facilitate the disintegration of a specific solid dose formulation is unpredictable.
  • the disintegration rate of many solid dosage forms of pharmaceutical products can remain slow, adversely affecting active ingredient bioavailability.
  • the solid dosage forms disclosed herein include certain combinations and/or amounts of disintegration agents, resulting in a decrease in the disintegration time of the composition (e.g., 2-fold, 3-fold, 4-fold, 5-fold, 6-fokl, 7-fold, 8-fold, 9-fold) as compared to conventional solid dosage forms (e.g., solid dosage forms containing conventional amounts of disintegration agents).
  • the solid dosage forms provided herein result in an increase in therapeutic efficacy and/or physiological effect as compared to a pharmaceutical product having conventional solid dosage forms.
  • the solid dosage form comprises a pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria, (e.g., bacteria and/or a powder comprising bacteria).
  • the solid dosage forms maintain their stability, e.g., for three, six, twelve, eighteen and/or twenty-four months under long-term (2-8°C) and/or accelerated (25 °C / 60% RH) storage conditions, e.g., as determined by total cell count (TCC), e.g., as determined by Quantom Tx and described herein.
  • a TCC range is set at 50% to 150% of a target amount, e.g., at a given time point (e.g., at a three, six, twelve, eighteen and/or twenty-four month time point, e.g., under long-term (2-8°C) and/or accelerated (25 "C / 60% RH) storage conditions), and the solid dosage form comprises a TCC within the set TCC range.
  • a target amount of 3.2x10 11 TCC the acceptable TCC range is set at 1.6x10 11 to 4.8x10 11 , and stability is maintained wherein the solid dosage form comprises a TCC within the set TCC range.
  • stability is maintained (e.g., as determined by being within a TCC range of 50% to 150% of the target, amount) at three months under long-term (2-8 °C) and/or accelerated (25 °C / 60% RH) storage conditions).
  • stability is maintained (e.g., as determined by being within a TCC range of 50% to 150% of the target amount) at twelve months under long-term (2-8°C) and/or accelerated (25°C I 60%) RH) storage conditions).
  • the solid dosage form comprises a pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella hislicola bacteria (e.g., bacteria and/or a powder comprising bacteria).
  • the water content of the solid dosage forms is between about 3% and about. 6% (e.g., about 4.5% to about 5.5%, e.g., about 5 %), e.g., as determined by the Karl-Fischer method for water content analysis provided in Ph. Ear. method 2.5.32, and as described herein.
  • the solid dosage forms maintain their water content, e.g., for three, six, twelve, eighteen and/or twenty- four months under long-term (2-8°C) and/or accelerated (25°C / 60% RH) storage conditions. In some embodiments, the solid dosage forms maintain their water content, e.g., for three months under long-term (2-8°C) and/or accelerated (25 °C / 60% RH) storage conditions. In some embodiments, the solid dosage forms maintain their water content, e.g., for twelve months under long-term (2-8°C) and/or accelerated (25 C / 60% RH) storage conditions.
  • the solid dosage form comprises a pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria), and one or more disintegration agents (e.g., one, two or three disintegration agents).
  • the solid dosage form comprises a pharmaceutical agent, wherein the pharmaceutical agent comprises Prevolella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria), and three disintegration agents.
  • the total pharmaceutical agent mass is at least 20% of the total mass of the pharmaceutical composition. In some embodiments, the total pharmaceutical agent mass is no more than 25?% of the total mass of the pharmaceutical composition.
  • the total mass of the one or more disintegrating agents is at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% of the total mass of the pharmaceutical composition. In some embodiments, the total mass of the one or more disintegrating agents is no more than 70%, 65%, 60%, or 55% of the total mass of the pharmaceutical composition.
  • the one or more disintegration agents comprise low-substituted hydroxypropyl cellulose (L-HPC, e.g., LH-B1), croscarmellose sodium (Ac-Di-Sol, e.g., Ac-Di-Sol SD-711), and/or crospovidone (PVPP, e.g., Koliidon, e.g., Koliidon CL-F).
  • L-HPC low-substituted hydroxypropyl cellulose
  • Ac-Di-Sol e.g., Ac-Di-Sol SD-711
  • PVPP crospovidone
  • the solid dosage forms provided herein comprise L-HPC.
  • the L-HPC is of grade LH-B1.
  • the total L-HPC mass is at least 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceutical composition.
  • the total L-HPC mass is no more than 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceutical composition. In certain embodiments, the total L-HPC mass is about 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31 %, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41 %, or 42% of the total mass of the pharmaceutical composition.
  • the total L-HPC mass is about 29% to about 35% of the total mass of the pharmaceutical composition. In certain embodiments, the total L-HPC (e.g., LH- Bl) mass is about 32% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise Croscarmellose Sodium (e.g., Ac-Di-Sol).
  • the Croscarmellose Sodium e.g., Ac-Di-Sol
  • the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is at least 0.01%, 0.1 %, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition.
  • the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is no more than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of tire total mass of the pharmaceutical composition. In certain embodiments, the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition.
  • the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is about 3% to about 9 % of the total mass of the pharmaceutical composition. In certain embodiments, the total Croscarmellose Sodium (e.g., Ac-Di-Sol) (e.g., Ac-Di-Sol SD-711) mass is about 6 % of the total mass of the pharmaceutical composition , [009] In certain embodiments, the solid dosage forms provided herein comprise PVPP (crospovidone, e.g., Koliidon, e.g., Kollidon CL-F).
  • PVPP crospovidone, e.g., Koliidon, e.g., Kollidon CL-F.
  • the total PVPP mass is at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21 %, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition.
  • the total PVPP mass is no more than 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition , In certain embodiments, the total PVPP mass is about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition. In certain embodiments, the total PVPP mass is about 12% to about 18% of the total mass of the pharmaceutical composition. In certain embodiments, the total PVPP mass is about 15% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise: (i) a pharmaceutical agent having a total pharmaceutical agent mass that is at least 20% and no more than 25% of the total mass of the pharmaceutical composition, (ii) L-HPC (e.g., L-HPC of grade LH-B1) having a total L-HPC mass that is at least 22% (e.g., at least 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42%) and no more than 42% (e.g., no more than 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42%) of tire total mass of the pharmaceutical composition; (iii) Croscarmellose Sodium
  • PVPP having a total PVPP mass that is at least 5% (e.g., at least.
  • the total L-HPC mass plus the total Croscarmeliose Sodium (e.g., Ac-Di-Sol) mass plus the total PVPP mass is at least 35%, 40%, 45%, or 50% of the total mass of the pharmaceutical composition.
  • the solid dosage form comprises: a total L-HPC mass is about 32% of the total mass of the pharmaceutical composition; a total Croscarmeliose Sodium (e.g., Ac-Di-Sol) mass is about 6% of the total mass of the pharmaceutical composition; and a total PVPP mass is about 15% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein further comprise mannitol.
  • the mannitol is mannitol SD200.
  • tlie total mannitol mass is at least 18% of the total mass of the pharmaceutical composition.
  • the total mannitol mass is no more than 25% of the total mass of the pharmaceutical composition.
  • the total mannitol mass is about 18%, 18.5%, 19%, 19.5%, 20%, 20.5%, 21%, 21.5%, 22%, 22.5%, 23%, 23.5%, 24%, 24.5%, or 25% of the total mass of the pharmaceutical composition.
  • the total mannitol (e.g., mannitol SD200) mass is about 18% to about 25% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol (e.g., mannitol SD200) mass is about 22% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol (e.g., mannitol SD200) mass is about 21.5% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise magnesium stearate.
  • the total magnesium stearate mass is at least 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is no more than 0.01%, 0.1%, 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • tire total magnesium stearate mass is about 0.01%, 0.1%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 0.5% to about 1.5% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 1% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 1 .5% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise colloidal silica.
  • the colloidal silica is Aerosil 2.00.
  • the total colloidal silica mass is at least 0.01%, 0.1%, 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11 % of the total mass of the pharmaceutical composition.
  • tlie total colloidal silica mass is no more than 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total colloidal silica mass is about 0.01 %, 0, 1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition. In certain embodiments, the total colloidal silica mass is about 0.5% to about 1.5% of the total mass of the pharmaceutical composition. In certain embodiments, the total colloidal silica (e.g., Aerosil 200) mass is about 1 % of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise about 23% pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g,, bacteria and/or a powder comprising bacteria); about 22% mannitol (e.g,, mannitol SD200); about 32% L-HPC (e.g., L-HPC LH-Bl ); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD-7I1); about 15% crospovidone (e.g., PVPP); about 1% magnesium stearate; and about 1% colloidal silica (e.g., Aerosil 200).
  • the pharmaceutical agent comprises Prevotella histicola bacteria (e.g, bacteria and/or a powder comprising bacteria); about 22% mannitol (e.g,, mannitol SD200); about 32% L-HPC (e.g., L-HPC LH-Bl ); about 6% croscarmellose sodium (e
  • the solid dosage forms provided herein comprise about 23% pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 21.5% mannitol; about 32% L-HPC (e.g., L-HPC LH-Bl); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD- 711); about 15% crospovidone; about 1.5% magnesium stearate; and about 1% colloidal silica (e.g., Aerosil 200P).
  • the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 21.5% mannitol; about 32% L-HPC (e.g., L-HPC LH-Bl); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD- 711); about 15% crospovidone; about 1.5% magnesium stearate
  • the solid dosage forms of a pharmaceutical agent as described herein include tablets and minitablets.
  • the solid dosage form is enterically coated (e.g., comprises an enteric coating; e.g., is coated with an enteric coating).
  • the tablets or minitablets are coated with one layer of enteric coating or with two layers of enteric coatings (e.g., an inner enteric coating and an outer enteric coating).
  • the enterically-coated minitablets (with one layer of enteric coating or with two layers of enteric coatings (e.g., an inner enteric coating and an outer enteric coating)) can be loaded into a capsule; e.g., the capsule is not enterically coated.
  • the solid dosage form comprises a tablet.
  • the tablet e.g., enterically coated tablet
  • the tablet is a 5mm, 5,5mm, 6mm, 6.5mm, 7mm, 7.5mm, 8mm, 8.5mm, 9mm, 9.5mm, 10mm, 11mm, I2mm, 13mm, 14mm, 15mm, 16mm, 17mm, or 18mm tablet.
  • die tablet e.g., enterically coated tablet
  • the tablet is a 17mm tablet.
  • the solid dosage form comprises a minitablet.
  • the minitablet e.g., enterically coated minitablet
  • the minitablet is a 1mm minitablet, 1.5 mm minitablet, 2mm minitablet, 3mm minitablet, or 4mm minitablet.
  • a plurality of enterically coated minitablets are contained in a capsule (e.g., a size 0 capsule can contain about 31 to about 35 (e.g., 33) minitablets, wherein the minitablets are 3mm in size).
  • the capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule.
  • the capsule comprises HPMC (hydroxyl propyl methyl cellulose) or gelatin.
  • the enteric coating comprises one enteric coating.
  • the enteric coating comprises an inner enteric coating and an outer enteric coating.
  • the enteric coating comprises an inner enteric coating and an outer enteric coating, and wherein the inner and outer enteric coatings are not identical (e.g., the inner and outer enteric coatings do not contain identical components in identical amounts).
  • the enteric coating (e.g., the one enteric coating or the inner enteric coating and/or the outer enteric coating) comprises a polymethacrylate-based copolymer.
  • the enteric coating (e.g., the one enteric coating or the inner enteric coating and/or the outer enteric coating) comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1).
  • MAE methacrylic acid ethyl acrylate
  • the one enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1) (such as Kollicoat MAE 100P).
  • MAE methacrylic acid ethyl acrylate
  • the one enteric coating comprises a Eudragit copolymer, e.g., a Eudragit L (e.g., Eudragit L 100-55; Eudragit L 30 D-55), a Eudragit S, a Eudragit RL, a Eudragit RS, a Eudragit E, or a Eudragit FS (e.g,, Eudragit FS 30 D).
  • a Eudragit L e.g., Eudragit L 100-55; Eudragit L 30 D-55
  • Eudragit S e.g., Eudragit L 100-55; Eudragit L 30 D-55
  • Eudragit S e.g., Eudragit S
  • RL Eudragit RL
  • Eudragit RS Eudragit RS
  • Eudragit E Eudragit E
  • Eudragit FS e.g, Eudragit FS 30 D
  • the enteric coating (e.g., the one enteric coating or the inner enteric coating and/or the outer enteric coating) comprises cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), poly(vinyl acetate phthalate) (PVAP), hydroxypropyl methyl cellulose phthalate (HPMCP), a fatty acid, a wax, shellac (esters of aleurtic acid), a plastic, a plant fiber, zein, Aqua-Zein (an aqueous zein formulation containing no alcohol), amylose starch, a starch derivative, a dextrin, a methyl acrylate-methacrylic acid copolymer, cellulose acetate succinate, hydroxypropyl methyl cellulose acetate succinate (hypromellose acetate succinate), a methyl methacrylate -methacrylic acid copolymer, or sodium alginate.
  • CAP cellulose acetate phthalate
  • CAT
  • the enteric coating (e.g., the one enteric coating or the inner enteric coating and/or the outer enteric coating) comprises an anionic polymeric material.
  • the solid dosage form comprises a sub-coating, e.g., in addition to the enteric coating, e.g., the sub-coating is beneath the enteric coating (e.g., between the solid dosage form and the enteric coating).
  • the sub- coating comprises Opadry QX, e.g., Opadry QX Blue.
  • the pharmaceutical agent can be a powder that comprises the Prevotella histicola bacteria, and, can comprise additional agents such as, e.g., cryoprotectant.
  • the pharmaceutical agent is a lyophilized powder of Prevotella histicola bacteria that optionally, further comprises additional agents, such as a cryoprotectant.
  • the pharmaceutical agent has one or more beneficial immune effects outside the gastrointestinal tract, e.g,, when the solid dosage form is orally administered.
  • the pharmaceutical agent modulates immune effects outside the gastrointestinal tract in the subject, e.g., when the solid dosage form is orally administered.
  • the pharmaceutical agent causes a systemic effect (e.g., an effect outside of the gastrointestinal tract), e.g., when the solid dosage form is orally administered.
  • a systemic effect e.g., an effect outside of the gastrointestinal tract
  • the pharmaceutical agent acts on immune cells and/or epithelial cells in the small intestine (e.g., causing a systemic effect (e.g., an effect outside of the gastrointestinal tract), e.g., when tire solid dosage form is orally administered.
  • a systemic effect e.g., an effect outside of the gastrointestinal tract
  • the pharmaceutical agent comprises isolated Prevotella histicola bacteria (e.g., from one or more strains of bacteria (e.g., bacteria of interest) (e.g., a therapeutically effective amount thereof)). E.g., wherein at least 50%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the content of the pharmaceutical agent is the isolated Prevotella histicola bacteria (e.g., bacteria of interest).
  • the pharmaceutical agent comprises live bacteria.
  • the pharmaceutical agent comprises dead bacteria.
  • the pharmaceutical agent comprises non-replicating bacteria.
  • the pharmaceutical agent comprises bacteria that have been gamma-irradiated (e.g., at 17.5 or 25 kGy). [038] In some embodiments, the pharmaceutical agent comprises bacteria from one strain of bacteria.
  • the bacteria are lyophilized (e.g,, the lyophilized product further comprises a pharmaceutically acceptable excipient, e.g., such as a cryoprotectant) (e.g., a powder form).
  • a pharmaceutically acceptable excipient e.g., such as a cryoprotectant
  • the Prevotella histicola bacteria are from a strain comprising at least 90% (or at least 97%) genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329). In some embodiments, the Prevotella bacteria are from a strain comprising at least 99% genomic, 16S and/or CRISPR sequence i dentity to the nucleoti de sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329). In some embodiments, the Prevotella bacteria are from Prevotella Strain B 50329 (NRRL accession number B 50329).
  • the pharmaceutical agent comprises Prevotella histicola bacteria and the dose of bacteria is about 2.4 x 10 11 to about 4,0 x 10 11 cells (e.g., wherein cell number is determined by total cell count, which is determined by Coulter counter), wherein the dose is per tablet or per total number of minitablets in a capsule.
  • the pharmaceutical agent comprises Prevotella histicola bacteria and the dose of bacteria is about 2.8 x 10 11 to about 3.6 x 10 11 cells (e.g., wherein cell number is determined by total cell count, which is determined by Coulter counter), wherein the dose is per tablet or per total number of minitablets m a capsule.
  • the pharmaceutical agent comprises Prevotella histicola bacteria and the dose of bacteria is about 2.4 x 10 11 , about 2.8 x 10 11 , about 3.2 x 10 11 , about 3.6 x 10 11 , or about 4.0 x 10 11 , cells, wherein the dose is per tablet or per total number of minitablets in a capsule.
  • the pharmaceutical agent comprises Prevotella histicola bacteria and the dose of bacteria is about 3.2 x 10 11 cels, wherein the dose is per tablet or per total number of minitablets in a capsule.
  • the disclosure provides a method of treating a subject (e.g,, human) (e.g., a subject in need of treatment), the method comprising administering to the subject a solid dosage form provided herein.
  • a subject e.g,, human
  • a solid dosage form provided herein.
  • the disclosure provides use of a solid dosage form provided herein for the preparation of a medicament for treating a subject (e.g,, human) (e.g., a subject in need of treatment).
  • a subject e.g, human
  • the solid dosage form is orally administered (e.g., is for oral administration).
  • the solid dosage form is administered to a subject that is in a fed or fasting state. In some embodiments, the solid dosage form is administered to a subject on an empty stomach (e.g., one hour before eating or two hours after eating). In some embodiments, the solid dosage form is administered to a subject one hour before eating. In some embodiments, the solid dosage form is administered to a subject two hours after eating. [049] In some embodiments, the solid dosage form is administered (e.g., is for administration) 1, 2, 3, or 4 times a day. In some embodiments, 1, 2, 3, 4 or 5 solid dosage forms (e.g., tablets) are administered (e.g., are for administration) 1 , 2, 3, or 4 times a day.
  • 2, 4, 6, 8, or 10 solid dosage forms are administered (e.g., are for administration) I, 2, 3, or 4 times a day.
  • 1 solid dosage form e.g., tablet
  • 2 solid dosage forms e.g., tablets
  • 3 solid dosage forms are administered (e.g., are for administration) 1 or 2 times a day.
  • solid dosage forms e.g., tablets
  • 4 solid dosage forms are administered (e.g., are for administration) 1 or 2 times a day.
  • 5 solid dosage forms e.g., tablets
  • are administered e.g., are for administration 1 or 2 times a day.
  • 1 solid dosage form e.g., tablet
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 101 Icells.
  • 2 solid dosage forms e.g., tablets
  • the solid dosage form e.g., each solid dose form
  • 3 solid dosage forms are administered (e.g., are for administration) 1 or 2 times a day, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10”cells.
  • 4 solid dosage forms e.g., tablets
  • are administered e.g., are for administration) 1 or 2. times a day, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells.
  • 5 solid dosage forms e.g., tablets
  • are administered e.g., are for administration) I or 2 times a day, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells.
  • 1 solid dosage form e.g., tablet.
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells.
  • 2 solid dosage forms e.g., tablets
  • the soiid dosage form comprises a dose of bacteria of about 3.2. x 10 11 cells.
  • 3 solid dosage forms e.g., tablets
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells.
  • solid dosage forms e.g., tablets
  • solid dosage form comprises a dose of bacteria of about 3.2. x 10 11 cells.
  • 5 solid dosage forms e.g., tablets
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells.
  • the solid dosage form provides release of the pharmaceutical agent in the small intestine, e.g., in the upper small intestine, of the pharmaceutical agent contained in the solid dosage form.
  • the solid dosage form delivers the pharmaceutical agent to the small intestine, wherein the pharmaceutical agent can act on immune cells and/or epithelial cells in the small intestine, e.g., in the upper small intestine, e.g., to cause effects throughout the body (e.g., systemic effect).
  • the pharmaceutical agent provides one or more beneficial immune effects outside the gastrointestinal tract, e.g., when orally administered,
  • the pharmaceutical agent modulates immune effects outside die gastrointestinal tract in the subject, e.g., when orally administered.
  • the pharmaceutical agent causes a systemic effect (e.g., an effect outside of the gastrointestinal tract), e.g., when orally administered.
  • a systemic effect e.g., an effect outside of the gastrointestinal tract
  • the pharmaceutical agent acts on immune cells and/or epithelial cells in the small intestine (e.g., upper small intestine) (e.g., causing a systemic effect (e.g., an effect outside of the gastrointestinal tract), e.g., when orally administered.
  • the solid dosage form is administered orally and has one or more beneficial immune effects outside the gastrointestinal tract (e.g., interaction between the agent and cells in tire small intestine modulates a sy stemic immune response).
  • the solid dosage form is administered orally and modulates immune effects outside the gastrointestinal tract (e.g., interaction between agent and cells in the small intestine (e.g., upper small intestine) modulates a systemic immune response).
  • immune effects outside the gastrointestinal tract e.g., interaction between agent and cells in the small intestine (e.g., upper small intestine) modulates a systemic immune response.
  • the solid dosage form is administered orally and activates innate antigen presenting cells (e.g., in the small intestine, e.g., upper small intestine), [061]
  • the subject is in need of treatment (and/or prevention) of an autoimmune disease.
  • the subject is in need of treatment (and/or prevention) of an inflammatory disease.
  • the inflammatory disease is a Thl, T112, or Thl 7 inflammatory disease.
  • the inflammatory' disease is a Thl inflammatory disease.
  • the inflammatory' disease is a Th2 inflammatory disease.
  • the inflammatory disease is a Thl 7 inflammatory disease.
  • the subject is in need of treatment (and/or prevention) of a metabolic disease.
  • the subject is in need of treatment (and/or prevention) of a dysbiosis.
  • the subject is in need of treatment (and/or prevention) of psoriasis.
  • the subject is in need of treatment (and/or prevention) of psoriatic arthritis.
  • the subject is in need of treatment (and/or prevention) of atopic dermatitis.
  • the subject is in need of decreased inflammatory' cytokine expression (e.g., decreased IL-8, IL-6, IL-l ⁇ , and/or TNFa expression levels).
  • decreased inflammatory' cytokine expression e.g., decreased IL-8, IL-6, IL-l ⁇ , and/or TNFa expression levels.
  • the subject is in need of treatment (and/or prevention) of bacterial septic shock, cytokine storm and/or viral infection.
  • the subject is in need of treatment (and/or prevention) of a viral infection.
  • the viral infection is a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection.
  • the viral infection is a SARS-CoV-2 infection.
  • the solid dosage form is administered in combination with a therapeutic agent (e.g., additional therapeutic agent).
  • a therapeutic agent e.g., additional therapeutic agent
  • a solid dosage form of a pharmaceutical composition comprising combining into a pharmaceutical composition a pharmaceutical agent, wherein the pharmaceutical agent comprises Prevolella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria), and one or more (e.g., one, two or three) disintegration agents.
  • the total pharmaceutical agent mass is at least 20% of the total mass of the pharmaceutical composition.
  • the total pharmaceutical agent mass is no more than 25% of tire total mass of the pharmaceutical composition.
  • the total mass of the one or more disintegrating agents is at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% of the total mass of the pharmaceutical composition.
  • the total mass of the one or more disintegrating agents is no more than 70%, 65%, 60%, or 55% of the total mass of the pharmaceutical composition.
  • the one or more disintegration agents comprise low-substituted hydroxypropyl cellulose (L-HPC), croscarmellose sodium (Ac-Di-Sol), and/or crospovidone (PVPP).
  • the solid dosage forms provided herein comprise L-HPC.
  • the L-HPC is of grade LH-B 1.
  • the total L-HPC mass is at least 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31 %, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceutical composition.
  • the total L-HPC mass is no more than 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceutical composition. In certain embodiments, the total L-HPC mass is about 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31 %, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise Croscarmellose Sodium (e.g., Ac-Di-Sol).
  • the Croscarmellose Sodium e.g., Ac-Di-Sol
  • the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is at least 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition.
  • the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is no more than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition. In certain embodiments, the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is about 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise PVPP,
  • the total PVPP mass is at least 5%, 6%, 7%, 8%, 9%, 10%, 11 %, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition.
  • the total PVPP mass is no more than 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition.
  • the total PVPP mass is about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition.
  • the method further comprises combining mannitol.
  • the mannitol is mannitol SD200.
  • the total mannitol mass is at least 18% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol mass is no more than 25% of tire total mass of the pharmaceutical composition. In certain embodiments, the total mannitol mass is about 18%, 18.5%, 19%, 19.5%, 20%, 20.5%, 21%, 21.5%, 22%, 22.5%, 23%, 23.5%, 24%, 24.5%, or 25% of the total mass of the pharmaceutical composition.
  • the total mannitol (e.g., mannitol SD200) mass is about 18% to about 25% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol (e.g., mannitol SD200) mass is about 22% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol (e.g., mannitol SD200) mass is about 21.5% of the total mass of the pharmaceutical composition.
  • the method further comprises combining magnesium stearate.
  • the total magnesium stearate mass is at least 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is no more than 0.01%, 0.1%, 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • tire total magnesium stearate mass is about 0.01%, 0.1 %, 1%, 1 .5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 0.5% to about 1.5% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 1 % of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 1 .5% of the total mass of the pharmaceutical composition.
  • the method further comprises combining comprise colloidal silica.
  • the colloidal silica is Aerosil 200.
  • the total colloidal silica mass is at least 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total colloidal silica mass is no more than 0.01%, 0.1 %, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11 % of the total mass of the pharmaceutical composition.
  • the total colloidal silica mass is about 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%. or 11% of the total mass of the pharmaceutical composition. In certain embodiments, the total colloidal silica mass is about 0.5% to about 1.5% of the total mass of the pharmaceutical composition. In certain embodiments, the total colloidal silica (e.g., Aerosil 200) mass is about 1 % of the total mass of the pharmaceutical composition.
  • the method further comprises combining about 23% pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g,, bacteria and/or a powder comprising bacteria); about 22% mannitol (e.g,, mannitol SD200); about 32% L-HPC (e.g., L-HPC LH-B1 ); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD-711); about 15% crospovidone (e.g., PVPP); about 1% magnesium stearate; and about 1% colloidal silica (e.g., Aerosil 200).
  • the pharmaceutical agent comprises Prevotella histicola bacteria (e.g,, bacteria and/or a powder comprising bacteria); about 22% mannitol (e.g,, mannitol SD200); about 32% L-HPC (e.g., L-HPC LH-B1 ); about 6% croscarmellose sodium (e.g
  • the method further comprises combining about 23% pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 21.5% mannitol; about 32% L-HPC (e.g., L-HPC LH-B1); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD- 711); about 15% crospovidone; about 1.5% magnesium stearate; and about 1% colloidal silica (e.g., Aerosil 200P).
  • the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 21.5% mannitol; about 32% L-HPC (e.g., L-HPC LH-B1); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD- 711); about 15% crospovidone; about 1.5% magnesium stearate; and
  • the method further comprises compressing the pharmaceutical composition, thereby forming a tablet or a minitablet. In some embodiments, the method further comprises enterically coating the tablet or minitablet, thereby preparing the enterically coated tablet. In certain embodiments, the method further comprises loading the minitablets into a capsule.
  • Figure 1 is a graph showing a Total Celis/T ablet Stability Profile over 3 months long- term (2-8°C) and accelerated (25°C / 60% RH) storage conditions.
  • the lower trace (diamonds) in the graph provides values for accelerated (25 °C / 60% RH) storage conditions.
  • the upper trace (circles) in the graph provides values for long-term (2-8°C) storage conditions.
  • Total Cell Count (TCC) was determined by Quantom Tx.
  • Figure 2 is a graph showing a Water Content Stability Profile over 3 months long-term (2 -8 °C) and accelerated (25 °C / 60% RH) storage conditions.
  • the lower trace (diamonds) in the graph provides values for accelerated (25 °C / 60% RH) storage conditions.
  • the upper trace (circles) in the graph provides values for long-term (2-8°C) storage conditions.
  • Water content was determined by the Karl Fisher method .
  • Figure 3 is a graph showing a Total Cells/Tablet Stability Profile over 12 months long- term (2-8°C) and accelerated (25 C / 60% RH) storage conditions.
  • Total Cell Count (TCC) was determined by Quantom Tx.
  • FIG. 4 is a graph showing a Water Content Stability Profile over 12 months long- term (2-8 °C) and accelerated (25 °C / 60% RH) storage conditions. Water content was determined by the Karl Fisher method.
  • the disclosure provides solid dosage forms that comprise Prevotella histicola (e.g., Prevotella histicola powder) that maintain their stability, e.g., for three, six, twelve, eighteen and/or twenty-four months under long-term (2-8°C) and/or accelerated (25 C / 60% RH) storage conditions. Stability can be determined by total ceil count (TCC), e.g., as determined by Quantom Tx and described herein.
  • TCC total ceil count
  • the disclosure provides solid dosage forms that comprise Prevotella histicola (e.g,, Prevotella histicola powder) that have the water content between about 3% and about 6% (e.g., about 4.5% to about 5.5%, e.g., about 5%), e.g., as determined by the Karl-Fischer method for water content analysis provided in Ph. Eur. method 2.5.32, and as described herein.
  • the solid dosage forms maintain their water content, e.g., for three, six, twelve, eighteen and/or twenty-four months under long-term (2-8 °C) and/or accelerated (25°C / 60% RH) storage conditions.
  • an amount of one or more disintegration agents can improve the disintegration times of solid dosage forms that contain Prevotella histicola pow der.
  • an amount of one or more disintegration agents e.g., one, two or three disintegration agents
  • the amount of pharmaceutical agent (that contains the active ingredient) incorporated into a solid dosage form may be adjusted depending on the amount of active ingredient contained in a given preparation (e.g., batch) of pharmaceutical agent.
  • the amount of diluent (such as mannitol) is then adjusted accordingly.
  • the amount of pharmaceutical agent is increased, the amount of diluent is decreased; and vice versa.
  • adjustments can be made to the amounts of pharmaceutical agent and diluent, yet the amount of one or more disintegration agents (e.g., one, two or three disintegration agents) remains constant, e.g., batch to batch for a given solid dosage form recipe.
  • the amounts of magnesium stearate and colloidal silica can also remain constant, e.g., batch to batch for a given solid dosage form recipe.
  • the three disintegrants totaled 53% (w7w) of the tablet, specifically: 32% low substituted hydroxypropyl cellulose; 15% crospovidone; and 6% croscarmellose sodium.
  • the magnesium stearate and colloidal silica were each 1.5% and 1%, respectively in both preparations.
  • tire pharmaceutical agent was used at 25%. In the other, it was used at 23%.
  • the amount of mannitol was differed: 19.5% mannitol when 25% pharmaceutical agent was used; 21.5% mannitol when 23% pharmaceutical agent was used.
  • Adjuvant or “Adjuvant therapy” broadly refers to an agent that affects an immunological or physiological response in a subject (e.g., human).
  • an adjuvant might help absorb an antigen presenting cell antigen, activate macrophages and lymphocytes and support the production of cytokines.
  • an adjuvant might permit a smaller dose of an immune interacting agent to increase the effectiveness or safety of a particular dose of the immune interacting agent.
  • an adjuvant might prevent T cell exhaustion and thus increase the effectiveness or safety of a particular immune interacting agent.
  • administering broadly refers to a route of administration of a composition (e.g., a pharmaceutical composition such as a solid dosage form of a pharmaceutical agent as described herein) to a subject.
  • routes of administration include oral administration, rectal administration, topical administration, inhalation (nasal) or injection.
  • Administration by injection includes intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration.
  • a pharmaceutical composition described herein can be administered in any form by any effective route, including but not limited to oral, parenteral, enteral, intravenous, intraperitoneal, topical, transdermal (e.g., using any standard patch), intradermal, ophthalmic, (intra)nasally, local, non -oral, such as aerosol, inhalation, subcutaneous, intramuscular, buccal, sublingual, (trans)rectal, vaginal, intra-arterial, and intrathecal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), implanted, intravesical, intrapulmonary, intraduodenal, intragastrical, and intrabronchial.
  • transdermal e.g., using any standard patch
  • intradermal e.g., using any standard patch
  • intradermal e.g., using any standard patch
  • intradermal e
  • a pharmaceutical composition described herein is administered orally, rectally, topically, mtravesically, by injection into or adjacent to a draining lymph node, intravenously, by inhalation or aerosol, or subcutaneously.
  • a pharmaceutical composition described herein is administered orally, or intravenously.
  • a pharmaceutical composition described herein is administered orally.
  • a “carbohydrate” refers to a sugar or polymer of sugars.
  • saccharide ‘‘polysaccharide,” ‘'carbohydrate,” and “oligosaccharide” may be used interchangeably.
  • Most carbohydrates are aldehydes or ketones with many hydroxyl groups, usually one on each carbon atom of the molecule. Carbohydrates generally have the molecular formula CnH2nOn.
  • a carbohydrate may be a monosaccharide, a disaccharide, trisaccharide, oligosaccharide, or polysaccharide.
  • the most basic carbohydrate is a monosaccharide, such as glucose, sucrose, galactose, mannose, ribose, arabinose, xylose, and fructose.
  • Disaccharides are two joined monosaccharides.
  • Exemplar ⁇ ' disaccharides include sucrose, maltose, cellobiose, and lactose.
  • an oligosaccharide includes between three and six monosaccharide units (e.g., raffinose, stachyose), and polysaccharides include six or more monosaccharide units.
  • Exemplary polysaccharides include starch, glycogen, and cellulose.
  • Carbohydrates may contain modified saccharide units such as 2 ’-deoxyribose wherein a hydroxyl group is removed, 2 ’-fluororibose wherein a hydroxyl group is replaced with a fluorine, or N-acetylglucosamine, a nitrogen-containing form of glucose (e.g., 2’- fluororibose, deoxyribose, and hexose).
  • Carbohydrates may exist in many different forms, for example, conformers, cyclic forms, acyclic forms, stereoisomers, tautomers, anomers, and isomers.
  • Cellular augmentation broadly refers to the influx of cells or expansion of cells in an environment that are not substantially present in the environment prior to administration of a composition and not present in the composition itself.
  • Cells that augment the environment include immune cells, stromal cells, bacterial and fungal cells.
  • Clade refers to the OTUs or members of a phylogenetic tree that are downstream of a statistically valid node in a phylogenetic tree.
  • the clade comprises a set of terminal leaves in the phylogenetic tree that is a distinct monophyletic evolutionary unit and that share some extent of sequence similarity .
  • a “combination” of bacteria from two or more strains includes the physical co- existence of the bacteria, either in the same material or product or in physically connected products, as w ell as the temporal co-admimstration or co-localization of the bacteria from the two or more strains.
  • the term “decrease” or “deplete” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 1/100, 1/1000, 1/10,000, 1/100,000, 1/1,000,000 or undetectable after treatment when compared to a pre-treatment state.
  • Properties that may be decreased include tire number of immune cells, bacterial cells, stromal cells, myeloid derived suppressor cells, fibroblasts, metabolites; the level of a cytokine; or another physical parameter (such as ear thickness (e.g., in a DTH animal model) or tumor size).
  • ‘’Dysbiosis” refers to a state of the microbiota or microbiome of the gut or other body area, including, e.g., mucosal or skin surfaces (or any other microbiome niche) in which the normal diversity and/or function of the host gut microbiome ecological networks ⁇ ‘microbiome”) are disrupted.
  • a state of dysbiosis may result in a diseased state, or it may be unhealthy under only certain conditions or only if present for a prolonged period.
  • Dysbiosis may be due to a variety of factors, including, environmental factors, infectious agents, host genotype, host diet and/or stress.
  • a dysbiosis may result in: a change (e.g., increase or decrease) in the prevalence of one or more bacteria types (e.g., anaerobic), species and/or strains, change (e.g., increase or decrease) in diversity of the host microbiome population composition; a change (e.g., increase or reduction) of one or more populations of symbiont organisms resulting in a reduction or loss of one or more beneficial effects; overgrowth of one or more populations of pathogens (e.g. , pathogenic bacteria); and/or the presence of, and/or overgrowth of, symbiotic organisms that cause disease only when certain conditions are present.
  • a change e.g., increase or decrease
  • the prevalence of one or more bacteria types e.g., anaerobic
  • species and/or strains e.g., increase or decrease
  • change e.g., increase or decrease
  • change e.g., increase or decrease in diversity of the host microbiome population composition
  • ecological consortium is a group of bacteria which trades metabolites and positively co-regulates one another, in contrast to two bacteria which induce host synergy through activating complementary host pathways for improved efficacy.
  • engineered bacteria are any bacteria that have been genetically altered from their natural state by human activities, and the progeny of any such bacteria.
  • Engineered bacteria include, for example, the products of targeted genetic modification, the products of random mutagenesis screens and the products of directed evolution.
  • genomic is used broadly to refer to any nucleic acid associated with a biological function.
  • the term “gene” applies to a specific genomic sequence, as well as to a cDNA or an mRNA encoded by that genomic sequence.
  • “Identity” as between nucleic acid sequences of two nucleic acid molecules can be determined as a percentage of identity using known computer algorithms such as the “FASTA” program, using for example, the default parameters as in Pearson et. al. (1988) Proc. Natl. Acad. Sci. USA 85:2444 (other programs include the GCG program package (Devereux, J., et al., Nucleic Acids Research 12(I):387 (1984)), BLASTP, BLASTN, FASTA Atschul, S. F., et al., J Molec Biol 215:403 (1990); Guide to Huge Computers, Mrtin J.
  • the term “immune disorder” refers to any disease, disorder or disease symptom caused by an activity of the immune system, including autoimmune diseases, inflammatory diseases and allergies.
  • Immune disorders include, but are not limited to, autoimmune diseases (e.g., psoriasis, atopic dermatitis, lupus, scleroderma, hemolytic anemia, vasculitis, type one diabetes, Grave’s disease, rheumatoid arthritis, multiple sclerosis, Goodpasture’s syndrome, pernicious anemia and/or myopathy), inflammatory diseases (e.g., acne vulgaris, asthma, celiac disease, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis and/or interstitial cystitis), and/or an allergies (e.g., food allergies, drag allergies and/or environmental allergies).
  • Immunotherapy is treatment that uses a subject’s immune system to treat disease (e.g., immune disease, inflammatory disease, metabolic disease) and includes, tor example, cytokines, cell therapy, CAR-T cells, and dendritic cell therapy.
  • disease e.g., immune disease, inflammatory disease, metabolic disease
  • cytokines e.g., cytokines, cell therapy, CAR-T cells, and dendritic cell therapy.
  • the term “increase” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 2-fold, 4-fold, 10- fold, 100-fold, 10 ⁇ 3 fold, 10 ⁇ 4 fold, 10 ⁇ 5 fold, 10 ⁇ 6 fold, and/or 10 ⁇ 7 told greater after treatment when compared to a pre-treatment state.
  • Properties that may be increased include the number of immune cells, bacterial cells, stromal cells, myeloid derived suppressor cells, fibroblasts, metabolites; the level of a cytokine; or another physical parameter (such as ear thickness (e.g., in a DTH animal model) or tumor size).
  • “Innate immune agonists” or “immuno-adjuvants” are small molecules, proteins, or other agents that specifically target innate immune receptors including Toll-Like Receptors (TLR), NOD receptors, RLRs, C-type lectin receptors, STING-cGAS Pathway components, inflammasome complexes.
  • TLR Toll-Like Receptors
  • NOD receptors NOD receptors
  • RLRs C-type lectin receptors
  • STING-cGAS Pathway components inflammasome complexes.
  • LPS is a TLR-4 agonist that is bacterially derived or synthesized and aluminum can be used as an immune stimulating adjuvant
  • immuno- adjuvants are a specific class of broader adjuvant or adjuvant therapy.
  • STING agonists include, but are not limited to, 2'3'- cGAMP, 3'3'-cGAMP, c-di-AMP, c-di-GMP, 2’2'-cGAMP, and 2'3'-cGAM(PS)2 (Rp/Sp) (Rp, Sp-isomers of the bis-phosphorothioate analog of 2'3'-cGAMP).
  • TLR agonists include, but are not limited to, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, Tl RIO and TLRI 1.
  • NOD agonists include, but are not limited to, N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyldipeptide (MDP)), gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP), and desmuramylpeptides (DMP) .
  • MDP N-acetylmuramyl-L-alanyl-D-isoglutamine
  • iE-DAP gamma-D-glutamyl-meso-diaminopimelic acid
  • DMP desmuramylpeptides
  • ITS is a piece of non-functional RNA located between structural ribosomal RN As (rRN A ) on a common precursor transcript often used for identification of eukaryotic species in particular fungi.
  • the rRNA of fungi that forms the core of the ribosome is transcribed as a signal gene and consists of the 8S, 5.8S and 28S regions with ITS4 and 5 between the 8S and 5.8S and 5.8S and 2.8S regions, respectively.
  • isolated or “enriched” encompasses a microbe (such as a bacterium) or oilier entity or substance that has been (1) separated from at least some of the components with which it was associated when initially produced (whether in nature or in an experimental setting), and/or (2.) produced, prepared, purified, and/or manufactured by the hand of man.
  • isolated microbes are more than about 80%, about 85%, about 90%, about 91 %, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure.
  • a substance is “pure” if it is substantially free of other components.
  • purify refers to a microbe or other material that has been separated from at least some of the components with which it was associated either when initially produced or generated (e.g., whether m nature or in an experimental setting), or during any time after its initial production.
  • a microbe or a microbial population may be considered purified if it is isolated at or after production, such as from a material or environment containing the microbe or microbial population, and a purified microbe or microbial population may contain other materials up to about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or above about 90% and still be considered “isolated.”
  • purified microbes or microbial population are more than about 80%, about 85%. about 90%. about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure.
  • the one or more microbial types present in the composition can be independently purified from one or more other microbes produced and/or present in the material or environment containing the microbial type.
  • Microbial compositions thereof are generally purified from residual habitat products.
  • lipid includes fats, oils, triglycerides, cholesterol, phospholipids, fatty acids in any form including free fatty acids. Fats, oils and fatty acids can be saturated, unsaturated (cis or trans) or partially unsaturated (cis or trans).
  • LPS mutant or lipopolysaccharide mutant broadly refers to selected bacteria that comprises loss of LPS. Loss of LPS might be due to mutations or disruption to genes involved in lipid A biosynthesis, such as IpxA, IpxC, and IpxD. Bacteria comprising LPS mutants can be resistant to aminoglycosides and polymyxins (polymyxin B and colistin).
  • Metal refers to any and all molecular compounds, compositions, molecules, ions, co-factors, catalysts or nutrients used as substrates in any cellular or microbial metabolic reaction or resulting as product compounds, compositions, molecules, ions, co-factors, catalysts or nutrients from any cellular or microbial metabolic reaction.
  • Merobe refers to any natural or engineered organism characterized as a archaeaon, parasite, bacterium, fungus, microscopic alga, protozoan, and the stages of development or life cycle stages (e.g., vegetative, spore (including sporulation, dormancy, and germination), latent, biofilm) associated with the organism.
  • gut microbes examples include: Actinomyces graevenitzii, Actinomyces odontolyticus, AJdcermansia muciniphila, Bacteroides caccae, Bacteroides fragilis, Bacteroides putredinis, Bacteroides thetaiotaomicron, Bacteroides vultagus, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bilophila wadsworthia, Blautia, Butyrivibrio Campylobacter gracilis, Clostridia cluster 111, Clostridia cluster IV, Clostridia cluster IX (Acidaminococcaceae group), Clostridia cluster XI, Clostridia cluster XIII (Peptostreptococcus group), Clostridia cluster XIV Clostridia cluster XV, Collinsella aerofaciens, Coprococcus, Coryn
  • Microbiome broadly refers to the microbes residing on or in body si te of a subject or patient.
  • Microbes in a microbiome may include bacteria, viruses, eukaryotic microorganisms, and/or viruses.
  • Individual microbes in a microbiome may be metabolically active, dormant, latent, or exist as spores, may exist planktonically or in biofilms, or may be present in the microbiome in sustainable or transient manner.
  • the microbiome may be a commensal or healthy-state microbiome or a disease-state microbiome.
  • the microbiome may be native to the subject or patient, or components of the microbiome may be modulated, introduced, or depleted due to changes m health state or treatment conditions (e.g., antibiotic treatment, exposure to different microbes).
  • the microbiome occurs at a mucosal surface.
  • the microbiome is a gut microbiome.
  • a “microbiome profile” or a “microbiome signature” of a tissue or sample refers to an at least partial characterization of the bacterial makeup of a microbiome.
  • a microbiome profile indicates whether at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more bacterial strains are present or absent in a microbiome.
  • “Modified” in reference to a bacteria broadly refers to a bacteria that has undergone a change from its wild-type form.
  • Bacterial modification can result from engineering bacteria. Examples of bacterial modifications inc hide genetic modification, gene expression modification, phenotype modification, formulation modification, chemical modification, and dose or concentration. Examples of improved properties are described throughout this specification and include, e.g., attenuation, auxotrophy, homing, or antigenicity.
  • Phenotype modification might include, by way of example, bacteria growth in media that modify the phenotype of a bacterium such that it increases or decreases virulence.
  • “Operational taxonomic units” and “OTU(s)” refer to a terminal leaf in a phylogenetic tree and is defined by a nucleic acid sequence, e.g., the entire genome, or a specific genetic sequence, and all sequences that share sequence identity to this nucleic acid sequence at the level of species.
  • the specific genetic sequence may be the 16S sequence or a portion of the 16S sequence.
  • the entire genomes of two entities are sequenced and compared.
  • select regions such as multilocus sequence tags (MLST), specific genes, or sets of genes may be genetically compared.
  • OTUs that share > 97% average nucleotide identity across the entire 16S or some variable region of the 16S are considered the same OTU. See e.g., Claesson MJ, Wang Q, O’Sullivan O, Greene-Dmiz R, Cole JR, Ross RP, and O'Toole PW. 2.010.
  • OTUs are frequently defined by comparing sequences between organisms. Generally, sequences with no more than 95% sequence identity are not considered to form part of the same OTU. OTUs may also be characterized by any combination of nucleotide markers or genes, in particular highly conserved genes (e.g., “house-keeping” genes), or a combination thereof. Operational Taxonomic Units (OTUs) with taxonomic assignments made to, e.g., genus, species, and phylogenetic clade are provided herein.
  • a gene is “overexpressed” in a bacteria if it is expressed at a higher level in an engineered bacteria under at least some conditions than it is expressed by a wdld- type bacteria of the same species under the same conditions.
  • a gene is “underexpressed” in a bacteria if it is expressed at a lower level in an engineered bacteria under at least some conditions than it is expressed by a wild-type bacteria of the same species under the same conditions.
  • polynucleotide and “nucleic acid” are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxy ribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three-dimensional structure, and may perform any function.
  • polynucleotides coding or non-coding regions of a gene or gene fragment, loci (locus) defined from linkage analysis, exons, introns, messenger RNA (mRNA), micro RNA (miRNA), silencing RNA (siRNA), transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers.
  • a polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs.
  • modifications to the nucleotide structure may be imparted before or after assembly of the polymer.
  • a polynucleotide may be further modified, such as by conjugation with a labeling component.
  • L ! nucleotides are interchangeable with T nucleotides.
  • the term “preventing” a disease or condition in a subject refers to administering to the subject to a pharmaceutical treatment, e.g., the administration of one or more agents (e.g., pharmaceutical agent), such that onset of at least one symptom of the disease or condition is delayed or prevented.
  • a pharmaceutical treatment e.g., the administration of one or more agents (e.g., pharmaceutical agent)
  • agents e.g., pharmaceutical agent
  • a substance is “'pure” if it is substantially free of other components.
  • “Residual habitat products” refers to material derived from the habitat for microbiota within or on a subject.
  • fermentation cultures of microbes can contain contaminants, e.g., other microbe strains or forms (e.g., bacteria, virus, niycopiasm, and/or fungus).
  • microbes live in feces in the gastrointestinal tract, on the skin itself, in saliva, mucus of the respiratory tract, or secretions of the genitourinary' tract (i.e., biological matter associated with the microbial community').
  • Substantially free of residual habitat products means that the microbial composition no longer contains the biological matter associated with the microbial environment on or in the culture or human or animal subject and is 100% free, 99% free, 98% free, 97% free, 96% free, or 95% free of any contaminating biological matter associated with the microbial community.
  • Residual habitat products can include abiotic materials (including undigested food) or it can include unwanted microorganisms.
  • Substantially free of residual habitat products may also mean that the microbial composition contains no detectable cells from a culture contaminant or a human or animal and that only- microbial cells are detectable.
  • substantially' free of residual habitat products may also mean that the microbial composition contains no detectable viral (including bacteria, viruses (e.g., phage)), fungal, mycoplasmal contaminants.
  • it means that fewer than 1x10 -2 %, 1x10 -3 %, 1x10 -4 %, 1x10 -5 %, 1x10- 6 %, 1x10 -7 %, 1x10 -8 % of the viable cells in the microbial composition are human or animal, as compared to microbial cells. There are multiple ways to accomplish this degree of purity, none of w hich are limiting.
  • contamination may be reduced by isolating desired constituents through multiple steps of streaking to single colonies on solid media until replicate (such as, but not limited to, two) streaks from serial single colonies have showm only a single colony morphology.
  • reduction of contamination can be accomplished by multiple rounds of serial dilutions to single desired cells (e.g., a dilution of 10 -8 or 10 -9 ), such as through multiple 10-fold serial dilutions. This can further be confirmed by showing that multiple isolated colonies have similar cell shapes and Gram staining behavior.
  • strain refers to a member of a bacterial species with a genetic signature such that it may be differentiated from closely-related members of the same bacterial species, the genetic signature may be the absence of all or part of at least one gene, the absence of all or part of at least on regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the absence (“curing”) of at least one native plasmid, the presence of at least one recombinant gene, the presence of at least one mutated gene, the presence of at least one foreign gene (a gene derived from another species), the presence at least one mutated regulatory region (e.g., a promoter, a terminator, a rib
  • strains may be identified by PCR amplification optionally followed by DNA sequencing of the genomic region(s) of interest or of the whole genome.
  • strains may be differentiated by selection or counter-selection using an antibiotic or nutrient/metabolite, respectively.
  • subject refers to any mammal.
  • a subject or a patient described as “in need thereof” refers to one in need of a treatment (or prevention) for a disease.
  • Mammals i.e., mammalian animals
  • mammals include humans, laboratory' animals (e.g., primates, rats, mice), livestock (e.g., cows, sheep, goats, pigs), and household pets (e.g., dogs, cats, rodents).
  • the subject may be a human.
  • the subject may' be a non-human mammal including but.
  • a “systemic effect” in a subject treated with a pharmaceutical composition containing bacteria (e.g., a pharmaceutical agent comprising bacteria) of the instant invention means a physiological effect occurring at one or more sites outside the gastrointestinal tract.
  • Systemic effect(s) can result from immune modulation (e.g., via an increase and/or a reduction of one or more immune cell types or subtypes and/or one or more cytokines).
  • Such systemic effect(s) may be the result of the modulation by bacteria of the instant invention on immune or other cells (such as epithelial cells) in the gastrointestinal tract which then, directly or indirectly, result in the alteration of activity' (activation and/or deactivation) of one or more biochemical pathways outside the gastrointestinal tract.
  • the systemic effect may include treating or preventing a disease or condition in a subject.
  • treating refers to administering to the subject to a pharmaceutical treatment, e.g., the administration of one or more agents, such that at least one symptom of the disease is decreased or prevented from worsening.
  • a pharmaceutical treatment e.g., the administration of one or more agents, such that at least one symptom of the disease is decreased or prevented from worsening.
  • “treating” refers inter alia to delaying progression, expediting remission, inducing remission, augmenting remission, speeding recovery, increasing efficacy of or decreasing resistance to alternative therapeutics, or a combination thereof,
  • a value is “greater than” another value if it is higher by any amount (e.g., each of 100, 50, 20, 12, 11, 10.6, 10.1, 10.01, and 10.001 is at least 10). Similarly, as used herein, a value is “less than” another value if it is lower by any amount (e.g., each of 1, 2, 4, 6, 8, 9, 9.2, 9.4, 9.6, 9.8, 9.9, 9.99, 9.999 is no more than 10).
  • a test value “is” an anchor value when the test value rounds to the anchor value (e.g., if “an ingredient mass is 10% of a total mass,” in which case 10% is the anchor value, the test values of 9.5, 9.6, 9.7, 9.8, 9.9, 10, 10.1, 10.2, 10,3, and 10.4 would also meet the “ingredient mass is 10% of the total mass” feature).
  • the pharmaceutical agent of tire pharmaceutical composition s di sclosed herein comprise Prevotella histicola bacteria.
  • the pharmaceutical agent of the pharmaceutical compositions disclosed herein can comprise a powder comprising Prevotella histicola bacteria.
  • the bacteria of the pharmaceutical agent are lyophilized.
  • the phase of growth can affect the amount or properties of Prevotella histicola bacteria.
  • bacteria can be isolated, e.g., from a culture, at the start of the log phase of growth, midway through the log phase, and/or once stationary phase growth has been reached.
  • the pharmaceutical agent comprises Prevotella histicola bacteria therefrom, e.g., from a strain comprising at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8% or 99.9% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).
  • the pharmaceutical agent comprises Prevotella bacteria from Prevotella Strain B 50329 (NRRL accession number B 50329).
  • the pharmaceutical agent comprises one strain of Prevotella bacteria.
  • solid dosage forms e.g., pharmaceutical products having a solid dosage form
  • a pharmaceutical agent that contains Prevotella histicola bacteria.
  • the pharmaceutical agent can optionally contain one or more additional components, such as a cryoprotectant.
  • the pharmaceutical agent can be lyophilized (e.g., resulting in a powder).
  • the pharmaceutical agent can be combined with one or more excipients (e.g., pharmaceutically acceptable excipients) in the solid dose form.
  • the solid dosage form comprises a pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria), and one or more disintegration agents (e.g.. one, two or three disintegration agents).
  • the solid dosage form comprises a. pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g, bacteria and/or a powder comprising bacteria), and three disintegration agents.
  • the total pharmaceutical agent mass is at least 20% of the total mass of the pharmaceutical composition. In some embodiments, the total pharmaceutical agent mass is no more than 25% of the total mass of the pharmaceutical composition.
  • the total mass of the one or more disintegrating agents is at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% of the total mass of the pharmaceutical composition. In some embodiments, the total mass of the one or more disintegrating agents is no more than 70%, 65%, 60%, or 55% of the total mass of the pharmaceutical composition.
  • the one or more disintegration agents comprise low-substituted hydroxypropyl cellulose (L-HPC, e.g, LH-B1), croscarmellose sodium (Ac-Di-Sol, ⁇ -.g, Ac-Di-Sol SD-711), and/or crospovidone (PVPP, e.g, Kollidon, e.g, Kollidon CL-F).
  • L-HPC low-substituted hydroxypropyl cellulose
  • croscarmellose sodium croscarmellose sodium
  • PVPP crospovidone
  • the solid dosage forms provided herein comprise L-HPC.
  • the L-HPC is of grade LH-B1.
  • the total L-HPC mass is at least 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of tire total mass of tire pharmaceutical composition.
  • the total L-HPC mass is no more than 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceutical composition. In certain embodiments, the total L-HPC mass is about 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceutical composition.
  • the total L-HPC mass is about 29% to about 35% of the total mass of the pharmaceutical composition. In certain embodiments, the total L-HPC (e.g., LH- Bl) mass is about 32% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise Croscarmellose Sodium (e.g., Ac-Di-Sol).
  • the Croscarmellose Sodium e.g., Ac-Di-Sol
  • the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is at least 0,01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition.
  • the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is no more than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition. In certain embodiments, the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition.
  • the total Ac-Di-Sol mass is about 3% to about 9 % of the total mass of the pharmaceutical composition.
  • tlie total Croscarmellose Sodium (e.g., Ac-Di-Sol) (e.g., Ac-Di-Sol SD-711) mass is about 6 % of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise PVPP (crospovidone, e.g., Kollidon, e.g., Kollidon CL-F).
  • the total PVPP mass is at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition.
  • the total PVPP mass is no more than 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition. In certain embodiments, the total PVPP mass is about 5%, 6%, 7%, 8%, 9%, 10%, 11 %, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition. In certain embodiments, the total PVPP mass is about 12% to about 18% of the total mass of the pharmaceutical composition. In certain embodiments, the total PVPP mass is about 15% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise: (i) a pharmaceutical agent having a total pharmaceutical agent mass that is at least 20% and no more than 25% of the total mass of the pharmaceutical composition, (ii) L-HPC (e.g., L-HPC of grade LH-B1) having a total L-HPC mass that is at least 22% (e.g., at least 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42%) and no more than 42% (e.g., no more than 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42%) of the total mass of the pharmaceutical composition; (iii) Croscarmellose Sodium
  • the total L-HPC mass plus the total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass plus the total PVPP mass is at least 35%, 40%, 45%, or 50% of the total mass of the pharmaceutical composition.
  • the solid dosage form comprises: a total L-HPC mass is about 32% of the total mass of the pharmaceutical composition; a total Croscarmellose Sodium (e.g., Ac-Di-Sol) mass is about 6% of the total mass of the pharmaceutical composition; and a total PVPP mass is about 15% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein further comprise mannitol.
  • the mannitol is mannitol SD200.
  • the total mannitol mass is at least 18% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol mass is no more than 25% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol mass is about 18%, 18.5%, 19%, 19.5%, 20%, 20.5%, 21%, 21.5%, 22%, 22.5%, 23%, 23.5%, 24%, 24,5%, or 25% of the total mass of the pharmaceutical composition.
  • the total mannitol (e.g., mannitol SD200) mass is about 18% to about 25% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol (e.g., mannitol SD2.00) mass is about 22% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol (e.g., mannitol SD200) mass is about 21 .5% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise magnesium stearate.
  • the total magnesium stearate mass is at least 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition. In certain embodiments, the total magnesium stearate mass is no more than 0.01%, 0.1%, 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • tire total magnesium stearate mass is about 0.01%, 0.1%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 0.5% to about 1 .5% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 1 % of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 1 .5% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise colloidal silica.
  • the colloidal silica is Aerosil 200.
  • the total colloidal silica mass is at least 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11 % of the total mass of the pharmaceutical composition.
  • the total colloidal silica mass is no more than 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total colloidal silica mass is about 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11 % of the total mass of the pharmaceutical composition. In certain embodiments, the total colloidal silica mass is about 0.5% to about I .5% of the total mass of the pharmaceutical composition. In certain embodiments, the total colloidal silica (e.g., Aerosil 200) mass is about 1% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise about 23% pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 22% mannitol (e.g., mannitol SD200); about 32% L-HPC (e.g,, L-HPC LH-B1); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD-711); about 15% crospovidone (e.g., PVPP); about 1% magnesium stearate; and about 1% colloidal silica (e.g., Aerosd 200).
  • the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 22% mannitol (e.g., mannitol SD200); about 32% L-HPC (e.g,, L-HPC LH-B1); about 6% croscarmellose sodium (e.g
  • the solid dosage forms provided herein comprise about 23% pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 21.5% mannitol; about 32% L-HPC (e.g., L-HPC LH-B1); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD- 711); about 15% crospovidone; about 1.5% magnesium stearate; and about 1% colloidal silica (e.g., Aerosil 200P).
  • the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 21.5% mannitol; about 32% L-HPC (e.g., L-HPC LH-B1); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD- 711); about 15% crospovidone; about 1.5% magnesium stearate
  • solid dosage forms comprising a pharmaceutical agent that contains Prevotella histicola bacteria.
  • the bacteria can be live bacteria (e.g., powder or biomass thereof); non-live (dead) bacteria (e.g., powder or biomass thereof); non replicating bacteria (e.g., powder or biomass thereof); gamma-irradiated bacteria (e.g,, powder or biomass thereof); and/or lyophilized bacteria (e.g., powder or biomass thereof).
  • the pharmaceutical agents comprise lyophilized Prevotella histicola bacteria.
  • total cell count can be used to quantify the numbers of Prevotella histicola bacteria present in a sample.
  • electron microscopy e.g., EM of ultrathin frozen sections
  • solid dosage forms comprising pharmaceutical agents that comprise Prevotella histicola bacteria useful for the treatment and/or prevention of disease (e.g., an autoimmune disease, an inflammatory disease, a metabolic disease, or a dysbiosis); or treatment and/or prevention of bacterial septic shock, cytokine storm and/or viral infection (such as a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection); or to decrease inflammatory cytokine expression (e.g..).
  • disease e.g., an autoimmune disease, an inflammatory disease, a metabolic disease, or a dysbiosis
  • treatment and/or prevention of bacterial septic shock, cytokine storm and/or viral infection such as a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection
  • bacterial septic shock such as a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection
  • viral infection such as a cor
  • the pharmaceutical agents comprise Prevotella histicola bacteria (e.g,, whole bacteria) (e.g., live bacteria, dead (e.g,, killed) bacteria, non-replicating bacteria, gamma-irradiated bacteria; attenuated bacteria).
  • compositions for administration to a subject are combined with additional active and/or inactive materials in order to produce a final product, which may be in single dosage unit or in a multi-dose fonnat.
  • the pharmaceutical agent is combined with an adjuvant such as an immuno-adjuvant (e.g., a STING agonist, a TLR agonist, or a NOD agonist).
  • an adjuvant such as an immuno-adjuvant (e.g., a STING agonist, a TLR agonist, or a NOD agonist).
  • the solid dosage form comprises at least one carbohydrate.
  • the solid dosage form comprises at least one lipid.
  • the lipid comprises at least one fatty acid selected from lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16: 1), margaric acid (17:0), heptadecenoic acid (17: 1), stearic acid (18:0), oleic acid (18: 1), linoleic acid (18:2), linolenic acid (18:3), octadecatetraenoic acid (18:4), arachidic acid (20:0), eicosenoic acid (20: 1), eicosadienoic acid (20:2), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5) (EP A), docosanoic acid (22:0), docosenoic acid (22: 1), docosapentaenoic acid (22:5), do
  • the solid dosage form comprises at least one mineral or mineral source.
  • minerals include, without limitation: chloride, sodium, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium.
  • Suitable forms of any of the foregoing minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals, and reduced minerals, and combinations thereof.
  • the solid dosage form comprises at least one vitamin.
  • the at least one vitamin can be fat-soluble or water-soluble vitamins.
  • Suitable vitamins include but are not limited to vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid, and biotin.
  • Suitable forms of any of the foregoing are salts of the vitamin, derivatives of the vitamin, compounds having tire same or similar activity of the vitamin, and metabolites of the vitamin.
  • the solid dosage form comprises an excipient.
  • suitable excipients include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and a coloring agent.
  • Suitable excipients that can be included in the solid dosage form can be one or more pharmaceutically acceptable excipients known in the art. For example, see Rowe, Sheskey, and Quinn, eds., Handbook of Pharmaceutical Excipients, sixth ed.: 2009; Pharmaceutical Press and American Pharmacists Association. Solid Dosage Forms
  • the solid dosage form described herein can be, e.g., a tablet or a minitablet. Further, a plurality of minitablets can be in (e.g., loaded into) a capsule.
  • the solid dosage form comprises a tablet (> 4mm) (e.g., 5mm- 17mm).
  • the tablet is a 5mm, 5.5mm, 6mm, 6.5mm, 7mm, 7.5mm, 8mm, 8.5mm, 9mm, 9.5mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm or 18mm tablet.
  • the tablet is a 13mm, 14mm, 15mm, 16mm, 17mm or 18mm tablet.
  • the tablet is a 17mm tablet.
  • the size refers to the diameter of the tablet, as is known in the art. As used herein, the size of the tablet refers to the size of the tablet prior to application of an enteric coating.
  • the solid dosage form comprises a minitablet.
  • the minitablet can be in the size range of lmm-4 mm range.
  • the minitablet can be a 1mm minitablet, 1.5 mm minitablet, 2mm minitablet, 3mm minitablet, or 4mm minitablet.
  • the size refers to the diameter of the minitablet, as is known in the art.
  • the size of the minitablet refers to the size of the minitablet prior to application of an enteric coating.
  • the minitablets can be in a capsule.
  • the capsule can be a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule.
  • the capsule that contains the minitablets can comprise HPMC (hydroxyl propyl methyl cellulose) or gelatin.
  • the minitablets can be inside a capsule: tlie number of minitablets inside a capsule will depend on the size of the capsule and the size of the minitablets. As an example, a size 0 capsule can contain 31-35 (an average of 33) minitablets that are 3mm minitablets.
  • the solid dosage form (e.g., tablet or minitablet) described herein can be enterically coated, e.g., with one enteric coating layer or with two layers of enteric coating, e.g,, an inner enteric coating and an outer enteric coating.
  • the inner enteric coating and outer enteric coating are not identical (e.g., the inner enteric coating and outer enteric coating do not contain the same components in the same amounts).
  • the enteric coating allows for release of the pharmaceutical agent, e.g., in the small intestine, e.g., upper small intestine, e.g., duodenum and/or jejunum .
  • release of the pharmaceutical agent in the small intestine allows the pharmaceutical agent to target and affect cells (e.g., epithelial cells and/or immune cells) located at these specific locations, e.g., which can cause a local effect in the small intestine and/or cause a systemic effect (e.g., an effect outside of the gastrointestinal tract).
  • cells e.g., epithelial cells and/or immune cells
  • EUDRAGIT is the brand name for a diverse range of polymethacrylate-based copolymers. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives.
  • Examples of other materials that can be used in the enteric coating include cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), poly( vinyl acetate phthalate) (PVAP), hydroxypropyl methylcellulose phthalate (HPMCP), fatty acids, waxes, shellac (esters of aleurtic acid), plastics, plant fibers, zein, AQUA-ZEIN® (an aqueous zein formulation containing no alcohol), amylose starch, starch derivatives, dextrins, methyl acrylate-methacrylic acid copolymers, cellulose acetate succinate, hydroxypropyl methyl cellulose acetate succinate (hypromellose acetate succinate), methyl methacrylate- methacrylic acid copolymers, and/or sodium alginate,
  • CAP cellulose acetate phthalate
  • CAT cellulose acetate trimellitate
  • PVAP poly( vinyl acetate phthalate)
  • HPPMCP
  • the enteric coating (e.g., the one enteric coating or the inner enteric coating and/or the outer enteric coating) can include a methacrylic acid ethyl acrylate (MAE) copolymer ( 1:1).
  • MAE methacrylic acid ethyl acrylate
  • the one enteric coating can include methacrylic acid ethyl acrylate (MAE) copolymer ( 1:1) (such as Kollicoat MAE 100P).
  • MAE methacrylic acid ethyl acrylate
  • the one enteric coating can include a Eudragit copolymer, e.g., a Eudragit L (e.g., Eudragit L 100-55; Eudragit L 30 D-55), a Eudragit S, a Eudragit RL, a Eudragit RS, a Eudragit E, or a Eudragit FS (e.g., Eudragit FS 30 D).
  • a Eudragit copolymer e.g., a Eudragit L (e.g., Eudragit L 100-55; Eudragit L 30 D-55), a Eudragit S, a Eudragit RL, a Eudragit RS, a Eudragit E, or a Eudragit FS (e.g., Eudragit FS 30 D).
  • enteric coating examples include those described in, e.g., U.S. 6312728; U.S. 6623759; U.S. 4775536; U.S. 5047258; U.S. 5292522; U.S. 6555124; U.S. 6638534; U.S. 2006/0210631; U.S. 2008/200482; U.S. 2005/0271778; U.S. 2.004/0028737; WO 2005/044240.
  • methacrylic acid copolymers include: poly(methacry1ic acid, methyl methacrylate) 1: 1 sold, for example, under the Eudragit LI 00 trade name; poly(methacrylic acid, ethyl acrylate) 1: 1 sold, for example, under the Eudragit L100-55 trade name; partially-neutralized poly(methacrylic acid, ethyl acrylate) 1: 1 sold, for example, under the Kollicoat MAE-100P trade name; and poly(methacrylic acid, methyl methacrylate) 1:2 sold, for example, under the Eudragit SI
  • the solid dosage form (e.g., tablet or minitablet) described herein further comprises a sub-coating.
  • the solid dosage form comprises a sub-coating, e.g., in addition to the enteric coating, e.g., the sub-coating is beneath the enteric coating (e.g., between the solid dosage form and the enteric coating).
  • the sub-coating comprises Opadry QX, e.g., Opadry QX Blue.
  • the dose of the pharmaceutical agent is the dose per tablet or per total number of minitablets (e.g., total number of minitablets in a capsule).
  • total cell count can be determined by Coulter counter
  • the pharmaceutical agent comprises Prevotella histicola bacteria and the dose of bacteria is about 2.4 x 10 11 to about 4.0 x 10 11 cells (e.g., wherein cell number is determined by total cell count, which is determined by Coulter counter), wherein the dose is per tablet or per total number of minitablets in a capsule.
  • the pharmaceutical agent comprises Prevotella histicola bacteria and the dose of bacteria is about 2.8 x 10 11 to about 3.6 x 10 11 ceils (e.g., wherein cell number is determined by total cell count, which is determined by Coulter counter), wherein the dose is per tablet or per total number of minitablets in a capsule.
  • the pharmaceutical agent comprises Prevotella histicola bacteria and the dose of bacteria is about 3.2 x 10 11 cells (e.g., wherein cell number is determined by total cell count, which is determined by Coulter counter), wherein the dose is per tablet or per total number of minitablets in a capsule.
  • the pharmaceutical agent comprises Prevotella histicola bacteria and the dose of bacteria is about 2.4 x 10 !1 , about 2.8 x 10 11 , about 3,2 x 10 11 , about 3.6 x 10 11 , or about 4.0 x 10 11 , cells, wherein the dose is per tablet or per total number of minitablets in a capsule.
  • the pharmaceutical agent comprises Prevotella histicola bacteria and the dose of bacteria is about 3.2 x 10 11 cells, wherein the dose is per tablet or per total number of minitablets in a capsule.
  • the disclosure provides a method of treating a subject (e.g., human) (e.g., a subject in need of treatment), the method comprising administering to the subject a solid dosage form provided herein.
  • the disclosure provides use of a solid dosage form provided herein for the preparation of a medicament for treating a subject (e.g., human) (e.g., a subject in need of treatment).
  • a subject e.g., human
  • a subject in need of treatment e.g., a subject in need of treatment
  • the solid dosage form is orally administered (e.g., is for oral administration).
  • the solid dosage form is administered (e.g., is for administration) 1 , 2, 3, or 4 times a day.
  • 1 , 2, 3, 4 or 5 solid dosage forms e.g., tablets
  • 2, 4, 6, 8, or 10 solid dosage forms e.g., tablets
  • 1 solid dosage form is administered (e.g., is for administration) 1 or 2 times a day.
  • 2 solid dosage forms are administered (e.g., are for administration) 1 or 2 times a day.
  • 3 solid dosage forms are administered (e.g., are for administration) I or 2 times a day.
  • 4 solid dosage forms are administered (e.g., are for administration) 1 or 2 times a day.
  • 5 solid dosage forms are administered (e.g., are for administration) 1 or 2 times a day.
  • 1 solid dosage form e.g., tablet
  • 1 solid dosage form is administered (e.g., is for administration) 1 or 2 times a day, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells.
  • 2 solid dosage forms e.g., tablets
  • the solid dosage form comprises a. dose of bacteria of about 3.2 x 10 11 cells.
  • 3 solid dosage forms e.g., tablets
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells.
  • solid dosage forms e.g,, tablets
  • solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells.
  • 5 solid dosage forms e.g., tablets
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells
  • I solid dosage form e.g., tablet
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells (e.g., resulting in a total of about 3.2 x 10 11 cells being administered).
  • 2 solid dosage forms e.g., tablets
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells (e.g., resulting in a total of about 6.4 x 10 11 cells being administered with the 2 tablets).
  • 3 solid dosage forms are administered (e.g., are for administration) per day, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells (e.g., resulting in a total of about 9.6 x 10 11 cells being administered with the 3 tablets).
  • 4 solid dosage forms are administered (e.g., are for administration) per a day, wherein the solid dosage form comprises a dose of bacteria of about 3,2 x 10 11 cells (e.g., resulting in a total of about 12.8 x 10 11 cells being administered with the 4 tablets).
  • 5 solid dosage forms e.g., tablets
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 cells (e.g., resulting in a total of about 16 x 10 11 cells being administered with the 5 tablets).
  • a human dose can be calculated appropriately based on allometric scaling of a dose administered to a model organism (e.g., mouse).
  • a model organism e.g., mouse
  • the solid dosage form is administered orally. In some embodiments, the administration to the subject once daily. In some embodiments, the solid dosage form is administered in 2 or more doses (e.g., 3 or more, 4 or more or 5 or more doses).
  • the administration to the subject of the two or more doses are separated by at least 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, I day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days or 21 days.
  • the solid dosage form is administered once daily for 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 2.6 days, 27 days, 2.8 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, or 42 days.
  • the solid dosage form is administered once daily for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks. In some embodiments, the solid dosage form is administered once daily for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks.
  • the solid dosage form is administered twice daily for 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, or 42 days.
  • the solid dosage form is administered twice daily for 1, 2, 3, 4,
  • the solid dosage form is administered once daily for at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks.
  • one or two solid dosage forms can be administered one or two times a day.
  • one or two solid dosage forms can be administered daily.
  • 3, 4, or 5 solid dosage forms can be administered one or two times a day.
  • 3, 4, or 5 solid dosage forms can be administered daily.
  • 4 solid dosage forms can be administered one or two times a day.
  • 4 solid dosages form can be administered daily.
  • the pharmaceutical agent contains the Prevotella histicola bacteria or contains a powder comprising Prevotella histicola bacteria, and can also contain one or more additional components, such as a cryoprotectant.
  • the solid dosage forms having the disclosed combinations and/or amounts of disintegration agents provide a decrease in disintegration times (e.g., 2. -fold, 4-fold, 6-fold, 8- fold), which can further result in an increase in therapeutic efficacy and/or physiological effect as compared to the same solid dosage forms that do not have the disclosed combinations of the disintegration agents,
  • solid dosage forms described herein allow, e.g., for oral administration of a pharmaceutical agent contained therein.
  • the solid dosage forms described herein can be used in the treatment and/or prevention of inflammation, autoimmunity, a metabolic condition, or a dysbiosis.
  • the solid dosage forms described herein can be used in the treatment and/or prevention of bacterial septic shock, cytokine storm and/or viral infection (such as a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection).
  • the solid dosage forms described herein can be used to decrease inflammatory' cytokine expression (e.g., decreased IL-8, IL-6, IL- I ⁇ , and/or TNFa expression levels).
  • inflammatory' cytokine expression e.g., decreased IL-8, IL-6, IL- I ⁇ , and/or TNFa expression levels.
  • a solid dosage form e.g., for oral administration
  • a pharmaceutical agent e.g., a therapeutically effective amount thereof
  • the pharmaceutical agent comprises Prevotella histicola bacteria
  • the solid dosage form further comprises the disclosed components are described herein.
  • the methods and administered solid dosage forms described herein allow', e.g., for oral administration of a pharmaceutical agent contained therein.
  • the solid dosage form can be administered to a subject is a fed or fasting state.
  • the solid dosage form can be administered, e.g., on an empty stomach (e.g., one hour before eating or two hours after eating).
  • the solid dosage form can be administered one hour before eating.
  • the solid dosage form can be administered two hours after eating.
  • a solid dosage form for use in the treatment and/or prevention of inflammation, autoimmunity, a metabolic condition, or a dysbiosis is provided herein.
  • a solid dosage form for use in the treatment and/or prevention of bacterial septic shock, cytokine storm and/or viral infection (such as a coronavirus infection, an influenza infection, and/or a respiratory' syncytial virus infection) is provided herein.
  • a solid dosage form for use in decrease inflammatory cytokine expression (e.g.. decreased IL-8, IL-6, IL- I ⁇ , and/or TNFa expression levels) is provided herein.
  • a solid dosage form for the preparation of a medicament for the treatment and/or prevention of bacterial septic shock, cytokine storm and/or viral infection (such as a coronavirus infection, an influenza infection, and/or a respiratory' syncytial virus infection) is provided herein.
  • bacterial septic shock, cytokine storm and/or viral infection such as a coronavirus infection, an influenza infection, and/or a respiratory' syncytial virus infection
  • Solid dosage form for the preparation of a medicament for decreasing inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL- I ⁇ , and/or TNFa expression levels) is provided herein.
  • a solid dosage form of a pharmaceutical composition comprising combining into a pharmaceutical composition a pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria), and one or more (e.g., one, two or three) disintegration agents.
  • the total pharmaceutical agent mass is at least 20% of the total mass of the pharmaceutical composition.
  • the total pharmaceutical agent mass is no more than 25% of the total mass of the pharmaceutical composition.
  • the total mass of the one or more disintegrating agents is at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% of the total mass of the pharmaceutical composition.
  • the total mass of tlie one or more disintegrating agents is no more than 70%, 65%, 60%, or 55% of the total mass of the pharmaceutical composition.
  • the one or more disintegration agents comprise low-substituted hydroxypropyl cellulose (L-HPC), croscarmellose sodium (Ac-Di-Sol), and/or crospovidone (PVPP).
  • the solid dosage forms provided herein comprise L-HPC.
  • the L-HPC is of grade LH-B1 .
  • the total L-HPC mass is at least 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31 %, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceutical composition.
  • the total L-HPC mass is no more than 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceu tical composition. In certain embodiments, the total L-HPC mass is about 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, or 42% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise croscarmellose sodium (Ac-Di-Sol).
  • the croscarmellose sodium (Ac-Di-Sol) is Ac-Di-Sol of grade SD-711.
  • the total croscarmellose sodium (Ac-Di-Sol) mass is at least 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition.
  • the total croscarmellose sodium (Ac- Di-Sol) mass is no more than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition.
  • the total croscarmellose sodium (Ac-Di-Sol) mass is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or 16% of the total mass of the pharmaceutical composition.
  • the solid dosage forms provided herein comprise PVPP.
  • tire total PVPP mass is at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition.
  • the total PVPP mass is no more than 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition.
  • the total PVPP mass is about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% of the total mass of the pharmaceutical composition.
  • the method further comprises combining mannitol.
  • the mannitol is mannitol SD200.
  • the total mannitol mass is at least 18% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol mass is no more than 25% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol mass is about 18%, 18.5%, 19%, 19.5%, 20%, 20.5%, 21%, 21.5%, 22%, 22.5%, 23%, 23.5%, 24%, 24.5%, or 25% of the total mass of the pharmaceutical composition.
  • the total mannitol ( ⁇ ?.g, mannitol SD200) mass is about 18% to about 25% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol (e.g., mannitol SD200) mass is about 22% of the total mass of the pharmaceutical composition. In certain embodiments, the total mannitol (e.g., mannitol SD200) mass is about 21.5% of the total mass of the pharmaceutical composition.
  • the method further comprises combining magnesium stearate.
  • the total magnesium stearate mass is at least 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is no more than 0.01%, 0.1%, 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 0.01%, 0.1 %, 1%, 1 .5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%), 8%, 8.5%, 9%, 9.5%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 0.5% to about 1.5% of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 1 % of the total mass of the pharmaceutical composition.
  • the total magnesium stearate mass is about 1 .5% of the total mass of the pharmaceutical composition.
  • the method further comprises combining comprise colloidal silica.
  • the colloidal silica is Aerosil 2.00.
  • the total colloidal silica mass is at least 0.01%, 0.1%, 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11 % of the total mass of the pharmaceutical composition.
  • tlie total colloidal silica mass is no more than 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition.
  • the total colloidal silica mass is about 0.01 %, 0, 1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% of the total mass of the pharmaceutical composition. In certain embodiments, the total colloidal silica mass is about 0.5% to about 1.5% of the total mass of the pharmaceutical composition. In certain embodiments, the total colloidal silica (e.g., Aerosil 200) mass is about 1 % of the total mass of the pharmaceutical composition.
  • the method further comprises combining about 23% pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g,, bacteria and/or a powder comprising bacteria); about 22% mannitol (e.g,, mannitol SD200); about 32% L-HPC (e.g., L-HPC LH-B1 ); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD-7I1); about 15% crospovidone (e.g., PVPP); about 1% magnesium stearate; and about 1% colloidal silica (e.g., Aerosil 200).
  • the pharmaceutical agent comprises Prevotella histicola bacteria (e.g,, bacteria and/or a powder comprising bacteria); about 22% mannitol (e.g,, mannitol SD200); about 32% L-HPC (e.g., L-HPC LH-B1 ); about 6% croscarmellose sodium (e.
  • the method further comprises combining about 23% pharmaceutical agent, wherein the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 21.5% mannitol; about 32% L-HPC (e.g., L-HPC LH-B1); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD- 711); about 15% crospovidone; about 1.5% magnesium stearate; and about 1% colloidal silica (e.g., Aerosil 200P).
  • the pharmaceutical agent comprises Prevotella histicola bacteria (e.g., bacteria and/or a powder comprising bacteria); about 21.5% mannitol; about 32% L-HPC (e.g., L-HPC LH-B1); about 6% croscarmellose sodium (e.g., Ac-Di-Sol SD- 711); about 15% crospovidone; about 1.5% magnesium stearate; and
  • the method further comprises compressing the pharmaceutical composition, thereby forming a tablet or a minitablet. In some embodiments, the method further comprises enterically coating the tablet or minitablet, thereby preparing the enterically coated tablet. In certain embodiments, the method further comprises loading the minitablets into a capsule.
  • solid dosage forms e.g., as described herein, comprising a pharmaceutical agent
  • the pharmaceutical agent comprises
  • Prevotella histicola bacteria and wherein the solid dosage form further comprises the described components, can provide a therapeutically effective amount of the pharmaceutical agent to a subject, e.g., a human.
  • the solid dosage forms e.g., as described herein, comprising a pharmaceutical agent (e.g., a therapeutically effective amount thereof), wherein the pharmaceutical agent comprises Prevotella histicola bacteria, and wherein the solid dosage form further comprises the described components, can provide a non-natural amount of the therapeutically effective components (e.g., present in the pharmaceutical agent) to a subject, e.g., a human.
  • a pharmaceutical agent e.g., a therapeutically effective amount thereof
  • the pharmaceutical agent comprises Prevotella histicola bacteria
  • the solid dosage form further comprises the described components
  • the solid dosage forms e.g., as described herein, comprising a pharmaceutical agent (e.g., a therapeutically effective amount thereof), wherein the pharmaceutical agent comprises Prevotella histicola bacteria, and wherein the solid dosage form further comprises the described components, can provide an unnatural quantity of the therapeutically effective components (e.g., present in the pharmaceutical agent) to a subject, e.g., a human.
  • a pharmaceutical agent e.g., a therapeutically effective amount thereof
  • the pharmaceutical agent comprises Prevotella histicola bacteria
  • the solid dosage form further comprises the described components
  • any solid dosage forms comprising a pharmaceutical agent (e.g., a therapeutically effective amount thereof), wherein the pharmaceutical agent comprises Prevotella histicola bacteria, and wherein the solid dosage form further comprises the described components, can bring about one or more changes to a subject, e.g., human, e.g., to treat or prevent a disease or a health disorder.
  • a pharmaceutical agent e.g., a therapeutically effective amount thereof
  • the pharmaceutical agent comprises Prevotella histicola bacteria
  • the solid dosage form further comprises the described components
  • the solid dosage forms e.g., as described herein, comprising a pharmaceutical agent (e.g., a therapeutically effective amount thereof), wherein the pharmaceutical agent comprises Prevotella histicola bacteria, and wherein the solid dosage form further comprises the described components, has potential for significant utility, e.g,, to affect a subject, e.g., a human, e.g., to treat or prevent a disease or a health disorder.
  • a pharmaceutical agent e.g., a therapeutically effective amount thereof
  • the pharmaceutical agent comprises Prevotella histicola bacteria
  • the solid dosage form further comprises the described components
  • the methods provided herein include the administration to a subject of a solid dosage form described herein either alone or in combination with an additional therapeutic agent.
  • the additional therapeutic agent is an immunosuppressant, an anti-inflammatory agent, and/or a steroid.
  • the solid dosage form is administered to the subject before the additional therapeutic agent is administered (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days before).
  • additional therapeutic agent e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days before.
  • the solid dosage form is administered to the subject after the additional therapeutic agent is administered (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours after or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days after).
  • the solid dosage form and the additional therapeutic agent are administered to the subject simultaneously or nearly simultaneously (e.g., administrations occur within an hour of each other).
  • an antibiotic is administered to the subject before the solid dosage form is administered to the subject (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
  • an antibiotic is administered to the subject after the solid dosage form is administered to the subject (e.g., at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
  • the solid dosage form and the antibiotic are administered to the subject simultaneously or nearly simultaneously (e.g., administrations occur within an hour of each other).
  • the additional therapeutic is an antibiotic.
  • antibiotics broadly refers to compounds capable of inhibiting or preventing a bacterial infection . Antibiotics can be classified in a number of ways, including their use for specific infections, their mechanism of action, their bi oava.il ability, or their spectrum of target microbe (e.g.. Gram-negative vs. Gram-positive bacteria, aerobic vs.
  • antibiotics can be used to selectively target bacteria of a specific niche.
  • antibiotics know n to treat a particular infection that includes a disease niche may be used to target disease-associated microbes, including disease-associated bacteria in that niche.
  • antibiotics are administered after the solid dosage form. In some embodiments, antibiotics are administered before the solid dosage form.
  • antibiotics can be selected based on their bactericidal or bacteriostatic properties.
  • Bactericidal antibiotics include mechanisms of action that disrupt tire cell wall (e.g., p-lactams), the cell membrane (e.g., daptomycin), or bacterial DNA (e.g,, fluoroquinolones).
  • Bacteriostatic agents inhibit bacterial replication and include sulfonamides, tetracyclines, and macrolides, and act by inhibiting protein synthesis.
  • some drugs can be bactericidal in certain organisms and bacteriostatic in others, knowing the target organism allows one skilled in the art to select an antibiotic with tlie appropriate properties.
  • bacteriostatic antibiotics inhibit the activity of bactericidal antibiotics.
  • bactericidal and bacteriostatic antibiotics are not combined.
  • Antibiotics include, but are not limited to aminoglycosides, ansamycins, carbacephems, carbapenems, cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, oxazolidonones, penicillins, polypeptide antibiotics, quinolones, fluoroquinolone, sulfonamides, tetracyclines, and anti -mycobacterial compounds, and combinations thereof.
  • Aminoglycosides include, but are not limited to Amikacin, Gentamicin, Kanamycin, Neomycin, Netilmicin, Tobramycin, Paromomycin, and Spectinomycin. Aminoglycosides are effective, e.g., against Gram-negative bacteria, such as Escherichia coll, Klebsiella, Pseudomonas aeruginosa, and Francisella tularensis, and against certain aerobic bacteria but less effective against obligate/facultative anaerobes. Aminoglycosides are believed to bind to the bacterial 30S or 50S ribosomal subunit thereby inhibiting bacterial protein synthesis.
  • Gram-negative bacteria such as Escherichia coll, Klebsiella, Pseudomonas aeruginosa, and Francisella tularensis
  • Ansamycins include, but are not limited to, Geldanamycin, Herbimycin, Rifamycin, and Streptovaricin.
  • Geldanamycin and Herbimycin are believed to inhibit or alter the function of Heat Shock Protein 90.
  • Carbacephems include, but are not limited to, Loracarbef. Carbacephems are believed to inhibit bacterial cell wall synthesis.
  • Carbapenems include, but are not limited to, Ertapenem, Doripenem, Imipenem/Cilastatin, and Meropenem. Carbapenems are bactericidal for both Gram-positive and Gram-negative bacteria as broad-spectrum antibiotics. Carbapenems are believed to inhibit bacterial cell wall synthesis.
  • Cephalosporins include, but are not limited to, Cefadroxil, Cefazolin, Cefalotin, Cefalothin, Cefalexin, Cefaclor, Cefamandole, Cefoxitin, Cefprozil, Cefuroxime, Cefixime, Cefdinir, Cefditoren, Cefoperazone, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Ceftaroline fosamil, and Ceftobiprole.
  • Cephalosporins are effective, e.g., against Gram-negative bacteria and against Gram-positive bacteria, including Pseudomonas, certain Cephalosporins are effective against methicillin resistant Staphylococcus aureus (MRSA). Cephalosporins are believed to inhibit bacterial cell wail synthesis by disrupting synthesis of the peptidoglycan layer of bacterial ceil wails.
  • Glycopeptides include, but are not limited to, Teicopianin, Vancomycin, and Telavancin. Glycopeptides are effective, e.g., against aerobic and anaerobic Gram-positive bacteria including MRSA and Clostridium difficile. Glycopeptides are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • Lincosamides include, but are not limited to, Clindamycin and Lincomycin. Lincosamides are effective, e.g., against anaerobic bacteria, as well as Staphylococcus, and Streptococcus. Lincosamides are believed to bind to the bacterial 50S ribosomal subunit thereby inhibiting bacterial protein synthesis.
  • Lipopeptides include, but are not limited to, Daptomycin. Lipopeptides are effective, e.g., against Gram-positive bacteria. Lipopeptides are believed to bind to the bacterial membrane and cause rapid depolarization,
  • Macrolides include, but are not limited to, Azithromycin, Clarithromycin, Dirithromycin, Erythromycin, Roxithromycin, Troleandomycin, Telithromycin, and Spiramycin. Macrolides are effective, e.g., against Streptococcus and Mycoplasma. Macrolides are believed to bind to the bacterial or 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis.
  • Monobactams include, but are not limited to, Aztreonam. Monobactams are effective, e.g., against Gram-negative bacteria. Monobactams are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • Nitrofurans include, but are not limited to, Furazolidone and Nitrofurantoin.
  • Oxazolidonones include, but are not limited to, Linezolid, Posizolid, Radezolid, and Torezolid. Oxazolidonones are believed to be protein synthesis inhibitors.
  • Penicillins include, but are not limited to, Amoxicillin, Ampicillin, Azlocillin, Carbenicillin, Cloxaciltin, Dicloxacillin, Flucioxacillin, Mezlocillin, Methicillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin, Temocillin and Ticarcillin.
  • Penicillins are effective, e.g., against Gram-positive bacteria, facultative anaerobes, e.g., Streptococcus, Borrelia, and Treponema. Penicillins are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • Penicillin combinations include, but are not. limited to, Amoxicillin/clavulanate, Ampicillin/sulbactam, Piperacillin/tazobactam, and Ticarcillin/clavulanate.
  • Polypeptide antibiotics include, but are not limited to, Bacitracin, Colistin, and Polymyxin B and E. Polypeptide Antibiotics are effective, e.g., against Gram-negative bacteria. Certain polypeptide antibiotics are believed to inhibit isoprenyl pyrophosphate involved in synthesis of the peptidoglycan layer of bacterial cell walls, while others destabilize the bacterial outer membrane by displacing bacterial counter-ions.
  • Quinolones and Fluoroquinolone include, but are not limited to, Ciprofloxacin, Enoxacin, Gatifloxacin, Gemifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin, Trovafloxacin, Grepafloxacin, Sparfloxacin, and Temafloxacin. Qumolones/Fluoroquinolone are effective, e.g., against Streptococcus and Neisseria. Quinolones/Fluoroquinolone are believed to inhibit the bacterial DNA gyrase or topoisomerase IV, thereby inhibiting DNA replication and transcription.
  • Sulfonamides include, but are not limited to, Mafenide, Sulfacetamide, Sulfadiazine, Silver sulfadiazine, Sulfadimethoxine, Sulfametlnzole, Sulfamethoxazole, Sulfamlimide, Sulfasalazine, Sulfisoxazole, Trimethoprim-Sulfamethoxazole (Co-trimoxazole), and Sulfonamidochrysoidine.
  • Sulfonamides are believed to inhibit folate synthesis by competitive inhibition of dihydropteroate synthetase, thereby inhibiting nucleic acid synthesis.
  • Tetracyclines include, but are not limited to, Demeclocycline, Doxycycline, Minocycline, Oxytetracycline, and Tetracycline. Tetracyclines are effective, e.g., against Gram-negative bacteria. Tetracyclines are believed to bind to the bacterial 30S ribosomal subunit thereby inhibiting bacterial protein synthesis.
  • Anti-mycobacterial compounds include, but are not limited to, Clofazimine, Dapsone, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Pyrazinamide, Rifampicin, Rifabutin, Rifapentine, and Streptomycin.
  • Suitable antibiotics also include arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocm, platensimycin, quinupristin/dalfopristin, tigecycline, tinidazole, trimethoprim amoxicillin/clavulanate, ampicillin/sulbactam, amphomycin ristocetin, azithromycin, bacitracin, buforin II, carbomycin, cecropin Pl, clarithromycin, erythromycins, furazolidone, fusidic acid, Na fusidate, gramicidin, imipenem, indolicidin, josamycin, magainan II, metronidazole, nitroimidazoles, mikamycin, mutacin B-Ny266, mutacin B-JH1 140, mutacin J-T8, nisin, nisin A, novobiocin, oleando
  • the additional therapeutic agent is an immunosuppressive agent, a DMARD, a pain-control drag, a steroid, a non-steroidal anti-inflammatory drag (NS AID), or a cytokine antagonist, and combinations thereof.
  • Representative agents include, but are not limited to, cyclosporin, retinoids, corticosteroids, propionic acid derivative, acetic acid derivative, enolic acid derivatives, fenamic acid derivatives, Cox-2 inhibitors, lumiracoxib, ibuprophen, cholin magnesium salicylate, fenoprofen, salsalate, difiinisal, tolmetin, ketoprofen, flurbiprofen, oxaprozin, indomethacin, sulindac, etodolac, ketorolac, nabumetone, naproxen, valdecoxib, etoricoxib, MK0966; rofecoxib, acetominophen, Celecoxib, Diclofenac, tramadol, piroxicam, meloxicam, tenoxicam, droxicam, lomoxicam, isoxicam, mefanamic acid, meclofenamic acid
  • the additional therapy can comprise a JAK inhibitor such as baricitinib, ruxolitinib, tofacitinib, and/or pacritinib.
  • a JAK inhibitor such as baricitinib, ruxolitinib, tofacitinib, and/or pacritinib.
  • the additional therapeutic agent is an immunosuppressive agent.
  • immunosuppressive agents include, but are not limited to, corticosteroids, mesalazine, mesalamine, sulfasalazine, sulfasalazine derivatives, immunosuppressive drugs, cyclosporin A, mercaptopurine, azathiopurine, prednisone, methotrexate, antihistamines, glucocorticoids, epinephrine, theophylline, cromolyn sodium, anti-leukotrienes, anti- cholinergic drugs for rhinitis, TLR antagonists, inflammasome inhibitors, anti-cholinergic decongestants, mast-cell stabilizers, monoclonal anti-lgE antibodies, vaccines (e.g., vaccines used for vaccination where the amount of an allergen is gradually increased), cytokine inhibitors, such as ant i-IL-6 antibodies
  • the additional therapeutic agent is an RNA molecule, such as a double stranded RNA.
  • the additional therapeutic agent is an anti-sense oligonucleotide.
  • provided herein is a method of delivering a solid dosage form described herein to a subject.
  • the solid dosage form is administered in conjunction with the administration of an additional therapeutic agent.
  • the solid dosage form comprises a pharmaceutical agent co-fonnulated with the additional therapeutic agent.
  • the solid dosage form is co-administered with the additional therapeutic agent.
  • the additional therapeutic agent is administered to the subject before administration of the solid dosage form (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 2.0, 25, 30, 35, 40, 45, 50 or 55 minutes before, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours before, or about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13 or 14 days before).
  • the solid dosage form e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 2.0, 25, 30, 35, 40, 45, 50 or 55 minutes before, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours before, or about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13 or 14 days before.
  • the additional therapeutic agent is administered to the subject after administration of the solid dosage form (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes after, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours after, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days after).
  • the same mode of delivery' is used to deliver both the solid dosage form and the additional therapeutic agent.
  • different modes of delivery are used to administer the solid dosage form and the additional therapeutic agent.
  • the solid dosage form is administered orally while the additional therapeutic agent is administered via injection (e.g., an intravenous and/or intramuscular).
  • the dosage regimen can be any of a variety of methods and amounts, and can be determined by one skilled in the art according to known clinical factors. As is known in the medical arts, dosages for any one patient can depend on many factors, including the subject's species, size, body surface area, age, sex, immunocompetence, and general health, the particular microorganism to be administered, duration and route of administration, the kind and stage of the disease, and other compounds such as drugs being administered concurrently or near-concurrently . In addition to the above factors, such levels can be affected by the infectivity' of the microorganism, and the nature of the microorganism, as can be determined by one skilled in the art.
  • appropriate minimum dosage levels of microorganisms can be levels sufficient for the microorganism to survive, grow and replicate.
  • the dose of a pharmaceutical agent (e.g., in a solid dosage form) described herein may be appropriately set or adjusted in accordance with the dosage form, the route of administration, the degree or stage of a target disease, and the like.
  • the general effective dose of the agents may range between 0.01 rng/kg body weight/day and 1000 mg/kg body weight/day, between 0.1 mg/kg body weight/day and 1000 mg/kg body weight/day, 0.5 mg/kg body weight/day and 500 mg/kg body weight/day, 1 mg/kg body weight/day and 100 mg/kg body weight/day, or between 5 mg/kg body weight/day and 50 mg/kg body weight/day.
  • the effective dose may be 0.01, 0.05, 0.1, 0.5, I, 2, 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500, or 1000 mg/kg body weight/day or more, but the dose is not limited thereto.
  • the dose administered to a subject is sufficient to prevent disease (e.g., autoimmune disease, inflammatory disease, or metabolic disease), delay its onset, or slow or stop its progression, or relieve one or more symptoms of the disease.
  • disease e.g., autoimmune disease, inflammatory disease, or metabolic disease
  • dosage will depend upon a variety of factors including the strength of the particular agent (e.g., pharmaceutical agent) employed, as well as the age, species, condition, and body weight of the subject.
  • the size of the dose will also be determined by the route, timing, and frequency of administration as well as the existence, nature, and extent of any adverse side-effects that might accompany the administration of a particular pharmaceutical agent and the desired physiological effect.
  • Suitable doses and dosage regimens can be determined by conventional range-finding techniques known to those of ordinary skill in the art. Generally, treatment is initiated with smaller dosages, which are no more than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached.
  • An effective dosage and treatment protocol can be determined by routine and conventional means, starting e.g., with a low dose in laboratory animals and then increasing the dosage while monitoring the effects, and systematically varying the dosage regimen as well. Animal studies are commonly used to determine the maximal tolerable dose ("MTD”) of bioactive agent per kilogram weight. Those skilled m the art regularly extrapolate doses for efficacy, while avoiding toxicity, in other species, including humans.
  • MTD maximal tolerable dose
  • the dosages of the pharmaceutical agents used in accordance with the invention vary depending on the active agent, the age, weight, and clinical condition of the recipient patient, and the experience and judgment of the clinician or practitioner administering the therapy, among other factors affecting the selected dosage.
  • the dose should be sufficient to result in slowing of progression of the disease for which the subject is being treated, and preferably amelioration of one or more symptoms of the disease for which the subject is being treated.
  • Separate administrations can include any number of two or more administrations, including two, three, four, five or six administrations.
  • One skilled in the art can readily determine the number of administrations to perform or the desirability of performing one or more additional administrations according to methods known in the art for monitoring therapeutic methods and other monitoring methods provided herein.
  • the methods provided herein include methods of providing to the subject one or more administrations of a solid dosage form, where the number of administrations can be determined by monitoring the subject, and, based on the results of the monitoring, determining whether or not to provide one or more additional administrations. Deciding on whether or not to provide one or more additional administrations can be based on a variety of monitoring results,
  • the time period between administrations can be any of a variety of time periods.
  • the time period between administrations can be a function of any of a variety of factors, including monitoring steps, as described in relation to the number of administrations, the time period for a subject to mount an immune response.
  • the time period can be a function of the time period for a subject to mount an immune response; for example, the time period can be more than the time period for a subject to mount an immune response, such as more than about one week, more than about ten days, more than about two weeks, or more than about a month; in another example, the time period can be no more than tire time period for a subject to mount an immune response, such as no more than about one week, no more than about ten days, no more than about two weeks, or no more than about a month.
  • the delivery of an additional therapeutic agent in combination with the solid dosage form described herein reduces the adverse effects and/or improves the efficacy of the additional therapeutic agent.
  • Tire effective dose of an additional therapeutic agent described herein is the amount of tire additional therapeutic agent that is effective to achieve the desired therapeutic response for a particular subject, composition, and mode of administration, with the least toxicity to the subject.
  • the effective dosage level can be identified using the methods described herein and will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions or agents administered, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employ ed, the age, sex, weight, condition, general health and prior medical history of the subject being treated, and like factors well known in the medical arts.
  • an effective dose of an additional therapeutic agent will be the amount of the additional therapeutic agent which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above.
  • the toxicity of an additional therapeutic agent is the level of adverse effects experienced by the subject during and following treatment.
  • Adverse events associated with additional therapy toxicity can include, but are not limited to, abdominal pain, acid indigestion, acid reflux, allergic reactions, alopecia, anaphylaxis, anemia, anxiety, lack of appetite, arthralgias, asthenia, ataxia, azotemia, loss of balance, bone pain, bleeding, blood clots, low blood pressure, elevated blood pressure, difficulty breathing, bronchitis, bruising, low white blood cell count, low red blood cell count, low platelet count, cardio toxicity, cystitis, hemorrhagic cystitis, arrhythmias, heart valve disease, cardiomyopathy, coronary artery' disease, cataracts, central neurotoxicity, cognitive impairment, confusion, conjunctivitis, constipation, coughing, cramping, cystitis, deep vein thrombosis, dehydration, depression, diarrhea, dizziness, dry mouth, dry skin, dyspeps
  • the methods and solid dosage forms described herein relate to the treatment or prevention of a disease or disorder associated a pathological immune response, such as an autoimmune disease, an allergic reaction and/or an inflammatory disease.
  • a disease or disorder associated a pathological immune response, such as an autoimmune disease, an allergic reaction and/or an inflammatory disease.
  • the disease or disorder is an inflammatory bowel disease (e.g., Crohn’s disease or ulcerative colitis).
  • the disease or disorder is psoriasis.
  • the disease or disorder is psoriatic arthritis.
  • the disease or disorder is atopic dermatitis.
  • a “subject in need thereof” includes any subject that has a disease or disorder associated with a pathological immune response (e.g., an inflammatory bowel disease), as w ell as any subject with an increased likelihood of acquiring a such a disease or disorder.
  • a pathological immune response e.g., an inflammatory bowel disease
  • the solid dosage forms described herein can be used, for example, as a pharmaceutical composition for preventing or treating (reducing, partially or completely, the adverse effects of) an autoimmune disease, such as chronic inflammatory bowel disease, systemic lupus erythematosus, psoriasis, muckle-wells syndrome, rheumatoid arthritis, multiple sclerosis, or Hashimoto's disease; an allergic disease, such as a food allergy, pollenosis, or asthma; an infectious disease, such as an infection with Clostridium difficile; an inflammatory disease such as a TNF-mediated inflammatory disease (e.g., an inflammatory disease of the gastrointestinal tract, such as pouchitis, a cardiovascular inflammatory condition, such as atherosclerosis, or an inflammatory lung disease, such as chronic obstructive pulmonary disease); a pharmaceutical composition for suppressing rejection in organ transplantation or other situations in which tissue rejection might occur; a supplement, food, or beverage for improving immune functions; or a reagent for suppressing the autoimmune disease
  • the methods and solid dosage forms provided herein are useful for the treatment of inflammation.
  • the inflammation of any tissue and organs of the body including musculoskeletal inflammation, vascular inflammation, neural inflammation, digestive system inflammation, ocular inflammation, inflammation of the reproductive system, and other inflammation, as discussed below.
  • Immune disorders of the musculoskeletal system include, but are not limited, to those conditions affecting skeletal joints, including joints of the hand, wrist, elbow, shoulderjaw, spine, neck, hip, knew, ankle, and foot, and conditions affecting tissues connecting muscles to bones such as tendons.
  • immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, arthritis (including, for example, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, acute and chronic infectious arthritis, arthritis associated with gout and pseudogout, and juvenile idiopathic arthritis), tendonitis, synovitis, tenosynovitis, bursitis, fibrositis (fibromyalgia), epicondylitis, myositis, and osteitis (including, for example, Paget's disease, osteitis pubis, and osteitis fibrosa cystic).
  • arthritis including, for example, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, acute and chronic infectious arthritis, arthritis associated with gout and pseudogout, and juvenile idiopathic arthritis
  • tendonitis synovitis, ten
  • Ocular immune disorders refers to a immune disorder that affects any structure of the eye, including the eye lids.
  • ocular immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, blepharitis, blepharochalasis, conjunctivitis, dacryoadenitis, keratitis, keratoconjunctivitis sicca (dry eye), scleritis, trichiasis, and uveitis.
  • Examples of nervous system immune disorders which may be treated with the methods and solid dosage forms described herein include, but are not limited to, encephalitis, Guillain-Barre syndrome, meningitis, neuromyotonia, narcolepsy, multiple sclerosis, myelitis and schizophrenia.
  • Examples of inflammation of the vasculature or lymphatic sy stem which may be treated with the methods and compositions described herein include, but are not limited to, arthrosclerosis, arthritis, phlebitis, vasculitis, and lymphangitis.
  • Examples of digestive system immune disorders which may be treated with the methods and solid dosage forms described herein include, but are not limited to, cholangitis, cholecystitis, enteritis, enterocolitis, gastritis, gastroenteritis, inflammatory bowel disease, ileitis, and proctitis.
  • Inflammatory bowel diseases include, for example, certain art- recognized forms of a group of related conditions.
  • Crohn's disease regional bowel disease, e.g., inactive and active forms
  • ulcerative colitis e.g., inactive and active forms
  • the inflammatory bowel disease encompasses irritable bowel syndrome, microscopic colitis, lymphocytic-plasmocytic enteritis, coeliac disease, collagenous colitis, lymphocytic colitis and eosinophilic enterocolitis.
  • Other less common forms of IBD include indeterminate colitis, pseudomembranous colitis (necrotizing colitis), ischemic inflammatory bowel disease, Behcet’s disease, sarcoidosis, scleroderma, IBD- associated dysplasia, dysplasia associated masses or lesions, and primary sclerosing cholangitis.
  • reproductive system immune disorders which may be treated with the methods and solid dosage forms described herein include, but are not limited to, cervicitis, chori oamnionitis, endometritis, epididymitis, omphalitis, oophoritis, orchitis, salpingitis, tubo-ovarian abscess, urethritis, vaginitis, vulvitis, and vulvodynia.
  • autoimmune conditions having an inflammatory’ component include, but are not limited to, acute disseminated alopecia uni versalise, Behcet's disease, Chagas' disease, chronic fatigue syndrome, dysautonornia, encephalomyelitis, ankylosing spondylitis, aplastic anemia, hidradenitis suppurativa, autoimmune hepatitis, autoimmune oophoritis, celiac disease, Crohn's disease, diabetes mellitus type 1, giant cell arteritis, Goodpasture's syndrome, Grave's disease, Guillain-Barre syndrome, Hashimoto's disease, Henoch- Schonlein purpura, Kawasaki's disease, lupus erythematosus, microscopic colitis, microscopic polyarteritis, mixed connective tissue disease, Muckle-Wells syndrome, multiple sclerosis, myasthenia
  • T-cell mediated hypersensitivity diseases having an inflammatory component.
  • Such conditions include, but are not limited to, contact hypersensitivity, contact dermatitis (including that due to poison ivy), uticaria, skin allergies, respiratory allergies (hay fever, allergic rhinitis, house dustmite allergy) and gluten-sensitive enteropathy (Celiac disease).
  • immune disorders which may be treated with the methods and solid dosage forms include, for example, appendicitis, dermatitis, dermatomyositis, endocarditis, fibrositis, gingivitis, glossitis, hepatitis, hidradenitis suppurativa, ulceris, laryngitis, mastitis, myocarditis, nephritis, otitis, pancreatitis, parotitis, percarditis, peritonoitis, pharyngitis, pleuritis, pneumonitis, prostatistis, pyelonephritis, and stomatisi, transplant rejection (involving organs such as kidney, liver, heart, lung, pancreas (e.g., islet cells), bone marrow, cornea, small bowel, skin allografts, skin homografts, and heart valve xengrafts, sewrum sickness, and graft v
  • Preferred treatments include treatment of transplant rejection, rheumatoid arthritis, psoriatic arthritis, multiple sclerosis, Type 1 diabetes, asthma, inflammatory bowel disease, systemic lupus erythematosus, psoriasis, chronic obstructive pulmonary' disease, and inflammation accompanying infectious conditions (e.g., sepsis).
  • Metabolic Disorders include treatment of transplant rejection, rheumatoid arthritis, psoriatic arthritis, multiple sclerosis, Type 1 diabetes, asthma, inflammatory bowel disease, systemic lupus erythematosus, psoriasis, chronic obstructive pulmonary' disease, and inflammation accompanying infectious conditions (e.g., sepsis).
  • the methods and solid dosage forms described herein relate to the treatment or prevention of a metabolic disease or disorder a, such as type II diabetes, impaired glucose tolerance, insulin resistance, obesity, hyperglycemia, hyperinsulinemia, fatty' liver, non-alcoholic steatohepatitis, hypercholesterolemia, hypertension, hyperlipoproteinemia, hyperlipidemia, hypertriglylceridemia, ketoacidosis, hypoglycemia, thrombotic disorders, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), Nonalcoholic Steatohepatitis (NASH) or a related disease.
  • a metabolic disease or disorder a such as type II diabetes, impaired glucose tolerance, insulin resistance, obesity, hyperglycemia, hyperinsulinemia, fatty' liver, non-alcoholic steatohepatitis, hypercholesterolemia, hypertension, hyperlipoproteinemia, hyperlipidemia, hypertriglylceridemia, ketoacidosis, hypoglycemia, thrombotic disorders, dyslipidemia, non-
  • the related disease is cardiovascular disease, atherosclerosis, kidney disease, nephropathy, diabetic neuropathy, diabetic retinopathy, sexual dysfunction, dermatopathy, dyspepsia, or edema.
  • the methods and pharmaceutical compositions described herein relate to the treatment of Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH).
  • NAFLD Nonalcoholic Fatty Liver Disease
  • NASH Nonalcoholic Steatohepatitis
  • a “subject in need thereof’ includes any subject that has a metabolic disease or disorder, as well as any subject with an increased likelihood of acquiring a such a disease or disorder.
  • the solid dosage forms described herein can be used, for example, for preventing or treating (reducing, partially or completely, the adverse effects of) a metabolic disease, such as type II diabetes, impaired glucose tolerance, insulin resistance, obesity, hyperglycemia, hyperinsulinemia, fatty liver, non-alcoholic steatohepatitis, hypercholesterolemia, hypertension, hyperlipoproteinemia, hyperlipidemia, hypertriglylceridemia, ketoacidosis, hypoglycemia, thrombotic disorders, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), or a related disease.
  • the related disease is cardiovascular disease, atherosclerosis, kidney disease, nephropathy, diabetic neuropathy, diabetic retinopathy, sexual dysfunction, dermatopathy, dyspepsia, or edema.
  • the methods and solid dosage forms described herein relate to the treatment of liver diseases.
  • diseases include, but are not limited to, Alagille Syndrome, Alcohol -Related Liver Disease, Alpha- 1 Antitrypsin Deficiency, Autoimmune Hepatitis, Benign Liver Tumors, Bihary' Atresia, Cirrhosis, Galactosemia, Gilbert Syndrome, Hemochromatosis, Hepatitis A, Hepatitis B, Hepatitis C, Hepatic Encephalopathy, Intrahepatic Cholestasis of Pregnancy (ICP), Lysosomal Acid Lipase Deficiency (LAL-D), Liver Cysts, Liver Cancer, Newborn Jaundice, Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC), Reye Syndrome, Type I Glycogen Storage Disease, and Wilson Disease.
  • ICP Pregnancy
  • LAL-D Lysosomal Acid Lipase
  • the methods and solid dosage forms described herein may be used to treat neurodegenerative and neurological diseases.
  • the neurodegenerative and/or neurological disease is Parkinson’s disease, Alzheimer’s disease, prion diseas ⁇
  • Huntington s disease, motor neuron diseases (MND), spinocerebellar ataxia, spinal muscular atrophy, dystonia, idiopathicintracranial hypertension, epilepsy, nervous system disease, central nervous system disease, movement disorders, multiple sclerosis, encephalopathy, peripheral neuropathy or post-operative cognitive dysfunction.
  • MND motor neuron diseases
  • spinocerebellar ataxia spinal muscular atrophy
  • dystonia dystonia
  • idiopathicintracranial hypertension epilepsy
  • nervous system disease central nervous system disease
  • movement disorders multiple sclerosis
  • encephalopathy peripheral neuropathy or post-operative cognitive dysfunction.
  • gut microbiota also called the “gut microbiota”
  • gut microbiota can have a significant impact on an individual’s health through microbial activity and influence (local and/or distal) on immune and other cells of the host
  • a healthy host-gut microbiome homeostasis is sometimes referred to as a “eubiosis” or “normobiosis,” whereas a detrimental change in the host microbiome composition and/or its diversity can lead to an unhealthy imbalance in the microbiome, or a “dysbiosis” (Hooks and O’Malley . Dysbiosis and its discontents . American Society for Microbiology . Oct 2017. Vol. 8. Issue 5. mBio 8:e01492-17. https://doi.org/10.1128/mBio.01492-r7).
  • Dysbiosis, and associated local or distal host inflammatory or immune effects may occur where microbiome homeostasis is lost or diminished, resulting in: increased susceptibility to pathogens; altered host bacterial metabolic activity; induction of host proinflammatory activity and/or reduction of host anti-inflammatory activity.
  • Such effects are mediated in part by interactions between host immune cells (e.g., T cells, dendritic cells, mast cells, NK cells, intestinal epithelial lymphocytes (IEC), macrophages and phagocytes) and cytokines, and other substances released by such cells and other host cells.
  • host immune cells e.g., T cells, dendritic cells, mast cells, NK cells, intestinal epithelial lymphocytes (IEC), macrophages and phagocytes
  • a dysbiosis may occur within the gastrointestinal tract (a “gastrointestinal dysbiosis” or “gut dysbiosis”) or may occur outside the lumen of the gastrointestinal tract (a “distal dysbiosis”).
  • Gastrointestinal dysbiosis is often associated with a reduction in integrity of the intestinal epithelial barrier, reduced tight junction integrity and increased intestinal permeability.
  • Citi, S. Intestinal Barriers protect against disease, Science 359: 1098-99 (2016); Srinivasan et al., TEER measurement techniques for in vitro barrier model systems. J Lab. Autorn. 20: 107-126 (2015).
  • a gastrointestinal dysbiosis can have physiological and immune effects within and outside the gastrointestinal tract.
  • dysbiosis has been associated with a wide variety of diseases and conditions including: infection, cancer, autoimmune disorders (e.g., systemic lupus erythematosus (SLE)) or inflammatory disorders (e.g., functional gastrointestinal disorders such as inflammatory bowel disease (IBD), ulcerative colitis, and Crohn’s disease), neuroinflammatory diseases (e.g., multiple sclerosis), transplant disorders (e.g., graft-versus- host disease), fatty liver disease, type I diabetes, rheumatoid arthritis, Sjogren’s syndrome, celiac disease, cystic fibrosis, chronic obstructive pulmonary disorder (COPD), and other diseases and conditions associated with immune dysfunction.
  • autoimmune disorders e.g., systemic lupus erythematosus (SLE)
  • inflammatory disorders e.g., functional gastrointestinal disorders such as inflammatory bowel disease (IBD), ulcerative colitis, and Crohn’s disease
  • neuroinflammatory diseases e.g.
  • compositions e.g., solid dosage forms
  • such compositions can modify a dysbiosis via effects on host immune cells, resulting in, e.g., an increase in secretion of anti-inflammatory cytokines and/or a decrease in secretion of pro-inflammatory cytokines, reducing inflammation in the subject recipient or via changes in metabolite production.
  • compositions e.g., solid dosage forms
  • immunomodulatory bacteria e.g., anti-inflammatory bacteria
  • Such compositions are capable of affecting the recipient host’s immune function, in the gastrointestinal tract, and/or a systemic effect at distal sites outside the subject’s gastrointestinal tract.
  • compositions e.g., solid dosage forms
  • a population of immunomodulatory' bacteria of a single bacterial species e.g., a single strain
  • Such compositions are capable of affecting the recipient host’s immune function, in the gastrointestinal tract, and /or a systemic effect at distal sites outside the subject’s gastrointestinal tract.
  • compositions containing an isolated population of Prevotella histicola bacteria are administered (e.g., orally) to a mammalian recipient in an amount effective to treat a dysbiosis and one or more of its effects in the recipient.
  • the dysbiosis may be a gastrointestinal tract dysbiosis or a distal dysbiosis.
  • compositions e.g., solid dosage forms
  • the pharmaceutical compositions can treat a gastrointestinal dysbiosis and one or more of its effects by modulating the recipient immune response via cellular and cytokine modulation to reduce gut permeability by increasing the integrity of the intestinal epithelial barrier.
  • compositions e.g,, solid dosage forms
  • compositions are useful for treatment of disorders associated with a dysbiosis, which compositions contain one or more types of bacteria capable of altering the relative proportions of host immune cell subpopulations, e.g., subpopulations of T cells, immune lymphoid cells, dendritic cells, NK cells and other immune cells, or the function thereof, in the recipient.
  • host immune cell subpopulations e.g., subpopulations of T cells, immune lymphoid cells, dendritic cells, NK cells and other immune cells, or the function thereof, in the recipient.
  • compositions are useful for treatment of disorders associated with a dysbiosis, which compositions contain a population of immunomodulatory bacteria of a single bacterial species e.g., a single strain) capable of altering the relative proportions of immune cell subpopulations, e.g., T cell subpopulations, immune lymphoid cells, NK cells and other immune cells, or the function thereof, in the recipient subject.
  • a population of immunomodulatory bacteria of a single bacterial species e.g., a single strain
  • immune cell subpopulations e.g., T cell subpopulations, immune lymphoid cells, NK cells and other immune cells, or the function thereof, in the recipient subject.
  • the invention provides methods of treating a gastrointestinal dysbiosis and one or more of its effects by orally administering to a subject in need thereof a pharmaceutical composition which alters the microbiome population existing at the site of the dysbiosis.
  • the pharmaceutical composition can contain one or more types of immunomodulatory bacteria or a population of immunomodulatory bacteria of a single bacterial species (e.g., a single strain).
  • the invention provides methods of treating a distal dysbiosis and one or more of its effects by orally administering to a subject in need thereof a pharmaceutical composition (e.g., solid dosage forms) which alters the subject’s immune response outside the gastrointestinal tract.
  • a pharmaceutical composition e.g., solid dosage forms
  • the pharmaceutical composition can contain one or more topes of immunomodulatory bacteria or a population of immunomodulatory bacteria of a single bacterial species (e.g., a single strain).
  • compositions useful for treatment of disorders associated with a dysbiosis stimulate secretion of one or more anti-inflammatory cytokines by host immune cells.
  • Anti-inflammatory cytokines include, but are not limited to, IL-10, IL-13, IL-9, IL-4, IL-5, TGF ⁇ , and combinations thereof.
  • pharmaceutical compositions useful for treatment of disorders associated with a dysbiosis that decrease (e.g., inhibit) secretion of one or more pro-inflammatory cytokines by host immune cells.
  • Pro-inflammatory' cytokines include, but are not limited to, IFNy, IL- 12p70, IL-la, IL-6, IL-8, MCP1, MIPla, MIP I ⁇ , TNFa, and combinations thereof.
  • Other exemplary' cytokines are known in the art and are described herein,
  • the invention provides a method of treating or preventing a disorder associated with a dysbiosis in a subject in need thereof, comprising administering (e.g., orally administering) to the subject a therapeutic composition in the form of a probiotic or medical food comprising bacteria an amount sufficient to alter the microbiome at a site of the dysbiosis, such that the disorder associated with the dysbiosis is treated.
  • a therapeutic composition of the instant invention in the form of a probiotic or medical food may be used to prevent or delay the onset of a dysbiosis in a subject at risk for developing a dysbiosis.
  • Inflammation can be a protective response to harmful stimuli, such as invading pathogens, damaged cells, toxic compounds, or cancerous cells.
  • harmful stimuli such as invading pathogens, damaged cells, toxic compounds, or cancerous cells.
  • excessive inflammatory responses to such stimuli can result in serious adverse effects, including tissue damage and even death.
  • pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin- 1 beta (IL- I ⁇ ), and tumor necrosis factor alpha (TNF ⁇ ) in response to many viral infections is one of the primary causes of the adverse symptoms associated with infection (including, in some cases, death).
  • inflammatory cytokines has been associated with disease severity resulting from infection by a number of viruses, including infection by coronaviruses (e.g, SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19)), influenza viruses, and respiratory' syncytial viruses.
  • coronaviruses e.g, SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19)
  • influenza viruses e.g., influenza viruses that causes Coronavirus Disease 2019 (COVID-19)
  • respiratory' syncytial viruses e.g, coronaviruses (e.g, SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19)
  • coronaviruses e.g, SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19)
  • influenza viruses e.g., influenza viruses that causes Coronavirus Disease 2019 (COVID-19)
  • respiratory' syncytial viruses e.g., influenza virus that
  • the methods and solid dosage forms described herein relate to the treatment or prevention of bacterial septic shock, cytokine storm and/or viral infection.
  • the methods and solid dosage forms described herein relate to the treatment or prevention of a viral infection such as a respiratory' viral infection, such as a coronavirus infection (e.g., a MERS (Middle East Respiratory Syndrome) infection, a severe acute respiratory' syndrome (SARS) infection, such as a SARS-CoV-2 infection), an influenza infection, and/or a respiratory' syncytial virus infection.
  • a viral infection such as a respiratory' viral infection
  • a coronavirus infection e.g., a MERS (Middle East Respiratory Syndrome) infection, a severe acute respiratory' syndrome (SARS) infection, such as a SARS-CoV-2 infection
  • SARS severe acute respiratory syndrome
  • the methods and solid dosage forms described herein provided herein are for the treatment, of a coronavirus infection (e.g., a MERS infection, a severe acute respiratory syndrome (SARS) infection, such as a SARS-CoV-2 infection).
  • provided herein are methods and solid dosage
  • the methods and solid dosage forms described herein relate to tiie treatment or prevention of a viral infection.
  • the infection is a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection.
  • the viral infection is a SARS-CoV-2 infection.
  • an additional therapy is administered to the subject.
  • the additional therapy comprises an antiviral medication.
  • the additional therapy comprises an antiviral medication such as ribavirin, neuraminidase inhibitor, protease inhibitor, recombinant interferons, antibodies, oseltamivir, zanamivir, peramivir or baloxavir marboxil.
  • the additional therapy comprises hydroxychloroquine and/or chloroquine.
  • tire additional therapy comprises remdesivir.
  • the additional therapy' comprises plasma from a subject who has recovered from infection by the same virus that is infecting the subject (e.g., plasma from a subject who has recovered from SARS-CoV-2 infection).
  • the additional therapy comprises an anti-inflammatory' agent such as NSAIDs or anti-inflammatory steroids.
  • the additional therapy' comprises dexamethasone.
  • the additional therapy comprises an antibody specific for IL-6 and/or the IL-6 receptor.
  • the additional therapy comprises tocilizumab (Actemra®).
  • the additional therapy comprises sarilumab (Kevzara®).
  • the additional therapy can comprise an anti-viral therapy.
  • the anti-viral therapy can comprise a nucleotide analog, such as rerndesivir, galidesivir or clevudine; a viral RNA polymerase inhibitor such as favipiravir or galidesivir; a protease inhibitor such as ritonavi r, darunavir, or danoprevir; an inhibitor of viral membrane fusion such as umifenovir; and/or anti-SARS-CoV-2 plasma.
  • the additional therapy can comprise an anti-inflammatory therapy.
  • the anti -inflammatory therapy can comprise a corticosteroid; sirolimus; anakmra; filamod; or an antibody.
  • the antibody can comprise a GMSF inhibitor, such as lenzilumab or gimsilurnab; an anti-ILl beta inhibitor such as canakinumab; an IL-6 inhibitor such as tocilizumab or siltuximab; an 1L-6R inhibitor such as sarilumab; and/or a CCR5 antagonist such as leronlimab.
  • the additional therapy can comprise a JAK inhibitor such as baricitinib, ruxolitinib, tofacitinib, and/or pacritinib.
  • a JAK inhibitor such as baricitinib, ruxolitinib, tofacitinib, and/or pacritinib.
  • the additional therapy can comprise a TLR7 agonist such as imiquimod or reisquimod.
  • the additional therapy can comprise a cell-based therapy.
  • the cell based therapy can comprise Remestemcel- L; bone marrow stem cell therapy, such as MultiStem or Bm-Allo-MSC; mesenchymal stromal cells; and/or adiopose derived mesenchymal stem cells such as AstroStem.
  • the additional therapy can comprise an ACE receptor inhibitor.
  • the additional therapy can comprise a regulator of tire Sigma 1 and/or Sigma 2 receptor.
  • cryoprotectant may contain, e.g., maltodextrin, sodium ascorbate, sodium glutamate, and/or calcium chloride.
  • a freeze drier e.g., operating in automated mode with defined cycle parameters. The freeze dried product is fed into a milling machine and tire resulting powder is collected.
  • Powders are stored (e.g,, in vacuum sealed bags) at 2-8 degrees C (e.g., at. 4 degrees
  • Powders are gamma-irradiated at 17.5 kGy radiation unit at ambient temperature.
  • Frozen biomasses are gamma-irradiated at 25 kGy radiation unit in the presence of dry ice.
  • Example 3 Preparation of a Tablet Comprising Prevotella histicola
  • the tablet is prepared as a 17.4mm x 7.1 mm tablet.
  • the tablet is enteric coated.
  • the tablet contains 3.2 x 10 11 TCC of Prevotella histicola Strain B (NRRL accession number B 50329).
  • Prevotella histicola strain referred to above has been deposited as Prevotella histicola Strain B (NRRL accession number B 50329).
  • Example 4 Preparation of a Solid Dosage Form comprising Prevotella histicola
  • Tablets according to the recipe in Table 2 were prepared. Tableting was performed and manufactured batches were first sub-coated with Opadry QX blue before top-coating for enteric release with Kollicoat MAE 1 OOP.
  • Table 2 Prevotella histicola Tablet Composition, 3.2x 10 11 cells/tablet
  • Prevotella histicola strain referred to above has been deposited as Prevotella histicola Strain B (NRRL accession number B 50329).
  • the target weight per tablet is 650 mg (dose strength 162.5mg).
  • Example 5 Preparation of a Tablet Comprising Prevotella histicola
  • Total coated tablet weight was 777 mg .
  • TCC Total Cell Count
  • TCC Total Cell Count
  • TCC Total cell count
  • TCC Total Cell Count
  • Total cell count (TCC) method using Fluorescence Microscopy by Quantom TxTM is developed and qualified for drug product release and stability studies along with coulter counter method. It counts fluorescence-stained microbial cells through fluorescence imaging and analysis to produce accurate and objective bacterial cell counts.
  • [331] 1. The water content of tablets prepared according to the recipe in Example 5 was assessed.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des procédés et des compositions associés à des formes posologiques solides qui facilitent l'administration orale de bactéries Prevotella histicola.
PCT/US2021/050886 2020-09-21 2021-09-17 Formes posologiques solides à profils de désintégration améliorés WO2022061123A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202063081108P 2020-09-21 2020-09-21
US63/081,108 2020-09-21
US202163161528P 2021-03-16 2021-03-16
US63/161,528 2021-03-16

Publications (1)

Publication Number Publication Date
WO2022061123A1 true WO2022061123A1 (fr) 2022-03-24

Family

ID=78135165

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2021/050886 WO2022061123A1 (fr) 2020-09-21 2021-09-17 Formes posologiques solides à profils de désintégration améliorés

Country Status (2)

Country Link
TW (1) TW202227111A (fr)
WO (1) WO2022061123A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023177875A1 (fr) 2022-03-17 2023-09-21 Evelo Biosciences, Inc. Procédés et compositions pour un test de contaminant anaérobie

Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4775536A (en) 1986-02-24 1988-10-04 Bristol-Myers Company Enteric coated tablet and process for making
US5047258A (en) 1989-07-14 1991-09-10 Sterling Drug Inc. Aqueous spray-coating process
US5292522A (en) 1989-06-20 1994-03-08 Rohm Gmbh Aqueous film coating agent for solid medicaments
US6555124B1 (en) 1996-08-01 2003-04-29 Basf Aktiengesellschaft Use of (meth)acrylic acid copolymers to increase the permeability of mucous membranes
US6623759B2 (en) 1996-06-28 2003-09-23 Astrazeneca Ab Stable drug form for oral administration with benzimidazole derivatives as active ingredient and process for the preparation thereof
US6638534B1 (en) 1998-07-28 2003-10-28 Tanabe Seiyaku Co., Ltd. Preparation capable of releasing drug at target site in intestine
US20040028737A1 (en) 2002-08-12 2004-02-12 Kopran Research Laboratories Limited Enteric coated stable oral pharmaceutical composition of acid unstable drug and process for preparing the same
WO2005044240A2 (fr) 2003-10-31 2005-05-19 Dexcel, Ltd. Formulation stable contenant du lansoprazole
US20050271778A1 (en) 2002-12-20 2005-12-08 Roehm Gmbh & Co., Kg Method for producing coated pharmaceuticals and food supplements with concentration gradients in the coating thereof
US20060210631A1 (en) 2005-03-21 2006-09-21 Patel Ashish A Multi-particulate, modified-release composition
US20080200482A1 (en) 2005-07-12 2008-08-21 Evonik Roehm Gmbh Use of a Partially Neutralized, Anionic (Meth)Acrylate Copolymer as a Coating for the Production of a Medicament Releasing Active Substance at Reduced Ph Values
WO2012085043A2 (fr) * 2010-12-22 2012-06-28 Basf Se Forme pharmaceutique solide enrobée à désagrégation rapide
JP5204976B2 (ja) * 2006-01-27 2013-06-05 富山化学工業株式会社 イグラチモドを含有する速崩壊性錠剤
US9233074B2 (en) 2013-03-01 2016-01-12 Bpsi Holdings, Llc Delayed release film coatings containing calcium silicate and substrates coated therewith
WO2019051380A1 (fr) * 2017-09-08 2019-03-14 Evelo Biosciences, Inc. Vésicules extracellulaires (ev) bactériennes
US10555975B2 (en) * 2009-10-30 2020-02-11 Mayo Foundation For Medical Education And Research Prevotella histicola preparations and the treatment of autoimmune conditions

Patent Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4775536A (en) 1986-02-24 1988-10-04 Bristol-Myers Company Enteric coated tablet and process for making
US5292522A (en) 1989-06-20 1994-03-08 Rohm Gmbh Aqueous film coating agent for solid medicaments
US5047258A (en) 1989-07-14 1991-09-10 Sterling Drug Inc. Aqueous spray-coating process
US6623759B2 (en) 1996-06-28 2003-09-23 Astrazeneca Ab Stable drug form for oral administration with benzimidazole derivatives as active ingredient and process for the preparation thereof
US6555124B1 (en) 1996-08-01 2003-04-29 Basf Aktiengesellschaft Use of (meth)acrylic acid copolymers to increase the permeability of mucous membranes
US6638534B1 (en) 1998-07-28 2003-10-28 Tanabe Seiyaku Co., Ltd. Preparation capable of releasing drug at target site in intestine
US20040028737A1 (en) 2002-08-12 2004-02-12 Kopran Research Laboratories Limited Enteric coated stable oral pharmaceutical composition of acid unstable drug and process for preparing the same
US20050271778A1 (en) 2002-12-20 2005-12-08 Roehm Gmbh & Co., Kg Method for producing coated pharmaceuticals and food supplements with concentration gradients in the coating thereof
WO2005044240A2 (fr) 2003-10-31 2005-05-19 Dexcel, Ltd. Formulation stable contenant du lansoprazole
US20060210631A1 (en) 2005-03-21 2006-09-21 Patel Ashish A Multi-particulate, modified-release composition
US20080200482A1 (en) 2005-07-12 2008-08-21 Evonik Roehm Gmbh Use of a Partially Neutralized, Anionic (Meth)Acrylate Copolymer as a Coating for the Production of a Medicament Releasing Active Substance at Reduced Ph Values
JP5204976B2 (ja) * 2006-01-27 2013-06-05 富山化学工業株式会社 イグラチモドを含有する速崩壊性錠剤
US10555975B2 (en) * 2009-10-30 2020-02-11 Mayo Foundation For Medical Education And Research Prevotella histicola preparations and the treatment of autoimmune conditions
WO2012085043A2 (fr) * 2010-12-22 2012-06-28 Basf Se Forme pharmaceutique solide enrobée à désagrégation rapide
US9233074B2 (en) 2013-03-01 2016-01-12 Bpsi Holdings, Llc Delayed release film coatings containing calcium silicate and substrates coated therewith
WO2019051380A1 (fr) * 2017-09-08 2019-03-14 Evelo Biosciences, Inc. Vésicules extracellulaires (ev) bactériennes

Non-Patent Citations (19)

* Cited by examiner, † Cited by third party
Title
"Guide to Huge Computers", 1994, ACADEMIC PRESS
"Handbook of Pharmaceutical Excipients", 2009, PHARMACEUTICAL PRESS AND AMERICAN PHARMACISTS ASSOCIATION
ACHTMAN M.WAGNER M.: "Microbial diversity and the genetic nature of microbial species", NAT. REV. MICROBIOL., vol. 6, 2008, pages 431 - 440, XP037115178, DOI: 10.1038/nrmicro1872
ATSCHUL, S. F. ET AL., J MOLEC BIOL, vol. 215, 1990, pages 403
CARDING ET AL.: "Dysbiosis of the gut microbiota in disease", MICROB. ECOL. HEALTH DIS., vol. 26, no. 10, 2015, pages 3402
CARILLO ET AL., SIAM J APPLIED MADI, vol. 48, 1988, pages 1073
CITI, S: "Intestinal Barriers protect against disease", SCIENCE, vol. 359, 2018, pages 1098 - 99
CLAESSON MJWANG QO.SULLIVANO. GREENE-DINIZ RCOLE JRROSS RPO'TOOLE PW: "Comparison of two next-generation sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions", NUCLEIC ACIDS RES, vol. 38, 2010, pages e200, XP055250083, DOI: 10.1093/nar/gkq873
DEVEREUX. J., NUCLEIC ACIDS RESEARCH, vol. 12, no. 1, 1984, pages 387
HOOKSO'MALLEY: "Dysbiosis and its discontents", AMERICAN SOCIETY FOR MICROBIOLOGY, vol. 8, no. 8, October 2017 (2017-10-01), pages e01492 - 17, Retrieved from the Internet <URL:https://doi.org/i0!i28/mBio0!492-t7>
KONSTANTINIDIS KTRAMETTE ATIEDJE JM: "The bacterial species definition in the genomic era", PHILOS TRANS R SOC LOND B BIOL SCI, vol. 361, 2006, pages 1929 - 1940
LEEKHA ET AL.: "General Principles of Antimicrobial Therapy", MAYO CLIN PROC, vol. 86, no. 2, 2011, pages 156 - 167, XP055372896, DOI: 10.4065/mcp.2010.0639
LEVY ET AL.: "Dysbiosis and the Immune System", NATURE REVIEWS IMMUNOLOGY, vol. 17, no. 219, April 2017 (2017-04-01), pages 1280
LYNCH ET AL.: "The Human Microbiome in Health and Disease", N. ENGL. J. MED ., vol. 375, 2016, pages 2369 - 79
PEARSON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 85, 1988, pages 2444
SCHOCH ET AL.: "Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi", PNAS, vol. 1, no. 09, 2012, pages 6241 - 6246
SRINIVASAN ET AL.: "TEER measurement techniques for in vitro barrier model systems", J. LAB. AL/TOM., vol. 20, 2015, pages 107 - 126, XP055560328, DOI: 10.1177/2211068214561025
WALKER. W.A.: "The Microbiota in Gastrointestinal Pathophysiology", 2017, article "Dysbiosis"
WEISSTHIERRY: "Mechanisms and consequences of intestinal dysbiosis", CELLULAR AND MOLECULAR LIFE SCIENCES, vol. 74, no. 16, 2017, pages 2959 - 2977, XP036272294, DOI: 10.1007/s00018-017-2509-x

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023177875A1 (fr) 2022-03-17 2023-09-21 Evelo Biosciences, Inc. Procédés et compositions pour un test de contaminant anaérobie

Also Published As

Publication number Publication date
TW202227111A (zh) 2022-07-16

Similar Documents

Publication Publication Date Title
CA3143994A1 (fr) Compositions et procedes de traitement d&#39;une affection mediee par th2 a l&#39;aide de prevotella
WO2021146523A1 (fr) Formes posologiques solides à profils de désintégration améliorés
WO2022187064A1 (fr) Compositions et procédés de traitement d&#39;une inflammation à l&#39;aide de prevotella histicola
TW202228653A (zh) 細菌之固體劑型
WO2022061141A1 (fr) Compositions et méthodes de traitement d&#39;une inflammation à l&#39;aide de prevotella histicola
CN115551486A (zh) 具有改善的崩解谱的固体剂型
WO2022061123A1 (fr) Formes posologiques solides à profils de désintégration améliorés
EP4185276A1 (fr) Souche c de prevotella histicola en tant que thérapie orale contre des maladies inflammatoires
WO2021142279A1 (fr) Compositions et procédés de traitement à l&#39;aide de veillonella parvula
EP4284400A1 (fr) Préparations de vésicules extracellulaires de prevotella
TW202304415A (zh) 含有細菌的藥物製劑
TW202302125A (zh) 固體劑型
WO2023200837A1 (fr) Compositions et méthodes de traitement d&#39;une inflammation à l&#39;aide de prevotella histicola
WO2022020326A1 (fr) Souche de veillonella parvula en tant que thérapie orale pour des maladies neuro-inflammatoires
WO2022098961A1 (fr) Induction d&#39;effets immunitaires à l&#39;aide de bactéries veillonella parvula
US20240148797A1 (en) Compositions and methods for reducing cytokine expression
WO2022061119A1 (fr) Compositions et méthodes pour moduler des réponses immunitaires avec prevotella histicola
WO2023146843A1 (fr) Compositions de vésicules extracellulaires et méthodes d&#39;utilisation
WO2023150376A1 (fr) Compositions et procédés pour affecter des niveaux de cytokine à l&#39;aide de prevotella histicola
WO2023183396A1 (fr) Compositions et méthodes de traitement d&#39;une inflammation à l&#39;aide de prevotella histicola
WO2023239728A1 (fr) Compositions et méthodes de traitement d&#39;une inflammation à l&#39;aide de vésicules extracellulaires de prevotella histicola
CN117136065A (zh) 普雷沃菌属细胞外囊泡制剂
WO2022178209A1 (fr) Compositions et méthodes de traitement de maladies et de troubles métaboliques à l&#39;aide de bactéries christensenellaceae
TW202322787A (zh) 包含細菌和微生物胞外囊泡之固體劑型

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21791145

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21791145

Country of ref document: EP

Kind code of ref document: A1