Microbiome protection from oral antibiotics

Patent metadata

Field	Value
Publication number	US-11517614-B2
Application number	US-201716313488-A
Country	US
Kind code	B2
Filing date	Jun 28, 2017
Priority date	Jun 28, 2016
Publication date	Dec 6, 2022
Grant date	Dec 6, 2022

Abstract

This invention provides, in part, various compositions and methods for protecting the gastrointestinal microbiome from antibiotic disruption from orally administered antibiotics.

First claim

What is claimed is:

1. A method of protecting a subject's gastrointestinal (GI) microbiome from an oral antibiotic, comprising administering a formulation comprising a beta-lactamase capable of deactivating the oral antibiotic to a subject who is undergoing treatment or has recently undergone treatment with the oral antibiotic, wherein:
the formulation comprises an enterically coated capsule comprising an enterically coated pellet, the pellet comprising, relative to a pellet's weight:
about 20% to 25% sucrose sphere;
about 30% to 40% binder excipient;
about 12% to 18% beta-lactamase;
about 1% to 2% buffer salts;
about 0.5% to 3% plasticizer;
about 15% to 30% EUDRAGIT® (poly(methacrylic acid, methylmethacrylate) coating, and
optionally about 0.5% to about 1.5% KH 2 PO 4 and about 2.5% to 5% hydroxypropyl methylcellulose (HPMC) 603; and

the capsule is coated with FS EUDRAGIT® FS 30 D.

2. The method of claim 1 , wherein the EUDRAGIT® coating is selected from EUDRAGIT® FS 30 D or EUDRAGIT® S100.

3. The method of claim 1 , wherein:
the binder excipient is hydroxypropylcellulose (HPC); and/or
the beta-lactamase is selected from P1A, P2A, P3A, or P4A; and/or
the plasticizer is triethyl citrate.

4. The method of claim 3 , wherein the beta-lactamase is P3A.

5. The method of claim 1 , wherein the capsule is coated with FS EUDRAGIT® FS 30 D at about 10% of the total capsule weight.

6. The method of claim 1 , wherein the capsule has a body capacity of less than about 15 μL and is coated with FS EUDRAGIT® FS 30 D.

7. The method of claim 6 , wherein one or more capsules having body capacities of less than about 15 μL are loaded into a larger capsule.

8. The method of claim 1 , wherein the capsule further comprises a beta-lactamase inhibitor.

9. The method of claim 8 , wherein the beta-lactamase inhibitor is clavulanic acid.

10. The method of claim 1 , wherein the protection of the subject's microbiome comprises treatment or prevention of a microbiome-mediated disorder.

11. The method of claim 10 , wherein the microbiome-mediated disorder is selected from antibiotic-induced adverse effect, C. difficile infection (CDI), C. difficile -associated disease, ulcerative colitis, Crohn's disease, and irritable bowel syndrome.

12. The method of claim 11 , wherein the microbiome-mediated disorder is one or more of an antibiotic-induced adverse effect, C. difficile infection (CDI), and a C. difficile -associated disease.

13. The method of claim 12 , wherein the antibiotic-induced adverse effect, CDI, and/or C. difficile -associated disease is one or more of: antibiotic-associated diarrhea, C. difficile diarrhea (CDD), C. difficile intestinal inflammatory disease, colitis, pseudomembranous colitis, fever, abdominal pain, dehydration and disturbances in electrolytes, megacolon, peritonitis, and perforation and/or rupture of the colon.

14. The method of claim 1 , wherein the protection of the subject's microbiome comprises maintenance of a normal intestinal microbiota.

15. The method of claim 1 , wherein the method treats and/or prevents the overgrowth of one or more pathogenic microorganisms in the GI tract of a subject.

16. The method of claim 1 , wherein the method treats or prevents a nosocomial infection and/or a secondary emergent infection.

17. The method of claim 1 , wherein the beta-lactamase does not substantially interfere with plasma levels of a systemically absorbed orally administered antibiotic.

18. The method of claim 1 , wherein the beta-lactamase deactivates residual oral antibiotic residue excreted into the GI tract, wherein the residual oral antibiotic is not absorbed from the GI tract after an oral dose or is returned in active form to the intestinal tract from the systemic circulation.

19. The method of claim 1 , wherein the beta-lactamase is formulated for release in a location in the GI tract in which it does not substantially interfere with the systemic activity of the orally administered antibiotic.

20. The method of claim 1 , wherein the beta-lactamase is formulated for release in a location in the GI tract that is distal to the release of the orally administered antibiotic.

Assignees

• Synthetic Biologies Inc
• Synthetic Biologics Inc

Inventors

• Kaleko Michael
• Connelly Sheila

Classifications

• A61K38/50 Primary

  acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase · CPC title

• C12Y305/02006

  Beta-lactamase (3.5.2.6) · CPC title

• A61K9/5026

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K9/4866

  Organic macromolecular compounds · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title