IP Library Granted Patent US 9,725,466
Granted Patent B2
US 9,725,466 · App. 15/155,733 · Granted Aug 8, 2017

Rifaximin derivative and uses thereof

Inventors: Pam Golden (Durham, NC); Mohammed A. Kabir (Cary, NC); Giuseppe Claudio Viscomi (Bologna, IT); Manuela Campana (Bologna, IT); Donatella Confortini (Bologna, IT); Miriam Barbanti (Bologna, IT)
Assignees: Salix Pharmaceuticals, Ltd; Alfa Wassermann S.P.A.
C07D498/22A61K31/437A61K45/06C07D491/22
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Quick Facts
Patent No.
US 9,725,466
App. No.
15/155,733
Granted
Aug 8, 2017
Kind
B2
Abstract

25-desacetyl rifaximin or a pharmaceutically acceptable salt thereof is provided. Methods of treatment of bowl related disorders using isolated and/or purified 25-desacetyl rifaximin or a pharmaceutically acceptable salt thereof are also provided.

Claims (20)

1. A sodium, potassium, calcium, magnesium, ammonium, or chlorine pharmaceutically acceptable salt of 25-desacetyl rifaximin, wherein the 25-desacetyl rifaximin is of the formula:

2. A pharmaceutically acceptable acid addition salt of 25-desacetyl rifaximin, wherein the 25-desacetyl rifaximin is of the formula:

3. The pharmaceutically acceptable acid addition salt of claim 2 , wherein the acid addition salt is selected from hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydriodic, hydrofluoric, phosphorous, sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, acetate, trifluoroacetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinates suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzensoulfonate, toluenesulfonate, phenylacetate, citrate, lactate, maleate, tartrate, and methanesulfonate.

4. A pharmaceutically acceptable base addition salt of 25-desacetyl rifaximin, wherein the 25-desacetyl rifaximin is of the formula:

5. The pharmaceutically acceptable acid addition salt of claim 4 , wherein the base addition salt is selected from sodium, potassium, magnesium, and calcium.

6. A pharmaceutical composition comprising the pharmaceutically acceptable salt of 25-desacetyl rifaximin according to claim 1 ; and a pharmaceutically acceptable carrier.

7. A pharmaceutical composition comprising the pharmaceutically acceptable salt of 25-desacetyl rifaximin according to claim 2 ; and a pharmaceutically acceptable carrier.

8. A pharmaceutical composition comprising the pharmaceutically acceptable salt of 25-desacetyl rifaximin according to claim 4 ; and a pharmaceutically acceptable carrier.

9. A method for treating irritable bowel syndrome, travelers' diarrhea, small intestinal bacterial overgrowth, or hepatic encephalopathy, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutically acceptable salt of 25-desacetyl rifaximin according to claim 1 .

10. The method of claim 9 , wherein the traveler's diarrhea is caused by exposure to one or more enteric pathogens.

11. The method of claim 10 , wherein the one or more enteric pathogens is selected from Salmonella spp., Shigella spp., Campylobacter spp., Aeromonas, Plesiomonas, Vibro spp., Yersinia entercolitica, E. coli , Enterotoxigenic Escherichia coli (ETEC), E. coli 0157:H7 , C. difficile and H. pylori.

12. The method of claim 10 , wherein the enteric pathogens comprise one or more of a gram-positive bacteria, a gram-negative bacteria, an aerobic bacteria or an anaerobic bacteria.

13. A method for treating irritable bowel syndrome, travelers' diarrhea, small intestinal bacterial overgrowth, or hepatic encephalopathy, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutically acceptable salt of 25-desacetyl rifaximin according to claim 2 .

14. The method of claim 13 , wherein the traveler's diarrhea is caused by exposure to one or more enteric pathogens.

15. The method of claim 14 , wherein the one or more enteric pathogens is selected from Salmonella spp., Shigella spp., Campylobacter spp., Aeromonas, Plesiomonas, Vibro spp., Yersinia entercolitica, E. coli , Enterotoxigenic Escherichia coli (ETEC), E. coli 0157:H7 , C. difficile and H. pylori.

16. The method of claim 14 , wherein the enteric pathogens comprise one or more of a gram-positive bacteria, a gram-negative bacteria, an aerobic bacteria or an anaerobic bacteria.

17. A method for treating irritable bowel syndrome, travelers' diarrhea, small intestinal bacterial overgrowth, or hepatic encephalopathy, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutically acceptable salt of 25-desacetyl rifaximin according to claim 4 .

18. The method of claim 17 , wherein the traveler's diarrhea is caused by exposure to one or more enteric pathogens.

19. The method of claim 18 , wherein the one or more enteric pathogens is selected from Salmonella spp., Shigella spp., Campylobacter spp., Aeromonas, Plesiomonas, Vibro spp., Yersinia entercolitica, E. coli , Enterotoxigenic Escherichia coli (ETEC), E. coli 0157:H7 , C. difficile and H. pylori.

20. The method of claim 18 , wherein the enteric pathogens comprise one or more of a gram-positive bacteria, a gram-negative bacteria, an aerobic bacteria or an anaerobic bacteria.

Assignments (18)
RELEASE OF SECURITY INTEREST Recorded Nov 20, 2025
From: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
To: BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH AMERICAS, INC.
Reel/Frame 073654/0242 →
RELEASE OF SECURITY INTEREST Recorded Nov 20, 2025
From: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
To: ATON PHARMA, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH & LOMB PHARMA HOLDINGS CORP.; COMMONWEALTH LABORATORIES, LLC; DOW PHARMACEUTICAL SCIENCES, INC.; ECR PHARMACEUTICALS CO., INC.; LABORATOIRE CHAUVIN S.A.S.; MEDICIS PHARMACEUTICAL CORPORATION; ONPHARMA INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, LTD.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; SOLTA MEDICAL, INC.; SYNERGETICS USA, INC.; TECHNOLAS PERFECT VISION GMBH; VALEANT CANADA LP; VALEANT PHARMACEUTICALS INTERNATIONAL; VALEANT PHARMACEUTICALS INTERNATIONAL, INC.; VALEANT PHARMACEUTICALS NORTH AMERICA LLC; WIRRA IP PTY LIMITED; VALEANT PHARMA POLAND SP. Z O.O.; VALEANT PHARMACEUTICALS LUXEMBOURG S.A R.L.; VALEANT PHARMACEUTICALS IRELAND LIMITED
Reel/Frame 073637/0001 →
RELEASE OF SECURITY INTEREST Recorded Nov 20, 2025
From: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
To: BAUSCH HEALTH AMERICAS, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.
Reel/Frame 073637/0126 →
U.S. PATENT SECURITY AGREEMENT Recorded Jun 13, 2025
From: MEDICIS PHARMACEUTICAL CORPORATION; ORAPHARMA, INC.; BAUSCH HEALTH US, LLC (F/K/A VALEANT PHARMACEUTICALS NORTH AMERICA LLC); PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; BAUSCH HEALTH AMERICAS, INC.; SOLTA MEDICAL, INC.
To: JPMORGAN CHASE BANK, N.A.
Reel/Frame 071566/0200 →
U.S. PATENT SECURITY AGREEMENT Recorded Jun 13, 2025
From: MEDICIS PHARMACEUTICAL CORPORATION; ORAPHARMA, INC.; BAUSCH HEALTH US, LLC (F/K/A VALEANT PHARMACEUTICALS NORTH AMERICA LLC); PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; BAUSCH HEALTH AMERICAS, INC.; SOLTA MEDICAL, INC.
To: THE BANK OF NEW YORK MELLON
Reel/Frame 071564/0463 →
RELEASE OF SECURITY INTEREST Recorded Apr 8, 2025
From: BARCLAYS BANK PLC, AS COLLATERAL AGENT
To: SOLTA MEDICAL, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH IRELAND LIMITED (F/K/A/ VALEANT PHARMACEUTICALS IRELAND LIMITED); SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD; SANTARUS, INC.; MEDICIS PHARMACEUTICAL CORPORATION; HUMAX PHARMACEUTICAL S.A.; SOLTA MEDICAL IRELAND LIMITED; BAUSCH & LOMB MEXICO, S.A. DE C.V.; BAUSCH+LOMB OPS B.V.; BAUSCH HEALTH AMERICAS, INC.; BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH HOLDCO LIMITED; BAUSCH HEALTH MAGYARORSZAG KFT (A/K/A BAUSCH HEALTH HUNGARY LLC); BAUSCH HEALTH POLAND SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA (F/K/A VALEANT PHARMA POLAND SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA); BAUSCH HEALTH US, LLC; BAUSCH HEALTH, CANADA INC. / SANTE BAUSCH, CANADA INC.; ICN POLFA RZESZOW SPOLKA AKCYJNA (A/K/A ICN POLFA RZESZOW S.A.); ORAPHARMA, INC.; PRZEDSIEBIORSTWO FARMACEUTYCZNE JELFA SPOLKA AKCYJNA (A/K/A PRZEDSIEBIORSTWO FARMACEUTYCZNE JELFA S.A.); SOLTA MEDICAL DUTCH HOLDINGS B.V.; V-BAC HOLDING CORP.; VRX HOLDCO LLC; 1261229 B.C. LTD.; 1530065 B.C. LTD.
Reel/Frame 070778/0199 →
SECURITY AGREEMENT (SECOND LIEN) Recorded Oct 5, 2022
From: BAUSCH HEALTH US, LLC; BAUSCH HEALTH AMERICAS, INC.; MEDICIS PHARMACEUTICAL CORPORATION; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; SOLTA MEDICAL, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 061606/0468 →
SECURITY AGREEMENT (FIRST LIEN) Recorded Oct 4, 2022
From: BAUSCH HEALTH US, LLC; BAUSCH HEALTH AMERICAS, INC.; MEDICIS PHARMACEUTICAL CORPORATION; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; SOLTA MEDICAL, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 061595/0066 →
SECURITY AGREEMENT Recorded Feb 10, 2022
From: BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH AMERICAS, INC.
To: THE BANK OF NEW YORK MELLON
Reel/Frame 059121/0001 →
SECURITY INTEREST Recorded Jun 8, 2021
From: BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH AMERICAS, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 056811/0814 →
CHANGE OF ADDRESS Recorded Oct 15, 2019
From: ALFASIGMA S.P.A.
To: ALFASIGMA S.P.A.
Reel/Frame 050727/0652 →
SECURITY INTEREST Recorded Mar 11, 2019
From: BAUSCH HEALTH AMERICAS, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 048556/0758 →
SECURITY INTEREST Recorded Feb 26, 2018
From: ATON PHARMA, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH & LOMB PHARMA HOLDINGS CORP.; COMMONWEALTH LABORATORIES, LLC; DOW PHARMACEUTICAL SCIENCES, INC.; ECR PHARMACEUTICALS CO., INC.; LABORATOIRE CHAUVIN S.A.S.; MEDICIS PHARMACEUTICAL CORPORATION; ONPHARMA INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, LTD.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; SOLTA MEDICAL, INC.; SYNERGETICS USA, INC.; TECHNOLAS PERFECT VISION GMBH; VALEANT CANADA LP; VALEANT PHARMACEUTICALS INTERNATIONAL; VALEANT PHARMACEUTICALS INTERNATIONAL, INC.; VALEANT PHARMACEUTICALS NORTH AMERICA LLC; WIRRA IP PTY LIMITED; VALEANT PHARMA POLAND SP. Z O.O.; VALEANT PHARMACEUTICALS LUXEMBOURG S.A R.L.; VALEANT PHARMACEUTICALS IRELAND LIMITED
To: THE BANK OF NEW YORK MELLON, AS COLLATERAL AGENT
Reel/Frame 045444/0634 →
SECURITY INTEREST Recorded Feb 26, 2018
From: ATON PHARMA, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH & LOMB PHARMA HOLDINGS CORP.; COMMONWEALTH LABORATORIES, LLC; DOW PHARMACEUTICAL SCIENCES, INC.; ECR PHARMACEUTICALS CO., INC.; LABORATOIRE CHAUVIN S.A.S.; MEDICIS PHARMACEUTICAL CORPORATION; ONPHARMA INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, LTD.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; SOLTA MEDICAL, INC.; SYNERGETICS USA, INC.; TECHNOLAS PERFECT VISION GMBH; VALEANT CANADA LP; VALEANT PHARMACEUTICALS INTERNATIONAL; VALEANT PHARMACEUTICALS INTERNATIONAL, INC.; VALEANT PHARMACEUTICALS NORTH AMERICA LLC; WIRRA IP PTY LIMITED; VALEANT PHARMA POLAND SP. Z O.O.; VALEANT PHARMACEUTICALS LUXEMBOURG S.A R.L.; VALEANT PHARMACEUTICALS IRELAND LIMITED
To: BARCLAYS BANK PLC, AS COLLATERAL AGENT
Reel/Frame 045444/0299 →
MERGER Recorded Nov 14, 2017
From: ALFA WASSERMANN S.P.A.
To: ALFASIGMA S.P.A.
Reel/Frame 045061/0645 →
SECURITY AGREEMENT Recorded May 25, 2017
From: ALDEN OPTICAL LABORATORIES, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH & LOMB PHARMA HOLDINGS CORP.; DENDREON PHARMACEUTICALS, INC.; DOW PHARMACEUTICAL SCIENCES, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; SPROUT PHARMACEUTICALS, INC.; SYNERGETICS USA, INC.
To: BARCLAYS BANK PLC, AS COLLATERAL AGENT
Reel/Frame 042584/0861 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 18, 2016
From: VISCOMI, GIUSEPPE CLAUDIO; BARBANTI, MIRIAM; CAMPANA, MANUELA; CONFORTINI, DONATELLA
To: ALFA WASSERMAN S.P.A.
Reel/Frame 039472/0132 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 18, 2016
From: GOLDEN, PAM; KABIR, MOHAMMED A.
To: SALIX PHARMACEUTICALS, INC.
Reel/Frame 039472/0039 →
Continuity (5)
Continuation 14707858 · May 8, 2015
Continuation 14319060 · Jun 30, 2014
Continuation PCTUS2013023110 · Jan 25, 2013
Provisional Application 61590516 · Jan 25, 2012
Related Publication 20160257700A1 · Sep 8, 2016