IP Library Granted Patent US 9,273,066
Granted Patent B2
US 9,273,066 · App. 14/062,333 · Granted Mar 1, 2016

Forms of rifaximin and uses thereof

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Quick Facts
Patent No.
US 9,273,066
App. No.
14/062,333
Granted
Mar 1, 2016
Kind
B2
Abstract

The present invention relates to Rifaximin polymorphic forms, to their use in medicinal preparations and to therapeutic methods using them.

Claims (34)

1. A polymorphic Form ζ of rifaximin, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) comprising 4.69, 7.63, 12.52, 13.87.

2. The polymorph Form ζ of rifaximin of claim 1 , comprising an XRPD pattern as substantially depicted in FIG. 4 or FIG. 15 wherein peaks in the XRPD patterns have a variation of +/−0.2 theta.

3. A polymorphic Form η of rifaximin, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) comprising

6.1, 7.3, and 7.5 degrees 2-θ; or

6.1, 7.3, and 7.9 degrees 2-θ; or

5.3, 6.1, 7.3, 7.5, 8.8, and 12.7 degrees 2-θ.

4. A polymorphic Form ι of rifaximin, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) comprising

5.49, 5.88, 7.86, 9.03, 12.66, and 13.89; or

5.5, 5.9, 7.9, and 9.0; or

12.7, 13.9, and 14.9; or

5.5, 5.9, 7.9, and 12.7; or

5.5, 5.9, 9.0, and 12.7; or

5.9, 13.9, and 14.9; or

5.5, 5.9, 7.9, and 14.9; or

5.5, 9.0, 12.7, and 14.9; or

5.5, 5.9, 7.9, 9.0, and 14.9; or

5.5, 5.9, 7.9, 9.0, and 12.7; or

5.9, 7.9, 9.0, 12.7, 13.9, and 14.9.

5. The polymorph Form ι of rifaximin of claim 4 , comprising an XRPD pattern as substantially depicted in FIG. 3 or FIG. 9 wherein peaks in the XRPD patterns have a variation of +/−0.2 theta.

6. The polymorph Form ι of rifaximin of claim 4 , comprising thermal data as substantially depicted in FIG. 10 or proton NMR spectrum as substantially depicted in FIG. 12 or vapor data as substantially depicted in FIG. 11 or FT-IR spectrum as substantially depicted in FIG. 13 .

7. A polymorphic Form ι-dry of rifaximin, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ(+/−0.10 degree θ) comprising 6.04, 7.90, 8.92, 9.49, 12.76, and 14.14.

8. The polymorph Form ι-dry of rifaximin of claim 7 , comprising an XRPD pattern as substantially depicted in FIG. 1 or FIG. 6 or thermal data as substantially depicted in FIG. 7 .

9. A polymorphic Form ι-dry' of rifaximin, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ(+/−0.15 degree θ) comprising 6.16, 7.92, 8.89, 9.55, 12.80, and 14.25.

10. The polymorph Form ι-dry' of rifaximin of claim 9 , comprising an XRPD pattern as substantially depicted in FIG. 2 or FIG. 8 wherein peaks in the XRPD patterns have a variation of +/−0.15 theta.

11. The polymorph Form ι of claim 1 , wherein the polymorph comprises from between about 50 to about 100% pure polymorphous form before or after formulation, or from between about 75 to about 100% pure polymorphous form before or after formulation.

12. A pharmaceutical dosage form comprising the polymorphic Form ι of claim 1 .

13. The polymorph Form η of claim 3 , wherein the polymorph comprises from between about 50 to about 100% pure polymorphous form before or after formulation, or from between about 75 to about 100% pure polymorphous form before or after formulation.

14. A pharmaceutical dosage form comprising the polymorphic Form η of claim 3 .

15. The polymorph Form ι of claim 4 , wherein the polymorph comprises from between about 50 to about 100% pure polymorphous form before or after formulation, or from between about 75 to about 100% pure polymorphous form before or after formulation.

16. A pharmaceutical dosage form comprising the polymorphic Form ι of claim 4 .

17. The polymorph Form ι-dry of claim 7 , wherein the polymorph comprises from between about 50 to about 100% pure polymorphous form before or after formulation, or from between about 75 to about 100% pure polymorphous form before or after formulation.

18. A pharmaceutical dosage form comprising the polymorphic Form ι-dry of claim 7 .

19. The polymorph Form ι-dry' of claim 9 , wherein the polymorph comprises from between about 50 to about 100% pure polymorphous form before or after formulation, or from between about 75 to about 100% pure polymorphous form before or after formulation.

20. A pharmaceutical dosage form comprising the polymorphic Form ι-dry' of claim 9 .

Assignments (19)
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: THE BANK OF NEW YORK MELLON
Reel/Frame 071564/0463 →
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 →
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 →
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 →
SECURITY INTEREST Recorded Jul 19, 2017
From: SALIX PHARMACEUTICALS, LTD
To: THE BANK OF NEW YORK MELLON
Reel/Frame 043041/0880 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 19, 2016
From: APTUIT, INC.
To: SALIX PHARMACEUTICALS, LTD.
Reel/Frame 039763/0541 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2016
From: GUSHURST, KAREN S.; YANG, DONGLAI; ROE, MELANIE; SCHULTHEISS, NATHAN; VALHOVA, PETINKA; STULTS, JEFFREY S.; HOUSTON, TRAVIS L.
To: APTUIT, INC.
Reel/Frame 039653/0847 →
SECURITY AGREEMENT Recorded Apr 2, 2015
From: GLYCYX PHARMACEUTICALS, LTD.; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.
To: BARCLAYS BANK PLC, AS COLLATERAL AGENT
Reel/Frame 035364/0396 →
RELEASE OF SECURITY INTEREST Recorded Apr 1, 2015
From: JEFFERIES FINANCE LLC
To: SALIX PHARMACEUTICALS, LTD.
Reel/Frame 035353/0661 →
SECURITY AGREEMENT Recorded Jan 2, 2014
From: SALIX PHARMACEUTICALS, LTD.
To: JEFFERIES FINANCE LLC, AS COLLATERAL AGENT
Reel/Frame 031896/0752 →