IP Library › Granted Patent US 7,893,097
Granted Patent B2
US 7,893,097 · App. 12/012,413 · Granted Feb 22, 2011

Methods and compositions for increasing solubility of azole drug compounds that are poorly soluble in water

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Quick Facts
Patent No.
US 7,893,097
App. No.
12/012,413
Granted
Feb 22, 2011
Kind
B2
Abstract

The combination of any two of a polyol, a polyol ether, and a low carbon organic alcohol provides a synergistic effect on the solubility of azole compounds, such as metronidazole, in aqueous fluid.

Claims (29)

1. An aqueous solution comprising water at a concentration of about 55% w/w or higher, a poorly water-soluble imidazole or triazole chemical compound, and at least two of a polyol, a polyol ether, and a low carbon organic alcohol, wherein the at least two of a polyol, a polyol ether, and a low carbon organic alcohol are present in the aqueous solution in amounts sufficient to provide a synergistic effect on the solubility of the chemical compound in the aqueous solution.

2. The aqueous solution of claim 1 wherein the imidazole or triazole chemical compound is selected from the group consisting of metronidazole, ketoconazole, itraconazole, miconazole, dimetridazole, secnidazole, omidazole, tinidazole, carnidazole, and panidazole.

3. The aqueous solution of claim 2 wherein the chemical compound is metronidazole.

4. The aqueous solution of claim 1 which comprises a polyol and a polyol ether.

5. The aqueous solution of claim 1 which comprises a polyol and a low carbon organic alcohol.

6. The aqueous solution of claim 1 which comprises a polyol ether and a low carbon organic alcohol.

7. The aqueous solution of claim 1 which comprises a polyol, a polyol ether, and a low carbon organic alcohol.

8. The aqueous solution of claim 7 wherein the polyol is propylene glycol, the polyol ether is diethylene glycol monoethyl ether, and the low carbon organic alcohol is benzyl alcohol.

9. The aqueous solution of claim 1 wherein the polyol is selected from the group consisting of polyether glycol, propylene glycol, hexylene glycol, and sugar alcohol.

10. The aqueous solution of claim 9 wherein the polyol is propylene glycol.

11. The aqueous solution of claim 1 wherein the polyol ether is selected from the group consisting of diethylene glycol monoethyl ether, ethers of pentaerythritol, ethers of alkylene glycol, ethers of a fatty alcohol, and ethers of a sugar.

12. The aqueous solution of claim 11 wherein the polyol ether is diethylene glycol monoethyl ether.

13. The aqueous solution of claim 1 wherein the low carbon organic alcohols is selected from the group consisting of ethyl alcohol, propyl alcohol, phenol, and benzyl alcohol.

14. The aqueous solution of claim 1 wherein the polyol is propylene glycol, the polyol ether is diethylene glycol monoethyl ether, and the low carbon organic alcohol is benzyl alcohol.

15. The aqueous solution of claim 1 which is stable when stored for a period of two weeks at room temperature or for a period of one week or more at a temperature of 5° C.

16. A method for making an aqueous solution of a poorly water-soluble imidazole or triazole chemical compound comprising combining in an aqueous fluid the chemical compound and at least two of a polyol, a polyol ether, and a low carbon organic alcohol, wherein the at least two of a polyol, a polyol ether, and a low carbon organic alcohol are combined in the aqueous fluid in amounts sufficient to provide a synergistic effect on the solubility of the chemical compound in the aqueous fluid, and wherein the concentration of water in the aqueous fluid is about 55% w/w or higher.

17. The method of claim 16 wherein the imidazole or triazole chemical compound is selected from the group consisting of metronidazole, ketoconazole, itraconazole, miconazole, dimetridazole, secnidazole, ornidazole, tinidazole, carnidazole, and panidazole.

18. The method of claim 17 wherein the chemical compound is metronidazole.

19. The method of claim 16 wherein a polyol and a polyol ether are combined in the aqueous fluid.

20. The method of claim 16 wherein a polyol and a low carbon organic alcohol are combined in the aqueous fluid.

21. The method of claim 16 wherein a polyol ether and a low carbon organic alcohol are combined in the aqueous fluid.

22. The method of claim 16 wherein a polyol, a polyol ether, and a low carbon organic alcohol are combined in the aqueous fluid.

23. The method of claim 22 wherein the polyol is propylene glycol, the polyol ether is diethylene glycol monoethyl ether, and the low carbon organic alcohol is benzyl alcohol.

24. The method of claim 16 wherein the polyol is selected from the group consisting of polyether glycol, propylene glycol, and sugar alcohol.

25. The method of claim 24 wherein the polyol is propylene glycol.

26. The method of claim 16 wherein the polyol ether is selected from the group consisting of diethylene glycol monoethyl ether, ethers of pentaerythritol, ethers of alkylene glycol, ethers of a fatty alcohol, and ethers of a sugar.

27. The method of claim 26 wherein the polyol ether is diethylene glycol monoethyl ether.

28. The method of claim 16 wherein the low carbon organic alcohol is selected from the group consisting of ethyl alcohol, propyl alcohol, phenol, and benzyl alcohol.

29. The method of claim 16 wherein the polyol is propylene glycol, the polyol ether is diethylene glycol monoethyl ether, and the low carbon organic alcohol is benzyl alcohol.

Assignments (17)
U.S. PATENT SECURITY AGREEMENT Recorded Nov 25, 2025
From: BAUSCH HEALTH IRELAND LIMITED
To: JPMORGAN CHASE BANK, N.A.
Reel/Frame 073715/0375 →
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 →
RELEASE OF SECURITY INTEREST Recorded Nov 20, 2025
From: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
To: BAUSCH HEALTH IRELAND LIMITED; BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH, CANADA INC.; TECHNOLAS PERFECT VISION GMBH; VALEANT PHARMACEUTICALS LUXEMBOURG S.A R.L.; VALEANT PHARMA POLAND SPOLKA Z ORGANICZONA ODPOWIEDZIALNOSCIA; VALEANT SP. Z.O.O.
Reel/Frame 073637/0222 →
RELEASE OF SECURITY INTEREST Recorded Nov 20, 2025
From: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
To: BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH, CANADA INC.; BAUSCH HEALTH IRELAND LIMITED; SOLTA MEDICAL IRELAND LIMITED
Reel/Frame 073654/0300 →
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 Nov 4, 2022
From: BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH IRELAND LIMITED; SOLTA MEDICAL IRELAND LIMITED
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 062078/0276 →
SECURITY AGREEMENT (FIRST LIEN) Recorded Nov 4, 2022
From: BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH IRELAND LIMITED; SOLTA MEDICAL IRELAND LIMITED
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 061882/0708 →
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 INTEREST Recorded Jun 13, 2022
From: BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH, CANADA INC.; BAUSCH HEALTH IRELAND LIMITED; SOLTA MEDICAL IRELAND LIMITED
To: THE BANK OF NEW YORK MELLON
Reel/Frame 060346/0705 →
SECURITY INTEREST Recorded Oct 5, 2021
From: BAUSCH & LOMB IRELAND LIMITED; BAUSCH HEALTH COMPANIES INC.; DR. GERHARD MANN CHEM.-PHARM. FABRIK GMBH; TECHNOLAS PERFECT VISION GMBH
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 057821/0800 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 22, 2019
From: DOW PHARMACEUTICAL SCIENCES, INC.
To: BAUSCH HEALTH IRELAND LIMITED
Reel/Frame 050129/0705 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Jul 3, 2019
From: BAUSCH HEALTH IRELAND LIMITED; BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH, CANADA INC.; TECHNOLAS PERFECT VISION GMBH; VALEANT PHARMACEUTICALS LUXEMBOURG S.À R.L.; VALEANT PHARMA POLAND SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA; VALEANT SP. Z O. O.
To: THE BANK OF NEW YORK MELLON, AS COLLATERAL AGENT
Reel/Frame 049672/0652 →
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: BARCLAYS BANK PLC, AS COLLATERAL AGENT
Reel/Frame 045444/0299 →
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 →