IP Library Granted Patent US 8,546,364
Granted Patent B2
US 8,546,364 · App. 12/840,487 · Granted Oct 1, 2013

Stabilized steroid composition and method for its preparation

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Quick Facts
Patent No.
US 8,546,364
App. No.
12/840,487
Granted
Oct 1, 2013
Kind
B2
Abstract

Stabilized, 17-substituted hydrocortisone containing compositions and methods of manufacture are disclosed. Isomerization of the hydrocortisone component of topical steroid compositions is markedly reduced by including an omega-6 acid component in the form of a free acid or as a compound such as an ester. Specifically disclosed are methods for preventing the isomerization of hydrocortisone 17-butyrate into hydrocortisone 21-butyrate through the use of safflower oil.

Claims (45)

1. A composition of matter comprising:

(a) About 0.1% (w/w) hydrocortisone 17-butyrate;

(b) About 60% to about 80% (w/w) of a lipid system,

(i) Said lipid system comprising at least one omega-6 fatty acid or omega-6 acid ester;

(ii) Said lipid system comprising up to about 24% (w/w) of a fatty alcohol (and/or ester formable by condensing said fatty alcohol with a fatty acid);

(c) Quantum sufficit of water;

(d) Surfactant having a hydrophilic:lipophilic balance of less than about 12;

(i) said surfactant present in an amount sufficient to emulsify said lipid system and said water to form an emulsion suitable for topical application;

(ii) said emulsion having a pH of less than about 5;

(iii) said omega-6 acid or omega-6 acid ester present in an amount whereby said composition of matter contains not more than about 0.05% (w/w) of hydrocortisone 21-butyrate.

2. The composition of claim 1 , wherein said lipid system comprises not more than about 5% of the fatty alcohol and/or ester formable by condensing the fatty alcohol with a fatty acid.

3. The composition of claim 1 , wherein said lipid system comprises at least about 10% of the fatty alcohol and/or ester formable by condensing the fatty alcohol with a fatty acid.

4. The composition of claim 1 , said emulsion selected from the group consisting of: an oil-in-water emulsion; a water-in-oil emulsion; and a complex emulsion.

5. The composition of claim 4 , wherein said emulsion comprises an oil-in-water emulsion.

6. The composition of claim 4 , wherein said emulsion comprises a complex emulsion.

7. The composition of claim 1 , wherein said surfactant comprises a surfactant system comprised of at least two surfactants, wherein said surfactant system has a hydrophilic:lipophilic balance of less than about 14.

8. The composition of claim 1 , wherein said Omega-6 acid or omega-6 acid ester comprises safflower oil.

9. The composition of claim 1 , wherein said composition contains not more than about 0.02% (w/w) of hydrocortisone 21-butyrate.

10. A composition of matter comprising:

(a) Hydrocortisone 17-butyrate in an amount sufficient to treat the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses;

(b) About 60% to about 80% (w/w) of a lipid system,

(i) Said lipid system comprising at least one omega-6 fatty acid or omega-6 acid ester;

(ii) Said lipid system comprising up to about 24% (w/w) of a fatty alcohol (and/or ester formable by condensing said fatty alcohol with a fatty acid);

(c) Quantum sufficit of water;

(d) Surfactant having a hydrophilic:lipophilic balance of less than about 12;

(i) said surfactant present in an amount sufficient to emulsify said lipid system and said water to form an emulsion suitable for topical application;

(ii) said emulsion having a pH of less than about 5;

(iii) said omega-6 acid or omega-6 acid ester thereof present in an amount whereby said composition of matter contains not more than about 0.05% (w/w) of hydrocortisone 21-butyrate.

11. The composition of claim 10 , wherein said lipid system comprises not more than about 5% of the fatty alcohol and/or ester formable by condensing the fatty alcohol with a fatty acid.

12. The composition of claim 10 , wherein said lipid system comprises at least about 10% of the fatty alcohol and/or ester formable by condensing the fatty alcohol with a fatty acid.

13. The composition of claim 10 , said emulsion selected from the group consisting of: an oil-in-water emulsion; a water-in-oil emulsion; and a complex emulsion.

14. The composition of claim 13 , wherein said emulsion comprises an oil-in-water emulsion.

15. The composition of claim 13 , wherein said emulsion comprises a complex emulsion.

16. The composition of claim 10 , wherein said surfactant comprises a surfactant system comprised of at least two surfactants, wherein said surfactant system has a hydrophilic:lipophilic balance of less than about 14.

17. The composition of claim 10 , wherein said Omega-6 acid or omega-6 acid ester comprises safflower oil.

18. The composition of claim 10 , wherein said composition contains not more than about 0.02% (w/w) of hydrocortisone 21-butyrate.

19. A composition of matter comprising:

(a) About 0.1% (w/w) hydrocortisone 17-butyrate;

(b) About 60% to about 80% (w/w) of a lipid system,

(i) Said lipid system comprising at least one omega-6 fatty acid or omega-6 acid ester;

(c) Quantum sufficit of water;

(d) At least one surfactant;

(i) said surfactant present in an amount sufficient to emulsify said lipid system and said water to form an emulsion suitable for topical application;

(ii) said emulsion having a pH of less than about 5;

(iii) said omega-6 acid or omega-6 acid ester present in an amount whereby said composition of matter contains not more than about 0.05% (w/w) of hydrocortisone 21-butyrate.

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 →
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 →
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 →
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 →
SECURITY INTEREST Recorded Jul 19, 2017
From: PRECISION DERMATOLOGY, INC.
To: THE BANK OF NEW YORK MELLON
Reel/Frame 043041/0864 →
SECURITY AGREEMENT Recorded Jul 6, 2015
From: ECR PHARMACEUTICALS CO., INC.; PRECISION DERMATOLOGY, INC.
To: BARCLAYS BANK PLC, AS COLLATERAL AGENT
Reel/Frame 036091/0257 →
RELEASE OF SECURITY INTEREST Recorded Sep 27, 2013
From: MIDCAP FUNDING III, LLC
To: PRECISION DERMATOLOGY COMPANY, INC.; ONSET DERMATOLOGICS, LLC; PROSKIN, LLC; PRECISION MD, LLC; TP CREAM SUB, LLC; TP LOTION SUB, LLC
Reel/Frame 031296/0492 →
SECURITY AGREEMENT Recorded Sep 20, 2013
From: PRECISION DERMATOLOGY, INC.
To: GCI CAPITAL MARKETS LLC
Reel/Frame 031249/0011 →