IP Library › Granted Patent US 12,390,506
Granted Patent B2
US 12,390,506 · App. 17/853,761 · Granted Aug 19, 2025

Compositions containing silymarin and sulfoalkyl ether cyclodextrin and methods of using the same

Inventors: James D. Pipkin (Lawrence, KS); Roger A. Rajewski (Lawrence, KS); Beau Mainous (Duluth, GA)
Assignees: CyDex Pharmaceuticals, Inc.; University of Kansas
A61K36/28A61K8/498A61K8/738A61K8/96A61K9/0014A61K9/06A61K31/353A61K31/357A61K47/40A61P1/16A61P17/06A61Q19/08A61K2300/00A61Q17/04
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Quick Facts
Patent No.
US 12,390,506
App. No.
17/853,761
Granted
Aug 19, 2025
Kind
B2
Abstract

Cosmetic and dietary supplement compositions containing silymarin and sulfoalkyl ether cyclodextrin, particularly sulfobutyl ether cyclodextrin, are described. The compositions and methods are useful in reducing appearance of facial redness in rosacea-prone skin, rejuvenating skin, preventing skin aging, inhibiting oxidative stress in epidermal and dermal cells, increasing collagen production, reducing the likelihood of skin cancer, treating or reducing liver damage from a toxin, or treating a liver disease.

Claims (37)

1. A pill, capsule, tablet or emulsion comprising:

taxifolin, silychristin, silydianin, silybin A, silybin B, isosilybin A, isosilybin B, and

sulfoalkyl ether cyclodextrin,

wherein the molar ratio of taxifolin to sulfoalkyl ether cyclodextrin is in the range of about 0.02 to 0.25, wherein the molar ratio of silycristin to sulfoalkyl ether cyclodextrin is in the range of about 0.06 to 0.25, wherein the molar ratio of silydianin to sulfoalkyl ether cyclodextrin is in the range of about 0.08 to 0.25, wherein the molar ratio of silybin A to sulfoalkyl ether cyclodextrin is in the range of about 0.01 to 0.07, wherein the molar ratio of silybin B to sulfoalkyl ether cyclodextrin is in the range of about 0.04 to 0.15, wherein the molar ratio of isosilybin A to sulfoalkyl ether cyclodextrin is in the range of about 0.02 to 0.09, and wherein the molar ratio of isosilybin B to sulfoalkyl ether cyclodextrin is in the range of about 0.002 to 0.03.

2. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin is a compound, or a mixture thereof, of Formula I:

wherein:

n is 4, 5, or 6;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are each, independently, —O— or a —O—(C 2 -C 6 alkylene)-SO 3 − group, wherein at least one of R 1 to R 9 is independently a —O—(C 2 -C 6 alkylene)-SO 3 − group, a —O—(CH 2 )mSO 3 − group wherein m is 2 to 6, —OCH 2 CH 2 CH 2 SO 3 − , or —OCH 2 CH 2 CH 2 CH 2 SO 3 − ; and

S 1 , S 2 , S 3 , S 4 , S 5 , S 6 , S 7 , S 8 , and S 9 , are each, independently, a pharmaceutically acceptable cation.

3. The composition of claim 1 , wherein the sulfoalkyl ether cyclodextrin is a compound, or a mixture thereof, of Formula II

or a pharmaceutically acceptable salt thereof, wherein:

p is 4, 5, or 6, and each R 1 is independently —O—(C 1 -C 8 alkylene)-SO 3 T or —OH, and;

each T is independently hydrogen or pharmaceutically acceptable cation,

provided that at least one R 1 is —OH.

4. The composition of claim 1 , wherein the amount of sulfoalkyl ether cyclodextrin in the composition is in the range of about 0.0001% to about 50% by weight, based on the total weight of composition.

5. The composition of claim 1 , wherein the weight ratio of the silymarin and sulfoalkyl ether cyclodextrin is in the range of about 0.001:1 to about 10:1.

6. The composition of claim 1 , wherein the molar ratio of the isosilybin B and sulfoalkyl ether cyclodextrin is in the range of about 0.001:1 to about 10:1.

7. The composition of claim 1 , wherein the molar ratio of the isosilybin A and sulfoalkyl ether cyclodextrin is in the range of about 0.001:1 to about 10:1.

8. The composition of claim 1 , wherein the molar ratio of the silybin A and sulfoalkyl ether cyclodextrin is in the range of about 0.001:1 to about 10:1.

9. The composition of claim 1 , wherein the molar ratio of the silybin B and sulfoalkyl ether cyclodextrin is in the range of about 0.001:1 to about 10:1.

10. The composition of claim 1 , wherein the molar ratio of the isosilybin B and sulfoalkyl ether cyclodextrin is in the range of about 0.001:1 to about 10:1.

11. The composition of claim 1 , wherein the concentration of sulfoalkyl ether cyclodextrin in the composition is in the range of about 0.001 mol/L to about 10 mol/L.

12. The composition of claim 1 , wherein the weight percentage of silybin A is in the range of about 3% to about 12% based on the total weight of all flavonolignan components.

13. The composition of claim 1 , wherein the molar percentage of silybin A is in the range of about 3% to about 12% based on the total moles of all flavonolignan components.

14. The composition of claim 1 , wherein the weight percentage of silybin B is in the range of about 5% to about 25% based on the total weight of all flavonolignan components.

15. The composition of claim 1 , wherein the molar percentage of silybin B is in the range of about 5% to about 25% based on the total mole of all flavonolignan components.

16. The composition of claim 1 , wherein the weight percentage of isosilybin A is in the range of about 5% to about 16% based on the total weight of all flavonolignan components.

17. The composition of claim 1 , wherein the molar percentage of isosilybin A is in the range of about 5% to about 16% based on the total moles of all flavonolignan components.

18. The composition of claim 1 , wherein the weight percentage of isosilybin B is in the range of about 1% to about 5% based on the total weight of all flavonolignan components.

19. The composition of claim 1 , wherein the molar percentage of isosilybin B is in the range of about 1% to about 5% based on the total moles of all flavonolignan components.

20. The composition of claim 1 , wherein the molar ratio of silybin A to silybin B to isosilybin A to isosilybin B is in the range of about (6-12):(15-25):(10-20):(2-6).

21. The composition of claim 1 , wherein the molar ratio of silybin A to silybin B to isosilybin A to isosilybin B is about 10:22:14:4.

22. The composition of claim 1 , further comprising one or more anti-oxidants.

23. The composition of claim 1 , further comprising one or more solvents.

24. The composition of claim 1 , further comprising a pharmaceutically acceptable excipient, diluent or carrier.

25. The composition of claim 1 , further comprising a cosmetically acceptable excipient, diluent or carrier.

26. The composition of claim 1 , wherein the composition is in a solid or liquid form.

Assignments (4)
SECURITY INTEREST Recorded Jul 14, 2026
From: CYDEX PHARMACEUTICALS, INC.; LIGAND PHARMACEUTICALS INCORPORATED; METABASIS THERAPEUTICS, INC.; XOMA (US) LLC; APEIRON BIOLOGICS GMBH
To: CITIBANK, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 075969/0966 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 6, 2022
From: PIPKIN, JAMES D.
To: CYDEX PHARMACEUTICALS, INC.
Reel/Frame 061337/0097 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 6, 2022
From: MAINOUS, BEAU
To: CYDEX PHARMACEUTICALS, INC.
Reel/Frame 061337/0148 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 6, 2022
From: RAJEWSKI, ROGER A.
To: UNIVERSITY OF KANSAS
Reel/Frame 061337/0199 →
Continuity (4)
Division 16920127 · Jul 2, 2020
Division 15559005
Provisional Application 62135625 · Mar 19, 2015
Related Publication 20230233638A1 · Jul 27, 2023
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