Compositions containing silymarin and sulfoalkyl ether cyclodextrin and methods of using the same
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.
1. A composition, comprising silymarin and a sulfoalkyl ether cyclodextrin, wherein silymarin comprises isosilybin A and at least one more flavonoligan compound selected from silychristin A, silydianin, silychristin B, silybin A, silybin B, 2,3-cis-silybin A, 2,3-cis-silybin B, isosilybin A, isosilybin B, and 2,3-cis-isosilybin, and wherein the amount of isosilybin A in the composition is increased by at least 10% based on the total weight of all flavonolignan compounds compared to the amount of isosilybin A in the absence of the sulfoalkyl ether cyclodextrin.
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 ) m SO 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 , comprising isosilybin B.
5. The composition of claim 4 , 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.
6. The composition of claim 4 , 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.
7. The composition of claim 1 , comprising silybin A.
8. The composition of claim 7 , 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 7 , 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.
10. The composition of claim 1 , comprising silybin B.
11. The composition of claim 10 , 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.
12. The composition of claim 10 , 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.
13. The composition of claim 1 , wherein the amount of silymarin in the composition is in the range of about 0.0001% to about 20% by weight, based on the total weight of composition.
14. The composition of claim 13 , wherein the amount of silymarin is in the range of about 0.001% to 10% by weight, based on the total weight of the composition.
15. 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.
16. 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.
17. 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.
18. The composition of claim 1 , wherein the concentration of silymarin in the composition is in the range of about 0.01 mg/g to about 100 mg/g.
19. 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.
20. 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.
21. The composition of claim 1 , further comprising one or more anti-oxidants.
22. The composition of claim 1 , further comprising one or more solvents.
23. The composition of claim 1 , further comprising a pharmaceutically acceptable excipient, diluent or carrier.
24. The composition of claim 1 , further comprising a cosmetically acceptable excipient, diluent or carrier.
25. The composition of claim 1 , wherein the composition is in a solid or liquid form.