WO2009043671A1 - Use of a silybum marianum extract - Google Patents
Use of a silybum marianum extract Download PDFInfo
- Publication number
- WO2009043671A1 WO2009043671A1 PCT/EP2008/061647 EP2008061647W WO2009043671A1 WO 2009043671 A1 WO2009043671 A1 WO 2009043671A1 EP 2008061647 W EP2008061647 W EP 2008061647W WO 2009043671 A1 WO2009043671 A1 WO 2009043671A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- silybum marianum
- extract
- use according
- radiodermatitis
- Prior art date
Links
- 235000010841 Silybum marianum Nutrition 0.000 title claims abstract description 33
- 244000272459 Silybum marianum Species 0.000 title claims abstract description 31
- 239000000203 mixture Substances 0.000 claims abstract description 48
- 208000006934 radiodermatitis Diseases 0.000 claims abstract description 24
- 239000004480 active ingredient Substances 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 10
- 230000002265 prevention Effects 0.000 claims abstract description 10
- 238000011200 topical administration Methods 0.000 claims abstract description 7
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 claims description 19
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical group C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 claims description 19
- 229960004245 silymarin Drugs 0.000 claims description 18
- 235000017700 silymarin Nutrition 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 11
- 238000010521 absorption reaction Methods 0.000 claims description 7
- 230000003381 solubilizing effect Effects 0.000 claims description 7
- 230000009885 systemic effect Effects 0.000 claims description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- 239000004359 castor oil Substances 0.000 claims description 4
- 235000019438 castor oil Nutrition 0.000 claims description 4
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 4
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 4
- 230000003020 moisturizing effect Effects 0.000 claims description 4
- RGZSQWQPBWRIAQ-CABCVRRESA-N (-)-alpha-Bisabolol Chemical compound CC(C)=CCC[C@](C)(O)[C@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-CABCVRRESA-N 0.000 claims description 3
- 244000103926 Chamaenerion angustifolium Species 0.000 claims description 3
- 235000006890 Chamerion angustifolium subsp angustifolium Nutrition 0.000 claims description 3
- RGZSQWQPBWRIAQ-LSDHHAIUSA-N alpha-Bisabolol Natural products CC(C)=CCC[C@@](C)(O)[C@@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-LSDHHAIUSA-N 0.000 claims description 3
- 229930003231 vitamin Natural products 0.000 claims description 3
- 239000011782 vitamin Substances 0.000 claims description 3
- 229940088594 vitamin Drugs 0.000 claims description 3
- 235000013343 vitamin Nutrition 0.000 claims description 3
- WTVHAMTYZJGJLJ-UHFFFAOYSA-N (+)-(4S,8R)-8-epi-beta-bisabolol Natural products CC(C)=CCCC(C)C1(O)CCC(C)=CC1 WTVHAMTYZJGJLJ-UHFFFAOYSA-N 0.000 claims description 2
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 claims description 2
- 239000004909 Moisturizer Substances 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- 229940036350 bisabolol Drugs 0.000 claims description 2
- HHGZABIIYIWLGA-UHFFFAOYSA-N bisabolol Natural products CC1CCC(C(C)(O)CCC=C(C)C)CC1 HHGZABIIYIWLGA-UHFFFAOYSA-N 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 230000001333 moisturizer Effects 0.000 claims description 2
- 229920002414 procyanidin Polymers 0.000 claims description 2
- 235000000346 sugar Nutrition 0.000 claims description 2
- 150000008163 sugars Chemical class 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
- 238000001959 radiotherapy Methods 0.000 description 11
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 210000003491 skin Anatomy 0.000 description 8
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 208000012641 Pigmentation disease Diseases 0.000 description 3
- 208000003251 Pruritus Diseases 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 230000019612 pigmentation Effects 0.000 description 3
- 230000001012 protector Effects 0.000 description 3
- 208000017520 skin disease Diseases 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- CYGIJEJDYJOUAN-UHFFFAOYSA-N Isosilychristin Natural products C1=C(O)C(OC)=CC(C2C3C=C(C4C(C3=O)(O)OCC42)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 CYGIJEJDYJOUAN-UHFFFAOYSA-N 0.000 description 2
- 241000320380 Silybum Species 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- PFTAWBLQPZVEMU-ZFWWWQNUSA-N (+)-epicatechin Natural products C1([C@@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-ZFWWWQNUSA-N 0.000 description 1
- KZJWDPNRJALLNS-VPUBHVLGSA-N (-)-beta-Sitosterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@@H](C(C)C)CC)C)CC4)CC3)CC=2)CC1 KZJWDPNRJALLNS-VPUBHVLGSA-N 0.000 description 1
- PFTAWBLQPZVEMU-UKRRQHHQSA-N (-)-epicatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-UKRRQHHQSA-N 0.000 description 1
- CSVWWLUMXNHWSU-UHFFFAOYSA-N (22E)-(24xi)-24-ethyl-5alpha-cholest-22-en-3beta-ol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(CC)C(C)C)C1(C)CC2 CSVWWLUMXNHWSU-UHFFFAOYSA-N 0.000 description 1
- 239000001500 (2R)-6-methyl-2-[(1R)-4-methyl-1-cyclohex-3-enyl]hept-5-en-2-ol Substances 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- KLEXDBGYSOIREE-UHFFFAOYSA-N 24xi-n-propylcholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CCC)C(C)C)C1(C)CC2 KLEXDBGYSOIREE-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 206010009208 Cirrhosis alcoholic Diseases 0.000 description 1
- LPZCCMIISIBREI-MTFRKTCUSA-N Citrostadienol Natural products CC=C(CC[C@@H](C)[C@H]1CC[C@H]2C3=CC[C@H]4[C@H](C)[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C LPZCCMIISIBREI-MTFRKTCUSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- ARVGMISWLZPBCH-UHFFFAOYSA-N Dehydro-beta-sitosterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)C(C)C)CCC33)C)C3=CC=C21 ARVGMISWLZPBCH-UHFFFAOYSA-N 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 241001643597 Evas Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- FDQAOULAVFHKBX-UHFFFAOYSA-N Isosilybin A Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC(=CC=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 FDQAOULAVFHKBX-UHFFFAOYSA-N 0.000 description 1
- 208000001907 Mushroom Poisoning Diseases 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 206010033733 Papule Diseases 0.000 description 1
- VLGROHBNWZUINI-UHFFFAOYSA-N Silybin Natural products COc1cc(ccc1O)C2OC3C=C(C=CC3OC2CO)C4Oc5cc(O)cc(O)c5C(=O)C4O VLGROHBNWZUINI-UHFFFAOYSA-N 0.000 description 1
- RIAZZJBPJQWPIS-UHFFFAOYSA-N Silychristin Natural products COc1cc(ccc1O)C2OC3C(C=C(C=C3O)C4Oc5cc(O)cc(O)c5C(=O)C4O)C2CO RIAZZJBPJQWPIS-UHFFFAOYSA-N 0.000 description 1
- MZBGBHVFCYCYLX-UHFFFAOYSA-N Silydianin Natural products COc1cc(ccc1O)C2C3COC4(O)C3C=C(C5Oc6cc(O)cc(O)c6C(=O)C5O)C2C4=O MZBGBHVFCYCYLX-UHFFFAOYSA-N 0.000 description 1
- 208000031709 Skin Manifestations Diseases 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000010002 alcoholic liver cirrhosis Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- YLFIGGHWWPSIEG-UHFFFAOYSA-N aminoxyl Chemical compound [O]N YLFIGGHWWPSIEG-UHFFFAOYSA-N 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MJVXAPPOFPTTCA-UHFFFAOYSA-N beta-Sistosterol Natural products CCC(CCC(C)C1CCC2C3CC=C4C(C)C(O)CCC4(C)C3CCC12C)C(C)C MJVXAPPOFPTTCA-UHFFFAOYSA-N 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229950001002 cianidanol Drugs 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- LPTRNLNOHUVQMS-UHFFFAOYSA-N epicatechin Natural products Cc1cc(O)cc2OC(C(O)Cc12)c1ccc(O)c(O)c1 LPTRNLNOHUVQMS-UHFFFAOYSA-N 0.000 description 1
- 235000012734 epicatechin Nutrition 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940087559 grape seed Drugs 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 229940096421 milk thistle extract Drugs 0.000 description 1
- 235000020727 milk thistle extract Nutrition 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000020748 rosemary extract Nutrition 0.000 description 1
- IKGXIBQEEMLURG-NVPNHPEKSA-N rutin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-NVPNHPEKSA-N 0.000 description 1
- UEJSSZHHYBHCEL-UHFFFAOYSA-N silver(1+) sulfadiazinate Chemical compound [Ag+].C1=CC(N)=CC=C1S(=O)(=O)[N-]C1=NC=CC=N1 UEJSSZHHYBHCEL-UHFFFAOYSA-N 0.000 description 1
- 229940043175 silybin Drugs 0.000 description 1
- 235000014899 silybin Nutrition 0.000 description 1
- BMLIIPOXVWESJG-LMBCONBSSA-N silychristin Chemical compound C1=C(O)C(OC)=CC([C@H]2[C@@H](C3=C(C(=CC(=C3)[C@@H]3[C@H](C(=O)C4=C(O)C=C(O)C=C4O3)O)O)O2)CO)=C1 BMLIIPOXVWESJG-LMBCONBSSA-N 0.000 description 1
- BMLIIPOXVWESJG-UHFFFAOYSA-N silychristin A Natural products C1=C(O)C(OC)=CC(C2C(C3=C(C(=CC(=C3)C3C(C(=O)C4=C(O)C=C(O)C=C4O3)O)O)O2)CO)=C1 BMLIIPOXVWESJG-UHFFFAOYSA-N 0.000 description 1
- CYGIJEJDYJOUAN-JSGXPVSSSA-N silydianin Chemical compound C1=C(O)C(OC)=CC([C@H]2[C@H]3C=C([C@@H]4[C@@](C3=O)(O)OC[C@@H]42)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 CYGIJEJDYJOUAN-JSGXPVSSSA-N 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 description 1
- 235000015500 sitosterol Nutrition 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- -1 sodium alginate Chemical class 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 229940126702 topical medication Drugs 0.000 description 1
- 239000003646 toxicity reducer Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
Definitions
- the present invention relates to a novel use of a composition with a Silybum marianum extract, as well as to the use of a composition containing the mentioned extract for topical administration.
- Silymarin a bioflavonoid formed by three structural isomers: silybin, silydianin and silychristin, is extracted from Silybum marianum, commonly known as milk thistle. Since the Middle Ages the extract of Silybum marianum seeds has been used as a potent liver protector. Its action as a liver cell protector against the toxicity of certain drugs, for example against acetaminophen-induced toxicity, is currently being demonstrated, as described in "Acetaminophen-induced Toxicity to Human Epidermoid Cell Line A431 and Hepatoblastoma Cell Line Hep G2, in vitro, Is diminished by Silymarin" Skin Pharmacological 1995;8:279-291.
- Silymarin is also used as a liver protector of patients for the treatment of chronic hepatitis caused by antiviral drugs in patients with acquired immunodeficiency syndrome.
- Other extended uses of silymarin are the treatment of alcoholic cirrhosis and the treatment of mushroom poisoning.
- the application of silymarin in all these indications furthermore has the advantage that it has no side effects.
- the silymarin of the Silybum marianum seed extract is also used in cosmetics as an antioxidant, especially in body creams and lotions, for the treatment of delicate skin, skin exposed to the sun or exposed to other oxidizing agents.
- compositions comprising the extract of Silybum marianum seeds.
- WO0234275 describes a pharmaceutical preparation, comprising milk thistle extract or an active ingredient therefrom, and one or several terpenes, as well as the most suitable excipients. Said preparation is indicated for liver diseases, specifically cirrhosis of the liver.
- DE 4226866 describes another plant preparation comprising milk thistle seeds, which have been irradiated with infrared radiation, then immediately being subjected to fermentation. This preparation is used as an anti-inflammatory medium in the form of capsules, granules, powder or tablets. It can also be added as a nutritional supplement.
- JP 2000136124 describes a composition that is able to keep the skin fresh, elastic and young, skin cell differentiation as well as proliferation being controlled by means of elastase activity inhibition.
- the composition comprises oligopeptides and an extract selected from multiple plant species, including Silybum marianum.
- BG105507 describes a composition applicable as an antioxidant in the prevention of the effects of chemotherapy and in treatment with irradiation, or any other condition in which cell oxidation-reduction is compromised.
- the composition comprises vitamins, a Rosmarinus officinalis extract, Silybum marianum extract, phytocyanins, Ginko biloba, as well as synthetic nitroxyl radical products.
- radiodermatitis Due to the increase of the treatment of diseases by means of radiation therapy, the number of people affected by a skin disease known by the name of radiodermatitis is increasing more and more.
- the radiodermatitis is a disease that especially affects doctors and healthcare professionals who give diagnoses by means of applying X-rays to patients.
- doctors and healthcare professionals who give diagnoses by means of applying X-rays to patients.
- radiodermatitis Some of the effects of radiodermatitis are the onset of erythema, papules or vesicles, lesions with exudation, glossy skin, and in extreme cases, the onset of tumors.
- Radiodermatitis can also have a psychological repercussion on the patient who is being treated for another disease upon observing that a second disease is acquired and the treatment must be stopped.
- lotions or creams For the purpose of alleviating symptoms of this disease, lotions or creams generally comprising calcium and sodium salts, such as sodium alginate, are often topically administered to those patients to whom radiation therapy is applied. These lotions or creams on many times cause allergic or intolerance reactions which further aggravate the problem. Different formulations are also necessary according to the symptomatology of the radiodermatitis, therefore the cost of treatment is high and multiple formulations must be available in order to treat the different skin manifestations.
- compositions with a Silybum marianum extract are very beneficial for alleviating the symptoms of radiodermatitis. They are furthermore compositions which are effective in all manifestations of the disease. Disclosure of the Invention
- the object of the present invention is the use of a composition comprising a Silybum marianum extract or an active ingredient therefrom, at a concentration by weight of 0.05% to 1.00%, for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis.
- the active ingredient of the Silybum marianum extract is silymarin.
- composition for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis is characterized in that the Silybum marianum extract has a silymarin content of 80% by weight.
- the composition for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis further comprises an Epilobium angustifolium extract, at least one vitamin, preferably vitamin E, procyanidines, linoleic acid, moisturizing sugars, natural moisturizers and bisabolol.
- Another object of the present invention is the use of a composition for topical administration, comprising a Silybum marianum extract or an active ingredient therefrom, at a concentration by weight of 0.05% to 1 .00%, for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis.
- composition for topical administration comprises at least one compound for solubilizing the active ingredients of the Silybum marianum extract and at least one compound for reducing the systemic absorption of said active ingredients.
- the compounds for solubilizing and for reducing the systemic absorption of active ingredients are ethoxydiglycol, hydrogenated castor oil or a mixture of both. - A -
- compositions containing a Silybum marianum extract or an active ingredient therefrom for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis
- compositions with Silybum marianum extract are described below, which compositions comprise from 0.05% by weight to 1 .00% by weight of extract or active ingredient therefrom, which have been used in clinical trials by the inventors.
- Composition 1 Cream with Silybum marianum extract.
- Silybum marianum extract (80% by 0 25 weight of silymarin)
- Flavonoids (catechin and epicatechin) 0 5 from grape seed.
- excipients used in the composition are all those excipients that a person skilled in the art of formulations would use to obtain a creamy consistency.
- Composition 2 Gel with Silybum marianum extract.
- the gel of composition 2 has a pH of 5.50 ⁇ 0.30, and a viscosity at 20 Q C of 1.000 ⁇ 500 cps
- these compositions which must be administered topically further comprise a compound for solubilizing silymarin.
- Silymarin is a molecule that is not very soluble in water; therefore the inventors have developed a formulation which allows providing large amounts of the same in the compositions for topical administration.
- an agent for solubilizing silymarin in the composition allows assuring that the same will be in conditions for being applied on the skin and that aggregates, which would reduce its efficacy, will not be formed.
- topical compositions object of the invention with Silybum marianum extract which are used for the preparation of a medicament for the prevention or the treatment of radiodermatitis, further comprise a compound for reducing the systemic absorption of silymarin or any active ingredient of the Silybum marianum extract.
- Said agents for solubilizing silymarin, as well as compounds for reducing the systemic absorption the active ingredients are preferably ethoxydiglycol, hydrogenated castor oil or a mixture of both.
- Silybum marianum extract with 80% silymarin is therefore gradually released and acts on the skin, which is where it is to perform its function, before or after treatment with radiation therapy.
- the purpose was to evaluate acute radiodermatitis, pigmentation, pruritus and subjective comfort. A baseline evaluation was conducted before the treatment. Then evaluations were conducted in weekly controls and at the end of treatment.
- Radiodermatitis has been classified according to the toxicity scale of the RTOG (Radiation Therapy Oncology Group) and the pigmentation, pruritus and subjective comfort by means of an EVA scale (0-10).
- the following table shows the percentages and degree of radiodermatitis depending on the week of treatment.
- the pruritus, pigmentation and subjective comfort recordings have indicated low EVAs, with a median score of 3.
- Topical medication was used in nine patients: four patients were given hyaluronic acid and four other patients were given silver sulphadiazine, and one patient was given corticoids.
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to the use of a composition comprising a Silybum marianum extract or an active ingredient therefrom, for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis. The invention also relates to the use of the composition for topical administration.
Description
D E S C R I P T I O N
"USE OF A SILYBUM MARIANUM EXTRACT"
Technical Field of the Invention
The present invention relates to a novel use of a composition with a Silybum marianum extract, as well as to the use of a composition containing the mentioned extract for topical administration.
Background of the Invention Silymarin, a bioflavonoid formed by three structural isomers: silybin, silydianin and silychristin, is extracted from Silybum marianum, commonly known as milk thistle. Since the Middle Ages the extract of Silybum marianum seeds has been used as a potent liver protector. Its action as a liver cell protector against the toxicity of certain drugs, for example against acetaminophen-induced toxicity, is currently being demonstrated, as described in "Acetaminophen-induced Toxicity to Human Epidermoid Cell Line A431 and Hepatoblastoma Cell Line Hep G2, in vitro, Is diminished by Silymarin" Skin Pharmacological 1995;8:279-291. Its action as a toxicity reducer is possibly due to its capacity of retaining, capturing or neutralizing oxidizing substances such as free radicals. Silymarin is also used as a liver protector of patients for the treatment of chronic hepatitis caused by antiviral drugs in patients with acquired immunodeficiency syndrome. Other extended uses of silymarin are the treatment of alcoholic cirrhosis and the treatment of mushroom poisoning. The application of silymarin in all these indications furthermore has the advantage that it has no side effects.
There are also studies showing that the administration of silymarin reduces the negative effects of irradiation of the body or parts of the body with X-rays, especially reducing the hepatotoxicity caused by radiation, as deduced from "Die therapeutische Wirkung von Sylimarin bei rόntgenbestrahlten Mausen", von K. Flemming, Arzneimittel-Forschung; Jahrgang 21-Nr 9 (1971): 1373- 1375.
The silymarin of the Silybum marianum seed extract is also used in cosmetics as an antioxidant, especially in body creams and lotions, for the treatment of delicate skin, skin exposed to the sun or exposed to other oxidizing agents.
There is considerable literature which describes compositions comprising the
extract of Silybum marianum seeds. For example, WO0234275 describes a pharmaceutical preparation, comprising milk thistle extract or an active ingredient therefrom, and one or several terpenes, as well as the most suitable excipients. Said preparation is indicated for liver diseases, specifically cirrhosis of the liver. DE 4226866 describes another plant preparation comprising milk thistle seeds, which have been irradiated with infrared radiation, then immediately being subjected to fermentation. This preparation is used as an anti-inflammatory medium in the form of capsules, granules, powder or tablets. It can also be added as a nutritional supplement. JP 2000136124 describes a composition that is able to keep the skin fresh, elastic and young, skin cell differentiation as well as proliferation being controlled by means of elastase activity inhibition. The composition comprises oligopeptides and an extract selected from multiple plant species, including Silybum marianum.
Finally, BG105507 describes a composition applicable as an antioxidant in the prevention of the effects of chemotherapy and in treatment with irradiation, or any other condition in which cell oxidation-reduction is compromised. The composition comprises vitamins, a Rosmarinus officinalis extract, Silybum marianum extract, phytocyanins, Ginko biloba, as well as synthetic nitroxyl radical products.
Due to the increase of the treatment of diseases by means of radiation therapy, the number of people affected by a skin disease known by the name of radiodermatitis is increasing more and more. The radiodermatitis is a disease that especially affects doctors and healthcare professionals who give diagnoses by means of applying X-rays to patients. However, many patients who must undergo radiation therapy to be treated for cancer, for example, also suffer this disease today.
Some of the effects of radiodermatitis are the onset of erythema, papules or vesicles, lesions with exudation, glossy skin, and in extreme cases, the onset of tumors.
Radiodermatitis can also have a psychological repercussion on the patient who is being treated for another disease upon observing that a second disease is acquired and the treatment must be stopped.
For the purpose of alleviating symptoms of this disease, lotions or creams generally comprising calcium and sodium salts, such as sodium alginate, are often topically administered to those patients to whom radiation therapy is applied. These
lotions or creams on many times cause allergic or intolerance reactions which further aggravate the problem. Different formulations are also necessary according to the symptomatology of the radiodermatitis, therefore the cost of treatment is high and multiple formulations must be available in order to treat the different skin manifestations.
The inventors have surprisingly discovered that compositions with a Silybum marianum extract are very beneficial for alleviating the symptoms of radiodermatitis. They are furthermore compositions which are effective in all manifestations of the disease. Disclosure of the Invention
The object of the present invention is the use of a composition comprising a Silybum marianum extract or an active ingredient therefrom, at a concentration by weight of 0.05% to 1.00%, for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis. Preferably, the active ingredient of the Silybum marianum extract is silymarin.
The use of the composition for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis is characterized in that the Silybum marianum extract has a silymarin content of 80% by weight. The composition for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis further comprises an Epilobium angustifolium extract, at least one vitamin, preferably vitamin E, procyanidines, linoleic acid, moisturizing sugars, natural moisturizers and bisabolol.
Another object of the present invention is the use of a composition for topical administration, comprising a Silybum marianum extract or an active ingredient therefrom, at a concentration by weight of 0.05% to 1 .00%, for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis.
The composition for topical administration according to the invention comprises at least one compound for solubilizing the active ingredients of the Silybum marianum extract and at least one compound for reducing the systemic absorption of said active ingredients.
Preferably, the compounds for solubilizing and for reducing the systemic absorption of active ingredients are ethoxydiglycol, hydrogenated castor oil or a mixture of both.
- A -
Detailed Disclosure
For the purpose of demonstrating the object of the present invention, i.e., the use of a composition containing a Silybum marianum extract or an active ingredient therefrom for the preparation of a medicament for the prevention and/or the treatment of radiodermatitis, several compositions with Silybum marianum extract, are described below, which compositions comprise from 0.05% by weight to 1 .00% by weight of extract or active ingredient therefrom, which have been used in clinical trials by the inventors.
Composition 1. Cream with Silybum marianum extract.
Compound Amount (in grams)
Silybum marianum extract (80% by 0 25 weight of silymarin)
Natural moisturizing factor 2 00
Moisturizing carbohydrate complex 2 00
Mixture of fatty acids + vitamin B + β- 0 5 sitosterol
Flavonoids (catechin and epicatechin) 0 5 from grape seed.
Natural alpha-bisabolol 0 15
Epilobium angustifolium extract 1 00
Vitamin E acetate 0 5
Excipients 26.28
Purified water q s.f. 100 grams
The excipients used in the composition are all those excipients that a person skilled in the art of formulations would use to obtain a creamy consistency.
Composition 2. Gel with Silybum marianum extract.
The gel of composition 2 has a pH of 5.50 ± 0.30, and a viscosity at 20QC of 1.000 ± 500 cps
Preferably, these compositions which must be administered topically further comprise a compound for solubilizing silymarin. Silymarin is a molecule that is not very soluble in water; therefore the inventors have developed a formulation which allows providing large amounts of the same in the compositions for topical administration.
The presence of an agent for solubilizing silymarin in the composition allows assuring that the same will be in conditions for being applied on the skin and that aggregates, which would reduce its efficacy, will not be formed.
Another problem which must be overcome in topical compositions intended for palliating or improving symptoms of skin diseases, even though in this case they are not caused by the presence of a not very soluble substance, is the of the systemic absorption of the active ingredients. It is important to bear in mind that the permeability of the epidermis aids the composition in being able to enter the blood circulation, and in the case of skin diseases the idea is for the active ingredients to be retained and to act precisely in the skin. Therefore, the topical compositions object of the invention with Silybum marianum extract which are used for the preparation of a medicament for the prevention or the treatment of radiodermatitis, further comprise a compound for reducing the systemic absorption of silymarin or any active ingredient of the Silybum marianum extract.
Said agents for solubilizing silymarin, as well as compounds for reducing the
systemic absorption the active ingredients, are preferably ethoxydiglycol, hydrogenated castor oil or a mixture of both.
Both ethoxydiglycol and hydrogenated castor oil form intracutaneous deposits containing the active ingredients therein. The Silybum marianum extract with 80% silymarin is therefore gradually released and acts on the skin, which is where it is to perform its function, before or after treatment with radiation therapy.
Clinical trial with cancer patients. Efficacy of the use according to the invention:
A group of 60 women who had been diagnosed with breast cancer received adjuvant radiation therapy treatment. In parallel, they were administered a composition with Silybum marianum, such as compositions 1 and 2, with a frequency of 2 times a day. The administration began after each patient's first visit.
The purpose was to evaluate acute radiodermatitis, pigmentation, pruritus and subjective comfort. A baseline evaluation was conducted before the treatment. Then evaluations were conducted in weekly controls and at the end of treatment.
Radiodermatitis has been classified according to the toxicity scale of the RTOG (Radiation Therapy Oncology Group) and the pigmentation, pruritus and subjective comfort by means of an EVA scale (0-10).
The following table shows the percentages and degree of radiodermatitis depending on the week of treatment.
Table 1.
As the weeks advance, the percentage of women with radiodermatitis and with higher degrees of the disease increases, as is logical due to the prolonged radiation therapy treatment. However, it should be emphasized that only the third degree of radiodermatitis is reached in 13% of the women treated and at the sixth week of radiation therapy. In the same manner it is surprisingly observed that 1 month after the radiation therapy treatment is interrupted, the radiodermatitis that is observed in the women belongs to degree 1 (33%) or degree 2 (4%). Most of the women who were treated (63%) did not suffer the disease.
The pruritus, pigmentation and subjective comfort recordings have indicated low EVAs, with a median score of 3.
Topical medication was used in nine patients: four patients were given hyaluronic acid and four other patients were given silver sulphadiazine, and one patient was given corticoids.
All these results show that the prophylactic administration of Silybum marianum allows controlling radiodermatitis, furthermore presenting a high tolerance in patients diagnosed with breast cancer subjected to radiation therapy. Surprisingly, the use of compositions with Silybum marianum at concentrations of 0.05% to 1.00% by weight have as a result, as shown by the previous results, rates of recovery and of prevention of radiodermatitis that have not yet been described. It furthermore involves an advantage compared to the compositions that have been used for the preparation of medicaments for radiodermatitis, which were formulated according to the degree or stage of the disease, different compounds being used in each case.
Claims
1 .- Use of a composition comprising a Silybum marianum extract or an active ingredient therefrom, at a concentration by weight of 0.05% to 1 .00%, for the preparation of a medicament for the prevention and/or treatment of radiodermatitis.
2.- Use according to claim 1 , wherein the active ingredient of the Silybum marianum extract is silymarin.
3.- Use according to any one of the preceding claims 1 and 2, wherein the
Silybum marianum extract has a silymarin content of 80% by weight.
4.- Use according to any one of the preceding claims 1 to 3, wherein the composition further comprises an Epilobium angustifolium extract, at least one vitamin, procyanidines, linoleic acid, moisturizing sugars, natural moisturizers and bisabolol.
5.- Use according to claim 4, wherein the composition comprises vitamin E.
6.- Use according to any one of the preceding claims, wherein the composition is a composition for topical administration.
7.- Use according to claim 6, wherein the composition for topical administration comprises at least one compound for solubilizing the active ingredients of the Silybum marianum extract and at least one compound for reducing the systemic absorption of said active ingredients.
8.- Use according to claim 7, wherein the compounds for solubilizing and for reducing the systemic absorption of active ingredients are ethoxydiglycol, hydrogenated castor oil or a mixture of both.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200702600A ES2325291B1 (en) | 2007-10-04 | 2007-10-04 | "USE OF A SILYBUM MARIANUM EXTRACT" |
| ESP200702600 | 2007-10-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2009043671A1 true WO2009043671A1 (en) | 2009-04-09 |
Family
ID=39838713
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2008/061647 WO2009043671A1 (en) | 2007-10-04 | 2008-09-03 | Use of a silybum marianum extract |
Country Status (2)
| Country | Link |
|---|---|
| ES (1) | ES2325291B1 (en) |
| WO (1) | WO2009043671A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014008361A2 (en) | 2012-07-05 | 2014-01-09 | Nutramax Laboratories, Inc. | Compositions comprising a sulforaphane or a sulforaphane precursor and milk thistle extract or powder |
| CN105796831A (en) * | 2016-04-19 | 2016-07-27 | 北京欣普迪生物科技有限公司 | Medical ray protection agent and preparation method thereof |
| CN106176843A (en) * | 2016-08-30 | 2016-12-07 | 青海民族大学 | Willow herb suppresses HDAC1 enzyme effective site and preparation method and application |
| CN106176845A (en) * | 2016-08-30 | 2016-12-07 | 青海民族大学 | Willow herb suppresses CDC25 enzyme effective site and preparation method and application |
| CN106344631A (en) * | 2016-08-30 | 2017-01-25 | 青海民族大学 | Effective parts of willow herb and preparing method and application tehreof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999048386A1 (en) * | 1998-03-24 | 1999-09-30 | Stueckler Franz | Natural substance based agent |
| WO2002072051A2 (en) * | 2001-03-02 | 2002-09-19 | Indena S.P.A. | Pharmaceutical and cosmetic compositions for the protection of the skin from damages induced by sun radiations |
| JP2003171310A (en) * | 2002-05-02 | 2003-06-20 | Noevir Co Ltd | Skin barrier function-reinforcing agent |
| WO2003088986A1 (en) * | 2002-04-16 | 2003-10-30 | Isis Innovation Limited | Curcumin for the prevention and/or treatment of tissue damage |
| WO2007041327A1 (en) * | 2005-10-01 | 2007-04-12 | Elc Management Llc | Compositions comprising hypsizygus ulmarius extract |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6524599B2 (en) * | 2001-02-21 | 2003-02-25 | Skinceuticals, Inc. | Use of milk thistle extract in skin care compositions |
-
2007
- 2007-10-04 ES ES200702600A patent/ES2325291B1/en active Active
-
2008
- 2008-09-03 WO PCT/EP2008/061647 patent/WO2009043671A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999048386A1 (en) * | 1998-03-24 | 1999-09-30 | Stueckler Franz | Natural substance based agent |
| WO2002072051A2 (en) * | 2001-03-02 | 2002-09-19 | Indena S.P.A. | Pharmaceutical and cosmetic compositions for the protection of the skin from damages induced by sun radiations |
| WO2003088986A1 (en) * | 2002-04-16 | 2003-10-30 | Isis Innovation Limited | Curcumin for the prevention and/or treatment of tissue damage |
| JP2003171310A (en) * | 2002-05-02 | 2003-06-20 | Noevir Co Ltd | Skin barrier function-reinforcing agent |
| WO2007041327A1 (en) * | 2005-10-01 | 2007-04-12 | Elc Management Llc | Compositions comprising hypsizygus ulmarius extract |
Non-Patent Citations (4)
| Title |
|---|
| ABASCAL K ET AL: "The many faces of Silybum marianum (milk thistle): Part 1 - Treating cancer and hyperlipidemia and restoring kidney function", ALTERNATIVE AND COMPLEMENTARY THERAPIES, MARY ANN LIEBERT, LARCHMONT, NY, US, vol. 9, no. 4, 1 January 2003 (2003-01-01), pages 170 - 175, XP009107569, ISSN: 1076-2809 * |
| DATABASE WPI Week 200406, Derwent World Patents Index; AN 2004-055898, XP002500694 * |
| LI L H ET AL: "Silymarin prevents UV irradiation-induced A375-S2 cell apoptosis", 20041201, vol. 26, no. 6, 1 December 2004 (2004-12-01), XP018001494 * |
| MCDOUGALL CAROL J ET AL: "Management of radiation dermatitis in a patient after mastectomy", JOURNAL OF WOUND, OSTOMY AND CONTINENCE NURSING, MOSBY-YEAR BOOK, ST. LOUIS, MO, US, vol. 32, no. 5, 1 September 2005 (2005-09-01), pages 337 - 340, XP009107567, ISSN: 1071-5754 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014008361A2 (en) | 2012-07-05 | 2014-01-09 | Nutramax Laboratories, Inc. | Compositions comprising a sulforaphane or a sulforaphane precursor and milk thistle extract or powder |
| EP3409280A1 (en) | 2012-07-05 | 2018-12-05 | Nutramax Laboratories, Inc. | Compositions comprising a sulforaphane and milk thistle extract or powder |
| EP3821895A1 (en) | 2012-07-05 | 2021-05-19 | Nutramax Laboratories, Inc. | Compositions comprising a sulforaphane or a broccoli extract and milk thistle extract or powder |
| CN105796831A (en) * | 2016-04-19 | 2016-07-27 | 北京欣普迪生物科技有限公司 | Medical ray protection agent and preparation method thereof |
| CN106176843A (en) * | 2016-08-30 | 2016-12-07 | 青海民族大学 | Willow herb suppresses HDAC1 enzyme effective site and preparation method and application |
| CN106176845A (en) * | 2016-08-30 | 2016-12-07 | 青海民族大学 | Willow herb suppresses CDC25 enzyme effective site and preparation method and application |
| CN106344631A (en) * | 2016-08-30 | 2017-01-25 | 青海民族大学 | Effective parts of willow herb and preparing method and application tehreof |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2325291B1 (en) | 2010-04-22 |
| ES2325291A1 (en) | 2009-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7069490B2 (en) | Yuricoma longifolia extract and its use in enhancing and / or stimulating the immune system | |
| US10350256B2 (en) | Compositions for the treatment of dermatological conditions, disorders or diseases | |
| EA032439B1 (en) | Compositions and methods for treating surface wounds | |
| CN109331095A (en) | A kind of clearing damp rash composition and preparation method thereof | |
| JP6298819B2 (en) | Companion beauty composition | |
| KR100905386B1 (en) | Composition of oriental cosmetics for atopy skin containing herbal extract | |
| KR20170050062A (en) | Composition for Beverage and Cosmetics Containing Asiaticoside Madecassoside Asiatic acid Madecasic acid Extracted from Centella Asiatica Manufacturing Method Thereof | |
| WO2009043671A1 (en) | Use of a silybum marianum extract | |
| US20150238462A1 (en) | Composition comprising plant phenols for preventing or reducing tewl and associated disorders and diseases | |
| Deka et al. | Mechanism of action of wound healing activity of Calendula officinalis: a comprehensive review | |
| CN106163515A (en) | Anticancer and agents for relieving side effects | |
| KR20100026855A (en) | Skin external application composition for preventing or treating inflammatory skin disease | |
| KR101833025B1 (en) | Composition for protecting and treating acne comprising Siegesbeckia pubescens | |
| ES2700983T3 (en) | Treatment of cicatricial injury using tocotrienol | |
| CN101766731B (en) | Tea polyphenol acne resistant external preparation | |
| CN104840404A (en) | Cosmetic with deodorization function and preparation method thereof | |
| JP2006131572A (en) | Emollient for menstruation-related symptom | |
| CN114053286B (en) | Pharmaceutical composition and preparation method and application thereof | |
| EP2514429B1 (en) | Antioxidant | |
| CN108578549B (en) | Medicine for treating acne and application thereof | |
| JP2006131571A (en) | Mitigator for menstruation related symptom | |
| KR101924355B1 (en) | Composition for anti-stretch mark effect on the skin containing extracts of salicornia herbacea and ecklonia cava | |
| JP2023551281A (en) | Composition containing a fraction of Syzygium formosum extract as an active ingredient | |
| Kmail | The Benefits of Nigella Sativa for Skin Diseases and Heal Skin Injuries: An Overview of Phytochemicals and Pharmacological Properties | |
| KR101427035B1 (en) | Composition for treating acne |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 08803618 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 08803618 Country of ref document: EP Kind code of ref document: A1 |