EP4351609A1 - Oral composition for the treatment and/or prevention of disorders associated with menopause - Google Patents
Oral composition for the treatment and/or prevention of disorders associated with menopauseInfo
- Publication number
- EP4351609A1 EP4351609A1 EP22732337.5A EP22732337A EP4351609A1 EP 4351609 A1 EP4351609 A1 EP 4351609A1 EP 22732337 A EP22732337 A EP 22732337A EP 4351609 A1 EP4351609 A1 EP 4351609A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- extract
- magnesium
- citrus
- vitamin
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 82
- 230000009245 menopause Effects 0.000 title claims abstract description 41
- 238000011282 treatment Methods 0.000 title claims abstract description 23
- 230000002265 prevention Effects 0.000 title claims abstract description 11
- 239000000284 extract Substances 0.000 claims abstract description 148
- 240000004482 Withania somnifera Species 0.000 claims abstract description 36
- 235000001978 Withania somnifera Nutrition 0.000 claims abstract description 35
- 239000009405 Ashwagandha Substances 0.000 claims abstract description 28
- 235000020971 citrus fruits Nutrition 0.000 claims abstract description 28
- DBRXOUCRJQVYJQ-CKNDUULBSA-N withaferin A Chemical compound C([C@@H]1[C@H]([C@@H]2[C@]3(CC[C@@H]4[C@@]5(C)C(=O)C=C[C@H](O)[C@@]65O[C@@H]6C[C@H]4[C@@H]3CC2)C)C)C(C)=C(CO)C(=O)O1 DBRXOUCRJQVYJQ-CKNDUULBSA-N 0.000 claims abstract description 28
- 235000005979 Citrus limon Nutrition 0.000 claims abstract description 25
- 244000131522 Citrus pyriformis Species 0.000 claims abstract description 24
- 235000009088 Citrus pyriformis Nutrition 0.000 claims abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 17
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
- 208000008454 Hyperhidrosis Diseases 0.000 claims description 11
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 11
- 239000011669 selenium Substances 0.000 claims description 11
- 229910052711 selenium Inorganic materials 0.000 claims description 11
- 235000011649 selenium Nutrition 0.000 claims description 11
- 229940091258 selenium supplement Drugs 0.000 claims description 11
- 230000035900 sweating Effects 0.000 claims description 11
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 10
- 241000207199 Citrus Species 0.000 claims description 10
- 240000002319 Citrus sinensis Species 0.000 claims description 10
- 235000005976 Citrus sinensis Nutrition 0.000 claims description 10
- 206010022998 Irritability Diseases 0.000 claims description 10
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 10
- 239000011777 magnesium Substances 0.000 claims description 10
- 229910052749 magnesium Inorganic materials 0.000 claims description 10
- 235000001055 magnesium Nutrition 0.000 claims description 10
- 229940091250 magnesium supplement Drugs 0.000 claims description 10
- 208000019116 sleep disease Diseases 0.000 claims description 10
- 244000276331 Citrus maxima Species 0.000 claims description 9
- 235000001759 Citrus maxima Nutrition 0.000 claims description 9
- 240000000560 Citrus x paradisi Species 0.000 claims description 9
- 235000000882 Citrus x paradisi Nutrition 0.000 claims description 9
- 206010019233 Headaches Diseases 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 231100000869 headache Toxicity 0.000 claims description 9
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 9
- 239000011707 mineral Substances 0.000 claims description 9
- 235000010755 mineral Nutrition 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 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 8
- 235000016840 Citrus aurantium var. amara Nutrition 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 8
- 244000240100 sour orange Species 0.000 claims description 8
- 239000003826 tablet Substances 0.000 claims description 8
- 229940088594 vitamin Drugs 0.000 claims description 8
- 229930003231 vitamin Natural products 0.000 claims description 8
- 235000013343 vitamin Nutrition 0.000 claims description 8
- 239000011782 vitamin Substances 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 7
- 239000011574 phosphorus Substances 0.000 claims description 7
- 229910052698 phosphorus Inorganic materials 0.000 claims description 7
- 240000003791 Citrus myrtifolia Species 0.000 claims description 6
- 235000000228 Citrus myrtifolia Nutrition 0.000 claims description 6
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 6
- 229940024606 amino acid Drugs 0.000 claims description 6
- 150000001413 amino acids Chemical class 0.000 claims description 6
- 244000089742 Citrus aurantifolia Species 0.000 claims description 5
- 235000008733 Citrus aurantifolia Nutrition 0.000 claims description 5
- 244000175448 Citrus madurensis Species 0.000 claims description 5
- 235000001938 Citrus medica Nutrition 0.000 claims description 5
- 240000004307 Citrus medica Species 0.000 claims description 5
- 241001672694 Citrus reticulata Species 0.000 claims description 5
- 244000295848 Citrus x nobilis Species 0.000 claims description 5
- 235000017102 Citrus x nobilis Nutrition 0.000 claims description 5
- 235000017316 Fortunella japonica Nutrition 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 206010047791 Vulvovaginal dryness Diseases 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 239000013522 chelant Substances 0.000 claims description 5
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 5
- 159000000003 magnesium salts Chemical class 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 claims description 4
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 4
- 206010029216 Nervousness Diseases 0.000 claims description 4
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 4
- 229930003451 Vitamin B1 Natural products 0.000 claims description 4
- 229930003779 Vitamin B12 Natural products 0.000 claims description 4
- 229930003471 Vitamin B2 Natural products 0.000 claims description 4
- 229930003761 Vitamin B9 Natural products 0.000 claims description 4
- 229930003316 Vitamin D Natural products 0.000 claims description 4
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 4
- 229930003427 Vitamin E Natural products 0.000 claims description 4
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 4
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 claims description 4
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 4
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 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 4
- 235000010933 magnesium salts of fatty acid Nutrition 0.000 claims description 4
- 239000001778 magnesium salts of fatty acids Substances 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 239000011159 matrix material Substances 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 4
- 229960002477 riboflavin Drugs 0.000 claims description 4
- 239000000377 silicon dioxide Substances 0.000 claims description 4
- 235000012239 silicon dioxide Nutrition 0.000 claims description 4
- 229960003495 thiamine Drugs 0.000 claims description 4
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims description 4
- 235000010374 vitamin B1 Nutrition 0.000 claims description 4
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- 239000011715 vitamin B12 Substances 0.000 claims description 4
- 235000019164 vitamin B2 Nutrition 0.000 claims description 4
- 239000011716 vitamin B2 Substances 0.000 claims description 4
- 235000019158 vitamin B6 Nutrition 0.000 claims description 4
- 239000011726 vitamin B6 Substances 0.000 claims description 4
- 235000019159 vitamin B9 Nutrition 0.000 claims description 4
- 239000011727 vitamin B9 Substances 0.000 claims description 4
- 235000019166 vitamin D Nutrition 0.000 claims description 4
- 239000011710 vitamin D Substances 0.000 claims description 4
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 4
- 235000019165 vitamin E Nutrition 0.000 claims description 4
- 229940046009 vitamin E Drugs 0.000 claims description 4
- 239000011709 vitamin E Substances 0.000 claims description 4
- 229940011671 vitamin b6 Drugs 0.000 claims description 4
- 229940046008 vitamin d Drugs 0.000 claims description 4
- 206010019332 Heat exhaustion Diseases 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 235000015165 citric acid Nutrition 0.000 claims description 3
- 239000000975 dye Substances 0.000 claims description 3
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 229920001202 Inulin Polymers 0.000 claims description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
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- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 2
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- 238000013270 controlled release Methods 0.000 claims description 2
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- HUKIJZIDGFUNMG-UHFFFAOYSA-N dimethyl 4-oxocyclohexane-1,2-dicarboxylate Chemical compound COC(=O)C1CCC(=O)CC1C(=O)OC HUKIJZIDGFUNMG-UHFFFAOYSA-N 0.000 claims description 2
- WMVRXDZNYVJBAH-UHFFFAOYSA-N dioxoiron Chemical compound O=[Fe]=O WMVRXDZNYVJBAH-UHFFFAOYSA-N 0.000 claims description 2
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- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 2
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- 229960005336 magnesium citrate Drugs 0.000 claims description 2
- 239000004337 magnesium citrate Substances 0.000 claims description 2
- 235000002538 magnesium citrate Nutrition 0.000 claims description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 2
- 239000001755 magnesium gluconate Substances 0.000 claims description 2
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- 239000011742 magnesium glycerophosphate Substances 0.000 claims description 2
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- 239000000347 magnesium hydroxide Substances 0.000 claims description 2
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- OVGXLJDWSLQDRT-UHFFFAOYSA-L magnesium lactate Chemical compound [Mg+2].CC(O)C([O-])=O.CC(O)C([O-])=O OVGXLJDWSLQDRT-UHFFFAOYSA-L 0.000 claims description 2
- 239000000626 magnesium lactate Substances 0.000 claims description 2
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- HXTFHSYLYXVTHC-AJHDJQPGSA-N narirutin 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=C3O[C@@H](CC(=O)C3=C(O)C=2)C=2C=CC(O)=CC=2)O1 HXTFHSYLYXVTHC-AJHDJQPGSA-N 0.000 description 1
- HXTFHSYLYXVTHC-ZPHOTFPESA-N narirutin Natural products C[C@@H]1O[C@H](OC[C@H]2O[C@@H](Oc3cc(O)c4C(=O)C[C@H](Oc4c3)c5ccc(O)cc5)[C@H](O)[C@@H](O)[C@@H]2O)[C@H](O)[C@H](O)[C@H]1O HXTFHSYLYXVTHC-ZPHOTFPESA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 description 1
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- 206010029410 night sweats Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 208000024335 physical disease Diseases 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000035946 sexual desire Effects 0.000 description 1
- 230000036299 sexual function Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
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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)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- 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)
- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
Abstract
The present invention relates to an oral composition comprising at least a citrus fruit extract, preferably a lemon extract from Citrus limon (L.) Osbeck, and at least an Ashwagandha (Withania somnifera (L.) Dunal) extract, and use thereof in the treatment and/or prevention of disorders associated with menopause.
Description
Title
Oral composition for the treatment and/or prevention of disorders associated with menopause.
STATE OF THE ART
Menopause means the definitive cessation of menstrual cycles, resulting from the loss of ovarian follicular function, and is retrospectively diagnosed after 12 consecutive months of amenorrhea or absence of the menstrual cycle.
The climacteric is defined as the period that precedes and follows menopause. During this transition phase, the onset of physical and psychological disorders, which depend on the progressive deficiency of hormones (including estrogen) and the involution of the functional activity of the ovaries, is common. Indicatively, the climacteric begins around 40-50 years of age and lasts about 7-10 years. Although not a disease, this physiological phase is characterized by a series of disorders (hot flashes, insomnia, irritability, vaginal dryness, decreased libido), common to many women; we speak, in fact, of climacteric syndrome.
Hot flashes (or flushes) and sweating, secondary to vasomotor instability, affect 75 to 85% of women and usually appear before the interruption of the menstrual cycle. They last on average about 7.5 years, but also more than 10 years. Generally, the intensity and frequency of hot flashes decrease over time. They are the most common reason for which women seek medical attention during the perimenopausal period, especially if symptoms impair the quality of life.
Symptoms associated with menopause, both neurovegetative (hot flashes, sweating, headache) and psychoaffective (irritability, anxiety, depression, nervousness, sleep disorders), as well as osteoporosis and increased cardiovascular risk, which are known to manifest themselves in the climacteric, are attributable to the lack of estrogens.
Hormone replacement therapy therefore constitutes an effective therapeutic remedy. However, the administration of estrogen is not without risk, especially in the long term. Risks of estrogen therapy and combined estrogen/progestogen therapy include endometrial cancer, deep vein thrombosis, pulmonary embolism, stroke, breast cancer, cholecystopathy, and urinary stress incontinence. Additionally, estrogen therapy may be contraindicated in women who have had or are at high risk for breast cancer, stroke, coronary heart disease, or thrombosis.
A natural aid against menopause symptoms would seem to come from phytoestrogens. These are compounds of plant origin with a biphenolic structure similar to that of estrogens. This provides them with pseudo- hormonal properties, including the ability to bind estrogen receptors, and are therefore also known as plant estrogens. Although these molecules have been the object of extensive research, their role in the well-being of the human body remains controversial1 ,2 due to the estrogen-like effects that may be a risk for some individuals (for example in women undergoing treatment with tamoxifen, phytoestrogens could antagonize the desired antiestrogenic effect of the drug).
Due to the possible adverse effects of hormonal and phytoestrogen-based therapy, there is an increasing demand for alternative natural treatments
(certainly less powerful than hormones but surely free of serious side effects) for the symptoms and pathological processes associated with menopause.
Several studies have shown that the reduction in estrogens that occurs in menopause is associated with an increase in oxidative stress. In addition to being associated with a wide range of diseases (cardiovascular diseases, diabetes, Alzheimer’s disease, etc.), oxidative stress is also involved in the pathogenesis of vasomotor disorders of menopause (hot flashes and night sweats).3
Flavonoids or bioflavonoids represent a large class of phenolic compounds widespread in the plant world. From the numerous studies conducted on this large variety of compounds, it has emerged that flavonoids are able to exert various beneficial actions on the human body. More specifically, among the main biological activities ascribed to flavonoids4 we find: antioxidant and radical scavenger activity; anti-inflammatory activity and protective and strengthening activities against capillaries and microcirculation.
Their potential ability to capture and chelate metals and reactive oxygen species (ROS) depends on the chemical structure and the number and position of the hydroxy groups. This antioxidant action makes flavonoids very useful in all those conditions characterized by strong oxidative stress.
It has also been observed that flavonoids improve the quality of the blood vessel wall and protect against aging processes by reducing the risk of atherosclerosis5.
Plants belonging to the Citrus genus, more commonly known as citrus
fruits, are particularly rich in bioflavonoids. Among these, the lemon (deriving from the Citrus lirnon L. plant) is a fruit very rich in important natural compounds, including flavonoids, citric acid, ascorbic acid, minerals, and essential oils. Lemon extract is usually titrated in flavonoids (not belonging to the class of isoflavones).
Ashwagandha (also called Withania somnifera (L.) Dunal) is a plant which has been known for many years for its adaptogenic properties. Over 50 chemical constituents have been identified in the various parts of the Ashwagandha plant; among the major components we find alkaloids (isopelletierins, anaferins, etc.), steroidal lactones (withanolides, withaferins) and saponins.6 The extract is usually titrated in withanolides. Many pharmacological studies were conducted in order to describe the multiple biological activities of the Withania somnifera L. Dunal plant. Ashwagandha helps reduce stress, anxiety, mood swings, cortisol levels and stress-related food cravings.7 Ashwagandha exerts its beneficial effects on anxiety and related disorders thanks to its GABA-mimetic properties.8 The clinical study conducted by Chandrasekhar and collaborators9 showed that Ashwagandha is able to reduce cortisol levels in the blood, thus reducing the levels of stress and depression, and of physiological markers of anxiety. Moreover, by significantly reducing cortisol concentrations, Ashwagandha helps relieve insomnia. Ashwagandha exerts these positive effects on sleep disorders without causing drowsiness during the day or, on the contrary, possessing the excessively stimulating effects that other excellent phytotherapeutic drugs with a tonic action can sometimes have, such as real ginseng.
One study has shown that Ashwagandha can reduce the onset of vasomotor symptoms.10
Furthermore, Ashwagandha can be effective in improving both immediate and general memory, as well as improving executive function, attention, and information processing speed.11
The study conducted by Dongre and collaborators12 showed that Ashwagandha is able to improve sexual function in healthy women.
Finally, Ashwagandha also appears to have an anti-aging effect.13 Aging and lifespan of normal and healthy cells are linked to the telomerase shortening mechanism, which limits cells to a fixed number of divisions. Extracts from Ashwagandha root can significantly increase telomerase activity, thereby protecting against telomere loss and potentially delaying aging. A study conducted by Raguraman and collaborators13 showed that the incubation of human FleLa cells with Ashwagandha root extract improved telomerase activity by 45%.
Flowever, to date, none of the pharmacological treatments or natural treatments available on the market has allowed us to observe a particular and valid efficacy in the prevention and/or treatment of disorders associated with menopause.
The need for a new and improved therapeutic treatment that has the advantage of being a highly specific treatment with reduced or even absent side effects, as compared to the classic therapies known for the treatment and/or prevention of disorders associated with menopause, is therefore apparent.
DESCRIPTION OF THE INVENTION
An object of the present invention is therefore to provide a natural, innovative, and non-hormonal, effective and safe product for the treatment of menopause symptoms, both of neurovegetative and psychoaffective nature.
Reiterating the need for a formulation capable of treating as many as possible disorders associated with menopause, both of neurovegetative and psychoaffective nature, without having to resort to conventional hormonal therapies or therapies with phytoestrogens due to some of their undesirable effects, the inventors have surprisingly observed that the compositions object of the present invention are particularly effective in the treatment and prevention of disorders related to menopause.
In particular, it has been observed that a composition comprising a Citrus Limon (L.) Osbeck extract and an Ashwagandha ( Withania somnifera (L.) Dunal) extract is able to prevent and treat disorders associated with menopause in a group of women undergoing treatment.
An object of the present invention is therefore a composition comprising an Ashwagandha extract and at least a citrus fruit extract selected from Citrus Limon (L.) Osbeck extract; Citrus Aurantiifolia (Christm.) Swingle extract; Citrus Aurantium var. amara L. extract; Citrus Aurantium var. dulcis Hayne extract; Citrus x Bergamia Risso & Poit. extract; Citrus Maxima (Burm.) Merr. extract; Citrus Medica L. extract; Citrus Myrtifolia Raf. extract; Citrus Nobilis Lour extract; Citrus Paradisi Macfad. extract; Citrus Reticulata Blanco extract; Citrus Sinensis (L.) Osbeck extract or Citrus Japonica Thunb extract.
Preferably said citrus extract comprises a Citrus Limon (L.) Osbeck extract,
a Citrus Aurantium var. amara L. extract, a Citrus Maxima (Burm.) Merr extract, a Citrus Paradisi Macfad extract and/or a mixture thereof.
Preferably, said citrus fruit extract can be titrated in total bioflavonoids or in specific organic substances belonging to the class of bioflavonoids, selected from diosmin, hesperidin, hesperitin, narirutin, eriocitrin, tangeritin or catechins.
According to a preferred aspect of the present invention, said citrus fruit extract is in the form of a liquid extract, a dry extract, or a soft extract. Preferably said liquid extract is a hydroalcoholic, aqueous, alcoholic, or ethereal extract.
Preferably, said citrus fruit extract comprises the usable parts of the plant according to ministerial guidelines selected from folium (leaves), flos (flower), fructus (fruit), cortex ex ramis (bark from branches), pericarpum (pericarp), semen (seed) or aetheroleum (essential oil).
Preferably said citrus fruit extract has a bioflavonoid content comprised between 5% and 60%, preferably between 10% and 50%.
According to a preferred aspect, the composition of the present invention comprises an extract of Citrus Limon (L.) Osbeck, or synonyms thereof. More preferably, the Citrus Limon (L.) Osbeck extract has a titrated bioflavonoid content comprised between 10% and 50%.
Preferably said Citrus Limon (L.) Osbeck extract is obtained from the fruit (pulp and pericarp) of the plant.
In the composition of the present invention, Ashwagandha ( Withania somnifera) extracts, deriving from the traditionally used parts selected from flos (flower), herba (grass), radix (root), are preferably used. Preferably said
Ashwagandha extracts have a withanolides content comprised between 2 and 50% and/or an alkaloid content comprised between 5 and 10%.
More preferably, the Ashwagandha extract has a withanolides titer of 5%. According to a preferred aspect of the present invention, said Ashwagandha extract is in the form of a liquid extract, a dry extract, or a soft extract.
Preferably said liquid extract is a hydroalcoholic, aqueous, alcoholic, or ethereal extract.
According to a preferred aspect, the composition of the present invention comprises at least one further component selected from mineral salts, vitamins and/or physiologically acceptable excipients.
Preferably, said vitamins are selected from Vitamin A, Vitamin B1 , Vitamin B2, Vitamin B6, Vitamin B3, Vitamin B9 (folic acid or folate), Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K, Vitamin K2, biotin and/or a mixture thereof.
More preferably, the composition of the present invention comprises vitamins of group B, selected from Vitamin B1 , Vitamin B2, Vitamin B6, Vitamin B9, Vitamin B12, Vitamin D, Vitamin E and/or a mixture thereof. According to a preferred aspect, said vitamins are present in the composition in an amount comprised between 2.5 pg and 250 mg, more preferably in an amount comprised between 5 pg and 150 mg.
Preferably said vitamins are present in the composition in an amount by weight comprised between 0.0001% and 35%, more preferably between 0.001% and 25%, with respect to the total weight of the composition. Preferably, said mineral salts are selected from magnesium salts or other
sources of magnesium such as magnesium-enriched yeast, calcium salts, zinc salts, sources of phosphorus selected from phosphoserine or other amino acid chelate, monobasic potassium phosphate, phosphorus proteinate or phosphorus-enriched yeast, or selenium sources selected from selenomethionine, or other amino acid chelate, selenium aspartate, selenium proteinate, selenium ascorbate, sodium selenite or selenium- enriched yeast and/or a mixture thereof, more preferably magnesium salts. According to the present invention, magnesium salts means any of its salts, selected from magnesium citrate, magnesium orotate, magnesium pidolate, magnesium bisglycinate, magnesium chloride, magnesium oxide, magnesium carbonate, magnesium hydroxide, magnesium aspartate, magnesium acetate, magnesium gluconate, magnesium glycerophosphate, magnesium lactate, magnesium salts of orthophosphoric acid, magnesium pyruvate, magnesium lysinate, magnesium methionate, magnesium succinate, magnesium hypophosphate, magnesium ascorbate, or magnesium sulfate or magnesium chelated with amino acids.
Preferably said mineral salts are present in the composition so as to bring an amount of magnesium comprised between 5 mg and 450 mg, more preferably an amount of magnesium comprised between 56 mg and 375 mg.
Preferably, said mineral salts are present in the composition so as to bring an amount of calcium, zinc, or phosphorus comprised between 1 mg and 1200 mg, more preferably an amount of calcium, zinc or phosphorus comprised between 1.5 mg and 800 mg.
Preferably said mineral salts are present in the composition so as to bring
an amount of selenium comprised between 5 pg and 100 pg, more preferably an amount of selenium comprised between 8.5 pg and 55 pg. Preferably said mineral salts are present in the composition in an amount by weight comprised between 0.3% and 90%, more preferably comprised between 3.7% and 75%, with respect to the total weight of the composition. According to a further preferred aspect, the composition of the present invention comprises at least a citrus fruit extract selected from Citrus Limon (L.) Osbeck extract; Citrus aurantiifolia (Christm.) Swingle extract; Citrus aurantium var. amara L. extract; Citrus aurantium var. dulcis Hayne extract; Citrus x bergamia Risso & Poit. extract; Citrus maxima (Burm.) Merr. extract; Citrus medica L. extract; Citrus myrtifolia Raf. extract; Citrus nobilis Lour extract; Citrus paradisi Macfad. extract; Citrus reticulata Blanco extract; Citrus Sinensis (L.) Osbeck extract or Citrus japonica Thunb extract in an amount comprised between 10 mg and 2000 mg, preferably in an amount comprised between 25 mg and 500 mg.
Preferably said citrus extract comprises a Citrus Limon (L.) Osbeck extract, a Citrus Aurantium var. amara L. extract, a Citrus Maxima (Burm.) Merr extract, a Citrus Paradisi Macfad extract or a mixture thereof in an amount comprised between 10 mg and 2000 mg, preferably comprised between 25 mg and 500 mg.
Preferably, said composition comprises a Citrus Limon (L.) Osbeck extract in an amount comprised between 10 mg and 2000 mg, preferably comprised between 25 mg and 500 mg.
According to a further preferred aspect, the composition of the present invention comprises an Ashwagandha extract in an amount comprised
between 10 mg and 2000 mg, preferably comprised between 25 mg and 600 mg.
According to a further preferred aspect, the composition of the present invention comprises at least a citrus fruit extract selected from Citrus Limon (L.) Osbeck extract; Citrus aurantiifolia (Christm.) Swingle extract; Citrus aurantium var. amara L. extract; Citrus aurantium var. dulcis Hayne extract; Citrus x bergamia Risso & Poit. extract; Citrus maxima (Burm.) Merr. extract; Citrus medica L. extract; Citrus myrtifolia Raf. extract; Citrus nobilis Lour extract; Citrus paradisi Macfad. extract; Citrus reticulata Blanco extract; Citrus Sinensis (L.) Osbeck extract or Citrus japonica Thunb extract in an amount by weight comprised between 0.5% and 50%, preferably between 1 .5% and 40%, even more preferably between 5% and 35%, with respect to the total weight of the composition.
Preferably, the composition of the present invention comprises a Citrus Limon (L.) Osbeck extract in an amount by weight comprised between 0.5% and 50%, preferably between 1.5% and 40%, even more preferably between 5% and 35%, with respect to the total weight of the composition. According to a further preferred aspect, the composition of the present invention comprises an Ashwagandha extract in an amount by weight comprised between 0.5% and 50%, preferably between 1.5% and 47%, even more preferably between 5% and 45%, with respect to the total weight of the composition.
The invention relates to a form for oral administration and the compositions of the invention may be formulated in any form suitable for oral administration selected from capsules, tablets, effervescent or chewable
tablets, granules or powders in sachets, controlled release solid forms selected from gastro-resistant capsules or tablets, three-layer tablets, tablets with slow-release polymer matrix, gastro-resistant microgranules, microgranules with internal slow-release polymer matrix or chewable gums. A physiologically acceptable excipient according to the present invention is any excipient known to the person skilled in the art as useful in the preparation of pharmaceutical, dietary and/or cosmetic compositions, such as, but not limited to, dispersing agents, carrier agents, flavoring agents or dyes.
Preferably, suitable excipients according to the present invention are selected from inulin, maltodextrin, magnesium stearate, silicon dioxide, dibasic calcium phosphate, iron oxide, iron dioxide, titanium dioxide, citric acid, magnesium salts of fatty acids, microcrystalline cellulose, talc, polyethylene glycol, calcium carbonate, shellac, acetic esters of mono- and diglycerides, polyvinylpyrrolidone, hydroxypropyl methylcellulose or mixtures thereof.
The excipients are usually classified according to the function they have in the final composition. Preferably suitable excipients according to the present invention are, for example, diluents, adsorbents, glidants, binders, lubricants, surfactants, disintegrants, preservatives, antioxidants, or mixtures thereof.
Otherwise, excipients may be classified based on the functional group present in their chemical structure, such as, for example, sugars, amides, ethers, alcohols and the like.
Particularly preferred excipients according to the present invention are
magnesium salts of fatty acids, dibasic calcium phosphate, magnesium stearate, silicon dioxide, hydroxypropyl cellulose or dyes.
Preferably, the excipients usable for the purposes of the present invention are present in the above formulation in an amount by weight comprised between 10% and 60%, more preferably between 15% and 45%, with respect to the total weight of the formulation.
A further object of the present invention is the use of a composition according to the present invention, comprising an Ashwagandha extract and at least a citrus fruit extract selected from selected from Citrus Limon (L.) Osbeck extract; Citrus aurantiifolia (Christm.) Swingle extract; Citrus aurantium var. amara L. extract; Citrus aurantium var. dulcis Hayne extract; Citrus x bergamia Risso & Poit. extract; Citrus maxima (Burm.) Merr. extract; Citrus medica L. extract; Citrus myrtifolia Raf. extract; Citrus nobilis Lour extract; Citrus paradisi Macfad. extract; Citrus reticulata Blanco extract; Citrus Sinensis (L.) Osbeck extract or Citrus japonica Thunb extract as a medicament.
According to a preferred aspect, the composition according to the present invention is for use in the treatment and/or prevention of disorders associated with pre-menopause, menopause and/or post-menopause. Preferably, said citrus fruit extract is a Citrus Limon (L.) Osbeck extract, a Citrus Aurantium extract, a Citrus Maxima (Burm.) Merr extract, a Citrus Paradisi Macfad extract or a mixture thereof, more preferably said citrus fruit extract is a Citrus Limon (L.) Osbeck extract.
Preferably said disorders associated with pre-menopause, menopause and/or post-menopause are selected from heat exhaustion, sweating,
headache, vaginal dryness, reduced sex drive, irritability, anxiety, depression, nervousness, sleep disorders, osteoporosis and/or increased cardiovascular risk.
More preferably, the composition according to the present invention is for use in the treatment and/or prevention of disorders associated with pre menopause, menopause and/or post-menopause selected from headache, anxiety, depression, sleep disorders, osteoporosis and/or increased cardiovascular risk.
A further preferred aspect is the use of the composition according to the present invention in the treatment and/or prevention of disorders associated with pre-menopause, menopause and/or post-menopause, selected from heat exhaustion, sweating, vaginal dryness, reduced sex drive, irritability, and nervousness.
The compositions object of the present invention may be administered once or more times a day, preferably from one to two times a day.
Preferably said compositions are administered twice a day for a period of 1 month and subsequently once a day for another month.
According to a further preferred aspect, said compositions are administered for at least two weeks, more preferably for at least 8 weeks.
DEFINITIONS
Unless otherwise defined, all terms of the art, notations, and other scientific terms used herein are intended to have the meanings commonly understood by those skilled in the art to which this description belongs. In some cases, terms with meanings that are commonly understood are defined herein for clarity and/or ready reference; therefore, the inclusion of
such definitions in the present description should not be construed as being representative of a substantial difference with respect to what is generally understood in the art.
The term “physiologically acceptable excipient” refers to a substance devoid of any pharmacological effects of its own, and that does not produce any adverse reactions when administered to a mammal, preferably a human being. Physiologically acceptable excipients are well known in the art and are described, for example, in Handbook of Pharmaceutical Excipients, sixth edition 2009, incorporated herein by reference.
The terms “comprising”, “having”, “including” and “containing” are to be intended as open-ended terms (i.e., meaning “comprising, but not limited to”), and are to be considered as a support also for terms such as “consist essentially of”, “consisting essentially of”, “consist of”, or “consisting of”.
The terms “consists essentially of”, “consisting essentially of” are to be intended as semi-closed terms, meaning that no other ingredients affecting the novel features of the invention are included (optional excipients may therefore be included).
The terms “consists of”, “consisting of” are to be intended as closed terms. The term “citrus fruit extract” means a liquid (fluid extracts), solid (dry extracts) or intermediate consistency (soft extracts) pharmaceutical preparation obtained from the fruit and/or plant of citrus fruit (scientific name Citrus), by means of suitable extraction processes known in the art or as described, for example, in “Tecniche estrattive solido-liquido. Teoria e pratica, Aracne editore 2008”.
The term “lemon extract” means a liquid (fluid extracts), solid (dry extracts)
or intermediate consistency (soft extracts) pharmaceutical preparation obtained from the lemon fruit and/or plant (scientific name in Latin Citrus Limon (L.) Osbeck ), by means of suitable extraction processes known in the art or as described for example in “Tecniche estrattive solido-liquido. Teoria e pratica, Aracne editore 2008.”
The term “Ashwagandha ( Withania somnifera (L.) Dunal) extract” means a liquid (fluid extracts), solid (dry extracts) or intermediate consistency (soft extracts) pharmaceutical preparation, obtained starting from one or more parts of the Ashwagandha shrub (scientific name in Latin Withania somnifera (L.) Dunal), by means of suitable extraction processes known in the art or as described for example in “Tecniche estrattive solido-liquido. Teoria e pratica, Aracne editore 2008.”
According to the present invention, the term “titrated in total bioflavonoids” means a certified extract identified by a specific concentration of bioflavonoids, a class of secondary metabolites produced by plants characterized by a polyphenolic chemical structure, having 15 carbon atoms divided into 3 rings (two benzyl rings and a heterocycle).
The term “disorders associated with menopause” refers to a series of disorders of both neurovegetative and psych oaffective nature, which include hot flashes, sweating, insomnia and sleep disorders, irritability, mood swings, headaches, tiredness/fatigue, vaginal dryness, decreased libido, osteoporosis, and cardiovascular risks.
The term “pre-menopause” refers to a variable period of time that precedes menopause.
The term “post-menopause” refers to a period of time of variable duration
following menopause.
FIGURES
Figure 1 : Figure 1 shows the effect of the formulation tested for menopause symptoms.
Figure 2: Figure 2 shows the effect of the formulation tested for changes in decreased libido.
EXPERIMENTAL SECTION
Some examples of the formulation of the supplement object of the present invention are reported for illustrative but not limitative purposes.
EXAMPLE 1
EXAMPLE 2
EXAMPLE 3
EXAMPLE 4
EXAMPLE 5
EXAMPLE 6
CLINICAL STUDY
An observational epidemiological study was conducted on a group of 40 women in pre-menopause or post-menopause phases with classic autonomic and psychoaffective symptoms. The enrollment period was of 2 months and a follow-up check was performed at day 15, day 30 and day
60. The women were treated with the formulation of Example 1 , twice a day for a period of 1 month and then with 1 capsule a day for another month. The purpose of the study was to verify the efficacy of the formulation in improving the well-being of the woman during the study period, by relieving the neurovegetative and psycho-affective symptoms typical of menopause, such as hot flashes, sweating, sleep disorders, mood swings, irritability, headaches, feelings of tiredness/fatigue and decreased libido.
FOLLOW-UP AND OBSERVATIONAL RESULTS
A total of 40 women between the ages of 47 and 60 (average 51.7 ± 3.4 years) were enrolled for the observational study. Of these, 25 women were in a pre-menopause phase and the other 15 were in a post-menopause phase.
A numerical scale from 0 (no symptoms) to 5 (maximum intensity) was used for the evaluation of symptoms.
The 7 most common symptoms associated with menopause were evaluated: hot flashes, sweating, sleep disorders, mood swings, irritability, headaches, tiredness/fatigue.
The results, reported as the average value for each symptom ± the standard deviation, are summarized in Table 1 and graphically represented in Figure 1.
Table 1. Effect of the formulation of Example 1 on the classic symptoms of menopause.
Table 2 shows the percentage changes calculated with respect to visit 1. Table 2. Percentage change in symptoms associated with menopause calculated for visit 2 (day 15), visit 3 (day 30) and visit 4 (day 60) compared to the starting value recorded at visit 1.
% REDUCTION COMPARED TO VISIT 1
VISIT 2 VISIT 3 VISIT 4
HOT FLASHES 21.6 44.4 60.8
SWEATING 22.8 43.0 64.2 SLEEP DISORDERS 20.1 40.3 52.2 MOOD SWINGS 21.3 40.2 59.6 IRRITABILITY 26.4 43.8 54.8 HEADACHE 28.4 40.3 44.3 TIREDNESS/FATIGUE 28.7 42.4 54.8
All treated women reported a reduction in symptoms related to hot flashes, sweating, sleep disorders, mood swings, irritability, headache, and fatigue. An improvement in symptoms was observed already after 15 days of
treatment, while after 2 months of treatment the average reduction of all symptoms was of 55.8%. Hot flashes and sweating, the most annoying menopause symptoms, recorded a clear and surprising reduction after 2 months of treatment, equal to 60.8% and 64.2%, respectively.
In addition to the symptoms described above, the efficacy of the treatment in improving the decreased libido was also evaluated in a small group of patients compared to the total number of women enrolled (18 patients). The results are shown in Figure 2, where changes in decreased libido are observed.
After 2 months of treatment with the formulation of Example 1 , an improvement in sexual desire (libido) equal to 28.3% was obtained.
CONCLUSIONS
In general, the results of the observational study showed that the formulation containing a lemon extract (d.e. from Citrus Limon (L.) Osbeck) and an Ashwagandha ( Witania somnifera (L.) Dunal) extract is surprisingly effective in improving symptoms (both of neurovegetative and psychoaffective nature) associated with the menopause period (pre- and post-menopause).
BIBLIOGRAPHY
1. Messina M, Soy and Health Update: Evaluation of the Clinical and Epidemiologic Literature. Nutrients 8 (2016) 754.
2. Sukalingam K et al., An insight into the harmful effects of soy protein: A review. Clin. Ter. 166 (2015) 131.
3. Doshi SB et al., The role of oxidative stress in menopause. J. Midlife Health. 4 (2013) 140.
4. Ross JA et al., Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu. Rev. Nutr. 22 (2002) 19.
5. McCullough ML et al., Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am. J. Clin. Nutr. 95 (2012) 454.
6. Mirjalili MH et al., Steroidal lactones from Withania somnifera, an ancient plant for novel medicine. Molecules 14 (2009) 2373.
7. Andrade C et al., A double-blind, placebo-controlled evaluation of the anxiolytic efficacy ff an ethanolic extract of withania somnifera. Indian J. Psychiatry. 42 (2000) 295.
8. Candelario M et al., Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAp receptors. J. Ethnopharmacol. 171 (2015) 264.
9. Chandrasekhar K et al., A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full- spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian. J. Psychol. Med. 34 (2012) 255.
10. Modi MB et al., Clinical evaluation of Ashokarishta, Ashwagandha
Churna and Praval Pishti in the management of menopausal syndrome. Ayu. 33 (2012) 511.
11. Choudhary D et al., Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions. J. Diet. Suppl. 14 (2017) 599.
12. Dongre S et al., Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study. Biomed. Res. Int. 2015 (2015) 284154.
13. Raguraman V et al., Withania somnifera Root Extract Enhances Telomerase Activity in the Human HeLa Cell Line. Adv. Biosci. Biotechnol. 7 (2016) 199.
Claims
1. Composition comprising an Ashwagandha extract and at least a citrus fruit extract selected from Citrus Limon (L.) Osbeck extract; Citrus aurantiifolia (Christm.) Swingle extract; Citrus Aurantium var. amara L. extract; Citrus aurantium var. dulcis Hayne extract; Citrus x Bergamia Risso & Poit. extract; Citrus Maxima (Burm.) Merr. extract; Citrus Medica L. extract; Citrus Myrtifolia Raf. extract; Citrus Nobilis Lour extract; Citrus Paradisi Macfad. extract; Citrus Reticulata Blanco extract; Citrus Sinensis (L.) Osbeck extract or Citrus japonica Thunb extract.
2. Composition according to claim 1 , characterized in that said citrus fruit extract is a Citrus Limon (L.) Osbeck extract; a Citrus Aurantium var. amara L. extract, a Citrus Maxima (Burm.) Merr. extract, a Citrus Paradisi Macfad extract and/or a mixture thereof.
3. Composition according to claims 1 or 2, characterized in that said at least a citrus fruit extract is present in the composition in an amount comprised between 10 mg and 2000 mg, preferably in an amount comprised between 25 mg and 500 mg, and said Ashwagandha extract is present in the composition in an amount comprised between 10 mg and 2000 mg, preferably in an amount comprised between 25 mg and 600 mg.
4. Composition according to any one of the preceding claims, characterized in that it comprises at least a further component selected from mineral salts, vitamins and/or physiologically acceptable excipients.
5. Composition according to claim 4, characterized in that said mineral salts are selected from magnesium salts, or other magnesium sources such as magnesium-enriched yeast, calcium salts, zinc salts, phosphorus
sources selected from phosphoserine or other amino acid chelate, monobasic potassium phosphate, phosphorus proteinate or phosphorus- enriched yeast, or selenium sources selected from selenomethionine or other amino acid chelate, selenium aspartate, selenium proteinate, selenium ascorbate, sodium selenite, or selenium-enriched yeast or a mixture thereof, preferably said magnesium salts are selected from magnesium citrate, magnesium orotate, magnesium pidolate, magnesium bisglycinate, magnesium chloride, magnesium oxide, magnesium carbonate, magnesium hydroxide, magnesium aspartate, magnesium acetate, magnesium gluconate, magnesium glycerophosphate, magnesium lactate, magnesium salts of orthophosphoric acid, magnesium pyruvate, magnesium lysinate, magnesium methionate, magnesium succinate, magnesium hypophosphate, magnesium ascorbate, or magnesium sulfate or magnesium chelated with amino acids.
6. Composition according to claim 4, characterized in that said vitamins are selected from Vitamin A, Vitamin B1 , Vitamin B2, Vitamin B6, Vitamin B3, Vitamin B9, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K, Vitamin K2, biotin and/or a mixture thereof, preferably vitamins of group B, selected from Vitamin B1 , Vitamin B2, Vitamin B6, Vitamin B9, Vitamin B12, Vitamin D, Vitamin E and/or a mixture thereof.
7. Composition according to any one of the preceding claims, characterized in that said at least a citrus fruit extract, is present in a weight amount comprised between 0.5% and 50%, preferably between 1.5% and 40%, more preferably between 5% and 35%, with respect to the total weight of the composition, and said Ashwagandha extract is present in a
weight amount comprised between 0.5% and 50%, preferably between
I .5% and 47%, more preferably between 5% and 45% with respect to the total weight of the composition.
8. Composition according to claim 4, characterized in that it comprises at least a physiologically acceptable excipient selected from inulin, maltodextrin, magnesium stearate, silicon dioxide, dibasic calcium phosphate, iron oxide, iron dioxide, titanium dioxide, citric acid, magnesium salts of fatty acids, microcrystalline cellulose, talc, polyethylene glycol, calcium carbonate, shellac, acetic esters of mono- and diglycerides, polyvinylpyrrolidone, hydroxypropyl methylcellulose or mixtures thereof, more preferably said excipient is selected from magnesium salts of fatty acids, dibasic calcium phosphate, magnesium stearate, silicon dioxide, hydroxypropyl cellulose shell or dyes.
9. Composition according to claim 8, characterized in that said physiologically acceptable excipient is present in a weight amount comprised between 10% and 60%, more preferably between 15% and 45% with respect to the total weight of the composition.
10. Composition according to any one of the preceding claims, characterized in that it is formulated in a form suitable for oral administration, selected from capsule, tablet, effervescent or chewable tablets, granules or powders in sachets, controlled-release solid forms selected from gastro-resistant capsules or tablets, tri-layer tablets, tablets with slow-release polymer matrix, gastro-resistant microgranules, microgranules with internal slow-release polymer matrix or chewable gums.
I I . Composition according to any one of the preceding claims for use as
a medicament.
12. Composition for use according to claim 11 in the treatment and/or prevention of disorders associated with pre-menopause, menopause and/or post-menopause selected from headache, anxiety, depression, sleep disorders, osteoporosis and/or increased cardiovascular risk.
13. Use of the composition according to any one of claims 1-10 in the treatment and/or prevention of disorders associated with pre-menopause, menopause and/or post-menopause selected from heat exhaustion, sweating, vaginal dryness, reduced sex drive, irritability, and nervousness.
14. Composition for use or use of the composition according to claims 10-12, characterized in that it is administered one or more times a day, preferably from one to two times a day, more preferably said composition is administered for at least two weeks, more preferably for at least 8 weeks.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT102021000015242A IT202100015242A1 (en) | 2021-06-10 | 2021-06-10 | Oral composition for the prevention and/or treatment of disorders associated with menopause |
| PCT/IB2022/055367 WO2022259195A1 (en) | 2021-06-10 | 2022-06-09 | Oral composition for the treatment and/or prevention of disorders associated with menopause. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP4351609A1 true EP4351609A1 (en) | 2024-04-17 |
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ID=77801833
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP22732337.5A Pending EP4351609A1 (en) | 2021-06-10 | 2022-06-09 | Oral composition for the treatment and/or prevention of disorders associated with menopause |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP4351609A1 (en) |
| IT (1) | IT202100015242A1 (en) |
| WO (1) | WO2022259195A1 (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019195943A1 (en) * | 2018-04-13 | 2019-10-17 | Urban Juve Provisions Inc. | Cannabis root extract, method of manufacture, method of use |
| US10849948B2 (en) * | 2019-04-16 | 2020-12-01 | The Procter & Gamble Company | Supplement for menopause |
-
2021
- 2021-06-10 IT IT102021000015242A patent/IT202100015242A1/en unknown
-
2022
- 2022-06-09 WO PCT/IB2022/055367 patent/WO2022259195A1/en active Application Filing
- 2022-06-09 EP EP22732337.5A patent/EP4351609A1/en active Pending
Also Published As
| Publication number | Publication date |
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| IT202100015242A1 (en) | 2022-12-10 |
| WO2022259195A1 (en) | 2022-12-15 |
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