EP4087662A1 - Utilisation de la taxodione comme agent anti-glycation - Google Patents
Utilisation de la taxodione comme agent anti-glycationInfo
- Publication number
- EP4087662A1 EP4087662A1 EP21700375.5A EP21700375A EP4087662A1 EP 4087662 A1 EP4087662 A1 EP 4087662A1 EP 21700375 A EP21700375 A EP 21700375A EP 4087662 A1 EP4087662 A1 EP 4087662A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- taxodione
- skin
- cosmetic composition
- glycation
- nails
- 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
- FNNZMRSRVYUVQT-AZUAARDMSA-N Taxodione Chemical compound CC1(C)CCC[C@]2(C)C3=C(O)C(=O)C(C(C)C)=CC3=CC(=O)[C@H]21 FNNZMRSRVYUVQT-AZUAARDMSA-N 0.000 title claims abstract description 101
- ABFQREMAZQPJLS-UHFFFAOYSA-N taxodione Natural products CC(C)C1=CC2=CC(=O)C3C(C)(C)CCCC3(C)C2=CC1=O ABFQREMAZQPJLS-UHFFFAOYSA-N 0.000 title claims abstract description 100
- 230000036252 glycation Effects 0.000 claims abstract description 39
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 35
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 35
- 239000000203 mixture Substances 0.000 claims description 74
- 239000002537 cosmetic Substances 0.000 claims description 60
- 241001529742 Rosmarinus Species 0.000 claims description 19
- 230000032683 aging Effects 0.000 claims description 19
- 239000000284 extract Substances 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 150000002632 lipids Chemical class 0.000 claims description 12
- 238000005502 peroxidation Methods 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 3
- 210000003491 skin Anatomy 0.000 description 23
- 108010005094 Advanced Glycation End Products Proteins 0.000 description 18
- 230000001225 therapeutic effect Effects 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 108010035532 Collagen Proteins 0.000 description 14
- 102000008186 Collagen Human genes 0.000 description 14
- 229920001436 collagen Polymers 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 11
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 229940098773 bovine serum albumin Drugs 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000469 ethanolic extract Substances 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- 239000002035 hexane extract Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 201000001320 Atherosclerosis Diseases 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 6
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- 230000003859 lipid peroxidation Effects 0.000 description 5
- 230000007170 pathology Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 description 3
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- DOUMFZQKYFQNTF-WUTVXBCWSA-N (R)-rosmarinic acid Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-WUTVXBCWSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
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- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 235000015107 ale Nutrition 0.000 description 2
- 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 description 2
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
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- 235000013345 egg yolk Nutrition 0.000 description 2
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical class O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
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- 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
- WCGUUGGRBIKTOS-GPOJBZKASA-N (3beta)-3-hydroxyurs-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C WCGUUGGRBIKTOS-GPOJBZKASA-N 0.000 description 1
- 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 description 1
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- FNNZMRSRVYUVQT-UHFFFAOYSA-N 4-hydroxy-4b,8,8-trimethyl-2-propan-2-yl-5,6,7,8a-tetrahydrophenanthrene-3,9-dione Chemical compound CC1(C)CCCC2(C)C3=C(O)C(=O)C(C(C)C)=CC3=CC(=O)C21 FNNZMRSRVYUVQT-UHFFFAOYSA-N 0.000 description 1
- XUSYGBPHQBWGAD-PJSUUKDQSA-N Carnosol Chemical compound CC([C@@H]1C2)(C)CCC[C@@]11C(=O)O[C@@H]2C2=C1C(O)=C(O)C(C(C)C)=C2 XUSYGBPHQBWGAD-PJSUUKDQSA-N 0.000 description 1
- MMFRMKXYTWBMOM-UHFFFAOYSA-N Carnosol Natural products CCc1cc2C3CC4C(C)(C)CCCC4(C(=O)O3)c2c(O)c1O MMFRMKXYTWBMOM-UHFFFAOYSA-N 0.000 description 1
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 206010063493 Premature ageing Diseases 0.000 description 1
- 208000032038 Premature aging Diseases 0.000 description 1
- 102000005622 Receptor for Advanced Glycation End Products Human genes 0.000 description 1
- 108010045108 Receptor for Advanced Glycation End Products Proteins 0.000 description 1
- ZZAFFYPNLYCDEP-HNNXBMFYSA-N Rosmarinsaeure Natural products OC(=O)[C@H](Cc1cccc(O)c1O)OC(=O)C=Cc2ccc(O)c(O)c2 ZZAFFYPNLYCDEP-HNNXBMFYSA-N 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 1
- 239000004904 UV filter Substances 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003035 anti-peroxidant effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
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- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
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- 229920002674 hyaluronan Polymers 0.000 description 1
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- 102000039446 nucleic acids Human genes 0.000 description 1
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- 239000002674 ointment Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
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- AYEKKSTZQYEZPU-RYUDHWBXSA-N pentosidine Chemical compound OC(=O)[C@@H](N)CCCCN1C=CC=C2N=C(NCCC[C@H](N)C(O)=O)N=C12 AYEKKSTZQYEZPU-RYUDHWBXSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 239000013643 reference control Substances 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- DOUMFZQKYFQNTF-MRXNPFEDSA-N rosemarinic acid Natural products C([C@H](C(=O)O)OC(=O)C=CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-MRXNPFEDSA-N 0.000 description 1
- TVHVQJFBWRLYOD-UHFFFAOYSA-N rosmarinic acid Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=Cc2ccc(O)c(O)c2)C=O TVHVQJFBWRLYOD-UHFFFAOYSA-N 0.000 description 1
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- 235000000346 sugar Nutrition 0.000 description 1
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- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
-
- 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
- TITLE Use of taxodione as an anti-glycation agent
- the present invention relates to the cosmetic or therapeutic use of taxodione to inhibit protein glycation as well as to a cosmetic composition comprising taxodione.
- Reactive Carbonyl Species are compounds with highly reactive carbonyl groups and described for their detrimental effects on proteins, nucleic acids and lipids. They are often generated as metabolic products during lipid peroxidation and glycation (Negre-Salvayre et al., 2008; Semchyshyn, 2014). They are also involved in the formation of advanced glycation end products (AGEs for Advanced Glycation End-products) and advanced lipoxidation end products (ALEs for Advanced Lipoxidation End-products) (Semchyshyn, 2014).
- AGEs Advanced Glycation End-products
- ALEs Advanced Lipoxidation End-products
- RCS, AGEs and ALEs accumulate during aging and oxidative stress related diseases such as atherosclerosis, diabetes and neurodegenerative diseases (Miyata et al., 2000; Gkogkolou et al., 2012; Aldini et al., 2012; Aldini et al. al., 2013; Vistoli et al., 2013; Ayala et al., 2014; Semchyshyn, 2014). Their accumulation in skin tissue leads to premature aging.
- Advanced glycation end products are formed by a non-enzymatic reaction between the aldehyde group of reducing sugars and a protein such as collagen or albumin.
- the reaction is well known as the Maillard reaction.
- an unstable Schiff's base is initially formed and rearranged into more stable ketoamines (Amadori products).
- ketoamines lead to the formation of various advanced glycation end products (AGEs), such as pentosidine (fluorescent compound) and N-carbomethyl lysine (CML, non-fluorescent compound) (Cervantes-Laurean et al. , 2006; Aldini et al., 2013).
- Glycation occurs naturally with dermal proteins, such as collagen, clinical signs increase steadily with age (Grasser et al., 2012).
- Collagen is the main structural protein in the extracellular matrix of various connective tissues in the body such as tendons, ligaments, and skin.
- AGEs accumulate in the tissues with age and reduce elasticity (Cervantes-Laurean et al., 2006), in particular the elasticity of the skin.
- Aminoguanidine also known as pimagedin, was one of the first substances identified as inhibitors of AGE formation (Joglekar et al., 2017). However, some side effects have appeared in clinical trials with diabetic patients (Gkogkolou et al., 2012; Joglekar et al., 2017).
- Flavonoids and biflavonoids are described as having an interesting anti-glycation effect (Gkogkolou et al., 2012; Hori et al., 2012).
- Patent application FR2951085A1 describes that various antioxidant molecules are known to inhibit the glycation reaction. It was subsequently shown that an antioxidant activity was not necessarily linked to the inhibition of the formation of AGEs (A. Schinkovitz et al., Fitorick 131 (2016) 182-188 and S. Morel et al. , Phytochemistry Letters 6 (2013) 498-503).
- the inventors identified from extracts a compound, taxodione, which inhibits the formation of advanced glycation end products and does not exhibit the toxic or adverse effects of known AGE formation inhibitors.
- an object of the present invention relates to the taxodione and / or a composition comprising at least 0.001% of taxodione for its use for inhibiting the glycation of proteins.
- the invention therefore relates to taxodione and / or a composition comprising at least 0.001% taxodione for its use as a medicament, preferably as a medicament which inhibits the glycation of proteins.
- This use can also be non-therapeutic and in particular cosmetic.
- the invention therefore relates to the non-therapeutic use of taxodione in a cosmetic composition and / or a cosmetic composition comprising at least 0.001% of taxodione for inhibiting the glycation of proteins in the skin and / or nails and / or for prevent and / or fight against the signs of aging of the skin and / or nails.
- the invention also relates to a cosmetic composition
- a cosmetic composition comprising at least 0.001% by weight of taxodione and at least 10% of fatty phase.
- Taxodione (CAS 19026-31 -4) is a diterpene also called (4bS, 8aS) - 4b, 5,6,7,8,8a-hexahydro-4-hydroxy-2-isopropyl-4b, 8,8-trimethylphenanthrene -3,9-dione or 11-hydroxyabieta-7,9 (11), 13-triene-6,12-dione, having the chemical structure below
- the taxodione of the various compositions according to the invention preferably comes from rosemary stems, more preferably from an extract of rosemary stems.
- Taxodione can in particular be extracted from rosemary stems by any chemical or mechanical process.
- the taxodione is extracted from rosemary stems by chemical extraction with an organic or hydroalcoholic solvent such as hexane or ethanol.
- rosemary stems can be reduced to a dry powder; the dry powder can be macerated in an organic or aqueous-alcoholic solvent for a given time, preferably at least 5 days; ultrasound can optionally be applied; the liquid phase can be recovered and the solvent can be evaporated.
- the extract of rosemary stems can include at least 0.5% taxodione, at least 1% taxodione, at least 2.5% taxodione, at least 5% taxodione, at least 7.5% taxodione, at least 10% of taxodione or at least 15% of taxodione.
- the cosmetic composition according to the invention comprises at least 0.001% by weight of taxodione and at least 10% of fatty phase.
- Taxodione has lipophilic properties (logP around 4). It is therefore a good candidate for its incorporation into cosmetic formulations, in particular cosmetic formulations having a high level of fatty phase.
- the cosmetic composition can comprise at least 10%, at least 20%, at least 30%, at least 50% or at least 70% of fatty phase.
- the cosmetic composition can be selected from the group consisting of a gel, an anhydrous composition such as oil, an ointment or a butter and an emulsion such as a cream or a milk.
- the cosmetic composition is anhydrous. It then comprises only a fatty phase. More preferably, the cosmetic composition is an oil.
- the inventors have shown that taxodione inhibited the peroxidation of lipids and therefore proved to be a particularly advantageous preservative, in particular for compositions with a high oily phase content. Also, according to one embodiment, the cosmetic composition does not include an additional preservative (ie other than taxodione).
- the taxodione of the cosmetic composition can come from rosemary stems.
- the cosmetic composition comprises, according to a preferred embodiment, an extract of rosemary stems.
- the composition comprises a cosmetically effective amount of taxodione with one or more excipients.
- a cosmetically effective amount here means the amount which is sufficient to produce an inhibitory effect on protein glycation.
- the effect of the cosmetic composition according to the invention can be easily verified by various assays, using tests (as disclosed in the examples below) or appropriate in vivo or in vitro models, in particular by comparison with an inhibitor of glycation of known proteins such as aminoguanidine.
- the cosmetic composition comprises at least 0.05% by weight, preferably at least 0.1% by weight, more preferably at least 1% by weight, at least 5% by weight or at least 10% by weight of taxodione.
- the cosmetic composition is intended for topical application, preferably application to the skin and / or nails, more preferably application to the skin.
- the cosmetic composition according to the invention can comprise an active principle other than taxodione. It may be an anti-aging compound such as hyaluronic acid, retinol, coenzyme Q10, collagen and / or vitamin C and / or a compound having another activity, for example moisturizing activity. , a UV filter and / or an anti-inflammatory agent. According to an alternative embodiment, the cosmetic composition does not comprise rosmarinic acid, ursolic acid, carnosol and / or carnosic acid.
- the cosmetic composition according to the invention is preferably intended to be used for preventing and / or combating the signs of aging of the skin and / or of the nails.
- Cosmetic use of taxodione as an anti-glycation agent relates to the non-therapeutic use of taxodione in a cosmetic composition and / or of a cosmetic composition comprising at least 0.001% by weight of taxodione to inhibit the glycation of proteins of the skin and / or nails, preferably skin proteins.
- Inhibition of protein glycation can be readily verified by various assays, using appropriate tests such as preferably that of Derbre et al. (2012) described in the examples or that of André et al. (2016). Suitable tests may also consist of methods measuring the expression of AGE receptors (Adeshara et al. 2018; Huang et al. 2019).
- the evaluation of the inhibition of the glycation of proteins can be made by comparison with a reference compound known to have an inhibitory activity of the glycation of proteins such as aminoguanidine.
- a compound which has a glycation inhibiting activity greater than or equal to aminoguanidine is an anti-glycation agent.
- a composition is considered to inhibit BSA glycation if the minimum inhibitory concentration (IC 5 o) is less than 0.17 mg / ml and as an inhibitor of collagen glycation if the minimum inhibitory concentration (IC 50 ) is less than 1 mg / ml.
- a pure compound is considered as an inhibitor of BSA glycation if the minimum inhibitory concentration (IC 50 ) is less than 1.5 mM and as an inhibitor of collagen glycation if the minimum inhibitory concentration (IC 50 ) is less than 10 mM .
- the skin proteins that can be inhibited from glycation are typically collagen and / or elastin.
- the nail proteins whose glycation can be inhibited are typically keratin.
- taxodione helps prevent and / or fight against the signs of aging of the skin and / or nails linked to the glycation of proteins.
- an embodiment of the present invention relates to the non-therapeutic use of taxodione in a cosmetic composition and / or of a cosmetic composition comprising at least 0.001% by weight of taxodione for preventing and / or controlling against the signs of aging of the skin and / or nails linked to protein glycation.
- taxodione in addition to its ability to inhibit protein glycation, taxodione can be used to inhibit lipid peroxidation.
- the taxodione can be used in a cosmetic composition to inhibit the peroxidation of skin and / or nail lipids, preferably together with its use to inhibit the glycation of skin and / or nail proteins.
- Inhibition of lipid peroxidation can easily be verified by various assays, using appropriate assays such as the TBARS test described in the examples.
- taxodione By inhibiting the peroxidation of lipids, taxodione makes it possible to prevent and / or fight against the signs of aging of the skin and / or nails associated with the peroxidation of lipids. Also, one embodiment of the present invention relates to the non-therapeutic use of taxodione in a cosmetic composition and / or of a cosmetic composition comprising at least 0.001% by weight of taxodione for preventing and / or combating the signs of aging. of the skin and / or of the nails linked to the peroxidation of lipids, preferably together with the prevention and / or the fight against the signs of aging of the skin and / or of the nails linked to the glycation of proteins.
- the present invention relates to the non-therapeutic use of taxodione in a cosmetic composition for preventing and / or combating the signs of aging of the skin and / or nails.
- Taxodione can be used in a cosmetic composition in particular for stimulating the elasticity of the dermis and the epidermis, strengthening dermo-epidermal cohesion, preventing, limiting the loss of firmness and / or improving the elasticity properties of the epidermis. .
- the present invention also relates to a cosmetic treatment process for preventing and / or combating the signs of aging of the skin and / or nails, in which a cosmetic composition comprising taxodione is applied to the skin and / or nails.
- a cosmetic composition comprising taxodione
- the cosmetic composition will be applied to a subject having or wishing to prevent signs of aging, in particular those caused by the glycation of proteins and possibly those caused by the peroxidation of lipids.
- the present invention also relates to the use of taxodione in the manufacture of a cosmetic composition intended for preventing and / or combating the signs of aging of the skin and / or nails, in particular those caused by the glycation of proteins and optionally. those caused by lipid peroxidation.
- the taxodione is added to at least one cosmetic excipient.
- the cosmetic composition is preferably applied topically, more preferably to the skin.
- the cosmetic composition may comprise a cosmetically effective amount of taxodione with one or more excipients.
- a cosmetically effective amount here means the amount which is sufficient to produce an inhibitory effect on protein glycation.
- the cosmetic composition can comprise at least 0.001% by weight of taxodione.
- the cosmetic composition comprises at least 0.05% by weight, preferably at least 0.1% by weight, more preferably at least 1% by weight, at least 5% by weight or at least 10% by weight of taxodione.
- the taxodione of the cosmetic composition can come from rosemary stems.
- the cosmetic composition comprises, according to a preferred embodiment, an extract of rosemary stems.
- This cosmetic composition can comprise at least 10%, at least 20%, at least 30%, at least 50% or at least 70% of fatty phase.
- the cosmetic composition according to the invention defined above is that preferred for the cosmetic uses and processes according to the invention.
- taxodione As an anti-glycation agent Due to its anti-glycation activity, taxodione can also be used for therapeutic purposes.
- the present invention also relates to taxodione for its use as a medicament, more particularly for its use as a medicament for inhibiting the glycation of proteins.
- EFAs are involved in many pathologies including pathologies such as diabetes, renal failure, atherosclerosis, neurodegenerative diseases and amyloidosis.
- the taxodione or the composition comprising at least 0.001% taxodione can therefore be used in the treatment or prevention of a pathology selected from the group consisting of diabetes, renal failure, atherosclerosis of neurodegenerative diseases and amyloidosis.
- the present invention also relates to a method of treatment or prevention in a subject to be treated, in particular a subject suffering from or having a risk of suffering from diabetes, renal failure, atherosclerosis, neurodegenerative diseases and / or. amyloidosis comprising administration of taxodione to said subject.
- the present invention also relates to the use of taxodione in the manufacture of a medicament, preferably a protein glycation inhibitor medicament, more preferably a medicament for treating a pathology selected from the group consisting of diabetes, insufficiency. renal, atherosclerosis, neurodegenerative diseases and amyloidosis.
- the present invention also relates to a composition comprising taxodione, preferably a composition comprising at least 0.001% taxodione, for its use as a medicament, preferably as a protein glycation inhibitor medicament, even more preferably for its use in the treatment or prevention of a pathology selected from the group consisting of diabetes, renal failure, atherosclerosis, neurodegenerative diseases and amyloidosis.
- a pathology selected from the group consisting of diabetes, renal failure, atherosclerosis, neurodegenerative diseases and amyloidosis.
- composition typically comprises a so-called therapeutically effective dose of the active principle: taxodione.
- the effective dose is determined and adjusted depending on factors such as the composition used, the route of administration, the physical characteristics of the individual considered, such as sex, age and weight, concomitant drugs and other factors that those skilled in the art will be able to determine. For example, it is well known to those skilled in the art to start doses of the active ingredient at levels lower than those required to obtain the desired therapeutic effect and to gradually increase the dose until the desired effect. is reached.
- the daily dosage of the products can vary over a wide range of 0.01 to 1000 mg per adult per day.
- the compositions contain 0.01, 0.05, 0.1, 0.5, 1, 0, 2.5, 5.0, 10.0, 15.0, 25.0, 50.0, 100 ,
- a medicament typically contains about 0.01 mg to about 500 mg of the active ingredient, typically 1 mg to about 100 mg of the active ingredient.
- An effective amount of the drug is usually provided at a dosage level of 0.0002 mg / kg to about 20 mg / kg of body weight per day, in particular about 0.001 mg / kg to 7 mg / kg of body weight per day. day.
- the so-called therapeutic composition intended for use as a medicament comprises at least 0.001% by weight of taxodione, at least 0.05% by weight of taxodione, at least 0.1% by weight of taxodione, at least 1% by weight, at least 5% by weight of taxodione or at least 10% by weight of taxodione.
- the taxodione of the therapeutic composition can be obtained from rosemary stems.
- the therapeutic composition comprises, according to a preferred embodiment, an extract of rosemary stems.
- FIG. 1 shows the measurement according to the method described in Derbré et al. (2012) of the percentage of pentosidine-like AGEs (pentosidine-like AGEs) on BSA as a function of the log concentration of aminoguanidine, ethanolic extract (RBEJ7), hexane extract (RBHex) or taxodione.
- FIG. 2 shows the measurement according to the method described in Derbré et al. (2012) of the percentage of pentosidine-like AGEs (pentosidine-like AGEs) on collagen as a function of the log concentration of aminoguanidine, ethanolic extract (RBEJ7), hexane extract (RBHex) or taxodione.
- Maceration was carried out from 150 g of crushed rosemary stems, in the dark, at room temperature, with 900 g of absolute ethanol; manual stirring was carried out every 24 hours for seven days.
- the stem extract was then filtered and evaporated under reduced pressure to dryness. 5.3 g of ethanolic extract were obtained and called RBEJ7.
- HPLC analysis was performed on an Ultimate 3000 (Thermo Fisher Scientific Inc., San Jose, USA) which included a quaternary pump module, an automatic injector and a DAD detector. The system was driven using Chromeleon software. Chromatographic separation was performed on a C18 Hypersyl ODS column (250 mm x 4.6 mm, 5 ⁇ m, Thermo Fisher Scientific Inc., San Jose, USA), with a column maintained at 35 ° C. The fractions were eluted at a flow rate of 1 ml / min using solvent A (water / formic acid 99.1: 0.1v / v) and solvent B (acetonitrile).
- solvent A water / formic acid 99.1: 0.1v / v
- solvent B acetonitrile
- the gradient used for the analysis was 0-10 min, 85% A; 10-20 min, 85-65% A; 20-25 min, 65-30% A; 25-30 min, 30% A; 30-50 min, 30-20% A; 50-60 min, 20-10% A; 60-70 min, 10-85% A; 70-80 min 85% A.
- the identification of taxodione in the crude extract was based on comparison with the retention time and UV spectrum of a sample of pure taxodione.
- a TBARS test (compounds reactive with thiobarbituric acid) was carried out according to the method of Lavaud et al. (2015) with some modifications. Dried and pasteurized egg yolk is used as a source of lipids (phospholipids, triacylglycerols) and proteins. Briefly, 30 ⁇ l of sample at different concentrations was added to a mixture containing 300 ⁇ l of egg yolk emulsified with 0.1 M phosphate buffer pH 7.4 and 30 ⁇ l of Fe 2+ (1 mM). After 1 h incubation at 37 ° C, 150 ⁇ l of 15% TC A and 300 mI of 1% TBA was added and was kept in a boiling water bath for 20 min. After cooling and centrifugation, the formation of TBARS was measured by absorbance at 532 nm. The results were expressed as a median inhibitory concentration (IC 5 o) (mg / ml).
- the ethanolic and hexane extracts were able to inhibit peroxidation in a complex mixture of lipids. Taxodione showed comparable activity to that of Trolox, the reference compound. It should be noted that the hexane extract is more active than the ethanolic extract which suggests a correlation between the taxodione content and the lipid anti-peroxidation activity of the extracts.
- Pioglitazone inhibits advanced glycation induced protein modifications and down-regulates expression of RAGE and NF-kB in renal cells. International Journal of Biological Macromolecules. 2018 Nov; 119: 1154-1163.
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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FR2000078A FR3105923B1 (fr) | 2020-01-07 | 2020-01-07 | Utilisation de la taxodione comme agent anti-glycation |
PCT/EP2021/050149 WO2021140131A1 (fr) | 2020-01-07 | 2021-01-07 | Utilisation de la taxodione comme agent anti-glycation |
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EP4087662A1 true EP4087662A1 (fr) | 2022-11-16 |
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EP21700375.5A Pending EP4087662A1 (fr) | 2020-01-07 | 2021-01-07 | Utilisation de la taxodione comme agent anti-glycation |
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EP (1) | EP4087662A1 (fr) |
FR (1) | FR3105923B1 (fr) |
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FR2951085B1 (fr) * | 2009-10-09 | 2012-05-18 | Inst Substances Vegetales | Utilisation de composes phenoliques pour la deglycation des proteines |
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