WO2005011566A2 - Cosmetic use of a biguanide derivative as an anti-ageing active substance for the skin - Google Patents
Cosmetic use of a biguanide derivative as an anti-ageing active substance for the skin Download PDFInfo
- Publication number
- WO2005011566A2 WO2005011566A2 PCT/FR2004/002039 FR2004002039W WO2005011566A2 WO 2005011566 A2 WO2005011566 A2 WO 2005011566A2 FR 2004002039 W FR2004002039 W FR 2004002039W WO 2005011566 A2 WO2005011566 A2 WO 2005011566A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- group
- use according
- skin
- biguanide derivative
- represent
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Classifications
-
- 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
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/43—Guanidines
-
- 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
Definitions
- the present invention relates to the cosmetic use of a biguanide derivative as an anti-aging and restructuring active ingredient for the skin.
- the skin In mammals in general, especially in humans, the skin consists of two main parts, namely an outer layer, the epidermis and an inner layer, the dermis.
- the epidermis ensures the impermeability of the skin and its resistance. It is renewed approximately every four weeks by the elimination of superficial dead cells.
- the epidermis is mainly composed of three types of cells which are the keratinocytes, very majority, the melanocytes and the Langerhans cells. Each of these cell types contributes by its own functions to the essential role played in the body by the skin.
- the dermis provides the epidermis with solid support. It is also its nourishing element. It is mainly composed of fibroblasts dispersed in a complex medium, called extracellular matrix, mainly composed of collagen fibers, elastin, hyaluronic acid and proteoglycans.
- Collagen represents the "cement" of the dermis. It gives the skin solidity, resistance and ensures hydration (therefore its flexibility). Elastin provides elasticity and tone. Hyaluronic acid gives volume and participates in hydration.
- the skin ages, which manifests itself firstly by the appearance of fine lines and then of wrinkles, especially on the face and / or by sagging of the skin. Aging first affects the epidermis whose thickness is reduced.
- the power of cell division in its basal layer decreases and the renewal time of the superficial corneal layer lengthens.
- the maturation of these cells is imperfect and keratinization no longer leads to the creation of a regular horny layer. and homogeneous. There is concomitantly a disorganization of the deep part of the skin, a slowing down of cell renewal as well as a reduction in the production of collagen and elastin.
- the structuring elements of the skin are the first responsible for our appearance. Indeed, changes in the level of elastin and keratins as well as the density of the collagen network are responsible for the loss of elasticity, wrinkles and sagging of the skin. It is partly on them that cosmetic products act.
- a biguanide derivative advantageously metformin, had an anti-aging and restructuring effect on the epidermis and the papillary dermis and therefore on the skin.
- compositions based on biguanides are already known. They are used in oral form in the treatment of certain forms of diabetes, and mainly of type II diabetes insulin-dependent, as antihyperglycemic agents that promote the return to glycemic control.
- Metformin is the most widely used biguanide derivative in this type of treatment. This medicine is administered orally in the form of tablets containing 500, 850 mg or 1 g of active ingredient.
- the daily dosage is between 1 and 2 g.
- metformin in phase I showed the absence of toxicity of the molecule studied at hypoglycemic doses. Tolerance to the product appears to be good, its chronic toxicity almost zero. There is no change in the growth or behavior of the animals; blood count, uremia and liver function are not altered.
- metformin The antihyperglycemic effect of metformin is due on the one hand to the increase in the activity of endogenous insulin and on the other hand to the action of metformin through mechanisms independent of insulin. Indeed, the action of metformin results in a decrease in the intestinal absorption of glucose, an increase in cellular absorption of blood glucose and a decrease in the production of glucose by the liver (suppression of neoglucogenesis) as well as the amount of insulin needed to normalize blood sugar. These effects result, in part, from the power of metformin to enhance the action of existing insulin by an increase in the activity of the insulin receptor enzyme tyrosine kinase, which triggers the signaling cascade " post-receptor ".
- Metformin is also known in topical compositions to promote healing and as having an angiogenic action (FR 2
- the present invention therefore relates to the cosmetic use of a biguanide derivative of general formula I below:
- the groups R1 and R2 represent, independently of one another, a hydrogen atom, a C 1 -C 7 alkyl group, a cycloalkyl group, a heterocycle, a C 2 -C alkenyl group, an aryl group, an aralkyl group, an aryloxylalkyl group or a heteroaryl group or R1 and R2 taken together represent a C 2 -C alkylene which may contain one or more heteroatoms and the group R3 represents a primary, secondary or tertiary amine or its cosmetically acceptable salt with the exception of the compound of formula
- C- ⁇ -C alkyl group is meant within the meaning of the present invention any C ⁇ -C 7 alkyl group, linear or branched, such as for example methyl, ethyl, propyl, isopropyl or butyl groups as well as their isomers.
- cycloalkyl group is meant in the sense of the present invention any cycloalkyl group containing from 3 to 7 carbon atoms, such as for example the cyclohexanyl group.
- heterocycle By the term of “heterocycle”, one understands within the meaning of the present invention any cycle containing from 3 to 7 atoms, one or more of them being a heteroatom such as for example the atom of nitrogen, oxygen or of sulfur, the others being carbon atoms.
- C 2 -C alkenyl group is meant in the sense of the present invention any C 2 -C alkenyl group, linear or branched such as vinyl or allyl groups.
- aryl group one understands within the meaning of the present invention any aromatic hydrocarbon group such as for example the phenyl group, which can contain one or more substituents, such as for example, a C 1 -C 7 alkyl group as defined above, a C 2 -C 7 alkenyl group as defined above, or a halogen.
- heteroaryl group is meant within the meaning of the present invention any aromatic hydrocarbon group containing one or more heteroatoms, such as for example nitrogen or oxygen sulfur atoms, and which may carry one or more substituents, such as for example , a C- ⁇ -C 7 alkyl group as defined above, a C 2 -C 7 alkenyl group as defined above, or a halogen.
- heteroaryl groups are furyl, isoxazyl, pyridyl, pyrimidyl.
- C 2 -C 7 alkylene group is meant in the sense of the present invention any C 2 -C 7 alkylene group such as for example ethylene, trimethylene, tetramethylene or pentamethylene groups.
- cosmetically acceptable salt is meant within the meaning of the present invention any salt prepared from any non-toxic acid cosmetically acceptable, including organic and inorganic acids.
- Such acids include, acetic, benzenesulfonic, benzoic, citric, ethanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric-lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, tartaric and paratoluenesulfonic.
- hydrochloric acid is used.
- the biguanide derivative according to the present invention is used to increase the production of type III collagen in the papillary dermis, to stimulate the proliferation of keratinocytes in the epidermis and / or to increase the thickness of the epidermis.
- this biguanide derivative has a tightening and / or firming effect on the skin.
- the group R3 represents the secondary amine of the following formula:
- the group R3 represents NH 2 .
- the groups R1 and R2 represent, independently of one another, a hydrogen atom or a C 1 -C 7 alkyl group.
- the biguanide derivative is metformin, even more advantageously in the form of a hydrochloride.
- the derivative can be present in the form of a cosmetic composition for local use, advantageously of the oil, cream, foam, unit, lotion, ointment, liquid, gel, milk or "spray" type.
- the forms can be single-phase vehicles consisting of a neutral hydroxypropylcellulose gel or a charged gel formed of sodium carboxymethylcellulose. It is also possible to prepare creams, forms with a biphasic vehicle, comprising a hydrophilic phase dispersed in a lipophilic phase.
- this composition contains from 0.02 to 2% by weight of the biguanide derivative of general formula I or of its cosmetically acceptable salt and an appropriate excipient.
- excipients can be chosen from compounds having good compatibility with this active principle. These are, for example, water-soluble polymers of the natural polymer type, such as polysaccharides (xanthan gum, locust bean gum, peptine, etc.) or polypeptides, cellulose derivatives of methylcellulose type, hydroxypropylcellulose, hydroxypropyl-methylcellulose or also synthetic polymers, polaxamers, carbomers, PVA or PVP. Finally there .
- cosolvent type excipients such as ethanol, glycerol, benzyl alcohol, humectants (glycerol), agents facilitating the diffusion (transcurol, urea) to this cosmetic composition ), or antibacterial preservatives (methyl p-hydroxybenzoate 0.15%). It can also contain surfactants, stabilizing agents, emulsifiers, thickeners, other active ingredients leading to a complementary or possibly synergistic effect, trace elements, essential oils, perfumes, dyes, collagen, chemical or mineral filters, moisturizers or thermal waters.
- cosolvent type excipients such as ethanol, glycerol, benzyl alcohol, humectants (glycerol), agents facilitating the diffusion (transcurol, urea) to this cosmetic composition ), or antibacterial preservatives (methyl p-hydroxybenzoate 0.15%). It can also contain surfactants, stabilizing agents, emulsifiers, thickeners, other active ingredients leading to a complementary or possibly
- the biguanide derivative or its cosmetically acceptable salt is combined with at least one other active principle.
- the present invention also relates to a cosmetic treatment method for aging the skin by applying a composition comprising a biguanide derivative of general formula I below:
- the groups R1 and R2 represent, independently of one another, a hydrogen atom, a C 1 -C 7 alkyl group, a cycloalkyl group, a heterocycle, a C alkenyl group 2 -C 7 , an aryl group, an aralkyl group, an aryloxylalkyl group or a heteroaryl group or R1 and R2 taken together represent a C 2 -C 7 alkylene which may contain one or more heteroatoms and the group R3 represents a primary amine, secondary or tertiary or its cosmetically acceptable salt with the exception of the compound of formula
- compositions according to the invention and of activity study are given by way of illustration and without limitation.
- Metformin 1%.
- Neutral hydroxypropylcellulose gel (Klucel d'Aqualon type 99 MF EP) at 2.9%: 100% supplement.
- Metformin 1%.
- Metformin 1% by weight relative to the lipophilic phase.
- Hydrocerin emulsion (fatty excipient from Roc® containing petrolatum, paraffin oil, triglycerides, polyoxyethylene ethers and cerisine) at 33% (H / L): complement to 100%.
- the purpose of this study is to evaluate the restructuring and anti-aging activity of an ointment containing metformin at 1% (example of formulation 3) by examining the general morphology following panoptic coloring and by evaluation of the number of keratinocytes in mitosis and of the density of collagen III by immunostaining.
- the products to be tested are applied topically to the explants at a rate of 4 mg per explant, for 10 days, the untreated batches receiving no treatment.
- the histological study is carried out: - on sections fixed in paraffin for observation of the general morphology after staining with Masson trichrome, - on frozen sections for the following immunostaining: I. Immunostaining of cells in mitosis with the anti-monoclonal antibody -Ki 67 (clone 7B11) with the nuclei counter-stained with propidium iodide. II. Immunolabelling of type III collagen with the polyclonal anti-collagen III antibody revealed in DAB (chromogenic revealing product of immunolabelling).
- the mitotic keratinocytes marked with anti-Ki 67, were counted over the entire length of the epidermis on the sections carried out.
- the mitotic index established with values obtained, is twice greater on D5 in the explants treated with the ointment containing metformin compared to the control explants and treated with the excipient.
- the values of the mitotic index on D5 had increased by 25% in the explants treated compared to those measured on D3.
- this index corresponds to the normal values for explants at this stage of survival.
- the labeling of type III collagen made it possible to examine its expression in the papillary dermis and along the JDE.
- the results obtained show that already on D3, in the batch of explants having received the ointment containing metformin, the labeling of collagen is slightly sharper along the JDE compared to that seen in the explants not treated and treated with the excipient.
- This acanthosis is confirmed for an increase in the mitotic index of keratinocytes which gives D5 for the ointment double values of those noted with the control and the excipient and with an increase of about 25% compared to J3. This index returns, at D7 and D10, to normal values.
- the ointment containing metformin also induces an increase in the expression of type III collagen in the papillary dermis and along the JDE which reaches its maximum on D7, and remains very visible on D10.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002534135A CA2534135A1 (en) | 2003-07-29 | 2004-07-29 | Cosmetic use of a biguanide derivative as an anti-ageing active substance for the skin |
EP04786009A EP1651171A2 (en) | 2003-07-29 | 2004-07-29 | Cosmetic use of a biguanide derivative as an anti-ageing active substance for the skin |
JP2006521624A JP2007500172A (en) | 2003-07-29 | 2004-07-29 | Cosmetic use of biguanide derivatives as skin anti-aging agents |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR03/09307 | 2003-07-29 | ||
FR0309307A FR2858227B1 (en) | 2003-07-29 | 2003-07-29 | COSMETIC USE OF A BIGUANIDE DERIVATIVE AS AN ANTI-AGING AGENT FOR SKIN |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2005011566A2 true WO2005011566A2 (en) | 2005-02-10 |
WO2005011566A3 WO2005011566A3 (en) | 2005-03-24 |
Family
ID=34043631
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR2004/002039 WO2005011566A2 (en) | 2003-07-29 | 2004-07-29 | Cosmetic use of a biguanide derivative as an anti-ageing active substance for the skin |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1651171A2 (en) |
JP (1) | JP2007500172A (en) |
CA (1) | CA2534135A1 (en) |
FR (1) | FR2858227B1 (en) |
WO (1) | WO2005011566A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111053700A (en) * | 2018-10-17 | 2020-04-24 | 程定超 | Metformin anti-aging skin care product |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2901133B1 (en) * | 2006-05-22 | 2013-04-26 | Oreal | USE OF GLYCOLYSIS MODULATORS AS ANTI-AGING AGENTS |
US20180092952A1 (en) * | 2015-05-05 | 2018-04-05 | Idunn Technologies | Anti-aging composition comprising a plant extract |
CN111346047B (en) * | 2020-03-12 | 2022-04-01 | 复旦大学 | Thermotropic hydrogel metformin sustained-release preparation and preparation method and application thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5886048A (en) * | 1996-07-16 | 1999-03-23 | Fresenius Ag | PHMB for the treatment of tumor disease |
WO2003037356A1 (en) * | 2001-10-26 | 2003-05-08 | Fresenius Kabi Deutschland Gmbh | Pharmaceutical preparation comprising a growth factor and/or a cytokine and an antiseptic biguanide |
-
2003
- 2003-07-29 FR FR0309307A patent/FR2858227B1/en not_active Expired - Fee Related
-
2004
- 2004-07-29 WO PCT/FR2004/002039 patent/WO2005011566A2/en not_active Application Discontinuation
- 2004-07-29 EP EP04786009A patent/EP1651171A2/en not_active Withdrawn
- 2004-07-29 CA CA002534135A patent/CA2534135A1/en not_active Abandoned
- 2004-07-29 JP JP2006521624A patent/JP2007500172A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5886048A (en) * | 1996-07-16 | 1999-03-23 | Fresenius Ag | PHMB for the treatment of tumor disease |
WO2003037356A1 (en) * | 2001-10-26 | 2003-05-08 | Fresenius Kabi Deutschland Gmbh | Pharmaceutical preparation comprising a growth factor and/or a cytokine and an antiseptic biguanide |
Non-Patent Citations (1)
Title |
---|
HARBORNE L ET AL: "Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome" LANCET THE, LANCET LIMITED. LONDON, GB, vol. 361, no. 9372, 31 mai 2003 (2003-05-31), pages 1894-1901, XP004428386 ISSN: 0140-6736 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111053700A (en) * | 2018-10-17 | 2020-04-24 | 程定超 | Metformin anti-aging skin care product |
Also Published As
Publication number | Publication date |
---|---|
WO2005011566A3 (en) | 2005-03-24 |
EP1651171A2 (en) | 2006-05-03 |
JP2007500172A (en) | 2007-01-11 |
FR2858227B1 (en) | 2005-12-23 |
CA2534135A1 (en) | 2005-02-10 |
FR2858227A1 (en) | 2005-02-04 |
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