(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2010/0168049 A1
`(43) Pub. Date:
`Jul. 1, 2010
`LABOUREAU et al.
`
`US 201001 68049A1
`
`(54) COMBINATION OF MONOSACCHARIDES
`AND ADENOSINE AND USE THEREOF
`
`(75) Inventors:
`
`Julien LABOUREAU, Issy Les
`Moulineaux (FR); Jean-Thierry
`Simonnet, Cachan (FR); Pascal
`Portes, Nogent Sur Marne (FR)
`
`Correspondence Address:
`OBLON, SPIVAK, MCCLELLAND MAIER &
`NEUSTADT, L.L.P.
`194O DUKE STREET
`ALEXANDRIA, VA 22314 (US)
`
`(73) Assignee:
`
`LOREAL, Paris (FR)
`
`(21) Appl. No.:
`
`12/649,367
`
`(22) Filed:
`
`Dec. 30, 2009
`
`Related U.S. Application Data
`(60) Provisional application No. 61/144,756, filed on Jan.
`15, 2009.
`Foreign Application Priority Data
`
`(30)
`
`Dec. 30, 2008 (FR) ...................................... O8591.51
`Publication Classification
`
`(51) Int. Cl.
`(2006.01)
`A6IR 8/49
`(2006.01)
`A61O 19/00
`(52) U.S. Cl. .......................................................... 514/46
`(57)
`ABSTRACT
`The present invention relates to a composition, especially a
`cosmetic and/or dermatological composition, containing, in a
`physiologically acceptable medium, a combination of at least
`one monosaccharide chosen from mannose, rhamnose and a
`mixture thereof, and of at least one additional compound
`chosen from adenosine, an analogue thereof and a mixture
`thereof.
`
`UNIVERSITY OF MASSACHUSETTS - EX. 2002
`
`

`

`Patent Application Publication
`Patent Application Publication
`
`Jul. 1, 2010 Sheet 1 of 2
`Jul. 1,2010 Sheet 1 of 2
`
`US 2010/01 68049 A1
`US 2010/0168049 Al
`
`
`
`
`
`
`
`
`
`i
`
`150
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`FIGURE 1
`FIGURE 1
`
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`FIGURE 2
`FIGURE 2
`
`
`
`Proliferation index on control in defined medium deficient in
`Proliferation index on control in defined medium deficientin
`growth factors - treatment by L-rhamnose
`growthfactors- treatment by L-rhamnose
`
`200 ng cents
`
`200 - - - - - - -
`
`-
`
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`
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`
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`XTT
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`Control
`100M
`500M
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`500uM
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`
`
`
`
`
`
`
`
`
`
`
`Proliferation index on control in defined medium deficient in
`Proliferation index on control in defined medium deficient in
`growth factors - treatment by D-mannose
`growth factors- treatment by D-mannose
`
`~
`XTT
`O XTT
`at Nile Red
`O Nile Red
`Cyguant
`mg Cyquant
`
`
`
`

`

`Patent Application Publication
`Patent Application Publication
`
`Jul. 1, 2010 Sheet 2 of 2
`Jul. 1,2010 Sheet 2 of 2
`
`US 2010/01 68049 A1
`US 2010/0168049 Al
`
`Count of dermal fibroblasts on reconstructed skin
`Count of dermal fibroblasts on reconstructed skin
`
`300 -
`3. O O
`
`
`
`2 5 O
`
`2 O O
`
`
`
`numberofcells
`
`Totalcumulative
`
`Image 2: Rhamnose 1 mM 120h
`
`mah
`m= 120h
`
`Control
`Control
`
`Rhamnose 5 mM
`Rhamnose 5 mM
`
`FIGURE 3
`FIGURE3
`
`150
`150
`
`100
`100
`
`onOo
`5 O
`
`
`
`Image 1: Control 120h
`Image 1: Control 120h
`
`Image 2 : Rhamnose 1 nM 120h
`
`FIGURE 4
`FIGURE4
`
`

`

`US 2010/01 68049 A1
`US 2010/0168049 Al
`
`Jul. 1, 2010
`Jul. 1, 2010
`
`COMBINATION OF MONOSACCHARIDES
`COMBINATION OF MONOSACCHARDES
`AND ADENOSINE AND USE THEREOF
`AND ADENOSINE AND USE THEREOF
`
`REFERENCE TO PRIOR APPLICATIONS
`REFERENCE TO PRIORAPPLICATIONS
`0001. This application claims priority to U.S. provisional
`[0001] This application claimspriority to U.S. provisional
`application Ser. No. 61/144,756, filed Jan. 15, 2009; and to
`application Ser. No. 61/144,756, filed Jan. 15, 2009; and to
`French patent application 0859151, filed Dec. 30, 2008, both
`French patent application 08 59151, filed Dec. 30, 2008, both
`incorporated herein by reference.
`incorporated herein by reference.
`
`BACKGROUND OF THE INVENTION
`BACKGROUND OF THE INVENTION
`0002 The present invention relates to a composition,
`[0002] The present
`invention relates to a composition,
`especially a cosmetic and/or dermatological composition,
`especially a cosmetic and/or dermatological composition,
`comprising, in a physiologically acceptable medium, a com
`comprising, in a physiologically acceptable medium, a com-
`bination of at least one monosaccharide selected from man-
`bination of at least one monosaccharide selected from man
`nose, rhamnose and a mixture thereof, and of at least one
`nose, rhamnose and a mixture thereof, and of at least one
`additional compound selected from adenosine, an analogue
`additional compound selected from adenosine, an analogue
`thereof and a mixture thereof.
`thereof and a mixture thereof.
`0003. Additional advantages and other features of the
`[0003] Additional advantages and other features of the
`present invention will be set forth in part in the description
`present invention will be set forth in part in the description
`that follows and in part will become apparent to those having
`that follows and in part will become apparentto those having
`ordinary skill in the art upon examination of the following or
`ordinary skill in the art upon examination ofthe following or
`may be learned from the practice of the present invention. The
`maybe learned from the practice ofthe present invention. The
`advantages of the present invention may be realized and
`advantages of the present invention may be realized and
`obtained as particularly pointed out in the appended claims.
`obtained as particularly pointed out in the appended claims.
`As will be realized, the present invention is capable of other
`Aswill be realized, the present invention is capable of other
`and different embodiments, and its several details are capable
`and different embodiments, and its several details are capable
`of modifications in various obvious respects, all without
`of modifications in various obvious respects, all without
`departing from the present invention. The description is to be
`departing from the present invention. The description is to be
`regarded as illustrative in nature, and not as restrictive.
`regardedas illustrative in nature, and notasrestrictive.
`BACKGROUND OF THE INVENTION
`BACKGROUND OF THE INVENTION
`0004 Human skin is made up of two main layers, namely
`[0004] Humanskin is made up of two main layers, namely
`the dermis and the epidermis that superficially covers the
`the dermis and the epidermis that superficially covers the
`dermis. Natural human epidermis is composed mainly of
`dermis. Natural human epidermis is composed mainly of
`three types of cells, namely keratinocytes, which form the
`three types of cells, namely keratinocytes, which form the
`vast majority, melanocytes and Langerhans cells. Each of
`vast majority, melanocytes and Langerhans cells. Each of
`these three types of cells contributes, via its intrinsic func
`these three types of cells contributes, via its intrinsic func-
`tions, to the essential role played in the body by the skin,
`tions, to the essential role played in the body by the skin,
`especially the role of protecting the body against external
`especially the role of protecting the body against external
`attacking factors (the climate, ultraviolet rays, tobacco, etc.),
`attacking factors (the climate, ultraviolet rays, tobacco, etc.),
`whichis also knownas the “barrier function”.
`which is also known as the “barrier function'.
`0005. The epidermis is a keratinized, stratified pavement
`[0005] The epidermisis a keratinized, stratified pavement
`epithelium 90% made up of keratinocytes. The gradual dif
`epithelium 90% made up of keratinocytes. The gradual dif-
`ferentiation of the cells of the basal membrane, which sepa
`ferentiation of the cells of the basal membrane, which sepa-
`rates the dermis from the epidermis, towards the surface of the
`rates the dermis from the epidermis, towards the surface ofthe
`epidermis especially includes the differentiation of kerati
`epidermis especially includes the differentiation of kerati-
`nocytes, which migrate towards the Surface of the skin, where
`nocytes, which migrate towardsthe surface ofthe skin, where
`they descquamate.
`they desquamate.
`0006 Ageing of the epidermis is manifested mainly by a
`[0006] Ageing of the epidermis is manifested mainly by a
`reduction in its thickness. Atrophy of the epidermis is the
`reduction in its thickness. Atrophy of the epidermis is the
`consequence of the slowing down of keratinocyte prolifera
`consequence of the slowing down of keratinocyte prolifera-
`tion and of the accumulation of senescent keratinocytes. The
`tion and of the accumulation of senescent keratinocytes. The
`horny layer becomes dull.
`horny layer becomesdull.
`0007. The dermis provides the epidermis with a solid Sup
`[0007] The dermis provides the epidermis with a solid sup-
`port. It is also its nourishing element. It is made up mainly of
`port. It is also its nourishing element. It is made up mainly of
`fibroblasts and an extracellular matrix composed mainly of
`fibroblasts and an extracellular matrix composed mainly of
`collagen, elastin and a substance known as ground Substance.
`collagen, elastin and a substance knownas ground substance.
`These components are synthesized by the fibroblasts. The
`These components are synthesized by the fibroblasts. The
`cohesion between the epidermis and the dermis is provided by
`cohesion betweenthe epidermis and the dermis is provided by
`the dermo-epidermal junction. This is a complex region about
`the dermo-epidermaljunction. This is a complex region about
`100 nm thick, which comprises the basal pole of the basal
`100 nm thick, which comprises the basal pole of the basal
`keratinocytes, the epidermal membrane and the Sub-basal
`keratinocytes, the epidermal membrane and the sub-basal
`Zone of the superficial dermis.
`zone of the superficial dermis.
`0008 Collagens are the major proteins of the extracellular
`[0008] Collagens are the majorproteins ofthe extracellular
`matrices of the skin. To date, 20 types of collagen have been
`matrices of the skin. To date, 20 types of collagen have been
`identified, and are noted from I to XX. The collagens pre
`identified, and are noted from I to XX. The collagens pre-
`
`dominantly present throughout the epidermis are collagens of
`dominantly present throughoutthe epidermis are collagens of
`the type I and III that form the extracellular matrix of the
`the type I and III that form the extracellular matrix of the
`entire dermis (these collagens constitute 70-80% of the dry
`entire dermis (these collagens constitute 70-80% of the dry
`weight of the dermis). Moreover, collagens are not all Syn
`weight of the dermis). Moreover, collagens are not all syn-
`thesized by the same cell types: collagens of type I and III are
`thesized by the samecell types: collagens of type I and III are
`essentially produced by the dermal fibroblasts, whereas type
`essentially produced by the dermal fibroblasts, whereas type
`VII collagen is produced by two categories of cell, kerati
`VII collagen is produced by two categories of cell, kerati-
`nocytes and fibroblasts. Regulation of their expression differs
`nocytes andfibroblasts. Regulation oftheir expression differs
`from one collagen to another, for example collagens I and VII
`from one collagen to another, for example collagens I and VI
`are not regulated in the same way by certain cytokines; spe
`are not regulated in the same wayby certain cytokines; spe-
`cifically, TNF-C. and leukoregulin stimulate collagen VII and
`cifically, TNF-a and leukoregulin stimulate collagen VIT and
`negatively regulate collagen I. Finally, all collagen molecules
`negatively regulate collagen I. Finally,all collagen molecules
`are variants of a common precursor, which is the C. chain of
`are variants of a common precursor, which is the a chain of
`procollagen.
`procollagen.
`0009. With age, collagen becomes thinner and wrinkles
`[0009] With age, collagen becomes thinner and wrinkles
`appear on the Surface of the skin. Cutaneous ageing is a
`appear on the surface of the skin. Cutaneous ageing is a
`genetically programmed mechanism.
`genetically programmed mechanism.
`0010 Moreover, certain environmental factors such as
`[0010] Moreover, certain environmental factors such as
`Smoking and above all exposure to Sunlight accelerate it. The
`smoking and aboveall exposure to sunlight accelerate it. The
`skin thus has a much more aged appearance on the areas
`skin thus has a much more aged appearance on the areas
`exposed to Sunlight, such as the back of the hands or the face.
`exposed to sunlight, such as the back ofthe handsorthe face.
`Thus, these other factors also have a negative impact on the
`Thus, these other factors also have a negative impact on the
`natural collagen of the skin.
`natural collagen ofthe skin.
`0011 Consequently, given the important role of collagen
`[0011] Consequently, given the importantrole of collagen
`in the integrity of the skin and in its resistance to external
`in the integrity of the skin and in its resistance to external
`attacking factors of mechanical type, Stimulation of the Syn
`attacking factors of mechanical type, stimulation of the syn-
`thesis of these collagens, and in particular of type I collagen,
`thesis of these collagens, and in particular of type I collagen,
`appears to be an effective means for overcoming the signs of
`appears to be an effective means for overcoming the signs of
`ageing of the skin. During chronological and/or actinic age
`ageing of the skin. During chronological and/or actinic age-
`ing, the epidermis also undergoes many changes and degra
`ing, the epidermis also undergoes many changes and degra-
`dations that are reflected, with age, by an impairment in the
`dations that are reflected, with age, by an impairment in the
`microrelief, impairment in the barrier function of the skin, the
`microrelief, impairmentin the barrier function ofthe skin,the
`appearance of wrinkles and fine lines, an impairment in the
`appearance of wrinkles and fine lines, an impairmentin the
`mechanical properties of the skin, especially lack of elasticity
`mechanicalproperties ofthe skin, especially lack of elasticity
`of the skin, and loss of radiance of the complexion.
`of the skin, and loss of radiance of the complexion.
`0012 Expression wrinkles are the result of mechanisms
`[0012] Expression wrinkles are the result of mechanisms
`different from those that generate the wrinkles caused by
`different from those that generate the wrinkles caused by
`ageing. Specifically, they are produced due to the effect of the
`ageing. Specifically, they are produced dueto the effect ofthe
`strain exerted on the skin by the skin muscles that allow facial
`strain exerted on the skin by the skin musclesthat allow facial
`expressions. Depending on the shape of the face, the fre
`expressions. Depending on the shape of the face, the fre-
`quency of facial expressions and possible tics, they may
`quency of facial expressions and possible tics, they may
`appear even from childhood. Expression wrinkles are char
`appear even from childhood. Expression wrinkles are char-
`acterized by the presence of grooves around the orifices
`acterized by the presence of grooves around the orifices
`formed by the nose (nasal grooves), the mouth (perioral
`formed by the nose (nasal grooves), the mouth (perioral
`wrinkles and “sour-face' wrinkles) and the eyes (crow's-feet
`wrinkles and “sour-face” wrinkles) and the eyes (crow’s-feet
`wrinkles), around which are the skin muscles, and also
`wrinkles), around which are the skin muscles, and also
`between the eyebrows (glabella wrinkles or lion wrinkles)
`between the eyebrows (glabella wrinkles or lion wrinkles)
`and on the forehead.
`and on the forehead.
`0013 Hitherto, the only means commonly used for acting
`[0013] Hitherto, the only means commonlyusedfor acting
`on expression wrinkles are, firstly, botulinum toxin, which is
`on expression wrinklesare,firstly, botulinum toxin, which is
`especially injected into the wrinkles of the glabella which are
`especially injected into the wrinkles ofthe glabella which are
`wrinkles between the eyebrows (see J. D. Carruters et al., J.
`wrinkles between the eyebrows(see J. D. Carruterset al., J.
`Dermatol. Sum. Oncol., 1992, 18, pp. 17-21), and, secondly,
`Dermatol. Sum. Oncol., 1992, 18, pp. 17-21), and, secondly,
`degradable implants based on collagen, hyaluronic acid or
`degradable implants based on collagen, hyaluronic acid or
`polylactic acid.
`polylactic acid.
`0014. The importance of having available compositions
`[0014] The importance of having available compositions
`whose effects are directed towards regenerating skin tissue
`whoseeffects are directed towards regenerating skin tissue
`via increasing keratinocyte proliferation and stimulating
`via increasing keratinocyte proliferation and stimulating
`fibroblast proliferation and/or metabolism, and especially
`fibroblast proliferation and/or metabolism, and especially
`stimulating the synthesis of procollagens and collagens, and
`stimulating the synthesis of procollagens and collagens, and
`also for combating cutaneous contractions that are respon
`also for combating cutaneous contractions that are respon-
`sible for the formation of expression wrinkles, may thus be
`sible for the formation of expression wrinkles, may thus be
`appreciated.
`appreciated.
`0015. It is known practice from the literature to use agents
`[0015]
`Itis knownpractice from theliterature to use agents
`Such as retinol, which promote keratinocyte proliferation and
`such asretinol, which promote keratinocyte proliferation and
`can stimulate epidermal renewal and maintain and/or
`can stimulate epidermal
`renewal and maintain and/or
`increase the thickness of the epidermis: this is then referred to
`increase the thickness ofthe epidermis: this is then referred to
`
`

`

`US 2010/01 68049 A1
`US 2010/0168049 Al
`
`Jul. 1, 2010
`Jul. 1, 2010
`
`thereof. As described previously, this is the combination of a
`thereof. As described previously, this is the combination of a
`biological action and a mechanical action, the latter being
`biological action and a mechanical action, the latter being
`intended to tighten and constrain the skin.
`intendedto tighten and constrain the skin.
`(0024 Patent application WO 2005/063194 describes a
`[0024]
`Patent application WO 2005/063194 describes a
`galenical base with very high tolerance especially comprising
`galenical base with very high tolerance especially comprising
`mannose or rhamnose. It is specified that Such a galenical
`mannose or rhamnose. It is specified that such a galenical
`base can function only in combination with an active agent of
`base can function only in combination with an active agent of
`which it is only the vehicle. The dermal and/or cosmetic
`which it is only the vehicle. The dermal and/or cosmetic
`galenical bases disclosed are based essentially on the pres
`galenical bases disclosed are based essentially on the pres-
`ence of the two polyols, namely mannitol and Xylitol.
`ence of the two polyols, namely mannitol and xylitol.
`0025. Moreover, the influence of adenosine and adenosine
`[0025] Moreover, the influence of adenosine and adenosine
`analogues on improving the appearance of the skin is
`analogues on improving the appearance of the skin is
`described in patent applications EP 1 424064 and EP 1 428
`described in patent applications EP 1 424 064 and EP 1 428
`522. In particular, it is specified therein that adenosine makes
`522. In particular, it is specified therein that adenosine makes
`it possible to relax or decontract the dermal contractile cells
`it possible to relax or decontract the dermal contractile cells
`that are assumed to be involved in the generation of expres
`that are assumed to be involved in the generation of expres-
`sion wrinkles.
`sion wrinkles.
`0026. The present invention thus relates in one embodi
`[0026] The present invention thus relates in one embodi-
`ment to a composition, especially a cosmetic and/or derma
`ment to a composition, especially a cosmetic and/or derma-
`tological composition, comprising, in a physiologically
`tological composition, comprising,
`in a physiologically
`acceptable medium, a combination of at least one monosac
`acceptable medium, a combination of at least one monosac-
`charide chosen from mannose and rhamnoseandofat least
`charide chosen from mannose and rhamnose and of at least
`one additional compound chosen from adenosine and adenos
`one additional compound chosen from adenosine and adenos-
`ine analogues.
`ine analogues.
`0027. The monosaccharides according to the invention are
`[0027] The monosaccharides accordingto the invention are
`in the D or L form of mannose and/or rhamnose, each form
`in the D or L form of mannose and/or rhamnose, each form
`itself possibly being the alpha and/or beta anomer. The forms
`itself possibly being the alpha and/or beta anomer. The forms
`that are preferred according to the invention are D-mannose
`that are preferred according to the invention are D-mannose
`and L-rhamnose.
`and L-rhamnose.
`0028 D-Mannose is present in plants, in particular certain
`[0028] D-Mannoseis present in plants, in particular certain
`fruit, including cranberries, or inhardwood (beech and birch).
`fruit, including cranberries, or in hardwood(beech andbirch).
`Rhamnose is found in nature in L form. D-Mannose and
`Rhamnose is found in nature in L form. D-Mannose and
`L-rhamnose are commercially available, for example from
`L-rhamnose are commercially available, for example from
`the companies Danisco Sweeteners(R and Symrise.
`the companies Danisco Sweeteners® and Symrise.
`0029. In the present invention, the monosaccharide is pref
`[0029]
`Inthe present invention, the monosaccharide1s pref-
`erably present as a monomer.
`erably present as a monomer.
`0030. For the purposes of the present invention, adenosine
`[0030]
`For the purposesof the present invention, adenosine
`is the nucleoside derived from the condensation of adenine
`is the nucleoside derived from the condensation of adenine
`with ribose (in ribofuranose form) via B-Noglucoside bond.
`with ribose (in ribofuranose form) via B-Noglucoside bond.
`Adenosine plays an important role in biochemical processes,
`Adenosineplays an importantrole in biochemical processes,
`Such as energy transfer when it is, for example, in the form of
`such as energy transfer whenit is, for example, in the form of
`adenosine triphosphate (ATP) and/or adenosine diphosphate
`adenosine triphosphate (ATP) and/or adenosine diphosphate
`(ADP), and also in signal transduction when it is, for
`(ADP); and also in signal
`transduction when it
`is,
`for
`example, in the form of cyclic adenosine monophosphate or
`example, in the form of cyclic adenosine monophosphate or
`cAMP. Adenosine has the following structural formula:
`cAMP. Adenosinehas the following structural formula:
`
`NH)
`NH2
`
`as a direct biological effect. However, retinol has a certain
`as a direct biological effect. However, retinol has a certain
`number of drawbacks when it is used in a cosmetic compo
`numberof drawbacks when it is used in a cosmetic compo-
`sition. Specifically, it has low stability towards oxidation and
`sition. Specifically, it has low stability towards oxidation and
`gives rise to adverse side effects on consumers, especially
`gives rise to adverse side effects on consumers, especially
`such as skin irritation. There is thus a need to find other
`such as skin irritation. There is thus a need to find other
`compounds with a direct biological effect, which are readily
`compounds with a direct biological effect, which are readily
`available and whose efficacy is acceptable for optimal use in
`available and whoseefficacy is acceptable for optimal use in
`cosmetics.
`cosmetics.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`BRIEF DESCRIPTION OF THE DRAWINGS
`0016 FIG. 1 shows the results obtained for the kerati
`[0016]
`FIG. 1 showsthe results obtained for the kerati-
`nocyte proliferation under certain conditions, described in
`nocyte proliferation under certain conditions, described in
`detail below.
`detail below.
`0017 FIG. 2 shows the results obtained for the kerati
`[0017]
`FIG. 2 showsthe results obtained for the kerati-
`nocyte proliferation under certain conditions, described in
`nocyte proliferation under certain conditions, described in
`detail below.
`detail below.
`0018 FIG. 3 shows the number of fibroblasts measured
`[0018]
`FIG. 3 shows the numberoffibroblasts measured
`between an untreated control whole reconstructed skin, on the
`between an untreated control whole reconstructed skin, on the
`left, and a whole reconstructed skin treated with 5 mM of
`left, and a whole reconstructed skin treated with 5 mM of
`rhamnose, on the right.
`rhamnose,on theright.
`0019 FIG. 4 shows images of frozen sections of recon
`[0019]
`FIG. 4 shows images of frozen sections of recon-
`structed skin 7 um thick.
`structed skin 7 um thick.
`
`DETAILED DESCRIPTION OF THE PREFERRED
`DETAILED DESCRIPTION OF THE PREFERRED
`EMBODIMENTS
`EMBODIMENTS
`0020. The inventors have discovered, surprisingly and
`[0020] The inventors have discovered, surprisingly and
`unexpectedly, that a combination of at least one monosaccha
`unexpectedly, that a combination of at least one monosaccha-
`ride selected from mannose, rhamnose and a mixture thereof,
`ride selected from mannose, rhamnose and a mixture thereof,
`and of at least one additional compound selected from
`and of at
`least one additional compound selected from
`adenosine, an adenosine analogue and mixtures thereof, leads
`adenosine, an adenosine analogue and mixturesthereof, leads
`to a complementarity of action both on the microrelief of the
`to acomplementarity of action both on the microrelief of the
`skin, making it possible especially to combat the formation of
`skin, makingit possible especially to combatthe formation of
`expression wrinkles, and also on the stimulation of dermal
`expression wrinkles, and also on the stimulation of dermal
`and/or epidermal regeneration by stimulating the metabolism
`and/or epidermalregeneration by stimulating the metabolism
`and the process of epidermal renewal, leading to a reduction
`and the process of epidermal renewal, leading to a reduction
`in the appearance of the signs of chronological ageing and
`in the appearance of the signs of chronological ageing and
`photoageing. Thus, the combination according to the inven
`photoageing. Thus, the combination according to the inven-
`tion causes relaxation, decontraction and a reduction in the
`tion causes relaxation, decontraction and a reduction in the
`differentiation of the dermal contractile cells involved in the
`differentiation of the dermal contractile cells involved in the
`generation of expression wrinkles, especially of the fibro
`generation of expression wrinkles, especially of the fibro-
`blasts located along the tension lines created under the effect
`blasts located along the tension lines created underthe effect
`of contraction of the skin muscles. The combination accord-
`of contraction of the skin muscles. The combination accord
`ing to the invention also makes it possible to synergistically
`ing to the invention also makesit possible to synergistically
`stimulate the production of type I procollagen by the dermal
`stimulate the production of type I procollagen by the dermal
`fibroblasts.
`fibroblasts.
`0021. As used herein the term “synergistic' and its deriva
`[0021] As used herein the term “synergistic” andits deriva-
`tives means a greater than additive effect.
`tives meansa greater than additive effect.
`0022. The present invention demonstrates the activation of
`[0022] The present invention demonstrates the activation of
`keratinocyte and fibroblast proliferation and the stimulation
`keratinocyte and fibroblast proliferation and the stimulation
`of procollagen I synthesis by mannose or rhamnose. The use
`of procollagen I synthesis by mannoseor rhamnose. The use
`of compositions containing them thus makes it possible to
`of compositions containing them thus makesit possible to
`counter the signs of ageing of the skin, and in particular
`counter the signs of ageing of the skin, and in particular
`age-related epidermal and/or dermal atrophy.
`age-related epidermal and/or dermal atrophy.
`0023 The use of these monosaccharides for the direct
`[0023] The use of these monosaccharides for the direct
`biological effects outlined above was hitherto unknown.
`biological effects outlined above was hitherto unknown.
`Patent application WO 2007/128 939 mentions, however,
`Patent application WO 2007/128 939 mentions, however,
`anti-ageing activity obtained via a biomechanical effect of a
`anti-ageing activity obtained via a biomechanicaleffect of a
`tensioning agent in combination with saccharide compounds,
`tensioning agent in combination with saccharide compounds,
`which make it possible to increase the expression of the skin
`which makeit possible to increase the expression of the skin
`cell mechanoreceptors. This increase in the expression of
`cell mechanoreceptors. This increase in the expression of
`mechanoreceptors is described as increasing the sensitization
`mechanoreceptorsis described as increasing the sensitization
`of skin cells to respond to the effects of tensioning agents.
`of skin cells to respond to the effects of tensioning agents.
`Similarly, patent application FR 2 900 572 describes the
`Sunilarly, patent application FR 2 900 572 describes the
`combined use of a cosmetic composition comprising saccha
`combineduse of a cosmetic composition comprising saccha-
`ride compounds and a device for applying mechanical con
`ride compounds and a device for applying mechanical con-
`straints to the skin, in order to improve the homeostasis
`straints to the skin, in order to improve the homeostasis
`
`HO.
`HO
`
`{l
`C13
`
`N
`N
`
`N
`N
`
`O
`O
`
`“S N
`n N
`
`a
`2
`N
`N
`
`OH OH
`OH OH
`
`0031. Among the adenosine analogues that may be used
`[0031] Among the adenosine analogues that may be used
`according to the invention, mention will be made especially
`according to the invention, mention will be made especially
`of adenosine receptor agonists and compounds that increase
`of adenosine receptor agonists and compoundsthat increase
`the intracellular or extracellular levels of adenosine.
`the intracellular or extracellular levels of adenosine.
`0032 Examples of adenosine analogues include:
`[0032] Examples
`of
`adenosine
`analogues
`include:
`2'-deoxyadenosine; 2',3'-isopropylideneadenosine; toyoca
`2'-deoxyadenosine; 2',3'-isopropylideneadenosine;
`toyoca-
`
`

`

`US 2010/01 68049 A1
`US 2010/0168049 Al
`
`Jul. 1, 2010
`Jul. 1, 2010
`
`mycin; 1-methyladenosine; N-6-methyladenosine; adenos
`mycin; 1-methyladenosine; N-6-methyladenosine; adenos-
`ine N-oxide: 6-methylmercaptopurine riboside and 6-4 chlo
`ine N-oxide; 6-methylmercaptopurine riboside and 6-4 chlo-
`ropurine riboside.
`ropurineriboside.
`0033. Other adenosine analogues include adenosine
`[0033] Other adenosine analogues
`include adenosine
`receptor agonists, including phenylisopropyladenosine
`receptor
`agonists,
`including phenylisopropyladenosine
`(PIA).
`1-methylisoguanosine, N6-cyclohexyladenosine
`(PIA),
`1-methylisoguanosine, N6-cyclohexyladenosine
`(CHA), N6-cyclopentyladenosine (CPA), 2-chloro-N6-cy
`(CHA), N6-cyclopentyladenosine (CPA), 2-chloro-N6-cy-
`clopentyladenosine, 2-chloroadenosine, N6-phenyladenos
`clopentyladenosine, 2-chloroadenosine, N6-phenyladenos-
`ine, 2-phenylaminoadenosine, MECA, N6-phenethyladenos
`ine, 2-phenylaminoadenosine, MECA, N6-phenethyladenos-
`ine,
`2-p-(2-carboxyethyl)phenethylamino-5'-N-
`ine,
`2-p-(2-carboxyethyl)phenethylamino-5'-N-
`ethylcarboxamidoadenosine
`(CGS-21680),
`ethylcarboxamidoadenosine
`(CGS-21680),
`N-ethylcarboxamidoadenosine (NECA), 5'-(N-cyclopropyl)
`N-ethylcarboxamidoadenosine (NECA), 5'-(N-cyclopropyl)
`carboxamidoadenosine, DPMA (PD 129,944) and metrifudil.
`carboxamidoadenosine, DPMA (PD 129,944) and metrifudil.
`0034 Among the adenosine analogues that increase the
`[0034] Among the adenosine analogues that increase the
`intracellular adenosine concentration in the composition
`intracellular adenosine concentration in the composition
`according to the invention, the compounds included in the
`according to the invention, the compoundsincluded in the
`group formed by erythro-9-(2-hydroxy-3-nonyl)-adenine
`group formed by erythro-9-(2-hydroxy-3-nonyl)-adenine
`(EHNA) and iodotubercidine are preferred.
`(EHNA)andiodotuberci