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WO2001068048A2 - Fragments d'adn non-physiologiques permettant le bronzage de la peau - Google Patents

Fragments d'adn non-physiologiques permettant le bronzage de la peau Download PDF

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Publication number
WO2001068048A2
WO2001068048A2 PCT/EP2001/003093 EP0103093W WO0168048A2 WO 2001068048 A2 WO2001068048 A2 WO 2001068048A2 EP 0103093 W EP0103093 W EP 0103093W WO 0168048 A2 WO0168048 A2 WO 0168048A2
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WO
WIPO (PCT)
Prior art keywords
skin
composition
dna fragment
assay
physiologic
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.)
Ceased
Application number
PCT/EP2001/003093
Other languages
English (en)
Other versions
WO2001068048A3 (fr
Inventor
Michael James Barratt
Ian Richard Scott
Kelly Hua Zhang
Albert Lukin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hindustan Unilever Ltd
Unilever NV
Original Assignee
Hindustan Lever Ltd
Unilever NV
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Hindustan Lever Ltd, Unilever NV filed Critical Hindustan Lever Ltd
Priority to AU2001262108A priority Critical patent/AU2001262108A1/en
Publication of WO2001068048A2 publication Critical patent/WO2001068048A2/fr
Publication of WO2001068048A3 publication Critical patent/WO2001068048A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning 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
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic acids
    • 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

  • melanocytes Skin color in humans is due largely to the abundance of a brown/black pigment, melanin, that is oroduced in the basal epidermis by specialized cells called melanocytes.
  • Melanocytes transfer melanin to adjacent keratmocytes where it serves to protect cellular DNA from UV- prised damage by virtue of its ability to absorb UV-radiation .
  • melanin synthesis increases, as does the transfer of melanin to the keratmocytes, resulting in a visual darkening of skin color, known as a tan.
  • Modifications which render DNA resistant to enzymatic attack are known in the art.
  • WO99/60167 describes pharmaceutical or cosmetic compositions containing at least some of such modified DNA molecules.
  • the present invention is based at least in part on the surprising discovery that at least some of such modified enzyme-resistant DNA fragment analogs retain their ability to stimulate melanin production by melanocytes.
  • Previous DNA-based sunless tanning methods were based on simulating the physiological process, and thus employed physiological DNA fragments. It is surprising that even when modified to deviate from their physiological structure, DNA fragments still evoke the same physiological response from melanocytes.
  • skin as used herein includes the skin on the face, neck, chest, back, arms, hands, legs, feet and scalp.
  • non-physiologic DNA fragment analog means a DNA analog molecule which is not naturally occurring within the human body.
  • Non-physiologic DNA fragment analogs suitable for use in the present invention must satisfy two criteria: they must remain at least 80% intact after 1 hour at 37°C in a skin homogenate assay, yet they must also increase melanin production by melanocytes (in vitro melanogenesis test) .
  • Skin Homogenate Assay :
  • Non-physiologic DNA fragment analogs suitable for use in the present invention must remain at least 80%, preferably at least 85%, and most preferably at least 90%, intact after 1 hour at 37°C in a skin homogenate assay.
  • the assay is described in detail in Example 3 below.
  • DNA fragment analogs may be included in the present invention, as long as they satisfy the two tests described above and may be selected from the following DNA fragment analogs: phosphathioates phosphorodithioate, phosphorothiolates, phosphoramidate, alkyl or aryl phosphonates (e . g.methylphosphonate) boranophosphates, boranophosphorothioates and combinations of such linkages. These modifications may be internal (some or all of the linkages modified) and/or at the 5' end of the fragment. In each case, oligonuclotides should possess a terminal 5' charged functionality, preferably phosphate or modified phosphate (as above) . This 5' terminal group may optionally be covalently linked to cholesterol or fatty groups (chain lengths 2-24 carbon atoms, either saturated
  • nucleic acid bases and sugar moieties may also be modified.
  • 2' -O-methylnucleoside, 2'-0- thionucleoside and 2' -O-allylnucleoside may all be incorporated into the modified fragments, either partially or completely replacing the deoxy ⁇ bose sugars.
  • DNA fragment analogs included in the present invention contain from 2 to 100 nucleotides (or modified nucleotides) .
  • the DNA fragment analogs included in the present invention contain less than 10, or even more preferably less than 8 nucleotides, optimally from 2 to 8 nucleotides (or modified nucleotides).
  • the non-physiologic DNA fragment analog is employed m the present composition in an amount of from 0.001 to 20 wt.%, preferably from 0.01 to 10%, most preferably from 0.1 to 5wt.%.
  • inventive compositions preferably include a sunscreen and/or chelating agent, or nuclease/phosphatase inhibitors m order to further improve the performance of the composition.
  • Sunscreens provide additional protection against photodamage, while chelating agents and the inhibitors further improve the stability of the non- physiologic DNA fragment analogs.
  • Sunscreens include those materials commonly employed to block ultraviolet light.
  • Illustrative compounds are the derivatives of PABA, cmnamate and salicylate, titanium dioxide and zinc oxide.
  • avobenzophenone is the derivatives of PABA, cmnamate and salicylate, titanium dioxide and zinc oxide.
  • sunscreen octyl methoxycmnamate and 2-hydroxy-4- methoxy benzophenone (also known as oxybenzone) can be used. Octyl methoxycmnamate and 2-hydroxy-4-methoxy benzophenone are commercially available under the trademarks, Parsol MCX and Benzophenone-3, respectively.
  • the exact amount of sunscreen employed in the compositions can vary depending upon the degree of protection desired from the sun's UV radiation; generally the amount is from 0.1 to 10 wt . % , preferably from 1 to 5 wt.% .
  • Metal chelators increase the stability of the non- physiologic DNA fragments by inhibiting nuclease activity, especially cosmetically acceptable amount of metal chelators with strong affinity for magnesium and zinc.
  • a group of these chelators includes, but is not limited to, citrate, o- phenanthrol e, ethylenediam otetraacetic acid (EDTA) , DTPA, ethylenedioxy-diethylene-dmit ⁇ lo-tetraacetic acid (EGTA) , 8-hydroxyqumolme, nitrilotriacetic acid, tartaric acid.
  • Chelating agent and or nuclease/phosphatate inhibitors may suitably be present in an amount of from 0.1 to 20%, preferably from 1 to 5%.
  • the vehicle may be aqueous, anhydrous or an emulsion.
  • the compositions are aqueous or an emulsion, especially water-in-oil or oil-m-water emulsion. Water when present will be in amounts which may range from 5 to
  • relatively volatile solvents may also serve as carriers within compositions of the present invention.
  • mononydric C1-C3 alkanols include ethyl alcohol, methyl alcohol and isopropyl alcohol.
  • the amount of monohyd ⁇ c alkanol may range from 1 to 70%, preferably from 10 to 50%, optimally between 15 to 40% by weight.
  • Emollient materials may also serve as cosmetically acceptable carriers. These may be in the form of silicone oils and synthetic esters. Amounts of the emollients may range anywhere from 0.1 to 50%, preferably between 1 and 20% by weight .
  • the essentially non-volatile polyalkyl siloxanes useful herein include, for example, polydimethyl siloxanes with viscosities of from about 5 to about 25 million centi-stokes at 25°C.
  • polydimethyl siloxanes with viscosities of from about 5 to about 25 million centi-stokes at 25°C.
  • preferred non-volatile emollients useful in the present compositions are the polydimethyl siloxanes having viscosities from about 10 to about 400 centistokes at 25°C.
  • ester emollients are:
  • Alkenyl or alkyl esters of fatty acids having 1C to 20 carbon atoms examples thereof include isoarachidyl neopentanoate, isononyl isonanonoate, oleyl myristate, oleyl stearate, and oleyl oleate.
  • Ether-esters such as fatty acid esters of ethoxylated fatty alcohols.
  • Ethylene glycol mono and di-fatty acid esters diethylene glycol mono- and di- fatty acid esters, polyethylene glycol (200-6000) mono- and di-fatty acid esters, propylene glycol mono- and di-fatty acid esters, polypropylene glycol 2000 monooleate, polypropylene glycol 2000 monostearate, ethoxylated propylene glycol monostearate, glyceryl mono- and di-fatty acid esters, polyglycerol poly-fatty esters, ethoxylated glyceryl monostearate, 1, 3-butylene glycol monostearate, 1, 3-butylene glycol distearate, polyoxyethylene polyol fatty acid ester, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters are satisfactory polyhyd ⁇ c alcohol esters.
  • Wax esters such as beeswax, spermaceti, my ⁇ sty
  • Sterol esters of which cholesterol fatty acid esters are examples thereof.
  • Fatty acids having from 10 to 30 carbon atoms may also be included as cosmetically acceptable carriers for compositions of this invention.
  • Illustrative of this category are pelargomc, lau ⁇ c, myristic, palmitic, stearic, isostearic, hydroxystearic, oleic, lmoleic, ⁇ cinoleic, arachidic, behenic and erucic acids.
  • Humectants of the polyhydric alcohol-type may also be employed as cosmetically acceptable carriers compositions of this invention. The humectant aids in increasing the effectiveness of the emollient, reduces scaling, stimulates removal of built-up scale and improves skin feel.
  • Typical polyhydric alcohols include glycerol, polyalkylene glycols and more preferably alkylene polyols and their derivatives, including propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1, 3-butylene glycol, 1, 2, 6-hexanetr ⁇ ol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof.
  • the humectant is preferably propylene glycol or sodium hyaluronate.
  • the amount of humectant may range anywhere from 0.5 to 30%, preferably between 1 and 15% by weight of the composition.
  • Thickeners may also be utilized as part of the cosmetically acceptable carrier of compositions according to the present invention.
  • Typical thickeners include crosslmked acrylates (e.g. Carbopol 982), hydrophobically- modified acrylates (e.g. Carbopol 1382), cellulosic derivatives and natural gums.
  • useful cellulosic derivatives are sodium carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose and hydroxymethyl cellulose.
  • Natural gums suitable for the present invention include guar, xanthan, sclerotium, carrageenan, pectin and combinations of these gums.
  • Amounts of the thickener may range from 0.0001 to 5%, usually from 0.001 to 1%, optimally from 0.01 to 0.5% by weight.
  • the water, solvents, silicones, esters, fatty acids, humectants and/or thickeners will constitute the cosmetically acceptable carrier in amounts from 1 to 99.9%, preferably from 80 to 99% by weight.
  • Surfactants may also be present in cosmetic compositions of the present invention. Total concentration of the surfactant will range from 0.1 to 40%, preferably from 1 to 20%, optimally from 1 to 5% by weight of the composition.
  • the surfactant may be selected from the group consisting of anionic, nonionic, cationic and amphoteric actives.
  • Preferred anionic surfactants include soap, alkyl ether sulfate and sulfonates, alkyl sulfates and sulfonates, alkylbenzene sulfonates, alkyl and dialkyl sulfosuccinates, C8-C20 acyl isethionates, acyl glutamates, C8-C20 alkyl ether phosphates and combinations thereof.
  • Physiologoc DNA fragments such as those disclosed by US 5,470,577;US 5,532,001; US 5,580,547; US 5,643,556, incorporated by reference herein, may also be included. Such physiologic DNA fragments may provide competitive binding to stratum corneum/epidermal enzymes, thus increasing the stability of non-physiologic DNA fragment analogs .
  • the preferred compositions avoid the extremes of pH, : • order to further improve the stability of non-physiologic DNA fragment analogs.
  • the preferred compositions have a pH in the range of from 3.8 to 8, preferably from 5.5 to 7.5.
  • the composition may optionall j be used in conjunction with a device known in the literature for enhancing delivery through the skin including but not limited to occlusive patches, lontophoretic systems and sonic energy devices.
  • Freshly obtained pigmented pig skin was scrubbed thoroughly with bactericidal soap, and dermatomed to 0.2mm.
  • DMEM Dulbecco' s Modified Eagle's Medium
  • biopsies were harvested, rinsed m PBS to remove excess surface pTpT and then snap frozen at -80°C overnight.
  • Epidermis and stratum corneum were separated from the dermis by scraping with a scalpel and then extracted on ice with PBS + 0.1% Tween 20. After 30 minutes, samples were centifuged at 15,000xg and the soluble fraction (containing extracted pTpT) was analysed by HPLC (OD 260nm) to assess the pTpT content.
  • Phosphorothioate thymidine dinucleotides are prepared using standard automated solid phase synthesis using a commerically available synthesizer (l ⁇ M scale).
  • Compound 1 is prepared from CPG supported DMTrO-dT loaded through a succinyl linker. After 5' detritylation with 3% DCA in CH (90 sec), and washing with acetonitrile (30 sec), the support bound T nucleoside is reacted with 0. IM T-cyanoethyl phosphoramidite in acetonitrile in the presence of 0.5M tetrazole (30 sec) . The bound phosphotriester is then oxidized for 50 seconds with 0.
  • IM iodine in pyridine/ THF / water (20/80/2) is phosphitilated with 150 ⁇ l of 0.
  • the resulting phosphite is sulphurized with Beaucage's reagent as previously described (Iyer et al., J. Am . Chem . Soc , Vol . 112 : 1253 (1990) and J. Org . Chem . 55 : 4699) and the DMT group cleaved with 3% DCA in CHC12 (90 sec) .
  • the supported dinucleotide is then worked up in a conventional manner.
  • Compound 2 is prepared in a similar fashion to compound 1 except that instead of oxidizing with iodine, the initial phosphotriester is first reacted with Beaucage's reagent, detritylated, then 5' phosphorylated as described ' for compound 1, and further with the addition of a second sulfurization step after 5' phosphorylation using Beaucage's reagent .
  • This example describes the skin homogenate assay which determines whether a non-physiologic DNA fragment is sufficiently stable for use in the present invention.
  • the example investigated the melanogenic activity of the non- physiologic DNA fragment analogs prepared in example 2.
  • Skin Homogenate Assay :
  • reaction buffer was prepared as follows :
  • This example investigated the melanogenic activity of the non-physiologic DNA fragment analogs prepared in example 2.
  • Biopsies were maintained at 37C, 5% CO in serum- free DMEM supplemented with L-Glutamine (2mM) + lOO ⁇ /ml penicillin, lOO ⁇ g/ml streptomycin, 0.5 ⁇ g/ml Fungizone.
  • pTpT analogues dissolved in water were added to the appropriate wells at a final concentration in the media of lOO ⁇ M. Control wells were treated with diluent (water) only.
  • the media was changed and fresh analogs, added

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Biochemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Cosmetics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des compositions et des procédés permettant, d'une part, de protéger la peau contre les dommages provoqués par les ultraviolets et, d'autre part de bronzer sans soleil. Ces compositions contiennent, comme agent actif, un analogue de fragment d'ADN non-physiologique sensiblement stable face à la détérioration induite par les enzymes cutanés, mais capable d'accroître la production de mélanine par les mélanocytes.
PCT/EP2001/003093 2000-03-17 2001-03-19 Fragments d'adn non-physiologiques permettant le bronzage de la peau Ceased WO2001068048A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001262108A AU2001262108A1 (en) 2000-03-17 2001-03-19 Non-physiologic dna fragments for tanning skin

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US19041900P 2000-03-17 2000-03-17
US60/190,419 2000-03-17

Publications (2)

Publication Number Publication Date
WO2001068048A2 true WO2001068048A2 (fr) 2001-09-20
WO2001068048A3 WO2001068048A3 (fr) 2002-02-21

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AU (1) AU2001262108A1 (fr)
WO (1) WO2001068048A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003082231A3 (fr) * 2002-03-28 2004-04-01 Johnson & Johnson Consumer Compositions de coloration de la peau
WO2008129307A1 (fr) * 2007-04-23 2008-10-30 Oxford Ancestors Limited Milieux contenant de l'acide nucléique
BG65639B1 (bg) * 2004-06-25 2009-04-30 Диана СТЕФАНОВА Регенериращ състав

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0260697B1 (fr) * 1986-09-18 1993-03-17 Lion Corporation Composition pour application capillaire
US5256775A (en) * 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
WO1990015065A1 (fr) * 1989-06-05 1990-12-13 Gilead Sciences, Inc. Oligonucleotides resistant a l'exonuclease, et procedes pour leur preparation
FR2705099B1 (fr) * 1993-05-12 1995-08-04 Centre Nat Rech Scient Oligonucléotides phosphorothioates triesters et procédé de préparation.
EP2363133A1 (fr) * 2000-03-31 2011-09-07 Trustees of Boston University Formulation comprenant des fragments d' ADN et utilisations médicales et cosmétiques de celle-ci

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003082231A3 (fr) * 2002-03-28 2004-04-01 Johnson & Johnson Consumer Compositions de coloration de la peau
BG65639B1 (bg) * 2004-06-25 2009-04-30 Диана СТЕФАНОВА Регенериращ състав
WO2008129307A1 (fr) * 2007-04-23 2008-10-30 Oxford Ancestors Limited Milieux contenant de l'acide nucléique

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Publication number Publication date
WO2001068048A3 (fr) 2002-02-21
AU2001262108A1 (en) 2001-09-24

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