comparative effects of alpha hydroxy acids int j cosmet sci vol 18pp-75-831996

8/13/2019 Comparative Effects of Alpha Hydroxy Acids Int J Cosmet Sci Vol 18PP-75-831996

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International Journal of Cosm etic Science 18,7543 1996)

Com parative effect iveness o f a-h yd ro xy acids onskin p ropert iesW . P . S M I T HWalter Smith Consultanls, 46 Wakeman Road, New Canaan, CT, 06840 USAReceived 20 October 1995Keywords: lactic acid; L +) and D -) forms; cosmetic benefits; skin irritationSynopsisA number of a-hy drox y acids, including glycolic, lactic L +) and D ( -) forms) citric, hydroxybutyric and malicacids, were evaluated for their effects on various skin prop ertie s at concentrations of 0.5-1.15 M .Th e acids wereevaluated for their stinging potential on sensitive skin, the ability to increase skin cell renewal, an d their ability toimprove moisture co nten t and reduce lines and wrinkles over a six-week period. R esults indicated that lactic L +)and glycolic were the most effective acids when tested at equimolar concentrations. Both materials were lessirritating than the D( -) lactic acid form an d the ot her acids tested. Even though with long-term use both D -) andL ( + ) lactic acid an d glycolic acid produced comp arative improvem ents in skin hydration and lines and wrinkleimprovement, the L +) form of lactic acid did so with fewer consumer complaints than any of the oth er acidstested. When the concentration of lactic and glycolic acids was increased to m ore than 1.5 ~a grea ter difference inirritation potential w as observed with respect t o stinging, with the L +) form of lactic acid being less irritatingthan glycolic acid and th e D( -) form. Our results suggest tha t L( +) and D( -) lactic acid an d glycolic acid are thetwo most effective materials for developing a-hyd roxy acid products. Lactic acid has a slight technical advan tageover glycolic acid. Both L + ) and the D(-) forms are better moisturizers when fully or partially neutralized.Moreover the L ( + ) form is also less irritating than D -) and glycolic acid. Oth er acids such as citric, malic, andhydroxybutyric acids appe ar to be less effective materials but may be useful additions to lactic or glycolic acidmixes.ResumeCertains alpha hydroxy acides, don t les acides glycolique, lactique L +) et D -), citrique, hydroxybutyrique etmalique, ont t t testes pour leurseffetssu r la peau, desco ncen trations de 0.5 a 1.15M . Le ur pouvoir irritant, leurcap acit i a activer le renouvellemen t cellulaire, leur pouvoir hydratant et leur capacitC rCduire rides et ridulesont 6tC mesu res sur six semaines. Les resultats montrent qu e les acides glycolique et lactique L ( + ) sont les plusefficaces, a concentrations tquimolaires. Ces deux produits sont moins irritants q ue Iacide lactique D -) ouq u eles aut res testis. M& me si long term e les acides lactiques L +) e t D -) et lacide glycolique amtnent uneamelioration de Ihydratation de la peau et une diminution des rides et ridules, cest la forme L( +) d e Iacidelactique qui a provoque le moins de plaintes de la part des utilisateurs. D e plus, lorsque les concentrations dacidelactiqu e et glycolique on t CtC portCes plus de 1.5 M , ne difference significative de pouvoir irritant a et6 observke,Iacide lac tique L + ) se rc%elant moins irritant qu e les acides glycolique et lactique D( -). Nos rksultats sug gtren tque Iacide lactique D -) et L +) et Iacide glycolique son t les plus intkressants itiliser pour developper de sproduits aux AHA, Iacide lactique ay ant un lkger avantage sur Iacide glycolique. Ses deu x fo rm es L( +) e t D -)sont de meilleurs hydratants lorsquelles sont partiellement ou complktement neutralisees. D e plus la forme L( +)est moins irritante que Iacide glycolique ou que la forme D -). Dautres acides tels que les acides citrique,malique et hydroxybutirique sont moins efficaces mais pourraien t cepe ndan t & tredes additifs inttressants po urdes m elanges dacides glycolique ou lactique.

In t roduct iona-Hydroxy acids (AHAs) are clearly one of the most exciting cosmetic ingredients usedtoday to combat the visible effect of ageing. Num erous companies have launched skin care0142-5463 1996 International Journal of Cosmetic Science


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a-Hy droxy acids on skin 77Assessment of subjective skin irritationTh e irritation potential of the test materials was evaluated on th e nasal fold area of testsubjects. Test materials were applied (a different material applied to each side of th e nose,separated by 15min) to the nasal fold area on subjects which had previously washed theirfaces (with Ivory Soap twice a day ) and refrained from m oisturizer use for at least threedays. Irritation was graded on a 5-point scale every minute for 15min and the totalirritation score was summed. The g rading scale was as follows: 0, no reaction; 1, slightstinging, hardly noticeable; 2, stinging easily noticeable; 3, stinging and slightly painfulburning; 4, stinging, burning , itching, quite distracting.Subject selectionSubjects were selec ted by the following criteria: moderate signs of d ry skin , some of thevisible signs of ageing inc luding lines and wrink les, loss of skin firmness, and skindiscoloration.Subjects were excluded from the study if they fell into any of the following categories:currently using or having used within the last six months Retin A, or analogues,corticosteroids, benzoyl peroxide, and topical anti-biotics; having had facial peeling o rdermabrasion within the last year; having psoriasis, eczema, or atopic derm atitis; currentlyon test in any o the r clinical study for topical o r systemic medications o r products; having aknown com municable disease. Subjects on medication were reviewed on a case-by-casebasis.Product useTo en sure that all subjects were at a baseline value and to factor ou t differences in currentskin care regimens, for five days before the study started subjects were required to refrainusing any moisturizer, sunscreen, or liquid m ake-up. They w ere also instructed to avoidexcessive UV expo sure, and n ot allowed to visit tanning salons. They were allowed to useeye, face (blush only) and lip products during this and subsequent phases of the study andwere supp lied with a bland non-em ollient soap. Unless otherwise indicated p roduc ts wereapplied to the entire face, including the neck and eye areas, by the subjects in the morningand evening. Subjects were instructed on how much product to use and this wasdeterm ined to be abou t 2 mg cm-*.Skin hydration assessment via impedanceThe impedance meter is a widely used device tomeasure changes in skin moisture conten t[13]. Each test day the unit (Nova Impedance Meter DPM 9003, Nova Corporation,Gloucester, MA) was calibrated according to instrument instructions. Subjects wererequired to equilibrate for 30min prior to testing at a controlled temperature (68-72F:20-22.2 C) and a relative hum idity of 4040 .Subjects applied test product (2mgcrn-') to each side of th e face (the cheek area) an dthree separate readings with the N ova Impedan ce Meter were m ade w ithin a 4 cm X 4 cmarea on each side of the face, recorded and averaged. The m eter was lightly placed up onthe test site and held there until a constant reading was achieved for at least 5 s.


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78 SmithSkin firmness via ballistometryBallistometry was used to me asure skin firmness [14, 151. A small lightweight Plexiglasprobe (linked t o a linear distance to force transducer) was dropp ed o nt o the skin surfacevia a fre e falling pendulum from a distance of 5 cm. This droppin g caused an indentation ofthe skin surface; the firmness or resilience of th e skin caused t he pro be t o rebo un d a finitedistance back above the skin surface. T he p robe reached the p eak of the rebou nd and againdrop ped to the skin surface, causing less indentation, etc. Th e m ovement of the prob e w aslinked to the transducer w hich conv erts distance in to millivoltage, and this millivoltage w asconverted in to a graphics display on a 486 P C monitor through the use of an imagecapturing software program . T h e resultant display was essentially a dam pen ed sinusoidalwave pattern.Although a number of different analyses have be en used to d eterm ine skin firmness thevalue of the height of first rebound pea k ( H l ) to th e second reboun d peak (H2 ) was used inthis study.

Ultrasound analysis of skin thicknessA D ermascan C Ultrasound (Cortex Technology, D en m ark ) was used to measure skinfirmness [16]. T h e unit has a resolution of 2 0M H z, and the A scan was used. With thisdevice, differences between th e epidermis, dermis and sub cutan eou s fat layers can b emeasu red. In addition to m easuring the thickness of each layer of skin, in the zoom mo de,images were im ported into a PC -based image-analysis system a nd relative tissue densitywas measured. Since fluid doe s not pro du ce an ultrasound image, relative tissue densitywas determined by calculating the density of the ultrasound signal in each of the tissuelayers of interest. If an increase in dermal tissue thickness was observed this could havebeen du e to a swelling of the tissue (inflammation or o ed em a), o r a stimu lation of newprotein synthesis. A n increase in derm al thickness with a decreased density would not bepositive an d reflect an inflammatory process. A n increase in thickness with maintained o rincreased density would reflect a stimulation of der m al metabo lism, a positive effect.

Clinical assessments of skin conditionA trained clinician evaluated each subjects skin condition w ith respect t o dryness, redness,colour, erythema, smoothness, etc. An arbitrary 0 4 -p o in t scale was used fo r eachevaluation. In addition the nu m ber of superficial lines an d wrinkles w ere assessed via thePackman method [17].

Wrinkle reduction via image analysisSkin replicas were taken on the cheek area (one side randomly assigned) using Silfloreplicating materials [MI. The replicas were photographed with black and white film,under a low incidence angle (12) illumination. T h e pho tog rap hs were scanned into aPC-based image-processing system, and t he percentage area of skin surface covered bywrinkles or fine lines was computed. Pre -treatm ent and four a nd eight week values werecompared.


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a-Hydroxy acids o n skin 79Results and discussionIncreases in skin cell renewalT he data in Table I dem onstrates very little differences were observe d betwe en th e abilityof glycolic acid an d D -) and L( +) lactic acid to stimulate cell renew al a t similar molarratios when tested over the rang e of 0.5-1.5 M and at a pH ran ge of 3-7. T h e thre e acidseach stimulated cell renewal from 23 to 31% at p H 3 and from 4 o 11 a t p H 7 . N ostatistically significant differences were found betw een t he thr ee materials w hen m atchedpH values and concentrations were com pared. Several of the o th er acids tested includingcitric acid, hydrox ybutyric and malic were m uch less effective a t increasing cell renew al,showing increases of only 20% even at low pH and at th e highest concentrations. A t th e1 concentration, these three acids were significantly less effective P


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80 SmithTable 11. T h e e f fe c t of pH a n d c o n c e n t r a t io n on h y d r o x y ac id i n d u ced sk ini r r i t a t i o n ( mean S D )Test materials Irritation score atConc.

M) P H 3 P H 5 P HGlycolic acid 0.5 27.2(2.3) 24.3(3.3) 15.4(2.3)1 35.4 (4.7) 33.4 (2.9) 16 (4.4)1.5 44.1 (5.9) 37.1 (5.9) 21 .9(2.1 )D( -) lact ic acid 0.5 24 (2 .9) 21.8 (4.7 ) 13.3 (1.8)

1 34( 6.2) 30.2 (2.2 ) 19.1 (1.4 )1.5 40.8(3.8) 36.3(5.7) 21.2(2.2)1 24 (3 .9) 17.1 (3.3) 13.8 (2.8)1.5 26.7(4.1) 25.6 (2.8 ) 17.1 (2.6)

Cit r ic ac id 1 38 (2 .7) 34.8 (4.1) 23.6 (2.7)H y d r o x y b u ty r i c ac id 1 41 (2.9) 35.4 (4.7) 22.4 (2.9)Malic ac id 1 39.4(3.6) 37.1 (4.5) 23.1 (4.1 )Test product was applied (2mgcm-*) to the nasal fold area 10m in after washing withIvory Soap. Irritation was rated by the subjec ts on a 0-4-point scale every min ute for15min. The irritation score presented is an average of the summation of eachindividual irritation score over the 15min test period. Standard deviations are shown inparentheses. The data presented are averages of at least te n subjects.

L( +) lact ic acid 0.5 21.2(1.7) 15(1.8) l l (1 .7 )

Immediate skin hydrationWe observed t hat both L( +) and D( -) lactic acid were b ette r moisturizing ingredients th anglycolic acid. A t equ al m olar concen trations no ne of th e materials were very effective asmoisturizers at p H 3 (Table 111). How ever, as th e pH increased, lactic acid, bo th L( +) a ndD( -) forms, were far more effective moisturizers than glycolic acid with respect to thedura tion of skin hydration. A 0.75 M lactic acid-sodium lactate mixture (abo ut 5% ) at a pHof 5 provided skin hydration fo r more than 6 h, compared to 2 h by a similar glyco lic acidmixture.

Six week clinical study resultsSkin hydration. We observed that after six weeks of treatment all test groups showedmodest increases in skin moisturization. Althou gh this was only a small pilot study, an d astatistical comparison between th e different treatm ents was not ma de, both L( +) and D( -)lactic acid treatme nts were m ore hydrating t ha n th e comp arable glycolic acid treatm ent.This might be expected from o ur previous results wherein ne utralized lactic acid was amore effective moisturizer than glycolic acid (Table IV).Skin firmness and thickness. After six weeks of treatment all test groups showedcom parable increases in skin firmness (17-24%) and skin (epiderm al) thickness (5-7%).While statistically significant differences from pre-treatment values were observed, nodifferences between the different t rea tm en ts were ob served P>0.1). Therefore i tappears each test material is capable of inducing long-term changes in the skin whichshould provide perceivable con sum er benefits (Table V).


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a-Hydroxy acids on skin 81Table 111. The effect of hydroxy acids on the duration of skinmoisturization

Conc.Test material ( M ) p H 3 p H 5 p H 7Glycolic acid 0.75 < l h 2h 3.5 hD ( -) lactic acid 0.75 l h 6h >6hL +) lactic acid 0.75 l h 6h >6hCitric acid 0.75 < l h l h 2hSkin impeda nce values (DPM units) were determined on he face of at leastten subjects prior to application of each test material. After th e product wasapplie d by clinicians at a dose of 2 mgcm-, readings were mad e every 15 minuntil they returned to within 5 of the original pre-treatment values.

Reduction of lines an d wrinkles. We also observed that glycolic acid treatm en t and L +)and D( -) lactic acid treatments provided significant improvem ents in the ap pea ran ce oflines and wrinkles when p roduc ts were used twice a day over a six-week period. T he lacticacid treatments were somewhat more favourable than the glycolic acid treatment,although these differences were not statistically significant P>0.1). This may reflect th esuper ior moisturizing potential of lactic acid o ve r glycolic acid (Tab le V).Consumer complaints. Finally, when we tabulated consumer complaints (from testsubjects dairies), a considerable difference was noted between the three treatments.Glycolic acid treated subjects registered the most com plaints (63) compared to 46 for D( -)lactic acid and 28 from L +) lactic acid. These results can be explained by the increasedmoisturizing potential of lactic acid compared to glycolic acid. Also as we noted in theacute phase of this study glycolic acid had a greate r stinging potential than D( -) lactic acidwhich was slightly more irritating than the L +) form.ConclusionW e have examined a number of different a-hydroxy acids for their ability t o improv e th ecosmetic properties of th e skin with the objective of identifying materials w hich may be

Table IV. Increases in skin moisturization a fte r long-term use of hydroxy acidsTest material M) weeks 3 weeks 6 weeksGlycolic acid 0.75 NA 11.2 14.1

Conc

(102.5 13.6) (114 12.1) (116.9 11.2)(111.6 10.5) (128.3 14.1) (139.3 14.4)(105.2 17.6) (122 10.7) (134.42 10.6)

L +) lactic acid 0.75 NA 15 (1.6) 24.8D -) lactic acid 0.75 NA 16 27.8Skin impedance (DPM units) w as determined on the face (cheek area) of at least six subjectsprior to the study start. After three and six weeks of applying the product twice a day(2 mg cm-), readings were repea ted on he cheek area and compared to the original values.Percentage changes from week 0 and, in parentheses raw data with standard deviation, arepresented. All changes from baseline values were statistically significant (Students pairedI-test, P < 0.05) unless indicated otherwise. NA = n o t applicable.


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82 SmithTable V. The effect of six weeks treatment with hydroxy acids on improve-ments in skin firmness, thickness and the appearance of lines and wrinklesTest material M) Firmness Thickness WrinklesGlycolic acid 0.75 17.4 6.70 19L +) lactic acid 0.75 24 5.60 27D( -) lactic acid 0.75 21 6.80 24

Conc.

Skin firmness, thickness and lines and wrinkles were assessed on the cheek and eye areaof at least six subjectsas indicated n Methods before the study started. After six weeks ofapplying the product twice a day (2 rngcm-) measurements were repeated on the sametest sites and compared to the original values. Percentage changes from baseline areshown. All changes from baseline values were statistically significant (Students pairedf-test,


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comparative effects of alpha hydroxy acids int j cosmet sci vol 18pp-75-831996

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