Whitening Effect of Cosmetics Containing … after an exposure to UV rays results from ... problem,...

Skin color varies depending on the genetics,age, race, seasonal change, UV irradiation, hor-

monal influences and the presence of pigmentary dis-ease. Constitutive skin color is the genetically de-termined level of skin pigmentation in the ab-sence of direct or indirect influences such as solar ra-diation and other environment factors. In con-trast, facultative skin color is characterized by the in-crease in melanin pigmentation above the constitu-tive level and is brought about by ultraviolet(UV)rays, so called suntanning1. The increase inmelanin after an exposure to UV rays results fromthe activation of tyrosinase in melanocytes andthe increase in the number of active melanocytes2.The best way to avoid this UV-induced tanning orpigmentation is the usage of materials that screen outUV rays. Nevertheless, the materials that inhibit

Whitening Effect of Cosmetics Containing Magnesium L-Ascorbyl-2-Phosphate(VC-PMG, Vitamin C Derivatives)

Assessed by ColorimeterYoon-Kee Park, M.D., Won Soon Chung, M.D.*, Hoon Lee**, Sungwon Jung**

Department of Dermatology, Yonsei University College of Medicine, Seoul, KoreaDepartment of Dermatology, Pochon CHA University College of Medicine, Pundang CHA hospital,Pundang*,

Skin Science R & D center, Enprani Co, LTD.**

Backgrounds : An inhibitory effect of magnesium L-ascorbyl-2-phosphate(VC-PMG, astable derivative of ascorbic acid) on melanogenesis has been described. Furthermore,glabridin in licorice is known to have inhibitory effects on melanogenesis and widely used forraw materials for depigmenting agents.

Objective : The purposes of this study are to provide objective data by measuring the visu-al clinical effects of VC-PMG with the colorimeter and to promote the development of de-pigmenting agents.

Methods : 20 volunteers joined the study. With an artificial UVB irradiation, eighttanned areas were made on the inner side of the forearm. During two months, each tanned areawas treated with five whitening cosmetics with 3% VC-PMG and increasing concentration oflicorice from 0% to 3%. Darkness degree of each area was measured weekly by the colorimeterand the visual assessment.

Results : For all cosmetics, whitening effect was measured by colorimeter and visual as-sessment. The cosmetic containing VC-PMG 3% and licorice 1% had more whitening effectthan any other cosmetics of different concentrations. Moreover, VC-PMG 3% alone also hadwhitening effect in some volunteers.

Conclusion : VC-PMG was clinically found to have whitening effect.(Ann Dermatol 14(2) 63-70, 2002).

Key Words : VC-PMG Whitening Colonmeter.

Received April 16, 2001.

Accepted for publication March 7, 2002.

Reprint request to : Yoon-Kee Park, M.D., Department

of Dermatology, Yonsei University College of Medi-

cine, Shin-chon dong, Seoul, Korea.

657, Hannam-Dong, Youngsan-Gu, Seoul, 140-743,

Korea

Tel. (02)361-5720, Fax. (02)393-9157

*Supported by a grant from the Skin Science R&D

center, ENPRANI Co, LTD., 51-1, 3 Ga, Shinhung-

dong, Chung-Ku, Inchon, 400-103, Korea

The head : Hee Chang Ryoo)

63

tyrosinase and melanin production and have se-lective melanocyte toxicity or nonselective sup-pression of melanogenesis may also have depig-menting effects on the already tanned skin or thepigmentary conditions such as postinflammatoryhyperpigmentation, lentigenes, and melasma3. Phe-nol/catechol compounds such as hydroquinone,monobenzyl ether of hydroquinone(MBEH) are alsoknown as whitening materials4. In addition, it is re-ported that trans-retinoic acid, azelaic acid, kojicacid, arbutin and ascorbic acid have effects onmelanogenesis5,6. Furthermore, natural extractssuch as paper mulberry and glabridin are in develop-ment to utilize in whitening cosmetics7.

Ascorbic acid(AsA) inhibits melanin produc-tion by reducing o-quinones8 so that melanin cannotbe formed by the action of tyrosinase until all AsA isoxidized. Melanin can be changed from jet black tolight tan by AsA by the reduction of oxidizedmelanin.8 However, it is rapidly oxidized and de-composes in aqueous lotion and thus is not generallyuseful as a depigmenting agent. To resolve thisproblem, magnesium-L-ascorbyl-2-phosphate(VC-PMG) was synthesized9. It is stable in water, espe-cially in neutral or alkaline solution containingboric acid or its salt.10 VC-PMG is hydrolyzed byphosphatases of live or skin to AsA and thus exhibitsvitamin C-reducing activity10. Moreover, VC-PMG in cream base can suppress melanin formationby tyrosinase inhibition. Therefore, with the additive

effect of L1-methyleneglycol-bis, it is effective in re-ducing skin pigmentation.

Skin-color measurement is the common clinicalmethod to determine whitening effects of cosmetics.In the past, the way to determine skin color wasmostly to see with naked eyes. This method, how-ever, had much room for intervening subjectiveopinions and disabled one from explaining skincolor exactly to others11. Much research on methodsfor measuring skin color have been carried out tillnow. Among these measuring methods, colorimeteris now widely used in the methodology, for example,for research on cosmetics, because this method is notbased on examiner’s subjective feeling but makesit possible to measure skin colors objectively and sci-entifically12.

In this study, we aimed to measure the visualclinical whitening effects of VC-PMG via the col-orimeter, a new objective methodology.

64 YK Park, et al.Annals of Dermatology

Vol. 14, No. 2, April 2002

Table 1. Volunteer profile

Age No. of volunteer

20-29 3

30-39 9

40-49 7

50-59 1

Table 2. MEDs and irradiation doses of volunteers

volunteer MED irradiation volunteer MED irradiation

amount amount

1 30 60 11 40 60

2 45 67.5 12 50 75

3 35 52.5 13 75 120

4 50 75 14 30 60

5 35 70 15 45 67.5

6 80 120 16 45 90

7 35 70 17 30 60

8 45 67.5 18 40 80

9 40 80 19 10 60

10 40 80 20 50 100

mean 42.5 75.75

Unit : (mJ/cm)

MATERIALS AND METHODS

Subjects and Materials20 Korean volunteers (20 males, the mean age

of 37) joined the study. All gave written consents af-ter explanation of the experimental procedure.Examinees are healthy people over 18 years oldand those were excluded who had experience ofUV irradiation during the last three months orhad a history of photosensitive disease or took aphotosensitive medicine(Table 1).

MethodsAA.. DDeetteerrmmiinnaattiioonn ooff MMEEDDWe evaluated minimal erythemal doses(MEDs)

of each subject after 16 to 24 hours from causingidentifiable erythema with irradiating UVB ray onthe back. YS UVB-400 with FS 72 T12-UVB-HOlamp(Philips, Holland), was used as the source ofUVB ray and the wavelength of lamp was 290-325nm and its maximum at 301 and 302nm. Ra-diometer measured the UVB strength by using IL700(International Light Inc.). During irradiation, theradiation intensity of lights was made to increase inequal ratio and the size of the region to which UVrays are applied was more than 0.5cm2. Skilled ex-perts assessed MEDs after 16 to 24 hours from irra-diation of UVB rays and finally determined anarithmetic means of them as MEDs. It was foundthat MEDs of 20 volunteers were 10-75mJ/cm2(42.5mJ/cm2 onthe average)(Table 2).

BB.. TTaannnniinnggA relatively clean region in the inner side of the

forearm was chosen as the region for this study be-cause of its accessibility. We first measured L-valuesin the internal side of forearm by using colorimeter,CR-300(Minolta camera Co., Ltd, Osaka, Japan),and then patched square templates(3cm2) used in thelight patch test. Then, by using the same UVBlamp for measuring MEDs, we irradiated 1.5MED tomake 8 tanned areas. Erythema appeared after 24hours and pigmentation appeared within 1 to 3days after irradiation. After 9 days, for 11 out of 20volunteers, tanned patches almost disappeared.Therefore, for 10 out of these 11 volunteers,2MED was applied again to the inner side of the op-posite forearm and for the remaining one, 6MED wasirradiated to gain the final tanned areas(Table 2).

CC.. WWhhiitteenniinngg CCoossmmeettiiccssFive cosmetics were used for whitening effect. SW-27 : Control (VC-PMG 0%, Licorice 0%)

CJ enprani lotionSW-28 : VC-PMG 3%, Licorice 0% SW-29 : VC-PMG 3%, Licorice 1%SW-30 : VC-PMG 3%, Licorice 2%SW-31 : VC-PMG 3%, Licorice 3%

VC-PMG : magnesium-L-ascorbyl-2-phosphate(Nikkol, the degree of purity 85%)

Licorice : licorice extracts(all of them from CJ enprani, Korea)

DD.. AApppplliiccaattiioonn ooff WWhhiitteenniinngg CCoossmmeettiiccssAfter irradiation for tanning, there was a stabiliz-

ing period( a time for the pigmentation) for about 7days. One control and four whitening cosmeticswere used in this double-blind vehicle-controlledstudy. Each examinee was given five cosmeticsand asked to evenly apply them twice a day by usinga swab not to mix with one another. Each applica-tion order for each examinee was different. Exami-nees were told to apply five cosmetics for 2months on 5 out of 8 tanned patches, nothing on 1out of remaining 3 patches and two out of five cos-metics were applied again on the remaining 2patches for reliability. Therefore, two out of fivecosmetics were applied respectively on two differentpatches for each examinee.

EE.. MMeeaassuurreemmeenntt ooff WWhhiitteenniinngg EEffffeeccttWhitening effects were evaluated at regular in-

tervals based on visible assessment, photographyand L-value of chromameter (CR300, MinoltaCamera Co., Ltd., Osaka, Japan).

aa)) VViissiibbllee AAsssseessssmmeennttTwo examiners measured the degree of pigmenta-

tion via visible assessment and recorded a mark inaccordance with the following grades. (0;unde-tectable, 1;mild pigmented, 2;moderately pig-mented, 3;highly pigmented)

bb)) PPhhoottooggrraapphhyyAn examiner took a photograph by using Nikon

camera with ISO100 Kodak film on each measure-ment.

Whitening Effect of Cosmetics Containing Magnesium L-Ascorbyl-2-Phosphate

(VC-PMG, Vitamin C Derivatives) Assessed by Colorimeter 65

cc)) LL--vvaalluuee ooff CCRR--330000An examiner measured L-value three times for

each tanned patch by using colorimeter (CR300, Mi-nolta Camera Co., Ltd., Osaka, Japan). L-value onthe colorimeter indicates a numerical expressionof color difference on black/white axis. Thus, thehigher L-value implies a color closer to its whitenessdegree.

After tanning, this measurement was taken at

weekly intervals for two months.

SSttaattiissttiiccssWe conducted ‘Mixed Procedure with SAS Sys-

tem’ to determine the differences of whitening effectsamong whitening cosmetics and ‘Repeated mea-sures ANOVA test’ to ascertain the significance of


Vol. 14, No. 2, April 2002

Table 3. Difference between Visible Assessment

Grades for Each Cosmetic

Cosmetics Difference

Control 1.75

SW-27 (VC-PMG 0%, Licorice 0%) 1.714286





p<0.05

Fig. 1. Whitening Effect Comparison between Cos-metics through Visible Assessment.

Fig. 2. A. Before any cosmetic application.

B. 56 days after application of each cosmetic.

SW-27 : Control (VC-PMG 0%, Licorice 0%) CJ enprani lotion

SW-28 : VC-PMG 3%, Licorice 0%




measurement interval.

RESULTS

11.. WWhhiitteenniinngg EEffffeecctt bbyy ccoolloorriimmeetteerrFor five cosmetics named SW-27, SW-28, SW-29,

SW-30 and SW-31, the higher TIME*CREAMEstimate (the increase ratio of L-values measured byusing colorimeter before and after application),means the greater whitening effect. The result isas follows: SW-29>SW-28>SW-27>SW-31>con-trol>SW-30 in the order of the greatness ofwhitening effect. Differences between them, how-ever, were not statistically significant(data are notshown).

22.. WWhhiitteenniinngg EEffffeecctt ffoorr EEaacchh MMeeaassuurreemmeenntt IInn--tteerrvvaall

For all whitening cosmetics, measurementsshowed statistically significant differences through56-day measurement period, except that of the in-terval between 42 and 49 days.

33.. RReelliiaabbiilliittyyTwo out of five cosmetics were applied respec-

tively on two different patches for each examinee. Asa result, most of examinees proved to be statisti-cally reliable. While two of them showed low relia-bility, the other 18 examinees turned out to behighly reliable (included in the visible assess-ment).

44.. VViissiibbllee AAsssseessssmmeenntt Through visible assessment for every measure-

ment, each mark was given in accordance with 4grades: 3 for highly pigmented, 2 for moderatelypigmented, 1 for mildly pigmented and 0 for unde-tectable. Differences between visible assessmentgrades on the 56th day after application and at thetime of tanning in the beginning were measuredfor each volunteer by each group of the cosmetics.Then, the means of the differences for each volun-teers were evaluated by each five group of cosmeticsto elucidate the visual whitening effects of thecosmetics(table 3).

As for SW-27 where only the vehicle was ap-plied, there seemed to have less whitening effect,compared to the control on which nothing wasapplied according to visible assessment. The otherfour cosmetics containing VC-PMG 3% and

licorice of different concentrations appeared tohave better whitening effect than control. The resultis as follows: SW-29 > SW-30 > SW-31 > SW-28 inthe order of the greatness of whitening effect(Fig.1).Therefore, SW-29 showed the greatest differencesin the degree of whitening.

Although the degree of differences in whitenesswas greatest in SW-29, the number of examineeswho experienced whitening effect, even a slightdifference, were slightly different. The number of ex-aminees who experienced whitening effect of eachcosmetic is as follows respectively: SW-28(6 out of20), SW-29(5/20), SW-30(5/20), SW-27(4/20),SW-31(3/20). Thus according to visible assess-ment, the cosmetic of SW-28 turned out to havewhitening effect on the most examinees.

55.. PPhhoottooggrraapphhyyWe continuously observed whitening effects by

taking a photograph for each measurement, andcompared them with those of visible assessments(Fig. 2 A,B)

DISCUSSION

This study deals with the whitening effect ofcosmetics. There are several materials which areknown for having whitening effects. Compoundsof catechol and phenol, such as hydroquinone, N-acetyl-4-S-cysteaminylphenol and monobenzylether ofhydroquinone(MBEH), are known as whitening mate-rials. In addition trans-retinoic acid, azelaic acidand ascorbic acid - both of them are saturated di-carboxylic acids- , Kojic acid(5-hydoxy-4-pyran-4-one-2-methyl), 4-hydroxyanisole, and arbutine alsofall under whitening materials. Besides, naturalextracts such as mulberry extract(paper mulberry),licorice extract(glabridin), bearberry extract,A.patula and A. viscida and green tea extract are al-so known as whitening materials3.

AsA affects collagen synthesis, drug-metaboliz-ing enzyme, production of interferon, antiviral,antibacterial, and antioxidization and photopro-tective actions13. AsA does not possess intrinsicabsortive capacity for UV radiation and are be-lieved to act after UV radiation has penetrated theskin and interacted with resident skin chro-mophores to generate reactive oxygen radicalsspecies14. It has been proposed that the influence ofAsA on the monopherase acitivty of tyrosinase is



from its ability to reduce the enzymatically generat-ed o-quinones15, so that melanin cannot be formedby the action of tyrosinase until AsA is oxidized.However the disadvantage of AsA is its instability,especially in aqueous solution. Magnesium-L-ascorbyl-2-phosphate(VC-PMG) was synthesizedto overcome this problem9. VC-PMG is stable inwater, especially in neutral or alkaline solutionscontaining boric acid10. VC-PMG is hydrolyzed byphosphatases of liver or skin to AsA and thus ex-hibits Vit C-reducing activity10. Moreover, VC-PMG in cream base can suppress melanin formationby tyrosinase inhibition. VC-PMG directly or indi-rectly suppresses melanin formation catalyzed bytyrosinase16. Tyrosinase related proteins 1(TRP1)had been suggested to have a variety of catalyticfunctions, including low levels of those enzymatic ac-tivities ascribed to tyrosinase17,18. TRP1 has alsobeen reproted to possess 5,6-dihydroxyindole-2-carboxylic acid oxidase activity, an activityblocked by AsA19. AsA probably suppressesmelanin formation at various oxidative steps ofmelanin formation, such as 5,6-dihyroxyindole oxi-dation. It is suggested that VC-PMG is absorbedpercutaneously, stays in the skin, and inhibits ty-rosinase activity of melanocytes. Therefore, withthe additive effect of L1-methyleneglycol-bis, it is ef-fective in reducing skin pigmentation. Kameyama etal. reported clinically significant lightening effect in19 out of 34 patients with melasma and solar damageinduced by UVB irradiation16. Also, application of10% VC-PMG cream to the skin of patients withhyperpigmented disorders, such as ephelides,chloasma, or senile freckles lightened the pigmen-tation is some16. Furthermore, VC-PMG also pro-duced the same lightening in normally pigmentedhealthy skin in the same report.

Licorice extract is also known for whitening effectand widely used for raw materials for cosmetics.Glabridin, one constituent of licorice, has been re-ported to inhibit melanogenesis7. Glabridin in-hibits tyrosinase activity of melanocytes withoutany cytotoxicity. They further showed that UVB-in-duced pigmentation and erythema was inhibitedby topical application of 0.5% glabridin. The anti-in-flammatory properties of glabridin were attributed toinhibition of superoxide anion production and cy-clooxygenase activity.

In this study, five whitening cosmetics wereused. Among them, SW-27 was a vehicle which

did not contain VC-PMG and licorice. SW-28,29, 30, 31 contained VC-PMG (Nikko, the degreepurity 85%) 3% and contained 0%, 1%, 2%, 3%licorice respectively.

The results of visible assessment for the differ-ences in the degree of whiteness revealed thegreater whitening effect in the following order:SW-29, SW-30, SW-31, SW-28 and SW-27.However, the number of examinees who experi-enced whitening effect of each cosmetic is as followsrespectively: SW-28(6 out of 20), SW-29(5/20),SW-30(5/20), SW-27(4/20), SW-31(3/20). Thissuggests that SW-28 showed better whitening effectin general and yet the degree of visual whitening ef-fect was greater in SW-29 whoever showed thedifferences. Thus, the result may propose that VC-PMG by itself has better whitening effect, butlicorice, which is known as a depigmenting agentmay enhance the degree of whiteness in some pa-tients.

Objective color measurement, as is nowadayspossible using different instrumental techniques,has proven very useful for measurements at differenttime intervals. The eye is very sensitive for thediscrimination of colors very close to each otherbut is rather poor in remembering colors, makingcomparison of color at different time intervalsvery difficult and subjective11. Hence, instrumentalnumerical quantification of colors seems to be wellsuited for the evaluation of pre- and post treat-ment colors. In the cosmetic field measuring skin col-or is an important tool for evaluating the efficacy ofwhitening products. Various types of colorimeters areintroduced in the cosmetic field, but objectivecomparison of their accuracy and sensitivity wasnecessary to choose a proper instrument in eachexperimental design20.

According to the results of colorimeter, whiteningeffects were greater compared to the control patchon which nothing was applied in the following order:SW-29, SW-28, SW-27, SW-31, SW-30. However,the measurements of the whitening effects by col-orimeter were statistically insignificant.

In general, according to the results of visible as-sessment and colorimeter, SW-29(VC-PMG 3%,licorice 1%) had more whitening effect than theother four cosmetics of different concentrations.Moreover, we evaluated the number of examineeswho demonstrated whitening effect through thevisible assessment for each cosmetic. There was


Vol. 14, No. 2, April 2002

better whitening effect in SW-28(VC-PMG 3%,licorice 0%, 6 out of 20 volunteers) than the controlgroup. Despite the lack of consistency, cosmeticscontaining licorice also demonstrated whiteningeffects. It can be interpreted as this unclear correla-tion between licorice concentration and whiten-ing effect was due to the some sort of reactions oc-curing when VC-PMG and licorice is mixedwhich is yet to be found.

The reason for the insignificant measurementsthe colorimeter is, first, that colorimeter is so sensi-tive that very little pressure could change valuesand thus deviation of measured values was great.In fact, according to a paper reported previously,colorimeter used in this research is more likely toproduce statistically insignificant results than othermethods such as maxameter and dermaspectrometer.Therefore, the possibility cannot be ruled out thatother instruments may have produced different re-sults. Secondly, this research chose the forearm asthe region of examination. This region has rela-tively less hair but the degree of hairiness couldvary according to individuals. An examinee mayhave hair on the forearm, which could cause col-orimeter to produce darker results.

CONCLUSIONS

1. This study is to apply whitening cosmetics onthe inner side of the forearm and to observewhitening effects.

2. VC-PMG and licorice extract were used aswhitening materials.

3. VC-PMG was clinically found to havewhitening effect. The cosmetic with greatestwhitening effect turned out to be SW-29(VC-PMG 3%, licorice 1%) and in case of SW-28(VC-PMG 3%, licorice 0%), whitening effects werefound in 6 out of 20 examinees.

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