21048 neostrata green phas.qxd

21048 Neostrata Green PHAs.qxd 2/12/02 5:13 PM Page 1 Polyhydroxy Acids (PHAs) Provide Conditioning Effects to Skin Without Increasing Sensitivity to UV Light Barbara A. Green, R.Ph., Richard H. Wildnauer, Ph.D., Brenda L. Edison NeoStrata Company, Inc., Princeton, NJ, USA Self Assessment
COMPATIBILITY OF A PHA REGIMEN WITH TOPICAL
Self assessment for improvement of acne and oiliness correlated with dermatological lesion count assessments demonstrating product efficacy.
RETINOIC ACIDY
The polyhydroxy acids (PHAs) are skin care ingredients that provide additional benefits to skin compared to traditional alpha hydroxyacids (AHAs) such as glycolic acid and lactic acid. Similar to AHAs, PHAs provide Self Assessment – Improvement of Condition
exfoliation, skin smoothing and anti-aging effects.1-3 PHAs are also humectants and moisturizers, and most Tretinoin + PHA Regimen
PHAs possess antioxidant properties.
4 , 5 In comparison to commonly used AHAs, PHAs do not cause sensory irritation responses that can limit the use of classical AHAs.2-4Moreover, PHAs are compatible withclinically sensitive skin including rosacea and atopic dermatitis, 2 and corrective cosmetics containing PHAs can be used to conceal skin color irregularities on sensitive skin, e.g. post-laser purpura (FIGURE 1), and PHAs are used adjunctively with topical drug therapies for the treatment of inflammatory skin conditions haemangiomas as in Sturge-Weber Syndrome.6 PHAs have also been shown to enhance stratum corneum including psoriasis, rosacea, acne, and seborrheic dermatitis; and various hyperkeratotic condtions including barrier function, increasing the skin's resistance to chemical challenge.
xerosis and keratosis pilaris, as well as fungal infections, hyperpigmentation, and pre- and post-treatment forlaser resurfacing.12,13 New study results indicate that use of PHAs does not Condition: Skin Discoloration
The following study was conducted to determine the compatibility of a PHA regimen with topical tretinoin result in an increase in sunburn cells in skin following UVB in the treatment of mild to moderate facial acne.
exposure. Therefore, PHAs are an important alternative to AHAs for individuals not able to use Population:
sunscreen protection with their AHAs on a daily basis. In Mean % Reduction in MED Compared to Untreated
27 healthy males and females, ages 19-54 years addition, PHAs are shown to be compatible with tretinoin Subjects exhibited mild to moderate facial acne use. Combination use of PHAs plus tretinoin may be Exclusion for use of: (i) any acne therapy (including topical OTCs or Rx, or systemic medications) preferable to glycolic acid plus tretinoin in view of the one month prior to study, (ii) PHA or AHA products 4 weeks prior to study, or (iii) topical retinoids Over 85% of the subjects reported that the cleanser, day lotion SPF 15, and night cream were potential increase in sun sensitivity by tretinoin.
within 3 months or oral retinoids within 6 months of study initiation compatible with their use of topical tretinoin. Study Design: Four week normal use regimen with comparisons to baseline
Test Materials:Products were applied to the entire face in a normal use manner as indicated
in the table. The PHA products were provided in blinded packaging.
Self Assessment
Compatibility of PHA Products with Tretinoin
The purpose of this poster is to describe recent study results regarding the benefits of PHAs as they * Significant reduction in MED compared to untreated control, p<0.01 Conclusions
PART I: THE EFFECT OF TOPICAL TREATMENTS ON THE SENSITIVITY
MEDs appear to be affected by topical product application.
OF HUMAN SKIN TO SOLAR SIMULATED RADIATIONX
Glycolic acid application significantly reduced the MED in study (I), and caused a directional but not statistically significant reduction in MED in study (II) compared to untreated.
PHAs (gluconolactone and glucoheptonolactone) did not significantly change the MED compared The Cosmetics, Toiletries and Fragrances Association (CTFA) and Food and Drug Administration (FDA) have Assessments
investigated the effects of AHA product usage on the sensitivity of normal human skin to UVB exposure by Clinical assessmentof efficacy included
acne lesion counts conducted by a board certified
Conclusions
measuring changes in minimal erythemal doses (MEDs) and numbers of sunburn cells (SBCs). Findings dermatologist. Scores were reported as total lesion counts: papules + pustules + open comedones The PHA regimen was well tolerated on facial adult acne when combined with tretinoin 0.1% gel.
There is inherent variability in MEDs within a person. Therefore small changes in the MED value among the studies indicate that there is a significant increase in the sensitivity of skin to UVB after AHA Use of the PHA regimen did not adversely affect tretinoin efficacy in treating acne.
(glycolic acid, 10%) use8,9; this effect subsides within seven days of discontinuing AHA use.8 The present two Clinical assessmentsof irritation were conducted by a board certified dermatologist and included:
studies were conducted to evaluate the effects of polyhydroxy acids (gluconolactone and glucoheptonolac- objective irritation (dryness and erythema), and inquiries about subjective irritation( i t c h i n g ,
This study supports the use of PHAs in combination with tretinoin for adult acne.
tone) on skin sensitivity to UVB using the model employed by CTFA and FDA.
burning, stinging, tightness) using a 5 point scale (none, barely perceptible, mild, moderate, severe).
Gluconolactone
Glucoheptonolactone
Self assessmentquestionnaires were completed to assess consumer perception of efficacy and
The polyhydroxy acids (PHAs) have gained important clinical uses as a result of their providing AHA benefits to skin, with additional gentleness and antioxidant characteristics resulting from the polyhydroxy molecule.
PHAs are commonly used adjunctively with other topical therapeutic regimens in the treatment of skin 12,13 The above study indicates that tretinoin 0.1% gel is both well tolerated and effective in the treatment of acne when combined with a PHA regimen. ➢ All dermatological parameters remained within normal limits throughout the study.
The Cosmetic Ingredient Review panel suggests use of AHAs (i.e., glycolic acid and lactic acid) in consumer Clinical Assessment - Acne Lesion Counts
products at a maximum concentration of 10%, and minimum pH of 3.5 when the products are formulated to Total lesion counts (including papules, pustules, open and closed comedones) significantly decreased avoid increasing the skin's sensitivity to sun, or when directions for use on packaging include the daily use of Research has shown that low level sunscreens in AHA formulations can prevent the throughout the study, thus demonstrating efficacy of the tretinoin formulation in combination with a development of SBCs after UV exposure.15Nonetheless, some individuals are sensitive to sunscreens and do ➢ Two separate studies utilizing a complete block design. Products were blinded and randomly assigned to not apply them on a daily basis. The above studies indicate that application of PHAs (gluconolactone and glucoheptonolactone) does not increase the sensitivity of skin to UVB, and therefore may provide an ➢ Population:Healthy males and females, Fitzpatrick skin types I, II, and III.
important formulation option to AHAs, especially for those individuals that are sensitive to sunscreens. In Total Acne Lesion Counts
addition, topical PHAs provide a safe and well-tolerated option for combination use with retinoids, which are Mean Sunburn Cell Count SBC/HPF
Tretinoin + PHA Regimen
known to cause photosensitizing effects.
➢ Test Materials: (study I)
Test Materials:( s t u d y I I )
PHA: 8% glucoheptonolactone cream, pH 3.8 Green B, Tseng C, Wildnauer R, Herndon J, Rizer R. Safety and efficacy of a gluconolactone (polyhydroxy acid) containing regimen on sensitive skin and photodamage following controlled consumer use. Amer Acad of Derm Poster Exhibit:New Orleans, March, 1999.
➢ Test Material Application:
Bergfeld WF, Remzi BK, Green B, Patel P, Ravas R. An evaluation of the gluconolactone sensitive skin care products. Exhibit:Orlando, February, 1998.
Once daily application to marked test sites on the back by study personnel using a 1c.c. disposable Bernstein, EF, Green, BA, Edison B, Wildnauer, RH. Poly hydroxy acids (PHAs): clinical uses for the next generation of hydroxy acids. plastic tuberculin syringe at a dose of 2mg/cm 2. Products were thoroughly rubbed into the test sites Van Scott EJ, Yu RJ. Bioavailability of Alpha-hydroxy acids in topical formulations. Cosmet Dermatol1996; 9(6):54-62.
*Significant improvements from baseline at Weeks 2 and 4, p<0.05 Yu RJ, Van Scott EJ. Alpha-hydroxy acids: science and therapeutic use. Products were applied 6 days per week for 4 weeks.
*Significant increase in SBCs compared to untreated, p<0.05 No significant differences among treatments, p<0.05 Green BA, Beer AE, Edison BL. Use of concealing cosmetics to reduce the visibility of topical skin afflictions for enhanced quality of life. ➢ Endpoint MEDs:
Psoriasis Symposium Poster Exhibit:San Francisco, June 2001.
Determined at each test site 20±4 hours after exposure to a solar simulator. Test sites were graded Berardesca E, Distante F, Vignoli GP, Oresajo C, Green B. Alpha hydroxyacids modulate stratum corneum barrier function. ➢ Conclusions
British J Dermatol1997;137:934-938.
visually for erythema under standardized lighting conditions. Glycolic acid caused a significant increase in SBC count in study (I) and a small, directional increase Clinical Assessment - Objective and Subjective Irritation
Ivy Laboratories, KGL protocol #4275. Final report. June 1999.
➢ Sunburn Cells( S B C s ) :
Mean scores for both objective (dryness and erythema) and subjective (itching, burning, stinging, in SBCs in study (II) compared to Untreated.
Ivy Laboratories, KGL protocol #3813. Final report. December 1996.
Induced by one exposure to 1.5x MED approximately 15 minutes following the last topical application and tightness) irritation remained less than “barely perceptible” on the 5 point grading scale after The PHAs (gluconolactone and glucoheptonolactone) did not significantly increase SBCs compared 1 0 . Personal communication. K. Kaidbey MD, 2001.
1 1 . Glycolic acid increases short-term skin sensitivity to UVB rays-FDA. The Rose Sheet.September 13, 1999: p 3-4.
Shave biopsies (4x4mm) were obtained 20±4 hours following irradiation. The skin specimens were 1 2 . Petratos MA. Drug therapies and adjunctive uses of alphahydroxy and polyhydroxy acids. 1 3 . L. Kakita, MD. Correspondence on file. Item#13039: NeoStrata Company, Inc., Princeton, NJ.
immediately fixed in 10% buffered formalin.
These findings are consistent with previous studies conducted by CTFA and FDA.8,9,11However, there 1 4 . 3 4 Report of the CIR Expert Panel - Safety of alpha hydroxy acid ingredients. Fixed specimens were processed routinely, paraffin embedded and then sectioned and stained with was a disparity in values for the two control cells (glycolic acid and untreated) between the two 1 5 . UV susceptibility of skin treated with 4% and 8% glycolic acid products. Correspondence to CTFA. December 1996. studies demonstrating variability with this model, possibly related to the difference in age groups of Numbers of SBCs were counted in a blinded manner by the investigator in at least 12 sections at 50 the participants between the two studies. Study conducted by KGL, Inc. (Ivy Laboratories), Philadelphia, PA micron intervals. A minimum of 70 high power fields (HPF) was counted from each biopsy and the Study conducted by Consumer Product Testing Company, Inc., Fairfield, NJ average number of SBCs per HPF determined.
American Academy of Dermatology Poster Exhibit: New Orleans, LA; February 22-27, 2002.

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