J. $oc. Cosmet. Chem. 29 201-205 (1978) Effect of a skin cream containing the sodium salt of pifrollidone oarboxiflio acid on dry and flaky skin J. D. MIDDLETON* and MARESE E. ROBERTS Inveresk Research International, Edinburgh, EH21 7UB, Scotland Synopsis Humectants added to skin creams can increase the moisture retention of isolated stratum corneum and reduce the incidence of dry and flaky skin in vivo. This paper gives results of an investigation into the efficacy of a humectant, the sodium salt of pyrollidone carboxylic acid (Na PCA), which occurs naturally in the corneum. A product containing 5• of Na PCA increased the water-holding capacity of isolated animal comeurn. In a consumer trial, with assessment of skin dryness and flakiness by trained assessors, the Na PCA product was more effective than a control product containing no humectant and equally effective as a similar established product with a different humectant system. INTRODUCTION The integrity of the surface layer of skin, the stratum corneum, depends upon its ability to adapt without cracking to the forces applied during normal body movement. A lack of adequate flexibility and extensibility will result in corneum surface cracking and flaking, a condition commonly seen in dry and cold conditions on exposed skin. One factor of importance in maintaining corneum extensibility is its water content (1, 2). Many skin creams are, therefore, formulated with the objective of increasing the water content of the corneum. It is now well established (2-5) that an adequate corneum water content depends upon the presence within the corneum of hygroscopic water-soluble materials which can hold water in drying atmospheres. The water held by these hygroscopic substances is re- sponsible for much of the extensibility of the corneum (2). The hygroscopic water-soluble material within the corneum contains a mixture of substances (3). Amongst the more important hygroscopic components of the mixture are the sodium salt of 5-pyrollidone-2-carboxylic acid (Na PCA) (6) and lactate (3). Sodium lactate and lactic acid in a skin cream have been shown to be effective in increasing the water-holding capacity of isolated animal corneum and in reducing the incidence of dry and flaky skin as judged by trained assessors in consumer trials (7). This report gives an account of a similar investigation into the efficacy of Na PCA in a skin cream. EXPERIMENTAL MEASUREMENT OF WATER CONTENT OF ISOLATED CORNEUM IN HUMID ATMOSPHERES Corneum was obtained from the rear footpads of guinea pigs. It was separated by incubating the whole footpad in 0.1 mol tris buffer, pH 7'2, containing 2 tool urea and * Present address: Toxicol Laboratories, Bromyard Road, Ledbury, Herefordshire, HR8 1LG. 0037-9832/78/0400-0000 $02.00 ¸ 1978 Society of Cosmetic Chemists of Great Britain 201

202 d. D. Middleton and M. E. Roberts 0.55/0 pancreatic trypsin for 18 h at 37øC (2). After this, the softened underlying tissues could be scraped away and the resulting corneum was washed by immersion in distilled water for 2 h. It was solvent-damaged by immersion in diethyl ether at ambient tem- perature for 18 h, followed by immersion in distilled water for 6 h. This procedure re- moves lipids and hygroscopic substances and reduces the water-holding capacity in humid atmospheres (2). The solvent-damaged corneum was used in experiments designed to increase the water-holding capacity towards the level for intact corneum. ß The technique for measuring water-holding capacity has been described previously (2). Briefly, it consisted of equilibrating pieces of corneum at 815/o r.h. and ambient temperature to constant weight. The pieces of corneum were then transferred to a dry atmosphere over self-indicating silica gel and re-equilibrated before weighing. Both equilibria took about 6 days to attain. The water-holding capacity was expressed as mg water held 100 mg -x dry weight of corneum at 81• r.h. The effect on water-holding capacity of a skin cream containing 55/0 Na PCA (ACO Fuktr•im, ACO L•ikemedel AB, Solna, Sweden) was compared with that of a cream with the same formulation except that it contained no Na PCA. The corneum was treated by rubbing the cream for 90 seconds into both sides of a piece of corneum with the fingertips while wearing rubber gloves. Excess cream was removed by wiping with tissues and the treated corneum equilibrated at 815/o r.h. before weighing. No attempt was made in these experiments to quantitate the amount of cream deposited on the corneum, as preliminary gravimetric experiments showed this to be a highly variable quantity owing to the loss of loose corneum flakes while applying the cream. It was not considered that more elaborate experimentation to determine the quantity deposited would be justified as the in vitro technique was regarded as a simple screening test only. Results were obtained on the corneum from 15 guinea pigs. One piece from each animal was treated with the test cream containing Na PCA and the other with the control cream containing no Na PCA. The mean values for water-holding capacity for each cream were compared statistically by Student's 't' test for paired observations. EVALUATION OF SKIN DRYNESS AND FLAKINESS IN CONSUMER TESTS OF HAND CREAMS The effects of three hand creams were investigated in a 6 week home-use trial in which groups of panelists used each cream under test for consecutive 2-week periods in all possible orders of use. Trained assessors evaluated the degree of hand skin dryness and flaking after the use of each cream. The three hand creams were (a) the test cream containing 5• of Na PCA, (b)the control cream with the same formulation but containing no Na PCA and (c) an estab- lished marketed cream with an alternative humectant system containing urea. One hundred and fifty women took part in the trial. Each woman used each of the three creams for a period of 2 weeks. There were approximately equal numbers of women using the creams in each of the six possible sequences. Only women with some degree of hand skin dryness and flaking were selected to take part. In order to obtain a reasonable degree of dryness and flakiness, the trial was carried out in southern Scotland during the late winter and early spring of 1976. The method of assessing hand skin dryness and flaking has been reported previously