UNIPERTAN VEG-24/242/2002

Transcription

1 UNIPERTAN VEG-24/242/2002 TANNING ACCELERATION COSMETIC ACTIVE INGREDIENT COMPLEX FOR TANNING ACCELERATION FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

2 CONTENTS 1. Introduction Principle of skin pigmentation Concept of the active ingredient complex Unipertan Efficacy test of the preparation Deep Tanning Cream with the active ingredient complex Unipertan Study design Characteristics of the HA-FI 200 UV Lamp Study protocol (n = 22) Clinical assessment of tanning attained Biometric analysis and assessment Results of follow-up measurements Activators and protein hydrolysates Unipertan P-24 / VEG Unipertan P-242 / VEG Unipertan P-2002 / VEG Summary of results Skin tolerance Skin challenge test Repeated irradiation test during sustained treatment with cream I Characteristics of Unipertan VEG Characteristics of Unipertan VEG Characteristics of Unipertan VEG References FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

3 1. Introduction Even today, sun protection using the natural sun protection mechanism is clearly still of benefit for supporting the sun protection factor of sunscreen agents. This can be achieved by stimulating the natural metabolism in the skin. By the daily application of natural active ingredients, which accelerate the natural sun protection mechanism, tanning protection is slowly built up, which is provided for human beings by Nature. The active ingredients contained in the active ingredient complex Unipertan are extremely effective in fulfilling the conditions as set out above and in achieving the aim of building up natural sun protection. It should not be assumed that Nature made a mistake when she gave us sunlight. All life on earth depends on sunlight; without it there would be no plants and no life. The literature on the effects of the sun on the human body has been summarised variously. Thus, for example, without sunlight, natural processes such as the formation of vitamin D, the regulation of blood pressure or of cholesterol levels, etc. would come to a halt. Moreover, our mental wellbeing depends on sunlight, as has been described previously on a number of occasions. Consequently, even up to a few years ago, tanning was equated with health. Unfortunately, however, the cult of excessive sun worship in past years has resulted in premature aging of the skin, progressing to skin cancer in some cases. This situation required a change in attitude. The mass media did their utmost to ensure that our mistaken attitude to sunlight was polarised, so that today the general public have, if anything a fear of sunlight. In scientific terms, however, here too that wellknown saying applies: it is the dose which makes a poison. Use of a tanning accelerator to support natural skin protection is indicated, especially since ever more creams with high sun protection factors are being used. This behaviour acts counter to the natural skin protection mechanisms. The rays of the sun are blocked out, and melanin cannot be formed. The natural skin protection mechanism is blocked. The higher the sun protection factor used, the longer one has to stay in the sun, in order to activate the natural skin protection mechanism. The same applies to the essential biological processes, which are also delayed. In theoretical terms, the duration of exposure to the sun required is no longer justifiable from the dermatological standpoint. Thus, for example, instead of 10 minutes exposure to the sun to induce the formation of melanin or for tanning, a 300 minutes (6 hour) stay would be needed, if a cream of SPF 30 was used. Moreover, the question remains unresolved, of the extent to which the amounts of substance(s) which have to be applied to the skin over the whole of the body to attain an SPF of 30 will influence the health of the skin or have more wide-reaching effects on the whole body. Using a tanning-enhancing agent, which preconditions the skin and produces pre-tanning, would therefore make it possible to use a cream with a lower SPF. These are advantages, which even today favour the daily application of a tanning accelerator. By daily application of the biological accelerator the skin becomes tanned even in seasons with low levels of sunlight, which allows its natural protection against later burning to remain intact. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

4 2. Principle of skin pigmentation The yellowish-brown to brownish-black pigment melanin is formed in the melanocytes via biochemical reactions. Starting with the amino acid tyrosine, which occurs in natural proteins, this is oxidised by the enzyme tyrosinase under the influence of light and oxygen. The subsequent biochemical reactions which make up the pathway leading to the production of melanin and formation of melanoproteins largely proceed independently. Tyrosinase (O) HO (O) O CH 2 CH-COOH HO tyrosine CH 2 CH-COOH H 2 N CH 2 CH-COOH H 2 N HO DOPA 3,4-dihydroxyphenylalanine O H 2 N dopaquinone HO O HO COOH COOH HO N O N HO N H H H 5,6-dihydroxyindole dopachrome red leukodopachrome O O N H indol-5,6-quinone yellow O O N H tyrosinemelanin brown (eumelanin) yellow (pheomelanin) n + protein melanoprotein Figure 1: Production of melanin and formation of melanoproteins FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

5 The pigment formed in the melanocytes is then released to cells in the epidermis and migrates with these to the skin surface. In this manner the skin becomes pigmented brown and the skin is provided with protection against further effects of solar radiation. Two types of pigmentation are distinguished: direct and indirect. Direct pigmentation is produced chiefly by UV-A radiation, and also by radiation of longer wavelength and heat. In this process, the colourless pigment precursors already present in the skin, found in the cells of the epidermis, are converted into melanin. This type of pigmentation may occur, albeit weakly, within a few minutes of exposure to light. The pigmentation gives the skin only a transient, relatively weak tan. Indirect pigmentation is produced by UV-B radiation. These rays stimulate the melanocytes to increase the formation of melanin. The melanin formed in this manner is released into cells. With the cells, the melanin migrates through the whole thickness of the epidermis, up to the surface of the skin. This pigmentation develops after a few days and gives the skin a tan lasting for a few weeks to months. Since the untanned skin possesses relatively weak inherent protection, and is therefore exposed to the risk of sunburn in response to solar radiation, preparations containing light-absorbing substances have been developed to protect the skin. The main function of a cosmetic sun protection preparation, because of the appropriate UV filters which it contains in suitable skincare vehicles, is to protect the skin against sunburn and at the same time to provide the most intense possible tanning of the skin. The extent of protection, however, is inversely proportional to the tanning achieved, i.e. the greater the protection, the weaker is the tanning achieved. As ever, the wish of every sunbather is to obtain the optimal tanning with minimal skin damage after the shortest possible exposure to sunlight, and to increase the natural protection of the skin. Thus the task is to develop a complex of active ingredients, which when applied together with a sun protection preparation with the usual sunlight protection and the caring properties, allows more rapid, more intensive and longer-lasting tanning of the skin in sunbathing. This task has been fulfilled by the development of the active ingredient complex Unipertan. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

6 3. Concept of the active ingredient complex Unipertan Following extensive studies of the specialist literature on skin pigmentation, pigmentation mechanisms and pigment formation, the following fundamental findings were drawn together: Pigmentation is entirely independent of the number of pigment-forming cells. The intensity of pigment formation is dependent only on the efficacy of the metabolic processes in the pigment cells of the skin. It is further known that in the skin the pigment melanin is derived from the amino acid tyrosine. Tyrosine is converted via oxidative bioreactions only in response to light, heat and oxygen. This reaction, i.e. the addition of oxygen to tyrosine, is mediated in the skin by an enzyme, tyrosinase (an oxidase). As soon as this oxidation has taken place, the subsequent biochemical reactions are able to occur, including the reactions which lead spontaneously to the formation of melanin. Since melanin formation in the special organelles of the melanocytes is an enzymatic oxidative process, an increase in the supply of tyrosine is likely to result in an increase in the quantity of melanin. Biochemists know that in an enzymatic process, increasing the supply of substrate increases the yield of end product, within certain limits. On the basis of an understanding of these biological processes, the hope was that enhanced tanning would occur during sunbathing, if tyrosine, the starter substance for the formation of melanin, was added to sunscreen preparations. Further justification for the addition of tyrosine was lent by another finding. It is known that UV radiation causes the normal content of tyrosine in the skin to diminish. The resulting deficiency of tyrosine in response to UV irradiation can be compensated by the addition of tyrosine, favouring melanin formation. On the basis of all these findings, attempts have frequently been made to enhance pigmentation by adding tyrosine or tyrosine + tyrosinase to sun protection preparations. However, in practice all these studies showed that only very weak, barely discernible enhancement of tanning was attained by the use of these additives. In these studies, tyrosine derivatives or tyrosine complexes were used either in insufficient quantities or without taking into account skin penetration capacity and the degree of absorption. Adding the endogenous enzyme tyrosinase, as found in the skin, as an activator to sun protection preparations containing tyrosine is not feasible in practice because of the difficulty and high cost of obtaining the enzyme and above all because of the instability of the enzyme. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

7 It is known that melanocytes are stimulated to form melanin by UV radiation. An excess of tyrosine in and around melanocytes may lead to an increase in natural melanin thanks to the increased supply, but only if the melanocytes have been stimulated either by UV light or by UV light + an activator similar to tyrosinase. Thus a tyrosine derivative would have to be used, which would be well absorbed by the skin and which would be able to penetrate to the melanocytes, and an activator, which would be able to replace the function of tyrosinase, even if only partially. Through intensive research, a mixture of a water-soluble tyrosine derivative and a protein hydrolysate, which contains tyrosine, was found, which acts optimally both with respect to its spreadability on the skin and the formation of skin protection. The penetration of the tyrosine derivative into the skin is favoured by proteins of molecular weight 2 kda. The protective effect on the skin is attained by using proteins of molecular weight up to 100 kda. The protective film which forms reduces additional skin irritation and the drying of the skin resulting from sunbathing and elicits more rapid reactivation of the damaged skin structures. By adding an activator the desired tanning of the skin is then produced. Sun protection preparations to which Unipertan has been added result in more rapid, more intensive and longer-lasting tanning of the skin in response to solar irradiation. The addition of Unipertan to sun protection preparations thus produces an increase in pigment formation and a reduction in skin cell damage in response to solar irradiation. This effect is mediated via the principle underlying natural pigmentation of the skin, the formation of melanin. By using a biological precursor, the skin-damaging effects of the sun are counteracted. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

8 4. Efficacy test of the preparation Deep Tanning Cream with the active ingredient complex Unipertan In earlier studies, it was demonstrated that L-tyrosine, which was incorporated in a cream at a proportion of 1%, accumulates in the skin. The purpose of a further study is to investigate whether a cream with a sun protection filter (SPF 3), which contains added L-tyrosine, can significantly improve tanning. 4.1 Study design The following 3 creams were used: Cream I containing tyrosine, activator, sun protection filter (SPF 3) Cream II containing tyrosine, sun protection filter (SPF 3) Cream III containing sun protection filter (SPF 3) The studies were performed by the company Pharmatox GmbH with the collaboration of E. Heisler, Prof. Dr. med. S. Marghescu, Privat Dozent Dr. Lubach and Prof. Dr. Ing. Reinhard. 22 middle-aged subjects of both sexes were available. Initially, the sun protection factor was measured in the subjects according to Alsins J. et al. (1). In order to create irradiation conditions as natural as possible, a UV lamp of type HA-FI 200 was selected Characteristics of the HA-FI 200 UV Lamp Irradiation distance 50 cm Irradiation field (50% value) 40 cm diam. UV irradiator power 105 W Radiation strength UV-A (mw/cm 2 ) 0.6 (sun 0.6/0.4) Radiation strength UV-B (mw/cm 2 ) 0.4 (sun 0.4/0.1) Erythema threshold time 4 minutes (sun 3/12 min.) The qualitative, subjective assessment of the tanning of the skin attained was performed by dermatologists and laboratory personnel. Quantitative, objective data on the intensity of tanning was measured using the LF 90 colour measuring device supplied by Dr. B. Lange (Neuss, Federal Republic of Germany). FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

9 Three fields were marked out on the backs of 22 subjects (5 x 10 cm) and the skin colour was measured with the LF 90 colour measuring device on every occasion immediately before treatment and before each irradiation. The measurements in each case were performed with 3 XYZ filters, and the mean values were noted for all persons for the relevant filter, field, and cream. A total of 13 colour measurements were performed. In each case, the three fields were treated with the same cream (I, II or III) before irradiation. A quantity of 0.1 g of cream was applied on each occasion, so that the layer of cream was about 20 µ thick. After applying the cream, an interval of 10 minutes was observed before rubbing the cream in. Thereafter, the treated areas of skin were irradiated with the HA-FI 200 UV lamp at a distance of 50 cm. Each subject was irradiated 12 times at the same time of day with an interval of 48 hours between irradiations. The irradiation duration selected was an ascending sequence from 10 to 27 minutes. The irradiation durations were in all cases appreciably below the MED (minimum erythema dose). In the preliminary study and in the determination of the SPF, the MED for untreated skin was 4.4 minutes. The MED for skin pre-treated with cream III (mean of 22 measurements) was 14.8 minutes. Experience has shown that skin reactions combined with increased scale formation occur if the maximum MED is exceeded as a result of excessive irradiation. This, in turn, produces incorrect measurements. 5 to 6 hours after irradiation, the irradiated fields were again treated with the appropriate creams. Since irradiation was performed 12 times, each subject was treated with the appropriate cream on the site specified 24 times. Subsequently, colour measurements were performed at a later time in 13 subjects, in order to establish how the intensity of tanning decreased with time. These studies are marked with an asterisk *. The table below presents the time sequence of colour measurements (X, Y and Z filters), treatments of the fields with the creams before and after treatment, and the irradiation duration itself. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

10 4.2 Study protocol (n = 22) Time elapse in days Time of colour measurment Time of treatment with creams approx. Start of irradiation Duration of irradiation Time of followup treatment with creams min min min min min min min min min min min min * * * Table 1: Study protocol The X, Y and Z values obtained, which represent the skin colour measurements made on the fields treated with creams I, II and III, were presented diagrammatically both for the study proper and for the follow-up measurements. Since the remission values X, Y and Z obviously fall as the intensity of tanning increases, supplementary counts up to 100 were calculated for all values exhibiting a positive trend and used for the graphical (Figure 2) presentations. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

11 71.0 Tanning Efficacy Placebo 64.0 with Tyrosin 63.0 with 5% Unipertan P Days Figure 2: Tanning efficacy FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

12 4.3 Clinical assessment of tanning attained After the subjects had been irradiated 3 to 4 times, unequivocal tanning was discernible. For cream I, the tanning as assessed by eye alone was found to be unequivocally better than that seen with cream III and still slightly better than that observed with cream II. This difference remained in evidence up to the end of the study. After 8 to 9 irradiations, we had the subjective impression that maximum tanning had been attained. In purely mathe-matical terms, this shows that maximum tanning with cream I was attained some 3 to 4 irradiations before cream III, and some 1 or 2 irradiations before cream II. Summarising from these findings, both cream I and cream II intensified late-type (delayed) pigmentation. 4.4 Biometric analysis and assessment In 22 subjects, standard colour values X, Y and Z in accordance with DIN (German Standard) 5033 were measured on 13 occasions at three skin sites which had been treated differently. The data were subjected to analysis of variance on a two-factorial plan, the subjects being treated as groups (E. Weber: Grundriss der biologischen Statistik (Outline of biological statistics), Stuttgart 1972). The statistical analysis of all values was performed by computer. The results for the X-filter demonstrated significant differences between cream I and II from day 4 of treatment. The standard colour value X was appreciably lower for cream I. For the Y-filter, significant differences were evident between the two creams from day 3 of the study. For the standard colour value Z, significant differences between cream I and cream II were apparent from day 3 of the study. The results of colour measurements and the statistical analysis of these results showed that cream I with Unipertan significantly improved tanning, in the following respects: a) the tan appeared earlier b) an optimum tan was attained earlier c) the intensity of tanning was greater than with cream II and cream III. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

13 4.5 Results of follow-up measurements Follow-up measurements of the skin colour on the sites treated with the three creams were performed 12 and 27 days after the last measurement. The values obtained were subjected to biometric analysis. Cream I again exhibited significant tanning. The intensity of tanning was significantly greater than on the sites treated with cream III. The sites treated with cream II continued to exhibit slight tanning as compared with cream III. In the follow-up measurements, the values for the sites treated with cream III were almost the same as the initial values measured before the irradiation test. The follow-up measurements demonstrated that the permanence of the tanning on the sites treated with cream I was still significantly higher than for cream I even 15 and 30 days after the last irradiation. These results thus demonstrate that cream I with tyrosine, activator (riboflavine) and sun filter (SPF 3) affords more rapid, more intensive and more sustained tanning of human skin in response to UV irradiation. 5. Activators and protein hydrolysates 5.1 Unipertan P-24 / VEG-24 During the course of the development of the Unipertan Series, various activators were investigated: riboflavine, adenosine triphosphate (ATP), and a combination of the two. In addition, the market demanded a change in the original protein hydrolysate, which consisted of collagen of animal origin. This series was called the P-series (P-24, P-242, P-2002). The subsequent series was called Veg (Veg-24, Veg-242, Veg-2002), because the collagen was replaced by a vegetable protein hydrolysate. The precise composition of each individual product is given in the relevant data sheets. At the start of testing, ribo-flavine was first used, and all previous studies had also been performed with riboflavine. Riboflavine naturally exhibits an intense yellow coloration. As a consequence of this, all products containing Unipertan P-24/VEG-24 were of necessity recognisable by their yellow colour. The wish to produce colourless or white cosmetic products prompted a search for other biochemical activators to accelerate tanning. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

14 5.2 Unipertan P-242 / VEG-242 Pigmentation is largely dependent on the activity of the enzyme tyrosinase, which is naturally present in the skin. In normal skin, the concentration of tyrosinase is very low. Moreover, tyrosinase occurs chiefly in an inactive form. This is evident in the long induction period which has to elapse before the tyrosine-tyrosinase reaction can take place in response to irradiation. It is known from the specialist literature in biochemistry that adenosine phosphate biocatalytically stimulates the activation of tyrosinase. This activates melanogenesis and thus accelerates and enhances the formation of melanin. Moreover, the distribution of melanin-bearing melanosomes in the skin is improved, resulting in uniform and improved tanning. On the basis of these findings, and after extensive studies of efficacy, the active ingredient complex Unipertan P-242 was developed based on a combination of the active ingredients tyrosine/adenosine triphosphate (ATP) with the following composition: total tyrosine content 8.0%, adenosine phosphate 1.0% and protein hydrolysate 21.0%. Adenosine triphosphate is notable for possessing a whole range of very desirable properties from the cosmetological point of view: it increases DNA synthesis and DNA replication (DNA = deoxyribonucleic acid, the building blocks of the cell nucleus). In particular, ATP prevents light-induced damage to DNA caused by solar radiation; increases the formation of new collagen and accelerates wound healing; exhibits antitumour activity; and supplies biochemical energy for the metabolism in the epidermis. Applied topically, ATP also increases the moisture-retaining capacity of the skin and improves the smoothness of the skin. In terms of efficacy, Unipertan P-242 affords better results than those obtainable with Unipertan P-24 with respect both to the rate of tanning and the intensity of tanning. 5.3 Unipertan P-2002 / VEG-2002 The obvious next step was to combine the advantages of the proven active ingredient complexes Unipertan P-24 and P-242 in a new product Unipertan P Thus Unipertan P-2002 contains all the active ingredients required to afford physiologically optimal acceleration of tanning without risk to health. The total content of tyrosine is 8.0%. Tyrosine is present both as a bioavailable, watersoluble derivative, and as a constituent of the protein hydrolysate, which forms 21.0% of the product. Riboflavine, present in a proportion of 0.3%, provides a photooxidative activator. Adenosine phosphates are present (total content 1.0%) to supply biocatalytically activated tyrosinase. Comparative tanning studies with creams containing 5% of Unipertan P-24, P-242 and P-2002, respectively, showed that the cream containing 5% Unipertan P-2002 achieved the highest intensity of tanning of the skin. As compared with controls, the increase obtained was more than 40%. The results are presented in the accompanying tanning curves (Figure 3). FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

15 70.00 Comparison of different Unipertans Tanning intensity Control Placebo P-24 P-242 P Days Figure 3: Comparison of different types of Unipertan 6. Summary of results Systematic investigations of the sunscreen preparations containing Unipertan showed that: tyrosine, applied to the skin as a constituent of Unipertan in a cream accumulates in the skin and penetrates to the epidermal melanocytes. Clinical studies on the human skin showed that: tyrosine and riboflavine, applied as part of Unipertan, afford more rapid, more intensive and more sustained tanning in response to UV irradiation. Unipertan is non-toxic and is very well tolerated by the skin. No allergic, photoallergic or photodynamic effects were seen, even after long exposure to UV radiation. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

16 7. Skin tolerance Unipertan VEG 2002 has been investigated extensively in comprehensive tests, and is well tolerated by the skin without problems. 7.1 Skin challenge test This skin challenge test was performed with the Läppchen probe. The test site chosen was the inner aspect of the lower arm, and the test plaster used was No supplied by Beiersdorf, Hamburg. 45 subjects aged years, both male and female, of various skin types and different degrees of sensitivity, were tested. Unipertan P-24 at a concentration of 50% was placed in the chamber of the plaster (about 0.1 g); this was affixed to the skin and removed after 24 hours. Assessment of the test responses was performed in accordance with Bandmann/Dohn Die Epikutantestung (Skin challenge testing) 1967, page 31. For each subject, a repeat reading was made after 24 hours. The aim of performing follow-up over a total period of 48 hours was to document delayed reactions. The preparation elicited only 2 reactions, both without significance dermatologically, and was thus well tolerated by the skin. 7.2 Repeated irradiation test during sustained treatment with cream I In a tanning test, cream I (Deep Tanning Cream with Unipertan P-24, SPF 3) with tyrosine derivative and activator (riboflavine) was applied 24 times to the same skin site on 22 persons. After each second application of the cream, the same site was irradiated for 10 to 27 minutes with an HA-FI 200 UV source. None of the subjects tested displayed adverse effects which might have indicated that the product possessed allergic, photoallergic or photodynamic properties. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

17 8. Characteristics of Unipertan VEG-24 Cosmetic complex of vegetable based ingredients for tanning acceleration, without preservative Composition Total tyrosine content approx. 8% Riboflavin approx. 0.3% Protein hydrolysate (vegetable) approx. 2% Butylene glycol approx. 20% Appearance Liquid. Analytical Data See specifications. Solubility Properties Soluble in water in any ratio. Soluble in propylene glycol. Soluble in ethanol/water mixtures with up to 60% ethanol. Insoluble in lipids. Unipertan VEG-24 has been similar in overall composition to Unipertan P-24 with the same tanning accelerating properties. Instead of animal derived hydrolyzed protein, Unipertan VEG-24 contains exclusively of vegetable origin. Both products have the same total tyrosine content. Its content of butylene glycol provides excellent hydrating properties. Unipertan VEG-24 does not contain a preservative. Unipertan VEG-24 is dermatologically tested and presents no problems of skin tolerance. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

18 Use Unipertan VEG-24 is used as a tan accelerator. It does not have any UV absorbing properties and therefore is used in sun protection preparations containing UV absorbents to achieve a quicker, more intense and longer lasting suntan. In addition, Unipertan VEG-24 is also recommended for use in tanning accelerator containing preparations applied as a pre-tan product for sun bathing or in combination with a common sun protection preparation during sun bathing. Unipertan VEG-24 can, in principle, be integrated into existing formulations of sun protection preparations. On account of its solubility in water, Unipertan VEG-24 is recommended for use not only in O/W emulsions but also in W/O emulsions. Dosage 5% Storage Processing Storage conditions: see safety data sheet. Shelf life: see specifications. Unipertan VEG-24 is relatively stable and can easily be processed under conditions common in the production of cosmetics. Identification INCI name CAS No. Butylene Glycol Acetyl Tyrosine Hydrolyzed Vegetable Protein Riboflavin FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

19 9. Characteristics of Unipertan VEG-242 Cosmetic complex of vegetable based ingredients for tanning acceleration, without preservative Composition Total tyrosine content approx. 8% Total adenosine phosphates content approx. 1% Protein hydrolysate (vegetable) approx. 2% Butylene glycol approx. 20% Appearance Liquid. Analytical Data See specifications. Solubility Properties Soluble in water in any ratio. Soluble in propylene glycol. Soluble in ethanol/water mixtures with up to 60% ethanol. Insoluble in lipids. Unipertan VEG-242 is similar in overall composition to Unipertan P-242 with the same tanning accelerating properties. Instead of animal derived hydrolyzed protein, Unipertan VEG-242 contains exclusively vegetable hydrolyzed protein. Both products have the same total tyrosine content. Its content of butylene glycol provides excellent hydrating properties. Unipertan VEG-242 does not contain a preservative. Unipertan VEG-242 has been dermatologically tested and presents no problems of skin tolerance. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

20 Use Unipertan VEG-242 is used as a tan accelerator. It does not have any UV absorbing properties and therefore is used in sun protection preparations containing UV absorbents to achieve intense and longer lasting suntan. In addition, Unipertan VEG-242 is also recommended for use in tanning accelerator containing preparations applied as a pre-tan product for sun bathing or in combination with a common sun protection preparation during sun bathing. Unipertan VEG-242 can, in principle, be integrated into existing formulations of sun protection preparations. On account of its solubility in water, Unipertan VEG-242 is recommended for use not only in O/W emulsions but also in W/O emulsions. Dosage 5% Storage Processing Storage condition: see safety data sheet. Shelf life: see specifications. Unipertan VEG-242 is relatively stable and can easily be processed under conditions common in the production of cosmetics. Identification INCI name CAS No. Butylene Glycol Acetyl Tyrosine Hydrolyzed Vegetable Protein Adenosine Triphosphate FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

21 10. Characteristics of Unipertan VEG-2002 Cosmetic complex of vegetable based ingredients for tanning acceleration and to support DNA repair, without preservative Composition Total tyrosine content approx. 8% Total adenosine phosphates content approx. 1% Riboflavin approx. 0.3% Protein hydrolysate (vegetable) approx. 2% Butylene glycol approx. 20% Appearance Liquid. Analytical Data See specifications. Solubility Properties Soluble in water in any ratio. Soluble in propylene glycol. Soluble in ethanol/water-mixtures with up to 60% ethanol. Insoluble in lipids. Unipertan VEG-2002 is similar in overall composition to Unipertan P-2002 with the same tanning accelerating properties. Instead of animal derived hydrolyzed protein, Unipertan VEG-2002 contains exclusively vegetable hydrolyzed protein. Both products have the same total tyrosine content. Its content of butylene glycol provides excellent hydrating properties. Unipertan VEG-2002 does not contain a preservative. Unipertan VEG-2002 is dermatologically tested and presents no problems of skin tolerance. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22

22 Use Unipertan VEG-2002 has been used as a tan accelerator. It does not have any UV absorbing properties and therefore is used in sun protection preparations containing UV absorbents to achieve a quicker, more intense and longer lasting suntan. In addition, Unipertan VEG-2002 is also recommended for use in tanning accelerator containing preparations applied as a pre-tan product for sun bathing or in combination with a common sun protection preparation during sun bathing. Unipertan VEG-2002 can, in principle, be integrated into existing formulations of sun protection preparations. On account of its solubility in water, Unipertan VEG-2002 is recommended for use not only in O/W emulsions but also in W/O emulsions. Dosage 5% Storage Processing Storage condition: see safety data sheet Shelf life: see specifications Unipertan VEG-2002 is relatively stable and can easily be processed under conditions common in the production of cosmetics. Identification INCI name CAS No. Butylene Glycol Acetyl Tyrosine Hydrolyzed Vegetable Protein Adenosine Triphosphate Riboflavin References ** 1. Alsins, J. et al. Acta Dermato-Venerologica (Stockholm) 55, (1975). Our indications and recommendations have been worked out to the best of our knowledge and conscience, but without any obligation from our part. In particular, we do not take any responsibility concerning protection rights of a third party. FM-097B TDS Unipertan VEG en(03) Version: 03/ /22