Jin Ho Chung

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Moon Kyun Cho

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Nowadays, we find out new anti-wrinkle-care-ingredients by in vitro searching methods using many kind of cell-culture-models for investigation of the effective anti-wrinkle-care-ingredients. But, theses new ingredients don't have effect on the human-model for anti-wrinkle, not likely on in vitro. In other words, there are so many differences between the effects on in vitro models and the clinical human models, practically. But, we actually have difficulty in putting all of the new anti-wrinkle-care-ingredients to the test on human models directly. To solve this problem, we have investigated that by using the artificial skin-culture-model or the animal model, In this lecture I will review the detail of assessment method far evaluation of anti-wrinkle agents in vitro and animal model and discuss the pros and cons of each method. Then I will present the results of Preclinical Screening trials, And especially animal model may be a good candidate for evaluation of anti-wrinkle agents.

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Hitoshi Masaki

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Two categories of cosmetic products, cosmetics and quasi-drugs, have been established by the Ministry of Health, Labor and Welfare (MHLW) in Japan. Japanese pharmaceutical law has defined that products categorized as cosmetics do not exhibit any effects on human skin. In fact, cosmetic products are not permitted to claim any efficacy. On the other hand, products in the quasi-drug category can claim several efficacies such as anti-inflammatory effects, whitening/lightning effects, hair growth effects and so on. Unfortunately, the Japanese MHLW has not yet approved the efficacy of anti-aging/anti-wrinkle effects as a claim point. However, the population is aging, and the demand for anti-aging/anti-wrinkle products is increasing year by year. Japanese cosmetic companies have proposed to the MHLW that anti-aging/anti-wrinkle agents be approved as a claim concept of a quasi-drug. However, unified evaluation methods for anti-aging/anti-wrinkle effects have not been established. Currently, each company evaluates the efficacy of products/materials using their own original methods. Thus, to request approval of the MHLW, the establishment of a unified evaluation method is needed. Consequently, the Japan Cosmetic Industry Association (JCIA) has established a task force to develop guidelines for evaluating anti-wrinkle effects in 1998. In conclusion, the JCIA would like to adopt visual and image analysis scales to evaluate the anti-wrinkle effects objectively. Generally, wrinkles are roughly classified into three groups as fine wrinkles, linear deep wrinkles and crow's feet. However, academic societies of dermatology or cosmetics have not yet established a definition of wrinkles in Japan. Thus, in advance of setting up an evaluation method, the definition of wrinkles f3r evaluation must be decided. Wrinkles are defined by the task force of the JCIA as follows; furrows that people can recognize visually and that appear on the forehead, the corners of the eyes and the backs of the neck with aging. In addition, furrows are emphasized by exposure to solar light and by dry conditions. Visual evaluation is the most sensitive method and can be applied to most types of wrinkles. However, visual evaluation is hard to express digitally as results. Besides, in the case of image analysis, comparisons of data obtained from distinct examinations can not be done, because data from image analysis are relative values. Thus, to enhance the reliability of the evaluations, the adoption of an objective scale was required. The principle of the evaluation method is to analyze images taken from silicone replicas of wrinkle areas using several parameters, such as the proportion of the wrinkle $area({\%})$, the mean depth of the wrinkles (mm), the mean depth of the deepest wrinkle (m) and the deepest point on the deepest wrinkle. Lights are shown on the skin replica from an orthogonal direction of the main orientation of the wrinkle, and the resulting shadow images are quantified by the image analysis method. To increase the precision of the data or to allow comparisons of independent examinations, a scale with furrows of several depths, 200, 400, 600, 800, and 1000μm, is adapted in the evaluation system. I will explain the guidelines established by the JCIA in the presentation.

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Se Won Kang

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Introducing to the market place, safe and effective product is an important responsibility of clinical investigators as well as regulatory agencies in all developed countries. Products claiming to improve skin wrinkles are no exceptions. To date, Renova(R) (all-trans retinoic acid), Avage(R) (tazarotene), and Botox(R) (botulinum toxin) are the only agents FDA approved to ameliorate wrinkles associated with photoaged skin in the USA. For all three, clinical evaluation of wrinkle severity was the primary endpoint required for the approval process. No sophisticated instrument measurements of wrinkles were required, nor used in the pivotal studies. The Division of Dermatologic & Dental Products of the US FDA (Director, Jonathan Wilkin, MD) is not against the use of mechanical instruments in assessing wrinkle severity. Its position on this issue however, remains that any such device must be grounded in patients' or product users' perspective, which means that the evaluation instrument must be clinically relevant and clinically perceptible. Sophisticated devices that can detect minimal improvement, but imperceptible to the users are considered useless in the eyes of the US FDA. Two instruments that have been tried in some antiwrinkle studies in the USA are silicone replicas and Primos. Despite their sophistications, they have clear limitations; thus have never replaced clinical evaluations in these studies. At most, they have served as secondary measures to provide corroborative data on the clinical efficacy of antiwrinkle products. For the foreseeable future, at least in the USA, careful clinical assessment of wrinkles will continue to serve as the critical benchmark to determine whether an antiwrinkle product has enough efficacy to benefit its users. We must not lose sight of the fact that sophisticated devices are only to serve in generating supportive evidence, and not the primary evidence, in any clinical studies.

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Abdoelwaheb El Ghalbzouri

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Human skin equivalents, also designated as cultured skin substitute (Boyce and Warden, 2002) or organotypic co-cultures (Maas-Szabowski et al., 1999, 2000, 2003), are three-dimensional systems that are engineered by seeding fibroblasts into a three-dimensional dermal matrix. Such a dermal equivalent is then subsequently seeded with human keratinocytes. After cell attachment, the culture is kept first under submerged condition to allow keratinocyte proliferation. Thereafter, the culture is lifted the air-liquid interface (A/L) to expose the epidermal compartment to the air, and to further induce keratinocyte differentiation. During the air-exposure, nutrients from the medium will diffuse through the underlying dermal substrate towards the epidermal compartment and support keratinocyte proliferation and differentiation. Under these conditions, a HSE is formed that shows high similarity with the native tissue from which it was derived (Figure 1) (Bell et at., 1981. Boyce et al., 1988; Ponec et al., 1997;El Ghalbzouri et al.., 2002).

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Jinah Jang

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In the 21st century, the development of cosmetics is led to pursue the high functionality of cosmetics with excellent effectiveness and safety. As Cosmetic Act took effect in 2000, functional cosmetics is provided in the law. As a result, the research and development of functional cosmetics has continually increased, and the number of patent applications in functional cosmetics has also rapidly increased as a plan for preoccupying in the functional cosmetics age. Now, the cosmetic industry has a great interest in developing anti-wrinkle cosmetics among functional cosmetics, because women's desire for having young resilient skin has increased since Korea entered an aging society thanks to the advanced medical technology. The patent application trends of anti-wrinkle cosmetics at home since 2000 particularly show the rapid increase in the applications in natural plant extracts. It may be because Korean consumers preference of vegetable cosmetics has resulted in the development of raw materials based on the traditional medicine. As for the existing preparation such as Retinoid or Ascorbic acid, the patent application itself will be an essential technical element in the future because patent applications are filed in the field of a preparation of cosmetics for stabilizing ingredients, reducing skin irritability or promoting absorbance, and in the field of cosmetic formulation technology. As there are many studies on the causes of skin wrinkles, it is expected that new raw materials of cosmetics can be developed due to new mechanisms, and that the number of patent applications in new technologies will increase due to a change in the thought of cosmetics accompanied by the integration of cosmetics with biotechnology using Genetic Engineering, including the practical application of the medicine previously used far treating skin diseases to an anti-wrinkle agent and the mass production of active ingredients of cosmetics.

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장이섭 Ih Seop Chang

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In-young Kim , Joo-dong Lee , Hee-chang Ryoo , Choon-koo Zhoh

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This study described about method that form liquid crystal gel (LCG) by main ingredient with hydrogenated lechin (HL) in OW emulsion system. Result of stability test is as following with most suitable LCG's composition. Composition of LCG is as following. To form liquid crystal, an emulsifier used 4.0 wt% of cetostearyl alcohol (CA) by 4.0 wt% of HL as a booster, Moisturizers contained 2 wt% of glycerin and 3.0 wt% of 1.3-butylene glycol (1,3-BG). Suitable emollients used 3.0 wt% of cyclomethicone, 3.0 wt% of isononyl isononanoate (ININ), 3.0 wt% of cerpric/carprylic triglycerides (CCTG), 3.0 wt% of macademia nut oil (MNO) in liquid crystal gel formation. On optimum conditions of LCG formation, the pHs were formed all well under acidity or alkalinity conditions. Considering safety of skin, PH was the most suitable 6±1.0 ranges. The stable hardness of LCG formation appeared best in 32dyne/cm². Particle of LCG is forming size of 1~20μm um range, and confirmed that the most excellent LCG is formed in 1~6μm range. According to result that observe shape of LCG with optical or polarization microscope, LCG could was formed, and confirmed that is forming multi-layer lamellar type structure around the LCG. Moisturizing effect measured clinical test about 20 volunteers. As a result, moisturizing effect of LCG compares to placebo cream was increased 30.6\%. This could predicted that polyol group is appeared the actual state because is adsorbed much to round liquid crystal droplets to multi-lamellar layer's hydrophilic group. It could predicted that polyol group is vast quantity present phase that appear mixed because is adsorbed to round liquid crystal to multi-lamellar layer's hydrophilic group. This LCG formation theory may contribute greatly in cosmetics and pharmacy industry development.

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Hye-in Jang , Kyung-chul Lee , Jong-eul Park , Hee-chang Lyoo

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new materials, mesopore, surface active agent, CMC, PEO, LES, lecithine, pore, organic/inorganic hybrid silica, polymerization, carbon, carbon-silica pigment, mascara, mesoporous silica, dispersibility, crack, template, density control

Suk Won Lim , Sung Won Jung , Sung Ku Ahn , Bora Kim , Hee Chang Ryoo , Seung Hun Lee

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Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromeroJ and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1 mg/ml UA or 0.1-1 mg/ml ONA after tape stripping, and TEWL (Transepidermal water loss) was measured. The recovery rate increased in those UA or ONA treated groups (0.1 mg/ml UA and 0.5 mg/ml ONA) at 6 h more than 20% compared to vehicle treated group (p<0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/ml per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from 1 week without TEWL alteration (p< O.005). EM examination using Ru04 and Os04 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent (ONA ≥ UA >Vehicle). LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Veh). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via PPAR a. Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either ONA (10 μM) or UA (10 μM) for 24h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via PPAR a. Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

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ursolic acid, oleanolic acid, epidermal permeability barrier, dermal function, TEWL, hydration, keratinocyte terminal differentiation, collagen, elastic fiber, elastase

전상훈 Sang-hoon Jeon , 김주덕 Ju-duck Kim

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We often use the KCID(Korean Cosmetic Ingredient Dictionary) and ICID(International Cosmetic Ingredient Dictionary) within cosmetics research and within their export and import. so far, we do not have a database of a cosmetics' raw materials. Because of this, we consume a lot of time to find the raw material data that is needed. This study constructs a cosmetics' raw material database and develops the program to retrieve it. We used a Linux machine as the equipment for this study and we used Apache web server, MySQL database server and PHP as the tools of this study. 11,817 kinds of raw materials data were registered as ICID, 866 kinds of raw materials data were registered as KCID and 28,008 kinds of raw materials data with registered trade name into the database. Also, The database was composed of the database of the association form. The database of the online form could ultimately reduce the task time as soon as it did its purpose. The product of this study can become a good basis of data to reconfigure. In the future, it can become a good database in relation with different databases.

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배유경 Yu-kyung Bae , 김주덕 Ju-duck Kim

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Cosmetics have had only simple efficacy such as cleansing, beautification, and so on. The latest development tendency for cosmetics turned to make goods that is effective and efficacious for whitening, anti-wrinkle, etc., due to various wants of consumers, development of relative technical, etc. According to this stream, Korea Cosmetics Law has been enacted by the Notification of the Korea Food and Drug Administration in 2000. The establishment of Korea Cosmetics industry and opened regular 'Cosmeceuticals Time'. Since the Korea Cosmetics Law took effect on July 2000, the cosmeceuticals system has settled down according to its lights. This research studied how women consumers were understanding the cosmeceuticals system focused on their life style. This study is considered to offer a basic information about consumer's type and to be a groundwork data for working out a marketing strategy about the subdivision of cosmeceuticals market.

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