Abstract:
An external dermal agent includes (a) at least one substance selected from the group consisting of a vitamin A compound and a derivative thereof; (b) at least one substance selected from the group consisting of a hinokitiol and a derivative thereof; and (c) at least one substance selected from the group consisting of an epidermal lipid and a similar component thereof. The external dermal agent corrects dry and rough skin, and promotes skin tautness and elasticity thereby reducing wrinkle formation.

Description:
BACKGROUND OF THE INVENTION  
         [0001]    1. Field of the Invention  
           [0002]    The present invention relates to a external dermal agent, particularly a external dermal agent effectively preventing and improving dry skin and rough skin, and wrinkle formation and the like due to loss of skin tautness and elasticity.  
           [0003]    2. Description of the Related Art  
           [0004]    Skin problems such as dry skin, rough skin, and wrinkles due to loss of skin tautness and elasticity are induced not only by aging and exposure to sunlight, but also by nutrient deficiencies of the skin due to poor circulation, irregular lifestyle, ineffective skin care, environmental factors such as cold weather and dry air, and so on.  
           [0005]    Several drug components have been developed for the purpose of preventing and improving problems such as dry skin, rough skin, and wrinkles and the like.  
           [0006]    Recently, the technique of improving and preventing wrinkles with retinol, vitamin A acids and derivatives thereof has been used for preventing and improving these problems such as dry skin, rough skin, and wrinkles. However, the effects of improving and preventing problems such as wrinkles are not yet sufficient.  
           [0007]    Therefore, a need exists for the development of more effective external dermal agents.  
           [0008]    In consideration of the above background and in order to solve the above problems, other external agents including various components extracted from natural products have been developed, and methods of smoothing wrinkles physically and temporarily by use of membrane forming agents have been utilized. However, these agents and methods are not yet sufficient.  
         SUMMARY OF THE INVENTION  
         [0009]    Accordingly, it is an object of the present invention to provide an external dermal agent capable of preventing and/or improving skin problems such as dry skin, rough skin, and wrinkles and the like due to loss of skin tautness and elasticity.  
           [0010]    After intensive research by the inventors of the present invention to obtain a substance effective in improving skin problems such as dry skin, rough skin, and wrinkles due to loss of skin tautness and elasticity, using safe substances in order to accomplish the above object, it has been found that a composition including vitamin A, a hinokitiol, and an epidermal lipid solves the problems and achieves the object of the invention. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWING  
       [0011]    [0011]FIG. 1 is a graph showing the variations with time of the corneum moisture content in the rough skin samples shown in Table 3. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0012]    The present invention provides a external dermal agent comprising: (A) a vitamin A compound or and/or a derivative thereof; (B) a hinokitiol and/or a derivative thereof; and (C) an epidermal lipid and/or a similar component thereof. The present invention is described in detail as follows.  
         [0013]    The vitamin A compounds used in the present invention include compounds having vitamin A activity and are generally utilized as active elements for prevention and therapy of skin keratosis and the like, and furthermore for the prevention and recovery of skin aging, particularly wrinkles and the like. Among the compounds, retinol, retinal, retinoic acid and the like, isomers thereof, and derivatives thereof (for example, retinol palmitate and retinol acetate) are particularly preferable.  
         [0014]    The contents of the vitamin A compound included in the external dermal agent of the present invention are not limited, and are preferably about 0.001-5.0 wt %, and more preferably about 0.01-1.0 wt %.  
         [0015]    Hinokitiol used in the present invention is tropolone compounds such as beta-thujaplicin, occurring in nature and extracted from essential oils of trees such as Aomori Hiba ( Thujopsis dotabrata  Sied. et Zucc. var. hondai Makino) and Taiwan Hinoki ( Chamaecyparis Taiwanensis , Masamune et. Suzuki) The hinokitiols, whether natural compounds or synthetic compounds, are utilized widely and generally in pharmaceutical and cosmetic fields as fungicides, cell activation agents and the like.  
         [0016]    Hinokitiol and derivatives are especially preferable among the compounds.  
         [0017]    The contents of the hinokitiol included in the external dermal agent of the present invention are not limited, and are preferably about 0.0001-2.0 wt %, and more preferably about 0.0005-0.5 wt %.  
         [0018]    The epidermal lipids used in the present invention are common lipids existing in the skin and utilized widely and generally in pharmaceutical and cosmetic fields as base and emollient agents. Sterols and/or derivatives thereof, sphingolipids and/or derivatives thereof, phospholipids and/or derivatives thereof, and glycerides and/or derivatives thereof are especially preferable among the components.  
         [0019]    Also, the sterols include cholesterol, dehydrocholesterol, ergosterol, sitosterol, campesterol, stigmasterol, brassicasterol, fucosterol, and the like, and esters thereof as a derivative.  
         [0020]    Also, the sphingolipids include sphingosine, sphingomyelin, sphingoglycolipid, cerebroside, phytosphingosine, ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6, and the like, and derivatives thereof.  
         [0021]    Also, the phospholipids include phosphatidyl choline, lysophosphatidyl choline, phosphatidylethanolamine, phosphatidyl inositol, and the like, and derivatives thereof.  
         [0022]    Also, the glycerides include fats and oils occurring naturally in plants and animals and derivatives thereof, including monoglycerides, diglycerides, triglycerides, and the like.  
         [0023]    The contents of the epidermal lipids and/or the similar components included in the external dermal agent of the present invention are not limited, and are preferably about 0.01-20.0 wt %, and more preferably about 0.1-10.0 wt %.  
         [0024]    In addition to the above mentioned essential components, the external dermal agents of the present invention may further include, if necessary, various conventional components generally used in pharmaceutical and cosmetic fields, quasi drugs, and the like such as aqueous components, humectants, thickeners, ultraviolet light absorbers, ultraviolet light scattering agents, aseptic agents, antioxidants, flavors, coloring materials, medical agents, herbal medicines, and the like, providing the effects of the present invention are not impaired.  
         [0025]    Also, the external dermal agent of the present invention may be prepared in many forms, for example, liquid formulations such as lotions and the like, emulsions such as milky lotions, creams, and the like, ointments, compositions including powders, water/oil two-phase type agents, water/oil/powder three-phase type agents and the like.  
       EXAMPLE  
       [0026]    The invention is further illustrated by reference to the following examples. These examples are not meant to limit the scope of the invention. In these examples, each agent was prepared by adding an oil phase heated to 80° C. to an aqueous phase heated to the same temperature, stirring to emulsify, and cooling the mixture to room temperature.  
         [0027]    The compositions described below were prepared and the effects on rough skin improvements were evaluated. It is known that dry skin causes rough skin, which progresses and leads to wrinkles and deep lines.  
                                                         TABLE 1                                           Comparative   Comparative   Comparative           Example 1   example 1   example 2   example 3                        retinal palmitate   0.1   —   —   —       hinokitiol   0.001   —   —   0.001       phytosterol   1.0   —   1.0   —       ceramide III   0.01   —   0.01   —       meadow-foam oil   0.1   —   0.1   —       hydroxyethyl-   0.8   0.8   0.8   0.8       cellulose       glycerin   15.0   15.0   15.0   15.0       paraben   0.2   0.2   0.2   0.2       polyglycerin   3.0   3.0   3.0   3.0       fatty acid ester       isotridecyl   8.0   8.0   8.0   8.0       myristate       purified water   balance   balance   balance   balance                   Com-           parative   Comparative   Comparative   Comparative       example 4   example 5   example 6   example 7               retinol   0.1   0.1   —   0.1       palmitate       hinokitiol   —   0.001   0.001   —       phytosterol   —   —   1.0   1.0       ceramide III   —   —   0.01   0.01       meadow-foam oil   —   —   0.1   0.1       hydroxyethyl-   0.8   0.8   0.8   0.8       cellulose       glycerin   15.0   15.0   15.0   15.0       paraben   0.2   0.2   0.2   0.2       polyglycerin   3.0   3.0   3.0   3.0       fatty acid ester       isotridecyl   8.0   8.0   8.0   8.0       myristate       purified water   balance   balance   balance   balance                  
 
         [0028]    (The units in the tables are weight %.)  
         [0029]    &lt;Method of Rough Skin Improvement Test&gt; 
         [0030]    The samples of rough skin area are prepared by applying films which has absorbed 10% solution of sodium lauryl sulfate to 3 cm square areas of human foream skin, taking off the films six hours later and washing the areas by water. Then samples of 0.05 g of the Example 1 and the Comparative examples 1-7 were applied to the rough skin testing areas three times a day. After four days and after eight days, the rough skin testing areas were examined with the naked eye and then the corneum moisture contents were measured to evaluate the improvements with a skin surface corneum moisture measuring device, SKICON-200 (IBS Corporation) The results are shown in Tables 2 and 3  
                                                                                                   TABLE 2                           Rough skin improvement tests 1 (evaluations with the naked eye)                    Comparative   Comparative   Comparative   Comparative   Comparative   Comparative   Comparative               Example 1   example 1   example 2   example 3   example 4   example 5   example 6   example 7   control                        the day of   rough skin   rough skin   rough skin   rough skin   rough skin   rough skin   rough skin   rough skin   rough skin       application       after 4 days   slight   no change   no change   no change   No change   no change   no change   no change   no change           improvement       after 8 days   considerable   slight   slight   slight   slight   slight   slight   slight   no change           improvement   improvement   improvement   improvement   improvement   improvement   improvement   improvement                  
 
         [0031]    [0031]                                                                                                           TABLE 3                           Rough skin improvement tests 2 (the units in the corneum moisture contents are μS)                    Comparative   Comparative   Comparative   Comparative   Comparative   Comparative   Comparative       healthy           Example 1   example 1   example 2   example 3   example 4   example 5   example 6   example 7   control   area                        the day of   14.0   17.7   16.3   15.7   22.0   5.7   7.0   6.3   19.7   36.0       application       after 4 days   64.3   11.7   8.7   19.3   21.7   18.0   16.3   24.3   3.0   40.3       after 8 days   183.7   96.0   67.7   82.7   48.7   90.3   69.3   73.3   0.0*   28.3                            
         [0032]    The results of Tables 2 and 3 revealed that Example 1 according to the present invention was much more effective at rough skin improvement compared with Comparative examples 1-7.  
         [0033]    In another experiment, the compositions in Table 4 (Example 2 and Comparative examples 8-10) were prepared using conventional manufacturing processes and actual application test using each of Example 2 and Comparative examples 8-10 were carried out on human for two months. For each experiment, a group of twenty women with notably dry skin, wrinkles and the like from their late thirties to fifties were respectively selected. These compositions were applied to their face two times a day (once in the morning and once in the evening) for two months, and their skin conditions before and after theses experiments were evaluated according to the criteria as follows: “improvement”, “slight improvement” and “no change”. The results of the experiments are shown in Table 5 as the total of subjects in each evaluation.  
                                                         TABLE 4                                       Comparative   Comparative   Comparative           Example 2   example 8   example 9   example 10                                    retinal   0.1   0.1   —   0.1       palmitate       hinokitiol   0.001   0.001   0.001   —       phytosterol   1.0   —   1.0   1.0       ceramide III   0.01   —   0.01   0.01       meadow-foam oil   0.1   —   0.1   0.1       hydroxyethyl-   0.8   0.8   0.8   0.8       cellulose       glycerin   15.0   15.0   15.0   15.0       paraben   0.2   0.2   0.2   0.2       polyglycerin   3.0   3.0   3.0   3.0       fatty acid ester       ester oil   8.0   8.0   8.0   8.0       squalane   2.0   2.0   2.0   2.0       plant extract   0.5   0.5   0.5   0.5       flavor   0.03   0.03   0.03   0.03       purified water   balance   balance   balance   balance                  
 
         [0034]    (The units in the table are weight %.)  
                                                             TABLE 5                                       Com-   Com-   Com-               parative   parative   parative           Example   example   example   example           2   8   9   10                                    dry skin   improvement   5   0   0   0           slight   15   4   6   8           improvement           no change   0   16   14   12       skin   improvement   4   0   0   0       tautness   slight   16   3   2   7       and   improvement       elasticity   no change   0   17   18   13       wrinkles   improvement   2   0   0   0           slight   18   3   1   5           improvement           no change   0   17   19   15                  
 
         [0035]    The results of Table 5 revealed that Example 2 according to the present invention was much more effective at improving dry skin, skin tautness and elasticity loss, wrinkles, and the like, compared with Comparative examples 8-10. Also, no skin epispastic reaction and skin sensitizing reaction against the compositions of the above Examples 1 and 2 occurred in the subjects.  
         [0036]    The prescription examples of the external dermal agents including the vitamin A compound, the hinokitiol and the epidermal lipid according to the present invention are shown as follows.  
       Example 3  
     Skin lotion  
       [0037]    [0037]                                                                         retinol palmitate   0.01   (wt %)           hinokitiol   0.001           hydrogenated soybean phospholipid   0.1           hydroxyethylcellulose   0.1           1,3-butyleneglycol   3.0           paraben   0.2           polyoxyethylene hydrogenated castor oil   0.3           alcohol   10.0           plant extract   0.5           flavor   0.03                purified water   balance                        
       Example 4  
     Milky lotion  
       [0038]    [0038]                                                                         retinol acetate   0.1   (wt %)           hinokitiol   0.01           phosphatidylethanolamine   0.5           ceramide 3   0.01           carboxyvinylpolymer   0.3           1,3-butyleneglycol   5.0           paraben   0.2           polyoxyethylene hydrogenated castor oil   0.1           polyglycerin fatty acid ester   1.0           polyoxyethylene sorbitan fatty acid ester   0.3           liquid paraffin   3.0           potassium hydroxide   0.07           plant extract   0.5           flavor   0.03                purified water   balance                        
       Example 5  
     Cream  
       [0039]    [0039]                                                                         retinol   0.1   (wt %)           hinokitiol   0.1           cholesterol   1.0           lysophosphatidyl choline   0.1           olive oil   2.0           glycerine   15.0           paraben   0.2           carboxyvinylpolymer   0.3           polyoxyethylene hydrogenated castor oil   0.1           monoglycerin fatty acid ester   5.0           propylene glycol fatty acid ester   5.0           polyethylene glycol fatty acid ester   0.5           squalane   10.0           behenyl alcohol   3.0           stearic acid   1.0           plant extract   0.5           flavor   0.03                purified water   balance                        
       Example 6  
     Essence  
       [0040]    [0040]                                                                         retinol acetate   0.1   (wt %)           hinokitiol   0.001           safflower oil   1.0           ceramide 3   0.01           hydroxyethylcellulose   0.6           dipropyleneglycol   10.0           paraben   0.2           polyoxyethylene hydrogenated castor oil   0.1           polyglycerin fatty acid ester   2.0           polyoxyethylene sorbitan fatty acid ester   0.5           squalane   5.0           stearic acid   1.0           plant extract   0.5           flavor   0.03                purified water   balance                        
         [0041]    As described above, the external dermal agents according to the present invention provide superior preventions and improvements to dry skin, rough skin, wrinkles and the like, loss of skin tautness and elasticity compared with the other conventional compositions.