WO2005097054A1

WO2005097054A1 - A novel uv-shielding complex and production method thereof

Info

Publication number: WO2005097054A1
Application number: PCT/KR2004/000831
Authority: WO
Inventors: Dong-Il Jang
Original assignee: Cotde Inc.
Priority date: 2004-04-10
Filing date: 2004-04-10
Publication date: 2005-10-20

Abstract

The present invention relates to a UV-shielding complex having a structure of melanin coupled onto the surface of a particle of nontoxic oxidized inorganic material, a production method thereof, and a cosmetic composition containing the complex. In the present invention, it is preferable that the ratio of an oxidized inorganic material and melanin is 1 . (0.01 - 0.99) by weight. The UV-shielding complex produced by the present invention can be added into cosmetics as an ingredient and make the cosmetics effective in UV-shielding. According to the present invention, using a bio-compatible material makes it possible to produce a new UV shielding complex. Furthermore, the present invention enables to economically produce UV-shielding cosmetics of which color-control had formerly been difficult.

Description

A NOVEL UV-SHTELDING COMPLEX AND PRODUCTION METHOD THEREOF

Technical Field

The present invention relates to a UV-blocking agent having a structure in which melanin is coupled with surfaces of particles constituting oxidized inorganic material that is harmless to humans, and a method of producing the same.

Background Art

Ultraviolet light emitted from "the sun includes a long wavelength (a range of about 320 - 400 ran) that is called UV A (ultraviolet A) , and a short wavelength (about 290 - 320 ran) , which is called UV B (ultraviolet B) . In sunbeams, about 6 % of the ultraviolet A and the ultraviolet B arrive at the earth' s surface, and ultraviolet C is absorbed or scattered by the ozone layer and the atmosphere, thus not reaching the earth's surface. Ultraviolet light has positive aspects, such as the synthesis of vitamin D in the body, treating dermatitis, and sterilization, but also negative aspects, such as induction of sunburn, skin cancer, skin aging, photosensitive dermatitis, and mutations . It is known that ultraviolet A penetrates even a cor±um layer, causing discoloration of pigments, skin aging, and photosensitive dermatitis, and ultraviolet B, which h_as shorter wavelengths and higher energy, penetrates the epidermis and the upper side of the corium, causing sunburn, discoloration of pigments, and skin cancer. From ancient times, effort has been made to block the sunbeams so as to prevent the above-mentioned side effects of the sunbeams. A UV-blocking agent is classified into a chemical UV-blocking agent and a physical UV-blocking agent. The chemical UV-blocking agent usually blocks the sunbeam through its absorption, and the physical UV- blocking agent blocks the sunbeam through its reflection and scattering. Performance of the physical or chemical UV-blocking products is expressed by a sun protection factor (SPF) . In detail, the sun protection factor is a factor relating to blocking UV B. A minimum erythema dose (MED) that is obtained by radiating UV B onto an area on which the UV- blocking products are not applied is divided by a minimum erythema dose that results from the application of the UV- blocking products, thus giving the sun protection factor. The minimum erythema dose is a minimum amount of ultraviolet light required to form erythema in most of a radiated area after UV B is radiated onto the human skin for 16 - 24 hours. On the other hand, a minimal amount of ultraviolet light causing faint darkening throughout a radiated area after the UV A is radiated for 2 - 4 hours is called a minimal persistent pigment darkening dose (MPPD) . A MPPD ratio between the areas which are and are not c-oated with the products is called a protection factor of UV Α (PFA) . A protection grade of UV A (PA) is a factor denoting a degree of blocking of UV A. In the ancient times, attempts have been conducted to use a physical method in which the sunbeam is avoided or blocked and to apply a mixture of tar, medical plants, mud and the like on the skin. If the sunbeam irradiates the skin, the amount of melanin increases in the epidermis layer of the skin. Melanin is a vital substance capable of scattering and absorbing ultraviolet light, and removes free radicals formed by the ultraviolet light during its generation. Accordingly, melanin has acted as a very important and nice vital UV-blocking agent capable of preventing damage to the skin. Regular use of the chemical UV-blocking agent began with the appearance of an emulsion product containing benzyl salicylate and benzyl cinnamate in the year 1928 in the USA. Thereafter, a patent for PABA as a sunscreen was granted in the year 1943, after which the development of sunscreen exploded. The demand for sunscreen has been explosively growing in accordance with improvements in the standard of living after the year 1975, and it has continuously been improved. The chemical UV-blocking agent contains one or more components capable of absorbing ultraviolet light, and is exemplified by PABA, PABA esters (amyl dimethyl PABA, octyl dimethyl PABA) , cinnamates (cinoxate) , salicylate (homomenthyl salicylate) , or camphor, which block ultraviolet B, and benzophenone (oxybenzone, dioxybenzone, suliso benzene) , dibenzoyl methane, or anthranilate, which block ultraviolet A. Even though the exemplified chemical UV-blocking agents absorb and block the ultraviolet light, undesirably, it is reported that they stimulate the skin or eyes to a certain extent (PABA, PABA esters, benzophenones, and cinnamates are frequently reported to cause contact dermatitis), and cause a photosensitive reaction in the skin. Accordingly, their use is limited or the amount used is regulated. The physical UV-blocking agent is a component existing in the natural world, and reflects and scatters the ultraviolet light arriving at the skin to protect the skin. It is exemplified by titanium dioxide, talc (magnesium silicate) , magnesium oxide, zinc oxide, and kaolin. The physical UV-blocking agent can block both ultraviolet A and the ultraviolet B, and has advantages in that it does not cause side effects, such as contact dermatitis, and is not easily removed by water. However, it is disadvantageous in that it is difficult to retain an effective content so as to realize desired dosage form, and in that white turbidity occurs when it is applied on the skin. In order to avoid the disadvantages of the physical or chemical UV-blocking agents, many studies have been conducted to develop UV-blocking products which include as much PABA-free and benzophenone-free physical UV-blocking agent content as possible and provide an excellent sensation when used on the skin. Melanin is an important pigment in the human hair, skin, and eyes. Naturally existing in animals, plants, and microorganisms in addition to humans, melanin has various colors, such as black, brown, or red color. Melanin is roughly classified into eumelanin having a black or brown color, and pheomelanin having a yellow or reddish brown color. Suntan occurs naturally when the skin is exposed to ultraviolet light having a wavelength of 280 - 400nm. Melanin is a complicated heteropolymer, and its polymerization procedure and its precise structure are not known. Melanin is a copolymer of 3, 4-dihydroxyphenylalanine (DOPA) and cystenyldopa. In a living body, tyrosine, an amino acid, is oxidized to DOPA with the aid of tyrosinase acting as an enzyme, continuously oxidized using oxygen through DOPAchrome into DOPAquinone, and finally polymerized into melanin. Melanin may be produced using automatic oxidation of DOPA without tyrosinase. Melanin is a macromolecular substance blocking ultraviolet light and acting as a pigment, and physicochemical properties of a polymerization product (melanin) slightly depend on the use of the enzyme during polymerization and the kind of material participating in the polymerization. The light blocking property of melanin belongs to its physical and biochemical properties, and melanin converts ultraviolet light into heat to absorb heat or promote oxidation, and promotes the removal of free radicals generated by the ultraviolet light. The removal of free radicals by melanin means that melanin shields people having melanin in the skin thereof from the solar radiation. As described above, various UV-blocking products applied on the skin have been developed to avoid danger caused by exposure to ultraviolet light. Various salicylic derivatives have been considered as UV-blocking agents because of their ability to absorb ultraviolet light. For example, U.S. Patent Nos. 3,506,758 and 4,256,664 disclose a UV-blocking composition which includes para-aminobenzoic acid (PABA) and salicylic acid, esterified using lecithin, choline, or imidazole having a reactive hydroxyl group. U.S. Patent No. 4,454,112 discloses that tocopherol acetylsalicylic acid, which is useful as a UV-blocking agent, is used externally on the skin. However, salicylic derivatives may stimulate the skin and cause allergies, thus it is undesirable to add it in a great amount to a UV- blocking product. Generally, a PABA ester compound, such as PABA or octyl dimethyl PABA, is used as a UV-absorbing substance in the UV-blocking product. U.S. Patent No. 4,434,154 discloses a UV-blocking composition containing only octyl dimethyl PABA. However, recently, the FDA has regulated the use of PABA as the UV-blocking agent because of its harmfulness. Meanwhile, a UV-blocking composition containing melanin, that is, a natural UV-blocking agent, has already been used. However, conventional methods of producing melanin have disadvantages. Melanin produced through an enzyme-automatic oxidation method is unsuitable for application to the skin. Particularly, since this melanin is contained in a final product in a granular form, it is difficult to uniformly apply on the skin. Accordingly, the effectiveness of melanin is significantly limited in views of absorption of ultraviolet light. Particularly, melanin has a poor ability to absorb light having a short wavelength in an ultraviolet range. U.S. Patent No. 4,806,344 discloses a melanin composition which is produced using additionally ferric chloride, triethanolamme, and PABA as a UV-blocking agent. Many current UV-blocking products cannot protect the skin from all wavelengths within an ultraviolet range. Almost all UV-absorbing substances, which are useful as the UV-blocking agent, absorb only a narrow range of ultraviolet light. Accordingly, UV-blocking products include various compounds rather than one type of UV- blocking agent, so that the absorption of ultraviolet light is maximized to block a wide range of ultraviolet light. However, the UV-blocking products including various materials may readily cause an allergy or a photoallergy, thus bringing about dermatitis or photodermatitis. Some persons may suffer from peeling of skin even due to UV A having a long wavelength or visible rays. Hence, blocking of light having a wide wavelength range is important to them. Therefore, there is a need to provide a UV-blocking product which can effectively block a very wide spectrum of ultraviolet light and be applied on the human skin without stimulation.

Disclosure of the Invention

An object of the present invention is to provide a novel UV-blocking composition and a method of producing the same. The composition is produced by coupling melanin, which is a UV-absorbing and blocJing agent made of natural vital material, with a physical UV-blocking agent, that is, inorganic material which cannot effectively block ultraviolet light because of a limited content in a dosage form even though it scatters and reflects ultraviolet light in a wide ultraviolet A and ultraviolet B range and even though it does not stimulate the skin. Accordingly, from another point of view, the present Invention provides a complex of inorganic material and melanin, such as titanium dioxide melanin or zinc oxide melanin, in which melanin is chemically coupled with a physical UV-blocking agent, such as titanium dioxide or zinc oxide. In other words, the present invention provides a titanium dioxide melanin sunscreen complex which includes melanin coupled with titanium dioxide. In detail, the present invention provides a method of producing a complex of titanium dioxide and melanin. The method comprises enzymatically or naturally converting derivatives of substances, such as 3,4- dihydroxyphenylalanine, catechol, or resorcinol, which can be easily coupled with other molecules through electron migration to achieve oxidative polymerization, into melanin or pseudo-melanin polymer in the presence of titanium dioxide so that melanin is coupled with titanium dioxide. In order to accomplish the above object, the present invention provides a UV-blocking agent having a structure in which melanin is coupled with surfaces of particles constituting oxidized inorganic material harmless to humans, a method of producing the same, and a cosmetic containing the same. A particle diameter of the oxidized inorganic material according to the present invention is not limited, but is preferably 0.01 - 1000 μm in consideration of ease of handling of raw material and sense of touch. The oxidized inorganic material is any one of titanium dioxide, zinc oxide, or magnesium oxide, or a mixture thereof. In the present invention, it is preferable that the weight ratio of the oxidized inorganic material to melanin be 1 : (0.01 - 0.99). If the content of melanin is less than the above-mentioned value, UV-blocking performance is poor. If the content of melanin is more than the above- mentioned value, there is a high possibility that some of the melanin will not couple with the oxidized inorganic material. A predetermined amount of UV-blocking complex of the present invention is added to various cosmetics so as to give the cosmetics UV-blocking performance. A method of producing the UV-blocking complex according to the present invention comprises dispersing 1 part by weight of oxidized inorganic material which has a particle diameter of 0.01 - 1000 μm and which is harmless to humans, and 0.01 - 0.99 parts by weight of melanin precursor in an inorganic solvent or an organic solvent, oxidizing the resulting solution, and drying the oxidized solution through a typical process. In connection with this, the oxidization may be conducted employing various processes used in a conventional process of producing melanin from the melanin precursor. In other words, the oxidization comprises adding air containing oxygen to a reaction solution, adding an enzyme, such as tyrosinase or phenol oxydase, to the reaction solution, or adding an oxidizing agent, such as potassium permanganate or hydrogen peroxide, to the reaction solution. In the present invention, the melanin precursor is a DOPA derivative including hydroquinone, catechol, resorcinol, o-quinone, p-quinone, DOPA methyl ester, dihydroxyphenylacetic acid, dihydroxyphenylglycol, or dihydroxyphenylserine . Meanwhile, in order to control the color of the complex, the method of producing the complex according to the present invention may further comprise adding 0.01 - 60.0 parts by weight of amino acid having a -SH functional group, based on 1 part by weight of oxidized inorganic material. Amino acid having the -SH functional group may be exemplified by cystein or glutathione. A color of the UV-blocking complex according to the present invention (for example, the titanium dioxide- melanin complex disclosed in the following examples) can be variously controlled when an amino acid having the -SH functional group is added during production of the complex (see examples) . Furthermore, the UV-blocking complex according to the present invention absorbs or scatters ultraviolet light, particularly, ultraviolet B having a short wavelength., in an amount of 2 - 3 times as much as a UV-blocking complex containing only titanium dioxide, thus a high sun protection factor is assured (see Experimental Example) . As well, the blocking performance of ultraviolet A increases (see Experimental Example) . Even though no data are suggested herein, in the complex of the present invention, for example titanium dioxide-melanin complex, white turbidity does not occur when it is applied on the skin, and it is possible to produce skin-friendly goods, thus it is evaluated that it is significantly useful as raw material for UV-blocking goods .

Brief Description of the Drawings The above and other objects, features and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which: FIG. 1 illustrates pictures of UV-blocking complex powders according to the present invention.

Best Mode for Carrying Out the Invention

In the following examples, DOPA and titanium dioxide are chemically coupled with each other to form a complex, but, needless to say, derivatives of DOPA may be used instead of DOPA in the present invention. The reason is that, as well known in the art, predetermined derivative compounds of DOPA (including synthetic derivatives or naturally existing derivatives) have an unstable structure capable of easily causing electron migration, thus being easily oxidative-polymerized into melanin or pseudo-melanin polymer having a black color. Illustrative, but non- limiting examples of the derivatives of DOPA include hydroquinone, catechol, o-quinone, p-quinone, DOPA methyl ester, dihydroxyphenylacetic acid, dihydroxyphenylglycol, and dihydroxyphenylserine. Additionally, it is well known that, in the course of producing melanin, oxidation is conducted in air (including forcible feeding of air) , or oxidation is carried out using an enzyme (for example, tyrosinase, phenol oxidase, etc.) or an oxidizing agent, for example potassium permanganate or hydrogen peroxide. As described above, tyrosinase in melanocyte in an epidermis tissue or a hair follicle of the skin is activated by ultraviolet light, and then subjected to successive oxidation procedures in which tyrosine → DOPA →

DOPAquinone → DOPAchrome → 5, 6-dihydroxyindole → melanin conversions occur to produce a dark brown polymer, that is, melanin. In connection with this, it is known that, when there is a substance having an -SH group, such as cystein or glutathione, it is coupled with DOPAquinone to form cysteinylDOPA, resulting in the generation of red or yellow melanin. Black or brown melanin is called eumelanin, and red or yellow melanin is called pheomelanin. Therefore, in the present invention, cystein is added in the course of producing a complex to produce pheomelanin, resulting in the generation of complexes having various colors . A better understanding of the present invention may be obtained through the following examples and experimental examples which are set forth to illustrate, but are not to be construed as the limit of the present invention. According to a simple preliminary experiment, there is an insignificant difference in physical properties of complexes produced under conditions of a wide range of reaction temperature, various agitation rates, and various reaction times. However, for convenience, in the following examples, DOPA is used as a precursor of melanin, and a mixture is agitated at 37^°C and 100 rpm for 30 min using spontaneously fed air to be oxidized. However, needless to say, it is to be understood that modifications will be apparent to those skilled in the art. With respect to the modifications, it is possible to change reaction conditions, for example, various different types of melanin precursors may be used, and, in addition to oxidation using spontaneously fed air, oxidation may be conducted using predetermined amounts of the above-mentioned various oxidation promoting agents, contributing to reduced reaction time.

EXAMPLE: Production of melanin-titanium dioxide complex

A sample of comparative example and melanin-titanium dioxide complexes (examples 1 and 2) to be used in a UV- blocking test were produced as described in the following Table. Mixtures were agitated at 37 ^°C and 100 rpm for 30 min so as to react with each other, and then dried to produce complex powders .

TABLE 1

ST-495M (average particle size 50 - 150 /-an) manufactured by Titan Kogyo Kabushiki Kaisha in Japan was used as Ti0₂, and DOPA and cystein manufactured by SIGMA Inc. were employed. Pictures of the complex powders thus produced are illustrated in FIG. 1. As shown in this drawing, the powder (cont.) of comparative example, which did not include a melanin precursor, had a gray color due to titanium dioxide having a gray color, but the complex (El) of example 1, which included the melanin precursor, had a very dark black color. The complex (E2) of example 2 including the melanin precursor and cystein had a reddish brown color, which coincided with the fact that pheomelanin was formed due to amino acid having an -SH active group as described above. Thereby, it was confirmed that it was possible to produce UV-blocking complexes having various brightnesses (colors) when a predetermined amount of amino acid having the -SH active group was added in the course of producing the complex of the present invention.

EXPERIMENTAL EXAMPLES 1 - 3: Analysis of UV-blocking performance of melanin-titanium dioxide complex

UV-blocking performance of the complex according to the present invention was analyzed in vitro, employing a typical method. A UV-blocking experiment was conducted in vitro using SPF-290S, which is considered to be closely connected with an in vivo SPF (Solar Protection Factor) experiment and which was manufactured by OPTOMETRICS, Inc., and the results are described in the following Table 2.

TABLE 2

From this Table, it can be seen that the complex of the present invention is better than a conventional UV- blocking agent for cosmetics (comparative example) . That is to say, SPFs (examples 1 and 2) are improved by 315 % and 260 %, respectively, and PFs of UV A (examples 1 and 2) are improved by 257 % and 243 %, respectively, in comparison with the sample of comparative example. Accordingly, when using the complex of the present invention, it is possible to obtain UV-blocking performance that is much better than that of the conventional UV- blocking agent (titanium dioxide, etc.).

Industrial Applicability

According to the present invention, it is possible to produce a novel UV-blocking complex having excellent UV- blocking performance using low-priced bio-compatible material. Furthermore, in the present invention, since it is possible to produce UV-blocking complexes having various colors, it is possible to economically produce UV-blocking cosmetics, the color of which is conventionally difficult to control.

Claims

1. A UV-blocking agent having a structure in which melanin is coupled with surfaces of particles constituting oxidized inorganic material that is harmless to humans.

5 2. The UV-blocking agent as set forth in claim 1, wherein the particles of the oxidized inorganic material are 0.01 - 10O0 μs in diameter.

3. The UV-blocking agent as set forth in claim 1, wherein the oxidized inorganic material is any one or a0 mixture selected from the oxidized inorganic material group consisting of titanium dioxide, zinc oxide, and magnesium

) oxide .

4. The UV-blocking agent as set forth in claim 1, wherein a content of melanin is 0.01 - 0.99 parts by weight 5 based on 1 part by weight of oxidized inorganic material.

5. A cosmetic comprising the UV-blocking agent according to any one of claims 1 to 4.

6. A method of producing the UV-blocking agent according to any one of claims 1 to 4, comprising: 0 dispersing 1 part by weight of oxidized inorganic material, which has a particle diameter of 0.01 - 1000 μ and which is harmless to humans, and 0.01 - 0.99 parts by weight of melanin precursor, in a solvent; and oxidizing a resulting solution.

7. The method as set forth in claim 6, wherein the oxidization comprises adding air containing oxygen to a reaction solution, adding an enzyme including tyrosinase or phenol oxydase to the reaction solution, or adding an oxidizing agent including potassium permanganate or hydrogen peroxide to the reaction solution.

8. The method as set forth in claim 6, wherein the oxidized inorganic material is any one or a mixture selected from the oxidized inorganic material group consisting of titanium dioxide, zinc oxide, and magnesium oxide .

9. The method as set forth in claim 6, wherein the melanin precursor is a DOPA derivative including hydroquinone, catechol, resorcinol, o-quinone, p-quinone, DOPA methyl ester, dihydroxyphenylacetic acid, dihydroxyphenylglycol, or dihydroxyphenylserine.

10. The method as set forth in claim 6, further comprising adding 0.01 - 60.0 parts by weight of amino acid having an -SH functional group based on 1 part by weight of oxidized inorganic material.

11. The method as set forth in claim 10, wherein the amino acid having the -SH functional group is cystein or glutathione.

12. A cosmetic comprising a UV-blocking agent produced through the method according to any one of claims 7 to 11.