WO2005107729A1

WO2005107729A1 - Compositions comprising lycopene and phytoestrogen

Info

Publication number: WO2005107729A1
Application number: PCT/KR2005/001340
Authority: WO
Inventors: Sang Mo Kang
Original assignee: Ecotech Co., Ltd.
Priority date: 2004-05-07
Filing date: 2005-05-07
Publication date: 2005-11-17
Also published as: KR20060045943A; KR100739531B1

Abstract

Disclosed herein is a composition that is useful for the prevention and treatment of dermal disorders or diseases, such as acne, seborrheic dermatitis, freckles, etc., which are readily visible with the naked eye and difficult to treat because of the side effects caused by the long term administration of conventional drugs, as well as woman's diseases including pre-menstrual syndrome and menopausal symptoms. Additionally, the composition can effectively fade acnes and/or seborrheic dermatitis marks. The composition comprises phytoestrogen and lycopene as essential components plus a supplement selected from among vitamin C, a vitamin B and C complex, vitamin E, squalene, J3-glucan, a soybean fermentation extract, a ginkgo extract, beta-carotene, an Acanthopanax species (Acanthopanax senticosus) extract, resveratrol and combinations thereof, which is helpful in making the skin fine and smooth.

Description

COMPOSITIONS COMPRISING LYCOPENE AND PHYTOESTROGEN

Technical Field The present invention relates to a composition containing lycopene and phytoestrogen as essential components. More particularly, the present invention relates to a composition which can greatly improve skin condition and effectively treat women' s diseases without causing side effects which may result from the administration of phytoestrogen alone.

Background Art Phytoestrogen, also called plant estrogen, is similar in function and molecular structure to the female hormone estrogen and is abundantly found in leguminous plants, peanuts, pine nuts, green vegetables, rice, etc. Isoflavones, which fall into a class of phytoestrogens, are used for the improvement and treatment of various premenstrual, menstrual and menopausal syndromes. For example, isoflavones are found to alter menstrual cycles to reduce or prevent premenstrual syndrome. In addition many studies show a strong association between the consumption of isoflavones and reduced risk of various hormone-related cancers such as breast cancer. Further, it is known that these naturally occurring compounds are useful in preventing menopausal women from developing symptoms of senility. Increasing the level of neurotransmitters, such as endorphin and serotonin, as well as the absorption of calcium, isoflavones are effective for the prevention of osteoporosis, obesity and aging, for the strengthening of cell membranes and blood vessel walls and for the treatment of cardiovascular disorders, such as heart disease, hypertension, atherosclerosis, etc . Moreover, with the function of inhibiting 5 alpha- reductase, isoflavones are applied for the prevention and treatment of seborrheic dermatitis and freckles as materials for clearing the skin. For example, many patents disclose isoflavones as cosmetic materials for treating acne (WO 00/22728, WO 99/48496, WO 01/52840, WO 98/08503) . Isoflavones, in which soybeans are very rich, are representatively exemplified by daidzein, genistein, genistin and glycitein. Such pharmaceutical and cosmetic effects require the uptake of a certain amount of isoflavones over the long term. However, the long-term uptake of isoflavones makes the skin cloudy, itchy, and rough, and causes the formation of pimples, the inflammation of gums, and the generation of erythema. In addition, those who take isoflavones suffer from shoulder pain. The side effects caused by isoflavone intake can be eliminated if the intake is stopped. In the case that isoflavones are administered over the long term to treat acne, side effects accompany such treatment. When administration is ceased because of the side effects, the acne condition worsens . It is thus difficult to treat acne with isoflavones alone. According to the present inventors' experimental results, cosmetic formulations comprising isoflavones show little or no effects when perspiration occurs. When applied for the treatment of acne, isoflavones cause itchiness, tiny pimples, erythema, and inflammation of the skin on the face. Additionally, the application of highly concentrated isoflavones causes numbness in the face. Patients thus refuse to continue to use isoflavones because of such side effects and thus, it is difficult to treat acne with isoflavones. Upon oral administration, isoflavones produce the same side effects as described above, such as cloudiness, itchiness and roughness, erythema and inflammation of the skin on the face. The pimple reduction effect is less produced upon oral administration than upon topical application. In severe cases, not only is shoulder pain generated, but also gums are swollen. For these reasons, the treatment of acne through the oral administration of isoflavones is also difficult. Even when applied for the treatment of menopausal symptoms and osteoporosis, isoflavones cause cloudiness, erythema, and even pimples on the face, thus patients refuse to take isoflavones. Due to such various severe side effects, isoflavones are actually difficult to develop into products for treating acne. Phytoestrogen is found in pomegranate extract. Like isoflavones, pomegranate extract, when orally administered, causes skin cloudiness and erythema formation, although to a lesser extent.

Leading to the present invention, the intensive and thorough studies on the application of phytoestrogens for pharmaceutical and cosmetic purposes, conducted by the present inventors, resulted in the finding that, phytoestrogens, especially isoflavones or pomegranate extracts, when used in combination with lycopene, not only are effective for the prevention and treatment of acne, seborrheic dermatitis and freckles, but also fade marks resulting from acne and seborrheic dermatitis so as to make the skin clear and smooth, without the side effects caused upon the application of isoflavones alone.

Disclosure Accordingly, a principal object of the present invention to provide a composition containing lycopene and phytoestrogen, which provide the pharmaceutical and cosmetic benefits of phytoestrogen while reducing or eliminating various side effects of isoflavones or pomegranate extract, such as acne, seborrheic dermatitis, and freckles. Another object of the present invention is to provide a composition containing lycopene and phytoestrogen, which is effective for fading or alleviating marks resulting from acne or seborrheic dermatitis.

Phytoestrogens, especially isoflavones or pomegranate extract, are ineffective for the treatment of acne and seborrheic dermatitis because the chemicals, when taken by those who suffer from such skin troubles, do not circulate well in the blood. The chemicals agglomerate to cause the side effects, such as inflammation, at the facial epidermis. In contrast, the composition of the present invention, although its precise pharmaceutical mechanism has yet to be proven, exhibits therapeutic effects on acne and seborrheic dermatitis without the side effects, so as to make the face smooth, attributable, in the present inventors' opinion, to the fact that lycopene aids the circulation of isoflavones or pomegranate extract in the blood. As such, isoflavones or pomegranate extract in combination with lycopene can be used to treat acne and seborrheic dermatitis, thereby providing a cosmetic effect of making the face smooth. On the whole, those who take isoflavones or pomegranate extract suffer from itchiness and pimples on the face in the evening. When associated with lycopene, isoflavones or pomegranate extract are believed to smoothly circulate through blood vessels with the aid of the lycopene, so as not to produce the side effects. Rather, those who take the composition of the present invention experience improvements in their appearance and no adverse side effects. If it is supplemented with a chemical that aids blood circulation, such as vitamin C, vitamin B and C complex, vitamin E, squalene, etc., the composition containing phytoestrogens, especially isoflavone or pomegranate extract, and lycopene exhibits improved pharmaceutical and cosmetic effects on the face. Additionally, supplementation with Eleutherococcus senticosus, resveratrol, ginkgo leaf extract, and/or fermented bean extract further improves the pharmaceutical and cosmetic effects . Because acne patients may have weak immunity, the composition of the present invention is preferably supplemented with β -glucan (Ganoderma Lucidum extracts). β- carotene, which can be converted into vitamin A, is a useful supplement for the composition of the present invention. A detailed description is given of the components used in the composition of the present invention, below. Phytoestrogens are naturally occurring phenolic plant compounds, found in various plants. In addition to isoflavones, for example, phytoestrogens can be exemplified by naringin and naringenin, found in oranges, citrons, lemons, grapefruits, etc., phloretin, found in hollyhock, Malva verticillata LIN E, etc., quercetin, which is a principal component of Herba Houttuynia cordata, and biochanin A, found in red clover. All of these compounds are effective for the treatment of acne when administered in combination with lycopene. The phytoestrogen which is extracted from pomegranate is structurally the same as that of human estrogen. Available in the present invention are the phytoestrogens which are found in foods and of which soybean isoflovones are representative. In the case of soybean isoflavones, daidzein, genistein, genistin and glycitein may be used alone or in combination. Alternatively, commercially available isoflavone-containing soybean powders may be used. Genistein, also called genistein aglucon, is metabolized to genistin, the glycoside form of genistein, and thus is also called genistein glycosides, by microorganisms in the gut. Daidzein is also naturally found in aglucon form or glycoside form. Like vitamin C and E and carotene, lycopene, which is found in significant amounts in tomato and watermelon, is known to have significant antioxidant activity. As a potent antioxidant, lycopene is reported to effectively treat and prevent various cancers, prostate problems and skin troubles. Tomato extract containing 5% lycopene is commercially available. Pomegranate extracts are generally used to treat menopausal syndromes and 50% extract may be found on the market .

In accordance with the present invention, the composition may comprise other components or additives in addition to the essential components described above. A typical ginkgo extract, that is, a ginkgo biloba extract currently available, is standardized to contain 24% ginkgo flavone glycosides. For oral administration, the composition of the present invention preferably further comprises β -glucan. Mushroom- or microorganism-derived β -glucan is suitable . More suitable is the β -glucan derived from mushrooms, especially, Ganoderma Lucidum, which has been studied for pharmaceutical effects including immunopotentiation and anticancer activity (Sone, Y., Okuda, R., Wada, N. , Kishida, E., Misaki, A. 1985., Agric. Biol. Chem. , 49:2641-2653). Examples of microorganism-derived β -glucan include cell walls of yeast and lactic acid bacteria, and polysaccharides produced by microorganisms. Particularly, the polysaccharides produced by the genus Oreobacidium, which consist mainly of β- glucan, are already utilized in foods. For oral administration, the composition of the present invention preferably further comprises a soybean fermentation extract. Containing a Bacillus-derived protease included therein, a soybean fermentation extract shows thrombolystic activity and thus is used as a health food (Sumi, H., Maruyama, M., Yoneta, T., Mihara, H. 1983, Experientia 43:1110-1111) . In addition to the additives described above, the composition to be orally administered preferably further comprises an extract from Acanthopanax (or Acanthopanax senticosus) and resveratrol, which functions to improve blood circulation. Both of the additives are well known as antioxidants . Acanthopanax, especially Acanthopanax senticosus, has been proven to have excellent skin care functionality as disclosed in Korean Pat. No. 0284120, yielded to the present inventor. Without problems, it may be used in combination with phytoestrogen. When taken orally, the composition of the present invention is administered on the basis of isoflavone (soybean isoflavone content 30%) at a dose of 5 to 200 mg a day and preferably at a dose of 10 to 160 mg a day for adults. When calculated using pure isoflavone (100%) , the suitable dose ranges from 1.5 to 67 mg a day for adults. For persons weighing more than 60 kg, the daily dose increases in proportion to the body weight. The increase of dose with body weight is also true of the other components. In the case of pomegranate extract (content 50%) , its appropriate daily dosage ranges from 20mg to 4g and preferably from 20mg to 3g. Daidzein, genistein, genistin, glycitein, naringin, naringenin, phloretin, uercetin or biochanin preferably ranges in daily dosage from 1 to 80 mg. Lycopene (content 5%) is administered at a dose from 5 to 200 mg per day and preferably at a dose from 5 to 160 mg per day for adults . As described above, the composition may comprise supplements for compensating for the side effects which may be generated by the essential component thereof. The composition may preferably contain vitamin C or vitamin C and B complex in an amount from lOOmg to lg, vitamin E in an amount from 100 to 1000 IU, and squalene in an amount from 0.1 to 2g on the basis of a daily dosage for adults. Preferably, β -glucan is added to a unit composition for daily dosage to adults in an amount from 3 to lOOmg in the case of Ganoderma Lucidum fruit body or in an amount from 5 to 100 mg in the case of microorganism-derived polysaccharides. On the basis of a daily dosage for adults, the composition preferably comprises a soybean fermentation extract powder (enzyme activity 13000 FU/g) in the amount of 3 to 200 mg, ginkgo extract in an amount of 3 to 50 mg (ginkgo flavone glycosides 1.7 to 25 mg) , and Acanthopanax (Acanthopanax senticosus) in an amount of 5 to 100 mg. In a daily dosage of the composition, resveratrol is preferably present in an amount of 1 to 100 mg, and beta carotene ranges from 2 to 500 mg. The ranges of amount of the components in the composition of the present invention are limit values. When the amount of a component exceeds the limits, its additive effect or synergistic effect with other components is decreased.

The composition of the present invention, although its precise pharmaceutical mechanism has yet to be proven, exhibits therapeutic effects on acne and seborrheic dermatitis without the side effects, so as to make the face smooth, attributable, in the present inventors' opinion, to the fact that lycopene aids the circulation of isoflavones or pomegranate extract in the blood. As such, isoflavones or pomegranate extract in combination with lycopene can be used to treat acne and seborrheic dermatitis, thereby providing a cosmetic effect of making the face smooth. On the whole, those who take isoflavones or pomegranate extract suffer from itchiness and pimples on the face in the evening. When associated with lycopene, isoflavones or pomegranate extract are believed to smoothly circulate through blood vessels with the aid of the lycopene, so as not to produce the side effects. Rather, those who take the composition of the present invention experience improvements in their appearance and no adverse side effects. If it is supplemented with a chemical that aids blood circulation, such as vitamin C, vitamin B and C complex, vitamin E, squalene, etc., the composition containing phytoestrogens, especially isoflavone or pomegranate extract, and lycopene exhibits improved pharmaceutical and cosmetic effects on the face. Additionally, supplementation with Eleutherococcus senticosus, resveratrol, ginkgo leaf extract, and/or fermented bean extract further improves the pharmaceutical and cosmetic effects . Because acne patients may have weak immunity, the composition of the present invention is preferably supplemented with β -glucan (Ganoderma Lucidum extracts) . β- carotene, which can be converted into vitamin A, is a useful supplement for the composition of the present invention. A detailed description is given of the components used in the composition of the present invention, below. Phytoestrogens are naturally occurring phenolic plant compounds, found in various plants. In addition to isoflavones, for example, phytoestrogens can be exemplified by naringin and naringenin, found in oranges, citrons, lemons, grapefruits, etc., phloretin, found in hollyhock, Malva verticillata LINNE, etc., quercetin, which is a principal component of Herba Houttuynia cordata, and biochanin A, found in red clover. All of these compounds are effective for the treatment of acne when administered in combination with lycopene. The phytoestrogen which is extracted from pomegranate is structurally the same as that of human estrogen. Available in the present invention are the phytoestrogens which are found in foods and of which soybean isoflovones are representative. In the case of soybean isoflavones, daidzein, genistein, genistin and glycitein may be used alone or in combination. Alternatively, commercially available isoflavone-containing soybean powders may be used. Genistein, also called genistein aglucon, is metabolized to genistin, the glycoside form of genistein, and thus is also called genistein glycosides, by microorganisms in the gut. Daidzein is also naturally found in aglucon form or glycoside form. Like vitamin C and E and carotene, lycopene, which is found in significant amounts in tomato and watermelon, is known to have significant antioxidant activity. As a potent antioxidant, lycopene is reported to effectively treat and prevent various cancers, prostate problems and skin troubles. Tomato extract containing 5% lycopene is commercially available . Pomegranate extracts are generally used to treat menopausal syndromes and 50% extract may be found on the market. In accordance with the present invention, the composition may comprise other components or additives in addition to the essential components described above. A typical ginkgo extract, that is, a ginkgo biloba extract currently available, is standardized to contain 24% ginkgo flavone glycosides. For oral administration, the composition of the present invention preferably further comprises β -glucan. Mushroom- or microorganism-derived β -glucan is suitable. More suitable is the β -glucan derived from mushrooms, especially, Ganoderma Lucidum, which has been studied for pharmaceutical effects including immunopotentiation and anticancer activity (Sone, Y. , Okuda, R., Wada, N. , Kishida, E., Misaki, A. 1985., Agric. Biol. Chem., 49:2641-2653). Examples of microorganism-derived β -glucan include cell walls of yeast and lactic acid bacteria, and polysaccharides produced by microorganisms. Particularly, the polysaccharides produced by the genus Oreobacidium, which consist mainly of β- glucan, are already utilized in foods . For oral administration, the composition of the present invention preferably further comprises a soybean fermentation extract. Containing a Bacillus-derived protease included therein, a soybean fermentation extract shows thrombolystic activity and thus is used as a health food (Sumi, H., Maruyama, M., Yoneta, T. , Mihara, H. 1983, Experientia 43:1110-1111) . In addition to the additives described above, the composition to be orally administered preferably further comprises an extract from Acanthopanax (or Acanthopanax senticosus) and resveratrol, which functions to improve blood circulation. Both of the additives are well known as antioxidants . Acanthopanax, especially Acanthopanax senticosus, has been proven to have excellent skin care functionality as disclosed in Korean Pat. No. 0284120, yielded to the present inventor. Without problems, it may be used in combination with phytoestrogen. When taken orally, the composition of the present invention is administered on the basis of isoflavone (soybean isoflavone content 30%) at a dose of 5 to 200 mg a day and preferably at a dose of 10 to 160 mg a day for adults. When calculated using pure isoflavone (100%) , the suitable dose ranges from 1.5 to 67 mg a day for adults. For persons weighing more than 60 kg, the daily dose increases in proportion to the body weight. The increase of dose with body weight is also true of the other components. In the case of pomegranate extract (content 50%) , its appropriate daily dosage ranges from 20mg to 4g and preferably from 20mg to 3g. Daidzein, genistein, genistin, glycitein, naringin, naringenin, phloretin, quercetin or biochanin preferably ranges in daily dosage from 1 to 80 mg. Lycopene (content 5%) is administered at a dose from 5 to 200 mg per day and preferably at a dose from 5 to 160 mg per day for adults. As described above, the composition may comprise supplements for compensating for the side effects which may be generated by the essential component thereof. The composition may preferably contain vitamin C or vitamin C and B complex in an amount from lOOmg to lg, vitamin E in an amount from 100 to 1000 IU, and squalene in an amount from 0.1 to 2g on the basis of a daily dosage for adults. Preferably, β -glucan is added to a unit composition for daily dosage to adults in an amount from 3 to lOOmg in the case of Ganoderma Lucidum fruit body or in an amount from 5 to 100 mg in the case of microorganism-derived polysaccharides. On the basis of a daily dosage for adults, the composition preferably comprises a soybean fermentation extract powder (enzyme activity 13000 FU/g) in the amount of 3 to 200 mg, ginkgo extract in an amount of 3 to 50 mg (ginkgo flavone glycosides 1.7 to 25 mg) , and Acanthopanax (Acanthopanax senticosus) in an amount of 5 to 100 mg. In a daily dosage of the composition, resveratrol is preferably present in an amount of 1 to 100 mg, and beta carotene ranges from 2 to 500 mg. The ranges of amount of the components in the composition of the present invention are limit values . When the amount of a component exceeds the limits, its additive effect or synergistic effect with other components is decreased.

Description of Drawings FIG. 1 is a photograph showing erythema formed on the face of a menopausal woman as a side effect of the administration of isoflavone. FIG. 2 is a photograph showing erythema and pimples formed on the ridge of the nose and the cheek, respectively, as side effects in an acne patient. FIG. 3 is a photograph showing the elimination of the side effects of FIG. 2 as a result of the co-administration of isoflavone and lycopene. FIG. 4 is a photograph showing a side effect caused by the administration of both isoflavone and lycopene. FIG. 5 is a photograph showing the elimination of the side effect of FIG. 4 as a result of supplementation with vitamin C. FIG. 6 is a graph showing skin clarity after the administration of isoflavone. FIG. 7 is a graph showing skin clarity after the co- administration of isoflavone and lycopene. FIG. 8 is photographs showing distinct acne marks before the co-administration of isoflavone and lycopene (8a and 8c) and faded acne marks after the administration of both isoflavone and lycopene (8b and 8d) .

Best Mode A better understanding of the present invention may be obtained through the following examples which are set forth to illustrate, but are not to be construed as the limit of the present invention.

Formulation examples of the composition for oral administration are as follows. <Formulation Example 1> Soybean Isoflavone (content 30%) 25 g Lycopene (content 5%) 60 g This formulation was tableted to prepare 2000 tablets.

<Formulation Example 2> Soybean isoflavone (content 30 %) 25 g Lycopene (content 5%) 60 g Vitamin B and C Complex 189 g This formulation was filled into 2000 capsules.

<Formulation Example 3> Soybean Isoflavone (content 30%) 25 g Lycopene (content 5%) 60 g Vitamin C 250 g Ganoderma Lucidum extract 10 g The formulation was filled into 2000 capsules.

<Formulation Example 4> Soybean Isoflavone (content 30%) 250 g Lycopene (5%) 60 g Squalene 150 mg Ganoderma Lucidum Extract 10 g Soybean Fermentation Extract 10 g Ginkgo Extract 5 g Acanthopanax senticosus extract 5 g Resveratrol 10 g Beta-Carotene 10 g This formulation was filled into 2,000 capsules.

<Formulation Example 5> Soybean Isoflavone (content 30%) 25 g Lycopene (content 5%) 60 g Vitamin E 100 IU Pomegranate Extract 100 g 2,000 capsules were prepared from this formulation.

In Formulation Examples 1 to 4, pomegranate extracts 100 g may be used instead of isoflavone 30 g. In this case, the formulation is loaded into 3000 to 4000 capsules.

<Formulation Example 6> Naringin 5 g Lycopene (content 5%) 60 g Vitamin B and C Complex 189 g Ganoderma Lucidum extract 10 g Beta-Carotene (content 5%) 10 g Resveratrol 10 g

This formulation was tableted to prepare 2,000 capsules. The vitamin B and C complex used in this formulation is a product found in markets. For example, 754 mg of the complex is comprised of thiamine nitrate 15.5 mg, riboflavin 10 mg, pyridoxine hydrochloride 5.2 mg, cyanocobalamin 5 μg, ascorbic acid 600 mg, calcium pantothenate 23.2 mg, and nicotinic acid amide 100 mg. In order to demonstrate the effect of the composition according to the present invention, experiments were carried out as follows.

Experimental Example 1: Side Effects Attributed to the Intake of Isoflavone and Lycopene 20 persons were divided into two groups of ten: persons in Group 1 were given 60 mg of isoflavone (total isoflavone content 30%) alone while 60 mg of isoflavone, together with 40 mg of lycopene (total lycopene 5%) , was administered to Group 2, for three weeks. The subjects were monitored for skin condition and the results are given in Table 1, below. The side effects were graded from 10 to zero according to decreasing level of severity, with zero representing the absence of side effects. As the side effect, facial itch, erythema (see FIG. 1) , pimples or roughness, and shoulder pain were considered while facial cloudiness was used as a reference .

TABLE 1

Almost all of the subjects of Group 1 to whom isoflavone alone was administered developed skin cloudiness, roughness and itchiness. Erythema or pimples were formed on the face of six of them and two suffered from shoulder pain. In Group 2 to which isoflavone and lycopene were administered together, all subjects experienced skin clearing and smoothness, with little or no shoulder pain. However, facial erythema was found in two persons. When the subjects of Group 2 ingested 500 mg of vitamin C, 378 mg of vitamin B and C complex (composition of Formulation Example 2), 200 IU of vitamin E, and/or 0.3 g of squalene, the shoulder pain and facial erythema disappeared. Similar results were found in the case of premenstrual syndrome . FIG. 1 shows the erythema formed around the eye as a side effect in a subject from Group 1.

Experimental Example 2: Therapeutic Effect on Acne Patients with severe acne and patients with severe seborrheic dermatitis were separately divided into four groups. Each group consisted of two subjects, except for ten subjects in each of Groups 1 (acne) and 2 (acne) . Subjects were administered with 60 mg of soybean isoflavone (total isoflavone content 30%) for Group 1, with 60 mg of isoflavone + 40 mg of lycopene (lycopene content 5%) for Group 2, with 60 mg of isoflavone + 40 mg of lycopene + 20 mg of Ganoderma Lucidum extract (β -glucan) for Group 3, and with 60 mg of isoflavone + 40 mg of lycopene + 20 mg of Oreobacidium- produced β -glucan polysaccharides for Group 4 each day for four weeks. Before the administration, the skin condition was graded from 10 to 1 according to decreasing severity of the dermal condition, where the facial skin with no dermal diseases was graded zero. Likewise, the side effects were graded from 10 to zero according to decreasing order of severity. The results are given in Table 2, below.

As seen in Table 2, a good therapeutic effect was obtained in Group 1, with concomitant significant side effects. After the ingestion of isoflavone alone, all the subjects had skin cloudiness, with facial erythema or pimples found in as many as eight persons. Two experienced facial itching. FIG. 2 shows an acne patient of Group 1, whose acne condition was largely alleviated, but who had pimples form on the ridge of the nose and one cheek. The subjects of Group 2, who were supplemented with lycopene plus isoflavone, experienced skin clearing and smoothness, and were satisfied in all aspects of interest. The therapeutic effect on acne was considered twice as good as that for Group 1. In contrast to menopausal women, no subject of Group 2 suffered from shoulder pain. Additional supplementation with β -glucan resulted in better therapeutic effects on acne, with lesser side effects caused. As seen in FIG. 3, the patient of FIG. 2 developed a clear face after the four-week oral administration of both isoflavone and lycopene, as in Group 2 of Experimental Example 2. In accordance with the present invention, it has been found that the excellent blood circulation function of lycopene is effective for preventing or reducing the side effects resulting from a local excess of isoflavones. In addition, as is apparent from the data of Table 2,

Ganoderma lucidum or Oreobacidium-derived polysaccharides, consisting mainly of β -glucan, are certainly helpful in the killing of acne bacteria, which is believe to result from the immunopotentiation thereof. Consequently, the use of isoflavone alone is accompanied by various side effects such as facial roughness, cloudiness, itching and pimples, shoulder pain, gum pain, etc. whereas the side effects can be eliminated or significantly reduced by the administration of lycopene. Additionally, supplementation with β -glucan-containing material provides improved therapeutic effect against acne and seborrheic dermatitis .

Therefore, a composition containing all of them is very effective for skin care. On the whole, isoflavone is ingested for at least one month to treat menopausal syndromes or acne, however, the accompanying side effects make it difficult to take isoflavone over the long term. A higher dosage of isoflavone may result in greater therapeutic effects, but worse side effects. The side effects can be reduced or eliminated by co-administration of lycopene and isoflavone. Of course, light acne can be cured with isoflavone alone, without significant side effects. However, severe acne is difficult to treat with isoflavone alone without causing the side effects . Isoflavone alone has poor therapeutic effects on severe acne. Even if severe acne is cured to some extent, pimples tend to form to the same extent.

Experimental Example 3: Dose of Isoflavone Suitable for the Treatment of Acne Isoflavone was examined for suitable dosages for acne patients. Isoflavone (isoflavone content 30%) was administered in a total daily dose of 5, 10, 20, 40, 60, 100, 120, 160, or 200 mg to two patients for each dosage level, in two separate portions per day, e.g., once in the morning and in the evening, for four weeks. After one month, one patient selected from each dose group and one new patient were administered twice a day, e.g. once in the morning and in the evening, with half of the daily dose of isoflavone plus 20 mg of lycopene. The results are given in Table 3, below. In Table 3, groups are discriminated from one another by doses of isoflavone and by the mark 'Ly' if supplemented with lycopene. The severity of acne was graded from 10 for severe acne condition before administration to zero for when no acne formed. Likewise, the side effects were graded from 10 to zero in decreasing order of severity.

TABLE 3

As the dose of isoflavone administered alone increases, as seen in Table 3, the therapeutic effect also increased, but so did the side effects . Co-administration with 40 mg of lycopene considerably alleviated the side effects . As understood from the data of Table 3, an effective dosage of isoflavone ranges from 5 to 200 mg a day for adults, and preferably from 10 to 160 mg.

Experimental Example 4: Dose of Lycopene Suitable for the Treatment of Acne Lycopene was examined for suitable dosages for acne patients. Lycopene (lycopene content 5%) was administered in a daily total dose of 5, 10, 20, 40, 60, 100, 120, 160, or 200 mg, along with isoflavone in a daily total dose of 60 mg, to two patients for each dose, in two separate portions per day, e.g., once each in the morning and in the evening, for four weeks . The results are given in Table 4, below. In Table 4, the severity of acne was graded from 10 for severe acne condition before administration to zero for when no acne formed. Likewise, the side effects were graded from 10 to zero in decreasing order of severity. Groups are discriminated from one another by doses of lycopene.

TABLE 4

The data of Table 4 demonstrate that higher doses of lycopene bring about improved therapeutic effects on acne and lesser side effects. Spots, such as freckles, were sometimes found on the faces of those to whom lycopene had been administered at a dose of 80 mg or higher. The frequency of spots increased with the dose of lycopene. As can be understood from the data of Table 4, an effective dosage of lycopene falls within the range from 5 to 200 mg a day for adults and preferably from 5 to 160 mg.

Experimental Example 5: Elimination of Side Effects (1) Some of the patients with severe acne or seborrheic dermatitis of Group 2 in Experimental Example 2 suffered from side effects when 60 mg of isoflavone (content 30%) and 40 mg of lycopene (content 5%) were administered together, in two separate portions per day. In contrast to patients of Group 1 in Experimental Example 2, who suffered from considerable side effects, these patients experienced no significant side effects. For example, in most cases, erythema was found only on the ridge of the nose (but, contrary to FIG. 2, it is not readily recognizable in photographs) and caused slight pain, with the condition developing over time. Pimples were also formed (see FIG. 4) . In order to eliminate such side effects, experiments were carried out as follows. After being supplemented with 500 mg of vitamin C (Group 1), 400 IU of vitamin E (Group 2), or 0.3 g of squalene (Group 3) , a base composition comprising 60 mg of isoflavone and 40 mg of lycopene was orally administered to two patients with acne or seborrheic dermatitis in each group for four weeks. The results are given in Table 5, below. In Table 5, the severity of acne was graded from 10 for severe acne before administration to zero for when no acne formed. Likewise, the side effects were graded from 10 to zero in decreasing order of severity.

TABLE 5

As seen in Table 5, each group was cured without side effects such as erythema on the ridge of the nose. When a vitamin B and C complex (composition of Formulation Example 2) was used, instead of vitamin C, for Group 1, no side effects were found. The content of vitamin B and C in the complex was as follows: for a daily dose, thiamine nitrate 8 mg, riboflavin 5 mg, pyridoxine hydrochloride 2.6 mg, cyanocobalamin 3 μg, ascorbic acid 300 mg, calcium pantothenate 12 mg, and nicotinic acid amide 50 mg. It is believed that, with the aid of the vitamins or squalene, isoflavone can smoothly circulate in blood vessels rather than conglomerate locally, so as not to cause side effects . FIG. 5 shows the curing of the pimples formed upon the administration of isoflavone and lycopene for four weeks by supplementation with 500 mg of vitamin C. In additional experiments, a daily dose effective to eliminate the side effects as seen in FIG. 5 was found to range from 100 mg to 1 g for vitamin C, from 100 to 1000 IU for vitamin E, and from 0.1 to 2 g for squalene . It was also found that the vitamins and the antioxidant are more effective for alleviating the side effects when used in combination.

Experimental Example 6: Elimination of Side Effects (2) After being supplemented with 20 mg of a Ganoderma Lucidum extract, a kind of β -glucan, (Group 1), 20 mg of a soybean fermentation extract, which shows thrombolytic activity (Group 2) , 20 mg of a ginkgo extract (Group 3) , 20 mg of an Acanthopanax senticosus extract (Group 4) , 10 mg of resveratrol, which aids blood circulation (Group 5) , 20 mg of beta-carotene (Group 6) , or 200 mg of a pomegranate extract

(Group 7) , a base composition comprising 60 mg of isoflavone

(isoflavone content 30%) , 40 mg of lycopene (lycopene content 5%) and 377 mg of a vitamin B and C complex according to Experimental Example 5 was orally administered in two separate portions per day to two patients with acne in each group for four weeks. The subjects were examined for effects on acne and skin care effects and the results are given in Table 6, below.

TABLE 6 Therapeutic Effects Side Effects Group Week 0 Week 2 Week 4 Week 0 Week 2 Week 4

As apparent from the data of Table 6, excellent therapeutic effects on acne were obtained in all groups, without side effects. In terms of skin care, effectiveness is in the order of Group 1 > 2 > 3 > 4 > 5 > 6 > 7. Thus, β- glucan, a soybean fermentation extract, a ginkgo extract, an Acanthopanax (Acanthopanax senticosus) extract, resveratrol, beta-carotene, or a pomegranate extract is preferably supplemented to the base composition. In additional experiments, these supplements were proven to have better acne curing and skin care effects when used in combination. An effective amount was found to range from 3 to 100 mg for β -glucan in the form of Ganoderma Lucidum fruit body powder, from 5 to 100 mg for microorganism-derived polysaccharides (β -glucan), from 3 to 200 mg for soybean fermentation extract powder (enzyme activity 13000 FU/g) , from 3 to 50 mg for a ginkgo extract (from 1.7 to 25 mg for total ginkgo flavone glycosides) , from 5. to 100 mg for Acanthopanax senticosus, from 1 to 100 mg for resveratrol, and from 2 to 500 mg for beta-carotene, based on a daily dosage for adults.

Experimental Example 7: Elimination of Side Effects (3) To Groups 1 and 2, each consisting of one acne patient and one menopausal woman, 0.5 g of a sole pomegranate extract (extract content 50%) and a combination of 0.5 g of the pomegranate extract and 20 mg of lycopene were, respectively, administered in two separate portions per day, e.g., once in the morning and once in the evening, for two weeks. The severity of acne was graded from 10 for severe acne before administration to zero for when no acne formed. Likewise, the side effects were graded from 10 to zero in decreasing order of severity. The results are given in Table 7, below.

As seen in Table 7, erythema, even though formed locally on the face of the acne patient and the menopausal woman of Group 1 as in FIG. 1, was not as severe as that formed upon the administration of isoflavone alone. When administered in combination with lycopene as in Group 2, the pomegranate extract was more effective in treating acne without side effects. However, lycopene alone showed almost no therapeutic effect on acne. In all cases, the menopausal women had no spots formed on their skin, but . experienced greatly improved skin condition.

Experimental Example 8: Dose of Pomegranate Extract Suitable for the Treatment of Acne A pomegranate extract was examined for suitable dosages for acne patients. A commercially available pomegranate extract (pomegranate extract content 50%) was administered in a total daily dose of 20, 50, 100, 200, 400, 600, 800, 1000, 2000, 3000, or 4000 mg, along with 20 mg of lycopene, to two patients for each dose, in two separate portions per day, e.g., once in the morning and in the evening, for four weeks. The results are given in Table 8, below. In Table 8, the severity of acne was graded from 10 for severe acne before administration to zero for when no acne formed. Likewise, the side effects were graded from 10 to zero in decreasing order of severity. Groups were discriminated from one another by the dose of the pomegranate extract.

TABLE 8

As the dose of the pomegranate extract increased, as seen in Table 8, the therapeutic effect also increased, but so did the side effects. The data of Table 3 and the data obtained in additional experiments show that the effective dosage of the pomegranate extract ranged from 20 mg to 4 g a day for adults, preferably from 20 mg to 3 g. Experimental Example 9: Elimination of Side Effects (4) Side effects, even though mild, were found in some of the patients with acne in Experimental Example 7 when the pomegranate extract and lycopene were co-administered in two separate portions per day to them, in contrast to when isoflavone and lycopene were co-administered. After being supplemented with 500 mg of vitamin C (Group 1) , 400 IU of vitamin E (Group 2), or squalene 0.3 g (Group 3) , a base composition comprising a pomegranate extract 600 mg and lycopene 40 mg was orally administered to two patients with acne in each group for four weeks. The results are given in Table 9, below. In Table 9, the severity of acne was graded from 10 for severe acne before administration to zero for when no acne formed. Likewise, the side effects were graded from 10 to zero in decreasing order of severity.

TABLE 9

As seen in Table 9, excellent therapeutic effects against acne were found in all groups without side effects such as erythema on the ridge of the nose. When a vitamin B and C complex (composition of Formulation Example 5) was used, instead of vitamin C, for Group 1, no side effects were found. In additional experiments, an amount effective to eliminate the side effects was found to range from 100 mg to 1 g for vitamin C, from 100 to 1000 IU for vitamin E, and from 0.1 to 2 g for squalene, based on a daily dose for adults. It was also found that the vitamins and the antioxidant are more effective for alleviating the side effects when used in combination.

Experimental Example 10: Elimination of Side Effects (5) After being supplemented with 20 mg of a Ganoderma lucidum extract, a kind of β -glucan, (Group 1), 20 mg of a soybean fermentation extract (Group 2) , 20 mg of a ginkgo extract (Group 3) , 10 mg of resveratrol (Group 4) , 20 mg of an Acanthopanax senticosus extract (Group 5) , 20 mg of beta- carotene (Group 6) , or 20 mg of isoflavone (Group 7) , a base composition, comprising 600 mg of a pomegranate extract (pomegranate extract content 50%) , 40 mg of lycopene (lycopene content 5%) and 377 mg of a vitamin B and C complex (refer to the composition of Experimental Example 5) according to Experimental Example 9, was orally administered in two separate portions per day to two patients with acne in each group for four weeks. The compositions were examined for their effect on acne and skin care effects and the results are given in Table 10, below.

TABLE 10

As apparent from the data of Table 10, excellent therapeutic effects against acne were obtained in all groups, without side effects. In Group 7, co-administration with isoflavone was found to be more effective for the treatment of acne. In terms of skin care, preference is in the order of Group 1 > 2 > 3 > 4 > 5 > 6 > 7. Thus, β -glucan, a soybean fermentation extract, a ginkgo extract, an Acanthopanax (Acanthopanax senticosus) extract, resveratrol, beta-carotene, or isoflavone is preferably supplemented to the base composition. In additional experiments, these supplements were proven to show better acne curing and skin care effects when used in combination. An effective amount was found to range from 3 to 100 mg for β -glucan in the form of Ganoderma lucidum fruit body powder, from 5 to 100 mg for microorganism-derived polysaccharides (β -glucan), from 3 to 200 mg for soybean fermentation extract powder (enzyme activity 13000 FU/g) , from 3 to 50 mg for a ginkgo extract (from 1.7 to 25 mg for total ginkgo flavone glycosides) , from 5 to 100 mg for Acanthopanax senticosus, from 1 to 100 mg for resveratrol, and from 2 to 500 mg for beta-carotene, based on a daily dosage for adults.

Experimental Example 11: Effects According to Phytoestrogens To examine the inhibitory activity of phytoestrogens against sebum secretion, lotions containing phytoestrogens were applied to the forehead. Naringin, naringenin, phloretin, quercetin, and biochanin A were found to have inhibitory activity while zearalenone and kaempferol did not inhibit sebum secretion. A phytoestrogen capable of inhibiting sebum secretion was administered, alone or in combination with lycopene, to an acne patient in a daily dose of 20 mg for two weeks, as shown for naringin (Group 1) , naringin and lycopene (Group 2) , naringenin (Group 3), naringenin and lycopene (Group 4), phloretin (Group 5) , phloretin and lycopene (Group6) , quercetin (Group 7) , quercetin and lycopene (Group 8) , biochanin (Group 9) , and biochanin and lycopene (Group 10) . The dose of lycopene (content 5%) was 40 mg. The results are given in Table 11, below. In Table 11, the severity of acne was graded from 10 for severe acne before administration to zero for when no acne formed. Likewise, the side effects were graded from 10 to zero in decreasing order of severity.

TABLE 11

When the phytoestrogen was administered in combination with lycopene, as seen in Table 11, far better therapeutic effects, as well as almost no side effects, were obtained compared to when the phytoestrogen was administered alone. In addition, the phytoestrogen was found to be far more effective for skin care effects when administered in combination with lycopene than alone. Thus, it is preferred that lycopene is added even when acne treatment is carried out with different kinds of phytoestrogens. As in Experimental Examples 5 and 9, vitamin C, a vitamin B and C complex, vitamin E, and/or squalene can give the same effects. Their doses are determined within the ranges given in Experimental Examples 5 and 9. Also, a Ganoderma Lucidum extract, a soybean fermentation extract, a ginkgo extract, resveratrol, an Acanthopanax extract, and beta-carotene are preferably added as in Experimental Examples 6 and 10 and their doses are the same as in Experimental Example 10. When the phytoestrogens were administered in combination, good results were obtained. Suitable daily doses of naringin, naringenin, phloretin, quercetin, and biochanin fall in the range from 1 to 80 mg for adults.

Experimental Example 12 : Image Analysis for Change of Skin Texture (1) Analysis for Skin Color A person was administered with soybean 30 mg of isoflavone (total isoflavone content 30%) (Group 1) in two separate portions per day, e.g., once in the morning and in the evening, for two weeks and, one week later, with 0.4 g of a pomegranate extract (Group 3) in the same manner. Likewise, another person was administered with a combination of 30 mg of isoflavone and 40 mg of lycopene (total lycopene content 5%) (Group 2) in two separate portions per day, e.g., once in the morning and in the evening, for two weeks and, one week later, with a combination of 0.4 g of a pomegranate extract and 40 mg of lycopene (Group 4) in the same manner. Using a skin visio eter, the skin was analyzed for a color change. After Group 1 was administered, the brightness of the forehead was measured using a skin visiometer and input into a computer. Then, after two weeks of administration to Group 2, the forehead was measured for brightness (gray level) . The results of the analysis of Groups 1 and 2 are shown in FIGS. 6 and 7, respectively. In FIG. 7, a central portion is measured to have a gray level of 136, which is greater than that of FIG. 6 (central portion, 132) by about 9 %, indicating that the skin became brighter. After the administration of Group 1, the skin became more cloudy than before the administration. When lycopene was administered alone, the skin was whitened, as in the case of Group 2. Results obtained by using Groups 3 and 4 were similar to those obtained by Groups 1 and 2. Thus, a pomegranate extract is also preferably supplemented with lycopene. As understood from the data, isoflavone or pomegranate extract alone make the skin cloudy, but if lycopene is supplemented, the skin can be whitened as when lycopene alone is applied to the skin.

(2) Analysis for skin texture During the experiments described above, the skin was also monitored for the extent to which it became smooth, by using a skin visiometer. Cheek skin was measured five times and the average values are given in Table 12, below.

TABLE 12

In Table 12, "R" stands for the roughness of the skin, indicating that the higher the R is, the rougher the skin is. "LL" means the length of a selected skin area, Rl means the distance from the highest peak to the lowest portion in the skin, R2 is the average value of Rl measured for five different areas, R3 is the largest value in the Rl values of five areas, R4 is average smoothness, and R5 is average depth. As seen in Table 12, the skin became a little rougher after the administration to Group 1 compared to before the experiment, but was smoothed when administered to Group 2. That is, co-administration of isoflavone and lycopene brings about positive skin care effects. When lycopene was administered alone for two weeks, the overall 'R' values were positioned between those of Group 2 and pre-experimental values . Consequently, the administration of isoflavone together with lycopene makes the skin the smoothest while whitening the skin as when lycopene is administered alone. This trend is also true of pomegranate extract. An additional experiment demonstrated that supplementation with at least one selected from among vitamin C, a vitamin B and C complex, vitamin E, squalene, β -glucan, a soybean fermentation extract, a ginkgo extract, beta-carotene, an Acanthopanax (Acanthopanax senticosus) extract and resveratrol gives additional benefit to the skin in terms of brightness and texture.

Experimental Example 13: Lycopene's Optimal Dose to Dose of Isoflavone Suitable for the Treatment of Menopausal Syndrome Isoflavone (total isoflavone content 30%) was administered in a daily total dose of 10 mg (Group 1) , 160 mg (Group 2) or 200 mg (Group 3) to two menopausal women in each group in two separate portions per day, e.g., once in the morning and in the evening, for four weeks. At the same time, lycopene (total lycopene content 5%) was co-administered in an amount corresponding to one third (Lyl/3) of, the same amount (Lyl/l) as, and twice (Ly2/1) of the daily dose of the isoflavone, within an upper limit of 200 mg. The side effects caused by isoflavone were graded from 10, for greatest severity, to zero, for when no side effects were caused. The results are given in Table 13, below.

TABLE 13

As seen in Table 13, the groups to which no lycopene was administered suffered from typical side effects such as skin becoming cloudy and rough. Severe erythema, along with pimples, was formed upon the administration of 160 or 200 mg of isoflavone. However, co-administration with lycopene significantly reduced the side effects. The results of extensive experiments demonstrated that lycopene can be used in an amount from about 5 to about 200 mg based on the daily dose of isoflavone and preferably in an amount of half of the dose of isoflavone administered. Over 2 mg to 4 g of a pomegranate extract or 1 to 80 mg of genistein, genistin, glycitein, naringin, naringenin, phloretin, quercetin or biochanin, lycopene has a suitable dose from 5 to 200 mg. This dose range is also applicable for acne patients.

Experimental Example 14: Fading of Marks of Acne and Seborrheic Dermatitis Persons having acne marks were administered with no chemical (control, Group 1) , 25 mg of soybean isoflavone (total isoflavone content 30%) (Group 2) , 25 mg of isoflavone + 60 mg of lycopene (lycopene content 5%) (Group 3) , or 60 mg of lycopene (Group 4) in two separate portions per day, e.g., in the morning and in the evening. This procedure was also applied to persons having seborrheic dermatitis marks (Groups 5 to 8) . The marks were graded from 10 for the severest state before administration to zero for a completely cured state. The formation of pimples as side effects was monitored. The results are given in Table 14, below.

TABLE 14

The marks in Control Groups 1 and 5 had never faded. In Groups 2 and 6, which ingested isoflavone alone, there were insignificant mark fading effects while the face became cloudy and came to have 3-4 pimples thereon. On the other hand, the acne and seborrheic dermatitis marks were greatly faded and the skin became smooth in both Groups 3 and 7. In Groups 4 and 8, although the skin became smooth, the marks remained unfaded. FIG. 8 is photographs taken of the subjects of Group 3, whose faces became very clear, with acne marks faded, by co- administration of isoflavone and lycopene for 20 days.

Industrial Applicability According to the present invention, as described hereinbefore, dermal disorders or diseases, such as acne, seborrheic dermatitis, freckles, etc., which are readily apparent with the naked eye and difficult to treat because of the side effects caused by the long term administration of drugs, can be prevented and cured. In addition, various side effects which may be caused when conventional drugs are administered in a large amount or over the long term to treat pre-menstrual syndrome or menopausal symptoms can be alleviated or eliminated according to the present invention. Further, the present invention is useful in terms of skin care thanks to its ability to fade acne marks and seborrheic dermatitis and to make the skin smooth, being applicable to the cosmetic and medicinal industries. For these purpose, the present invention provides a composition comprising phytoestrogen, especially isoflavone or pomegranate extract, and lycopene, which functions to reduce or eliminate the side effects caused upon the administration of phytoestrogen alone, as essential components.

Claims

1. A composition, capable of being administered via an oral route, comprising phytoestrogen and lycopene as essential components .

2. The composition as set forth in claim 1, wherein the phytoestrogen is selected from the group consisting of naringin, naringenin, phloretin, quercetin, biochanin, a pomegranate extract, isoflavone and combinations thereof.

3. The composition as set forth in claim 1, further comprising a supplement selected from a group consisting of vitamin C, a vitamin B and C complex, vitamin E, squalene, β- glucan, a soybean fermentation extract, a ginkgo extract, beta-carotene, an Acanthopanax species (Acanthopanax senticosus) extract, resveratrol and combinations thereof.

4. The composition as set forth in claim 2, wherein the isoflavone is selected from a group consisting of daidzein, genistein, genistin, glycitein and combinations thereof.

5. The composition as set forth in claim 1, wherein the lycopene, when in the form of an extract having a lycopene content of 5%, is contained in an amount of 5 to 200 mg based on a daily dose for adults of the composition.

6. The composition as set forth in claim 2, wherein the isoflavone, when being in the form of an extract having an isoflavone content of 30%, is contained in an amount from 5 to 200 mg based on a daily dose of the composition for adults.

7. The composition as set forth in claim 2, wherein the pomegranate extract has a pomegranate content of 50% and is contained in an amount from 20 mg to 4 g based on a daily dose of the composition for adults.

8. The composition as set forth in claim 2, wherein the naringin, the naringenin, the phloretin, the quercetin or the biochanin is contained in an amount from 1 to 80 mg based on a daily dose of the composition for adults .