HK1164160A - Composition for alleviating ultraviolet radiation-induced damage - Google Patents

Description

Composition for reducing ultraviolet ray damage

Technical Field

The present invention relates to a composition for reducing ultraviolet ray damage, which comprises 1 or 2 or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, and L-cysteine, and derivatives and/or salts thereof; and a method for improving skin diseases and the cosmetic condition of the skin caused by ultraviolet exposure, which comprises the step of administering 1 or 2 or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine and their derivatives and/or salts; and a method for treating and/or preventing cataract comprising the step of administering the aforementioned compound.

Background

The ultraviolet rays may be classified into long wavelength region ultraviolet rays (UV-A) longer than about 320nm, middle wavelength region ultraviolet rays (UV-B) of about 320nm to about 280nm, and short wavelength region ultraviolet rays (UV-C) shorter than about 280 nm. Among them, UV-C is absorbed by the ozone layer, so that the sunlight reaching the ground does not contain UV-C. UV-A is not absorbed by the ozone layer and accounts for the majority of the UV light reaching the ground. In addition, although part of UV-B is absorbed by the ozone layer, skin damage is caused by the amount of light of 1/1000 of UV-A. Therefore, UV-A and UV-B are important causes of skin damage. According to non-patent document 1, examples of diseases related to ultraviolet rays include wrinkles, erythema, xeroderma pigmentosum, chronic actinic dermatitis, squamous cell carcinoma, basal cell carcinoma, malignant melanoma, Bowen disease (Bowen disease), solar keratosis, photosensitivity, vaccinia-like blister disease, and light-contact dermatitis; non-patent document 2 discloses solar dermatitis, chronic actinic dermatitis, actinic keratosis, actinic cheilitis, nodular elastosis (Favre-racuchot disease), photosensitivity, photo-contact dermatitis, berlock dermatitis, photosensitive drug eruption, polymorphous light eruption, vaccinia-like blistering disease, solar urticaria, chronic photosensitive dermatitis, xeroderma pigmentosum, freckle, porphyria, pellagra, Hartnupdisease, solar keratosis, dermatomyositis, lichen planus, follicular keratosis (Darier's disease), pityriasis rubra pilaris, rosacea, atopic dermatitis, chloasma, herpes simplex, lupus erythematosus, and the like.

Documents of the prior art

Non-patent document

Non-patent document 1: the most recent therapy of skin diseases 2005-one 2006 (southern Jiangtang)

Non-patent document 2: background science 7 th edition (medical yard)

Disclosure of Invention

Problems to be solved by the invention

Conventionally, as a prophylactic and/or therapeutic agent for skin damage caused by ultraviolet rays, an ultraviolet scattering agent such as titanium oxide for inhibiting skin absorption of ultraviolet rays, an ultraviolet absorber such as 2-ethylhexyl methoxycinnamate, or an antioxidant for removing free radicals generated by ultraviolet rays is known. However, the ultraviolet scattering agent and the ultraviolet absorber are effective for sun protection outdoors, but are not suitable for daily use. In addition, antioxidants have problems in terms of stability and safety. Further, only symptomatic drugs are known as therapeutic agents for skin damage caused by ultraviolet rays. Therefore, there is a need for the development of a stable and safe ultraviolet injury preventive and/or therapeutic agent that can be used on a daily basis, and a pharmaceutical, cosmetic and food containing the same.

Means for solving the problems

The present invention provides a composition for reducing ultraviolet ray damage, which comprises 1 or 2 or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine, and derivatives and/or salts thereof.

The composition for reducing ultraviolet ray damage of the present invention can be applied to a skin external preparation.

In the composition for reducing ultraviolet ray damage of the present invention, the external preparation for skin described above can be used as a cosmetic.

In the composition for reducing ultraviolet ray damage of the present invention, the cosmetic may be an anti-wrinkle agent.

In the composition for reducing ultraviolet ray damage of the present invention, the cosmetic may be a sunscreen agent.

In the composition for reducing ultraviolet ray damage of the present invention, the external preparation for skin described above can be used as a dermatological drug.

The aforementioned skin disease may be selected from the group consisting of erythema, solar dermatitis, chronic actinic dermatitis, actinic keratosis, actinic cheilitis, nodular elastosis, photosensitivity, light contact dermatitis, berrocco dermatitis, photosensitive drug eruption, polymorphous light eruption, vaccinia-like vesiculosis, solar urticaria, chronic photosensitive dermatitis, xeroderma pigmentosum, freckle, porphyria, pellagra, hart naprox disease, solar keratosis, dermatomyositis, lichen planus, follicular keratosis, pityriasis rubra pilaris, rosacea, atopic dermatitis, chloasma, herpes simplex, lupus erythematosus, squamous cell carcinoma, basal cell carcinoma and bower's disease.

In the composition for reducing ultraviolet ray damage of the present invention, the dermatological agent may be a therapeutic agent for dermatological use.

In the composition for reducing ultraviolet ray damage of the present invention, the drug for skin diseases may be a prophylactic agent for skin diseases.

The composition for reducing ultraviolet ray damage of the present invention can be used as food.

The composition for reducing ultraviolet ray damage of the present invention can be used as a medicine for cataract.

In the composition for reducing ultraviolet damage of the present invention, the drug for cataract may be a therapeutic agent for cataract or a prophylactic agent for cataract.

The composition for reducing ultraviolet ray damage of the present invention can be applied to eye drops.

The cataract may be senile cataract.

The present invention can provide a method for treating and/or preventing skin diseases caused by ultraviolet exposure, which comprises the step of administering a composition containing 1 or 2 or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, and L-cysteine and their derivatives and/or salts. The aforementioned skin disease may be selected from the group consisting of erythema, solar dermatitis, chronic actinic dermatitis, actinic keratosis, actinic cheilitis, nodular elastosis, photosensitivity, light contact dermatitis, berrocco dermatitis, photosensitive drug eruption, polymorphous light eruption, vaccinia-like vesiculosis, solar urticaria, chronic photosensitive dermatitis, xeroderma pigmentosum, freckle, porphyria, pellagra, hart naprox disease, solar keratosis, dermatomyositis, lichen planus, follicular keratosis, pityriasis rubra pilaris, rosacea, atopic dermatitis, chloasma, herpes simplex, lupus erythematosus, squamous cell carcinoma, basal cell carcinoma, and bower's disease.

The present invention can provide a method for improving the cosmetic condition of skin, comprising the step of administering a composition containing 1 or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine and their derivatives and/or salts. In the method for improving the cosmetic condition of the skin, the composition containing 1 or 2 or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, and L-cysteine, and derivatives and/or salts thereof may be a cosmetic composition or a food composition.

In the method for improving the cosmetic condition of the skin of the present invention, the improvement of the cosmetic condition of the skin may be, but is not limited to, wrinkle suppression and/or sunscreen.

The present invention provides a method for treating and/or preventing cataract, comprising the step of administering a composition containing 1 or more than 2 compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine and their derivatives and/or salts.

In the method for treating and/or preventing cataract according to the present invention, the drug for cataract may be an eye drop.

In the method for treating and/or preventing cataract of the present invention, the cataract may be senile cataract.

In the present specification, "salt" means: any salt including metal salts, amine salts and the like without impairing the effect of reducing ultraviolet ray damage by D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine. The aforementioned metal salt may include alkali metal salts, alkaline earth metal salts, and the like. The aforementioned amine salt may include triethylamine salt, benzylamine salt and the like.

In the present specification, "derivatives thereof" mean: and compounds in which D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, and L-cysteine, or amino groups thereof, or carboxyl groups thereof, or side chains thereof are covalently bonded to any atomic group, without impairing the effect of reducing ultraviolet ray damage to D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, and L-cysteine. The aforementioned arbitrary atomic groups include, but are not limited to, protecting groups such as N-phenylacetyl, 4' -Dimethoxytrityl (DMT), biomacromolecules such as proteins, peptides, sugars, lipids, nucleic acids, synthetic macromolecules such as polystyrene, polyethylene, polyvinyl compounds (polyvinyl), polyesters, and the like, and functional groups such as ester groups. The ester group may include, for example, an aliphatic ester such as a methyl ester or an ethyl ester, or an aromatic ester.

Among amino acids, there are the L-form and the D-form which are optical isomers, and natural proteins are proteins in which L-amino acids are bonded by peptide bonds, and only L-amino acids are used except for the cell wall of bacteria, and therefore, it is considered that only L-amino acids exist and only L-amino acids are used in mammals including humans. According to the above-mentioned publication (Gentianyinian, etc., proteinase, 50: 453-460(2005), レ - ニンジヤ, Siamese [ 2 nd version pp132-147(1993) Paita , ハ - パ -Prochem 22 version pp21-30 (1991)) and Wan, it has been known that it is industrially good, and only L-amino acid is mainly used as the amino acid.

Examples of D-amino acids that are used as exceptions include those used as a raw material for antibiotics that are produced by bacteria; and an example of a dietary supplement in which D-amino acid is directly used in the form of DL-amino acid mixture in order to save the cost of separating and extracting only L-amino acid from a mixture of L-amino acid and D-amino acid obtained in the same amount as when chemically synthesizing amino acid. However, there has been no example of using free D-amino acids or D-amino acids alone as physiologically active substances in the industry.

In recent years, it has been reported that D-serine and D-aspartic acid have physiological effects in humans, and it has been clarified that D-amino acids are present in mammals to exert physiological effects, and for example, it has been clarified that D-serine racemase is present in humans, but D-serine and L-serine, and D-aspartic acid and L-aspartic acid, which have been reported to have physiological effects in humans, show completely different physiological effects, and therefore it has been clarified that D-amino acids should be treated as substances different from L-amino acids, and conventionally known findings on amino acids are understood as findings on L-amino acids.

So far it is not known: as shown in the following examples, L-proline has no effect of reducing ultraviolet ray damage, while D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine have an effect of reducing ultraviolet ray damage. Therefore, the composition for reducing ultraviolet ray damage of the present invention containing 1 or 2 or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, L-cysteine and the like is a novel invention.

In recent years, it has been reported that, when ddY mice were allowed to freely take 10mM aqueous solution of D-amino acid for two weeks and then the concentration of D-amino acid in each organ was measured, the results were as follows: in the pineal body, the concentration of D-amino acid is 3 to 1000pmol relative to 1 pineal body as a secretion organ; in brain tissue, the D Amino acid concentration is 2-500nmol relative to 1 gram wet weight (Morikawa, A. et al, Amino Acids, 32: 13-20 (2007)). Based on this, the lower limit of the daily intake of L-glutamic acid or D-glutamic acid, D-proline, L-cysteine or D-cysteine contained in the composition of the present invention described below was calculated.

As shown in the following examples, L-glutamic acid and D-glutamic acid of the present invention have an effect of reducing ultraviolet ray damage to cultured human Keratinocytes (Keratinocytes) and fibroblasts in a concentration range of 0.1 to 100. mu.M as a single substance. Therefore, the amount of L-glutamic acid and/or D-glutamic acid contained in the composition of the present invention including the pharmaceutical composition, the anti-wrinkle agent and sunscreen agent, the cosmetic composition, and the food composition of the present invention may be any amount as long as the amount satisfies the condition that a single substance of L-glutamic acid and/or D-glutamic acid in the concentration range can be delivered to keratinocytes or fibroblasts of skin tissues of a living body. The content of L-glutamic acid and/or D-glutamic acid in the composition of the present invention as an external preparation may be in the range of 0.000015 to 10% by weight or the maximum weight concentration capable of being compounded in the total amount of the composition of the present invention. That is, when the composition is an external preparation, the content of L-glutamic acid and/or D-glutamic acid is preferably 0.00003 to 0.3 wt%, and most preferably 0.0003 to 0.03 wt%. When the composition of the present invention is an oral preparation, the content of L-glutamic acid and/or D-glutamic acid may be in the range of 0.00001 to 100% by weight. The content of L-glutamic acid and/or D-glutamic acid in the composition of the present invention is preferably 0.00002 to 80% by weight, and most preferably 0.0002 to 60% by weight, when the composition is administered orally. The lower limit of the daily intake amount of D-glutamic acid contained in the composition of the present invention may be 0.01ng, preferably 0.1ng, and more preferably 1ng per 1kg body weight. The lower limit of the daily intake amount of L-glutamic acid contained in the composition of the present invention is less than the amount of the clinical drug administered (80 mg or more per 1kg body weight), and may be 0.1mg, preferably 1mg, and more preferably 10mg per 1kg body weight.

As shown in the following examples, D-proline of the present invention has an effect of reducing ultraviolet ray damage to cultured human fibroblasts in a concentration range of 0.01 to 1 μ M as a single substance. Therefore, the amount of D-proline contained in the pharmaceutical composition, the anti-wrinkle agent and sunscreen agent, the cosmetic composition and the food composition of the present invention may be any amount as long as it satisfies the condition that a single substance of D-proline in the above concentration range can be delivered to fibroblasts of skin tissues of a living body. The content of D-proline in the case where the composition of the present invention is an external preparation may be in the range of 0.000015 wt% to 50 wt% or the maximum weight concentration that can be compounded in the total amount of the composition of the present invention. That is, when the composition is an external preparation, the content of D-proline is preferably 0.00003 to 30% by weight, and more preferably 0.0003 to 3% by weight. When the composition of the present invention is an oral preparation, the content of D-proline may be in the range of 0.00001 to 100% by weight. When the composition of the present invention is an oral preparation, the content of D-proline is preferably 0.00002 to 80% by weight, and most preferably 0.0002 to 60% by weight. The lower limit of the daily intake amount of D-proline contained in the composition of the present invention may be 0.01ng, preferably 0.1ng, and more preferably 1ng per 1kg body weight.

As shown in the following examples, L-cysteine and D-cysteine of the present invention have an effect of reducing ultraviolet ray damage to cultured human keratinocytes and fibroblasts in a concentration range of 0.1 to 100. mu.M as a single substance. Therefore, the amount of L-cysteine and/or D-cysteine contained in the composition of the present invention including the pharmaceutical composition, the anti-wrinkle agent and sunscreen agent, the cosmetic composition and the food composition of the present invention may be any amount as long as the amount satisfies the condition that a single substance of L-cysteine and/or D-cysteine at the concentration can be delivered to keratinocytes or fibroblasts of skin tissues of a living body. The content of L-cysteine and/or D-cysteine in the composition of the present invention as an external preparation may be in the range of 0.000015 to 10% by weight or the maximum weight concentration capable of being compounded in the total amount of the composition of the present invention. That is, when the composition is an external preparation, the content of L-cysteine and/or D-cysteine is preferably 0.00003 to 0.3% by weight, more preferably 0.0003 to 0.03% by weight. When the composition of the present invention is an oral preparation, the content of L-cysteine and/or D-cysteine may be in the range of 0.00001 to 100% by weight. The content of L-cysteine and/or D-cysteine in the composition of the present invention is preferably 0.00002 to 80% by weight, and most preferably 0.0002 to 60% by weight, when the composition is administered orally. The lower limit of the daily intake of D-cysteine contained in the composition of the present invention may be 0.01ng, preferably 0.1ng, more preferably 1ng per 1kg body weight. The lower limit of the daily intake of L-cysteine contained in the composition of the present invention is less than the amount of the clinical drug administered (3 mg or more per 1kg body weight), and may be 0.01mg, preferably 0.1mg, more preferably 1mg per 1kg body weight.

The pharmaceutical composition of the present invention contains a single substance selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine, d-glutamic acid, L-glutamic acid, D-proline, D-cysteine and salts of L-cysteine, 1 or 2 or more compounds selected from the group consisting of derivatives of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine, which are released in vivo by a drug metabolizing enzyme or the like, it is also possible to contain 1 or 2 or more pharmaceutically acceptable additives without impairing the effect of reducing the ultraviolet ray damage caused by D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine. The aforementioned additives include diluents and bulking agents, binders and binders, lubricants, glidants, plasticizers, disintegrants, carrier solvents, buffers, coloring materials, flavors, sweeteners, preservatives and stabilizers, adsorbents, and other pharmaceutical additives known to those skilled in the art, but are not limited thereto.

The anti-wrinkle agent and/or sunscreen agent of the present invention may be prepared using only a single substance of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, and L-cysteine, and a salt of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, and L-cysteine, and/or a derivative capable of releasing D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, and L-cysteine in vivo by a drug metabolizing enzyme, or the like, as an active ingredient, but other ingredients used in external preparations for skin such as cosmetics and drugs containing a quasi drug (quasi drug) may be appropriately blended as necessary within a range not impairing the effect of the present invention. Examples of the other components (optional components) include oils, surfactants, powders, coloring materials, water, alcohols, thickeners, chelating agents, silicones, antioxidants, ultraviolet absorbers, humectants, perfumes, various medicinal components, preservatives, pH regulators, and neutralizers.

The skin external preparation and cosmetic composition of the present invention may be used in any conventional skin external preparation and cosmetic composition, for example, ointment, cream, lotion, pack, bath agent, etc., and the dosage form thereof is not limited.

The cosmetic composition of the present invention may contain, as necessary, other components used in quasi-drug-containing cosmetics, external preparations for skin such as drugs, and the like, without impairing the effect of reducing ultraviolet ray damage by D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, and L-cysteine. Examples of the other components (optional components) include oils, surfactants, powders, coloring materials, water, alcohols, thickeners, chelating agents, silicones, antioxidants, ultraviolet absorbers, humectants, perfumes, various medicinal components, preservatives, pH regulators, and neutralizers.

The food composition of the present invention contains, in addition to a single substance of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine, a salt of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine and/or a derivative capable of releasing D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine in vivo by a drug metabolizing enzyme or the like, further, seasoning, coloring material, storage material and the like may be contained as components acceptable for food without impairing the effect of reducing the ultraviolet ray damage of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine.

The food composition of the present invention may be used in conventional food compositions such as soft drinks, gummy candies, candies (candy), and fruit drops, but is not limited to these examples.

Ultraviolet exposure is believed to be one of the causes of not only skin disorders but also eye disorders, particularly cataracts. It is known that prolonged exposure to ultraviolet light can cause clouding of the anterior cortex of the mouse lens, and in experiments, cataract models (Qianlidoume and reconia field, Crystal)An insert of biochemistryPage 318 & 323, Shu of Sedi, メデイカル Kuo published by Kung, imperial China (1986)). Further, it is considered that one of the causes of senile cataract is ultraviolet light (Tenong rich, "cataract eye MOOK NNo.17", 10 , Sanqian - ら, King, imperial publication, imperial Beijing (1982)), Zigman et al, according to an immunological investigation of Manila, tanpa and Rochester, show that the exposure to ultraviolet light is related to the incidence of cataract, and ultraviolet light is a risk factor of cataract (Zigman, S. et al, invest. Ophthalmol. visual Sci.18: 462-467 (1979)). Therefore, according to these findings and the examples below, D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine having an effect of reducing ultraviolet ray damage are effective for the prevention or treatment of cataract.

Drawings

FIG. 1 is a graph showing the effect of D-glutamic acid treatment on normal human epidermal keratinocytes.

FIG. 2 is a graph showing the effect of D-proline treatment after ultraviolet irradiation of normal human dermal fibroblasts.

FIG. 3 is a graph showing the effect of D-proline treatment on normal human dermal fibroblasts before ultraviolet irradiation.

FIG. 4 is a graph showing the effects of D-proline treatment and glutamic acid treatment before ultraviolet irradiation on normal human dermal fibroblasts.

FIG. 5 is a graph showing the effect of cysteine treatment on normal human epidermal keratinocytes.

FIG. 6 is a graph showing the effect of L-glutamic acid and D-glutamic acid treatment on XP cells.

FIG. 7 shows the effect of L-proline and D-proline treatment in XP cells.

FIG. 8 shows the effect of L-cysteine and D-cysteine treatment on XP cells.

Detailed Description

The examples of the present invention described below are for illustrative purposes only and do not limit the technical scope of the present invention. The technical scope of the present invention is limited only by the description of the patent claims.

Example 1

Ultraviolet ray damage reducing effect of D-glutamic acid

Cells

The cells were obtained from commercially available human neonatal epidermal keratinocytes (Cryo NHEK-Neo, Sanko pure drug). The above cells were expressed at 2X 10⁵Each/mL was seeded in a commercially available type I collagen-coated 35 mm-diameter petri dish (COL1, AGC TECHNOLASS CO., LTD.) and cultured using a commercially available serum-free medium (DefinedKeratinocyte-SFM, Gibco, hereinafter referred to as "common Medium 1"). The medium was changed every two days at 37 ℃ with 5% CO₂And culturing the cells under a saturated water vapor atmosphere for 5 to 7 days until the cells are fully confluent (confluent).

In order to examine the effect of the treatment in which glutamic acid was added before the irradiation with ultraviolet light (hereinafter referred to as "pretreatment"), the medium was replaced with a medium to which 0.1 to 100. mu.M of L-glutamic acid or D-glutamic acid was added before the irradiation for 24 hours.

Ultraviolet irradiation

The medium was replaced with PBS1mL prior to UV-B irradiation. UV-B irradiation was carried out as follows: using a self-made ultraviolet exposure apparatus (ultraviolet fluorescent lamp, Toshiba medical supplies TOREX FL20S-E-30/DMR, 2 roots), the cover of the culture dish was removed, and the thickness of the culture dish was set to 75J/cm from the upper part of the culture dish at 40cm²Irradiating ultraviolet rays of 280nm to 320 nm. The amount of ultraviolet light was measured using UV RADIOMETER UVR-3036/S (TOPCON, Inc.).

The cells treated with UV irradiation were returned to the normal medium 1 at 37 ℃ with 5% CO₂And culturing for 21 hours under a saturated steam atmosphere. In order to examine the effect of the treatment in which glutamic acid was added after ultraviolet irradiation (hereinafter referred to as "post-treatment"), 0.1 to 100. mu.M of L-glutamic acid or D-glutamic acid was added to the medium cultured for 21 hours.

Quantification of cellular damage

Thereafter, alamarBlue (trade name, Biosource, Biosource. International) was added to the medium so that the final concentration reached 10%, and 3 hours later, the fluorescence intensity of the supernatant was measured at an excitation wavelength of 544nm and a fluorescence wavelength of 590nm according to Ahmed S.A. et al (J.Immunol. method.170, 211-224(1994)) and the manufacturer's instructions.

Results

FIG. 1 shows the investigation of D-glutamic acid vs. UV-B75 mJ/cm²The effect of cell damage of keratinocytes due to ultraviolet irradiation was examined. Error bars for each experimental condition represent standard deviations of measured values of experimental results repeated 8 times under the same condition. Furthermore, the asterisks: (^**) This indicates that P was less than 1% under the Bonferroni test. In the case of UV non-irradiation, the fluorescence intensity of alamarBlue (trademark) was about 22000, and when the cells were damaged by UV-B irradiation, the fluorescence intensity was reduced to 5000 to 7000. However, when D-glutamic acid was added, the fluorescence intensity increased and cell damage decreased. The effect of reducing cell damage is not related to the D-glutamic acid treatment before or after UV irradiation, and the effect of reducing cell damage is also increased when the concentration of D-glutamic acid is increased. The effect of reducing cell damage was not observed by addition of L-glutamic acid (not shown). From the above results, it is clear that D-glutamic acid concentration-dependently reduces the cell damage of keratinocytes caused by UV-B.

Example 2

Ultraviolet ray injury reducing effect of D-proline

Cells

The cells used were commercially available human neonatal dermal fibroblasts (CryoNHDF-Neo, Sanko pure chemical). The foregoing description of the inventionCells were as per 2X 10⁵Each cell/mL was seeded on a commercially available 35 mm-diameter petri dish (BD FALCON 353001, Becton Dickinson, Japan) and cultured in a medium (hereinafter referred to as "general medium 2") prepared by adding 10% fetal bovine serum to a commercially available cell culture medium (D-MEM (1g/L glucose) and Wako pure chemical industries). At 37 deg.C, 5% CO₂And culturing the cells in a saturated steam atmosphere for about 24 hours.

Thereafter, the medium used for culturing the cells was changed to 1X 10 supplemented^-3% of BSO (L-buthionine- (S, R) -sulfoximine, Wako pure chemical industries, Ltd.) as a glutathione biosynthesis inhibitor in 1mL of BSO medium at 37 ℃ with 5% CO₂And culturing under a saturated steam atmosphere for about 24 hours. The aforementioned BSO medium was prepared as follows: the stock solution for preservation, in which 0.2% BSO was dissolved in ethanol, was diluted 200-fold with the aforementioned ordinary medium 2.

In order to examine the effect of the treatment with proline added before the irradiation with ultraviolet light (hereinafter referred to as "pretreatment"), the medium was changed to a medium to which 0.1. mu.M of L-proline or D-proline was added before the irradiation for 24 hours.

Culture medium for ultraviolet irradiation

Iron (II) chloride was added at 2X 10^-3% of the total amount of the components was dissolved in distilled water, and the solution was diluted 200-fold (final concentration: 1X 10) with phosphate buffer PBS (+) containing calcium ions and magnesium ions^-5%) was diluted to prepare a culture medium (hereinafter referred to as "medium for ultraviolet irradiation". ) Heated to 37 ℃ in advance and then used.

Ultraviolet irradiation

The medium was replaced with 1mL of the medium for ultraviolet irradiation before UV-A irradiation. UV-A irradiation was carried out as follows: using an ultraviolet uniform exposure apparatus UVE-502S + EL-160 (manufactured by Sanyon electric machine), 15J/cm was placed from above about 20cm of the dish with the lid of the dish removed²And 22.5J/cm²Irradiating ultraviolet rays of 320nm to 400 nm. UV RAD Using ultraviolet doseThe measurement was carried out using IOMETERUVR-3036/S (TOPCON, Co., Ltd.).

Treatment with addition of proline after UV irradiation

After the ultraviolet irradiation treatment, the medium was returned to the ordinary medium 2 and treated at 37 ℃ with 5% CO₂And culturing for 21 hours under a saturated steam atmosphere. In order to examine the effect of proline addition treatment after ultraviolet irradiation (hereinafter referred to as "post-treatment"), 0.01 to 1000. mu.M of L-proline or D-proline was added to the culture medium after 21 hours of culture.

Quantification of cellular damage upon post-treatment

Thereafter, the fluorescence intensity was measured by the method described in example 1.

Result of post-processing

FIG. 2 shows the D-proline pair consisting of UV-A15J/cm²And 22.5J/cm²The effect of damage of fibroblasts by ultraviolet irradiation in (2) was obtained. Error bars for each experimental condition represent standard deviations of measured values of experimental results repeated 4 times under the same condition. In addition, the asterisks: (^*) This represents a case where p is less than 5% under the Bonferroni test. In the case of non-UV irradiation, the fluorescence intensity of alamarBlue (trademark) was about 12000 as measured by UV-A15J/cm²When the irradiation of (2) causes cell damage, the fluorescence intensity is reduced to about 5000. In addition, UV-A22.5J/cm²When the irradiation of (2) causes cell damage, the fluorescence intensity is reduced to about 3000. However, when D-proline was added, the fluorescence intensity increased and cell damage decreased.

Table 1 shows the investigation of the ratio of L-proline and D-proline to UV-A12.5J/cm²And 15J/cm²The effect of damage of fibroblasts by ultraviolet irradiation in (2) was obtained. The error bars for each experimental condition represent the standard deviation of the measured values of the experimental results repeated 4 to 6 times under the same condition. Here, the asterisks: (^*)1 is the case where p is less than 0.1% compared to the control and 0.1% compared to L-proline under the Bonferroni test. In addition, theAsterisk (^*)2 represents the case where p is less than 0.1% compared with the control and less than 5% compared with L-proline under the Bonferroni test. In the case of non-UV irradiation, the fluorescence intensity of alamarBlue (trademark) was about 12000 as measured by UV-A12.5J/cm²And UV-A15J/cm²The fluorescence intensity is reduced to about 2500 a and about 1000 a when the irradiation of (b) causes cell damage. Cell damage was not substantially reduced by the addition of L-proline. However, when D-proline was added, the fluorescence intensity increased and cell damage decreased.

TABLE 1

Mean ± standard deviation; n-4-6^*1: p < 0.001 compared to control and P < 0.001 compared to L-proline

Bonferroni test^*2: p < 0.001 compared to control and P < 0.05 compared to L-proline

Quantification of cell damage during pretreatment

Cell damage was quantified by: cells were detached after 5 minutes of treatment with 0.25% trypsin-edta (gibco), centrifuged, washed, and then, life and death were confirmed by 0.2% trypan blue (GIB CO) staining for quantification.

Results of pretreatment

FIG. 3 shows the investigation of D-proline pair from 22.5J/cm²The effect of damage of fibroblasts by ultraviolet irradiation in (2) was obtained. Error bars for each experimental condition represent standard deviations of measured values of experimental results repeated 4 times under the same condition. In addition, the asterisks: (^**) This represents the case where p is less than 1% under the Bonferroni test.

In the case of non-UV irradiation, the viable cell rate was about 95%, measured by UV-A 22.5J/cm²When the irradiation of (2) causes cell damage, the viable cell rate is reduced to about 30%. However, when D-proline was added, the viable cell rate increased to about 50%, and cell death was reduced. From the above results, it was found that the effect of reducing cell damage was not related to the D-proline treatment before or after UV irradiation. Furthermore, D-proline concentration-dependently was shown to reduce the cell damage caused by UV-a of fibroblasts.

Example 3

Comparison of the effects of reducing ultraviolet ray damage by D-proline and D-glutamic acid

Method of producing a composite material

The cells were cultured in the same manner as described in example 2 using commercially available human neonatal dermal fibroblasts (CryoNHDF-Neo, san guan Chun Yao). To examine the effect of the treatment with D-proline or D-glutamic acid added before UV irradiation, the medium was changed to a medium supplemented with 0.1. mu.M of D-proline or 1. mu.M of L-glutamic acid or D-glutamic acid 24 hours before irradiation. The medium to which these amino acids were not added was directly irradiated with ultraviolet light as a control. UV-A ultraviolet irradiation (22.5J/cm)²) And quantification of cell damage using alamarBlue (trademark) were carried out in the same manner as described in example 2.

Results

FIG. 4 shows the investigation of the D-proline, L-glutamic acid or D-glutamic acid pair consisting of UV-A22.5J/cm²The effect of damage of fibroblasts by ultraviolet irradiation in (2) was obtained. Error bars for each experimental condition represent standard deviations of measured values of experimental results repeated 4 times under the same condition. In addition, the asterisks: (^**) This indicates that p is less than 1% under the Bonferroni/Dunn test.

The fluorescence intensity of the control was about 1100. The fluorescence intensity when D-proline, L-glutamic acid or D-glutamic acid was added was about 1750, about 1100 or about 1700. From the above results, it was shown that D-proline and D-glutamic acid statistically significantly reduced the cell damage caused by UV-A in normal human dermal fibroblasts. However, it is not seen that L-glutamic acid has a cell damage-reducing effect. In addition, it was shown that D-proline can reduce the UV damage at a concentration of 1/10 compared to D-glutamic acid.

Example 4

UV-ray damage reducing effect of L-cysteine and D-cysteine

Cells

The cells were obtained from commercially available human neonatal epidermal keratinocytes (Cryo NHEK-Neo, Sanko pure drug). The above cells were expressed at 1X 10⁵The individual/mL cells were sown into commercially available type I collagen-coated 35mm diameter petri dishes (COL1, AGC TECHNOGLASS co., LTD.). A commercially available serum-free medium (DefineedKeratinocyte-SFM, Gibco, hereinafter referred to as "Normal Medium 3") was supplemented with a proliferation additive (DefineedKeratinocyte-SFM growth, Gibco) and an antibiotic substance (PSF: penicillin, streptomycin, and amphotericin B (fungizone)) at 37 ℃ with 5% CO₂And culturing the cells in a saturated steam atmosphere for 3 days. Thereafter, 2mL of a common medium supplemented with 100. mu.M of D-alanine, D-serine, D-hydroxyproline, D-aspartic acid, D-cysteine or L-cysteine was cultured for 3 days. As a control, PBS was added to the ordinary medium 3 in place of the D-amino acid.

Ultraviolet irradiation

The medium was replaced with PBS1mL prior to UV-B irradiation. UV-B irradiation was carried out as follows: using a self-made ultraviolet exposure apparatus (ultraviolet fluorescent lamp, Toshiba medical supplies TOREX FL20S-E-30/DMR, 2 roots), 25J/cm was placed from above 40cm of the petri dish with the dish lid removed²Irradiating ultraviolet rays of 280nm to 320 nm. The amount of ultraviolet light was measured using UV RADIOMETER UVR-3036/S (TOPCON, Inc.).

900 μ L of normal plasmid supplemented with 100 μ M of D-alanine, D-serine, D-hydroxyproline, D-aspartic acid, D-cysteine or L-cysteine was usedMedium 3, 5% CO at 37 ℃₂And culturing the cells treated by the ultraviolet irradiation in a saturated water vapor atmosphere for 24 hours.

Quantification of cellular damage

Thereafter, the fluorescence intensity was measured by the method described in example 1.

Results

FIG. 5 shows the investigation of cysteine vs. UV-B25 mJ/cm²The effect of cell damage of keratinocytes due to ultraviolet irradiation was examined. Error bars for each experimental condition represent standard deviations of measured values of experimental results repeated 4 times under the same condition. Furthermore, the asterisks: (^**) This indicates that p is less than 1% under the t test of the student. The fluorescence intensity of alamarBlue (trademark) after cell damage by UV-B irradiation was about 570 in the case of D-alanine addition and about 550 in the case of no D-alanine addition. The fluorescence intensity was about 490 when D-serine was added and about 500 when D-serine was not added. The fluorescence intensity was about 550 when D-hydroxyproline was added, and about 550 when D-hydroxyproline was not added. The fluorescence intensity was about 600 in the case of adding D-aspartic acid, and about 600 in the case of not adding D-aspartic acid. The fluorescence intensity was about 700 when D-cysteine was added and about 600 when D-cysteine was not added. The fluorescence intensity was about 700 when L-cysteine was added and about 600 when L-cysteine was not added. From the above results, it was shown that both the L-and D-bodies of cysteine statistically significantly reduced cell damage.

Example 5

Effect of reducing ultraviolet ray damage in XP cell

Method of producing a composite material

Human dermal fibroblasts (XP30S (SVT), hereinafter referred to as "XP fine cells") derived from xeroderma pigmentosum (group A) patients obtained from the Japanese HEALTH science foundation (JAPAN HEALTH SCIENCESCIENCES FOUNDATION) were usedCells ". ) The culture was performed in the same manner as in example 3. Pretreatment of 0.1. mu.M of L-glutamic acid or D-glutamic acid, proline and cysteine and quantification of cell damage were carried out by the methods described in example 3. Furthermore, UV-a irradiation was carried out as follows: using an ultraviolet uniform exposure apparatus UVE-502S + EL-160 (manufactured by Sanyon electric machine), the cover of the dish was removed and the thickness of the dish was 1J/cm from the upper part of the dish about 20cm²Irradiating ultraviolet rays of 320nm to 400 nm. The amount of ultraviolet light was measured using UV RADIOMETERUVR-3036/S (TOPCON, Inc.).

Results of L-glutamic acid and D-glutamic acid

FIG. 6 shows the results of experiments to examine the effect of L-glutamic acid and D-glutamic acid on the damage of fibroblasts by ultraviolet irradiation. Error bars for each experimental condition represent standard deviations of measured values of experimental results repeated 2 times under the same condition.

The fluorescence intensity was about 690 under the condition of non-irradiation with ultraviolet rays and no addition of amino acids (hereinafter referred to as "ultraviolet non-irradiation condition"), and about 630 under the condition of irradiation with ultraviolet rays and no addition of amino acids (hereinafter referred to as "negative control"). The fluorescence intensity of the mixture added with 0.1. mu.M of L-glutamic acid or D-glutamic acid was about 658 or 675. From the above results, it was revealed that both L-glutamic acid and D-glutamic acid reduced UV-A induced cell damage of XP cells.

Results for L-proline and D-proline

FIG. 7 shows the results of experiments to examine the effect of L-proline and D-proline on the damage of fibroblasts by ultraviolet irradiation. Error bars for each experimental condition represent standard deviations of measured values of experimental results repeated 2 times under the same condition.

The fluorescence intensity was about 690 under the non-irradiation condition of ultraviolet rays and about 630 under the negative control. The fluorescence intensity when 0.1. mu.M of L-proline or D-proline was added was about 583 or about 664. From the above results, it was shown that D-proline reduced the cell damage caused by UV-A in XP cells.

Results for L-cysteine and D-cysteine

FIG. 8 shows the results of experiments to examine the effect of L-cysteine and D-cysteine on the damage of fibroblasts caused by UV irradiation. Error bars for each experimental condition represent standard deviations of measured values of experimental results repeated 2 times under the same condition.

The fluorescence intensity was about 690 under the non-irradiation condition of ultraviolet rays and about 630 under the negative control. The fluorescence intensity with the addition of 0.1. mu.M L-cysteine or D-cysteine was about 688 or about 638. From the above results, it was shown that both L-cysteine and D-cysteine reduced UV-A induced cell damage in XP cells.

Formulation examples of emulsion preparations, patches, tablets, soft capsules, granules, drinks, candies, biscuits, miso, french salad dressing, mayonnaise, french bread, soy sauce, yogurt, powdery food spread on rice, dressing of dressing natto, moromi vinegar, cream, body cream, gels, Peel-off mask (Peel-off mask), impregnated mask, emulsion, lotion, toner, and aerosol, which contain 1 or 2 or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, L-cysteine, and the like, according to the present invention, are shown below. These formulation examples are presented for illustrative purposes and are not intended to limit the scope of the present invention.

Formulation example 1 (emulsion preparation)

Formulation example 2 (Patch)

Formulation example 3 (tablet)

Formulation example 4 (tablet)

Formulation example 5 (Soft capsules)

Formulation example 6 (Soft capsules)

Formulation example 7 (granule)

Formulation example 8 (beverage)

Formulation example 9 (candy)

Formulation example 10 (biscuit)

Preparation method of formulation example 10 (biscuit)

Slowly adding granulated sugar while stirring butter, adding egg, spice and L-sodium glutamate or D-sodium glutamate, or D-proline, or L-cysteine or D-cysteine, and stirring. After mixing well, add the shaken whole low gluten flour, stir at low speed, put in a refrigerator in blocks. Then, the mixture was molded and baked at 170 ℃ for 15 minutes to make a biscuit.

Formulation example 11 (miso)

Preparation method of formulation example 11 (miso)

The rice koji and the salt are mixed well. Soaking cleaned semen glycines in 3 times of water overnight, removing water, adding new water, cooking, and sieving. Collecting the decoction (raw juice), and dissolving L-glutamic acid or D-glutamic acid, or D-proline, or L-cysteine or D-cysteine to make its concentration be 10% w/v. Immediately mashing the cooked beans, adding rice koji mixed with salt, and adding the raw juice dissolved with L-glutamic acid or D-glutamic acid, or D-proline, or L-cysteine or D-cysteine while uniformly mixing to have the hardness similar to that of clay. The kneaded dough was tightly packed into each corner of the tub without a gap, and after the surface was flattened, it was covered with a wrap and sealed. After 3 months, the container was replaced, the surface was leveled and covered with a wrap. In addition, instead of adding L-glutamic acid, D-proline, or L-cysteine or D-cysteine to the raw juice, rice koji which produces a large amount of L-glutamic acid, D-proline, or L-cysteine or D-cysteine may be used. In order to obtain the above-mentioned koji, L-glutamic acid or D-glutamic acid, D-proline, or L-cysteine or D-cysteine can be quantified and selected by the method described in Japanese patent application laid-open No. 2008-185558. Furthermore, D-glutamic acid, L-glutamic acid, D-proline, D-cysteine, L-cysteine, or a salt thereof may be added to commercially available miso.

Formulation example 12 (French salad dressing)

Preparation of formulation example 12 (French salad dressing)

Adding sodium chloride, and L-glutamic acid or D-glutamic acid, or D-proline, or L-cysteine or D-cysteine into vinegar, and stirring thoroughly to dissolve. Salad oil was added, stirred well and pepper was added.

Formulation example 13 (mayonnaise)

Preparation method of formulation example 13 (mayonnaise)

Vinegar, sodium chloride and pepper, and L-glutamic acid or D-glutamic acid, or D-proline, or L-cysteine or D-cysteine were added to egg yolk (room temperature), and thoroughly stirred with a whipper (whisper). Adding salad oil little by little while stirring to obtain emulsion. Finally adding granulated sugar and stirring.

Formulation example 14 (French bread)

Preparation method of formulation example 14 (French bread)

1g of granulated sugar and dry yeast were added to warm water to perform pre-fermentation. Placing strong flour, weak flour, sodium chloride, 5g granulated sugar, and L-sodium glutamate or D-sodium glutamate, or D-proline, or L-cysteine or D-cysteine into a bowl, and adding yeast after pre-fermentation. After kneading sufficiently, the mixture was formed into a spherical shape, and primary fermentation was carried out at 30 ℃. Kneading the material again, suspending, shaping to appropriate shape, and performing final fermentation with electronic fermentation machine. The mixture was placed in a cage and baked in an oven at 220 ℃ for 30 minutes.

Formulation example 15 (Soy sauce)

Formulation example 16 (Soy sauce)

Preparation of formulation examples 15 and 16 (Soy sauce)

Sodium L-glutamate or sodium D-glutamate, or D-proline, or L-cysteine or D-cysteine is added to commercially available soy sauce, and the mixture is sufficiently stirred. In addition, instead of adding sodium L-glutamate, sodium D-glutamate, or D-proline, or L-cysteine, D-cysteine, or a salt thereof, rice koji which produces a large amount of sodium L-glutamate, sodium D-glutamate, or D-proline, or L-cysteine or D-cysteine may be used to brew soy sauce. In order to obtain the above-mentioned koji, L-sodium glutamate or D-sodium glutamate, or D-proline, or L-cysteine or D-cysteine can be quantitatively determined by the method described in Japanese patent application laid-open No. 2008-185558 and selected. Further, D-sodium glutamate, L-sodium glutamate, D-proline, D-cysteine, L-cysteine, or salts thereof may be added to commercially available soy sauce.

Formulation example 17 (yogurt)

Preparation method of yogurt in formulation example 17

Fermenting at 40-45 deg.C. Other commercially available bacteria can be used, and sodium L-glutamate or sodium D-glutamate, or D-proline, or L-cysteine or D-cysteine can be added to commercially available yogurt. In addition, instead of adding L-sodium glutamate or D-sodium glutamate, or D-proline, or L-cysteine or D-cysteine or a salt thereof, bacteria that produce a large amount of L-sodium glutamate or D-sodium glutamate, or D-proline, or L-cysteine or D-cysteine may be used. In order to obtain the above-mentioned bacteria, L-sodium glutamate, D-proline, L-cysteine or D-cysteine can be quantitatively determined and selected by the method described in Japanese patent application laid-open No. 2008-185558. In addition, D-sodium glutamate, L-sodium glutamate, D-proline, D-cysteine or L-cysteine, or salts thereof may be added to commercially available yogurt.

Formulation example 18 (powdery food sprinkled on rice)

Formulation example 19 (seasoning Natto seasoning juice)

Formulation example 20 (seasoning, Natto sauce)

Formulation example 21 (Natto)

Preparation method of formulation example 21 (Natto)

Adding L-sodium glutamate or D-sodium glutamate, or D-proline, or L-cysteine or D-cysteine into commercially available natto, and stirring. Instead of adding sodium L-glutamate, sodium D-glutamate, D-proline, L-cysteine, D-cysteine or a salt thereof, a bacterium that produces a large amount of sodium L-glutamate, sodium D-glutamate, D-proline, L-cysteine or D-cysteine may be used to produce natto. In order to obtain the above-mentioned bacteria, L-sodium glutamate, D-proline, L-cysteine or D-cysteine can be quantitatively determined and selected by the method described in Japanese patent application laid-open No. 2008-185558. Further, D-sodium glutamate, L-sodium glutamate, D-proline, D-cysteine or L-cysteine, or salts thereof may be added to commercially available natto.

Formulation example 22 (fermented glutinous rice vinegar)

Formulation example 23 (fermented glutinous rice vinegar)

Preparation of formulation examples 22 and 23 (fermented glutinous Rice Vinegar)

L-glutamic acid or D-glutamic acid, or D-proline, or L-cysteine or D-cysteine is added to commercially available mash vinegar, and the mixture is sufficiently stirred. Instead of adding L-glutamic acid or D-glutamic acid, or D-proline, or L-cysteine or D-cysteine or a salt thereof, vinegar, black vinegar, and mash may be prepared using a bacterium that produces a large amount of L-glutamic acid or D-glutamic acid, or D-proline, or L-cysteine or D-cysteine. In order to obtain the above-mentioned bacteria, L-glutamic acid, D-proline, L-cysteine or D-cysteine can be quantitatively determined and selected by the method described in Japanese patent application laid-open No. 2008-185558. Further, D-glutamic acid, sodium L-glutamate, D-proline, D-cysteine, L-cysteine, or a salt thereof may be added to commercially available mash vinegar.

Formulation example 24 (cream)

Formulation example 25 (body cream)

Formulation example 26 (gel)

Formulation example 27 (Peel-off mask)

Formulation example 28 (impregnated mask)

Formulation example 29 (emulsion)

Formulation example 30 (emulsion)

Formulation example 31 (astringent)

Formulation example 32 (toner)

Formulation example 33 (stock solution of Aerosol Urea preparation for external use)

Formulation example 34 (Aerosol urea spray)

(composition) amount of composition (% by weight)

Aerosol urea external use agent stock solution 65.0

Dimethyl ether 35.0

100.00

Method for filling formulation example 34 (aerosol urea spray)

An aerosol was prepared by filling a stock solution of an aerosol urea external preparation and dimethyl ether in a pressure-resistant aerosol aluminum can whose inner surface was treated by coating with teflon (registered trademark).

Claims (13)

1. A composition for reducing ultraviolet ray damage, comprising 1 or 2 or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-proline, D-cysteine and L-cysteine, and derivatives and/or salts thereof.

2. The composition according to claim 1, characterized in that it is applied as a skin external preparation.

3. Composition according to claim 2, characterized in that it is used as a cosmetic.

4. Composition according to claim 3, characterized in that it is an anti-wrinkle agent.

5. Composition according to claim 3, characterized in that it is a sunscreen.

6. Composition according to claim 2, characterized in that it is used as a dermatological drug.

7. The composition of claim 6, wherein the skin disorder is selected from the group consisting of erythema, solar dermatitis, chronic actinic dermatitis, actinic keratosis, actinic cheilitis, nodular elastosis, photosensitivity, light contact dermatitis, berrock dermatitis, photosensitive drug eruptions, polymorphous light eruptions, vaccinia-like blistering disease, solar urticaria, chronic photosensitive dermatitis, xeroderma pigmentosum, freckles, porphyria, pellagra, hart napgenerally, solar keratosis, dermatomyositis, lichen planus, follicular keratosis, pityriasis rubra pilaris, rosacea, atopic dermatitis, chloasma, herpes simplex, lupus erythematosus, squamous cell carcinoma, basal cell carcinoma, and bower's disease.

8. The composition of claim 6 or 7, wherein the dermatological agent is a dermatological therapeutic agent.

9. The composition according to claim 6 or 7, wherein the dermatological agent is a prophylactic agent for dermatological use.

10. Composition according to claim 1, characterized in that it is used as a food product.

11. The composition according to claim 1, characterized in that it is used as a medicament for cataracts.

12. The composition according to claim 11, wherein the drug for cataract is a therapeutic agent for cataract or a prophylactic agent for cataract.

13. Composition according to claim 11 or 12, characterized in that it is applied as eye drops.