Composition for relieving ultraviolet injuries

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical and cosmetic industries and represents a composition for relieving an ultraviolet injury by post-irradiation administration of a composition containing one or more compounds specified in a group consisting of D-glutamic acid and/or its salts, and at least one acceptable additive.

EFFECT: invention provides effective relief of the ultraviolet skin injuries.

11 cl, 34 ex, 1 tbl, 8 dwg

 

The technical field to which the invention relates

The present invention relates to compositions for softening caused by ultraviolet radiation lesions, including one 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 method of facilitating caused by ultraviolet radiation skin diseases and improve the aesthetic condition of the skin, including the stage at which introduce one 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 method of treatment and/or prevention of cataract, including the stage at which impose the above connection.

The level of technology

Ultraviolet rays are classified into the ultraviolet rays of long wavelength range with a wavelength of more than about 320 nm (UV-A), medium-wave ultraviolet rays range from about 320 to about 280 nm (UV-B) and ultraviolet wavelength range with wavelengths shorter than about 280 nm (UV-C). Among them, UV-C radiation is not contained in the sunlight reaches the earth's surface, because it is absorbed by the ozone layer. Radiation UV-A is not absorbed by the ozone layer and is dominant in the ultra-violet rays, reaching the earth's surface. While the radiation of UV-B is partially absorbed by the ozone layer, it causes skin lesions in a dose comprising one-thousandth of the dose of radiation UV-A. Accordingly, are important as UV-a and UV-B, being the main factors of skin lesions. Non-patent document 1 discloses diseases which are caused by ultraviolet radiation, including the formation of wrinkles, erythema, pigmentary xeroderma, chronic actinic dermatitis, epidermoid carcinoma, basal cell carcinoma, malignant melanoma, Bowen's disease, solar keratosis, photodermatosis, light pox Bazin, photocontact dermatitis, whereas in non-patent document 2 provides examples of solar dermatitis, chronic actinic dermatopathy, actinic keratosis, actinic heylita syndrome favr-Rokusho, photodermatosis, photocontact dermatitis, breakover dermatitis, photosensitive drug rash, polymorphic light eruption, light pox Bazin, solar urticaria chronic photosensitive dermatitis, pigmented xeroderma, education freckles, porphyria, pellagra, a disease of Hartnup, solar keratosis, dermatomyositis, red flat lichen, disease Daria, red nails of pityriasis, rosacea, atopic derm is Titus, chloasma, subacute prurigo and lupus erythematosus.

The DOCUMENTS of the PRIOR art

Non-patent documents

Non-patent document 1: "HIHUSHIKKAN SAISHIN NO CHIRYO" ("the Latest methods of treatment of skin diseases"), 2005-2006 (Nankodo Co., Ltd.)

Non-patent document 2: "HYOJUN HIHUKAGAKU" ("General dermatology"), 7th edition (Igaku-Shoin Ltd.)

The INVENTION

The problem addressed by the invention

Known commonly used prophylactic and/or therapeutic agent for skin lesions caused by UV radiation, include a tool, a scattering of ultraviolet radiation, which inhibits the absorption of ultraviolet radiation by the skin, such as titanium oxide, UV absorbers, such as ethylhexyl-para-metaxalona acid, or an antioxidant that removes free radicals generated by UV radiation. However, the tool, the scattering of ultraviolet radiation, or UV absorbers are not used regularly every day, although it is effective outside to prevent sunburn. The antioxidant is problematic in terms of stability and reliability. In addition, a known therapeutic agent for due to ultraviolet radiation skin lesions limited is tsya only symptomatic therapeutic drugs. Accordingly, it is necessary to develop preventive and/or therapeutic agent for skin lesions caused by ultraviolet radiation, which can be used every day and which is stable and reliable, as well as pharmaceutical, cosmetic and food products containing it.

Part of the solution

The present invention is a composition for mitigating the destruction caused by ultraviolet radiation comprising one 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.

Composition to soften the lesions caused by UV radiation, according to the invention can be applied in the form of a composition for application to the skin.

In compositions to mitigate the destruction caused by ultraviolet radiation, according to the invention the above-described composition for application to the skin may be applied as a cosmetic product.

In the composition to soften the lesions caused by UV radiation, according to the invention described above, the cosmetic product may be a remedy against wrinkles.

In compositions to mitigate the destruction caused by ultraviolet radiation, the agreement is but the invention of the above-described cosmetic product can be a sunscreen.

In the composition to soften the lesions caused by UV radiation, according to the invention described above, the cosmetic product may be used as a pharmaceutical product for skin diseases.

The above skin disease may be selected from the group consisting of erythema, solar dermatitis, chronic actinic dermatopathy, actinic keratosis, actinic heylita syndrome favr-Rokusho, photodermatosis, photocontact dermatitis, breakover dermatitis, photosensitive drug rash, polymorphic light eruption, light pox Bazin, solar urticaria, chronic photosensitive dermatitis, pigmented xeroderma, education freckles, porphyria, pellagra, a disease of Hartnup, solar keratosis, dermatomyositis, red flat lichen, disease Daria, red nails of pityriasis, rosacea, atopic dermatitis, chloasma, subacute prurigo, systemic lupus, squamous cell cancer, basal cell carcinoma and disease Bowen.

In compositions to mitigate the destruction caused by ultraviolet radiation, according to the invention a pharmaceutical product for the above skin conditions can be a therapeutic agent for skin diseases.

In the composition for smahc is of lesions, caused by ultraviolet radiation, according to the invention a pharmaceutical product for the above skin conditions can be a preventive remedy for skin diseases.

Composition to mitigate the destruction caused by ultraviolet radiation, according to the invention can be used as food.

Composition to mitigate the destruction caused by ultraviolet radiation, according to the invention can be applied as a pharmaceutical product for cataract.

In compositions to mitigate the destruction caused by ultraviolet radiation, according to the invention a pharmaceutical product for the above cataract may be therapeutic or prophylactic agent for cataract.

Composition to mitigate the destruction caused by ultraviolet radiation, according to the invention can be applied in the form of eye drops.

Above the cataract can be an age-related cataracts.

The present invention can provide a method of treating and/or preventing skin diseases caused by exposure to ultraviolet radiation, including the stage at which impose a composition including one or more compounds selected from the group consisting of D-glutamic acid, L-glutaminovoi acid, D-Proline, D-cysteine and L-cysteine and their derivatives and/or salts. The above skin disease may be selected from the group consisting of erythema, solar dermatitis, chronic actinic dermatopathy, actinic keratosis, actinic heylita syndrome favr-Rokusho, photodermatosis, photocontact dermatitis, breakover dermatitis, photosensitive drug rash, polymorphic light eruption, light pox Bazin, solar urticaria, chronic photosensitive dermatitis, pigmented xeroderma, education freckles, porphyria, pellagra, a disease of Hartnup, senile keratosis, dermatomyositis, red flat lichen, disease Daria, red nails of pityriasis, rosacea, atopic dermatitis, chloasma, subacute prurigo, systemic lupus, squamous cell cancer, basal cell epithelioma and disease Bowen.

The present invention can provide a method for improving skin condition, including the stage at which impose a composition including one 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 described above to improve the aesthetic condition of the skin a composition comprising one or more compounds selected from the group status is the present of D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine and their derivatives and/or salts, may be a cosmetic composition and/or food composition.

The way to improve the aesthetic condition of the skin according to the invention the aesthetic improvement of the skin condition includes, but is not limited to such, the treatment against wrinkles and/or treatment for protection from the sun.

The present invention can provide a method of treatment and/or prevention of cataract, including the state in which the injected composition comprising one 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 of treatment and/or prevention of cataract according to the invention a pharmaceutical product for the above cataract may be in the form of eye drops.

In the method of treatment and/or prevention of cataract according to the invention described above, the cataract may be age-related cataract.

In the description, the term "salt" means any salt, including metal salt, ammonium salt and the like, provided that the mitigation effect caused by ultraviolet radiation lesions shown D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, reduced. Videoporn the I metal salt may include a salt of an alkali metal, salt, alkaline earth metal and the like. The above ammonium salt may include salt, triethylamine salt of benzylamine and the like.

The term "its derivative" means D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, each(initial) of which is covalently linked at its amino group, carboxyl group or the side chain of any Deputy, provided that there is no harmful effect on the mitigation effect caused by ultraviolet radiation lesions shown D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine. Any Deputy includes, but is not limited to such a protective group, such as N-phenylacetylene group, 4,4'-dimethoxytrityl (DMT) group, and the like, a biopolymer such as a protein, peptide, saccharide, lipid, nucleic acid, and the like, a synthetic polymer, such as polystyrene, polyethylene, polyvinyl, complex, polyester and the like, and a functional group, such as ester group and the like. The above ester group may include, for example, methyl ester, ethyl ester, other aliphatic ester or aromatic ester.

Because the amino acid can exist as an optical isomer, which is a L-the Orme or D-form, but natural protein has L-amino acids connected by peptide bonds and are used only L-amino acids, with a few exceptions such as the wall of bacterial cells, it was believed that in mammals, including humans, are present and are used only L-amino acids (Kinouchi, T. and others, TANPAKUSHITSU KAKUSAN KOSO (Proteins, nucleic acids and enzymes), 50: pp. 453-460 (2005), Lehninger Principles of Biochemistry [1], 2nd edition, pages 132-147 (1993), publisher Hirokawa Publishing Co., Harper's Biochemistry, Original version, 22nd edition, pages 21-30 (1991), Maruzen publishing Co., Ltd.). Accordingly, only L-amino acids for a long time was mostly used as the amino acids in research and in industry.

Exceptional case where it can be applied D-amino acid, for example, is the situation using as source material for antibiotic produced by a microorganism, and a food additive, in which the use of D-amino acid in the DL-mixture of amino acids, just to reduce costs fractionation emitting only L-amino acids from a mixture of L-amino acids and D-amino acids. However, it was not the case use free or undivided D-amino acids as such in the industry as bioactive substances.

Recently it was reported that D-serine and D-asparagine the traveler acid exhibit bioactivity and that even in the human body is D-surinaamse, and it was established that in mammals there is also a D-amino acid, where it shows the bioactivity. However, because there are different bioactivity for D-serine and L-serine, and D-aspartic acid and L-aspartic acid, the biological activity which is manifested in the human body, it is obvious that D-amino acid should be considered as a substance that differs from L-amino acids, and well-known scientific facts about amino acids should be understood as scientific information relating to L-amino acids.

As shown in the following examples, L-Proline does not show a cushioning effect against lesions caused by ultraviolet radiation, and any softening effect of D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine in relation induced by ultraviolet radiation lesion is generally unknown. Accordingly, the composition for softening lesions caused by ultraviolet radiation comprising one or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, according to the invention represents a new invention.

Recently it was reported that mice ddY opened access to 10 mm aqueous solution of D-am is necessaty for 2 weeks and then determined the concentration of D-amino acids in each organ, which ranged from 3 to 1000 pmol (picomoles) on the pituitary gland in the epiphysis and from 2 to 500 nmol per gram of wet brain tissue (Morikawa, A. and others, Amino Acids, vol 32: PP 13-20 (2007)). On this basis was calculated lower limit daily consumption of L - or D-glutamic acid, D-Proline, L - or D-cysteine contained in the composition according to the present invention.

As indicated in the following examples, L - and D-glutamic acid according to the present invention are, even when taken undivided, a softening effect on caused by ultraviolet radiation defeat at concentrations ranging from 0.1 to 100 μm, grown on human keratinocyte and fibroblast. Accordingly, the number of L - and/or D-glutamic acid contained in the composition according to the invention, including pharmaceutical composition according to the invention, the tool against wrinkles, sunscreen, cosmetic composition and a food composition may vary within a wide range, provided that L and/or D-glutamic acid as a whole is delivered in keratinocyte or fibroblast in skin tissue in vivo with a concentration in the above range. When the composition according to the invention is a composition for application to the skin, then the contents of the L - and/or D-glutamic acid may be varied within the range from 0,000015% for the Yeosu to 10% by weight of the total amount of the composition according to the invention or to the maximum concentration by weight, you can enter. Thus, when the composition according to the invention is a composition for application to the skin, then the contents of the L - and/or D-glutamic acid is preferably from 0.00003% by weight to 0.3% by weight, most preferably from 0.0003% by weight to 0.03% by weight. When the composition according to the invention is a composition for internal use, the content of L - and/or D-glutamic acid may range from 0.00001% by weight to 100% by weight. When the composition according to the invention is a composition for internal use, the content of L - and/or D-glutamic acid preferably ranges from 0.00002% by weight to 80% by weight, most preferably from 0.0002% by weight to 60% by weight. The lower limit of the daily dose of D-glutamic acid contained in the composition according to the invention, may be of 0.01 ng, preferably 0.1 ng, more preferably 1 ng per kg of body weight. The lower limit of the daily dose of L-glutamic acid contained in the composition according to the invention, is lower than the clinical dose of the medicinal product (80 mg or more per kg of body weight), and may be 0.1 mg, preferably 1 mg, more preferably 10 mg / kg of body weight.

As indicated in the following examples, D-Proline according to the invention manifests itself softening action is th at caused by ultraviolet radiation defeat at a concentration ranging from 0.01 to 1 μm, grown on human fibroblast. Accordingly, the number of D-Proline contained in the pharmaceutical compositions according to the invention, the tool against wrinkles, sun tool, cosmetic compositions and food compositions can vary within a wide range, provided that D-Proline is delivered to the fibroblast in the skin tissue in vivo with a concentration in the above range. When the composition according to the invention is a composition for application to the skin, then the contents of the D-Proline can vary in the range from 0,000015% by weight to 50% by weight of the total amount of the composition according to the invention, or to the maximum concentration by weight which you can enter. Thus, when the composition according to the invention is a composition for application to the skin, then the contents of the D-Proline is preferably from 0.00003% by weight to 30% by weight, most preferably from 0.0003% by weight to 3% by weight. When the composition according to the invention is a composition for internal use, the content of D-Proline may range from 0.00001% by weight to 100% by weight. When the composition according to the invention is a composition for internal use, the content of D-Proline, preferably ranges from 0.00002% by weight to 80% by weight, most preferred is sustained fashion from 0.0002% by weight to 60% by weight. The lower limit of the daily dose of D-Proline contained in the composition according to the invention, may be of 0.01 ng, preferably 0.1 ng, more preferably 1 ng per kg of body weight.

As indicated in the following examples, L - and D-cysteine according to the invention are, even if taken as a separate matter, a softening effect on caused by ultraviolet radiation defeat at concentrations ranging from 0.1 to 100 μm, grown on human keratinocyte and fibroblast. Accordingly, the number of L - and/or D-cysteine contained in the relevant invention compositions, including pharmaceutical compositions, the tool against wrinkles, sunscreen, cosmetic composition and a food composition may vary within a wide range, provided that L and/or D-cysteine is delivered to keratinocyte or fibroblast in skin tissue in vivo with a concentration in the above range. When the composition according to the invention is a composition for application to the skin, then the contents of the L - and/or D-cysteine can vary in the range from 0,000015% by weight to 10% by weight of the total amount of the composition according to the invention or to the maximum concentration by weight which you can enter. Thus, when the composition according to the invention is a composition for caused the deposits on the skin, then the contents of the L - and/or D-cysteine is preferably from 0.00003% by weight to 0.3% by weight, most preferably from 0.0003% by weight to 0.03% by weight. When the composition according to the invention is a composition for internal use, the content of L - and/or D-cysteine can range from 0.00001% by weight to 100% by weight. When the composition according to the invention is a composition for internal use, the content of L - and/or D-cysteine preferably ranges from 0.00002% by weight to 80% by weight, most preferably from 0.0002% by weight to 60% by weight. The lower limit of the daily dose of D-cysteine contained in the composition according to the invention, may be of 0.01 ng, preferably 0.1 ng, more preferably 1 ng per kg of body weight. The lower limit of the daily dose of L-cysteine contained in the composition according to the invention, is lower than the clinical dose of a drug (3 mg or more per kg of body weight), and may be 0.01 mg, preferably 0.1 mg, more preferably 1 mg per kg of body weight.

The pharmaceutical composition according to the invention may optionally include, in addition to one or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, each as a separate substances, salts of D-glutamic key is lots L-glutamic acid, D-Proline, D-cysteine and L-cysteine, and derivatives can undergo in vivo effects of metabolizing enzymes and the like, with the release in the D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, at least one pharmaceutically acceptable additive, provided that the softening effect caused by ultraviolet radiation lesion shown D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, not reduced. Such an additive includes, but is not limited to such, diluent, filler, binder, adhesive, lubricant means, control flowability, plasticizer, dezintegriruetsja tool, the solvent-carrier, buffer agent, a coloring additive, flavoring additive, sweetener, preservative, stabilizer, adsorbent, as well as other pharmaceutical additives known qualified specialists in this field of technology.

The remedy for wrinkles and/or sunscreen according to the invention can be prepared using D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, each as a separate substances, salts of D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, and derivatives, which can undergo in vivo effects of metabolizing enzymes and the like, with the release in the D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine. However, other components used in compositions for application to the skin, such as cosmetic and pharmaceutical products, including quatercentennial drugs can be properly introduced, if required, to such an extent that the effect of the invention is not reduced. Such other components (optional input components include, for example, oils, surfactants, detergents, coloring additives, water, alcohols, thickeners, chelating agents, silicones, antioxidants, UV absorbers of radiation, humidifiers, scented additives, a variety of pharmaceutically active ingredients, preservatives, regulators of pH, neutralizing reagents.

Composition for application to the skin and the cosmetic composition according to the present invention can be any of those which are traditionally used in the composition for application to skin and cosmetic compositions, such as ointment, cream, emulsion, lotion, pad, bath salt and the like, and their dosage forms are not particularly specified.

Cosmetic composition according to the present invention may appropriately contain other components used in the grease compositions for the skin, such as cosmetic and pharmaceutical products, including quatercentennial drugs, provided that the softening effect on the lesions caused by UV radiation, shown D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, is not reduced. Such other components (optional input components include, for example, oils, surfactants, detergents, coloring additives, water, alcohols, thickeners, chelating agents, silicones, antioxidants, UV absorbers of radiation, humidifiers, scented additives, a variety of pharmaceutically active ingredients, preservatives, regulators of pH, neutralizing reagents.

The food composition according to the present invention may optionally include, in addition to D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, as a separate matter, salts of D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, and/or derivatives can undergo in vivo effects of metabolizing enzymes and the like, thereby freeing up D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine acceptable to the food industry component, such as flavoring, coloring additive, preservative, provided that the softening effect on the defeat, caused by ultraviolet radiation, shown D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, is not reduced.

The food composition according to the present invention can be any of those which are traditionally used in food compositions, such as drink, chewing candy, Lollipop, tablet, which is not limited.

As is, the ultraviolet radiation causes not only a skin disease, but also eye disease such as cataract. As reported, prolonged exposure to ultraviolet radiation in mice causes opacification of the anterior layer of the lens, thereby causing the obtained experimental cataract model (Maeda, T., and Iwata, S., “SUISHOTAI SONO SEIKAGAKUTEKI KIKO” (“Lenses, their biochemical mechanisms”), pages 318-323, edited by Iwata, S., Medical publishing house-Aoi Publishings, Inc., Tokyo (1986)). In addition, ultraviolet radiation is referred to as one of the causes of age-related cataracts (Fujinaga, Y., “HAKUNAISHO (cataract), GANKA (ophthalmology) MOOK No. 17”, page 10, edited by Mishima and others, publishing Kanehara & Co., Ltd., Tokyo (1982)), and the authors Zigman et al conducted epidemiological surveillance in Manila, Tampa and Rochester, and reported that there is a correlation between the amount of UV exposure and the incidence of cataracts, and ultrafioletoviy rays are a risk factor for cataract (Zigman, S. and others, Invest. Ophthalmol. Visual Sci., volume 18: pages 462-467 (1979)). Accordingly, these scientific facts, in conjunction with the following examples suggest that D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine, exhibiting a softening effect on caused by ultraviolet radiation defeat, are effective for prophylaxis or treatment of cataract.

BRIEF DESCRIPTION of DRAWINGS

Figure 1 is a graph showing the effect of D-glutamic acid in normal human epidermal keratinocytes.

Figure 2 is a graph showing the effect of treatment D-Proline after ultraviolet irradiation in normal human dermal fibroblasts.

Figure 3 is a graph showing the effect of treatment D-Proline to ultraviolet irradiation in normal human dermal fibroblasts.

Figure 4 is a graph showing the effect of treatment D-Proline and glutamic acid to ultraviolet irradiation in normal human dermal fibroblasts.

Figure 5 is a graph showing the effect of treatment with cysteine in normal human epidermal keratinocytes.

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

Fig.7 is gr the FIC, showing the effect of L - and D-Proline in XP cells.

Fig is a graph showing the effect of L - and D-cysteine in XP cells.

Embodiments of the INVENTION

Examples of the present invention, described below, are designed only to illustrate the invention and not to limit its scope. Scope of the invention is limited only by the description in the patent equation.

Example 1

Softening effect of D-glutamic acid caused by ultraviolet radiation defeat

Cell culture

Used cell culture represented commercially available on the market human neonatal epidermal keratinocyte (Cryo NHEK-Neo, the company Sanko-Junyaku Co., Ltd.). This cell culture was inoculable at a concentration of 2×105cells/ml in commercially available on the market Cup for cultivation with a diameter of 35 mm, coated with collagen type I (COL1, firm Asahi Techno Glass Co., Ltd.), where it was grown commercially available on the market serum-free nutrient medium (Defined Keratinocyte-SFM, Gibco., hereinafter referred to as "ordinary environment 1"). This cell culture was cultured for 5 to 7 days in the containing 5% CO2and saturated water vapor atmosphere at a temperature of 37°C prior to the merger, while replacing the culture medium every 2 days.

To identify the effect is from the addition of glutamic acid to UV-irradiation (hereinafter referred to as "pre-processing") a nutrient medium for the culture for 24 hours before irradiation was replaced on Wednesday, supplemented with L - or D-glutamic acid in a concentration of from 0.1 to 100 microns.

UV-irradiation

Before UV irradiation nutrient medium for the culture was replaced with 1 ml of PBS (phosphate-saline buffer). UV-irradiation was performed using a homemade device for UV exposure (two UV lamp Toshiba Medical Supply Corporation, TOREX FL20S-E-30/DMR) under irradiation of UV-rays with a wavelength of from 280 to 320 nm) at the dose of 75 j/cm2from a distance of 40 cm above the Cup with the culture in the state where the cover with the appropriate cups with culture was removed. The dose of UV irradiation was measured using a UV RADIOMETER UVR-3036/S (firm Topcon Corporation).

Cell culture, irradiated thus UV rays, returned to the ordinary environment 1, where it is cultivated in the containing 5% CO2and saturated water vapor atmosphere at 37°C for 21 hours. To identify the effect of adding glutamic acid after UV-irradiation (hereinafter referred to as "post-treatment") this 21-hour culture medium was added L - or D-glutamic acid in a concentration of from 0.1 to 100 microns.

Quantitative assessment of lesion cell culture

After this nutrient medium for the culture was supplemented with dye Alamar Blue (trade mark firm Biosource International Inc.) to a final concentration of 10%, and the supernatant was tested for online is newest fluorescence after 3 hours at excitation radiation with a wavelength of 544 nm and the wavelength of fluorescence 590 nm, as described by the authors Ahmed S.A. and others (J. Immunol. Method., volume 170, pages 211-224 (1994)) and in accordance with the manufacturer's instructions.

Results

Figure 1 shows the results of experimental studies on the action of D-glutamic acid on the defeat of cell culture in keratinocytes induced by ultraviolet irradiation with UV-In at the dose of 75 MJ/cm2. Confidence intervals for the respective experimental conditions represent the standard deviation of the measured values for the results of the experiments, repeated eight times in identical conditions. The asterisk (**) denotes P<1% in the test of Bonferroni. The fluorescence intensity of the dye Alamar Blue (trade mark) in the absence of UV irradiation was about 22000, which decreased to a value of from 5000 to 7000, when due to UV-b irradiation was defeated cell culture. However, when I added D-glutamic acid, the fluorescence intensity increased and the defeat of cell culture was softened. While this effect mitigation destruction of the cell culture was observed regardless of the processing time D-glutamic acid, which was carried out before or after UV irradiation, a higher concentration of D-glutamic acid resulted in a more pronounced softening effect. No mitigating action is La destruction of cell culture were observed, when added L-glutamic acid (data not shown). Judging from the above results, D-glutamic acid softens caused by UV-a radiation lesion in keratinocytes in a concentration-dependent mode.

Example 2

Softening effect D-Proline caused by ultraviolet radiation defeat

Cell culture

Used cell culture represented commercially available on the market human neonatal dermal fibroblast (Cryo NHDF-Neo, the company Sanko-Junyaku Co., Ltd.). This cell culture was inoculable at a concentration of 2×105cells/ml in commercially available on the market Cup for cultivation with a diameter of 35 mm (BD FALCON 353001, Beckton Dickinson Japan), where it was grown commercially available on the market culture medium (D-MEM (1 g/ml glucose, the company Wako Pure Chemical Industries, Ltd.)), supplemented with 10% calf serum (hereinafter referred to as "ordinary environment 2"). This cell culture was grown for approximately 24 hours in a containing 5% CO2and saturated water vapor atmosphere at 37°C.

After that, the above-described nutrient medium for cultivation of the cells was replaced with 1 ml of medium BSO containing inhibitor of glutathione biosynthesis BSO (L-buthionine-(S,R)-sulfoximine, Wako Pure Chemical Industries, Ltd.) at a concentration of 1×10-3%where cultivation was carried out in the course the e about 24 hours containing 5% CO 2and saturated water vapor atmosphere at 37°C. the Above-described environment BSO was used to 200-fold dilution of the stock solution containing 0.2% BSO in ethyl alcohol, above the ordinary environment 2.

To identify the effect of the addition of Proline to UV-irradiation (hereinafter referred to as "pre-processing"), a nutrient culture medium for 24 hours before irradiation was replaced with medium supplemented with L - or D-Proline at a concentration of 0.1 ám.

Environment for UV exposure

In distilled water was dissolved chloride, iron(II) to a concentration of 2×10-3%, and the resulting solution was subjected to 200-fold dilution (to final concentration: 1×10-5%) phosphate buffer solution PBS containing calcium ions and magnesium ions (PBS+) to get the environment (hereinafter referred to as the "environment for UV-irradiation"), which was pre-heated before use.

UV-irradiation

Before UV-A-irradiation nutrient medium for the culture was replaced with 1 ml of the above medium for UV exposure. UV-A-irradiation was performed using a device for exhibiting a uniform UV light UVE-502S+EL-160 (SAN-EI ELECTRIC) under irradiation of UV-rays with a wavelength of from 320 to 400 nm at a total dose of 15 j/cm2and 22.5 j/cm2from a distance of about 20 cm above the Cup with the culture in the state where the cover according to the respective cups with culture was removed. The dose of UV irradiation was measured using a UV RADIOMETER UVR-3036/S (firm Topcon Corporation).

Treatment with Proline after UV-irradiation

After UV irradiation of the cell culture was returned to the above-described ordinary environment 2, where it is cultivated in the containing 5% CO2and saturated water vapor atmosphere at 37°C for 21 hours. To identify the effect of adding Proline after UV-irradiation (hereinafter referred to as "post-treatment") this 21-hour culture medium was supplemented with L - or D-Proline at a concentration of from 0.01 to 1000 μm.

Quantitative assessment of lesion cell culture in post-processing

Then measured the fluorescence intensity by the method described in example 1.

The results of subsequent processing

Figure 2 shows the results of experimental studies on the action of D-Proline to defeat cell culture fibroblasts caused by ultraviolet irradiation with UV-A at doses of 15 j/cm2and 22.5 j/cm2. Confidence intervals for the respective experimental conditions represent the standard deviation of the measured values for the results of the experiments repeated four times under identical conditions. The asterisk (*) indicates P<5% in test Bonferroni. The intensity of fluorescence color is La Alamar Blue (trade mark) in the absence of UV irradiation was about 12000, which was decreased to a value of about 5000, when the defeat of the cell cultures was due to UV-A-irradiation with a dose of 15 j/cm2. It also has about 3,000, where the defeat of cell cultures was due to UV-A-irradiation with a dose of 22.5 j/cm2. However, when I added D-Proline, the fluorescence intensity increased and the defeat of cell culture was softened.

Table 1 shows the results of experimental studies on the action of L - and D-Proline to defeat cell culture fibroblasts caused by ultraviolet irradiation with UV-A at doses of 12.5 j/cm2and 15 j/cm2. Confidence intervals for the respective experimental conditions represent the standard deviation of the measured values for the results of the experiments repeated four to six times in identical conditions. The asterisk (*)1, shown here, indicates p<0,1%, when compared with control, p=0.1%, when compared with L-Proline in the test of Bonferroni. The asterisk (*)2, shown here, indicates p<0,1%, when compared with control, p<5%, when compared with L-Proline in the test of Bonferroni. The fluorescence intensity of the dye Alamar Blue (trade mark) in the absence of UV irradiation was about 12000, which decreased up to about 2500 and about 1000 when struck by the e cell cultures was due to UV-A-irradiation with a dose of 12.5 j/cm 2and UV-A-irradiation with a dose of 15 j/cm2respectively. Almost no mitigation defeat cell culture is not marked, when it was added L-Proline. However, when I added D-Proline, the fluorescence intensity increased and the defeat of cell culture was softened.

Table 1
The dose of UV irradiation (j/cm2)ControlThe intensity of fluorescence with D-Proline (0.1 ám)L-Proline (0.1 ám)
012380±2112270±6812211±77
12,52503±6294615±1218*12877±834
151018±892365±548*21552±320
Mean ± standard deviation; N=4-6 test Bonferroni*1:relative to control, P<0,001,
with respect to L-Proline P<0,001/td>
*2:relative to control, P<0,001,
with respect to L-Proline P<0,05

Quantitative assessment of lesion of cell culture in the pre-treatment

Defeat cell culture quantify the separation of the cells by treatment with 0.25%solution of trypsin-EDTA, Gibco) for 5 minutes followed by centrifugation and washing, after which staining was performed with 0.2%Trifanova blue (firm Gibco) to confirm the viability or death.

The results of the preliminary processing

Figure 3 shows the results of experimental studies on the action of D-Proline to defeat cell culture fibroblasts caused by ultraviolet irradiation at a dose of 22.5 j/cm2. Confidence intervals for the respective experimental conditions represent the standard deviation of the measured values for the results of the experiments repeated four times under identical conditions. The asterisk (**) denotes p<1% in the test of Bonferroni.

The percentage of viable cells in the absence of UV irradiation was about 95%, which decreased to about 30%, when happens what about the defeat of the cells due to UV-A-irradiation with a dose of 22.5 j/cm 2. However, when I added D-Proline, the percentage of viable cells increased to about 50% cell death was reduced. Based on the above results, it was shown that the effect of mitigating the damage of cells is not dependent on the processing time D-Proline, i.e. before or after UV irradiation. It was also shown that D-Proline softens caused by UV-A-radiation damage cells in fibroblasts in a concentration-dependent mode.

Example 3

Comparison of the softening effect caused by ultraviolet radiation lesion between D-Proline and D-glutamic acid

Methods

Used cell culture represented commercially available on the market human neonatal dermal fibroblast (Cryo NHDF-Neo, the company Sanko-Junyaku Co., Ltd.), which were grown in the same manner as described in example 2. To identify the effect of adding D-Proline or D-glutamic acid to UV irradiation, the culture medium 24 hours before irradiation was replaced with medium supplemented with 0.1 μm D-Proline or 1 μm L - or D-glutamic acid. UV-irradiation environment without these amino acids was used as a control. UV-A-irradiation (at a dose of 22.5 j/cm2and quantitative assessment of lesion cells using the dye Alamar Blue (trade mark) was performed by the method described in example 2.

Results

Figure 4 shows the results of experimental studies on the action of D-Proline and L - or D-glutamic acid on the defeat of cell culture fibroblasts caused by UV-A-irradiation at a dose of 22.5 j/cm2. Confidence intervals for the respective experimental conditions represent the standard deviation of the measured values for the results of the experiments repeated four times under identical conditions. The asterisk (**) denotes p<1% in the test of Bonferroni/Dunn.

The fluorescence intensity was about 1100 in control. The values of fluorescence intensity in the presence of D-Proline, L - or D-glutamic acid were about 1750, about 1100 or 1700 respectively. On the basis of these results, it was shown that D-Proline and D-glutamic acid soften due to UV-A-irradiation defeat of normal human dermal fibroblasts with statistical significance. However, no moderating effect of lesion cells were observed with L-glutamic acid. It was shown that D-Proline softens caused by UV-irradiation damage cells at concentrations constituting one-tenth in comparison with D-glutamic acid.

Example 4

Mitigating the effects of L - and D-cysteine to defeat caused by ultraviolet radiation

Cell culture

Used cell culture represented commercially available on the market human neonatal epidermal keratinocyte (Cryo NHEK-Neo, the company Sanko-Junyaku Co., Ltd.). This cell culture was inoculable at a concentration of 1×105cells/ml in commercially available on the market Cup for cultivation with a diameter of 35 mm, coated with collagen type I (COL1, firm Asahi Techno Glass Co., Ltd.). This cell culture was grown commercially available on the market serum-free nutrient medium (Defined Keratinocyte-SFM, Gibco., hereinafter referred to as "ordinary environment 3"), supplemented by proliferation (growth Supplement Defined Keratinocyte-SFM Growth Supplement, the company Gibco) and antibiotics (PSF: penicillin, streptomycin and Fungizone) for 3 days in a containing 5% CO2and saturated water vapor atmosphere at 37°C. After that it was grown for 2 days in 2 ml of the ordinary medium 3 containing 100 mm D-alanine, D-serine, D-hydroxyproline, D-aspartic acid, D-cysteine or L-cysteine. As a control, to the ordinary environment 3 was added ordinary Wednesday 3 containing PBS instead of D-amino acids.

UV-irradiation

Before UV-b-irradiated culture medium was replaced with 1 ml of PBS (phosphate-saline buffer). UV-irradiation was performed using a homemade device for UV exposure (two UV lamp Toshiba Medical Supply Corporation, TOREX FL20S-E-30/DMR) and the irradiation of UV-rays with a wavelength of from 280 to 320 nm) at the dose of 25 j/cm 2from a distance of 40 cm above the Cup with the culture in the state where the cover with the appropriate cups with culture was removed. The dose of UV irradiation was measured using a UV RADIOMETER UVR-3036/S (firm Topcon Corporation).

Cell culture, irradiated with UV rays, were cultured in 900 ál of the ordinary medium 3 containing 100 mm D-alanine, D-serine, D-hydroxyproline, D-aspartic acid, D-cysteine or L-cysteine, containing 5% CO2and saturated water vapor atmosphere at 37°C for 24 hours.

Quantitative assessment of lesion cell culture

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

Results

Figure 5 shows the results of experimental studies on the action of cysteine to defeat cell culture in keratinocytes induced by ultraviolet irradiation with UV-In at the dose of 25 MJ/cm2. Confidence intervals for the respective experimental conditions represent the standard deviation of the measured values for the results of the experiments repeated four times under identical conditions. The asterisk (**) denotes p<1% in the test t-test. The fluorescence intensity of the dye Alamar Blue (trade mark) after the occurrence of damage of cells due to UV-b irradiation was about 570 in the presence of D-al is Nina and was about 550 in the absence of D-alanine. The intensity of fluorescence in the presence of D-serine was about 490, whereas the fluorescence intensity in the absence of D-serine was about 500. The intensity of fluorescence in the presence of D-hydroxyproline was about 550, while the fluorescence intensity in the absence of D-hydroxyproline was about 550. The intensity of fluorescence in the presence of D-aspartic acid was about 600, while the fluorescence intensity in the absence of D-aspartic acid was about 600. The intensity of fluorescence in the presence of D-cysteine was about 700, while the fluorescence intensity in the absence of D-cysteine was about 600. The intensity of fluorescence in the presence of L-cysteine was about 700, while the fluorescence intensity in the absence of L-cysteine was about 600. On the basis of these results, it was shown that cysteine, in both L-form and D-form, softens the defeat of cells with statistical significance.

Example 5

A softening effect on caused by ultraviolet radiation lesion in XP-a cells

Methods

Human dermal fibroblast taken from a patient suffering from pigment xeroderma (group a) (XP30S (SVT), hereafter referred to as "XP-cell"), which was reported by the Japan Health Science Foundation, used and cultivated in the same way that the AK is described in example 3. Pre-treatment with 0.1 μm of L - or D-glutamic acid, Proline and cysteine and quantitative assessment of lesion cells were conducted according to the methods described in example 3. UV-A-irradiation was performed using a device for exhibiting a uniform UV light UVE-502S+EL-160 (SAN-EI ELECTRIC) under irradiation of UV-rays with a wavelength of from 320 to 400 nm at the dose of 1 j/cm2from a distance of about 20 cm above the Cup with the culture in the state where the cover with the appropriate cups with culture was removed. The dose of UV irradiation was measured using a UV RADIOMETER UVR-3036/S (firm Topcon Corporation).

The results with L - and D-glutamic acid

Fig.6 shows the results of experimental studies on the action of L - or D-glutamic acid to defeat cells in fibroblasts due to UV-irradiation. Confidence intervals for the respective experimental conditions represent the standard deviation of the measured values for the results of the experiments repeated twice in identical conditions.

The fluorescence intensity was about 690 in conditions without UV irradiation in the absence of amino acids (hereinafter referred to as "condition without UV irradiation) and was about 630 in conditions with UV irradiation in the absence of amino acids (hereinafter referred to as "negative control"). The intensity f is uorescence in the presence of 0.1 mm L - or D-glutamic acid was about 658 or about 675 respectively. On the basis of these results, it was shown that both L - and D-glutamic acid soften caused by UV-A-irradiation damage cells in XP cells.

The results with L - and D-Proline

Fig.7 shows the results of experimental studies on the action of L - or D-Proline to defeat cells in fibroblasts induced by UV-irradiation. Confidence intervals for the respective experimental conditions represent the standard deviation of the measured values for the results of the experiments repeated twice in identical conditions.

The fluorescence intensity was about 690 in the condition without UV irradiation and was about 630 in the negative control. The intensity of fluorescence in the presence of 0.1 mm L - or D-Proline was about 583 or about 664 respectively. On the basis of these results, it was shown that D-Proline softens caused by UV-A-irradiation damage cells in XP cells.

The results with L - and D-cysteine

Fig shows the results of experimental studies on the action of L - or D-cysteine to defeat cells in fibroblasts due to UV-irradiation. Confidence intervals for the respective experimental conditions represent the standard deviation of the measured values for the results of the experiments repeated twice in identically the x terms.

The fluorescence intensity was about 690 in the condition without UV irradiation and was about 630 in the negative control. The intensity of fluorescence in the presence of 0.1 mm L - or D-cysteine was about 688 or about 638 respectively. On the basis of these results, it was shown that both L - and D-cysteine soften caused by UV-A-irradiation damage cells in XP cells.

On the basis of the present invention, the following examples of compositions of the emulsion composition, an adhesive composition, tablets, soft capsules, granules, beverage, candy, cookies, soy pasta, dressings for salad, mayonnaise, French bread, soy sauce, yogurt, dried powder seasoning for rice, sauce with spices/sauce for natto (Japanese enzymatic soybean paste), paste unrefined black vinegar, cream, body cream, gel composition, exfoliating mask, wet wraps, emulsion, lotion for the face and aerosol composition including one or more compounds selected from the group consisting of D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine and L-cysteine. These sample compositions are listed only for the purpose of illustration and are not intended to limit the scope of the invention.

The example 1 composition (emulsion composition)

(Composition)The content (% by weight)
L - or D-glutamic acid, D-Proline or L - or D-cysteine0,42
Beganovic alcohol0,2
The latter0,5
Complex monoether of glycerol and aliphatic acid1,8
Utverjdenie the polyoxyethylene (POE) castor oil (60)1,0
White petrolatum2,0
Liquid paraffin10,0
Isopropylmyristate3,0
Methylpolysiloxanes (viscosity 6 cs (CST))1,5
Concentrated glycerin13,0
Dipropyleneglycol2,0
Carboxyvinyl polymer0,25
Sodium hyaluronate0,005

The potassium hydroxide
if necessary
Lactic acidif necessary
Edetate sodiumif necessary
Ethylparabenif necessary
Distilled waterRest
100,00

Example 2 composition (adhesive composition)

(Composition)The content (% by weight)
L - or D-glutamic acid, D-Proline or L - or D-cysteine0,3
Polyacrylic acid3,0
Polyacrylate sodium2,5
Gelatin0,5
Sodium salt of carboxymethylcellulose4,0
Polyvinyl alcohol : 0,3
Concentrated glycerin14,0
1,3-Butyleneglycolto 12.0
Aluminum hydroxide0,1
Edetate sodium0,03
Methylparaben0,1
Distilled waterRest
100,00

Example 3 composition (pill)

(Composition)The content (% by weight)
L - or D-glutamic acid, D-Proline or L - or D-cysteine360,5
Lactose102,4
Calcium salt of carboxymethylcellulose29,9
Hydroxypropylcellulose6,8
Magnesium stearate5,2
Crystalline cellulose10,2
515,0

Example 4 composition (pill)

(Composition)Content (mg/tablet)
Ester of sucrose70
Crystalline cellulose74
The methylcellulose36
Glycerin25
L - or D-glutamic acid, D-Proline or L - or D-cysteine475
N-acetylglucosamine200
Hyaluronic acid150
Vitamin E30
Vitamin B620
Vitamin B210
α-lipoic acid20
Coenzyme Q1040
Ceramide (extract the konnyaku)50
L-Proline300
1500

Example 5 SOS is ava (soft capsule)

(Composition)Content (mg/tablet)
Food soybean oil530
The extract of Chinese rubber tree50
Extract of carrot50
L - or D-glutamic acid, D-Proline or L - or D-cysteine100
Royal jelly milk50
Poppy30
GABA (GABA, γ-aminobutyric acid)30
Beeswax60
Gelatin375
Glycerin120
Ester of glycerol and aliphatic acid105
1500

Example 6 composition (soft capsule)

(Composition) Content (mg/tablet)
Germ oil hulled rice659
L - or D-glutamic acid, D-Proline or L - or D-cysteine500
Resveratrol1
The germ extract Lotus100
Elastin180
DNA30
Folic acid30
1500

Example 7 composition (pellet)

(Composition)Content (mg/tablet)
L - or D-glutamic acid, D-Proline or L - or D-cysteine400
Vitamin C100
Soybean isoflavone250
Restored lactose300
Soy oligosaccharide36
Aritra36
Dextrin30
Odorant (corrigent)24
Citric acid24
1200

Example 8 composition (drink)

(Composition)Content (g/60 ml)
The extract of Chinese rubber tree1,6
Extract of carrot1,6

L - or D-glutamic acid, D-Proline or L - or D-cysteine1,6
Syrup restored maltose28
Aritra8
Citric acid2
Odorant (corrigent)1,3
N-acetylglucosamine1
Hyaluronate intothree the 0,5
Vitamin E0,3
Vitamin B60,2
Vitamin B20,1
α-lipoic acid0,2
Coenzyme Q101,2
Ceramide (extract the konnyaku)0,4
L-Proline2
Distilled waterRest
60

Example 9 composition (candy)

(Composition)The content (% by weight)
Sugar50
The purified syrup48
L - or D-glutamic acid, D-Proline or L - or D-cysteine1
Odorant (corrigent)1
100

When is EP 10 part (biscuits)

(Composition)The content (% by weight)
Weak flour45,0
Oilof 17.5
Sugar20,0
L - or D-glutamic acid, D-Proline or L - or D-cysteine4,0
Egg12,5
Odorant (corrigent)1,0
100,0

The method of obtaining of example 10 composition (cookie)

To the oil while stirring the portions added sugar to the mixture was added the egg and flavoring together with L - or D-glutamate sodium, D-Proline or L - or D-cysteine and stirred. After thorough mixing was added evenly sifted weak flour and stirred, and a lot was left to stand in the refrigerator. After that was othermobile and baked for 15 minutes at 170°C for receiving the cookie.

Example 11 composition (soybean paste miso with seasonings)

(Composition) Content (g)
Soybeans1000
Malted rice1000
Sol420
L - or D-glutamic acid, D-Proline or L - or D-cysteine158
WaterRest
4000

The method of obtaining of example 11 part (soybean paste miso with seasonings)

Malted rice thoroughly mixed with salt. Washed soybeans were soaked in triple relative to their volume of water, which was then merged, and added fresh water by boiling, and poured into the colander to collect broth (Tanya the wwe, seed water), which was dissolved L - or D-glutamic acid, D-Proline or L - or D-cysteine concentrations up to 10% (weight/volume). Cooked beans immediately passed through a meat grinder, combined with malted rice, mixed with salt, to which was added the above decoction Tanya the wwe containing dissolved L - or D-glutamic acid, D-Proline or L - or D-cysteine, and uniformly kneaded to obtain klinoobrazno dense mass. Did donuts and densely filled their container without forming voids, and p is the surface content smoothed and have sealed plastic wrap. After 3 months, the content was transferred into a new container, and the surface was smoothed and sealed with a plastic film. Instead of adding L - or D-glutamic acid, D-Proline or L - or D-cysteine to broth Tanya the wwe can be used malted rice, forming a large number of L - or D-glutamic acid, D-Proline or L - or D-cysteine. This malted rice can be selected for quantification of L - or D-glutamic acid, D-Proline or L - or D-cysteine by the method described in Japanese unexamined patent publication No. 2008-185558. Alternatively, commercially available on the market soybean paste miso with seasonings may be added D-glutamic acid, L-glutamic acid, D-Proline, D-cysteine or L-cysteine or salt.

Example 12 composition (dressing for salad)

1,0
(Composition)Content (g)
Vegetable oil for salad27,0
Vinegar30,0
Sodium chloride0,9
L - or D-glutamic acid, D-Proline or L - or D-cysteine1,1
Pepper
60,0

The method of obtaining of example 12 composition (dressings for salad)

Vinegar combined with sodium chloride, as well as with L - or D-glutamic acid, D-Proline or L - or D-cysteine, thoroughly mixed, and then added pepper.

Example 13 composition (mayonnaise)

(Composition)Content (g)
Vegetable oil for salad134,0
Vinegar5
Sodium chloride0,9
L - or D-glutamic acid, D-Proline or L - or D-cysteine1
Egg yolk18
Sugar0,2
Pepper0,9
160,0

The method of obtaining of example 13 part (mayonnaise)

Egg yolk (at room temperature) was combined with vinegar, sodium chloride and pepper, as well as with L - or D-glutamic acid, D-Proline or L - or D-cysteine, amatillo was stirred using a device for whipping. Stirring was continued at the same time with the addition of portions of vegetable oil for the salad with the formation of the emulsion. Finally, the sugar was added, and the mixture was stirred.

Example 14 composition (French bread)

(Composition)Content (g)
Super-strong flour140
Weak flour60
Sodium chloride3
Sugar6
L - or D-glutamic acid, D-Proline or L - or D-cysteine2
Dry yeast4
Warm water128
343

The method of obtaining of example 14 composition (French bread)

The warm water combined with 1 g of sugar and dry yeast, which is then left for exposure prior to fermentation. Super-strong flour, weak flour, sodium chloride and 5 g of sugar were placed in a pot together with L - or D-glutamic acid, D-Proline or L - or D-cysteine, which is placed in advance of fermented yeast. After thorough kneading, in a ball-shaped dough conducted primary fermentation at 30°C. the Dough was again kneaded and left to stand, and then stormville to give the proper forms, which were subjected to the final fermentation using e-fermenting machines. After forming the cakes were baking for 30 minutes in an oven with a temperature of 220°C.

Example 15 composition (soy sauce)

(Composition)Content (g)
Commercially available on the market soy sauce990
L - or D-glutamic acid, L - or D-cysteine10
1000

Example 16 composition (soy sauce)

(Composition)Content (g)
Commercially available on the market soy sauce900
D-Proline100
1000

The method of obtaining examples 15 and 16 composition (soy sauce)

Available in the Pro is even on the market soy sauce was supplemented with L - or D-glutamate sodium, D-Proline or L - or D-cysteine and thoroughly mixed. Instead of adding L - or D-glutamate sodium, D-Proline or L - or D-cysteine or their salts for digestion of soy sauce can be used malted rice, forming a large number of L - or D-glutamate sodium, D-Proline or L - or D-cysteine. This malted rice can be selected for quantification of L - or D-glutamate sodium, D-Proline or L - or D-cysteine by the method described in Japanese unexamined patent publication No. 2008-185558. Alternatively, commercially available on the market soy sauce can be added to D-glutamate, sodium L-glutamate sodium, D-Proline, D-cysteine or L-cysteine or salt.

Example 17 composition (yogurt)

(Composition)Content (g)
Milk880
Culture of L. bulgaricus50
The culture of S. thermophilus50
L - or D-glutamic acid, D-Proline or L - or D-cysteine20
1000

The method of obtaining of example 17 composition (yoghurt)

Digestion was performed PR the temperature from 40°C to 45°C. Can be applied to other commercially available on the market seed organisms for fermentation, and commercially available on the market yogurt can be supplemented with L - or D-glutamate sodium, D-Proline or L - or D-cysteine. Instead of adding L - or D-glutamate sodium, D-Proline or L - or D-cysteine, or their salts for digestion can be used bare body, forming a large number of L - or D-glutamate sodium, D-Proline or L - or D-cysteine. This organism can be selected for quantification of L - or D-glutamate sodium, D-Proline or L - or D-cysteine by the method described in Japanese unexamined patent publication No. 2008-185558. Alternatively, commercially available on the market yogurt can be added to D-glutamate, sodium L-glutamate sodium, D-Proline, D-cysteine or L-cysteine or salt.

Example 18 composition (dried powder seasoning to rice)

(Composition)Content (g)
L - or D-glutamic acid, D-Proline or L - or D-cysteine50
The Lavera (edible red seaweed)15
L-MSG10
is lorid sodium 2
Toasted sesame seeds10
Dried slices of mackerel10
Sugar1
Soy sauce2
100

Example 19 compound (seasoning sauce, natto)

(Composition)Content (g)
Commercially available on the market sauce for natto9,9
L - or D-glutamic acid, L - or D-cysteine0,1
10

Example 20 compound (seasoning sauce, natto)

(Composition)Content (g)
Commercially available on the market sauce for natto9
D-Proline1
10

Example 21 compound (natto)

(Composition)Content (g)
Commercially available on the market nattoto 19.9
L - or D-glutamic acid, D-Proline or L - or D-cysteine0,1
20

The method of obtaining of example 21 compound (natto)

Commercially available on the market natto added L - or D-glutamate sodium, D-Proline or L - or D-cysteine and thoroughly mixed. Instead of adding L - or D-glutamate sodium, D-Proline or L - or D-cysteine, or their salts to obtain natto can be used by the body, forming a large number of L - or D-glutamate sodium, D-Proline or L - or D-cysteine. This organism can be selected for quantification of L - or D-glutamate sodium, D-Proline or L - or D-cysteine by the method described in Japanese unexamined patent publication No. 2008-185558. Alternatively, commercially available on the market natto can be supplemented with D-glutamate, sodium L-glutamate sodium, D-Proline, D-cysteine or L-cysteine or salt.

Example 22 compound (unrefined black vinegar)

(Composition) Content (g)
Commercially available unrefined black vinegar950
L - or D-glutamic acid, L - or D-cysteine50
1000

Example 23 compound (unrefined black vinegar)

(Composition)Content (g)
Commercially available unrefined black vinegar900
D-Proline100
1000

The method of obtaining examples 22 and 23 of part (unrefined black vinegar)

Commercially available on the market unrefined black vinegar was supplemented with L - or D-glutamic acid, D-Proline or L - or D-cysteine and thoroughly mixed. Instead of adding L - or D-glutamic acid, D-Proline or L - or D-cysteine, or their salts to obtain vinegar, black vinegar and raw vinegar can be used in the body, forming a large number of L - or D-glutamic acid, D-Proline or L - or D-cysteine. This organism can be selected for quantification of L - or D-glutamic key is lots D-Proline, or L - or D-cysteine by the method described in Japanese unexamined patent publication No. 2008-185558. Alternatively, commercially available on the market unrefined black vinegar can be added to D-glutamate, sodium L-glutamate sodium, D-Proline, D-cysteine or L-cysteine or salt.

Example 24 compound (cream)

(Composition)Content (%)
Liquid paraffin3
Petrolatum1
Dimethylpolysiloxane1
Stearyl alcohol1,8
Beganovic alcohol1,6
Glycerin8
Dipropyleneglycol5
Oil macadamia nuts2
Utverjdenie vegetable oil3
Squalane6
Stearic acidCholesterolcholesterol0,5
Cetyl-2-ethylhexanoate4
Utverjdenie a polyoxyethylene castor oil0,5
Self emulsifiable glycerol monostearate3
The potassium hydroxide0,15
The sodium hexametaphosphate0,05
Trimethylglycine2
2-L-ascorbate, potassium and complex fluids phosphoric acid and α-tocopherol1
Tocopherol acetate0,1

L - or D-glutamic acid, D-Proline or L - or D-cysteine4
Parabenif necessary
Trisodium edetate0,05
4-Tert-butyl-4'-methoxybenzanilide0,05
the and-pair-methoxycinnamate-mono-2-ethylhexanoate glycerin 0,05
Dyeif necessary
Carboxyvinyl polymer0,05
Distilled waterRest
100,00

Example 25 composition (body cream)

(Composition)Content (%)
Dimethylpolysiloxane3
Decamethylcyclopentasiloxane13
Dodecamethylcyclohexasiloxane12
Polyoxyethylene-methylpolysiloxanes copolymer1
Ethanol2
Isopropanol1
Glycerin3
Dipropyleneglycol5
Polyethylene glycol 60005
The sodium hexametaphosphate0,05
Tocopherol acetate0,1
L - or D-glutamic acid, D-Proline or L - or D-cysteine5
Extract of fennel0,1
Extract hazel0,1
Extract of carrot0,1
L-menthol
A pair of oxybenzoic
Trisodium edetate0,05
Disorganization0,01
Methyl bis(trimethylsiloxy)silyl-isopentyl-trimethoxycinnamic0,1
Iron oxide yellowif necessary
The cobalt titanateif necessary
Dimethyl-distearyldimonium derived hectorite (clay)1,5
Polyvinyl alcohol : 0,1
Hydroxyethylcellulose0,1
Trimethylcyclohexylamine acid2
Perfumeif necessary
Distilled waterRest
100,00

Example 26 compound (gel composition)

(Composition)Content (%)
Dimethylpolysiloxane5
Glycerin2
1,3-Butyleneglycol5
Polyethylene glycol 15003
The polyethylene glycol 200003
Tetrachromat3
Citric acid0,01
Sodium citrate0,1
The sodium hexametaphosphate 0,1
Dipotassium glycyrrhizinate0,1
L - or D-glutamic acid, D-Proline or L - or D-cysteine2
Tocopherol acetate0,1
The root extract of Scutellaria0,1
Extract strawberry begonia0,1
Trisodium edetate0,1
Xanthan gum0,3
Alkylacrylate-methacrylate copolymer (Pemulen TR-2)0,05
Powdered agar1,5
Phenoxyethanolif necessary
Dibutylaminoethanolif necessary
Distilled waterRest
100,00

Example 27 compound (exfoliation)

(Composition) Content (%)
Ethanol10
1,3-Butyleneglycol6
Polyethylene glycol 40002
Olive oil1
Oil macadamia nuts1
Phytosterol-hydroxystearate acid0,05
Lactic acid0,05
Sodium lactate0,1
Disodium L-ascorbate-sulfate0,1
2-L-ascorbate, potassium and complex fluids phosphoric acid and α-tocopherol0,1
L - or D-glutamic acid, D-Proline or L - or D-cysteine10
Fish collagen0,1
Chondroitin sulfate sodium0,1
Sodium salt of carboxymethylcellulose0,2
Poly is injuly alcohol 12
A pair of oxybenzoicif necessary
Perfumeif necessary
Distilled waterRest
100,00

Example 28 composition (wet wrap)

(Composition)Content (%)
Glycerin1
1,3-Butyleneglycol8
Xylitol2
Polyethylene glycol 15002
Rosemary0,01
Sage oil0,1
Citric acid0,02
Sodium citrate0,08
The sodium hexametaphosphate0,01
Hydroxypropyl-β-cyclodextrin the 0,1
L - or D-glutamic acid, D-Proline or L - or D-cysteine0,5
Birch extract0,1
Lavender0,01
Xanthan gum0,05
Carboxyvinyl polymer0,15
A pair of oxybenzoicif necessary
Distilled waterRest
100,00

Example 29 composition (emulsion)

(Composition)Content (%)
Liquid paraffin7
Petrolatum3
Decamethylcyclopentasiloxane2
Beganovic alcohol1,5
Glycerin5
Dipropyleneglycol7
Polyethylene glycol 15002
Jojoba oil1
Ezoterikova acid0,5
Stearic acid0,5
Baganova acid0,5
Tetra-2-ethylhexanoate pentaerythritol3
Cetyl-2-ethylhexanoate3
Glycerol monostearate1
Polyoxyethylene-glycerol monostearate1
The potassium hydroxide0,1
The sodium hexametaphosphate0,05
Sterillization0,05
L - or D-glutamic acid, D-Proline or L - or D-cysteine1
Extract of Royal jelly Royal jelly0,1
Yeast extract0,1
Tocopherol acetate0,1
Acetylated hyaluronate sodium0,1
Trisodium edetate0,05
4-Tert-butyl-4'-methoxydibenzoylmethane0,1
2-Ethylhexyl-para-methoxycinnamate0,1
Carboxyvinyl polymer0,15
Parabenif necessary
Perfumeif necessary
Distilled waterRest
100,00

Example 30 composition (emulsion)

(Composition)Content (%)
Dimethylpolysiloxane2
Beganovic alcohol1
Batrawy alcohol 0,5
Glycerin5
1,3-Butyleneglycol7
Aritra2
Utverjdenie vegetable oil3
Squalane6
L - or D-glutamic acid, D-Proline or L - or D-cysteine0,3
Tetra-2-ethylhexanoate pentaerythritol2
Polyoxyethylene-isostearate glycerin1
Polyoxyethylene-glycerol monostearate1
The potassium hydroxideif necessary
The sodium hexametaphosphate0,05
Phenoxyethanolif necessary
Carboxyvinyl polymer0,1
Distilled waterRest
100,00

Example 31 composition (face lotion)

(Composition)Content (%)
Ethanol5
Glycerin1
1,3-Butyleneglycol5
Polyoxyethylene-polyoxypropylene-decyltetradeceth simple ether0,2
The sodium hexametaphosphate0,03
Trimethylglycine1
Sodium salt poliasparaginovaya acid0,1
2-L-ascorbate, potassium and complex fluids phosphoric acid and α-tocopherol0,1
Thiotaurine0,1
L - or D-glutamic acid, D-Proline or L - or D-cysteine8
Trinacria salt of EDTA (ethylenediaminetetraacetic acid)0,1
Carboxyvinyl polymer 0,05
The potassium hydroxide0,02
Phenoxyethanolif necessary
Perfumeif necessary
Distilled waterRest
100,00

Example 32 composition (face lotion)

(Composition)Content (%)
Ethanol10
Dipropyleneglycol1
Polyethylene glycol 10001
Polyoxyethyleneglycol1
Jojoba oil0,01
Tris-2-ethylhexanoate glycerin0,1
Utverjdenie a polyoxyethylene castor oil0,2
Polyglycerylmethacrylate0,15
0,1
Citric acid0,05
Sodium citrate0,2
The potassium hydroxide0,4
Dipotassium glycyrrhizinate0,1
Arginine hydrochloride0,1
2-Glucoside L-ascorbic acid2
L - or D-glutamic acid, D-Proline or L - or D-cysteine0,5
Trisodium edetate0,05
2-Ethylhexyl-para-methoxycinnamate0,01
Dibutylaminoethanolif necessary
Parabenif necessary
Deep sea water3
Perfumeif necessary
Distilled waterRest
100,00

Example 33 composition (basic solution for aerosol urea composition for skin)

(Composition)The content (% by weight)
Ethanol15,0
Utverjdenie a polyoxyethylene castor oil 501,5
Diphenhydramine1,0
The dibucaine2,0
Tocopherol acetate0,5
L - or D-glutamic acid, D-Proline or L - or D-cysteine0,1
Ezoterikova acid0,1
1,3-Butyleneglycol3,0
The polyethylene glycol 4003,0
Camphor0,05
Urea20,0
Distilled waterRest
100,00

Example 34 compound (urea aerosol spray)

(Composition)The content (% by weight)
The basic solution for aerosol urea composition for skin65,0
Dimethyl simple ether35,0
100,00

The method of filling composition of example 34 (urea aerosol spray)

The basic solution for aerosol urea compositions for skin and dimethyl simple ether were placed in a pressure-resistant aluminium aerosol container, the inner surface of which was coated with Teflon (Teflon, trade name), to obtain the aerosol composition.

1. Composition for relief caused by ultraviolet irradiation of the lesion through the introduction after ultraviolet irradiation, comprising one or more compounds selected from the group consisting of D-glutamic acid and/or its salts, and at least one acceptable additive.

2. The composition according to claim 1, where the composition is applied as a composition for application to the skin.

3. The composition according to claim 2, where the composition is applied to the operation of the cosmetic product.

4. The composition according to claim 3, where the composition is a tool against wrinkles.

5. The composition according to claim 3, where the composition is a sunscreen.

6. The composition according to claim 2, where the composition is used as a pharmaceutical product for skin diseases.

7. The composition according to claim 6, where the pharmaceutical product for the skin disease is a therapeutic drug treatment for skin diseases.

8. The composition according to claim 6, where the pharmaceutical product for skin diseases is a preventive remedy for skin diseases.

9. The composition according to claim 1, which is used as food.

10. The composition according to claim 1, which is used as a pharmaceutical product for the treatment of cataract.

11. The composition of claim 10, where the pharmaceutical product for cataract is a therapeutic drug for the treatment of cataract or a prophylactic against cataracts.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions concerns a toothpaste composition containing a metal ion source, and a method for stabilising the above metal ion source in the composition. What is disclosed is the toothpaste composition containing an orally acceptable base, and at least one metal ion source in a polymer matrix with the metal ion source containing at least one of zinc citrate, zinc lactate, zinc gluconate, zinc oxide, tin chloride, tin fluoride, tin oxide or copper sulphate or combinations thereof. The composition contains at least one of zinc oxide and zinc citrate in the polymer matrix. The amount of the metal ion source makes 20 to 60 wt % of the total weight of the polymer matrix and the above metal ion source; the amount of the polymer matrix and the metal ion source is 1 to 5 wt % of the total weight of the toothpaste composition. The polymer matrix represents a water-hydratable film having a matrix consisting of a water-soluble hydroxyalkyl cellulose polymer having the mucoadhesive properties. The toothpaste composition contains at least 10 wt % of water of the total weight of the composition. The base of the composition contains zinc citrate, and at least one phosphate specified in at least one of sodium hexametaphosphate, sodium tripolyphosphate and tetrasodium polyphosphate. The method for stabilising the above metal ion source in the toothpaste composition is implemented by including the above metal ion source into the above polymer matrix and combining the prepared polymer matrix with the orally acceptable base containing zinc citrate and at least one of the above phosphate compounds with water content less than 10 wt % of the total weight of the composition.

EFFECT: presented composition and method provide stabilising the metal ion source if the phosphate compound and zinc citrate is found in the base of the composition.

10 cl, 3 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to cosmetic industry and represents a cosmetic hair care composition containing an active ingredient presented by a locust bean gum hydrolysate prepared by mannanase enzyme, and cosmetically acceptable excipients containing reducing sugars within 10 to 60 wt % of dry weight of the hydrolysate.

EFFECT: invention provides absence of the unaesthetic and undesired weighting effect and ensures protective effect for all hair types.

11 cl, 6 ex

FIELD: cosmetology.

SUBSTANCE: invention is a mask for facial treatment, comprising pink clay, talc and water chestnut extract in a certain weight ratio of the wt %, which is dispersed in water to the consistency of thick cream before applying to the skin.

EFFECT: diversification of cosmetic products of functional purpose.

3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to antimicrobial compositions and methods for using them, and aims at the preoperative skin processing and disinfection, wound care, and as a disinfectant for sterilisation of surgical instruments. An antimicrobial composition contains at least approximately 30 wt % or more of C1-C6 alcohol, approximately 1.5 wt % to 15 wt % of citric acid, approximately 0.01 wt % to 1 wt % of paraben, and approximately 0.01 wt % to 0.2 wt % of a redox compound. The antimicrobial composition has pH from approximately 3 to approximately 7. The other aspects present an applicator that comprises an absorbent material and an absorbed antimicrobial composition, or an adsorbent material and a handle comprising an amount of the antimicrobial composition.

EFFECT: using the group of inventions provides effective and fast elimination of microorganisms particularly found on the skin surface, thereby providing the antimicrobial effect stable for a long period of time after use.

33 cl, 12 dwg, 2 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of cosmetology and represents preparation for decolouration of keratin fibres, characterised by the fact that it contains in cosmetic carrier: i) at least one cationic derivative of 2-acylpyridinium of formula , where R is alkyl group with the number of C atoms from 1 to 4, R1 is alkyl group with the number of C atoms from 1 to 6, R2 is hydrogen atom, X is physiologically acceptable anion, ii) at least one anionic surface-active substance, selected from sulfates of alkyl ethers, corresponding to formula (II) R"-(OC2H4)n-OSO3M, where R" is linear or branched saturated or unsaturated alkyl chain with the number of C atoms from 8 to 30, n is a number larger than 2 and M is proton or physiologically acceptable cation, and iii) hydrogen peroxide or solid product of hydrogen peroxide binding to inorganic or organic compounds.

EFFECT: method provides stronger decolouration of keratin fibres than application of comparable amount of hydrogen peroxide alone, which makes it possible to reduce amount of applied oxidiser and reduce damage to hair to minimum.

10 cl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and represents a non-aqueous composition of a tooth powder containing: a) at least one gum specified in a group consisting of carragheenan and carboxymethyl cellulose gums in an amount of 0.5 wt % to 5.0 wt %; b) at least one humidifier in an amount of 20.0 wt % to 80.0 wt % and c) biologically acceptable and biologically active glass representing mixed particles having a size of less than 20 mcm to less than 1 mcm and particles having a size of less than 90 mcm to less than 20 mcm in an amount of 1.0 wt % to 20.0 wt %.

EFFECT: invention provides creating the product containing biologically acceptable and biologically active glass that possesses stability and acceptable taste.

18 cl, 3 ex, 3 dwg, 5 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to film-generating composition capable of spreading. Composition is formed from water emulsion, which contains (I) particles with colloid silicon dioxide core with silicone envelope, consisting of (a) from 90 wt % to 10 wt % of colloid silicon dioxide cores and (b) from 10 wt % to 90 wt % of polyorganosiloxane envelopes; (II) polyalkylene oxide-modified trisiloxane; (III) complex of emulsifiers, consisting of, at least, one anionic surface-active substance; and (IV) salt of acidic polymerisation catalyst. Composition is included into emulsion or film. Composition can include optional ingredients, acceptable for personal hygiene, hair care, skin care, agricultural application and for house care. Invention makes it possible to realise said purpose.

EFFECT: obtaining film-generating composition capable of spreading.

21 cl, 6 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: disclosed is a vesicle-containing composition which is characterised by that it contains: (A) a silicone-based surfactant which is silicon modified with polyoxyalkylene, (B) one or more anionic surfactants selected from polyoxyethylenealkyl(12-15)ether-phosphate, acylmethyltaurate and acylglutamate in amount of 0.001-0.2 wt %, (C) polar oil having IOB of 0.05-0.80 and/or silicone oil, and (D) water, which contains a water-soluble medicinal agent, in amount of 0.5-5 wt % of the weight of the composition, where the silicone-based surfactant (A) forms vesicles; the anionic surfactant(s) (B) is attached to the surface of the vesicles; and the polar oil and/or silicone oil (C) is present inside the bilayer membrane of the vesicles.

EFFECT: disclosed composition has excellent stability even in the presence of high concentrations of a water-soluble medicinal agent.

6 cl, 8 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to chemical-pharmaceutical industry and represents a composition of a teeth care preparation, which contains amorphous quartz, with size particles, characterised by the fact that D90 constitutes less than approximately 50 microns, and a source of peroxides, with BET surface area of amorphous quartz being in the range from approximately 1 m2/g to approximately 50 m2/g.

EFFECT: improvement of the composition.

11 cl, 2 ex, 30 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to biomedical compositions and methods of treating skin-affecting diseases, disorders and states.

EFFECT: compositions and methods of treating skin states, resulting from production of active forms of oxygen in a subject's skin, include application of local composition, containing an antioxidant compound with a lipophilic, mitochondria targeted cation, and which delivers therapeutically efficient quality of the antioxidant compound to fibroblasts and keratocytes of the skin.

13 cl, 2 tbl, 3 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: present invention refers to immunology and biotechnology. What is presented is an IL-1β-binding antibody or its IL-1β-binding fragment containing V heavy and light chain regions. The above antibody binds to human IL-1β with dissociation constant less than 1pM. Versions of the antibody are described. There are disclosed corresponding coding nucleic acids (NA), as well as: a NA passage vector to a host cell, the host cell producing a coded polypeptide. What is described is using the antibody for preparing the other format of the above antibody: "camel-like", VHH antibody, nanobody. What is disclosed is a pharmaceutical composition for treating or preventing an IL-1β-related disease in a mammal on the basis of the antibody, as well as a method of treating or preventing the IL-1β-related disease in a mammal.

EFFECT: using the invention provides the novel IL-1β-specific antibodies with high IL-1β affinity that can find application in medicine for preventing, treating the diseases mediated by IL-1β activity.

39 cl, 20 dwg, 6 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethylbenzyloxyimino]ethyl}-2-ethyl benzyl)azetidine-3-carboxylic acid hemifumarate salt, as well as to its polymorphous forms, pharmaceutical compositions inhibiting EDG receptors containing the above salt and its polymorphs.

EFFECT: what is prepared is the novel 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethylbenzyloxyimino]ethyl}-2-ethyl benzyl)azetidine-3-carboxylic acid salt and the based pharmaceutical composition that can find application in treating the lymphocyte-mediated conditions.

22 cl, 9 dwg, 3 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compound of formula , where Z stands for phenyl, substituted with 1-5 halogen atoms, selected from fluorine and chlorine; R4 stands for C1-C4-alkyl with linear chain or C3-C4-alkyl with branched chain; or to its pharmaceutically acceptable salt. Invention also relates to pharmaceutical composition, inhibiting prolyl hydroxylase activity, based on said compounds.

EFFECT: obtained are novel compounds and based on them pharmaceutical composition, which can be applied in medicine for treatment of diseases, associated with immune response of organism.

18 cl, 20 dwg, 8 tbl, 13 ex

FIELD: medicine.

SUBSTANCE: claimed invention relates to immunology and biotechnology. Claimed are versions of an isolated monoclonal antibody, specific to hGM-CSF, where each version is characterised by a heavy and light chain. Each of the versions is characterised by the fact that it contains six appropriate CDR. Described are: a pharmaceutical composition, and a set, representing medication, based on the antibody application. Disclosed are: a coding isolated nucleic acid, an expression vector, containing it, and a vector-carrying host cell, used for the antibody obtaining. Described is a method of obtaining the antibody with the cell application.

EFFECT: claimed inventions can be applied for treating disease or disorder, associated with superexpression of hGM-CSF.

25 cl, 9 dwg, 14 tbl, 15 ex

FIELD: medicine.

SUBSTANCE: with underlying conventional treatment, a leukocyte serum preparation is used that is produced by incubation of 20-30 ml of a patient's whole blood bottled in three sealed flasks in a thermostat at a temperature of 37-38°C for 24, 48 and 66-68 hours respectively; then the flasks are removed from the thermostat; the leukocyte serum is aspirated by a sterile syringe; the leukocyte serum preparation prepared at different times is introduced into the patient three times subcutaneously in a dose of 2-5 ml daily or triduan.

EFFECT: method provides higher clinical effectiveness and reduced length of treatment.

2 tbl, 1 ex

Fused rage proteins // 2513695

FIELD: chemistry.

SUBSTANCE: claimed invention relates to field of biochemistry. Claimed is fused protein for treating diseases, mediated by advanced glycation end products (AGE), consisting of a fragment of a version of human receptor of advanced glycation end products (RAGE), which has two point mutations H217R and R221H, and a fragment of constant domain of human immunoglobulin IgG4, joined with linker if necessary. In addition, considered are: nucleic acid and recombinant host cell for obtaining fused protein, as well as pharmaceutical composition for treatment of AGE-mediated diseases, which contain fused protein.

EFFECT: invention ensures lower aggregation of fused protein.

13 cl, 19 dwg, 3 ex, 9 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of structural formula I that possess inhibitory activity on phosphatidyl inositol-3-kinase (PI3-kinase). In formula I: B represents group of formula II:, wherein Wc represents 6-10-merous aryl, q is equal to 0, 1, 2, 3 or 4; X is absent or represents -(CH(R9))z-, z is equal to 1; Y represents -N(R9)-; Wd represents R1 and R2 represents C1-6alkyl or halogeno; R3 represents hydrogen or C1-6alkyl; and in each case R9 independently represents hydrogen or C1-6alkyl.

EFFECT: invention refers to a pharmaceutical composition containing the above compounds, and to a method for P3I-kinase inhibition in a subject, wherein the subject suffers a disease representing cancer, a bone disorder, an inflammatory disease, an immune disease, a nervous system disease, a metabolic disease, a respiratory disease, thrombosis or a cardiovascular disease.

24 cl, 11 dwg, 6 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention relates to phenyl alkyl piperazines of formula (I) , in which: R1 represents independently on each other hydrogen atom, halogen atom, (C1-C5)alkyl group, (C1-C5)halogenalkyl group, (C1-C2)perfluoroalkyl group, (C1-C5)alkoxyl group or (C1-C2)perfluoroalkoxyl group; R2 stands for (C1-C5)alkyl group or (C1-C5)alkoxyl group, R3 represents (C1-C5)alkyl group; A represents =CH- and =N-; in form of base or additive salt with acid. Invention also relates to pharmaceutical composition for modulation of activity of TNF-alpha, which contains claimed compounds, and to method of their obtaining.

EFFECT: obtained are novel compounds which can be applied in medicine as medications for treating or preventing pain and/or diseases, associated with inflammatory of immune disorders.

24 cl, 3 ex

FIELD: medicine.

SUBSTANCE: present group of inventions relates to biotechnology. What is presented is a humanised anti-CD79b antibody and its antigen-binding fragment produced of murine antibody MA79b and CD79b having a substantially analogous binding affinity thereto. A polynucleotide, a vector, a host cell and a method for producing the anti-CD79b antibody according to the invention; immunoconjugates, compositions and methods for cell growth inhibition, a method of treating an individual suffering cancer, a method of treating a proliferative disease and tumour in a mammal, a method for B-cell proliferation inhibition; a method for detecting the presence of CD79b in a sample and method for binding the antibody to the CD79b expressing cell are also disclosed.

EFFECT: given invention can find further application in therapy of the CD79b associated diseases.

86 cl, 20 tbl, 9 ex, 51 dwg

FIELD: medicine.

SUBSTANCE: present invention refers to biotechnology and medicine. What is presented is a method for preventing or treating an inflammatory disease, comprising the stages of producing an NR10 antibody having NR10-neutralising activity, and selecting an antibody inhibiting IL-31-dependent cell line growth, and administering the antibody to a patient with an inflammatory disease that is atopic dermatitis, chronic dermatitis, rheumatism or osteoarthritis.

EFFECT: present invention can find further application in the therapy of the inflammatory diseases.

10 cl, 13 dwg, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine and concerns an antitumour preparation containing a combination of (1) a combined therapeutic agent S-1, (2) at least one ingredient specified in a group consisting of folinic acid and its pharmaceutically acceptable salts, and (3) cis-oxalate(1R,2R-diaminocyclohexane)platinum(II); a kit for treating cancer in a mammal comprising a combination of the pharmaceutical compositions for treating cancer in the mammal; a method of treating cancer involving administration of the above combination into the mammal.

EFFECT: group of inventions provides the synergetic effect in treating tumour.

20 cl, 1 ex, 1 tbl

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