JP2007261996A - Acrolein adduct-forming inhibitor, and skin external preparation and food and drink containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin aging care external preparation and an aging care food and drink which contain an acrolein adduct-forming inhibitor by inhibiting the reaction of forming an adduct of the acrolein formed in a living body with a protein, inhibits the formation of wrinkles, flabbiness or the like as to the skin aging care external preparation, and inhibits arteriosclerosis in a living body as to the aging care food and drink. <P>SOLUTION: The acrolein adduct-forming inhibitor comprises at lest one kind of extracts of Passiflora incatnata L. (Passifloraceae), Cornus officinalis (Cornaceae), Euphorbia aggregata (Euphovbiaceae), MAKJONG (Sterculia Lychnophora), Rosa canina (Rosaceae), Chimaphila umbellata L. (Pyrolaceae), Agrimonia pilosa var. japonica (Rosaceae), and Cinnamomum cassia (Lauraceae). <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

The present invention relates to an acrolein amino acid or protein adduct formation inhibitor, and relates to a skin anti-aging external preparation or anti-aging food or drink containing the adduct formation inhibitor.

Conventionally, various anti-aging agents that suppress aging have been developed. It is known that such biological aging is caused by two biological factors.

One is physiological aging and the other is called photo-aging skin that occurs in exposed areas such as ultraviolet rays. Physiological aging is influenced by active oxygen generated in the living body, and is related to degeneration of collagen fibers, which are the main components of blood vessels and skin, and a decrease in activity due to alteration of enzymes deeply related to physiological functions. Sensation of photoaging is limited to the skin because it is caused by UV exposure.

In physiological aging, removal of reactive oxygen species has been mainly studied, and removal agents for superoxide anion, hydroxy radical, singlet oxygen, peroxynitrite and the like have been proposed. In recent years, the involvement of acrolein as an aging factor other than active oxygen has attracted attention.

Acrolein is an α, β-unsaturated aldehyde that is highly reactive and is involved in the denaturation and cytotoxicity of proteins (enzymes and collagen). Formaldehyde and acetaldehyde. It has been reported that the cytotoxicity of acrolein is stronger than hydrogen peroxide, which can be a cause of active oxygen (Kenneth Ramos, etal, Toxicology and Applied Pharmacology, Vol. 95, 61-71 (1988)).

Acrolein can be produced in vivo from polyamines (Gunnar Houen, etal, Acta Chemia Scandinavica, Vol. 48, 52-60 (1994)) or in the process of lipid peroxidation (Koji Uchida, Nippon Oil Chemicals). (Journal, Vol. 47, No. 11, 29-37 (1998)). Acrolein is one of the environmental pollutants generated by burning plastic, cigarette smoke, exhaust gas and oil. In this way, the generation process of acrolein overlaps well with the process of generation of active oxygen, and until now the cause of aging has generally been active oxygen, but actually acrolein is involved. It may be possible. Further, in the study of protecting a living body from acrolein, since polyamine oxidase acts on polyamine to produce acrolein, a patent (Japanese Patent Laid-Open No. 2002-281999) that inhibits polyamine oxidase and acrolein is produced in the oxidation process by lipoxygenase. A patent (Japanese Patent Application Laid-Open No. 2002-138013) is proposed. However, these do not completely suppress the production of acrolein.
JP 2002-281999 A JP 2002-138013 A J. Biol. Chem., Vol. 273, No. 26, Issue of June 26, 16058-16066 (1998) Kenneth Ramos, etal, Toxicology and Applied Pharmacology, Vol. 95, 61-71 (1988) Gunnar Houen, etal, Acta Chemia Scandinavica, Vol. 48, 52-60 (1994) Koji Uchida, Journal of Japan Oil Chemists' Society, Vol. 47, No. 11, 29-37 (1998)

In the study of protecting a living body from acrolein, polyamine oxidase acts on polyamine to produce acrolein, so a patent (JP 2002-281999) that inhibits polyamine oxidase and acrolein is produced in the oxidation process by lipoxygenase inhibits lipoxygenase (Japanese Patent Laid-Open No. 2002-138013) is proposed. However, the production of acrolein is not completely suppressed by these, and a component having an action of directly capturing the produced acrolein is desired.

As a result of intensive studies to solve such problems, the present inventors have produced lipid peroxidation produced by the action of polyamine oxidase on polyamine or by peroxidation of lipids in vivo. The acrolein, which is a product, has completed the present invention by inhibiting adduct formation with proteins in the living body. And about the skin external preparation which mix | blends these, it can anticipate improving skin aging, such as skin wrinkles and tarmi, and arteriosclerosis etc. about food-drinks.

The method of directly capturing acrolein in the present invention is a method of measuring an addition product of acetyllysine and acrolein by Uchida et al. (J. Biol. Chem., Vol. 273, No. 26, Issue of June 26, 16058- 16066 (1998)).

Specifically, 100 mM N-acetyllysine was dissolved in 0.1 M phosphate buffer (pH 7.4), 10 mM acrolein was dissolved in 0.1 M phosphate buffer (pH 7.4), and 450 μL each was taken. Incubate at 37 ° C for 24 hours. 100 μL of a test sample is added thereto, the reaction solution is analyzed by HPLC, the addition product of acrolein and N-acetyllysine is analyzed, and the inhibition rate is calculated from the amount of the product.

The test sample in the present invention is an acrolein adduct formation inhibitor that suppresses the process of acrolein forming an adduct with a protein. Passion flower (Passiflora incatnata L (Passifloraceae)) whole plant, Sanshuyu (Cornus
officinalis (Cornaceae)) fruit, dragon fruit (Euphorbia aggregata (Euphorbiaceae)), MAKJONG (Sterculia)
lychnophora fruit, rose hips (Rosa canina (Rosaceae)), giant scorpion (Chimaphila umbellata L. (Pyrolaceae)), red-eared ground (Agrimonia)
pilosa var. japonica (Rosaceae)) and at least one extract of Cinnamomum cassia (Lauraceae).

In addition, the present invention provides a whole plant of such passionflower (Passiflora incatnata L (Passifloraceae)), sanshuyu (Cornus
officinalis (Cornaceae)) fruit, dragon fruit (Euphorbia aggregata (Euphorbiaceae)), MAKJONG (Sterculia)
lychnophora fruit, rose hips (Rosa canina (Rosaceae)), giant scorpion (Chimaphila umbellata L. (Pyrolaceae)), red-eared ground (Agrimonia)
pilosa var. japonica (Rosaceae)), cinnamon flower (Cinnamomum cassia (Lauraceae)) extract containing at least one or two or more skin anti-aging agents and anti-aging foods and drinks.

According to the present invention, the whole passionflower (Passiflora incatnata L (Passifloraceae)), sanshuyu (Cornus)
officinalis (Cornaceae)) fruit, dragon fruit (Euphorbia aggregata (Euphorbiaceae)), MAKJONG (Sterculia)
lychnophora fruit, rose hips (Rosa canina (Rosaceae)), giant scorpion (Chimaphila umbellata L. (Pyrolaceae)), red-eared ground (Agrimonia)
pilosa var. japonica (Rosaceae)) whole plant, cinnamon flower (Cinnamomum cassia (Lauraceae)) extract, safe and acrolein produced in vivo suppresses the reaction to form proteins and adducts It is a skin anti-aging external preparation and anti-aging food / beverage products containing an acrolein non-adduct formation inhibitor. With regard to skin anti-aging external preparations, it is intended to suppress the occurrence of wrinkles, tarmi, etc. Can suppress arteriosclerosis in the living body.

BEST MODE FOR CARRYING OUT THE INVENTION

The “passion flower” used in the present invention is mainly used as a medicinal herb in the leaves, vines, and trunks of incarnata species (Chatobodia) and edulis species (Polydiaceae). And flavonoids containing arkanoids. As a result of research, it has been reported that when either of these components is used alone, the sedative effect was not exhibited, and the sedative effect was confirmed only in a state where both components were combined. Moreover, since it can be safely used for children, it is also used to calm excited children.

As for "Ryuju" used in the present invention, Euphorbis is said to have used an emulsion for medicinal purposes. Milky white sap (milky lotion) is toxic and may cause irritating dermatitis. Milk is secreted from milk cells, which make up a tissue called the duct.

“MAKJONG” used in the present invention is also called Malva nuts, and fruits are edible in Southeast Asia. It suppresses cholesterol and is said to have effects such as diet.

The “rose hip” used in the present invention is a fruit of European wild roses. This rose hip contains vitamin C, which is said to be 20 times that of lemon, as well as A, B, E, and lycopene.

"Omegasasou" used in the present invention is distributed from Quebec to North America and Europe in North America, in the Pacific side north of Ibaraki Prefecture in Japan, in Hokkaido, and is widely used by American Indians for medicinal use of bladder stones It is offered to.

The term “Kinzuhiki” used in the present invention is a genus of the family Rosaceae belonging to the family Rosaceae, and is named after “Golden Mizuhiki” in the form of a long and narrow yellow floret that blooms like a spike in summer. Whole herbal extract has a blood coagulation promotion and hemostasis effect due to increased platelets, so it is regarded as a tonic hemostatic agent and used for hemostasis such as hemoptysis, bloody stool, and uterine bleeding. It also has antibacterial, anti-inflammatory and analgesic effects, and can be applied to prevent stomach upset and diarrhea.

  The “cinnamon flower” used in the present invention is a cinnamon flower of the family Aceraceae known as cinnamon. Used in meat spices and Chinese medicines, pharmacological effects include sedation, blood pressure lowering, peripheral vasodilation, cardiac contraction enhancement, stress gastric erosion prevention effect, promotion of bile secretion, antiallergy, antiinflammation, suppression of active oxygen production, etc. is there. However, the use of that flower is not well known.

That is, the extract according to the present invention can use various polar organic solvents and a mixture thereof as the extraction solvent. Various methods are used for the production of the extract. Depending on various activated carbons, styrene-divinylbenzene synthetic adsorbent (HP-20: manufactured by Mitsubishi Kasei Co., Ltd.) and octadecylsilane-treated silica (Chromatorex ODS: manufactured by Fuji Silysia Chemical). The method of adsorbing and eluting with an appropriate solvent is simple and practical.

Moreover, since the compounding quantity with respect to the various skin external preparation of the extract which concerns on this invention can be fluctuate | varied according to the embodiment of a skin external preparation, the usage form of a skin external preparation, etc., it is not specifically limited. In principle, an effective amount may be present, but generally 0.0001 to 100% by mass in terms of dry weight can be used in the composition, preferably 0.01 to 10% by mass. More preferably, it is 0.1-5.0 mass%. In particular, it can be assumed that the powdery preparation prepared at the time of use is used at a high blending rate including 100% by mass of the extract according to the present invention.

The application range of the external preparation for skin according to the present invention is not particularly limited. That is, the present invention can be applied to all external preparations for skin that can use each function and effect according to the function and effect of the active ingredient of the present invention.

For example, the active ingredient according to the present invention can be blended in various skin external preparation bases and applied to creams, emulsions, lotions, packs, face wash, and the like. Moreover, the various skin external preparations can be applied in various forms such as lotion, emulsion, ointment, sol, gel, powder, spray, and solid.

Moreover, the anti-aging food / beverage products according to the present invention can be made into dosage forms such as drinks, gels, powder formulations, tablets and the like.

EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to these.

This example shows a specific extraction example of the adduct formation inhibitor with the acrolein protein of the present invention.

The subjects included passionflower (Passiflora incatnata L (Passifloraceae)), Sanshuyu (Cornus)
officinalis (Cornaceae)) fruit, dragon fruit (Euphorbia aggregata (Euphorbiaceae)), MAKJONG (Sterculia)
lychnophora fruit, rose hips (Rosa canina (Rosaceae)), giant scorpion (Chimaphila umbellata L. (Pyrolaceae)), red-eared ground (Agrimonia)
The whole plant of pilosa var. japonica (Rosaceae)) and cinnamon flowers (Cinnamomum cassia (Lauraceae)) were used.

The extraction method for the extract can be extracted at 60 ° C. for several hours if it is water. If it is ethanol extraction, it can be obtained by performing Soxhlet extraction.

In this example, the inhibition rate of the acrolein protein adduct formation inhibitor of the present invention was tested.

[Experimental Example 3] Measurement of adduct formation inhibition rate of acrolein and N-acetyllysine (1) Experimental method
450 μL of 50 mM N-acetyllysine (50 mM PBS (pH 7.4)), 450 μL of 10 mM acrolein (50 mM PBS (pH 7.4)), and 100 μL of the sample were mixed, left at 37 ° C. for 24 hours, and then analyzed by HPLC. As a positive control, a comparison was made using aminoguanidine, which is known as an inhibitor of the Maillard reaction that occurs with sugars and amino acids and proteins that appear to be similar reactions. The sample concentration was 1%.

(2) HPLC condition column: DAISOPAK-SP120
ODS-BP (150mm × 6mm)
Temperature: Room temperature Mobile phase: 5% MeOH in 0.1% TFA
Detection: UV227nm
Injection volume: 5μL
Flow rate: 1.5mL / min

Table 1 shows the acrolein adduct formation inhibitory action of the water extract, and Table 2 shows the acrolein adduct formation inhibitory action of the ethanol extract.

From the results in Table 1, passion flower (Passiflora
incatnata L (Passifloraceae) whole plant, Sunshuyu (Cornus officinalis (Cornaceae)) fruit, dragon berries (Euphorbia aggregata (Euphorbiaceae)), MAKJONG (Sterculia lychnophora) fruit, Rosehip (Rosa canina (Rosaceae)), Giant beetle (Chimaphila umbellata L. (Pyrolaceae)), Agrimonia (Agrimonia)
pilosa var. japonica (Rosaceae)) and cinnamon flower (Cinnamomum cassia (Lauraceae)) extracts were confirmed to have a strong inhibitory effect on the formation of adducts of acrolein and N-acetyllysine.

The formulation example of this invention is given to the following.

<Formulation example 1> lotion (component name) (mass%)
Passion flower water extract 0.0001
Glycerin 5.0
Polyoxyethylene sorbitan monolaurate (20E.0) 1.5
Ethanol 8.0
Triethyl citrate 2.0
Preservative / Antioxidant
Purified water balance

<Formulation example 2> Cosmetic cream (component name) (mass%)
Sanshuyu ethanol extract 1.0
Beeswax 2.0
Stearyl alcohol 5.0
Stearic acid 8.0
Squalane 10.0
Self-emulsifying glyceryl monostearate 3.0
Polyoxyethylene cetyl ether (20E.0) 1.0
Glycerin 5.0
Potassium hydroxide 0.3
Perfume Appropriate amount of preservative / antioxidant Appropriate amount of purified water

<Prescription Example 3> Emulsion (component name) (mass%)
Dragon Juice Extract 5.0
Squalane 8.0
Vaseline 2.0
Beeslow 0.5
Sorbitan sesquioleate 0.8
Polyoxyethylene oleyl ether (20E.0) 1.2
Carboxyvinyl polymer 0.2
Glycerin 1.5
Potassium hydroxide 0.1
Ethanol 7.0
Perfume Appropriate amount of preservative / antioxidant Appropriate amount of purified water

<Prescription Example 4> Packing agent (component name) (mass%)
Rosehip water extract 0.001
Vinyl acetate resin emulsion 15.0
Polyvinyl alcohol 10.0
Jojoba oil 3.0
Glycerin 5.0
Titanium oxide 8.0
Kaolin 7.0
Ethanol 5.0
Perfume Appropriate amount of preservative / antioxidant Appropriate amount of purified water

<Prescription Example 5> Ointment (component name) (mass%)
Rosehip ethanol extract 0.01
Tocopherol acetate 0.5
Octyl paradimethylaminobenzoate 4.0
Butylmethoxybenzoylmethane 4.0
Stearyl alcohol 18.0
Owl 20.0
Glycerin monostearate 0.3
Vaseline 33.0
Perfume Appropriate amount of preservative / antioxidant Appropriate amount of purified water

<Formulation Example 6> Drink agent sanshuyu water extract 10.0
Citric acid 0.1
Vitamin C appropriate amount purified water balance

<Prescription Example 7> Powder preparation Cinnamon flower water extract 80.0
Eggshell calcium 10.0
Lactose 5.0
cellulose
The rest

<Prescription Example 8> Tablet Kinmizuki Water Extract 10.0
Eggshell calcium 10.0
Lactose 20.0
Starch 7.0
Dextrin 8.0
Hardened oil 5.0
cellulose
The rest

According to the present invention, passion flower (Passiflora)
incatnata L (Passifloraceae) whole plant, Sunshuyu (Cornus officinalis (Cornaceae)) fruit, dragon berries (Euphorbia aggregata (Euphorbiaceae)), MAKJONG (Sterculia lychnophora) fruit, Rosehip (Rosa canina (Rosaceae)), Giant beetle (Chimaphila umbellata L. (Pyrolaceae)), Agrimonia (Agrimonia)
pilosa var. japonica (Rosaceae)) whole plant, cinnamon flower (Cinnamomum cassia (Lauraceae)) extract, safe and acrolein produced in vivo suppresses the reaction to form proteins and adducts It is a skin anti-aging external preparation and anti-aging food / beverage products containing an acrolein non-adduct formation inhibitor. With regard to skin anti-aging external preparations, it is intended to suppress the occurrence of wrinkles, tarmi, etc. Can suppress arteriosclerosis in the living body.

HPLC chart measuring the inhibition rate of adduct formation between acrolein and N-acetyllysine

Claims (3)

Passion flower (Passiflora
incatnata L (Passifloraceae) whole plant, Sunshuyu (Cornus officinalis (Cornaceae)) fruit, dragon berries (Euphorbia aggregata (Euphorbiaceae)), MAKJONG (Sterculia lychnophora) fruit, Rosehip (Rosa canina (Rosaceae)), Giant beetle (Chimaphila umbellata L. (Pyrolaceae)), Agrimonia (Agrimonia)
An acrolein adduct formation inhibitor characterized by containing at least one extract of pilosa var. japonica (Rosaceae)) and cinnamon flowers (Cinnamomum cassia (Lauraceae)). A topical anti-aging agent for skin containing at least one or more of the acrolein adduct formation inhibitor according to claim 1 as an active ingredient. An anti-aging food or drink comprising at least one or more of the acrolein adduct formation inhibitor according to claim 1 as an active ingredient.