JP4155430B2 - Skin aging inhibitor and use thereof - Google Patents

Skin aging inhibitor and use thereof Download PDF

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Publication number
JP4155430B2
JP4155430B2 JP10035399A JP10035399A JP4155430B2 JP 4155430 B2 JP4155430 B2 JP 4155430B2 JP 10035399 A JP10035399 A JP 10035399A JP 10035399 A JP10035399 A JP 10035399A JP 4155430 B2 JP4155430 B2 JP 4155430B2
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Japan
Prior art keywords
skin aging
aging inhibitor
extract
skin
name
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Expired - Fee Related
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JP10035399A
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JP2000290165A (en
Inventor
紘明 三谷
浩一 大志万
良 曽田
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三省製薬株式会社
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Description

[0001]
BACKGROUND OF THE INVENTION
TECHNICAL FIELD The present invention relates to a skin aging inhibitor, and more specifically, a skin aging inhibitor comprising a solvent extract of a specific plant as an active ingredient, and a cosmetic, pharmaceutical, quasi-drug or food containing the same. It is about.
[0002]
[Prior art and problems]
Skin aging proceeds mainly due to a decrease in skin function due to aging and an external environment such as ultraviolet rays and food. In the external environment, it is said that active oxygen and free radicals generated by sunlight, metabolism, etc., and hyaluronidase activated by some stimulus from inside and outside the body promote skin aging.
[0003]
Sunlight and free radicals and free radicals generated in the body damage cells, biological components and tissues in the body, resulting in decreased function of cells and organs, resulting in arteriosclerosis, cerebrocardiovascular disorders, diabetes, It has been shown to cause various diseases such as cataracts, spots / sobacas, skin wrinkles / sagging, hypertension, senile dementia and cancer. In foods, lipid peroxides and polymers are formed, proteins are denatured, enzyme activity is decreased, and color components are degraded due to degradation of pigments, resulting in deterioration of the quality of foods containing these components. It has become.
[0004]
On the other hand, hyaluronidase usually exists in an inactive state in tissues in the living body, and hyaluronidase is activated by some kind of stimulation from inside and outside the body, and the high molecular weight hyaluronic acid as a substrate is reduced to a low molecular weight. It is said that inflammation progresses. In addition, it has been inferred that lowering the molecular weight of hyaluronic acid leads to a decrease in skin moisturizing property and tension.
[0005]
Accordingly, α-tocopherol, ascorbic acid, cysteine, glutathione and the like having active oxygen and radical scavenging action are used as skin aging inhibitors. α-tocopherol is composed of a chroman ring and a side chain having 16 carbon atoms, and has only an active oxygen scavenging action only on a substance having fat solubility due to its characteristics. Further, ascorbic acid has an enediol group at the 2nd and 3rd positions of carbon, which is a functional group for scavenging active oxygen, and is effective only for water-soluble substances due to its characteristics. Although these have an excellent active oxygen scavenging action, they are poor in stability, and in solution, they decompose by heat treatment or with time, and a sufficient effect is not recognized.
[0006]
Cysteine is particularly unstable in aqueous solution, and it turns into cystine within a few days, and precipitates are deposited.Glutathione decomposes over time in a hot and humid environment, generating a strange odor. Have.
Although attempts have been made to use BHT (butylated hydroxytoluene), BHA (butylated hydroxyanisole) and the like as synthetic antioxidants and skin aging inhibitors, animal experiments have pointed out the possibility of carcinogenesis.
[0007]
In addition, glycyrrhizic acid, cromoglycate sodium, baicalin, indomethacin, aspirin, and the like, which have been confirmed to have high hyaluronidase activity inhibitory activity in vitro, are used.
However, glycyrrhizic acid and baicalin have been used in natural products since ancient times, and are said to be relatively safe, but have a very small amount of sweetness or a vivid vermilion color tone. There are restrictions on the application and use concentration. In the case of cromoglycate sodium, there are reports of fetal toxicity when administered to pregnant women, and strict caution is required as a medicinal product. Indomethacin and aspirin have been observed to cause side effects such as rash and itching when used locally.
[0008]
As described above, conventional skin aging inhibitors have problems in safety, quality, usefulness, and the like, and the present situation is that they are limited to the use of some pharmaceuticals and the like whose use is restricted. Under such circumstances, it is safe to apply and eat to the skin for the human body, and can be easily manufactured with a markedly suppressed active oxygen / radical scavenging action and / or low molecular weight of hyaluronic acid. Development of a skin aging inhibitor that can be stably supplied has been desired.
[0009]
[Problems to be solved by the invention]
An object of the present invention is to provide a skin aging inhibitor that is highly safe for the human body and has a strong active oxygen scavenging action and / or hyaluronidase activity inhibitory action.
[0010]
[Means for Solving the Problems]
The present invention has been proposed in order to achieve the above-mentioned object, and an extract extracted from a specific Indonesian herb or medicinal tree found as a result of the inventors' long-term research is active. It has been completed based on the new finding that it has an oxygen scavenging action and / or a hyaluronidase activity inhibitory action.
[0011]
That is, according to the present invention, the scientific name: Pipturus argenteus (Forst.f.) (Indonesian name: Trembesi) and / or the scientific name: Phyllanthus pulcher (Baill.) MA (Indonesian name: Naga) A skin aging inhibitor comprising a solvent extract of a plant ( buana) as an active ingredient is provided.
[0012]
Further, according to the present invention, Scientific name: Piputurusu Al Gente mouse [Pipturus argenteus (Indonesia name: Trembesi) (Forst.f.)] Leaves, stems and bark and / or scientific name: (. Baill) Firantsusu Purukeru [Phyllanthus pulcher MA (Indonesian name: Naga buana)] The skin aging inhibitor containing the solvent extract of the plant of a leaf plant as an active ingredient is provided. The above skin aging inhibitor is usefully used in cosmetics, pharmaceuticals, quasi drugs and foods.
[0013]
DETAILED DESCRIPTION OF THE INVENTION
The above-mentioned specific plant used in the present invention is generally used in Indonesia as an ancient crude drug, and a plurality of mixtures of hot water extracts are drunk and used for the treatment of symptoms such as abdominal pain and headache.
[0014]
In the present invention, roots, stems, leaves, fruits (seed), flower buds, bark, insect gills and the like of the specific plant are used, and this extract has an active oxygen scavenging action and / or a hyaluronidase activity inhibiting action. Of particular significance.
Extraction is performed with a solvent, and a lower alcohol, a polyhydric alcohol, a low polarity solvent and a polar solvent are used as the extraction solvent.
[0015]
As the lower alcohol, methanol, ethanol, propanol, isopropyl alcohol and the like are used. Examples of the polyhydric alcohol include glycerin, polyethylene glycol and 1,3-butylene glycol, and examples of the low polarity solvent include saturated hydrocarbons such as pentane, hexane, heptane, octane, nonane and decane, and unsaturated hydrocarbons such as hexene and heptene. As the polar solvent, water, acetone, ethyl acetate, methyl acetate and the like are used, and these are used alone or in combination of two or more as an extraction solvent.
[0016]
Extraction is carried out by adding a solvent to Pipturus argenteus (Forst. F.) Or the like, with stirring if necessary, at 10 to 60 ° C., preferably at the boiling point of the solvent or below room temperature. However, in the case of water, it may be extracted with boiling hot water.
The amount of the mixed solvent used is not particularly limited, but as a guideline, the solvent may be used in an amount of 1 to 20 parts, preferably about 5 to 10 parts per 1 part of the dried plant (crushed material).
The extract thus obtained contains a high concentration of an active oxygen scavenging component and / or a hyaluronidase activity inhibiting component.
[0017]
The skin aging inhibitor according to the present invention uses the extract extracted by the above method as a useful component as it is, and a purified product of the extract can also be used as a useful component. As the treated product, a concentrate, a paste, a dried product, and / or a diluted product of useful components are widely used.
For example, the extract is directly vacuum (frozen) dried, concentrated under reduced pressure, then vacuum (frozen) dried, or concentrated under reduced pressure, followed by solvent fractionation with various solvents to remove active oxygen and / or hyaluronidase. The activity-inhibiting component may be purified and vacuum (freeze) dried, or the processed product may be produced by a concentration purification method using column chromatography in which the extract is loaded on the column and then vacuum (freeze) dried. . In addition, as a processed material, it is also possible to select and use the shape and concentrate according to the objective, without performing until the final drying process, stopping operation | movement at each process mentioned above in the middle.
[0018]
Further, the skin aging inhibitor according to the present invention can be used in cosmetics, foods, pharmaceuticals, quasi drugs and the like. In skin preparations for cosmetics and pharmaceuticals and quasi-drugs, various optional ingredients known per se (for example, oils, moisturizers, thickeners, preservatives, emulsifiers, chelating agents, pigments, pH adjusters, A medicinal component, an ultraviolet absorber, and a fragrance) can be appropriately blended to produce a cream, milk lotion, lotion or the like.
[0019]
In addition to the above, the dosage form can be arbitrarily selected according to the purpose such as foundation, pack, lotion, essence, ointment, gel, powder, lip balm, lipstick, sun care and bath salt. A whitening agent, an anti-inflammatory agent, an antioxidant, a hygroscopic agent, a moisturizing agent, and the like can be appropriately added and used depending on the purpose of the present invention as long as the purpose of the present invention is not impaired.
[0020]
Examples of the humectant include glycerin, propylene glycol, 1,3-butylene glycol, sorbitol, mannitol, polyhydric alcohols such as polyethylene glycol and dipropylene glycol, amino acids, NMF components such as sodium lactate and sodium pyrrolidonecarboxylate, hyaluronic acid And water-soluble polymer substances such as collagen, elastin, chondroitin sulfate, dermatan sulfate, fibronectin, heparin-like substance, and chitosan.
[0021]
Examples of thickeners include natural polymeric substances such as sodium alginate, xanthan gum, quince seed extract, tragacanth gum and starch, semi-synthetic polymeric compounds such as methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, soluble starch and cationized cellulose, carboxy Examples include synthetic polymer materials such as vinyl polymers and polyvinyl polymers.
[0022]
Examples of the preservative include benzoate, salicylate, sorbate, dehydroacetate, paraoxybenzoate, 2,4,4′-trichloro-2′-hydroxydiphenyl ether, 3,4,4′-trichlorocarbamate. Examples thereof include nido, benzalkonium chloride, hinokitiol, resorcin, and ethanol.
[0023]
Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate and ascorbic acid. Examples of the ultraviolet absorber / shielding agent include 4-methoxybenzophenone, octyldimethylparaaminobenzoate, ethylhexylparamethoxycinnamate, titanium oxide, kaolin, zinc oxide and talc.
[0024]
Furthermore, examples of the chelating agent include ethylenediaminetetraacetic acid, pyrophosphoric acid, hexametaphosphoric acid, citric acid, gluconic acid, tartaric acid, and salts thereof, and examples of the pH adjusting agent include sodium hydroxide, boric acid, boron. Examples thereof include sand and potassium hydrogen phosphate.
[0025]
【Example】
Hereinafter, the present invention will be described specifically by way of examples.
First, although the example of manufacture of the plant extract used by this invention is shown, the extraction method is not limited to this.
[0026]
[Production Example 1]
Phyllanthus pulcher (Baill.) MA Root crushed 100 g was added with 1,000 mL of 50 v / v% ethanol, and stirred and extracted in the dark at room temperature for 7 days.
This was centrifuged and filtered under pressure to obtain an extract.
[0027]
[Production Example 2]
Purified water (1,000 mL) was added to 100 g of the crushed Pipturus argenteus (Forst. F.) Leaf dried product, and the mixture was extracted with stirring for 1 hour in a hot water bath.
This was centrifuged and filtered under pressure to obtain an extract.
[0030]
[Production Example 3 ]
To 100 g of pulverized phyllanthus pulcher [ Phyllanthus pulcher (Baill.) MA ] leaf crushed material, 1,000 mL of glycerin was added, followed by stirring and extraction in the dark at room temperature for 7 days.
This was centrifuged and filtered under pressure to obtain an extract.
[0031]
[Example 1] Radical scavenging action test The radical scavenging action of the extract obtained in each production example was measured under the following conditions.
[0032]
(1) Measurement method Add 2 mL of ethanol and 1 mL of 0.5 mM α, α-diphenyl-β-picrylhydral (DPPH ·) ethanol solution to 2 mL of 0.1 M acetate buffer (pH 5.5) containing the sample, and 30 minutes later. Absorbance values were measured at a wavelength of 517 nm. Samples were diluted to 0.2% with acetate buffer.
Radical scavenging rate (%) =
{Blank OD-(OD at sample addition-OD at 0.02% BHT addition) x 100}
/ (Blank OD-OD with 0.02% BHT added)
BHT: Butylhydroxytoluene [0033]
(2) Measurement results Table 1 shows the results of radical scavenging action of the plant extract. Each extract was found to have a radical scavenging action corresponding to a concentration of 100 μM α-tocopherol.
[0034]
(3) Consideration
Extracts such as Phyllanthus pulcher (Baill.) MA are extracted at a concentration of 10% with respect to the dry sample, and the concentration added when measuring the radical scavenging rate is 0.02% or less in terms of dry matter. On the other hand, 100 μM α-tocopherol is about 0.004% in terms of weight concentration. From this result, each extract contains about 20% or more of a radical scavenging component corresponding to α-tocopherol, and these extracts can be used as an active oxygen scavenger with a very small addition amount. Can be used.
[0035]
[0036]
[Example 2] SOD-like activity The SOD-like activity of the extract obtained in each production example was measured under the following conditions.
[0037]
(1) Measuring method 0.1 mL each of 3 mM xanthine, 3 mM EDTA, 0.15% bovine serum albumin, and 0.75 mM nitroblue tetrazolium is added to 2.4 mL of 0.05 M sodium carbonate buffer (pH 10.2). To this was added a sample containing an SOD-like active ingredient and allowed to stand at 25 ° C. for 10 minutes, and then a xanthine oxidase solution was added and incubated at 25 ° C. After 20 minutes, 0.1 mL of 6 mM copper chloride solution was added to stop the reaction, and the absorbance at 560 nm was measured. The concentration at which 50% of the absorbance value when no sample was added was 1 unit / mL, and the SOD-like activity was measured by the dilution factor.
[0038]
(2) Measurement results Table 2 shows the results of the SOD-like activity of the plant extract. Each extract showed high activity of 20,000 units / mL or more.
[0039]
[0040]
(3) Discussion SOD is an enzyme that eliminates the superoxide anion and deactivates with heating, addition of sugar, and time. Moreover, since it is a polymer, it cannot be absorbed orally and transdermally. However, the above-mentioned plant-derived active oxygen scavenging component has a low molecular weight and good stability. Absorption from the oral and dermal routes is also expected.
[0041]
[Example 3] Hyaluronidase activity inhibitory action test The hyaluronidase activity inhibitory action of the extract obtained in each production example was measured under the following conditions.
[0042]
(1) Measurement method The sample was diluted to 10% with 0.1 M acetate buffer (pH 4.0), 0.1 mL of hyaluronidase (Type IV-S) solution was added to 0.2 mL of the diluted solution, and the mixture was incubated at 37 ° C. Incubated for 20 minutes. Thereafter, 0.2 mL of a reagent was added and further incubated at 37 ° C. for 20 minutes, 0.5 mL of 0.6% hyaluronic acid was added, and incubated at 37 ° C. for 40 minutes. The reaction is stopped by adding 0.2 mL of 0.4N sodium hydroxide solution. Thereafter, 0.2 mL of boric acid reagent is added and heated in a water bath for 3 minutes. 5 mL of p-DAB reagent (p-dimethylaminobenzaldehyde 10% hydrochloric acid-acetic acid solution) was added, incubated at 37 ° C. for 20 minutes, the absorbance value was measured at 585 nm, and the inhibition rate ( %).
Hyaluronidase activity inhibition rate (%) =
100-{(OD when sample is not added-OD when sample is added) / OD when sample is not added} × 100
[0043]
(2) Measurement results Table 3 shows the results of the hyaluronidase activity inhibitory action of the plant extract. Each extract was confirmed to have a hyaluronidase activity inhibitory effect corresponding to 20% sodium cromoglycate concentration.
[0044]
[0045]
(3) Consideration
Extracts such as Pipturus argenteus (Forst. F.) Are extracted at a concentration of 10% with respect to the dried sample, and the added concentration at the time of measuring the hyaluronidase activity inhibitory action is 10% or less in terms of the dried product. On the other hand, sodium cromoglycate has an inhibition rate comparable to that obtained when 10% of plant extract is added at a concentration of 0.2%. As a result, each extract contains about 20% or more of a hyaluronidase activity inhibitory component corresponding to sodium cromoglycate, and these extracts are hyaluronidase activity inhibitors with a very small addition amount. Can be used as a raw material.
[0046]
[Example 4] Skin improvement test by hairless mouse ultraviolet irradiation method Since the results of Examples 1, 2 and 3 were expected to improve skin looseness and rough skin, these tests were conducted. About Example 5, Formulation Example 1 and Formulation Example 3, the skin improvement test by the hairless mouse ultraviolet irradiation method was implemented.
(1) Test method A predetermined amount of ultraviolet light (UVA-BLB lamp) was irradiated for 4 months in advance to produce hairless mice that induced skin looseness and rough skin. These hairless mice (HR-1 female) were grouped into 5 groups (8 per group), and the creams and emulsions shown in Table 4 were continuously applied to the back of the hairless mice twice a day in the morning and evening for 3 months. Later, the degree of improvement in skin looseness and roughness was examined according to the criteria shown in Table 5.
Separately, side effects such as rash and erythema in continuous application were also examined.
[0047]
[0048]
[0049]
(2) The results of the test results are shown as a sum total, where “improvement level +” is 1+ and “improvement level 2+” is 2+.
The No. 2 sample and No. 4 sample of the extract blending prescription showed a remarkable effect of improving sag and rough skin even when compared with the respective bases. In addition, these samples showed no skin abnormality even after continuous use (Table 6).
[0050]
[0051]
(3) Consideration
In the cosmetics containing the extract of Phyllanthus pulcher (Baill. MA) , no significant side effects and no significant skin looseness / roughness improvement effects were observed. The same improvement effect can be expected from other extracts having an action of scavenging reactive oxygen and / or an action of inhibiting hyaluronidase activity.
[0052]
[Example 5] Preparation of external preparation for skin An external preparation for skin having the composition shown below was prepared using the extract obtained in Production Example as an active ingredient. In the formulation of the formulation examples, “appropriate amount” means an amount that is 100% by weight as a whole.
[0053]
The components belonging to A are dissolved by heating. Separately, the component belonging to B is dissolved by heating. B was added to A, stirred and emulsified, and then cooled to produce a cream.
[0054]
The components belonging to A are dissolved by heating. Separately, the component belonging to B is dissolved by heating. B was added to A, stirred and emulsified, and then cooled to produce a cream.
[0056]
<Prescription example 3 lotion>
(weight%)
Ethanol 15.0
Extract obtained in Production Example 1 1.0
Ethylparaben 0.1
Citric acid 0.1
Sodium citrate 0.3
1,3-butylene glycol 4.0
Edetate disodium 0.01
Purified water appropriate amount Each of the above components was mixed, stirred and dissolved uniformly to produce a skin lotion.
[0057]
<Prescription Example 4 Hydrophilic Ointment>
A (wt%)
Polyoxyethylene cetyl ether 2.0
Glycerol monostearate 10.0
Liquid paraffin 10.0
Vaseline 4.0
Cetanol 5.0
Extract obtained in Production Example 2 1.0
B
Propylene glycol 10.0
Methylparaben 0.1
Purified water Appropriate amount The ingredients belonging to A are dissolved by heating. Separately, the component belonging to B is dissolved by heating. B was added to A, stirred and emulsified, and then cooled to produce a hydrophilic ointment.
[0059]
[Example 6 ] Preparation of internal preparation Using the extract obtained in Production Example 2, an internal preparation was prepared with the composition shown below.
<Prescription Example 1 Granule>
(weight%)
Extract obtained in Production Example 2 1.0
Lactose 30.0
Cornstarch 60.0
Crystalline cellulose 8.0
Polyvinylpyrrolidone 1.0
Polyvinylpyrrolidone is dissolved in 50% ethanol, added to lactose, crystalline cellulose, and corn starch, mixed uniformly, and granulated using a granule apparatus. After drying, the particles were sized to produce granules.
[0060]
[Example 7 ] Preparation of tablet confectionery Using the extract obtained in Production Example 2, tablet confectionery was prepared with the composition shown below.
<Prescription Example 1 Tablet Confectionery>
(weight%)
Citric acid 1.0
Nonfat dry milk 15.0
Sucrose ester 1.0
Frevers 0.8
Powdered sugar 20.0
Extract obtained in Production Example 2 1.0
Lactose 61.2
The above raw materials are uniformly mixed, an appropriate amount of 50% ethanol solution is added, and granulation is performed using a granule apparatus. After drying, this was tableted to produce tablet confectionery.
[0061]
【The invention's effect】
The extract obtained from the plant according to the present invention has excellent active oxygen scavenging action and / or hyaluronidase activity inhibitory action and high safety, and therefore skin of cosmetics, foods, pharmaceuticals, quasi drugs and the like. It can be applied to all fields aimed at preventing aging and exert its effects.

Claims (6)

  1. Solvent extraction of plants of scientific name: Pipturus argenteus (Forst.f.) (Indonesian name: Trembesi) and / or scientific name: Phyllanthus pulcher (Baill.) MA (Indonesian name: Naga buana) A skin aging inhibitor comprising a product as an active ingredient.
  2. Scientific name: Pipturus argenteus (Forst.f.) (Indonesian name: Trembesi)] leaves, stems and bark and / or scientific name: Phyllanthus pulcher (Baill.) MA (Indonesian name: Naga buana) The skin aging inhibitor according to claim 1, comprising a solvent extract of a leaf plant as an active ingredient.
  3.   Cosmetics containing the skin aging inhibitor of Claim 1 or 2.
  4.   A pharmaceutical comprising the skin aging inhibitor according to claim 1 or 2.
  5.   A quasi-drug containing the skin aging inhibitor according to claim 1 or 2.
  6.   A food containing the skin aging inhibitor according to claim 1 or 2.
JP10035399A 1999-04-07 1999-04-07 Skin aging inhibitor and use thereof Expired - Fee Related JP4155430B2 (en)

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JP4155430B2 true JP4155430B2 (en) 2008-09-24

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Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001139417A (en) * 1999-08-31 2001-05-22 Lion Corp Inhibiting/improving agent for lesion caused by oxidation
US6531166B2 (en) * 2000-12-26 2003-03-11 Council Of Scientific And Industrial Research Use of betel leaf extract to induce IFN-gamma production from human peripheral blood T cells and as a Th1 type immunomodulator
US7618662B2 (en) * 2004-12-22 2009-11-17 Avon Products, Inc Use of natural plant extracts in cosmetic compositions
JP4970442B2 (en) * 2006-06-30 2012-07-04 株式会社ノエビア Whitening agent
NZ577766A (en) * 2006-12-21 2012-02-24 Piramal Life Sciences Ltd Herbal composition comprising Piper betle leaf extract for treating imatinib-resistance chronic myeloid leukemia
US9301987B2 (en) 2007-09-24 2016-04-05 Laila Nutraceuticals Anti-adipogenic compositions containing Piper betle and Dolichos biflorus

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