JP2006265186A - Silymarin-containing photoaging agent kit - Google Patents

Abstract

[PROBLEMS] To prevent photoaging, and to prevent photoaging due to ultraviolet rays and the like, and to significantly prevent photoaging by using an external preparation and an internal use together. The purpose is to provide an anti-aging agent kit with improved aging.
[Solution]
Provided is an anti-aging agent characterized by containing silymarin, and an anti-aging agent kit characterized by comprising an external preparation containing silymarin and an internal preparation containing silymarin. That is.

Description

  The present invention relates to a photoaging inhibitor kit comprising a photoaging inhibitor containing silymarin, or an external preparation containing silymarin and an internal preparation containing silymarin.

  Silymarin is useful in preventing aging, promotes healing in the treatment of erythema, burns, dystrophic conditions of the skin or mucous membranes, dermatitis, etc., and protects the skin from external environmental stimuli (radiation, wind, sun, etc.) It is known that it is useful to do (patent document 1). In addition, silymarin suppresses sebum secretion (Patent Document 2), enhances epidermal permeation barrier (Patent Document 3), treats psoriasis and atopic dermatitis (Patent Document 4), improves epidermis flattening (Patent Document 5) ) Cosmetics for preventing skin aging caused by antioxidant ability (Patent Document 6), production promotion effect of type I collagen and elastin (Patent Document 7) are known.

  On the other hand, a method for measuring the amount of tryptophan in the skin by measuring the fluorescence excitation spectrum of the skin has been established, and it has been confirmed that the amount of tryptophan increases due to photoaging (Non-Patent Documents 1 to 3). . That is, the amount of tryptophan in the skin is useful as an indicator of photoaging.

In the prior art, mention is made of anti-aging of silymarin, but the anti-aging effect of silymarin has not been evaluated. In addition, it has been separately studied as an external preparation or an internal preparation, and no attempt has been made to synergistically prevent skin photoaging by using both external and internal administration routes together.
Japanese Patent Laid-Open No. 1-100132 JP 2000-169332 A JP 2000-169328 A JP-A-5-286864 JP 2004-91397 A Japanese Patent Publication No. 5-9406 International Publication No. WO2004 / 85429 Japanese Patent Publication No. 63-41396 Nikiforos K.M. , Et al. , J .; of Investigative Dermatology, 111, 776, 1998. Lorenzo B.I. , Et al. , J .; of Investigative Dermatology, 113, 977, 1999. Wei D.D. T. T. et al. , Et al. , J .; of Investigative Dermatology, 113, 977, 1999. Natural drug encyclopedia, edited by Takuo Okuda, Yodogawa Shoten, March 3, 1986 Wagner H.M. , Et al. , Arznein. Forsch, 18, 696, 1968. Wagner H.M. , Et al. , Arznein. Forsch, 24, 466, 1974. Titleel G. , Et al. , J .; Chromatogr. , 135, 499, 1977. Titleel G. , Et al. , J .; Chromatogr. 153, 227, 1978. Quercia V. , Et al. , Chromatography in Biochemistry, Medicine and Environmental Research, Frigerio A. et al. (Ed). Elsevier Scientific Publishing Company, Amsterdam, 1983, p1.

  The skin of the face, neck, hands, and arms, which are easily exposed to sunlight in the body, is less elastic compared to the skin of the buttocks and body parts that are shielded from sunlight by clothes, It is well known that the occurrence is significant and there is a large difference in the degree of aging. In order to prevent skin aging, it is particularly important to prevent photoaging.

  The present invention is intended to prevent photoaging, and is an anti-aging agent that has an excellent anti-aging effect on the skin due to ultraviolet rays, etc., and an anti-aging agent that has significantly improved the anti-aging effect by using an external preparation and an internal preparation in combination. The purpose is to provide a kit.

The main configuration of the present invention is as follows.
1. An anti-aging agent characterized by containing silymarin,
2. A photoaging inhibitor kit, characterized by comprising an external preparation containing silymarin and an internal preparation containing silymarin,
About.

1. An anti-aging agent containing silymarin having an excellent anti-aging effect could be provided.
2. By using the external preparation containing silymarin and the internal preparation in combination, it was possible to realize a higher photoaging prevention effect than applying the external preparation and the internal preparation alone.

Silymarin (CAS No. 65666-07-1) is a flavono extracted from the Asteraceae Maria Thistle (scientific name Silibam marianam Gaertn, also known as thistle, giant thistle, milk thistle; CAS No. 84604-20-6) is a generic term for lignans, silybin represented by the molecular formula _{C 25 H 22 O 10 (silybin} ; CAS No.22888-70-6), silidianin (silydianin; CAS No.29782-68-1), silichristin (silychristin; CAS No. 33889-69-9), isosiribin (CAS No. 72581-71-6), etc. (nonpatent literature 4). In the present invention, the composition containing these flavonolignans contained in the extract of thistle is called silymarin as in the prior art. Silymarin is a mixture of flavonolignans as described above, and the content of plant extracts and plants as silymarin is determined by a method based on measurement with a spectrophotometer (Non-patent Document 5), a method by thin layer chromatography ( Non-patent document 6), and can be measured by a method using high-performance liquid chromatography (non-patent documents 7 to 9). Among these measurement methods, 2,4-dinitrohydrazine analysis, which is one of the methods based on measurement by a spectrophotometer, has been reported to the German Pharmacopoeia (Monograph on Sillybum marium fruit) and is widely used. It has been. Also in the present invention, when the mixed composition of the above components is quantified, it is expressed in mass% converted to silymarin using a 2,4-dinitrohydrazine analysis method.

  As a method for isolating silymarin with high purity from the fruit of thistle, methods of isolating with a purity of 70-80% and a method of isolating with a purity of 90-96% have already been reported (Patent Document 8). . Silymarin is usually marketed as an extract raw material that is extracted from the seeds of Maria thistle with ethanol, ethyl acetate, acetone, etc., and obtained as a dry powder by spray drying. The silymarin used in the present invention is prepared in this manner, and commercially available silymarin can be used as it is. In addition, extracts obtained by concentrating constituents of silymarin such as silybin, silydinine, silycristin, and isosiribine from Maria thistle, and those isolated and purified can be used as compounds.

  The plant body containing silymarin in the present invention can be used in all parts such as leaves, stems, buds, flowers, woody parts, bark parts (bark), ground parts such as roots, tubers, seeds, resins, etc. is there.

  The silymarin and the plant body containing the same in the present invention can be used as a dried product obtained by drying itself and a dissolved product obtained by dissolving them using various solvents. For example, it can be used as a dissolved product using water or alcohols such as ethanol and methanol, polyhydric alcohols such as propylene glycol and 1,3-butylene glycol, and organic solvents such as ether, acetone and ethyl acetate.

  The plant body containing silymarin in the present invention can be used as it is by natural drying, hot air drying, freeze drying, or fermentation. Moreover, when preparing a plant extract, what was obtained by performing processes, such as extraction, concentration, and pulverization, according to a conventional method can be used.

  The concentration of silymarin blended in the external preparation of the present invention is preferably 0.1% or more, more preferably 0.3% or more, and most preferably 0.7% or more. If it is less than 0.1%, the photoaging prevention effect is not sufficiently exhibited.

  The external preparation according to the photoaging inhibitor kit of the present invention includes a nonionic surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant, and a naturally derived surfactant as appropriate depending on the application form. , Oils and fats such as polyhydric alcohols, vegetable oils, hydrocarbons such as waxes, higher fatty acids, silicones, preservatives, sugars, sequestering agents, polymers such as water-soluble polymers, thickeners, powders Ingredients, ultraviolet absorbers, ultraviolet blockers, humectants such as hyaluronic acid, fragrances, pH adjusters and the like can be included. In addition, vitamins, skin activators, blood circulation promoters, resident bacteria control agents, active oxygen scavengers, anti-inflammatory agents, whitening agents, bactericides, and other medicinal components and physiologically active components can also be contained.

  Nonionic surfactants include, for example, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, sucrose fatty acid esters, polyoxyethylene polyoxypropylene alkyl ethers, polyglycerin fatty acid Examples include esters.

  Examples of the anionic surfactant include fatty acid salts such as sodium laurate, higher alkyl sulfates such as sodium lauryl sulfate, alkyl ether sulfates such as POE lauryl sulfate triethanolamine, N-acyl sarcosine acid and sulfosuccinic acid. Salts, N-acylamino acid salts and the like.

  Examples of the cationic surfactant include alkyltrimethylammonium salts such as stearyltrimethylammonium chloride, benzalkonium chloride, and benzethonium chloride.

  Examples of amphoteric surfactants include betaine surfactants such as alkyl betaines and amide betaines.

  Examples of naturally occurring surfactants include phospholipids, bile acids, and sugar ceramides.

  Examples of the polyhydric alcohol include glycerin, polyethylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, and propylene glycol.

  Examples of oils and fats include camellia oil, evening primrose oil, macadamia nut oil, olive oil, rapeseed oil, corn oil, sesame oil, jojoba oil, germ oil, wheat germ oil, glycerin trioctanoate, and the like, cocoa butter, coconut oil, Hardened coconut oil, palm oil, palm kernel oil, owl, owl kernel oil, hardened oil, hardened castor oil and other solid fats, beeswax, candelilla wax, cotton wax, nutca wax, lanolin, lanolin acetate, liquid lanolin, sugarcane wax, etc. Waxes.

  Examples of the hydrocarbons include liquid paraffin, squalene, squalane, and microcrystalline wax.

  Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the like.

  Examples of the higher alcohol include hydrogenated rapeseed oil alcohol, lauryl alcohol, stearyl alcohol, cetyl alcohol, cetostearyl alcohol, lanolin alcohol, octyldodecanol and the like.

  Examples of silicone include linear polysiloxanes such as dimethylpolysiloxane and methylphenylpolysiloxane, and cyclic polysiloxanes such as decamethylcyclopentasiloxane.

  Examples of preservatives include methyl paraben and ethyl paraben.

  Examples of the sequestering agent include edetates such as disodium ethylenediaminetetraacetate, edetic acid, and sodium edetate.

  Examples of the polymer include gum arabic, gum tragacanth, galactan, guar gum, carrageenan, pectin, agar, quince seed, dextran, pullulan, carboxymethyl starch, collagen, casein, gelatin, methylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, carboxymethylcellulose Examples thereof include sodium (CMC), sodium alginate, vinyl polymers such as carboxyvinyl polymer, and the like.

  Examples of the thickener include carrageenan, tragacanth gum, quince seed, casein, dextrin, gelatin, CMC, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxyvinyl polymer, guar gum, xanthan gum, sodium carboxymethyldextran, bentonite and the like.

Examples of the powder component include talc, kaolin, mica, silica, zeolite, polyethylene powder, polystyrene powder, cellulose powder, inorganic white pigment, inorganic red pigment, titanium oxide coated mica, titanium oxide coated talc, and colored titanium oxide coated mica. And organic pigments such as Red No. 201 and Red No. 202.

  Examples of the ultraviolet absorber include paraaminobenzoic acid, phenyl salicylate, isopropyl paramethoxycinnamate, octyl paramethoxycinnamate, 2,4-dihydroxybenzophenone, and the like.

  Examples of the ultraviolet blocking agent include titanium oxide, talc, carmine, bentonite, kaolin, and zinc oxide.

  Examples of the humectant include xylitol, maltitol, maltose, sorbitol, glucose, fructose, sodium chondroitin sulfate, sodium hyaluronate, sodium lactate, pyrrolidone carboxylic acid, cyclodextrin and the like.

The medicinal ingredient, for example, vitamin A oil, vitamin A such as retinol, vitamin B ₂ such as riboflavin, B ₆ such as pyridoxine hydrochloride, L- ascorbic acid, L- ascorbic acid phosphoric acid ester, L- Vitamin Cs such as ascorbic acid monopalmitate, L-ascorbic acid dipalmitate, L-ascorbic acid-2-glucoside, pantothenic acids such as calcium pantothenate, vitamin Ds such as vitamin D ₂ and cholecalciferol Vitamins such as vitamin E such as α-tocopherol, tocopherol acetate, DL-α-tocopherol nicotinate; Whitening agents such as placenta extract, glutathione, and Yukinosita extract, skin activators such as royal jelly, beech extract, capsaicin, gingeron, cantalis tincture, ictamol, caffeine, tannic acid, blood circulation promoters such as γ-oryzanol, glycyrrhizic acid Derivatives, glycyrrhetinic acid derivatives, anti-inflammatory agents such as azulene, amino acids such as arginine, serine, leucine and tryptophan, maltose sucrose condensates of resident bacteria control agents, lysozyme chloride and the like. In addition, chamomile extract, parsley extract, beech extract, wine yeast extract, grapefruit extract, honeysuckle extract, rice extract, grape extract, hop extract, rice bran extract, loquat extract, buckwheat extract, yakuinin extract, assembly extract, merirot extract, birch extract, licorice extract , Peony extract, bonito extract, loofah extract, capsicum extract, lemon extract, gentian extract, perilla extract, aloe extract, rosemary extract, sage extract, thyme extract, tea extract, seaweed extract, cucumber extract, clove extract, carrot extract, Examples include various extracts such as maroni extract, hamamelis extract and mulberry extract.

  The external preparation according to the photoaging inhibitor kit of the present invention can be a cosmetic, a quasi-drug, or a pharmaceutical, for example, a solution such as an aqueous solution, an oil, an emulsion, a suspension, a semi-solid such as a gel or cream. The present invention can be applied in the form of a solid agent such as a solid agent, powder or solid. It can be prepared in these forms by a conventionally known method, and can be made into various dosage forms such as lotions, emulsions, gels, creams, ointments, plasters, haps, aerosols and the like. These can be applied to the body by application, sticking, spraying, or the like. The cosmetics may be facial cosmetics such as lotion, milky lotion, cream and pack, and body cosmetics such as hand cream, leg cream and body lotion.

  The internal preparation according to the photoaging agent kit of the present invention contains silymarin as an essential component, but is in the form of a preparation such as a suspension, syrup, powder, granule, pill, tablet, film and capsule. Other optional components can be added as required. Oral liquid preparations such as suspensions and syrups include sugars such as water, sucrose, sorbitol, lactose and fructose, glycols such as polyethylene glycol, oils such as sesame oil, olive oil and soybean oil, alkyl hydroxybenzoates Can be produced by using preservatives such as strawberry flavors and flavors such as peppermint.

  Powders, granules, pills, tablets, films and capsules are excipients such as lactose, glucose, sucrose and mannitol, disintegrants such as starch and sodium alginate, lubricants such as magnesium stearate and talc , Polyvinyl alcohol, hydroxypropylcellulose, gelatin and other binders, fatty acid esters and other surfactants, glycerin and other plasticizers. Tablets and capsules are most useful because they are easy to administer.

  As such capsules, those obtained by coating an internal composition containing liquid, suspension, paste, powder or granular silymarin with a capsule base such as gelatin or a mixture of gelatin and glycerin are preferable. . In order to encapsulate this internal preparation composition, for example, tocotrienol and the following components may be blended as required, and filled in a capsule base material in which gelatin and glycerin are mixed by a conventional method. Further, if necessary, ceramide, silk peptide, glucosamine, biotin, pantothenic acid and derivatives thereof, DHA and EPA may be blended in the contents at the same time. Usually, oils such as wheat germ oil, soybean oil, beeswax and lecithin added to the contents of the capsule, excipients such as corn starch, lactose and reduced maltose, etc. are properly formulated within a range not impairing the effects of the present invention. be able to.

  The internal preparation according to the photoaging inhibitor kit of the present invention may be in the form of food.

  The dosage of silymarin by internal use is about 1 to 3000 mg / person / day, and the number of doses can be 1 to 3 times / day. In addition, it is desirable that the external preparation and the internal preparation according to the photoaging inhibitor kit of the present invention are used or taken almost simultaneously. However, the use of the external preparation and the internal use may be used once a day. Absent.

Preparation of silymarin-containing external preparation Silymarin-containing external preparation (Example 1) was prepared with the composition shown in Table 1. The same base containing no silymarin was prepared and used as a placebo topical preparation (Comparative Example 1).

製法：１，２を混合し、１１を加え溶解する（Ａ）。３〜５を１０に溶解し、８０℃に加熱し、Ａを投入する（Ｂ）。６〜８を混合し、８０℃に過熱してＢに投入し、攪拌する（Ｃ）。Ｃを３０℃に冷却し、９を添加して攪拌、混合する。

Production method: 1 and 2 are mixed, and 11 is added and dissolved (A). 3 to 5 are dissolved in 10, heated to 80 ° C., and A is charged (B). 6-8 are mixed, heated to 80 ° C., charged into B, and stirred (C). C is cooled to 30 ° C., 9 is added and stirred and mixed.

Preparation of silymarin-containing internal preparation A silymarin-containing internal preparation (Example 2) in the form of a soft capsule was prepared with the composition shown in Table 2. The composition shown in Table 3 and containing no silymarin was prepared as a placebo internal use (Comparative Example 2).

  Silymarin extract contained 77 mg (50 mg as silymarin) per tablet, and in addition, 329 mg per capsule containing grape seed oil and beeswax as excipients. The placebo used was a soft capsule similar in appearance to a silymarin-containing oral preparation.

[External treatment containing silymarin, continuous test of internal use, and measurement of photoaging prevention effect]
(1) Test period and subject test period: The test period was 16 weeks and was performed from March to August.
Subject: Women over the age of 40 (63).

(2) The test design subjects were divided into two groups, the silymarin-containing internal use group of Example 2 and the placebo internal use group of Comparative Example 2 so that there was no age bias. In both groups, the silymarin-containing external preparation of Example 1 was used for the right half of the face, and the placebo external preparation of Comparative Example 2 was used for the left half.

(3) How to use external preparations and internal preparations External preparations: Daily application during the test, twice a day, after applying face lotion after morning and evening face washing, the right half face contains the silymarin-containing external preparation of Example 1, left half About 0.2 g (1 push) of the placebo external preparation of Comparative Example 1 was applied to the face.
Internal use: The drug was taken after meals in the morning and evening, 3 tablets twice a day, once daily during the study period.

(4) Tryptophan measurement device: SKINSKAN (Jobin Yvon spec.)
Measurement site: Eye corner excitation wavelength: 295 nm
Fluorescence wavelength: 360nm
The fluorescence intensity at 360 nm at an excitation wavelength of 295 nm reflecting the amount of tryptophan before and after the start of the test (0 week) and after 16 weeks was measured, and the rate of change after 16 weeks with respect to the start of the test (week 0) was determined.

(5) Measurement results The measurement results are shown in FIG. The change rate of the amount of tryptophan was 87% after 16 weeks from the start of the test when the comparative example 1 placebo topical preparation and the comparative example 2 placebo internal use were used, Example 1 silymarin-containing external preparation, and the comparative example 2 placebo internal use. 9%, comparative example 1 placebo topical preparation, Example 2 using silymarin-containing internal preparation 81.2%, example 1 using silymarin-containing external preparation, example 2 using silymarin-containing internal preparation, 73.6%. Compared to the use of a placebo topical preparation or a placebo internal use, the use of a silymarin-containing external preparation for external use alone does not significantly reduce the tryptophan change rate. Furthermore, when the silymarin-containing agent was used in combination for both the external preparation and the internal use, the rate of change in tryptophan decreased by 17.0%. In daily life, photoaging progresses due to constant exposure to ultraviolet light, but as a result, the amount of tryptophan produced in the skin is the use of silymarin-containing external preparations, silymarin-containing internal preparations, especially silymarin-containing external uses. It was found that the use of the drug and the silymarin-containing internal medicine decreased significantly. Therefore, combined use of an anti-aging agent containing silymarin, particularly an external preparation containing silymarin and an internal preparation containing silymarin is effective in preventing photoaging.

Photo-aging inhibitor kit composed of the following external preparations and internal preparations.
External preparation (cream)
A cream was produced according to the following formulation (unit:% by weight).
(1) Stearyl alcohol 6.0
(2) Stearic acid 2.0
(3) Hydrogenated lanolin 4.0
(4) Squalane 9.0
(5) Octyldodecanol 10.0
(6) POE (25) cetyl alcohol ether 3.0
(7) Glycerol monostearate 2.0
(8) Silymarin extract 0.1
(9) Preservative appropriate amount (10) perfume appropriate amount (11) 1, 3 butylene glycol 6.0
(12) PEG 1500 4.0
(13) Purified water
Residue [Production Method] The above components (1) to (10) are heated and dissolved at 80 ° C. to obtain an oil phase. Ingredients (11) to (13) are heated and dissolved at 70 ° C. to obtain an aqueous phase. The aqueous phase was gradually added to the oil phase to emulsify, cooled to 40 ° C. with stirring, and further cooled to 30 ° C. with stirring to obtain a cream.
Internal use (tablet)
Tablets were produced according to the following formulation (unit:% by weight).
(1) Silymarin 20.0
(2) Lactose 65.0
(3) Cornstarch 14.0
(4) Guar gum 1.0

The rate of change after 16 weeks of the fluorescence intensity at 360 nm at the excitation wavelength of 295 nm reflecting the amount of tryptophan before the start of the test (week 0).

Claims (2)

An anti-aging agent containing silymarin. An anti-aging agent kit comprising an external preparation containing silymarin and an internal preparation containing silymarin.

Images