JP2006241148A - Collagenase inhibitor and external preparation for skin for preventing aging - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new collagenase inhibitor, and a new external preparation for the skin for preventing aging, capable of preventing or ameliorating wrinkles and flabbiness. <P>SOLUTION: The collagenase inhibitor comprises an extract of a fruit of Rosa roxburghii. The external preparation for the skin for preventing the aging contains the collagenase inhibitor. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a collagenase inhibitor using an extract of Isaiyoibara fruit, and a skin external preparation for preventing aging using the same.

  Prevention and improvement of wrinkles and sagging that occur with aging is an important cosmetic issue. Wrinkles and sagging are remarkable in areas exposed to sunlight, and the phenomenon in which wrinkles and sagging occur in the skin exposed to sunlight is called photoaging. It is known that the amount of collagen in the dermis is remarkably reduced in photoaged wrinkles. On the other hand, collagen accounts for 90% or more of the dermal matrix, and it is also known that degradation is enhanced by collagenase activated by ultraviolet rays. From these facts, it is considered that the reduction of collagen in the skin is the main cause of wrinkling and sagging of the skin. Therefore, if an agent capable of suppressing the decrease in collagen can be provided, not only photoaging but also wrinkles and sagging associated with aging can be prevented and improved.

  On the other hand, various components derived from natural products have been proposed as active ingredients for external preparations for skin. For example, a skin external preparation containing an extract of Isaiyobara has been proposed (see Patent Documents 1 to 3). However, there is no description about the relationship between the extract of Izayoi rose and collagen or collagenase.

JP 2002-241299 A JP 2002-370963 A JP 2003-012495 A

  The present invention effectively prevents the decrease of collagen by preventing hydrolysis of matrix fibers such as collagen generated in vivo by the action of collagenase, thereby preventing the progression of skin aging symptoms, particularly wrinkles and sagging of the skin. It is an object to provide a collagenase inhibitor and an external preparation for skin that can be prevented.

  In order to solve the above-mentioned problems, the present inventor screened a collagenase inhibitor having high safety and high activity. As a result, an excellent collagenase inhibitory activity was found in the extract of Isaiyoibara fruit, and by incorporating this into an external preparation for skin, reduction of skin aging symptoms and prevention of progression were recognized.

That is, the present invention provides a collagenase inhibitor comprising an extract of Isaiyobara fruit and an anti-aging skin external preparation containing the extract of Isaiyobara fruit as a collagenase inhibitor in order to solve the above problems.
From another point of view, according to the present invention, a method for suppressing a decrease in collagen in dermal cells by applying an extract of Isaiyobara fruit; and a method for inhibiting collagenase by applying an extract of Isaiyobara fruit; Is provided.

Hereinafter, the present invention will be described in detail.
The present invention relates to a collagenase inhibitor comprising an extract of Izayoi rose fruit. Rosa roxburghii Traff. F. normalis Rehd. Et Wils. (Rosaceae), which can be used in the present invention, is a plant belonging to the family Rosaceae, also known as Togenashi, and its fruit is called Cili. The extract of Isaiyo Ibara fruit used in the present invention may be any component contained in Izayo Ibara fruit, and examples thereof include components obtained from pulp, fruit juice, pericarp, etc., or mixtures thereof. In addition, the extract of Isaiyoibara fruit is marketed as "Togenashi extract", and such a commercial item can also be used in the present invention.

  The method for preparing the extract of Isaiyobara fruit is not particularly limited, and a general extraction method can be used. The fruit may be subjected to the extraction operation as it is, but considering the extraction efficiency, it is preferable to perform the extraction after processing such as shredding, drying, and grinding. For example, it can be obtained by immersing a fruit that has been pretreated such as drying as desired in an extraction solvent for 1 to 5 days. The extraction is generally performed at room temperature or under heating, and the extraction temperature is not particularly limited, but generally about 0 to 100 ° C. is appropriate. Moreover, you may stir a liquid during immersion.

  As an extraction solvent, water and lower alcohols such as methanol, ethanol, propanol and isopropanol; polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol and glycerin; ethers such as ethyl ether and propyl ether Polar organic solvents such as esters such as ethyl acetate and butyl acetate; and ketones such as acetone and ethyl methyl ketone can be used, and one or more of these are selected and used. Of these, water, 1,3-butylene glycol, and the lower alcohols exemplified above are preferable. A phosphate buffer solution or the like may be used in consideration of blending into a skin external preparation.

  The extract of Isaiyobara fruit obtained by the above method can be added to a topical preparation base as it is as a collagenase inhibitor, but the concentrated and dried solid can be dissolved again in water or a polar solvent, or decolorized, deodorized, It may be added after a purification treatment such as desalting. For storage, it may be lyophilized after purification and dissolved in a solvent at the time of use.

  The blending amount of the collagenase inhibitor of the present invention in the external preparation for skin is about 0.001 to 10.0% by mass in the state of a crude extract obtained by extracting with a solvent capable of sufficiently immersing Isaiyobara fruit. Is appropriate.

  Furthermore, the external preparation for skin according to the present invention includes active oxygen scavengers, anti-inflammatory agents, whitening agents, skin cell activators, bactericides, oils, surfactants, moisturizers, ultraviolet absorbers, powders, General external preparations such as fragrances and preservatives and cosmetic raw materials can also be contained.

  The external preparation for skin according to the present invention can be provided in the form of liquid, gel, cream or powder. Further, the external preparation for skin according to the present invention can be provided in a dosage form such as a lotion, emulsion, gel, cream, ointment and the like, and also a skin cosmetic such as lotion, emulsion, cream, pack, and makeup. It can also be provided as makeup cosmetics such as base lotions, makeup base creams, liquid or cream-like or ointment-type foundations, and body cosmetics such as hand creams, leg creams and body lotions.

The present invention will be described more specifically with reference to the following examples. However, the scope of the present invention is not limited to the following examples.
[Example 1: Evaluation of collagenase inhibitory effect]
The following (1) to (6) were prepared. In the following (1) to (4), a type I collagenase activity measurement kit (manufactured by Yagai Co., Ltd.) was used.
(1) Type I collagenase (derived from human cells, 0.5 unit / mL) 100 μL (0.3 to 0.5 unit / mL)
(2) Fluorescent (fluorescein isothiocyanate) labeled type I collagen solution 1 μg / μL 45 μL
(3) 0.1 mol / L Tris-HCl buffer (pH 7.5) 50 μL
(4) Enzyme reaction terminator (mixture of 0.05 mol / L Tris-HCl buffer (pH 9.5) and ethanol containing o-phenanthroline) 200 μL
(5) Isaiyo Ibara Fruit Extract Solution (1,3-butylene glycol 50% aqueous solution, manufactured by Maruzen Pharmaceutical Co., Ltd.) Dry solid content 2%
(6) 1,3-butylene glycol 50% aqueous solution

First, the above (1) to (3), (5) and (6) were mixed, heated at 37 ° C. for 3 hours, and then the enzyme reaction terminator (4) was added. The amount of (5) was determined according to the target solid content concentration. (6) was added so that the total with (5) was 5 μL. Next, the solution was centrifuged to precipitate unreacted collagen, and the supernatant from which the fluorescent label was removed due to the degradation activity of collagenase was collected and the fluorescence intensity was measured. The fluorescence intensity was measured using a fluorescence spectrophotometer (excitation light 495 nm, fluorescence intensity 520 nm), and the absorbances Er and Es with and without the sample added were measured, respectively. Furthermore, the absorbances Ebr and Ebs when the same operation was performed without using collagenase (that is, without mixing (1)) were measured. These measured values were substituted into the following mathematical formula to calculate the collagenase inhibition rate (%). Further, as a reference example, ethylenediaminetetraacetic acid (EDTA), which is known to have a collagenase inhibitory action, was similarly tested.
Collagenase inhibition rate (%)
= [{(Es−Ebs) − (Er−Ebr)} / (Es−Ebs)] × 100
The results are also shown in Table 1 below.

  From the results in Table 1, it is clear that the extract of Isaiyobara fruit has a collagenase inhibitory effect equal to or higher than that of ethylenediaminetetraacetic acid (EDTA), which is already known to have a collagenase inhibitory effect.

[Example 2: Preparation of lotion]
(Ingredient) (%)
(1) Glycerin 10.0
(2) 1,3-butylene glycol 6.0
(3) Capsicum extract * 1 1.0
(4) Citric acid 0.1
(5) Sodium citrate 0.3
(6) Purified water remaining amount (7) polyoxyethylene (40EO) hydrogenated castor oil 0.5
(8) Ethyl alcohol 8.0
(9) Preservative appropriate amount (10) Fragrance appropriate amount * 1: Made by Maruzen Pharmaceutical Co., Ltd.

A. Components (1) to (6) were mixed and dissolved.
B. Components (7) to (10) were mixed and dissolved.
C. A and B were mixed and uniformed to obtain a skin lotion.

[Example 3: Preparation of emulsion]
(Ingredient) (%)
(1) New oil type glyceryl monostearate 0.3
(2) Stearic acid 0.5
(3) cetostearyl alcohol 0.5
(4) Squalane 3.0
(5) Liquid paraffin 5.0
(6) Glyceryl tri-2-ethylhexanoate 2.0
(7) Preservative appropriate amount (8) Carboxyvinyl polymer 0.1
(9) Purified water remaining amount (10) Sodium hydroxide 0.05
(11) Glycerin 10.0
(12) Capsicum extract * 1 0.01
(13) Tea extract * 2 0.01
(14) Phosphoric acid-L-ascorbyl magnesium * 3 0.01
(15) Perfume appropriate amount * 1: Maruzen Pharmaceutical * 2: Shin Nippon Pharmaceutical Co., Ltd. * 3: Nikko Chemicals

(Manufacturing method)
A. Components (8) to (11) were mixed by heating and maintained at 70 ° C.
B. Components (1) to (7) were mixed by heating and maintained at 70 ° C.
C. A and B were mixed and uniformly emulsified.
D. After cooling C, (12) to (15) were added and mixed uniformly to obtain an emulsion.

[Example 4: Preparation of serum]
(Ingredient) (%)
(1) Cholesterol 0.5
(2) Hydrogenated soybean phospholipid 2.0
(3) Glycerin 10.0
(4) 1,3-butylene glycol 5.0
(5) Dimethylpolysiloxane 1.0
(6) Vaseline 1.0
(7) Preservative appropriate amount (8) Alkyl-modified carboxyvinyl polymer 0.2
(9) Sodium hydroxide 0.08
(10) Purified water remaining amount (11) Capsicum extract * 1 2.0
(12) Yokuinin extract * 2 0.5
(13) Melosria extract * 3 0.5
(14) L-serine 0.5
* 1: Maruzen Pharmaceutical * 2: Maruzen Pharmaceutical * 3: Maruzen Pharmaceutical

(Manufacturing method)
A. Components (1) to (7) were mixed by heating and maintained at 70 ° C.
B. Components (8) to (10) were heated and mixed and maintained at 70 ° C.
C. A and B were mixed and uniformly emulsified.
D. After cooling C, (11) to (14) were added and mixed uniformly to obtain an emulsion.

[Example 5: Preparation of cream]
(Ingredient) (%)
(1) Sorbitan monostearate 0.3
(2) Cetostearyl alcohol 3.0
(3) Squalane 5.0
(4) Vaseline 3.0
(5) Glyceryl tri-2-ethylhexanoate 3.0
(6) Preservative appropriate amount (7) Sodium N-stearoyl glutamate 0.5
(8) Xanthan gum 0.05
(9) Carboxyvinyl polymer 0.1
(10) Purified water remaining amount (11) Sodium hydroxide 0.03
(12) Glycerin 10.0
(13) Dipropylene glycol 3.0
(14) Capsicum extract * 1 0.01
(15) Tea extract * 2 0.01
(16) Phosphate-L-ascorbyl magnesium * 3 0.01
(17) Fragrance Appropriate amount * 1: Made by Maruzen Pharmaceutical * 2: Shin Nippon Pharmaceutical Co., Ltd. * 3: Nikko Chemicals

(Manufacturing method)
A. Components (8) to (13) were mixed by heating and maintained at 70 ° C.
B. Components (1) to (7) were mixed by heating and maintained at 70 ° C.
C. A and B were mixed and uniformly emulsified.
D. After cooling C, (14) to (17) were added and mixed uniformly to obtain an emulsion.

[Example 6: Preparation of impregnation pack]
(Ingredient) (%)
(1) Ethyl alcohol 6.0
(2) Polyoxyethylene (40E.O.) hydrogenated castor oil 0.5
(3) Perfume appropriate amount (4) Sodium lactate solution (50%) 0.5
(5) Lactic acid 0.02
(6) Preservative appropriate amount (7) Purified water remaining amount (8) Glycerin 8.0
(9) Capsicum extract * 1 0.02
(10) Water-soluble collagen solution * 2 2.0
(11) Hyaluronic acid solution * 3 3.0
* 1: Maruzen Pharmaceutical * 2: Katakura Chikkarin * 3: Nikko Chemicals

(Manufacturing method)
A. Components (1) to (3) were mixed and dissolved.
B. Components (4) to (11) were mixed and dissolved.
C. A and B were mixed and made uniform, and the obtained lotion was contained in a nonwoven fabric to obtain a pack cosmetic.

[Example 7: Preparation of massage gel]
(Ingredient) (%)
(1) Glycerin 10.0
(2) Ethyl alcohol 0.5
(3) Capsicum extract * 1 1.0
(4) Dokudami extract * 2 0.5
(5) Yukinoshita extract * 3 0.1
(6) Purified water remaining amount (7) Hydroxymethylcellulose 0.1
(8) Carboxyvinyl polymer 0.1
(9) Sodium hydroxide 0.04
(10) Dimethylpolysiloxane 0.1
(11) Polyoxyalkylene-modified organopolysiloxane 0.1
(12) Perfume appropriate amount * 1: Made by Maruzen Pharmaceutical * 2: Made by Ichimaru Falcos * 3: Made by Ichimaru Falcos

(Manufacturing method)
A. Components (1) to (9) were mixed and dissolved.
B. Components (10) to (12) were mixed and dissolved.
C. A and B were mixed and uniformed to obtain a massage gel.

  Various types of external preparations for skin prepared in Examples 2 to 7 were all agents applied to the skin to keep the skin fresh and contribute to prevention and improvement of wrinkles and sagging. In addition, none of the agents caused problems such as discoloration or odor change due to the components.

  The extract of Isaiyoibara fruit used in the present invention is a component that exhibits an excellent collagenase inhibitory action and is also excellent in safety. Therefore, it can be blended into a wide range of preparations for external preparations for skin such as cosmetics, quasi drugs and pharmaceuticals. Since the skin external preparation of the present invention contains an extract of Izayoi rose fruit, it is excellent in the effect of preventing skin aging and can prevent or improve wrinkles and sagging caused by aging.

Claims (2)

A collagenase inhibitor comprising an extract of Izayoi rose fruit. An anti-aging skin external preparation containing the collagenase inhibitor according to claim 1.