JP3533392B1 - External preparation for skin - Google Patents

Abstract

[Problem] To provide an external preparation for skin which does not impair the effect of proanthocyanidin on a living body and further solves the problem of astringency of a protein possessed by proanthocyanidin. SOLUTION: The external preparation for skin of the present invention contains proanthocyanidin and a proteolytic peptide having an average molecular weight of 7,000 or less. This proanthocyanidin
2 parts per 1 part by weight of proanthocyanidin
It is preferable to contain a proanthocyanidin of 1 to 4 parts by weight or more.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a skin external preparation containing proanthocyanidins, and more particularly to a skin external preparation having an excellent effect of improving skin quality.

[0002]

BACKGROUND OF THE INVENTION Proanthocyanidins are flavan-3.
-A condensed tannin composed of a polycondensate having an all- and / or flavan-3,4 diol as a constituent unit and having a degree of polymerization of 2 or more. Was there. In recent years, proanthocyanidins have various activities such as an antioxidant effect and a whitening effect, and thus have been applied to foods and cosmetics (Patent Documents 1 and 2). For example, it is also applied to cosmetics containing protein (Patent Documents 3 to 6). In addition, various improvements have been made to enhance the stability of tannin and protein, particularly in a solution (Patent Document 7).

[0003] On the other hand, proanthocyanidins have a property of having a high ability to bind to proteins, and thus have been used as a gelatin high-melting point gel and as a crosslinking agent for collagen (Patent Documents 8 and 9).

[0004] However, since proanthocyanidins have a very high ability to bind to proteins, depending on the extraction method of proanthocyanidins, plant species, etc., they bind to proteins and cause aggregation and suspension. Therefore, not only is it difficult to formulate, but collagen and proanthocyanidin are precipitated, and the effect of each of them on the living body is greatly reduced, so the range of application to formulations and cosmetics has been limited.

[0005]

[Patent Document 1] JP-A-61-16982

[Patent Document 2] Japanese Unexamined Patent Publication No. 2-134309

[Patent Document 3] Japanese Patent Laid-Open No. 11-75708

[Patent Document 4] Japanese Patent Laid-Open No. 2000-60482

[Patent Document 5] JP-A-6-336423

[Patent Document 6] JP-A-2002-238497

[Patent Document 7] Japanese Unexamined Patent Publication No. 2002-51734

[Patent Document 8] Japanese Unexamined Patent Publication No. 2-163046

[Patent Document 9] Japanese Patent Laid-Open No. 2001-8634

[0006]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an external preparation for skin which does not impair the effect of proanthocyanidins on the living body and further solves the problem regarding the astringency of proteins possessed by proanthocyanidins.

[0007]

Means for Solving the Problems The present inventors have surprisingly found that, by combining a proanthocyanidin of 2 to 4 mer with a peptide having a certain molecular weight, aggregation and precipitation of protein does not occur, and as a result, The present invention has been completed by finding that the respective effects can be obtained without canceling each other.

That is, the present invention provides a skin external preparation containing proanthocyanidins and a proteolytic peptide having an average molecular weight of 7,000 or less, and the proanthocyanidins contain 2- to 4-mer proanthocyanidins.

In a preferred embodiment, the proanthocyanidin is a pentamer or more proanthocyanidin 1
2 to 4 parts of proanthocyanidin to 1 part by weight
It is contained in a proportion of at least parts by weight.

In a further preferred embodiment, the peptide is a collagen-derived peptide.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The external preparation for skin of the present invention will be described below. It is obvious to those skilled in the art that the configurations described below do not limit the present invention and can be variously modified within the scope of the present invention.

The proanthocyanidin used in the external preparation for skin of the present invention is a compound group consisting of a condensation polymer having flavan-3-ol and / or flavan-3,4-diol as a constituent unit and having a degree of polymerization of 2 or more. Say.

As the proanthocyanidin, those containing a large amount of polycondensation polymer having a low degree of polymerization are preferably used. The polycondensation polymer having a low degree of polymerization has a degree of polymerization of 2 to 3
0 polycondensation polymer (2 to 30 mer) is preferable, and the degree of polymerization is 2
A polycondensation polymer of 10 to 10 (2 to 10 mer) is more preferable, and a polycondensation polymer of 2 to 4 (2 to 4 mer) is particularly preferable. The polycondensate having a degree of polymerization of 2 to 4 is referred to as O in the present specification.
PC (oligomeric proanthocyanidin; oligom
eric proanthocyanidin). Proanthocyanidins, a type of polyphenol, are powerful antioxidants produced by plants and are concentrated in plant leaves, bark, fruit skins or seeds. Proanthocyanidins, especially OPC, specifically include bark of pine, oak, mountain peach, grape, blueberry, strawberry, avocado, black locust, fruit or seed of cowberry, barley, wheat,
It is contained in soybeans, black soybeans, cacao, red beans, conker shells, thin peanut skins, and ginkgo leaves. It is also known that cola nuts in West Africa, roots of Latania in Peru, and green tea in Japan also contain OPC. OP
C is a substance that cannot be produced in the human body.

As the proanthocyanidin contained in the external preparation for skin of the present invention, the above-mentioned bark, fruit or seed extract, a drug, a quasi drug, or a cosmetic material can be used. In particular, it is preferable to use an extract of pine bark. Since pine bark is rich in OPC among proanthocyanidins, it is preferably used as a raw material for proanthocyanidins.

A method for preparing proanthocyanidins will be described below by taking an extract of pine bark rich in OPC as an example.

Pine bark extracts include French coastal pine (Pinus Martima), larch, black pine, red pine,
Himekomatsu, Japanese pine, Japanese pine, Japanese pine,
A bark extract of a plant belonging to the order Pinus, such as Ryukyu pine, Utsukushimatsu, Rheuma pine, White pine, and Anneda in Quebec region of Canada, is preferably used. Above all,
A bark extract of French coastal pine (Pinus Martima) is preferred.

The French coastal pine is a marine pine that grows on a part of the Atlantic coast of southern France. The bark of this French coastal pine tree contains proanthocyanidins, organic acids, and other physiologically active components, and it is known that its main component, proanthocyanidins, has a strong antioxidant action to remove active oxygen. There is.

The pine bark extract is obtained by extracting the above pine bark with water or an organic solvent. When water is used, hot water or hot water is used. As the organic solvent used for extraction, an organic solvent acceptable for the production of foods or drugs is used, for example, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, acetone, hexane, cyclohexane. , Propylene glycol, hydrous ethanol, hydrous propylene glycol, ethyl methyl ketone, glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane,
Edible oils and fats, 1,1,1,2-tetrafluoroethane, and 1,1,2-trichloroethene are included. These water and organic solvent may be used alone or in combination. In particular, hot water, hydrous ethanol, and hydrous propylene glycol are preferably used.

The method for extracting proanthocyanidins from pine bark is not particularly limited, but for example, a heating extraction method,
A supercritical fluid extraction method or the like is used.

The supercritical fluid extraction method is a method of performing extraction using a supercritical fluid which is a fluid in a state of exceeding the gas-liquid critical point (critical temperature, critical pressure) of a substance. As the supercritical fluid, carbon dioxide, ethylene, propane, nitrous oxide (laughing gas), etc. are used, and carbon dioxide is preferably used.

The supercritical fluid extraction method comprises an extraction step of extracting the target component with the supercritical fluid and a separation step of separating the target component and the supercritical fluid. In the separation step, either extraction separation due to pressure change, extraction separation due to temperature change, or extraction separation using an adsorbent / absorbent may be performed.

Supercritical fluid extraction may be carried out by the entrainer addition method. This method applies to supercritical fluids
For example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols,
By adding about 2 to 20 W / V% of aliphatic hydrocarbons, aromatic hydrocarbons, or ketones and performing supercritical fluid extraction with the obtained extraction fluid, OPC, catechins (described later), etc. It is a method of dramatically increasing the solubility of the target extract in an extraction solvent or enhancing the selectivity of separation, and is a method of efficiently obtaining a pine bark extract.

Since the supercritical fluid extraction method can be operated at a relatively low temperature, it has the advantage that it can be applied to substances that are altered or decomposed at high temperatures; the advantage that no extraction fluid remains; and the solvent can be recycled. In addition, there is an advantage that the desolvation process and the like can be omitted and the process is simplified.

Extraction from pine bark can be carried out by the liquid carbon dioxide batch method, liquid carbon dioxide reflux method,
It may be carried out by a supercritical carbon dioxide reflux method or the like.

For extraction from pine bark, a plurality of extraction methods may be combined. By combining a plurality of extraction methods, it becomes possible to obtain pine bark extracts having various compositions.

The pine bark extract used in the external preparation for skin of the present invention is specifically prepared by the following method, but this is an example and not limited to this method.

1 kg of bark of French coastal pine is placed in 3 L of a saturated aqueous solution of sodium chloride and extracted at 100 ° C. for 30 minutes to obtain an extract (extraction step). Then, the extract is filtered, and the resulting insoluble matter is saturated with sodium chloride 5
Wash with 00 ml to obtain a washing liquid (washing step). A crude pine bark extract is obtained by combining the extract and the washing solution.

Then, ethyl acetate 250 was added to the crude extract.
The process of adding ml and separating the layers and collecting the ethyl acetate layer is performed 5 times. The collected ethyl acetate solutions are combined and directly added to 200 g of anhydrous sodium sulfate for dehydration. Then, the ethyl acetate solution was filtered, and the filtrate was reduced to 1/5 of the original volume.
Concentrate under reduced pressure to volume. The concentrated ethyl acetate solution is poured into 2 L of chloroform, and the precipitate obtained by stirring is collected by filtration. Then, a washing step is carried out in which the precipitate is dissolved in 100 ml of ethyl acetate and then added again to 1 L of chloroform for precipitation to repeat twice. By this method, for example, 2 to 4 mer OPCs
About 5 g of pine bark extract containing 0% by weight or more and 5% by weight or more of catechins is obtained.

The extract derived from a raw material plant such as the pine bark is preferably 20% by weight in terms of dry weight of OPC.
The above content is more preferably 30% by weight or more. A pine bark extract is preferably used as a raw material containing a high proportion of OPC.

The extract extracted from the plant body using water or ethanol as described above also contains a pentamer or more of proanthocyanidins, but most of them are due to the solubility of proanthocyanidins in polar solvents. Is 10 to 20
It is less than or equal to the quantity.

Proanthocyanidins containing OPC, such as the above pine bark extract, are unlikely to cause coagulation precipitation or suspension with collagen peptides. Precipitation is less likely to occur as the content of OPC increases, and usually 20% by weight or more, preferably
Proanthocyanidins containing 0% by weight or more, and more preferably 50% by weight or more are used. Particularly, proanthocyanidins containing OPC in an amount of 1 part by weight or more based on 1 part by weight of a pentamer or more of proanthocyanidins are preferable. Although the reason why aggregation and precipitation does not occur despite the fact that the pentamer or more proanthocyanidins are contained, it is not clear that when OPC is contained in the above predetermined ratio or more, the aggregation of proanthocyanidins and proteins occurs. And suspension can be prevented.

It is preferable that the plant extract contains proanthocyanidins, particularly OPC, and catechins in an amount of 5% by weight or more in the raw plant extract. Catechins are polyhydroxyflavan-3
-It is a general term for all. As catechins, (+)-
Catechin, (−)-epicatechin, (+)-gallocatechin, (−)-epigallocatechin, epigallocatechin gallate, epicatechin gallate and the like are known. In addition to (+)-catechin which is said to be catechin in a narrow sense, gallocatechin, afzerekin and 3-galloyl derivative of (+)-catechin or gallocatechin are isolated from an extract derived from a raw material plant such as pine bark. Has been done.
For catechins, carcinogenesis inhibitory action, arteriosclerosis preventive action, fat metabolism abnormality inhibitory action, blood pressure elevation inhibitory action, platelet aggregation inhibitory action, antiallergic action, antiviral action, antibacterial action, caries preventive action, bad breath prevention action, It is known to have a normalizing effect on the intestinal flora, an scavenging effect of active oxygen and free radicals, and an antioxidant effect. It is known that catechins have an antidiabetic effect of suppressing an increase in blood sugar. Catechins have the property of increasing water solubility in the presence of OPC and at the same time activating OPC, and when ingested together with OPC, the action of OPC is enhanced.

Even if catechins are contained in the above-mentioned raw material plant extract, they do not react with proteins and improve the solubility and function of OPC, so proanthocyanidins 1
It is preferable that 0.1 part by weight or more is contained with respect to parts by weight. More preferably, the raw material plant extract containing 20% by weight or more of OPC contains 5% by weight or more of catechins. For example, when the catechins content of the pine bark extract is less than 5% by weight, the catechins may be added so as to be 5% by weight or more. 5 catechins
Most preferably, a pine bark extract containing at least 20% by weight of OPC is used.

Since proanthocyanidins, especially OPC, are antioxidants as described above, they have a particularly high whitening effect, a wrinkle preventing effect, an anti-inflammatory effect against atopic dermatitis and the like, and an effect as a condensed tannin. That is, the effect of preventing sagging due to the tightening effect of the skin can be obtained.

Further, OPC not only has an antioxidant effect but also has a protective effect on vitamin C, so that it enhances the collagen production ability in the skin and also has an excellent skin quality improving effect.

The external preparation for skin of the present invention contains proanthocyanidin in an amount of preferably 0.000 in terms of dry weight in the composition.
001% to 5% by weight, more preferably 0.001% to 2% by weight, still more preferably 0.01% to 1%
Contains by weight%.

Another essential component of the skin external preparation of the present invention has an average molecular weight of 7,0 obtained by decomposing proteins.
00 or less peptides (herein referred to as proteolytic peptides). The proteolytic peptide may be a peptide obtained by organic synthesis. The proteolytic peptide is not particularly limited as long as it is obtained by decomposing various animal and plant proteins with an acid, an alkali, or an enzyme. Examples of the protein as a raw material include animal proteins derived from meats such as cows, pigs, chickens, fish, animal milk, eggs, etc .;
For example, vegetable proteins derived from soybean, wheat, corn, peas and the like can be mentioned. In particular, collagen is preferable as the raw material protein, and collagen peptide, which is a degradation product thereof, is most preferable as the proteolytic peptide. Collagen decomposed into peptides not only gives a sticky feeling but also has an excellent moisturizing effect.

[0038] Collagen is a major protein constituting animal connective tissue, and is abundant in bone, tendon, skin, blood vessel wall and the like. There are various types that have one or more triple helix structures in the molecule and differ in the amino acid sequences of the constituent polypeptide chains. Gelatin, which is a modified product of collagen, is a water-soluble protein having a molecular weight of 300,000 to tens of thousands, which is obtained by extracting a raw material containing collagen with warm (hot) water, and is an alkali-treated gelatin (isoelectric point 4.
8 to 5.3) and acid-treated gelatin (isoelectric point 7 to 9).

A specific method for preparing collagen or a collagen peptide from gelatin will be described below. First, add the skin or bones of cows, pigs, etc. to an alkaline solution for 2-3 times.
A pretreatment for removing impurities contained in the raw material and facilitating the extraction is performed by performing an alkali treatment which is soaked for a month or an acid treatment which is soaked in dilute hydrochloric acid for a short period of time. For example, when the raw material is beef bone, since the bone contains minerals such as calcium phosphate, it is preliminarily soaked in dilute hydrochloric acid to remove the mineral, and this is extracted with warm (hot) water to obtain gelatin. . In the hot (hot) water extraction, generally, the first extraction temperature is 50 to 60 ° C., the extraction temperature is gradually raised after the second extraction, and finally the water is boiled. Then, the obtained gelatin is hydrolyzed with a commonly used acid or enzyme to obtain a collagen peptide.

The collagen peptide thus obtained is
Average molecular weight less than about 7,000, preferably about 6,000
It is 0 or less. Among the collagen peptides having such a molecular weight, it can be stably dissolved in a solution together with OPC,
In order to obtain the effect as an external preparation for skin in the present invention, the molecular weight is about 200 or more, preferably about 3,000.
0 or more, more preferably about 5,000 or more peptides are used. When the average molecular weight is more than 7,000, a high molecular weight proanthocyanidin (10 to 30 mer) is bound to easily cause precipitation or suspension.

Commercially available collagen peptides having such a molecular weight can be easily obtained. For example, collagen peptides derived from animal collagen include Nippi Peptide PBF and Nippi Peptide PRA.
(All manufactured by Nippi Corporation), SCP-5000, SC
P-3100 (all manufactured by Nitta Gelatin Co., Ltd.), collagen peptide DS (manufactured by Kyowa High Foods Co., Ltd.), Falconics CTP (manufactured by Ichimaru Falcos Co., Ltd.) and the like can be mentioned. In addition to such animal-derived collagen peptides, those having an amino acid composition similar to that of animal collagen are preferable, and examples of the collagen-like peptides include carrot (Daucus carota L.)-Derived peptides.

The external preparation for skin of the present invention contains a proteolytic peptide, preferably collagen peptide, in the composition in terms of dry weight of preferably 0.00001% by weight to 10% by weight.
% By weight, more preferably 0.0001% to 5% by weight
contains.

In addition to the above-mentioned proanthocyanidins and proteolytic peptides, the external preparation for skin of the present invention may contain other components usually used in quasi drugs, cosmetics, etc. within a range that does not impair the effects of the external preparation for skin. May be included. Examples of such components include water, other medicinal components, other oils, moisturizers, surfactants, ultraviolet absorbers, absorption promoters, fragrances, dyes, preservatives, thickeners, chelating agents, antiseptic agents. Examples thereof include mildew agents. Examples of other medicinal components include active oxygen scavengers, antioxidants, antiphlogistic and analgesics, antihistamines, antipruritics, bactericides, vitamins, hormones and the like.

An antioxidant may be added for the purpose of enhancing the stability of proanthocyanidins. As a result, it is possible to obtain the effect of preventing the oxidation of skin proteins and oils and fats and improving and protecting the skin quality.

As the antioxidant, carotenoids such as vitamin A, vitamin Bs, ascorbic acid, vitamin E, and derivatives thereof or salts thereof, L-cysteine and derivatives thereof or salts thereof, riboflavin,
SOD, mannitol, hydroquinone, tryptophan, histidine, quercetin, gallic acid and its derivatives, BHT, BHA, and botanical extracts such as button pipi extract, tomato extract, parsley extract, melissa extract, and augon extract. .

Of these, ascorbic acid not only enhances the stability of proanthocyanidins, but also exerts a synergistic effect on the skin, improving the skin quality (for example, improving the firmness and luster) and protecting blood vessels. It also enhances the effect. When ascorbic acid is added to the external preparation for skin of the present invention, the weight ratio to proanthocyanidin is preferably 1: 0.1 to 50, more preferably 1: 0.2 to 20. May be included. The amount of ascorbic acid is
It may be higher than the above ratio.

The external preparation for skin of the present invention can be prepared by mixing the proanthocyanidins and proteolytic peptides with other components by a commonly used method.
It can be used as medicines, quasi-drugs, cosmetics, toiletries. For example, lotion, makeup cream, emulsion, cream, pack, hair tonic, hair cream, shampoo, hair rinse, treatment, body shampoo, face wash, soap, foundation, white powder, lipstick, lip gloss, blusher, eye shadow, hairdressing , Hair restorer, aqueous ointment, oily ointment, eye drop, eye wash, dentifrice, mouthwash, ship, gel and the like. In addition, local long-term administration can also be carried out by a method of holding and absorbing in a carrier such as ship or gel or a cross-linking agent, and sticking to a local area.

The daily application amount of the external preparation for skin of the present invention is not particularly limited and is preferably in the range of 0.00001 g to 1 g as proanthocyanidins. A suitable amount of proteolytic peptide for proanthocyanidins within this range is preferably 0.0001 g to 0.1 g.
Is.

The external preparation for skin of the present invention has an effect of improving skin quality and an effect of improving blood flow when applied in an appropriate amount.
Particularly, when an extract containing 20% by weight or more of OPC in terms of dry weight is used as proanthocyanidin, a particularly excellent effect is obtained.

[0050]

The present invention will be described below with reference to examples.
It goes without saying that the invention is not limited by this example.

(Preparation of Proanthocyanidins) Pine bark extract (2-4mer: 40% by weight, pentamer or higher: 8.7% by weight, catechin: 5.1% by weight, trade name: flavangenol, Toyo Shinyaku Co., Ltd.) 20 g, Sephade
x LH-20 (Pharmacia Biotech Co., Ltd.)
And separated to give 7.6 g of a 2-tetramer and 1.6 g of a pentamer or more of proanthocyanidins in terms of dry powder weight. 1 g of the obtained pentamer or more proanthocyanidin was mixed with 2 g of the powder of the above pine bark extract to obtain a pine bark extract containing a large amount of pentamer or more proanthocyanidin (2 to 4 mer: 27% by weight). Pentamer or higher: 39% by weight,
Catechin 1.7% by weight) was prepared. These pine bark extracts were dissolved in an aqueous solution to a final concentration of 0.2% by weight.

Separation with Sephadex LH-20 was performed twice under the following conditions. First, the column volume of Sephadex LH-20 swollen with water is 50
It was packed in a column of 50 × 500 mm so as to be 0 mL, and washed with 500 mL of ethanol. After dissolving 10 g of the pine bark extract in 200 mL of ethanol and passing this through a column for adsorption, 100-80% (v /
v) Gradient elution with an ethanol-water mixed solvent, 1
00 mL was collected. For each fraction, by silica gel chromatography (TLC), the OP of 2-4
Each preparation of C (dimer: proanthocyanidin B-2 (R
f value: 0.6) Trimer: Proanthocyanidin C-1
(Rf value: 0.4) Tetramer: cinnamtannin A
₂ (Rf value: 0.2)) was used as an index to detect the elution of OPC. The conditions of TLC are as follows: TLC: silica gel plate (manufactured by Merck & Co., Inc.) Developing solvent: benzene / ethyl formate / formic acid (2/7/1) Detection reagent: sulfuric acid and anisaldehyde sulfuric acid sample Volume: 10 μL each

Fractions in which OPC was detected were collected and freeze-dried to obtain a powder. Then, 50% (v / v) water-acetone mixed solvent 10 was applied to the column where OPC was not detected.
00 mL was passed through to elute pentamer or higher proanthocyanidins, and the collected fractions were lyophilized to obtain a powder.

(Preparation of collagen and collagen peptide) Collagen (average molecular weight 300,000: manufactured by Koken Co., Ltd.), Nippi peptide PA-100 (average molecular weight 1
50,000: manufactured by Nippi Co., Ltd., collagen peptide DS (average molecular weight 7,000: manufactured by Kyowa High Foods Co., Ltd.), S
CP-5000 (average molecular weight 5,000: manufactured by Nitta Gelatin Co., Ltd.), Falconics CTP (average molecular weight 3,000: manufactured by Ichimaru Falcos Co., Ltd.), Nippi Peptide PA-10 (average molecular weight 1,000: Nippi Corporation) Manufactured by K.K.) and glycine (molecular weight 75: manufactured by Wako Pure Chemical Industries, Ltd.) were used to prepare 10 mL of each aqueous solution such that the collagen, collagen peptide or amino acid content was 10.0% by weight.

(Example 1: Evaluation of flocculation-precipitation) 1 mL of each of the collagen, collagen peptide or amino acid solutions prepared as described above was mixed with the above-mentioned proanthocyanidin solution 1
mL was mixed and allowed to stand at room temperature for 1 week, and after 1 week, the presence or absence of precipitation and suspension was visually observed. The results are shown in Table 1.

[0056]

[Table 1]

As can be seen from Table 1, suspensions or precipitates were observed in all of the mixed solutions of pentamer or higher proanthocyanidins and collagen peptides or collagen of molecular weight. In contrast, almost no suspension was observed in the mixed solution of the proanthocyanidin of 2 to 4 mer and the collagen peptide or amino acid having a molecular weight of 7,000 or less. No precipitation was observed in the pine bark extract containing more proanthocyanidins of 2 to 4 mers than proanthocyanidins of 5 or more mer. Also, the average molecular weight is 30
When 20,000 collagen was used, gelled solid content was deposited. As described above, the 2- to 4-mer proanthocyanidin (OPC) or the pine resin extract containing a large amount of OPC as proanthocyanidin has a molecular weight of 7,000.
Does not cause suspension or precipitation with the following collagen peptides,
It was found to be stable as a mixture solution.

(Example 2: Evaluation of blood flow improving effect and moisturizing effect) The final concentration of the pine bark extract was 0.01% by weight.
And the final concentration of collagen peptide is 0.01% by weight
1 to 8 in the combination shown in Table 2
Was prepared.

[0059]

[Table 2]

Ten healthy people aged 20 to 50 were used as test subjects. First, 2.0 cm square markings were made on each of the left and right forearms of each subject at a total of 8 places, and a blood flow meter (laser blood flow imaging device PIM II; Swedish Permi) was used.
ed) was used to measure the blood flow volume under the skin, and the average value was defined as a. After measurement, 0.1 ml of the prepared lotion 1-8
Apply to each marking part one by one, 0.5 hours after application, 1
Subcutaneous blood flow was measured after 1 hour, 1.5 hours, and 2 hours, and the average value was defined as b. The blood flow improvement rate was calculated from the obtained average value of the blood flow rate at each time using the following formula: Blood flow improvement rate (%) = 100 × (ba) / a The results are shown in FIG. .

Two hours after the application, the electric conductivity (unit: μmho) of the lotion application site was measured by a high frequency conductivity measuring device (SKICON-200, IBS).
Company) and the average value was calculated to evaluate the moisturizing property. The results are shown in Table 3. The electric conductivity reflects the amount of water.

[0062]

[Table 3]

As can be seen from FIG. 1, the average molecular weight is 1,
000, 3,000, 5,000, or 10,000
A high blood flow improving effect was obtained when the lotion containing the collagen peptide of 1. and a pine bark extract containing proanthocyanidins containing a large proportion of 2 to 4 monomers was used.

From Table 3, the average molecular weights are 1,000 and 3,
A lotion containing 000, 5,000, or 10,000 collagen peptides and a pine bark extract containing proanthocyanidins having a large proportion of 2 to 4 is more electrically conductive than other lotions. The rate was high and the moisture retention was relatively high. When a collagen peptide having an average molecular weight of 1,000 was used, a relatively high moisturizing effect was obtained even with a mixture with a pine bark extract containing proanthocyanidins having a large proportion of pentamers or more. .

[0065]

The external preparation for skin of the present invention has more excellent blood flow improving effect and moisturizing effect than those obtained by the conventional combination of proanthocyanidin and proteolytic peptide. Since the external preparation for skin of the present invention is unlikely to cause aggregation and precipitation of proanthocyanidins and proteolytic peptides, it can be exerted without impairing other actions and effects possessed by each.

[Brief description of drawings]

FIG. 1 is a graph showing changes in blood flow improvement rate in the skin after application of various lotions.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI A61K 38/00 A61K 37/18 (56) References JP-A-52-111600 (JP, A) JP-A-11-171721 (JP) , A) JP 2000-26228 (JP, A) JP 2000-229834 (JP, A) JP 6-336423 (JP, A) JP 9-175945 (JP, A) JP 61- 16982 (JP, A) Special Table 2003-504402 (JP, A) International Publication 01/032131 (WO, A1) International Publication 96/00561 (WO, A1) FRAGRANCE JOURNA L, 1984, No. 69, pp. 111-115. FRAGRANCE JOURNA L, 2000, Vol. 28, No. 2, pp. 27-32. (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61K 7/00-7/50, 31/353 A61K 31/7048, 38/01

Claims (2)

(57) [Claims] 1. A proanthocyanidin and an average molecular weight
A peel Hadagaiyo agent you containing 3,000 7,000 The following proteolytic peptide, wherein the proanthocyanidin is a degree of polymerization of 5 or more proanthocyanidins pair 1 part by weight
1 part by weight or more of the proanthocyanidin of 2 to 4 mer
External preparation for skin contained in the ratio of . 2. The external skin preparation according to claim 1, wherein the peptide is a collagen-derived peptide.