JPH0967266A - Inhibitor of hyaluronidase - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an inhibitor of hyaluronidases, having excellent inhibiting activities against hyaluronidases and excellent in safety. SOLUTION: This inhibitor of hyaluronidases comprises an extract of a seaweed belonging to the genera Monostroma, Ulva, Enteromorpha, Bryopsis, Caulerpa and Codium which are green algae, the genera Analipus, Cladosiphon, Nemacystis, Ecklonia, Lessonia, Macrocystis, Fucus, Ascophyllum and Durvillea which are brown algae, the genera Porphyra, Gelidium, Beckerella, Pterocladia, Gloiopeltis, Eucheuma, Gigartina, Iridaea, Chondrus, Rhodymenia and Ceramium which are red algae as an active ingredient. Thereby, an active substance contained in the extract and inhibiting the hyaluronidases has suppressing actions on the decomposition of hyaluronic acid, is thereby capable of activating dermal cells and preventing the skin from aging and manifests excellent effects on the prevention of the occurrence of wrinkles and skin roughening and the impartment of the smooth, moist and fresh skin. The extract is blended in a dermal preparation for external use to thereby provide the inhibitor of hyaluronidases suitable as the dermal preparation for external use, etc., having high safety. The inhibitor maintains wettability of joints, is useful as even an therapeutic agent, etc., for the joints and further as an antiinflammatory and an antiallergic agent and can be used for various applications such as medicines, quasi-drugs, cosmetics, etc.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a hyaluronidase inhibitor comprising a highly safe seaweed extract having an excellent hyaluronidase inhibitory activity.

[0002]

2. Description of the Related Art Hyaluronidase is a hydrolase of hyaluronic acid and is widely distributed not only on the skin but also on animal tissues. Hyaluronic acid, which is the substrate for this enzyme, is a type of mucopolysaccharide that is often found in tissues such as skin, ligaments, synovial fluid, and the vitreous body of the eye.For example, in skin, protection of cells, transport of nutrients, and tissue For holding water, maintaining flexibility, etc.
It also plays an important role as synovial fluid in maintaining tissue structure, function, and maintaining lubricity.

It is known that the amount of hyaluronic acid in the living body in the skin and joints decreases due to aging or pathological conditions, and as a result, skin dryness, rough skin, firmness, loss of elasticity, increases in wrinkles and wrinkles, Alternatively, it causes joint pain and the like due to deterioration of wettability of the joint. For this situation,
It is considered that the hyaluronidase inhibitor contributes to the maintenance of the amount of hyaluronic acid in the living body by suppressing the decomposition of hyaluronic acid. Recently, measures such as application of cosmetics containing hyaluronic acid to the skin and injection of hyaluronic acid into joints have been taken.However, hyaluronidase inhibitors are also effective in stabilizing these exogenous hyaluronic acids. Can be used.

Further, hyaluronidase is activated during inflammation, destroys the connective tissue matrix, enhances the infiltration of cells of the inflammatory system into tissues, and enhances the permeability of blood vessels.
It is known that it is likely to be involved in the process of histamine release from mast cells in type 1 allergy. Therefore, the hyaluronidase inhibitory activity is not only involved in maintaining the hyaluronic acid level in the living body, but also shows a high correlation with anti-inflammatory and anti-allergic activities. In fact, the anti-inflammatory and anti-allergic agents developed so far, indomethacin, aspirin, sodium cromoglycate,
Hyaluronidase inhibitory activity is recognized in many such as tranilast.

From the above, it is expected to develop a hyaluronidase inhibitor having an excellent hyaluronidase inhibitory activity and having high safety when applied to the human body such as skin.

[0006]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a hyaluronidase inhibitor having excellent hyaluronidase inhibitory activity and excellent safety.

[0007]

[Means for Solving the Problems] In order to solve the above-mentioned problems, the present inventors have studied various natural products, particularly plant extracts. As for land plants, tea polyphenols extracted from tea that has already been used for drinking (JP-A-6-9391), extracts of chimpi, pheasant, and Rakan fruit used as crude drugs or food and drink (JP-A-6-9391). -80
No. 576), an extract of the Japanese beech family Vladimirium japonicum (JP-A-6-239757), a cashew nut shell oil (JP-A-6-329526), an extract of a botanical plant (JP-A-7-10765) and the like, and a hyaluronidase. Although a substance having inhibitory activity and the like has been found, the present inventors have conducted intensive studies in order to develop a new hyaluronidase inhibitor, and as a result, the target hyaluronidase inhibitory activity in the extract of seaweed shown below. They found out the present invention and completed the present invention.

[0008] That is, the hyaluronidase inhibitor of the present invention is a green alga of the genus Human Exa, Genus Aosa, Genus Aonori,
Genus Nematoda, genus Iwazu, genus Mill, genus Matsumo of brown algae, Okinawa mozuku genus, mozuku genus, Kajime genus, Lessonia genus,
Macrocystis genus, Hibamata genus, Ascophyllum genus,
Contains an extract of seaweeds belonging to the genus Darbili, red seaweed Amanori, Maxa, Hirakusa, Opacusa, Funori, Giraffe, Suginotori, Iridaea, Tsunomata, Dulus, and Aegis. It is characterized by

[0009]

[Function] Regarding the mechanism by which the seaweed extract of the present invention exerts an excellent antiaging effect on the skin and the like, the hyaluronidase inhibitory active substance contained in the extract suppresses the decomposition of hyaluronic acid in skin cells. It is presumed that, by maintaining that level, the deterioration of the skin's moisturizing property, flexibility and elasticity is suppressed, and a remarkable effect of preventing skin aging is exhibited. Further, due to its excellent hyaluronidase inhibitory activity, it is effective for the prevention and treatment of inflammation and allergies caused by hyaluronidase.

The details of the present invention will be described below.
Examples of seaweed used in the present invention include, for example, green algae,
In the genus Astragalus, human abalone (Monostroma nitidum),
Ulva pertusa, Ulva sublittoralis in the genus Ulva, Ulva sublittoralis, Enteromorphaprolifera in the genus Ulva
opsis plumosa), in the genus Ivy,
rpa lentillifera), a mill in the genus Mill (Codium fragil
e), of the brown algae, in the genus Pinus, Pinus (Analipus japoni)
cus), Okinawa mozuku (Cladosi)
phon okamuranus), Mozuku (Nemacystis
decipiens), in the genus Kajime, Kajime (Ecklonia cava),
Ecklonia maxima, Lessonia nigresce in Lessonia
ns, Macrocystis in the giant kelp (Mac
rocystis pyrifera), in the genus Hibamatata (Fucus)
evanescens), Ascophyllum nod
osum, Durvillea antarctica in Derbyria, red algae, and Porphyra tener in Porphyra.
a), Porphyra yezoensis, Gelidium amansii in Pleurotus, Beckerella subcostata in Pseudomonas, and Pterocl in Prunus
adia tenuis, Fukurofunori (Gloiopeltis in the genus Funori)
furcata), Mahunori (Gloiopeltis tenax), Eucheuma cottonii, Eucheuma spinosum in the genus Giraffe, Gigartina chamissoi in the genus Suginori, Iridaea pulchra in the genus Iridaea, Iridaea cornuspus in the genus Iridaea cornucopiae. Tsunomata (Chondrus occ
ellatus), dalus (Rhodymenia palmat)
a) and, in the genus Squid, there can be mentioned, for example, Axusa (Ceramium boydenii).

The method for extracting the substance of the present invention is not particularly limited, and an ordinary extraction method is adopted, such as water, a hydrophilic organic solvent,
It is extracted from seaweed by using a single solvent selected from the group consisting of other organic solvents and the like or an arbitrary mixed solvent of two or more kinds. Examples of the organic solvent include methanol, ethanol, isopropanol, n-butanol, 1,3-butylene glycol, propylene glycol, ethyl acetate, acetone, methyl ethyl ketone, acetonitrile,
Examples thereof include dimethyl sulfoxide, dimethylformamide, chloroform, n-hexane and benzene. Among these, it is particularly preferable to perform extraction using water or a mixture of water and a lower alcohol such as methanol, ethanol or isopropanol. In this case, the ratio of water to lower alcohol is 100/0 for water / lower alcohol.
It is preferably 30/70 (V / V, volume ratio).
The ratio of seaweed drug substance to extraction solvent is seaweed drug substance (dry matter) /
The solvent ratio is preferably in the range of 1/50 to 1/2. As other extraction conditions, the extraction temperature is not particularly limited, but it is preferably carried out in the range of 5 to 80 ° C. for 1 to 24 hours with stirring. The extraction pH is not particularly limited as long as it does not tend to be extremely acidic or extremely alkaline.

This extract may be used as it is, may be used as a dilute solution or as a concentrated extract, or may be a dry powder by freeze-drying or the like, or may be prepared as a paste. When prepared as a dry powder, it is preferably dissolved in water or a lower alcohol such as methanol, ethanol, isopropanol or the like in advance, or solubilized in an external composition containing water described below. .

The dosage form of the hyaluronidase inhibitor of the present invention can be, for example, tablets, capsules, powders, oral liquids, fine granules, and other oral drugs, and liniment agents, spray agents, lotions. It can be used for the outer skin such as ointment. When used as a skin external preparation, a seaweed extract, which is an essential component, can be blended at any concentration, but usually 0.01 to 30 wt% (hereinafter,
Simply called "%". ), Preferably 0.1 to 10%.

The skin external preparation containing the seaweed extract, which is an essential component of the present invention, contains, in addition to the above-mentioned essential components, raw materials usually used for external preparations such as surfactants, oils, alcohols and moisturizers. , Thickeners, antiseptics, antioxidants, chelating agents, pH adjusters, fragrances, dyes, ultraviolet absorbers / scatterers,
Vitamins, amino acids, water and the like can be added.

Specifically, the surfactants include lipophilic glycerin monostearate, self-emulsifying glycerin monostearate, polyglycerin monostearate, sorbitan monooleate, polyethylene glycol monostearate, polyoxyethylene sorbitan. Monooleate, polyoxyethylene cetyl ether, polyoxyethylene sterol, polyoxyethylene lanolin,
Polyoxyethylene beeswax, nonionic surfactant such as polyoxyethylene hydrogenated castor oil, sodium stearate, potassium palmitate, sodium cetyl sulfate,
Anionic surfactants such as sodium laurylphosphate, triethanolamine palmitate, sodium polyoxyethylenelaurylphosphate, sodium N-acylglutamate, cationic surfactants such as stearyldimethylbenzylammonium chloride and stearyltrimethylammonium chloride, alkyl chloride Aminoethylglycine solution,
Examples thereof include amphoteric surfactants such as lecithin.

Examples of oils include castor oil, olive oil, cacao oil, camellia oil, coconut oil, wax, jojoba oil, grape seed oil, vegetable oils such as avocado oil, animal oils such as mink oil and egg yolk oil, and honey. Wax such as wax, spermaceti, lanolin, carnauba wax, candelilla wax, liquid paraffin, squalane, microcrystalline wax, ceresin wax, paraffin wax, hydrocarbons such as petrolatum, lauric acid, myristic acid, stearic acid, oleic acid , Natural and synthetic fatty acids such as isostearic acid, behenic acid, cetanol, stearyl alcohol,
Examples thereof include natural and synthetic higher alcohols such as hexyldecanol, octyldodecanol, and lauryl alcohol; esters such as isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, octyldodecyl oleate, and cholesterol oleate.

Examples of moisturizers include polyhydric alcohols such as glycerin, propylene glycol, 1,3-butylene glycol, sorbitol, polyglycerin, polyethylene glycol, dipropylene glycol, amino acids, sodium lactate, sodium pyrrolidonecarboxylate and the like.
Examples thereof include MF components, water-soluble polymer substances such as hyaluronic acid, collagen, mucopolysaccharides and chondroitin sulfate.

As the thickener, sodium alginate,
Natural polymer substances such as xanthan gum, aluminum silicate, quince seed extract, tragacanth gum, starch, etc., semi-synthetic polymer substances such as methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, soluble starch, cationized cellulose, carboxyvinyl polymer, polyvinyl alcohol, etc. The synthetic polymer substance and the like can be exemplified.

As the preservative, benzoate, salicylate, sorbate, dehydroacetate, paraoxybenzoate, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'- Trichlorocarbanilide, benzalkonium chloride, hinokitiol,
Resorcinol, ethanol and the like can be exemplified.

Antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, and ascorbic acid, and chelating agents include disodium edetate, ethylenediaminetetraacetate, pyrophosphate, hexametaphosphate, and citrate. Acid, tartaric acid, gluconic acid, etc., as a pH adjuster, sodium hydroxide,
Examples include triethanolamine, citric acid, sodium citrate, boric acid, borax, potassium hydrogen phosphate and the like.

Examples of the UV absorbing / scattering agent include 2-hydroxy-4-methoxybenzophenone, octyldimethylparaaminobenzoate, ethylhexylparamethoxycinnamate, titanium oxide, kaolin, talc and the like. As vitamins, vitamin A,
Vitamin B, vitamin C, vitamin D, vitamin E, vitamin F, vitamin K, vitamin P, vitamin U, carnitine, ferulic acid, γ-oryzanol, α-lipoic acid,
Examples thereof include orotic acid and derivatives thereof. As the amino acids, glycine, alanine, valine, leucine, isoleucine, serine, threonine, phenylalanine, tyrosine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, glutamic acid, arginine,
Histidine, lysine, their derivatives, etc. can be illustrated.

The optional components are not limited to these. By appropriately blending the above essential components and optional components, for example, the seaweed extract of the present invention 0.01 to 3
0%, 0-80% oil as an optional component, 0-surfactant
It is possible to provide a skin external preparation containing 12%, a moisturizing agent 1 to 15%, a purified water balance, and a trace amount of a preservative. Specifically, creams, emulsions, lotions, beauty essences, packs,
Under makeup, foundation, jelly,
It can be used as a product form such as an ointment.

Specific examples of the case where the hyaluronidase inhibitor of the present invention is used as skin cosmetics are as follows (1) to (4)
It is as follows. (1) Skin cream 0.1-10% of seaweed extract of the present invention, oil content 20-70
%, Surfactant 2-7%, moisturizer 1-10%, purified water balance, preservative trace amount, fragrance trace amount.

(2) Emulsion 0.1 to 10% of seaweed extract of the present invention, 10 to 40 oil
%, Alcohols 0 to 15%, surfactants 1 to 5%, moisturizers 1 to 10%, thickeners 0 to 2%, purified water balance, preservative trace amounts, perfume trace amounts.

(3) For lotion and beauty essence: Seaweed extract of the present invention 0.1 to 10%, alcohols 5 to
20%, surfactant 0-2%, humectant 2-8%, thickener 0-2%, antioxidant 0-0.5%, chelating agent 0-
0.1%, pH adjuster 0-0.2%, purified water balance,
A lotion and beauty liquid containing a very small amount of antiseptic, a very small amount of pigment, and a very small amount of fragrance.

(4) In the case of a pack, the seaweed extract of the present invention is 0.1-10%, the alcohols are 2-
Packing agent containing 10%, moisturizing agent 2 to 10%, inorganic powder 0 to 20%, film forming agent 10 to 20%, purified water balance, preservative trace amount, perfume trace amount.

[0027]

EXAMPLES Next, the present invention will be specifically described with reference to examples, test examples, etc., but the present invention is not limited to the following examples.

Production Example (Production of Seaweed Extract) 100 g of dried pine wilt was stirred with 20 volumes of water for 3 hours, and the supernatant was concentrated and freeze-dried.
16 g of matsumo extract was obtained. Further, in the same manner, seaweeds other than Matsumo, namely, human algae of green algae, Anaaosa, Ooosaosa, Sujiaonori, Hanemomo, cuttlefish,
Mill, White-faced Juzumo, Brown Alga Okinawa Mozuku, Mozuku, Kajime, Ecklonia maxima, Giant Kelp, L
essonia nigrescens, Hiba Mata, Ascophyllum nodosu
m, Durvillea antarctica, Shio midoro, red algae horned horned, Asakusanori, Susabinori, Maxa, Hirakusa,
Pterocladia tenuis, Fukuro Funori, Mahunori, Eucheu
ma cottonii, Eucheuma spinosum, Gigartina chamisso
Extracts of each of i, Iridaea pulchra, Ezo Tsunomata, Tochaka, Tsunomata, Dulus, Kaginori, and Amixa were obtained. In addition, other solvents, namely methanol,
Ethanol, isopropanol, n-butanol, 1,
With respect to 3-butylene glycol, propylene glycol, ethyl acetate, acetone, methyl ethyl ketone, acetonitrile, dimethylsulfoxide, dimethylformamide, chloroform, n-hexane, and benzene, an extract was obtained from each of the seaweeds in the same manner as in the above water. It was

Test Example 1 (Hyaluronidase Inhibitory Activity Test) The hyaluronidase inhibitory activity of each seaweed extract (extract sample) obtained in the above Production Example was measured by the following method. To the enzyme (type IV-S from Bovine testis, SIGMA) solution 100 μl (1,580 unit / ml) was added each seaweed extract extract sample 200 μl obtained in the above Production Example, 37
It was left for 20 minutes at ℃. Next, the enzyme activator (Compound
48/80, SIGMA) solution (0.1 mg / ml) (200 μl) was added and left at 37 ° C. for 20 minutes, and then the substrate potassium hyaluronate (from rooster comb, Wako Pure Chemical Industries, Ltd.) solution (0.4 mg / ml) (500 ml) was added and left at 37 ° C. for 40 minutes. Next, 0.4N sodium hydroxide solution 200μ
After the reaction was stopped by adding 1, the amount of N-acetylhexosamine produced by the modified Morgan-Elson method (J. Biol. Chem., 217, 959 (1955)) was determined from the absorbance OD ₅₈₅ nm. In addition, 0.1 mM acetate buffer (pH 3.5) was used for enzyme reaction,
The hyaluronidase inhibitory activity was calculated by the inhibition rate calculated from the following formula.

[0030]

[Equation 1]

Table 1 shows the results of calculating the 50% inhibitory concentrations (IC ₅₀ ) from the inhibition rates at various sample concentrations for the water extracts (extract samples) of each seaweed obtained in the above Production Example. The lower the value, the higher the hyaluronidase inhibitory activity.

[0032]

[Table 1]

(Discussion of Table 1) As is clear from the results shown in Table 1 above, the seaweed extracts of the present invention, that is, the green algae of the human algae, Anaaosa, Ooosaosa, Sujiaonori, Hanemomo, Kubirezu, mill, brown algae Matsumo, Okinawa Mozuku, Mozuku, Kajime, Ecklonia maxima, Giant Kelp, Lessonia nigrescens, Hiba Mata, As
cophyllum nodosum, Durvillea antarctica, red algae Prickly Pear, Prickly Pear, Pteroc, Pteroc
ladia tenuis, fukuro funori, mafunori, Eucheuma cot
tonii, Eucheuma spinosum, Gigartina chamissoi, Iri
Most of the extracts of daea pulchra, Ezo tsunomata, Tochaka, Tsunomata, Dals, and Amixa showed extremely high hyaluronidase inhibitory activity comparable to that of sodium cromoglycate (control), which is known to have hyaluronidase inhibitory activity. The extracts obtained from other extraction solvents also showed almost the same results as the water extract. Especially,
Anosa of the genus Ulva, Ecklonia maxima of the genus Kamen
Lessonia nigrescens from the genus Lessonia, Ascophyllum nodosum from the genus Ascophyllum, and Durvillea a from the genus Darbyria
ntarctica, Funori mafunori, Iridea genus I
It was revealed that ridaea pulchra and Ezo tsunomata have remarkably high hyaluronidase inhibitory activity. On the other hand, even the same seaweed extract is a seaweed extract that is outside the scope of the present invention, that is, the green alga Juzumo genus Nematoda, brown algae Shiomidoro genus Shiomidoro, red alga Ogonori genus Ogonori, Kaginori Each extract of the genus Kaginori is
It did not show hyaluronidase inhibitory activity.

Example 1 and Comparative Example 1 (Production of Cream) Components 1 to 7 and 8 to 11 shown in Table 2 below were separately mixed and dissolved, and then the solution of components 8 to 11 was stirred therein. After the solutions 1 to 7 were added and emulsified, the component 12 was added during cooling and cooled to room temperature to prepare creams shown in Table 2 below. The numbers in the table indicate the blending amount (% by weight), and POE (20) indicates the polyoxyethylene and the number of moles added thereto (the same applies to the following examples etc.). Further, Comparative Example 1 is a case where a cream was prepared without blending the seaweed extract of the present invention as the component 8 (also prepared in the following Comparative Examples 2 to 4 without blending the seaweed extract). .

[0035]

[Table 2]

Example 2 and Comparative Example 2 (Production of lotion) Components 1 to 6 shown in Table 3 below were sequentially added to Component 7 and dissolved, and further Component 8 was added to prepare lotion shown in Table 3 below. .

[0037]

[Table 3]

Example 3 and Comparative Example 3 (Production of beauty essence) Components 1 to 4 and components 5 to 9 shown in Table 4 below were separately dissolved and mixed to prepare a beauty essence.

[0039]

[Table 4]

Example 4, Comparative Example 4 (Production of Emulsion) Components 1 to 7 shown in Table 5 below were heated and dissolved at 70 ° C. On the other hand, components 8 to 13 were heated and dissolved at 70 ° C., the oil and fat solution (components 1 to 7) was added thereto, and the mixture was emulsified. Then, while cooling, component 14 was added and cooled to room temperature. 5
The emulsion shown in was prepared.

[0041]

[Table 5]

Test Example 2 (Evaluation Result of Use Test) The above Example 1 containing the water extract of each seaweed obtained in the above Production Example.
.About.4 and the creams, lotions, beauty essences and emulsions of Comparative Examples 1 to 4 were evaluated by the following use test. (Usage test) Five women (30 to 50 years old), 5 times each, twice a day (morning and night), for three consecutive months, Examples 1 to 4 and Comparative Example 1
After using 4 to 4 separately on the left and right faces by the half-face method, a questionnaire survey was conducted on small wrinkles (A) and quality [gloss (B), moist (C)]. In the questionnaire survey, when the example (the product of the present invention) is good, ○ (there is an improvement effect),
When the example (the product of the present invention) and the comparative example are the same, Δ,
When the comparative example was good, it was evaluated as x (no improvement effect). The results of these usage tests are shown in Table 6 below.

[0043]

[Table 6]

(Discussion of Table 6) As is apparent from the results shown in Table 6 above, the preparations (Examples) [creams, lotions, beauty essences, emulsions] containing the extract of seaweed within the scope of the present invention are:
Improvement effects of small wrinkles (A), luster (B), and moisturization (C) were observed. This effect is that the hyaluronidase inhibitory active substance contained in the seaweed extract suppresses the decomposition of hyaluronic acid in the skin cells, and by maintaining the level thereof, the moisturizing property of the skin, flexibility, and suppressing the decrease in elasticity, It is presumed that it has achieved remarkable skin cell activation and skin aging prevention effects, etc., and has prevented the occurrence of wrinkles and rough skin, giving a smooth, moist and youthful skin. On the other hand, even in the same seaweed extract, the extract of seaweed which is outside the scope of the present invention, that is, the green alga Juzumo genus Hosojuzumo, brown algae Shiomidoro genus Shiomidoro, red alga Ogonori genus Ogonori, Kaginori genus The preparations (comparative examples) [creams, lotions, beauty essences, and emulsions] containing the respective extracts of Kaginori were not found to have any improving effect on wrinkles (A), luster (B) and moisturization (C).

[0045]

EFFECTS OF THE INVENTION According to the present invention, by inhibiting hyaluronic acid decomposition, skin cells are activated, skin aging is prevented, wrinkles and rough skin are prevented from occurring, and smooth, moist and youthful skin is obtained. By providing such an effect, it is possible to provide a highly safe hyaluronidase inhibitor suitable for external preparations for skin and the like. Further, the hyaluronidase inhibitor of the present invention maintains the wettability of joints, can be used as a therapeutic agent for joints, and is also useful as an anti-inflammatory or anti-allergic agent. Furthermore, the hyaluronidase inhibitor of the present invention, because it is extracted from seaweeds that have long been used for food and the like, is extremely safe for the human body, and furthermore, since it has an excellent hyaluronidase inhibitory activity, a drug, It can be used for various applications such as quasi drugs and cosmetics.

Claims (1)

[Claims] 1. A green alga, Human Genus, Ulva genus, Aonori genus, Anemone genus, Iwazuda genus, Mil genus, Brown algae Matsumo genus, Okinawa mozuku genus, Mozuku genus, Kadime genus, Resonia genus, Macrocystis genus, Hiba matata Extracts of seaweed belonging to the genera, Ascophyllum genus, Darbilia genus, red seaweed Amanori genus, Maxa genus, Hirakusa genus, Hawthorn genus, Funori genus, Ginseng genus, Suginori genus, Iridaea genus, Tsunomata genus, Dals genus, Iggis genus A hyaluronidase inhibitor which is contained as an active ingredient.