JP2000096050A - Promoter for production of hyaluronic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a safe promoter for production of hyaluronic acid, capable of being readily used and useful for prevention from getting older of the human skin, or for prevention and treatment arthritis or the like by adding an extract of a plant belonging to the family Rutaceae as an active ingredient. SOLUTION: This promoter for production of hyaluronic acid contains an extract obtained by extracting a flower, a leaf, a stem or a wooden part of a plant belonging to the family Rutaceae such as Citrus unshiu, Citrus Sinensis and Seville orange with a solvent such as water, methanol and ethanol as an active ingredient. The skin preparation for external use is preferably prepared by adding the promoter for the production of the hyaluronic acid preferably in the proportion of 0.001-10.0 wt.% (expressed in terms of dried weight).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a hyaluronic acid production promoter. More specifically, the present invention relates to a hyaluronic acid production promoter that promotes hyaluronic acid production in humans. The hyaluronic acid production promoter can be effectively applied to the prevention of aging of human skin (maintaining skin firmness and elasticity), the prevention and treatment of arthritis and the like, the initial treatment of burns, and the like. In particular, by incorporating the hyaluronic acid production promoter of the present invention, there is provided a skin external preparation capable of maintaining skin firmness and elasticity, preventing wrinkles, and maintaining a moist and youthful skin condition.

[0002]

2. Description of the Related Art In recent years, research on aging has been advanced. The cause of skin aging is that aging is an important factor from a macro perspective. In addition, the effects of dryness, oxidation, sunlight (ultraviolet rays), and the like are also direct factors related to skin aging. As specific phenomena of skin aging, reduction of mucopolysaccharides such as hyaluronic acid, collagen cross-linking reaction, damage of cells by ultraviolet rays, and the like are known.

[0003] Among them, hyaluronic acid retains water in the intercellular space, retains cells based on the formation of a jelly-like matrix in tissues, retains lubricity and flexibility of tissues, and exerts external forces such as mechanical obstacles. It has many functions, such as resistance to bacterial infection and prevention of bacterial infection ("Bio Industr
y ", vol. 8, p. 346 (1991). For example, it is said that the amount of hyaluronic acid in the skin decreases with aging, and along with that, skin aging such as fine wrinkles and dryness appears.
Many cosmetics containing hyaluronic acid and collagen have been proposed as such aging skin improving agents. However, these conventional cosmetics only exert a moisturizing effect on the skin surface and cannot essentially improve aging skin. In addition, cosmetics containing various vitamins and crude drugs as skin cell activators have been proposed, but these have not yet been able to improve and treat aging skin.

Further, hyaluronic acid contained in synovial fluid covers the surface of articular cartilage and contributes to smooth operation of joint functions. Hyaluronic acid concentration in normal human joint fluid is about 2.3 mg / ml, but in the case of rheumatoid arthritis,
The concentration of hyaluronic acid in the synovial fluid drops to about 1.2 mg / ml, and at the same time the viscosity of the synovial fluid drops significantly ("Arthrit
is Rheumatism ", vol. 10, p. 357 (1967). In addition, it is known that a decrease in the hyaluronic acid content occurs in suppurative arthritis and gouty arthritis as in the case of rheumatoid arthritis (" Combined composition "(Kanehara Publishing), p.481, 19
1984). In the above diseases, it is conceivable to increase the amount of hyaluronic acid in synovial fluid for improving lubrication function, covering and protecting articular cartilage, suppressing pain, and improving or normalizing pathological synovial fluid. For example, it has been reported that the above-mentioned improvement is observed when a joint injection therapy of sodium hyaluronate is performed in a rheumatoid arthritis patient ("inflammation").
(Japan Society of Inflammation), 11, 16, 1991). Similarly, in traumatic arthritis, osteoarthritis and osteoarthritis, the above-mentioned improvement effect has been reported by joint injection therapy of hyaluronic acid. ("Connective tissue and disease" (Kodansha),
246, 1980).

[0005] However, the treatment of the above-mentioned diseases is long-term and requires a doctor's prescription. Therefore, a skin external preparation containing a hyaluronic acid production promoter which can be easily treated in daily life has been desired.

In the healing process after burn injury, hyaluronic acid is significantly increased in granulation during the period from the initial stage of granulation tissue growing below the necrotic tissue until the entire tissue is replaced with granulation tissue. Is known ("Connective tissue and disease" (Kodansha), p. 153, 1980),
Hyaluronic acid production promoters are also expected as an initial therapeutic agent for burns.

On the other hand, drugs that produce human cell hyaluronic acid include insulin-like growth factor-1 and epidermal growth factor ("Biochemica Biophysica Acta", 1014, p. 305 (19)
89)) and cytokines such as interleukin-1 (Journal of the Japan Society of Obstetrics and Gynecology, 41, 1943, 1989), or phorbol ester ("Exper").
Imental Cell Research ", vol. 148, p. 377 (1983)) and the like, but none of them can be used easily and safely as cosmetics, bath additives, pharmaceuticals and the like.

[0008]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and provides a safe and easy-to-use hyaluronic acid production promoter which promotes hyaluronic acid production in humans. The purpose is to:
The hyaluronic acid production promoter of the present invention can prevent aging of human skin (maintaining skin elasticity and elasticity), prevent and treat arthritis, etc.
It can be effectively applied to the initial treatment of burns and the like. In particular, by incorporating the hyaluronic acid production promoter, there is provided a skin external preparation that can maintain skin firmness and elasticity, prevent wrinkles, and maintain a moist, youthful skin condition.

[0009]

Means for Solving the Problems The present inventors have investigated the ability of various substances to promote the production of hyaluronic acid in order to solve the above-mentioned problems. As a result, extracts obtained from flowers and the like of plants belonging to the family Rutaceae have been found. The present inventors have found that they have an excellent hyaluronic acid production promoting action, and based on this, completed the present invention.

[0010] That is, the present invention relates to Rutaceae.
And a hyaluronic acid production promoter containing, as an active ingredient, an extract of a plant belonging to

Here, extracts from flowers, leaves, stems or xylem of plants belonging to the family Rutaceae (Rutaceae) are preferably used, and extracts from flowers are particularly preferably used.

Among the plants of the Rutaceae family (Rutaceae), plants belonging to the genus Citrus are particularly preferably used.

[0013] The present invention further relates to an external preparation for skin comprising the above-mentioned hyaluronic acid production promoter.

With respect to the effect of the plant extract belonging to the family Rutaceae, the effect of crushing the seeds of the plant belonging to the citrus family Rutaceae and / or improving the wrinkles of the extract (Japanese Unexamined Patent Publication No.
126142) and the active oxygen scavenging ability of Ponkan Essence (JP-A-9-315993) are already known. However, there has never been a report that an extract of a plant of the family Rutaceae has a hyaluronic acid production-promoting action, and this was first found by the present inventors this time.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

Rutaceae (Rutaceae) used in the present invention
Plants belonging to the genus Citrus, Citrus, Fortunella, Poncirus, Skimmia, Ruta, etc., among which Citrus Are preferably used.

Examples of plants belonging to the genus Citrus include C. unshiu, C. natsudaidai, orange (sweet orange) (C. cinensis), and daidai (sour orange, bitter orange). (C. aurantium), Mandarin orange (including Ponkan) (C. reticulata), Hassaku (C.
hassaku), iyokan (C. iyo), grapefruit (C. paradisi), sudachi (C. sudachi), kabos (C.
sphaerocarpa). Among them, Unshiu (C. unshiu), orange (C. cinensis), and daidai (C. aurantium) are preferably used.

In the present invention, a plant belonging to the family Rutaceae can be used either as raw or dried, but it is preferable to use it as a dry powder or a solvent extract from the viewpoints of usability and formulation. The site of use of the Rutaceae plant may be the whole plant, but preferably flowers, leaves, stems, or xylem, and more preferably flowers or leaves, and particularly preferably flowers. In this case, the "flower" refers to a flower that includes various organs involved in sexual reproduction, including a so-called flower axis and flower leaves.
Includes petals, stamens, pistils, syrup, etc.

The extract of the Citrus family can be obtained by a conventional method. For example, a plant belonging to the Citrus family can be obtained by immersing or heating under reflux with an extraction solvent, followed by filtration and concentration. As the extraction solvent, any solvent can be used as long as it is a solvent usually used for extraction.
Water, methanol, ethanol, propylene glycol,
Alcohols such as 1,3-butylene glycol and glycerin, aqueous alcohols, and organic solvents such as chloroform, dichloroethane, carbon tetrachloride, acetone, ethyl acetate, and hexane can be used alone or in combination. The extract obtained by extraction with the above-mentioned solvent is directly adsorbed, or the concentrated extract is adsorbed by an adsorption method, for example, one obtained by removing impurities using an ion exchange resin, or a column of a porous polymer (eg, Amberlite XAD-2). After that, the product eluted with methanol or ethanol and concentrated can also be used. Further, a partitioning method, for example, an extract extracted with water / ethyl acetate and the like are also used.

The plant or extract thereof belonging to the family Rutaceae has an action of promoting hyaluronic acid production. Such a plant belonging to the Citrus family or an extract thereof is preferably used by being blended with an external preparation.

When the above-mentioned plant belonging to the family Rutaceae or its extract is used in the form of an external preparation for skin, it is preferably used in an amount of 0.0005 to 20.0% by weight, more preferably in terms of dry weight, based on the total amount of the external preparation. 0.001 to 10.0% by weight. If the amount is less than 0.0005% by weight, the effect of promoting the production of hyaluronic acid of the present invention is not sufficiently exerted.
If it exceeds 0.0% by weight, it is not preferable because it is difficult to prepare a formulation.
Further, even if the content exceeds 10.0% by weight, no significant improvement in the effect is recognized.

When the hyaluronic acid production enhancer of the present invention is used in an external preparation for skin, it may be used in addition to the above-mentioned components, and if necessary, to an external preparation for skin such as cosmetics and pharmaceuticals, as long as the effects of the present invention are not impaired. Components used, for example, humectants, antioxidants, oils, UV protection agents, surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water,
Various skin nutrients and the like can be appropriately compounded as needed.

Furthermore, sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, preservatives such as methylparaben, ethylparaben, butylparaben, caffeine Tannin, verapamil, tranexamic acid and its derivatives, licorice extract, glabridine, hot water extract of karin fruit, various crude drugs, drugs such as tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof, vitamin C, phosphorus ascorbate Whitening agents such as magnesium acid, glucoside ascorbic acid, arbutin and kojic acid, and sugars such as glucose, fructose, mannose, sucrose and trehalose can also be appropriately blended.

The external preparation for skin of the present invention can be widely applied to cosmetics, quasi-drugs and the like, particularly preferably cosmetics, applied to the outer skin. Any one that can be applied may be used, such as a solution system, a solubilizing system, an emulsifying system, a powder dispersion system, a water-oil two-layer system, a water-oil-powder three-layer system, an ointment, a lotion, a gel, and an aerosol. Any dosage form applies.

The form of use of the external preparation for skin of the present invention is also optional. For example, facial cosmetics such as lotions, emulsions, creams and packs, makeup cosmetics such as foundations, lipsticks, eye shadows, etc., aromatic cosmetics, It can be used as a bath agent and the like.

It should be noted that the form and use form of the external preparation for skin of the present invention are not limited to the above-mentioned forms and use forms.

The hyaluronic acid production promoter of the present invention has excellent hyaluronic acid production promoting ability.
In addition to being used as an external preparation for skin as described above, it can be applied as a preventive treatment for arthritis, an initial treatment for burns, and the like.

[0028]

EXAMPLES Next, the present invention will be described in more detail with reference to examples, but the technical scope of the present invention is not limited thereto. In addition, all compounding amounts are weight%.

Prior to the examples, a method for testing the hyaluronic acid production promoting effect of the solvent extract derived from Rutaceae plants of the present invention will be described.

1. Sample preparation Orange (C. sinensis), Unshu mandarin (C. unsh
iu) or Daidai (C. aurantium) flower 500g
Was immersed in methanol at room temperature for one week to obtain an extract.
The extract was concentrated to obtain 90 g of an extract of Rutaceae (hereinafter referred to as "the present extract").

The extract was treated with dimethyl sulfoxide (DMS)
O) to obtain a solution containing the present extract (hereinafter, referred to as “original solution”) to a concentration of 10%.

A solution whose concentration was adjusted by diluting the original solution was used as a test solution together with the original solution, and the following experiment was conducted.

2. Measurement of Hyaluronic Acid Production-Promoting Action Human skin-derived immortalized epidermal cells were seeded in a 24-well petri dish at 20,000 per well, and cultured in a growth factor-containing KGB medium (manufactured by Kurabo Industries, Ltd.) for 4 days. Thereafter, the medium was replaced with 2 ml of KGB medium containing the test solution, and culturing was further performed for 4 days. The concentration of the test solution was adjusted so that the final concentration of DMSO in the medium was 0.1%. The concentration of the present extract in the medium was 10 ⁻⁵ to 10 ⁻² wt%.

After the cultivation, the medium was collected and the amount of hyaluronic acid was measured. The measurement of hyaluronic acid was performed using a commercially available hyaluronic acid measurement kit (manufactured by Chugai Pharmaceutical Co., Ltd.). Further, the amount of DNA in the petri dish was measured and used as an index of the number of cells. The amount of DNA was measured by a fluorescence measurement method using “Hoechst 33258” (manufactured by Hoechst).

[0035] No cytotoxicity was observed with this extract at the above experimental concentrations.

The effect of promoting hyaluronic acid production was evaluated based on the rate of promoting hyaluronic acid production. The hyaluronic acid production promotion rate (%) was calculated using the extract-containing medium when the amount of hyaluronic acid per DNA of human skin-derived immortalized epidermal cells (control) cultured in a medium not containing the extract was 100. It was defined as the amount of hyaluronic acid per DNA of cultured human skin-derived immortalized epidermal cells. Table 1 shows the results.

Further, as a reference example, already subjected to the same test as in the also extract ginseng is known to have hyaluronic acid production promoting action (methanol extract), in 10 ^-3 wt% concentration The hyaluronic acid production promotion rate was measured. The results are shown in Table 1.

[0038]

[Table 1]

As is clear from Table 1, the extract of Rutaceae has an excellent hyaluronic acid production promoting effect.

The following are examples of the formulation of the hyaluronic acid production promoter according to the present invention in various dosage forms. In addition, the solvent extract of Rutaceae plant used in each Example was obtained by a conventional method. The amounts of these extracts are indicated by dry weight.

(Example 1) Cream (combination component) (% by weight) (1) Stearic acid 5.0 (2) Stearyl alcohol 4.0 (3) Isopropyl myristate 18.0 (4) Glycerin monostearin Acid ester 3.0 (5) Propylene glycol 10.0 (6) Methanol extract of orange flower 0.01 (7) Caustic potash 0.2 (8) Sodium bisulfite 0.01 (9) Preservative appropriate amount ( 10) Appropriate amount of fragrance (11) Purified water residue (Preparation method) (5) to (7) were added to (11), dissolved, and heated to 70 ° C (aqueous phase). On the other hand, (1) to (4),
(8) to (10) were mixed and melted by heating, and kept at 70 ° C. (oil phase). Next, the oil phase was gradually added to the aqueous phase with stirring, and after the addition was completed, the temperature was maintained for a while to cause a reaction. Thereafter, the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. with good stirring.

(Example 2) Cream (combination component) (% by weight) (1) Stearic acid 2.0 (2) Stearyl alcohol 7.0 (3) Hydrogenated lanolin 2.0 (4) Squalane 5. 0 (5) 2-octyldodecyl alcohol 6.0 (6) polyoxyethylene (25 mol) cetyl alcohol ether 3.0 (7) glycerin monostearate 2.0 (8) propylene glycol 5.0 (9) (10) Sodium bisulfite 0.03 (11) Ethyl paraben 0.3 (12) Perfume appropriate amount (13) Purified water residue (Production method) ), Dissolve and heat to 70
C. (aqueous phase). On the other hand, (1) to (7), (9) to
(12) was mixed and melted by heating, and kept at 70 ° C. (oil phase). Next, the oil phase was added to the water phase, preliminarily emulsified, and uniformly emulsified by a homomixer.
Cooled down.

Example 3 Cream (Blend Component) (% by Weight) (1) Solid Paraffin 5.0 (2) Beeswax 10.0 (3) Vaseline 15.0 (4) Glycerin Monostearate 2 0.0 (5) Polyoxyethylene (20 mol) Sorbitan monolaurate 3.0 (6) Soap powder 0.1 (7) Borax 0.2 (8) Acetone extract of Unshiu mandarin flower 0.05 (9) ) Ethanol extract of orange leaf 0.05 (10) Sodium bisulfite 0.03 (11) Ethyl paraben 0.3 (12) Appropriate amount of perfume (13) Purified water residue (Production method) ) To (7), and the mixture was dissolved by heating and kept at 70 ° C (aqueous phase). On the other hand, (1) to (5),
(8) to (12) were mixed, melted by heating, and kept at 70 ° C. (oil phase). Next, the oil phase was gradually added to the aqueous phase while stirring to carry out a reaction. After the completion of the reaction, the mixture was uniformly emulsified with a homomixer, and then cooled to 30 ° C. with good stirring.

(Example 4) Emulsion (combination component) (% by weight) (1) 2.5 stearic acid (2) cetyl alcohol 1.5 (3) Vaseline 5.0 (4) liquid paraffin 10.0 (5) Polyoxyethylene (10 mol) monooleate 3.0 (6) Polyethylene glycol 1500 3.0 (7) Triethanolamine 1.0 (8) Carboxyvinyl polymer 0.05 ("Carbopol 941") BFGoodrich Chemical Company) (9) Ethyl acetate extract of orange flower 0.05 (10) Sodium bisulfite 0.01 (11) Ethyl paraben 0.01 (12) Perfume appropriate amount (13) Purified water residue ( (Production method) (8) was dissolved in a small amount of (13) (phase A).
(6) and (7) were added to the remaining (13), and the mixture was dissolved by heating and maintained at 70 ° C. (aqueous phase). On the other hand, (1) to (5),
(9) to (12) were mixed, melted by heating, and kept at 70 ° C. (oil phase). Preliminary emulsification is performed by adding the oil phase to the aqueous phase.
The phases were added, and the mixture was uniformly emulsified with a homomixer. After the emulsification, the mixture was cooled to 30 ° C. with good stirring.

Example 5 Emulsion (combination component) (% by weight) (1) Microcrystalline wax 1.0 (2) Beeswax 2.0 (3) Lanolin 20.0 (4) Liquid paraffin 10.0 (5) Squalane 5.0 (6) Sorbitan sesquioleate 4.0 (7) Polyoxyethylene (20 mol) Sorbitan monooleate 1.0 (8) Propylene glycol 7.0 (9) Acetone extract of flower 10.0 (10) Sodium bisulfite 0.01 (11) Ethyl paraben 0.3 (12) Appropriate amount of perfume (13) Residual purified water (Preparation method) Add (8) to (13) And heated to 70 ° C. (aqueous phase). On the other hand, (1) to (7), (9) to (1)
2) was mixed, heated and melted, and kept at 70 ° C. (oil phase).
The aqueous phase was gradually added while stirring the oil phase, and the mixture was uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. with good stirring.

(Example 6) Jelly (combination component) (% by weight) (1) 95% ethyl alcohol 10.0 (2) dipropylenglycol 15.0 (3) polyoxyethylene (50 mol) oleyl Alcohol ether 2.0 (4) Carboxyvinyl polymer 1.0 ("Carbopol 941"; BFGoodrich Chemical Company) (5) Caustic soda 0.15 (6) L-arginine 0.1 (7) 50% of orange flowers Ethanol extract 7.0 (8) Sodium 2-hydroxy-4-methoxybenzophenonesulfonate 0.05 (9) Ethylenediaminetetraacetate trisodium dihydrate 0.05 (10) Methylparaben 0.2 (11) Appropriate amount of fragrance (12) Purified water residue (Production method) (4) was uniformly dissolved in (12) (aqueous phase).
On the other hand, (7) and (3) were dissolved in (1), and this was added to the aqueous phase. Next, (2) and (8) to (11) were added thereto, followed by neutralization with (5) and (6) to increase the viscosity.

(Example 7) Essence (combination component) (% by weight) (A phase) 95% ethyl alcohol 10.0 polyoxyethylene (20 mol) octyldodecanol 1.0 pantothenyl ethyl ether 1 Methanol Extract of Orange Flowers 1.5 Methylparaben 0.15 (Phase B) Potassium Hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylenglycol 10.0 Sodium Bisulfite 0.03 Carboxyvinyl Polymer 0 .2 (“Carbopol 941”; BFGoodrich Chemical Company) Purified water residue (Preparation method) A phase and C phase were each dissolved uniformly, and A was dissolved in C phase.
The phases were added and solubilized. Next, the phase B was added to perform filling.

(Example 8) Pack (combination component) (% by weight) (A phase) Dipropylene glycol 5.0 Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (B phase) Of methanol 0.01 Olive oil 5.0 Tocopherol acetate 0.2 Ethyl paraben 0.2 Fragrance 0.2 (C phase) Sodium bisulfite 0.03 Polyvinyl alcohol (degree of saponification 90, degree of polymerization 2000) 13.0 Ethanol 7.0 Purified water Residue (Preparation method) A phase, B phase, and C phase are each dissolved uniformly.
Phase B was added to solubilize. Next, the phase C was added to perform filling.

(Example 9) Solid foundation (combination component) (% by weight) (1) Talc 43.1 (2) Kaolin 15.0 (3) Sericite 10.0 (4) Zinc white 7.0 (5) Titanium dioxide 3.8 (6) Yellow iron oxide 2.9 (7) Black iron oxide 0.2 (8) Squalane 8.0 (9) Isostearic acid 4.0 (10) POE sorbitan monooleate 3 2.0 (11) Isocetyl octoate 2.0 (12) Ethanol extract of Satsuma mandarin leaf 1.0 (13) Preservatives appropriate amount (14) Flavor appropriate amount (Production method) Powders of (1) to (7) The components were sufficiently mixed in a blender, and the oily components (8) to (11) were added to the mixture.
2), (13), and (14) were added, and after kneading well, the mixture was filled into a container and molded.

(Example 10) Emulsion foundation (cream type) (combination component) (wt%) (powder part) titanium dioxide 10.3 seritite 5.4 kaolin 3.0 yellow iron oxide 0.8 bengara 0 0.3 Black iron oxide 0.2 (oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (aqueous phase) Purified water 50.0 1,3-butylene glycol 4.5 Ethanol extract of orange blossom 1.5 Preservative proper amount perfume proper amount (Production method) After heating and stirring the aqueous phase, a well mixed and pulverized powder portion was added thereto, followed by homomixer treatment. Further, the oil phase mixed by heating was added thereto, and the mixture was subjected to a homomixer treatment. Thereafter, a fragrance was added with stirring, and the mixture was cooled to room temperature.

(Example 11) Cream (combination component) (% by weight) (1) Stearic acid 2.0 (2) Stearyl alcohol 7.0 (3) Hydrogenated lanolin 2.0 (4) Squalane 0 (5) 2-octyldodecyl alcohol 6.0 (6) polyoxyethylene (25 mol) cetyl alcohol ether 3.0 (7) glycerin monostearate 2.0 (8) propylene glycol 5.0 (9) (10) Sodium bisulfite 0.03 (11) Ethyl paraben 0.3 (12) Appropriate amount of fragrance (13) Purified water residue (Production method) (13) (8) And heat it to 70
C. (aqueous phase). On the other hand, (1) to (7), (9) to
(12) was mixed and dissolved by heating, and kept at 70 ° C. (oil phase). Next, the oil phase was added to the water phase, preliminarily emulsified, and uniformly emulsified by a homomixer.
Cooled down.

Each of the skin external preparations of Examples 1 to 11 is excellent in promoting hyaluronic acid production.
By applying this to the skin, it is possible to maintain the firmness and elasticity of the skin, prevent wrinkles, and maintain a moist, youthful skin condition.

[0053]

As described above, the hyaluronic acid production promoter of the present invention has an excellent hyaluronic acid production accelerating action, and can prevent aging of human skin (skin firmness and elasticity retention), arthritis and the like. It can be effectively applied to prevention and treatment, initial treatment of burns, and the like. In particular, by blending the hyaluronic acid production promoter of the present invention with an external preparation for skin (including pharmaceuticals, quasi-drugs, and cosmetics), the production of hyaluronic acid, one of the extracellular matrix components, is promoted. It has the effect of maintaining skin firmness and elasticity to prevent wrinkles and maintaining a moist, youthful skin condition.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Koji Kobayashi Inventor 1050 Nippa-cho, Kohoku-ku, Yokohama-shi, Kanagawa Prefecture F-term in Shiseido Daiichi Research Center Co., Ltd. 4C083 AA082 AA111 AA112 AA122 AB032 AB152 AB212 AB232 AB242 AB352 AB432 AB442 AC012 AC022 AC072 AC092 AC102 AC122 AC182 AC242 AC352 AC402 AC422 AC442 AC482 AC532 AC542 AC582 AC642 AC792 AD042 AD092 AD112 AD172 AD512 AD662 CC02 CC04 CC05 CC07 CC12 DD21 DD23 DD31 DD41 EE10 EE12 EE13 FF05 4H025 AA82 BA01

Claims (6)

[Claims] 1. A hyaluronic acid production promoter comprising an extract of a plant belonging to the family Rutaceae as an active ingredient. 2. The hyaluronic acid production promoter according to claim 1, which comprises an extract from a flower, a leaf, a stem or a xylem of a plant belonging to the family Rutaceae (Rutaceae) as an active ingredient. 3. The hyaluronic acid production promoter according to claim 2, comprising an extract from a flower of a plant belonging to the family Rutaceae (Rutaceae) as an active ingredient. 4. A plant belonging to the family Rutaceae (Rutaceae),
The hyaluronic acid production promoter according to any one of claims 1 to 3, which is a plant belonging to the citrus family Citrus. 5. Citrus (Rutaceae) Citrus (Citru)
The hyaluronic acid production promotion according to claim 4, wherein the plant belonging to s) is one or more selected from C. unshiu, orange (C. sinensis), and sea bream (C. aurantium). Agent. 6. An external preparation for skin, comprising the hyaluronic acid production promoter according to any one of claims 1 to 5.