JPH0680553A - Hyaluronidase inhibitor - Google Patents

Abstract

PURPOSE:To provide the subject agent composed of the extract of Mimusops elengi, Eugenia jambolana, Saraca indica, KEIKETSUTOU (stalk of Mucuna birdwoodiana), SENKAKUSOU (whole grass of Agrimonia pilosa) and Machilus thunbergii which have been used as foods from ancient and are ensured to be safe to human body. CONSTITUTION:The objective hyaluronidase inhibitor is produced by extracting (A) Mimusops elengi which is an indeciduous small tree of the family AKATETSU grown in India and Nepal, (B) Eugenia jambolana which is an indeciduous tall tree of the family Myrtaceae grown in Nepal and India, (C) Saraca indica which is a sacred tree of Hinduism, (D) KEIKETSUTOU, (E) SENKAKUSOU and (F) Machilus thunbergii known as Chinese herb drugs with water, ethanol or their mixture and using the extract as an active component. The agent containing the extract of vegetables having guaranteed safety keeps the slipperiness and softness of the skin, suppresses the activity of hyaluronidase to decompose the age-preventing hyaluronic acid and prevents the wrinkles and dryness of the skin.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention uses hyaluronic acid, which has been used for many years as a drug for other purposes, for a long time to ensure the safety of the plant, and which keeps the lubricity and flexibility of the skin and prevents aging. By suppressing the activity of hyaluronidase, which decomposes acid,
The present invention relates to a hyaluronidase inhibitor which prevents fine wrinkles and roughness of the skin.

[0002]

2. Description of the Related Art Mimusop
selengi) originates from India in the Tarai region of Nepal. It is an evergreen small tree of the family Cathelaceae. It is called Misakinohana and is often planted as a garden tree. The bark is dark gray with cracks. The leaves are oval to oblong, and the flowers are axillary and simple, or fasciculate, small, pale yellow, and star-shaped, with a pleasant fragrance. Bark is an astringent and tonic agent for medicinal use,
It is also prescribed for heat. The leaves are also used for treatment when bitten by a snake.

The pulp of ripe fruits is astringent and is used for the treatment of chronic diarrhea. Seeds are used for bruising and, in some areas, for enema during childhood constipation.

Eugenia Jumborana (Eugen
ia jambolana) is called a jumbo lan or purple peach, which is a tall tree belonging to the family Myrtaceae, which is commonly found in Nepal and India and is an evergreen tree with a smooth gray bark. The fruit of jumbo lan makes wine. For medicinal use, the bark is an astringent, tonic and is also prescribed for heat. The leaves are also used for treatment when bitten by a snake.

The pulp of ripe fruits is astringent and is used in the treatment of chronic diarrhea. Seeds are used for bruising and, in some areas, for enema during childhood constipation.

Saraca indica
dica) is a plant of the legume family, called Muyuju, which is a sacred tree of Hinduism. Muyuju is an evergreen tree and is usually 4
It is about 8m, and there are rare cases where it exceeds 20m.
The bark is thick, grayish reddish brown, and the leaves are pinnate compound. The distribution is from central to Tobu Himalayan foothills, eastern Bengal, western Indian Peninsula,
It is distributed in northern India and is partly cultivated. This plant is used as a medicine, the leaves are used as a medicine for abdominal pain, the bark is used as a hemostatic agent for the treatment of excessive menstruation, and it is also used for the treatment of hemorrhoids after decoction.

Chicken blood wilt is Mukuna Bird Woodiana (M
ucuna birdwoodiana) or Millettia nitida,
Milletia d.
eelsiana) refers to dried stems and is used as a herbal medicine. It is used for blood supplements, tonics, analgesics for menstrual disorders, lower back and knee pain, rheumatism, paralysis of limbs, etc.

[0008] The whole plant of Senzuru grass is used. Its purpose is to stop bleeding, stop bleeding, extinguish, tonic, bleed, stool,
It is used for various bleeding symptoms such as urine, under the leaky zone, and Shigellosis. However, as a cosmetic, it is only used as a head cosmetic in JP-A-1-313414 and as a bactericidal composition in JP-A-60-184024.

[0009] The plants of the genus Agrimony belong to the dicotyledonous net, the isolated leaflet subweb, and the Rosaceae. In Japan, Agrimonia eu, Agrimonia eupatria (Agrimonia eu)
Patoria) grew up in Honshu, Shikoku, Kyushu, Ryukyu,
It is a perennial that grows in the mountains and on the roadside. Outside Japan, it is distributed in the warm to temperate regions of Korea, Taiwan, Siberia and the Himalayas.

Plants of the genus Tabanus belong to the family of dicotyledonous plants, leaflet subwebs, and duckweeds. In Japan, Tabuki, Machilus thumberg
gii) Synonymous with other names such as Ingus, Hosobatabu, and Machilus japonica, also known as Aogashi. Tabunoki is an evergreen tree that is distributed in Honshu, Shikoku, Kyushu, Ryukyu, South Korea, and China, and is often found on the coast of the warm district. On the other hand, Hosobatab is west of Honshu Kinki
It is an evergreen tree that is distributed in Ogasawara, Shikoku, Kyushu, Ryukyu, South Korea, etc.

The bark of this tree is used in Korea as a substitute for Korean magnolia, which is also called "Park" and is used as a medicine. However, Koboku is a magnolia family broom (Magnolia obobata).
Vata) is used, and in China, Magnolia officinalis (Magnolia officinalis)
The bark of is used. Regarding these, the inventors have already filed Japanese Patent Application Nos. 2-193030 and 2-1930.
No. 31 and Japanese Patent Application No. 2-193032 invented a method of using cosmetics. The present inventors have also found that those effects of koboku are expressed by magnolol and honokiol.

The bark and leaves of the genus Tabanus have not been used as a raw material for cosmetics, and in JP-A-63-196514, they are only slightly used as pharmaceuticals as prophylactic / therapeutic agents for protozoal diseases.

A natural product from the viewpoint of safety for human skin,
For many years, there has been a demand for a substance which has been guaranteed in terms of safety by being eaten by humans, has a strong hyaluronidase inhibitory action, and has other effects on the skin.

[0014]

An object of the present invention is to provide a raw material which is safe when applied to the skin and has a strong hyaluronidase inhibitory action.

[0015]

[Means for Solving the Problems] In order to solve the above-mentioned problems, the present inventors have screened and investigated plants that have been used for food for many years and confirmed to be safe for the human body, and have investigated hyaluronidase inhibitors. I examined what is useful as. As a result, Mimusops elengi, Eugenia jambola
na), Saraca indica (Saraca indi)
It has been found that ca), chicken blood mite, Senzuru-kusa, and Tabuki are materials with a very strong inhibitory effect on hyaluronidase.

That is, the present invention relates to Mimusops elengi, Eugenia jambolana,
Saraca indica,
It is a hyaluronidase inhibitor containing a solvent extract of chicken blood, Senzuru-kusa, and Tabuki.

As a method of utilizing these plants, water or a hydrophilic organic solvent such as ethanol, methanol,
Extract with acetone. However, it is natural that extraction with water, ethanol, or a mixed solvent thereof is preferable since it is extraction of cosmetic raw materials. In some cases, a polyhydric alcohol such as glycerin, 1,3 butylene glycol, propylene glycol or the like or a mixed liquid of polyhydric alcohol and water can be used for extraction. Further, freeze-drying and using it as powder is also effective depending on the method of use.

This substance is used as a raw material for other cosmetics, for example, liquid oils such as squalane and jojoba oil, solid oils such as beeswax and cetyl alcohol, various activators, moisturizing agents such as glycerin and 1,3 butylene glycol, and various agents. It can be added to adjust various dosage forms of cosmetics. For example, a lotion, a cream, a milky lotion, a pack, or the like may be used depending on the purpose.

Hyaluronidase is an enzyme widely distributed in the living body and also present in the skin. As its name implies, it decomposes hyaluronic acid. Hyaluronic acid is a linear polymeric polysaccharide in which β-D-N-acetylglucosamine and β-D-glucuronic acid are linked alternately. It is a glycosaminoglucan that exists widely in connective tissues of mammals along with chondroitin sulfate. It is a kind.

As a function of hyaluronic acid in connective tissue, water is retained in the intercellular spaces, and a jelly-like matrix is formed in the tissue to retain cells, and the lubricity and flexibility of the skin are maintained. It is believed to prevent external forces (mechanical disorders) and bacterial infections. It is said that hyaluronic acid in the skin decreases with age, resulting in aging such as wrinkles and roughness.

Therefore, suppressing the activity of hyaluronidase that decomposes this is the stability of hyaluronic acid used in the preparation, the hyaluronic acid of the preparation after being applied to the skin, and the hyaluronic acid present in the skin. Is considered to contribute to the stability of. Hyaluronidase is also known as an inflammatory enzyme, and it is known that suppressing the activity suppresses inflammation and also suppresses allergies.

[0022]

EXAMPLE An example of an actual usage will be described below, but the present invention is not limited to this example. Mimsops eringi (M used in the present invention
Examples of production of extracts of imusops elengi, Eugenia jambolana, Saraca indica, chicken blood moxibustion, medusa, and tabuki are shown below.

(Example 1) Mimsops eringi (Mi
10 g of leaves (dry product) of musops elengi)
300 ml of methanol was added to and the mixture was left for 5 days with occasional stirring. This was filtered and freeze-dried.

(Embodiment 2) Mimsops Erlengi (Mi
10 g of leaves (dry product) of musops elengi)
Add 300 ml of 50% methanol to the mixture and mix with stirring 5
Left for days. This was filtered and freeze-dried.

(Example 3) Mimsops Erlengi (Mi
10 g of roots (dry product) of musops elengi)
300 ml of purified water is added to and heated for 3 hours. This was filtered and freeze-dried.

(Embodiment 4) Mimsops Erlengi (Mi
10 barks (dry) of musops elengi)
300 ml of methanol was added to g and left for 5 days with occasional stirring. This was filtered and freeze-dried.

(Embodiment 5) Mimsops Erlengi (Mi
10 barks (dry) of musops elengi)
300 g of 50% methanol was added to g and left for 5 days with occasional stirring. This was filtered and freeze-dried.

(Embodiment 6) Mimsops Erlengi (Mi
10 barks (dry) of musops elengi)
Add 300 ml of purified water to g and heat for 3 hours. This was filtered and freeze-dried.

Example 7 To 10 g of bark (dry product) of Eugenia jambolana, 300 ml of methanol was added, and the mixture was left for 5 days with occasional stirring. This was filtered and freeze-dried.

Example 8 To 10 g of bark (dry product) of Eugenia jambolana, 300 ml of 50% methanol was added, and the mixture was left for 5 days with occasional stirring. This was filtered and freeze-dried.

Example 9 To 10 g of bark (dry product) of Eugenia jambolana, 300 ml of purified water was added and heated for 3 hours. This was filtered and freeze-dried.

(Embodiment 10) Saraca Indica (Sa
To 10 g of bark (dry product) of (raca indica) was added 300 ml of methanol, and the mixture was left for 5 days with occasional stirring. This was filtered and freeze-dried.

(Embodiment 11) Saraca Indica (Sa
To 10 g of bark (dry product) of (raca indica) was added 300 ml of 50% methanol, and the mixture was left for 5 days with occasional stirring. This was filtered and freeze-dried.

Example 12 Saraca Indica (Sa
To 10 g of bark (dry product) of (raca indica), 300 ml of purified water is added and heated for 3 hours. This was allowed to cool, then filtered and freeze-dried.

(Example 13) 10 g of chicken blood widow (dried product)
300 ml of ethanol was added to and the mixture was left for 5 days with occasional stirring. This was filtered and freeze-dried.

(Example 14) 10 g of chicken blood widow (dried product)
Add 300 ml of 50% ethanol to the mixture and stir 5 occasionally.
Left for days. This was filtered and freeze-dried.

(Example 15) 10 g of chicken blood widow (dried product)
300 ml of purified water is added to and heated for 3 hours. This was allowed to cool, then filtered and freeze-dried.

(Example 16) 10 g of Senzuruso (dry product)
300 ml of ethanol was added to and the mixture was left for 5 days with occasional stirring. This was filtered and freeze-dried.

(Example 17) 10 g of Senzakuso (dry product)
Add 300 ml of 50% ethanol to the mixture and stir 5 occasionally.
Left for days. This was filtered and freeze-dried.

(Embodiment 18) 10 g of Senzuru grass (dry product)
300 ml of purified water is added to and heated for 3 hours. This was allowed to cool, then filtered and freeze-dried.

Example 19 Tab bark bark (dry product)
300 g of ethanol was added to 10 g of the above and the mixture was left for 5 days with occasional stirring. This was filtered and freeze-dried.

Example 20 Tab bark bark (dry product)
300 g of 50% ethanol was added to 10 g and the mixture was allowed to stand for 5 days with occasional stirring. This was filtered and freeze-dried.

Example 21 Tab bark bark (dry product)
300 g of purified water is added to 10 g of the above and heated for 3 hours. This was allowed to cool, then filtered and freeze-dried.

Example 22 Lotion Olive oil 0.5 Methanol extract of Example 1 0.5 Polyoxyethylene (20 E.O.) sorbitan monostearate 2.0 Polyoxyethylene (60 E.O.) hydrogenated castor Oil 2.0 Ethanol 10.0 1.0% sodium hyaluronate aqueous solution 5.0 Purified water 80.0

(Example 23) Cream A Squalane 20.0 Olive oil 2.0 Mink oil 1.0 Jojoba oil 5.0 Beeswax 5.0 Cetostearyl alcohol 2.0 Glycerin monostearate 1.0 Sorbitan monostearate 2 0.0 50% methanol extract of Example 2 1.0 B Purified water 47.9 Polyoxyethylene (20 E.O.) sorbitan monostearate 2.0 Polyoxyethylene (60 E.O.) hydrogenated castor oil 1. 0 Glycerin 5.0 1.0% sodium hyaluronate aqueous solution 5.0 Methyl paraoxybenzoate 0.1 A and B were weighed and heated to 70 ° C., and A was gradually added to B while stirring. , Stirring slowly, 30
Cooled to ° C.

(Hyaluronidase activity inhibition test) (Test method) 0.4% sodium hyaluronate 0.1M
(PH 6.0) Weigh 6 g of phosphate buffer solution, and
After leaving it in a constant temperature water bath at ℃ for 5 minutes, 0.1 wt / v% aqueous solution of the above production example (freeze-dried product) (if it is difficult to dissolve, add ethanol and dissolve, then add purified water and evaporate to remove ethanol. After removing, 1.0 ml was prepared so as to be 0.1 wt / v%) and stirred, and 0.01% hyaluronidase (manufactured by Sigma Co., testis type I-S)
1 ml of 0.1 M (pH 6.0) phosphate buffer solution was added and immediately stirred, and this was placed in an Ostwald viscometer placed in a 37 ° C. constant temperature water bath. 1 minute later, 5 minutes later, 10 minutes later,
The viscosity was measured after 20 minutes and 40 minutes. As a control, pure water was added instead of the sample solution and the same measurement was performed. In this test, the final concentration of the sample is 0.0125%. The results are shown in Tables 1 to 7 by indexing the viscosity after 1 minute as 100.

[0047]

[Table 1]

[0048]

[Table 2]

[0049]

[Table 3]

[0050]

[Table 4]

[0051]

[Table 5]

[0052]

[Table 6]

[0053]

[Table 7]

(Use test) The faces of 6 women were divided into left and right, one side was applied with the lotion and cream of Examples 22 and 23, and the other was applied with the lotion and cream of Comparative Example once or more daily. After 3 months, I got a questionnaire. In addition, in the comparative example, the extracts of Examples 1 and 2 are replaced with water from Examples 22 and 23, respectively. (Comparative examples 1 and 2)

The criteria are as follows, and the following table shows the results of the questionnaire. Example is very good 3 Example is considerably good 2 Example is slightly good 1 No difference 0 Comparative example is good −1 Comparative example is good −2 Comparative example Is very good -3

[0056]

[Table 8]

[0057]

The effect of the extract of the present invention is the activity of suppressing hyaluronidase. Hyaluronidase is an enzyme that is widely distributed in the living body and is also present in the skin. As its name implies, it decomposes hyaluronic acid. Hyaluronic acid is β
It is a linear polymeric polysaccharide in which -DN-acetylglucosamine and β-D-glucuronic acid are alternately linked, and is a kind of glycosaminoglucan that widely exists in connective tissues of mammals along with chondroitin sulfate and the like.

As a function of hyaluronic acid in connective tissue, water is retained in the intercellular spaces, and a jelly-like matrix is formed in the tissue to retain cells, and the lubricity and flexibility of the skin are maintained. It is believed to prevent external forces (mechanical disorders) and bacterial infections. It is said that hyaluronic acid in the skin decreases with age, resulting in aging such as wrinkles and roughness.

Therefore, to suppress the activity of hyaluronidase that decomposes this, the stability of hyaluronic acid used in the preparation, the hyaluronic acid of the preparation after being applied to the skin, and the hyaluronic acid present in the skin Is considered to contribute to the stability of. Hyaluronidase is also known as an inflammatory enzyme, and it is known that suppressing the activity suppresses inflammation and also suppresses allergies.

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Claims (1)

[Claims] 1. Mimusops Erengi (Mimusop)
s elengi), Yugenia Jambolana (E
hyaluronidase inhibitor comprising a solvent extract of Ugenia jambola), Saraca indica, chicken blood mite, senzurusaku and tabuki.