JP7557192B2 - Skin preparations for external and internal use - Google Patents

Description

The present invention relates to an MMP inhibitor, a collagen production promoter, a wrinkle improvement agent, a hyaluronic acid production promoter, a cell proliferation promoter, a pharmaceutical product, and a food composition.

Skin is exposed to various physical and chemical stresses such as ultraviolet rays, dryness, cold, heat, and drugs every day. As a result, the skin's functions are impaired, and various skin aging phenomena become apparent. One of the skin aging phenomena is wrinkles. It is known that there are two types of wrinkles: epidermal wrinkles and dermal wrinkles. Epidermal wrinkles are called fine wrinkles, and are temporary wrinkles that occur when the moisture content in the epidermal stratum corneum decreases due to dry skin. On the other hand, dermal wrinkles are wrinkles that are formed by ultraviolet rays contained in sunlight and aging. The mechanism of their formation includes a decrease in the collagen synthesis ability of dermal fibroblasts due to ultraviolet rays and aging, and promotion of collagen decomposition due to an increase in matrix metalloproteinases (MMPs).

Epidermal wrinkles caused by dryness and dermal wrinkles have different histological morphology, onset mechanisms, and treatment methods, and dermal wrinkles caused by ultraviolet rays and aging are difficult to improve with the use of cosmetics with moisturizing effects.

To date, there have been reports of an agent for preventing and improving skin wrinkle formation, which contains hydrolyzed almonds as an active ingredient, for the purpose of improving dermal wrinkles caused by ultraviolet light (Patent Document 1), and an agent for improving wrinkles caused by ultraviolet light exposure, which contains extracts of Jochou-kei, Tensho, and Xylocentrotus nigricans as active ingredients (Patent Document 2).

The dermis also contains fibroblasts and collagen, with type I collagen accounting for 80% of the total. In addition to type I collagen, types III, V, XII, and XIV are known to exist. One of the causes of wrinkles and sagging is a decrease in type I collagen. Therefore, promoting the production of type I collagen is thought to be effective in preventing and improving wrinkles and sagging. Promoting the production of type I collagen is also effective in improving wound healing in the skin.

Collagen is the main structural protein that accounts for approximately one-third of mammalian tissues, and is an essential component of many matrix tissues, such as cartilage, bone, tendon, and skin. Gelatinase (MMP-2), which belongs to MMPs, is an enzyme produced by fibroblasts, endothelial cells, cancer cells, etc., and breaks down substrates such as collagen, gelatin, and elastin (structural proteins that are special components of elastic tissues such as arteries, tendons, and skin). Therefore, substances that have inhibitory activity against gelatinase are expected to have the effect of suppressing angiogenesis and cancer metastasis in cancer tissues, and are considered to be useful in the prevention and treatment of cancer diseases. Furthermore, inhibition of MMP is useful not only for cancer diseases, but also for the prevention, treatment, and improvement of ulcer formation, chronic rheumatoid arthritis, osteoporosis, periodontal inflammation, and various diseases caused by increased MMP production.

Fibroblasts also produce proteins such as collagen and glycosaminoglycans such as hyaluronic acid to form dermal connective tissue, which maintains skin firmness. It is believed that when this connective tissue loses its contractile force and further its elasticity, wrinkles and sagging of the skin occur.

In particular, hyaluronic acid is known as a polymeric polysaccharide widely distributed in connective tissues, and takes on a gel-like form in the dermis, maintaining the elasticity of the skin. Therefore, it is believed that the alteration or reduction of hyaluronic acid is important in skin aging. In addition, since hyaluronic acid is a polymer, there is a problem that cosmetics containing it are not easily absorbed even when directly applied to the skin. Therefore, up until now, a skin topical agent that can promote the production of collagen and hyaluronic acid by activating fibroblasts has been sought (Patent Document 3). In addition, hyaluronic acid is also present in joints, and is known to function to cushion the impact of load on the joints and to smooth the movement of the joints. In the case of joint diseases such as osteoarthritis, chronic rheumatoid arthritis, suppurative arthritis, gouty arthritis, traumatic arthritis, and osteoarthritis, it is known that the amount of hyaluronic acid in the synovial fluid decreases with age. In such joint diseases, it is believed that increasing the amount of hyaluronic acid in the synovial fluid is effective in improving lubrication, covering and protecting the articular cartilage, suppressing pain, and improving or normalizing pathological synovial fluid. For example, it is known that when sodium hyaluronate is injected into the joints of patients with chronic rheumatoid arthritis, traumatic arthritis, osteoarthritis, and osteoarthritis, the above-mentioned symptoms are improved. However, these treatments take a long time. Therefore, there is a demand for foods and medicines that contain hyaluronic acid production promoters so that prevention and treatment can be easily carried out in daily life.

Floaters are a symptom where a thin shadow resembling a lint or a mosquito appears in the field of vision. They occur when opacity in the vitreous body, which fills the inside of the eye, casts a shadow on the retina. Floaters can be broadly divided into two types: physiological floaters, which develop due to aging, ultraviolet rays, active oxygen, etc., and pathological floaters, which appear as a symptom of diseases such as retinal detachment, retinal tear, vitreous hemorrhage, and uveitis. Physiological floaters are caused by liquefaction due to a decrease in hyaluronic acid, the main component of the vitreous body, and the resulting collapse of collagen fibers, causing the vitreous body to become opaque. Treatments include vitrectomy surgery and laser treatment, but these procedures are not often performed in Japan due to safety concerns, and treatment abroad requires a large amount of money. Therefore, in order to prevent and improve physiological floaters, foods and medicines containing hyaluronic acid production promoters that can be used on a daily basis are desired.

As we age, the proliferation and division ability of epidermal cells declines, and the epidermal layer itself becomes thinner (Non-Patent Document 1). Biological factors such as epidermal growth factor (EGF) and female hormones (estrogen) promote the proliferation of epidermal cells, but their secretion declines with age. This decline in the metabolic function of epidermal cells due to aging slows down the turnover rate of the skin, causing rough skin and skin aging. In addition, when keratinocytes that peel off from the surface of the stratum corneum remain, the excretion of melanin in the epidermis is not carried out smoothly, causing pigmentation and dull skin. It is also known that epidermal wound healing slows down. In order to prevent or improve the progression of these phenomena, there has been a search for ingredients that promote the proliferation of epidermal cells, and many topical skin preparations have been proposed.

It is known that extracts from the plant body of the Aleurites tree (scientific name: Aleurites moluccanus) of the Euphorbiaceae family have melanin production inhibitory effects, serine protease inhibitory effects, and elastase inhibitory effects (Patent Document 4), and that its seed oil has a hair growth effect (Patent Document 5). However, it was not known that the seeds of the Aleurites tree have MMP inhibitory effects, collagen production promoting effects, hyaluronic acid production promoting effects, and cell proliferation promoting effects.

JP 2000-119125 A JP 2006-199611 A JP 2007-1924 A Japanese Patent Application Publication No. 9-87136 Japanese Patent Application Publication No. 11-286414

Varani J et al. , J Invest Dermatol, Vol. 3, pp 57-60, 1998

There is a demand for safe, stable materials that have excellent MMP inhibitory effects, collagen production promotion effects, hyaluronic acid production promotion effects, and cell proliferation promotion effects, but currently no fully satisfactory materials have been provided.

The inventors conducted intensive research to solve this problem and found that an extract from the seeds of the tree Moth has excellent MMP inhibitory effects, collagen production promotion effects, hyaluronic acid production promotion effects, and cell proliferation promotion effects, and is also highly stable. Furthermore, they found that topical or internal preparations containing the extract are safe and stable, and have excellent MMP inhibitory effects, collagen production promotion effects, hyaluronic acid production promotion effects, and cell proliferation promotion effects, and can be used as multifunctional beauty and health materials and medicines, leading to the completion of the present invention.

That is, the present invention comprises the following (1) to (7).

(1) An MMP inhibitor characterized by containing an extract from the seeds of Moluccana.
(2) A collagen production promoter characterized by containing an extract of the seeds of Moluccana.
(3) A wrinkle improving agent characterized by containing an extract of the seeds of Moluccana.
(4) A hyaluronic acid production promoter characterized by containing an extract of the seeds of the bark tree.
(5) A cell proliferation promoter comprising an extract of the seeds of Moluccana.
(6) A pharmaceutical comprising an extract of the seeds of Moluccana.
(7) A food composition for preventing and improving various diseases, joint diseases and physiological floaters caused by increased MMP production, characterized by containing an extract from the seeds of Moss Tree.

The present invention is described in detail below.

The kukui tree (Aleurites moluccanus) used in this invention is a deciduous tree native to Southeast Asia that belongs to the genus Aleurites in the family Euphorbiaceae and grows to a height of 10 to 20 meters. Its dark green, egg-shaped leaves grow in a spiral shape, and its yellow-green fruits are about 5 centimeters in diameter and consist of clusters of 3 to 6 fruits.

The "seeds of the kukui tree" used in this invention refer to the inside of the fruit, which is a brown to black lump with about two layers excluding the flesh. Furthermore, the white to light brown nut-like thing inside the lump is also considered to be the seed of this invention. These are also called kernels. These nut-like things are also called kukui nuts or candle nuts. The seeds can be obtained from the growing area or can be purchased commercially. Furthermore, the seeds themselves can be extracted as they are, or they can be processed by drying, crushing, chopping, etc.

Examples of the extraction solvent include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol, glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), and ethers (ethyl ether, tetrahydrofuran, propyl ether, etc.). Preferably, polar solvents such as water, lower alcohols, and liquid polyhydric alcohols are good, and more preferably, water, ethanol, 1,3-butylene glycol, and propylene glycol are good. These solvents may be used alone or in combination of two or more. Particularly preferred extraction solvents include water, ethanol, mixed polar solvents of water-ethanol system, 1,3-butylene glycol, and mixed polar solvents of water-1,3-butylene glycol system. There is no particular limit to the amount of solvent used; for example, it is sufficient if the amount is 10 times or more, and preferably 20 times or more, relative to the amount of the seeds of the kukui tree (dry weight), but it is preferable that the amount is 100 times or less for convenience of operations when concentrating or isolating after extraction. In addition, the extraction temperature and time can be appropriately selected depending on the type of solvent used, the pressure during extraction, etc.

The extraction method is not particularly limited, and may be performed by methods such as heating extraction, room temperature extraction, cooling extraction, stirring extraction, or column extraction. The extract may also be used in combination with the seeds.

The above extract may be used as it is in the form of an extracted solution, but if necessary, it may be used after being subjected to processes such as concentration (vacuum concentration, membrane concentration, etc.), dilution, filtration, decolorization with activated carbon, deodorization, ethanol precipitation, etc., within the scope of the effects of the present invention. Furthermore, the extracted solution may be concentrated to dryness, spray-dried, freeze-dried, etc., and used as a dried product.

In the present invention, the above extract may be used as is, or may contain ingredients such as fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, pigments, antioxidants, whitening agents, chelating agents, excipients, coating agents, sweeteners, acidulants, etc., which are used in cosmetics, quasi-drugs, medicines, foods, etc., within the scope that does not impair the effects of the extract.

The present invention can be used in any of cosmetics, quasi-drugs, medicines, and foods, and examples of the dosage forms include lotions, creams, milky lotions, gels, aerosols, essences, packs, cleansers, bath products, foundations, dusting powders, lipsticks, ointments, poultices, tablets, capsules, chocolates, gums, candies, beverages, powders, granules, tablets, sugar-coated tablets, capsules, syrups, pills, suspensions, liquids, emulsions, suppositories, and injectable solutions.

When used externally, the content of the above extract used in the present invention is preferably 0.0001% by weight or more, and more preferably 0.001 to 10% by weight, calculated as solid matter. Furthermore, 0.01 to 5% by weight is most preferable. If it is less than 0.0001% by weight, it is difficult to expect a sufficient effect. If it exceeds 10% by weight, it is difficult to see an increase in effect, and it is uneconomical.

When taken internally, the dosage varies depending on age, body weight, symptoms, therapeutic effect, administration method, administration period, etc. In general, the daily dosage for an adult is preferably 5 mg or more, more preferably 10 mg to 5 g. Furthermore, 20 mg to 2 g is most preferable.

In the following, in order to explain the present invention in detail, examples of the production of the extract used in the present invention, experimental examples and formulation examples are given as examples, but the present invention is not limited to these. Unless otherwise specified, the percentages shown in the examples are percentages by weight.

Production Examples of Moluccana Seed Extract Moluccana seed extract was produced as follows: In Production Examples 1 to 4, Moluccana seeds were used as the extraction material.

(Production Example 1) Preparation of hot water extract of aleurone seeds 200 mL of water was added to 10 g of dried aleurone seeds, and extraction was carried out for 2 hours at 95 to 100° C. The obtained extract was filtered, and the filtrate was concentrated and freeze-dried to obtain 2.1 g of hot water extract of aleurone seeds.

(Production Example 2) Preparation of 50% ethanol extract of Moluccana seeds 10 g of dried Moluccana seeds were soaked in 200 mL of 50% ethanol aqueous solution at room temperature for 7 days to perform extraction. The obtained extract was filtered and then concentrated to dryness using an evaporator to obtain 0.2 g of 50% ethanol extract of Moluccana seeds.

(Production Example 3) Preparation of ethanol extract of Moluccana seeds 10 g of dried Moluccana seeds were soaked in 200 mL of ethanol at room temperature for 7 days to perform extraction. The obtained extract was filtered and then concentrated to dryness using an evaporator to obtain 1.7 g of ethanol extract of Moluccana seeds.

(Production Example 4) Preparation of 1,3-butylene glycol extract of kukui seeds 10 g of dried kukui seeds were soaked in 200 mL of 1,3-butylene glycol at room temperature for 7 days to perform extraction. The obtained extract was filtered to obtain 192 g of 1,3-butylene glycol extract of kukui seeds.

Next, experimental examples will be presented to explain the effects of the present invention in detail.

Experimental Example 1 Measurement of mRNA expression levels of type I collagen (COL1A1), hyaluronic acid synthase 2 (HAS2) and MMP-2 Human fibroblasts NB1RGB were seeded at 1×10 ⁵ cells on a φ60 mm dish, and when the cells became confluent, samples were added to give a final concentration of 1 or 10 μg/mL. For controls, a solvent in which the sample was diluted was added. After 24 hours of culture, total RNA was extracted. Total RNA was extracted from the cells using RNAiso Plus (Takara Bio), and the amount of total RNA was determined by absorbance at 260 nm using a spectrophotometer (NanoDrop). The amount of mRNA expression was measured by real-time RT-PCR based on the total RNA extracted from the cells. For the real-time RT-PCR method, High Capacity RNA-to-cDNA Kit (Applied Biosystems) and SYBR Select Master Mix (Life Technologies) were used. That is, 500 ng of total RNA was subjected to reverse transcription reaction, followed by PCR reaction (95°C: 15 seconds, 60°C: 60 seconds, 40 cycles). Other operations were performed according to the prescribed method, and the expression levels of COL1A1, HAS2, and MMP-2 mRNA were calculated as a ratio to the expression level of GAPDH mRNA, which is an internal standard. The COL1A1 expression rate was calculated as the ratio of the expression level of COL1A1 mRNA in the sample addition group to the expression level of COL1A1 mRNA in the control. The HAS2 and MMP-2 expression rates were also calculated in the same manner. The primers used to measure the expression level of each gene are as follows.

Primer set for COL1A1 AGGACAAGAGGCATGTCTGGTT (SEQ ID NO: 1)
TTGCAGTGGTAGGTGATGTTCTG (SEQ ID NO: 2)
Primer set for HAS2 TGGATGACCTACGAAGCGATT (SEQ ID NO: 3)
GCTGGATTACTGTGGCAATGAG (SEQ ID NO: 4)
Primer set for MMP-2 CCGTCGCCCATCATCAA (SEQ ID NO:5)
CTTCTGCATCTTCTTTAGTGTGTCCTT (SEQ ID NO: 6)
Primer set for GAPDH CACTCTTCCAGCCTTCCTTCC (SEQ ID NO: 7)
GTGTTGGCGTACAGGTCTTTG (SEQ ID NO: 8)

The results of these experiments are shown in Tables 1 to 3. As a result, it was found that the seed extract of the tree Moth of the present invention had excellent COL1A1 expression promotion (collagen production promotion effect), HAS2 expression promotion (hyaluronic acid production promotion effect), and MMP-2 expression suppression (MMP inhibitory effect).
In particular, the ethanol extract (Production Example 3) had a significantly high COL1A1 expression promoting effect, the hot water extract (Production Example 1) had a significantly high HAS2 expression promoting effect, and the 50% ethanol extract (Production Example 2) had a significantly high MMP-2 expression inhibiting effect.

Experimental Example 2 Cell proliferation promotion test Human-derived keratinocytes were seeded in a 96-well plate at 1 x ^{103 cells} per well in DMEM culture medium containing 0.1% FBS, and each sample was added to a final concentration of 1 or 10 μg/mL, and then cultured for 4 days under conditions of 37°C and 5% CO2 by _volume . The cell number was measured by a staining method. That is, after the culture was completed, the culture medium was removed and the cells were fixed using methanol. Then, 0.1% methylene blue was added and the cells were stained for 1 hour. After drying, 100 μL of 0.1N HCl was added to each well and stirred well, and the absorbance at 650 nm was measured using a microplate reader. The cell proliferation rate was calculated as the ratio of the cell amount of the sample-added group to the cell amount of the control (no sample added) group.

The results of these experiments are shown in Table 4. As a result, the 50% ethanol extract (Production Example 2) and the ethanol extract (Production Example 3) of the seeds of the Mokkino Tree of the present invention showed particularly excellent cell proliferation promoting effects.

(Formulation Example 1) Lotion Formulation Content (%)
1. Hot water extract of kukui seeds (Production Example 1) 2.0
2. 1,3-butylene glycol 8.0
3. Glycerin 2.0
4. Xanthan gum 0.02
5. Citric acid 0.01
6. Sodium citrate 0.1
7. Ethanol 5.0
8. Methyl parahydroxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40 E.O.) 0.1
10. Fragrance, appropriate amount 11. Add purified water to make the total amount 100 [Manufacturing method] Dissolve ingredients 1-6 and 11 and ingredients 7-10 uniformly, mix the two, and filter to make the product.

(Formulation Example 2) Cream Formulation Content (%)
1. 50% ethanol extract of Moluccana seeds (Preparation Example 2) 1.0
2. Squalane 5.5
3. Olive oil 3.0
4. Stearic acid 2.0
5. Beeswax 2.0
6. Octyldodecyl myristate 3.5
7. Polyoxyethylene cetyl ether (20 E.O.) 3.0
8. Behenyl alcohol 1.5
9. Glyceryl monostearate 2.5
10. Fragrance 0.1
11. Methyl parahydroxybenzoate 0.2
12. 1,3-butylene glycol 8.5
13. Make up to 100% with purified water [Manufacturing method] Heat and dissolve ingredients 2-9, mix, and maintain at 70°C to make the oil phase. Heat and dissolve ingredients 1 and 11-13, mix, and maintain at 75°C to make the water phase. Add the water phase to the oil phase to emulsify, cool with stirring, add ingredient 10 at 45°C, and further cool to 30°C to make the product.

(Formulation Example 3) Emulsion Formulation Content (%)
1. Ethanol extract of Moluccana seeds (Production Example 3) 0.01
2. Squalane 5.0
3. Olive oil: 5.0
4. Jojoba oil 5.0
5. Cetanol 1.5
6. Glyceryl monostearate 2.0
7. Polyoxyethylene cetyl ether (20 E.O.) 3.0
8. Polyoxyethylene sorbitan monooleate (20 E.O.) 2.0
9. Fragrance 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12. Methyl parahydroxybenzoate 0.2
13. Make the total volume 100 with purified water. [Manufacturing method] Heat and dissolve ingredients 1-8, mix, and keep at 70°C to make the oil phase. Heat and dissolve ingredients 10-13, mix, and keep at 75°C to make the water phase. Add the water phase to the oil phase to emulsify, cool with stirring, add ingredient 9 at 45°C, and cool further to 30°C to make the product.

(Formulation Example 4) Gel Formulation Content (%)
1. 1,3-butylene glycol extract of kukui seeds (Production Example 4) 1.0
2. Ethanol 5.0
3. Methyl parahydroxybenzoate 0.1
4. Polyoxyethylene hydrogenated castor oil (60 E.O.) 0.1
5. Fragrance (appropriate amount) 6. 1,3-butylene glycol 5.0
7. Glycerin 5.0
8. Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. Add purified water to make the total volume 100. [Manufacturing method] Dissolve ingredients 2 to 5, 1, and 6 to 11 uniformly, and mix the two to make the product.

(Formulation Example 5) Pack Formulation Content (%)
1. Hot water extract of Moluccana seeds (Production Example 1) 1.0
2. 1,3-butylene glycol extract of Moluccana seeds (Production Example 4) 5.0
3. Polyvinyl alcohol 12.0
4. Ethanol 5.0
5. 1,3-butylene glycol 8.0
6. Methyl parahydroxybenzoate 0.2
7. Polyoxyethylene hydrogenated castor oil (20 E.O.) 0.5
8. Citric acid 0.1
9. Sodium citrate 0.3
10. Fragrance (as needed) 11. Add purified water to make a total of 100 parts. [Manufacturing Method] Dissolve ingredients 1 to 11 uniformly to make the product.

(Formulation Example 6) Foundation Formulation Content (%)
1. 50% ethanol extract of Moluccana seeds (Preparation Example 2) 1.0
2. Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20 E.O.) 1.0
4. Polyoxyethylene cetyl ether (20 E.O.) 2.0
5. Cetanol 1.0
6. Liquid Lanolin 2.0
7. Liquid paraffin 3.0
8. Isopropyl myristate 6.5
9. Sodium carboxymethylcellulose 0.1
10. Bentonite 0.5
11. Propylene glycol 4.0
12. Triethanolamine 1.1
13. Methyl parahydroxybenzoate 0.2
14. Titanium dioxide 8.0
15. Talc 4.0
16. Bengala 1.0
17. Yellow iron oxide 2.0
18. Flavoring, appropriate amount 19. Make the total volume 100 with purified water [Manufacturing method] Heat and dissolve ingredients 2 to 8, and keep at 80°C to make the oil phase. Allow ingredient 9 to swell well in ingredient 19, then add ingredients 1 and 10 to 13 and mix uniformly. Add ingredients 14 to 17, which have been ground and mixed in a grinder, and stir with a homomixer to make the water phase, keeping the temperature at 75°C. Add the water phase to the oil phase while stirring, and emulsify. Then cool, add ingredient 18 at 45°C, and cool to 30°C while stirring to make the product.

(Formulation Example 7) Bath additive Formulation Content (%)
1. Ethanol extract of Moluccana seeds (Production Example 3) 1.0
2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) appropriate amount 4. Fragrance appropriate amount 5. Sodium sulfate to make the total amount 100 [Manufacturing method] Mix ingredients 1 to 5 uniformly to make the product.

(Formulation Example 8) Ointment Formulation Content (%)
1. Hot water extract of Moluccana seeds (Production Example 1) 5.0
2. 1,3-butylene glycol extract of Moluccana seeds (Production Example 4) 1.0
3. Polyoxyethylene cetyl ether (30 E.O.) 2.0
4. Glyceryl monostearate 10.0
5. Liquid paraffin 5.0
6. Cetanol 6.0
7. Methyl parahydroxybenzoate 0.1
8. Propylene glycol 10.0
9. Make the total volume 100 with purified water. [Manufacturing method] Heat and dissolve ingredients 3-6, mix, and keep at 70°C to make the oil phase. Heat and dissolve ingredients 1, 2, and 7-9, mix, and keep at 75°C to make the water phase. Add the water phase to the oil phase to emulsify, and cool to 30°C while stirring to make the product.

(Formulation Example 9) Powder Formulation Content (%)
1. Hot water extract of Moluccana seeds (Production Example 1) 1.0
2. Dried cornstarch 39.0
3. Microcrystalline cellulose 60.0
[Manufacturing method] Mix ingredients 1 to 3 to make a powder.

(Formulation Example 10) Tablet Formulation Content (%)
1. Ethanol extract of Moluccana seeds (Production Example 3) 5.0
2. Dried cornstarch 25.0
3. Calcium carboxymethylcellulose 20.0
4. Microcrystalline cellulose 40.0
5. Polyvinylpyrrolidone 7.0
6. Talc 3.0
[Manufacturing method] Components 1 to 4 are mixed, and then an aqueous solution of component 5 is added as a binder to form granules. Component 6 is added to the formed granules and compressed into tablets. Each tablet weighs 0.52 g.

(Formulation Example 11) Tablets Formulation Content (%)
1. Ethanol extract of Moluccana seeds (Production Example 3) 2.0
2. Dry cornstarch 49.8
3. Erythritol 40.0
4. Citric acid 5.0
5. Sucrose fatty acid ester 3.0
6. Fragrance 0.1
7. Purified water 0.1
[Manufacturing method] Mix ingredients 1 to 4 and 7 and mold into granules. Add ingredients 5 and 6 to the molded granules and compress into tablets. Each tablet weighs 1.0 g.

(Formulation Example 12) Beverage Formulation Content (%)
1. Hot water extract of Moluccana seeds (Production Example 1) 0.05
2. Stevia 0.05
3. Malic acid 5.0
4. Fragrance 0.1
5. Add purified water to make the total volume 100. [Production method] Dissolve components 2 and 3 in a small amount of water. Next, add components 1, 4, and 5 and mix.

From the above, the extract of the seeds of the kukui tree of the present invention has excellent collagen production promoting effects, hyaluronic acid production promoting effects, MMP inhibitory effects, and cell proliferation promoting effects, and is also highly stable. Therefore, the extract of the seeds of the kukui tree of the present invention can be used not only in the cosmetic field, such as skin aging, but also in the medical field, such as suppressing the decline in joint function due to aging, and preventing and treating cancer, and is expected to be applied to foods, cosmetics, quasi-drugs, pharmaceuticals, etc.

Claims (7)

1. An MMP inhibitor comprising an extract of the seeds of Moluccana using water, aqueous ethanol or ethanol . A collagen production promoter comprising an extract of the seeds of Moluccana using water, aqueous ethanol or ethanol . A dermal wrinkle improving agent comprising an extract of the seeds of Moluccana using water, aqueous ethanol or ethanol . A hyaluronic acid production promoter comprising an extract of the seeds of the bark tree using water, aqueous ethanol or ethanol . A cell proliferation promoter comprising an extract of the seeds of Moluccana using water, aqueous ethanol or ethanol . A pharmaceutical for preventing and improving various diseases caused by increased MMP production, various diseases caused by decreased collagen production, and/or various diseases caused by decreased hyaluronic acid production (excluding uses for preventing and improving headache, fever, ulcers, swollen joints, constipation, rheumatoid arthritis, ankylosing spondylitis, and rheumatic heart disease), characterized by containing an extract of Kukui seed with water, hydroethanolamine, or ethanol . A food composition for preventing and improving various diseases caused by increased MMP production, various diseases caused by decreased collagen production, and/or various diseases caused by decreased hyaluronic acid production, characterized by containing an extract of kukui seed with water, hydroethanol or ethanol (excluding uses for preventing and improving rheumatoid arthritis, ankylosing spondylitis, and rheumatic heart disease) .