JP5913118B2 - Collagen production promoter, hyaluronic acid production promoter, fibroblast proliferation promoter, and anti-wrinkle agent - Google Patents

Description

Related applications

  This application claims the priority of Japanese Patent Application No. 2010-240684 filed on Oct. 27, 2010, and is incorporated herein.

  The present invention relates to a collagen production promoter, a hyaluronic acid production promoter, a fibroblast proliferation promoter, and an anti-wrinkle agent, and more particularly to a processed product of an organic solvent extract of plant seeds excellent in collagen production promotion effect and the like.

The skin consists of the stratum corneum, epidermis, basement membrane and dermis from the outside.
The dermis is the largest part of the area, and the cells are not packed as densely as the epidermis. Rather, it has a lot of extracellular space and is filled with a network of macromolecules called “extracellular matrix”. This extracellular matrix is produced in fibroblasts in the dermis and the like, and is composed of polysaccharides called acidic mucopolysaccharides such as hyaluronic acid and dermatan sulfate, and fibrous proteins such as collagen and elastin. The extracellular matrix is directly involved in skin elasticity, elasticity, freshness, metabolism, and the like. When the production of extracellular matrix in fibroblasts or the like is dull, the elasticity and freshness of the skin is lost, and rough skin is likely to occur, contributing to skin aging.

The fibrous protein is mainly composed of collagen, of which type I collagen accounts for 80%. In addition to type I collagen, the presence of type III, V, XII, and XIV type collagen is known. One cause of sagging in aging skin is due to thinning of skin tissue with age. In aging skin, the decrease in collagen fibers, which are the main matrix component of the dermis, is significant, which is likely to be the main cause of thinning of the skin. Therefore, it is thought that promoting collagen production and maintaining the amount of collagen is effective in preventing and improving sagging.
In addition to the above, the promotion of collagen production is effective in improving wound healing of skin, treating osteoporosis, arthritis, tendonitis, etc., and preventing hypertension.
Conventionally, as a collagen production promoter, a collagen production promoter containing a crude drug extract extracted from hakuzin (dried Konotegasiwa seeds) using only water as an extraction solvent is known (for example, Patent Document 1). reference). However, there is room for improvement in the collagen production promoting effect of the herbal extract.

On the other hand, the hyaluronic acid in the polysaccharide retains moisture in the cell gap, retains cells based on the formation of a jelly-like matrix in the tissue, retains the lubricity and flexibility of the tissue, mechanical failure, etc. It has many functions such as resistance to external force and prevention of bacterial infection. Recently, many studies have been conducted on the relationship with cancer metastasis.
In addition to skin, hyaluronic acid is widely distributed in living bodies such as joint fluid, vitreous, and ligaments. Therefore, in addition to improving the moisturizing effect, hyaluronic acid production is promoted by treating joint pain (degenerative knee osteoarthritis), improving skin sagging, treating keratoconjunctival epithelial disorders mainly with dry eyes, and cataract / corneal transplant surgery. It is also effective for holding the anterior chamber.
So far, as a hyaluronic acid production promoter, a hyaluronic acid production promoter containing, as an active ingredient, an extract of a seaweed belonging to the genus Davilia is known (see, for example, Patent Document 2).

  As described above, collagen and hyaluronic acid can be applied to an agent for improving knee joint disease, a preparation for ophthalmic surgery, etc., in addition to improving / preventing skin sagging and rough skin, and preventing skin aging. For this reason, if a substance having an effect of promoting production of both collagen and hyaluronic acid can be found, there is an advantage that it can be widely applied to symptom improvement and prevention / treatment.

On the other hand, in Patent Document 3, seeds of plants selected from Thuja, Rubus, Vaccinium, Actinidia, and Perilla plants are extracted to form a plant extract, and then the plant extract is extracted. A method for producing a plant whitening agent obtained by performing an alkali treatment is known.
However, it has not been known that the processed product of Konotegasiwa organic solvent extract has an excellent collagen production promoting effect and hyaluronic acid production promoting effect.

JP 2010-235482 A Japanese Patent Laid-Open No. 9-176036 JP 2007-223944 A

  This invention is made | formed in view of the said prior art, The objective is to provide the processed material of the organic solvent extract of the plant seed excellent in the collagen production promotion effect, the hyaluronic acid production promotion effect, etc.

  In order to solve the above-mentioned problems, the present inventors have conducted intensive studies, and as a result, extracted seeds of plants belonging to the genus Cupressaceae (Platycladus) using an organic solvent and containing oily components. It was found that a processed product obtained by washing with water after the alkali treatment and acid treatment of the extract had an excellent collagen production promoting effect, and the present invention was completed.

That is, the collagen production promoter according to the present invention obtains an extract containing an oily component by extracting a seed of a plant belonging to the genus Cupressaceae (Platycladus) using an organic solvent. It is characterized by being obtained by distilling off a part or all of the solvent, adding and mixing an alkaline aqueous solution having a concentration of 0.5 to 15 N, and then washing with water after acid treatment.
The hyaluronic acid production promoter according to the present invention obtains an extract containing an oily component by extracting a seed of a plant belonging to the family Cupressaceae (Platycladus) using an organic solvent, It is characterized by being obtained by distilling off part or all of the solvent, adding and mixing an alkaline aqueous solution having a concentration of 0.5 to 15 N, and then washing with water after acid treatment.
The fibroblast growth promoter according to the present invention is an extract containing an oily component obtained by extracting a seed of a plant belonging to the genus Cupressaceae (Platycladus) using an organic solvent. It is characterized by being obtained by distilling off a part or all of the solvent, adding and mixing an alkaline aqueous solution having a concentration of 0.5 to 15 N, and then washing with water after acid treatment.
An anti-wrinkle agent according to the present invention is obtained by extracting a seed of a plant belonging to the genus Cupressaceae (Platycladus) using an organic solvent to obtain an extract containing an oily component. It is characterized by being obtained by distilling off part or all, adding and mixing an alkaline aqueous solution having a concentration of 0.5 to 15 N, and then washing with water after acid treatment.
In the accelerator or anti-wrinkle agent, it is preferable that the amount of pure alkali added is 100 to 300 g / L extract.
In the promoter or the anti-wrinkle agent, it is preferable that the plant belonging to the genus Konotegasiwa is Platycladus orientalis.

The collagen production promoting method according to the present invention is characterized in that the collagen production promoting agent is applied.
The hyaluronic acid production promoting method according to the present invention is characterized by applying the hyaluronic acid production promoting agent.
The fibroblast proliferation promoting method according to the present invention is characterized in that the fibroblast proliferation promoting agent is applied.
The wrinkle improving method according to the present invention is characterized in that the anti-wrinkle agent is applied.
The method for promoting collagen production according to the present invention is characterized in that the collagen production promoter is orally ingested.
The method for promoting hyaluronic acid production according to the present invention is characterized in that the hyaluronic acid production promoter is orally ingested.
The fibroblast proliferation promoting method according to the present invention is characterized by orally ingesting the fibroblast proliferation promoting agent.
The wrinkle improving method according to the present invention is characterized by orally ingesting the anti-wrinkle agent.

  ADVANTAGE OF THE INVENTION According to this invention, the processed product of the organic solvent extract of a plant seed useful as a collagen production promoter, a hyaluronic acid production promoter, a fibroblast growth promoter, and an anti-wrinkle agent can be provided.

It is a figure which shows the comparison of the collagen production promotion effect of the water extract of Konotegasiwa seed, and the processed material of the organic solvent extract of this seed. It is a figure which shows the wrinkle improvement effect of the processed material of the organic solvent extract of Konotegasiwa seeds.

  The collagen production promoter according to the present invention provides an extract containing an oily component by extracting a seed of a plant belonging to the genus Cupressaceae (Platycladus) using an organic solvent, and the solvent of the extract It is characterized by being obtained by distilling off a part or all of the solution, adding and mixing an alkaline aqueous solution having a concentration of 0.5 to 15 N, and then washing with water after acid treatment.

The seed of the plant used in the present invention is a seed of a plant belonging to the genus Konotegasiwa. Of these, it is preferable to use seeds of Platycladus orientalis.
Microphylla, and Acer buergerianm is, China, the Korean Peninsula native, was brought over to Japan in about 250 years ago, which is a normally-green shrub or Odaka tree of tree height 5~15m is currently being planted in various places.
The seeds of Konotegasiwa have a black-brown, long oval shape and are also called “Hakushinin”. Widely used in Chinese medicine, it is used for nourishing tonic and extinguishing.

  For example, the following method can be used as a specific extraction method, alkali treatment method, and acid treatment method of the extract.

Extraction is performed for a certain period of time with an organic solvent having a mass of 1 to 100 times, preferably about 1 to 30 times the mass of the seeds of the cypress plant. The seed to be used can be appropriately pulverized as necessary, but may be used as it is in an unpulverized case when clogging becomes a problem during filtration.
Further, it is possible to repeatedly extract with a small amount of an organic solvent, and a reflux device such as Soxhlet may be used.

Although the organic solvent used for extraction will not be specifically limited if it is an organic solvent normally used for extraction, It is preferable that it is a volatile organic solvent.
As the organic solvent, for example, polar and nonpolar organic solvents such as alcohols such as methanol and ethanol, hydrous alcohols, acetone, ethyl acetate, hexane and ether can be used alone or in combination of two or more. . Of these, acetone, ethyl acetate, and hexane are particularly preferable because they are inexpensive and easy to concentrate under reduced pressure. In addition, extraction with supercritical carbon dioxide or squeezing seeds can be used.
On the other hand, an extraction solvent containing water is not preferable because extraction of the active ingredient is suppressed.

After removing the organic solvent from the extract obtained as described above, an alkali treatment is performed.
The method of alkali treatment is not particularly limited. For example, after part or all of the solvent of the organic solvent extract is distilled off, an alkali aqueous solution having a concentration of 0.5 to 15N, preferably 1 to 10N is added and mixed. Can be obtained.

More specifically, for example, 0.2 to 2 times volume of concentrated alkaline aqueous solution is added to the extract after distilling off the solvent, and then the mixture is sufficiently stirred and aged for about 30 minutes to several days. Examples of the concentrated alkaline aqueous solution include an aqueous solution composed of NaOH, KOH or the like having a concentration of 0.5 to 15N, preferably 1 to 10N. In addition, it is preferable to add concentrated alkali aqueous solution so that a pure alkali amount may be 100-300 g / L extract.
As temperature in the case of mixing, the range of room temperature-70 degreeC is preferable, and the range of 30-60 degreeC is further more preferable. It is desirable to appropriately stir so that the hydrophilic component and the lipophilic component do not separate during aging.

The processed material subjected to the alkali treatment as described above is subjected to an acid treatment.
Although the method of acid treatment is not particularly limited, for example, a method of adding an acid solution having a concentration of 0.5 to 15N and lowering the pH to about 0.5 to 2 can be mentioned.

When the acid treatment is performed, a liquid (oily) substance is separated. While this liquid substance has a very high collagen production promoting effect, it shows high safety to the skin.
Wash with water to promote liquid substance recovery. Thereafter, operations such as decolorization, deodorization, desalting, and distillation may be performed as necessary.

Ingredients extracted and treated as described above from the seeds of the genus Konotegasiwa are the effects of promoting hyaluronic acid synthesis in epidermal cells, the effect of promoting fibroblast proliferation, and the effect of improving wrinkles, in addition to the effect of promoting collagen production have.
For this reason, the collagen production promoter according to the present invention can also be used as a hyaluronic acid production promoter, a fibroblast proliferation promoter, and an anti-wrinkle agent.

  The collagen production promoting method, hyaluronic acid production promoting method, fibroblast proliferation promoting method, and wrinkle improving method according to the present invention are the collagen production promoting agent, hyaluronic acid production promoting agent, fibroblast proliferation promoting agent, anti-wrinkle of the present invention. An agent is applied.

In the above-described accelerating method or wrinkle improving method, an external composition for skin containing the accelerating agent or anti-wrinkle agent of the present invention may be applied.
The composition for external use in skin has a very wide application range, and is applied to various fields (for example, cosmetics including quasi-drugs, pharmaceuticals, injections using microneedles, etc.). The product form is arbitrary, for example, ointment, cream, milky lotion, lotion, essence, jelly, gel, pack, mask, foundation, microneedle, etc. are mentioned.

  When preparing a composition for external use on the skin, it is preferable to add 0.0001 to 20% by mass, particularly 0.001 to 2% by mass, as a liquid component, of an accelerator or an anti-wrinkle agent that is an active ingredient. preferable.

  The external composition for skin containing the promoter or anti-wrinkle agent according to the present invention can be produced according to a conventional method. In the composition for external skin, in addition to the promoter or anti-wrinkle agent that is an essential component, any component that is usually used in the composition for external skin can be appropriately blended within a range that does not impair the effects of the present invention.

Examples of optional components that can be blended into the composition for external use include physiologically active substances such as amino acids, lipids, sugars, hormones, enzymes, and nucleic acids.
Also, water (purified water, hot spring water, deep water, etc.), oil agent, surfactant, metal soap, gelling agent, powder, alcohols, water-soluble polymer, film forming agent, resin, clathrate compound, perfume , Deodorants, salts, pH adjusters, fresheners, animal and microbial extracts, blood circulation promoters, astringents, antiseborrheic agents, chelating agents, keratolytic agents, enzymes, hormones, vitamins, etc. The plant extract and the like can be appropriately blended.

  Others, disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, sequestering agents such as gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extract, grabrizine , Hot water extract of fire thorn fruit, various herbal medicines, drugs such as tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof, sugars such as glucose, fructose, psicose, allose, tagatose, mannose, sucrose, trehalose, xylitol , Β-alanine, glycine, GABA, sarcosine and other ion channel control substances, carnosine, retinoids, and the like can be appropriately blended.

Further, by combining the promoter or anti-wrinkle agent according to the present invention in combination with one or more other medicinal agents, each effect is further enhanced, or other external effects that exhibit other medicinal properties together with each effect. Compositions can also be prepared.
Examples of the medicinal agents include whitening agents, UV protection agents, antibacterial agents, anti-inflammatory agents, blood circulation promoters, various medicinal ingredients, active oxygen scavengers, moisturizers, other accelerators, and other anti-wrinkle agents. For example, but not limited to.

  The dosage form of the external composition for skin containing the accelerator or anti-wrinkle agent according to the present invention is not particularly limited as long as the effect of the present invention can be exhibited. The dosage form of the external composition for skin is arbitrary, for example, solution system, solubilization system, emulsification system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, ointment, gel, aerosol, etc. Is mentioned.

  Further, the collagen production promotion method, hyaluronic acid production promotion method, fibroblast proliferation promotion method, wrinkle improvement method according to the present invention include the collagen production promoter, hyaluronic acid production promoter, fibroblast proliferation promoter of the present invention, It is also suitable to take an anti-wrinkle orally.

The promotion method or the wrinkle improvement method may be orally ingested food or drink containing the promoter or anti-wrinkle agent of the present invention.
When the collagen production promoter, hyaluronic acid production promoter, fibroblast growth promoter, and anti-wrinkle agent of the present invention are blended in food and drink, the blending amount (dry mass) of the promoter or anti-wrinkle agent is determined by It can be determined as appropriate according to the type, purpose, form, usage method, and the like. For example, it is preferable that a compounding quantity is about 0.0001-50 mass% in food-drinks whole quantity. In particular, when blended with food for specified health use, it is preferable to blend the promoter or anti-wrinkle agent of the present invention in such an amount that the effect is sufficiently exhibited.

As a form of food / beverage products, it can shape | mold arbitrarily, for example to a granular form, paste form, gel form, solid form, liquid form, etc., for example.
For foods and drinks, various known substances that are permitted to be incorporated into foods and drinks, such as binders, disintegrants, thickeners, dispersants, reabsorption accelerators, corrigents, buffers, and surface active agents. Excipients such as agents, solubilizers, preservatives, emulsifiers, tonicity agents, stabilizers and pH adjusters can be contained as appropriate.

  The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. Unless otherwise specified, the amount is shown in mass%.

First, the present inventors prepared an organic solvent extract of cypress family Konotegasiwa plant (Konotegasiwa) seed and its treated product (A) by the following preparation method. And the test shown below was done about the fibroblast proliferation promotion effect of the extract and its processed material, and the type I collagen production promotion effect by a fibroblast.
The results are shown in Table 1, assuming that no extract and its treated product were added.

Preparation method of organic solvent extract of Konotegasiwa seeds Each seed (unground) of Konotegasiwa was immersed in 5 times (v / w) organic solvent (acetone) and extracted at room temperature for 10 days. The residue was previously removed with a nylon mesh (100 mesh), and further filtered with a filter paper. The solvent was removed from the filtrate with a rotary evaporator. In this way, an extract was obtained.

Preparation method A of an organic solvent extract of Konotegashira seed
While stirring the extract obtained as described above with a stirring blade, a 0.5 to 15 N NaOH solution was added to the extract as pure NaOH within a range of 100 to 300 g / L (temperature: 50 ° C. ). The treatment was performed for 5 hours while stirring at 200 rpm. Thereafter, 5N H ₂ SO ₄ was gradually added, the pH was lowered to around 1 while stirring, and the separated liquid (oil) material was recovered. An equal volume of water was added to the recovered liquid (oily) substance and washed with water to remove impurities, salts and excess acid. The liquid (oily) substance was dried under reduced pressure to obtain a liquid treated product (A).

<Cell activation test>
Human newborn fibroblasts HF0K are inoculated into Dulbecco's modified Eagle's MEM medium (DMEM, manufactured by Nissui) containing 10% calf serum (FBS), followed by seeding in 24-well plates at 37 ° C. It left still in the atmosphere of carbon concentration 5 volume%. After cell attachment, the medium was replaced with a medium containing low-concentration serum (0.5%), and the culture was continued for one day and night. Thereafter, the sample or the processed product is prepared so that the extract is 0, 0.5 × 10 ⁻⁴ , 1 × 10 ⁻⁴ , 2 × 10 ⁻⁴ , 3 × 10 ⁻⁴ vol% with respect to the medium. The liquid was added and mixed. On the third day of culture, the number of fibroblasts grown in each sample preparation solution was measured using Hoechst 33342 (manufactured by Dojin Chemical Co., Ltd.), and the extract or treated product was not added as a control. Cell activation was evaluated.
Cell culture supernatants were collected and the type I collagen production was evaluated.

<Measurement of type I collagen production>
The type I collagen in the collected cell culture supernatant was measured using the Procollagen Type IC-peptide (PIP) EIA kit (manufactured by TAKARA) according to the manual attached to the kit. This was used as an index of type I collagen production. The amount of cells per well was determined as the amount of DNA using Hoechst 33342, and the amount of type I collagen promoted by the extract or its treated product was evaluated as per unit cell.

According to Table 1, it turned out that it has a high cell activation ability with respect to the fibroblast HF0K derived from a human newborn by processing to the organic-solvent extract of Konotegasiwa seeds.
In addition, the organic solvent extract of Konotegasiwa seeds did not show an effect of promoting type I collagen production, but it was confirmed that the treatment increased type I collagen production at a very low concentration.
Therefore, the collagen production promoter and the fibroblast growth promoter according to the present invention require that the organic solvent extract of Konotegasiwa seeds be alkali-treated and acid-treated.

Next, further examination was conducted on the type I collagen production promoting effect using seeds of Konotegasiwa different from the above test.
The present inventors divided Konotegasiwa seeds into approximately three equal parts, and prepared a water (10 ° C. and 20 ° C.) extract of the seeds and a processed product (B) of an organic solvent extract by the following method. And the amount of type I collagen production per unit cell of the water extract and the treated product (B) was measured by the above test. The results are shown in FIG. 1, assuming that the water extract and treated product (B) are not added (control) as 100.
FIG. 1 shows an average value ± SD. In addition, statistical processing was performed by Student's t test (significance level * p <0.1, ** p <0.05), and a significant difference or a tendency difference was observed with respect to the control.

Preparation method of water extract of Konotegasiwa seeds The seeds of Konotegasiwa were immersed in 5 times the amount (v / w) of water and extracted at 10 ° C. or 20 ° C. for 24 hours. The residue was previously removed with a nylon mesh (100 mesh), and further filtered with a filter paper. In this way, a water extract was obtained.

Preparation method B of organic solvent extract of Konotegasiwa seed
The seeds of Konotegasiwa were immersed in 5 times (v / w) organic solvent (acetone) and extracted at 20 ° C. for 24 hours. The residue was previously removed with a nylon mesh (100 mesh), and further filtered with a filter paper. The solvent was removed from the filtrate with a rotary evaporator.
While stirring the obtained extract with a stirring blade, a 0.5 to 15 N NaOH solution was added to the extract as pure NaOH within a range of 100 to 300 g / L (temperature: 50 ° C.). The treatment was performed for 5 hours while stirring at 200 rpm. Thereafter, 5N H ₂ SO ₄ was gradually added, the pH was lowered to around 1 while stirring, and the separated liquid (oil) material was recovered. An equal volume of water was added to the recovered liquid (oily) substance and washed with water to remove impurities, salts and excess acid. The liquid (oily) substance was dried under reduced pressure to obtain a liquid treated product (B).

According to FIG. 1, it was confirmed that the processed product of the organic solvent extract has a significant collagen production promoting effect in a concentration-dependent manner.
However, the water extract had almost no effect under any conditions, and no significant collagen production promoting effect was observed.
Therefore, the collagen production promoter according to the present invention requires the use of an organic solvent that does not contain water for the extraction of Konotegasiwa seeds.

Next, using a seed of Konotegasiwa different from the above test, examination of the hyaluronic acid synthesis promoting effect of the treated product of the seed and confirmation of the type I collagen production promoting effect and the fibroblast proliferation promoting effect were performed.
That is, for the treated product of Konotegashira seed prepared by the above preparation method A, the hyaluronic acid synthesis promoting effect by epidermal cells was measured by the following test, and the fibroblast proliferation promoting effect, type I by fibroblast was measured by the above test. The effect of promoting collagen production was measured. The results are shown in Table 2 with 100 as the case where no treated product was added.

<Test for promoting hyaluronic acid synthesis in epidermal cells>
Human epidermis-derived keratinocytes HaCaT were seeded in a 96-well dish (6000 cells / well), and cultured for 24 hours in a medium containing 15% Humedia-KG2 (manufactured by Kurabo Co., Ltd.) and 85% Humedia-KB2. Then, it replaced | exchanged for the 100% Humeria-KB2 culture medium containing the processed material (0, 0.005, 0.01 volume% with respect to a culture medium) of the prepared Konotegasiwa seeds. The culture was continued for 2 days, and the cell culture supernatant was collected.
The amount of hyaluronic acid contained in the supernatant was measured using a hyaluronic acid measurement kit (manufactured by Mitsubishi Chemical Medience Corporation). The amount of cells per well was determined as the amount of DNA using Hoechst 33342 (manufactured by Dojin Chemical Co., Ltd.). The amount of hyaluronic acid promoted by the treated product of Konotegasiwa seeds was evaluated as per unit cell.

According to Table 2, it was also recognized that the seeds of Konotegasiwa according to the present invention, that is, the processed product of coconut seeds, also had an effect of promoting hyaluronic acid synthesis of epidermal cells.
It was also reconfirmed that the processed product of Choshijin had a fibroblast proliferation promoting effect and a type I collagen production promoting effect.

<Wrinkle improvement test>
Next, the wrinkle improvement effect of the treated product of the seed prepared by the preparation method A was confirmed using seeds of Konotegasiwa different from the above test.
That is, about the thing which mix | blended the processed product of the organic solvent extract of 0.35% Konotega washi seed (active) and the thing which is not mix | blended (placebo), the skin external preparation (cream) of the mixing | blending composition shown in following Table 3 is used. Prepared. Then, 28 expert panelists applied each skin external preparation to the left and right corners of the eyes twice a day for 2 months, and evaluated which small wrinkle became inconspicuous. The results are shown in FIG.

(Table 3)
Cream Active Placebo Dynamite Glycerin 1.0 1.0% by mass
Dipropylene glycol 5.0 5.0
1,3 butylene glycol 7.0 7.0
Carboxyvinyl polymer 0.3 0.3
Acrylic acid alkyl methacrylate polymer 0.05 0.05
Olefin oligomer 8.0 8.0
Di-methyl polysiloxane 1.0 1.0
Methylphenyl polysiloxane 1.0 1.0
Processing of microphylla, and Acer buergerianm species child acetone extract
0.35-
Caustic potash 0.09 0.09
EDTA 0.01 0.01
Preservative Appropriate amount Appropriate amount Fragrance Appropriate amount Appropriate amount
It was uniformly dissolved carboxyvinyl polymer and acrylic acid methacrylic acid alkyl polymer in deionized water, while the treated product of microphylla, and Acer buergerianm seeds olefin oligomers, di- methylpolysiloxane, was dissolved methylphenyl polysiloxane was added to the aqueous phase . After the addition of other ingredients, it was prepared thickened neutralized with caustic potash.

According to FIG. 2 , it became clear that more than half of the panelists recognized the wrinkle improvement effect in the treated product mixture of Konotegasiwa seeds.
Therefore, it was recognized that the seed of Konotegasiwa according to the present invention, that is, the processed product of coconut seed, also has a wrinkle improving effect.

Hereinafter, compositions for external use of skin and foods will be shown as examples of combination of the collagen production promoter, hyaluronic acid production promoter, fibroblast proliferation promoter and anti-wrinkle agent according to the present invention. The present invention is not limited by this blending example. In addition, all of the treated products of Konotegasiwa seed organic solvent extract have excellent collagen production promoting effect, hyaluronic acid production promoting effect, fibroblast proliferation promoting effect, and wrinkle improving effect in the same tests as in the above Examples. Was.

Formulation Example 1: Cream stearic acid 5.0% by mass
Stearyl alcohol 4.0
Isopropyl myristate 18.0
Glycerol monostearate 3.0
Propylene glycol 10.0
This collagen production promoter (treated product of Konotegasiwa seed acetone extract)
1.0
Caustic potash 0.2
Sodium bisulfite 0.01
Preservative Appropriate amount of perfume Appropriate amount of ion-exchanged water
Propylene glycol and caustic potash were added to ion-exchanged water, dissolved, heated and kept at 70 ° C. (aqueous phase). The other ingredients were mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was gradually added to the aqueous phase, and after the addition was completed, the temperature was maintained for a while to cause the reaction. Thereafter, the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well.

Formulation Example 2: Cream stearic acid 6.0% by mass
Sorbitan monostearate ester 2.0
Polyoxyethylene (20 mol) sorbitan monostearate
1.5
Propylene glycol 10.0
This hyaluronic acid production promoter (treated product of Konotegasiwa seed ethyl acetate extract)
0.1
Glycerin trioctanoate 10.0
Squalene 5.0
Sodium bisulfite 0.01
Ethylparaben 0.3
Perfume Appropriate amount of ion-exchange water Residue (Production method)
Propylene glycol was added to ion-exchanged water, dissolved, heated and kept at 70 ° C. (aqueous phase). The other ingredients were mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, and uniformly emulsified with a homomixer, and then cooled to 30 ° C. while stirring well.

Formulation Example 3: Cream stearyl alcohol 7.0% by mass
Stearic acid 2.0
Hydrogenated Lanolin 2.0
Squalane 5.0
2-Octyldodecyl alcohol 6.0
Polyoxyethylene (25 mol) cetyl alcohol ether
3.0
Glycerin monostearate ester 2.0
Propylene glycol 5.0
This fibroblast growth promoter (treated with Konotegasiwa seed hexane extract)
1.0
Perfume proper amount Sodium bisulfite 0.03
Ethylparaben 0.3
Ion-exchanged water remaining (production method)
Propylene glycol was added to ion-exchanged water, dissolved, heated and kept at 70 ° C. (aqueous phase). The other ingredients were mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, preliminarily emulsified, and uniformly emulsified with a homomixer, and then cooled to 30 ° C. while stirring well.

Formulation Example 4: Latex stearic acid 2.5% by mass
Cetyl alcohol 1.5
Vaseline 5.0
Liquid paraffin 10.0
Polyoxyethylene (10 mol) monooleate
2.0
Polyethylene glycol 1500 3.0
Triethanolamine 1.0
This collagen production promoter (treated product of Konotegasiwa seed acetone extract)
0.04
Carnosine 3.5
Nicotinamide 1.0
Sodium bisulfite 0.01
Ethylparaben 0.3
Carboxyvinyl polymer 0.05
Perfume Appropriate amount of ion-exchange water Residue (Production method)
Carboxyvinyl polymer was dissolved in a small amount of ion-exchanged water (A phase). Polyethylene glycol 1500, triethanolamine, carnosine, and nicotinamide were added to the remaining ion-exchanged water and dissolved by heating and maintained at 70 ° C. (aqueous phase). The other ingredients were mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase for preliminary emulsification, and the A phase was added, and the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well after the emulsification.

Formulation Example 5: Emulsion (oil phase part)
Stearyl alcohol 1.5% by mass
Squalene 2.0
Vaseline 2.5
Deodorized liquid lanolin 1.5
Evening primrose oil 2.0
Isopropyl myristate 5.0
Glycerol monooleate 2.0
Polyoxyethylene (60 mol) hydrogenated castor oil 2.0
Tocopherol acetate 0.05
This hyaluronic acid production promoter (treated product of Konotegasiwa seed hexane extract)
0.01
Ethylparaben 0.2
Butylparaben 0.1
Ethylglycine 1.0
Perfume appropriate amount (water phase part)
Sodium bisulfite 0.01
Nicotinamide 0.05
Glycerin 5.0
Sodium hyaluronate 0.01
Carboxyvinyl polymer 0.2
Potassium hydroxide 0.2
Purified water residue (production method)
The oil phase part was dissolved at 70 ° C. The aqueous phase was dissolved at 70 ° C., the oil phase was mixed with the aqueous phase, emulsified with an emulsifier, and then cooled to 30 ° C. with a heat exchanger.

Formulation Example 6: Gel serum (95% ethanol, 10.0% by mass)
Dipropylene glycol 15.0
Polyoxyethylene (50 mol) oleyl alcohol ether
2.0
Carboxyvinyl polymer 1.0
Caustic soda 0.15
This fibroblast proliferation promoter (treated product of Konotegasiwa seed ethyl acetate extract)
2.0
Retinol 0.04
L-Arginine 0.1
Sarcosine 1.0
Methylparaben 0.2
Perfume Appropriate amount of ion-exchange water Residue (Production method)
The carboxyvinyl polymer was uniformly dissolved in ion-exchanged water, while the treated product of Konotegasiwa seed ethyl acetate extract, polyoxyethylene (50 mol) oleyl alcohol ether, was dissolved in 95% ethanol and added to the aqueous phase. Subsequently, other components were added, and the mixture was neutralized with caustic soda and L-arginine to increase the viscosity.

Formulation Example 7: Cosmetic liquid (A phase)
Ethanol (95%) 10.0% by mass
Polyoxyethylene (20 mol) octyldodecanol 1.0
This collagen production promoter (treated product of Konotegasiwa seed hexane extract)
0.3
Methylparaben 0.15
Pantotenyl ethyl ether 0.1
(Phase B)
Potassium hydroxide 0.1
(Phase C)
Glycerin 5.0
Carnosine 3.0
Nicotinamide 3.0
Dipropylene glycol 10.0
Sodium bisulfite 0.03
Carboxyvinyl polymer 0.2
Purified water residue (production method)
The A phase and the C phase were uniformly dissolved, and the A phase was added to the C phase and solubilized. Subsequently, after adding B phase, it filled and manufactured.

Formulation Example 8: Pack (A phase)
Dipropylene glycol 5.0% by mass
Polyoxyethylene (60 mol) hydrogenated castor oil 5.0
(Phase B)
Olive oil 5.0
This hyaluronic acid production promoter (treated product of Konotegasiwa seed acetone extract)
1.0
Acetate Tokofe b Lumpur 0.2
Ethylparaben 0.2
Fragrance 0.2
(Phase C)
Sodium bisulfite 0.03
Carnosine 0.1
Polyvinyl alcohol (degree of saponification 90, degree of polymerization 2000)
13.0
Ethanol 7.0
Purified water residue (production method)
A phase, B phase, and C phase were uniformly dissolved, and B phase was added to A phase to solubilize. Subsequently, after adding this to the C phase, it filled and manufactured.

Formulation Example 9: Ointment polyoxyethylene (30 mol) cetyl ether 2.0% by mass
Glycerol monostearate 10.0
Liquid paraffin 10.0
Vaseline 40.0
Cetanol 6.0
Methylparaben 0.1
Butylparaben 0.1
Glycerin monostearate ester 2.0
This fibroblast growth promoter (treated product of Konotegasiwa seed acetone extract)
5.0
Propylene glycol 10.0
Ion exchange water Residual perfume appropriate amount (Manufacturing method)
Propylene glycol was added to ion-exchanged water, dissolved, heated and kept at 70 ° C. (aqueous phase). Other components were mixed and dissolved at 70 ° C. (oil phase). An oil phase was added to the aqueous phase, and the mixture was uniformly emulsified with a homomixer, and filled after cooling.

  Thereafter, creams of Formulation Examples 10 to 13 were produced in the same manner.

Formulation Example 10: Cream liquid paraffin 8.0% by mass
Vaseline 3.0
Dimethylpolysiloxane 2.0
Stearyl alcohol 3.0
Behenyl alcohol 2.0
Glycerin 5.0
Dipropylene glycol 4.0
Trehalose 1.0
Tetra-2-ethylhexanoic acid pentaerythrit 4.0
Polyisoethylene glyceryl monoisostearate 2.0
Polyoxyethylene glycerol monostearate 1.0
Lipophilic glyceryl monostearate 2.0
Citric acid 0.05
Sodium citrate 0.05
Potassium hydroxide 0.015
Oil-soluble licorice extract 0.1
Retinol palmitate (1 million units) 0.25
This collagen production promoter (treated product of Konotegasiwa seed ethyl acetate extract)
0.3
Carnosine 3.5
Nicotinamide 2.0
Tocopherol acetate 0.1
P-Hydroxybenzoate appropriate amount phenoxyethanol appropriate amount dibutylhydroxytoluene appropriate amount edetate trisodium 0.05
4-t-butyl-4′-methoxydibenzoylmethane 0.01
2-Ethylhexyl paramethoxycinnamate 0.1
β-carotene 0.01
Polyvinyl alcohol 0.5
Hydroxyethyl cellulose 0.5
Carboxyvinyl polymer 0.05
Purified water Residual fragrance

Formulation Example 11: Cream Vaseline 2.0% by mass
Dimethylpolysiloxane 2.0
Ethanol 5.0
Behenyl alcohol 0.5
Batyl alcohol 0.2
Glycerin 7.0
1,3-butylene glycol 5.0
Polyethylene glycol 20000 0.5
Jojoba oil 3.0
Squalane 2.0
Phytosteryl hydroxystearate 0.5
Tetra-2-ethylhexanoic acid pentaerythrit 1.0
Polyoxyethylene hydrogenated castor oil 1.0
Potassium hydroxide 0.1
Sodium pyrosulfite 0.01
Sodium hexametaphosphate 0.05
Stearyl glycyrrhetinate 0.1
Pantothenyl ethyl ether 0.1
Arbutin 7.0
Tranexamic acid methylamide hydrochloride 11.0
This hyaluronic acid production promoter (treated product of Konotegasiwa seed hexane extract)
0.001
Carnosine 3.5
Tocopherol acetate 0.1
Sodium hyaluronate 0.05
P-Hydroxybenzoate appropriate amount trisodium edetate 0.05
4-t-butyl-4'-methoxydibenzoylmethane 0.1
Diparamethoxycinnamic acid mono-2-ethylhexanoic acid glyceryl
0.1
Yellow iron oxide xanthane gum 0.1
Carboxyvinyl polymer 0.2
Purified water residue

Formulation Example 12: Cream Vaseline 2.0% by mass
Dimethylpolysiloxane 2.0
Ethanol 5.0
Behenyl alcohol 0.5
Batyl alcohol 0.2
Glycerin 7.0
1,3-butylene glycol 5.0
Polyethylene glycol 20000 0.5
Jojoba oil 3.0
Squalane 2.0
Phytosteryl hydroxystearate 0.5
Tetra-2-ethylhexanoic acid pentaerythrit 1.0
Polyoxyethylene hydrogenated castor oil 1.0
Potassium hydroxide 0.1
Sodium pyrosulfite 0.01
Sodium hexametaphosphate 0.05
Stearyl glycyrrhetinate 0.1
Pantothenyl ethyl ether 0.1
Arbutin 7.0
Tranexamic acid methylamide hydrochloride 11.0
This anti-wrinkle agent (treated product of Konotegasiwa seed acetone extract)
1.0
Tocopherol acetate 0.1
Sodium hyaluronate 0.05
P-Hydroxybenzoate appropriate amount trisodium edetate 0.05
4-t-butyl-4'-methoxydibenzoylmethane 0.1
Diparamethoxycinnamic acid mono-2-ethylhexanoic acid glyceryl
0.1
Yellow iron oxide xanthane gum 0.1
Carboxyvinyl polymer 0.2
Purified water residue

Formulation Example 13: Cream Vaseline 2.0% by mass
Dimethylpolysiloxane 2.0
Ethanol 5.0
Behenyl alcohol 0.5
Batyl alcohol 0.2
Glycerin 7.0
1,3-butylene glycol 5.0
Polyethylene glycol 20000 0.5
Jojoba oil 3.0
Squalane 2.0
Phytosteryl hydroxystearate 0.5
Tetra-2-ethylhexanoic acid pentaerythrit 1.0
Polyoxyethylene hydrogenated castor oil 1.0
Potassium hydroxide 0.1
Sodium pyrosulfite 0.01
Sodium hexametaphosphate 0.05
Stearyl glycyrrhetinate 0.1
Pantothenyl ethyl ether 0.1
4-Methoxybenzoic acid 3.0
Tranexamic acid methylamide hydrochloride 11.0
This collagen production promoter (treated product of Konotegasiwa seed hexane extract)
0.1
Carnosine 3.5
Tocopherol acetate 0.1
Sodium hyaluronate 0.05
P-Hydroxybenzoate appropriate amount trisodium edetate 0.05
4-t-butyl-4'-methoxydibenzoylmethane 0.1
Diparamethoxycinnamic acid mono-2-ethylhexanoic acid glyceryl
0.1
Yellow iron oxide xanthane gum 0.1
Carboxyvinyl polymer 0.2
Purified water residue

Formulation Example 14: Microneedle A manufacturing method according to the method described in Japanese Patent Application Laid-Open No. 2005-152180, wherein maltose having the following composition: 94.5% by mass
Dextran 5.0
Losartan 0.1
This hyaluronic acid production promoter (treated product of Konotegasiwa seed ethyl acetate extract)
0.4

Formulation Example 15: Soft capsule (1,500 mg / day)
Edible soybean oil 530 mg
Eucommia extract 50
Carrot extract 50
This collagen production promoter (treated product of water extract of water containing water from Konotegasiwa )
100
Royal Jelly 50
Maca 30
γ-aminobutyric acid (GABA) 30
Beeslow 60
Gelatin 375
Glycerin 120
Glycerin fatty acid ester 105

Claims (10)

An extract containing oily components is obtained by extracting seeds of Platycladus orientalis using an organic solvent, and a part or all of the solvent of the extract is distilled off, and then a concentration of 0.5 to 15 N is obtained. A collagen production promoter characterized by being obtained by adding and mixing an alkaline aqueous solution and then washing with water after acid treatment. An extract containing oily components is obtained by extracting seeds of Platycladus orientalis using an organic solvent, and a part or all of the solvent of the extract is distilled off, and then a concentration of 0.5 to 15 N is obtained. A hyaluronic acid production promoter obtained by adding and mixing an alkaline aqueous solution, and then washing with water after acid treatment. An extract containing oily components is obtained by extracting seeds of Platycladus orientalis using an organic solvent, and a part or all of the solvent of the extract is distilled off, and then a concentration of 0.5 to 15 N is obtained. A fibroblast growth promoter obtained by adding and mixing an alkaline aqueous solution, and then washing with water after acid treatment. An extract containing oily components is obtained by extracting seeds of Platycladus orientalis using an organic solvent, and a part or all of the solvent of the extract is distilled off, and then a concentration of 0.5 to 15 N is obtained. An anti-wrinkle agent obtained by adding and mixing an alkaline aqueous solution, and then washing with water after acid treatment.   The promoter or anti-wrinkle agent according to any one of claims 1 to 4, wherein the amount of pure alkali to be added is 100 to 300 g / L extract. Extraction of seeds of Platycladus orientalis using organic solvents A step of obtaining an extract containing a component, and after distilling off part or all of the solvent of the extract, Adding and mixing 0.5 to 15 N aqueous alkali solution, and then washing with water after acid treatment. A method for producing a collagen production promoter, comprising: Extraction of seeds of Platycladus orientalis using organic solvents A step of obtaining an extract containing a component, and after distilling off part or all of the solvent of the extract, Adding and mixing 0.5 to 15 N aqueous alkali solution, and then washing with water after acid treatment. A method for producing a hyaluronic acid production promoter, comprising:   Extraction of seeds of Platycladus orientalis using organic solvents A step of obtaining an extract containing a component, and after distilling off part or all of the solvent of the extract, Adding and mixing 0.5 to 15 N aqueous alkali solution, and then washing with water after acid treatment. A method for producing a fibroblast proliferation promoter, comprising:   Extraction of seeds of Platycladus orientalis using organic solvents A step of obtaining an extract containing a component, and after distilling off part or all of the solvent of the extract, Adding and mixing 0.5 to 15 N aqueous alkali solution, and then washing with water after acid treatment. The manufacturing method of the anti-wrinkle agent characterized by including. It adds in the manufacturing method of the promoter or anti-wrinkle agent in any one of Claims 6-9. Promoter or anti-wrinkle characterized in that the amount of pure alkali is 100 to 300 g / L extract Manufacturing method.