KR20150057916A - Composition for skin cell regeneration or anti-wrinkle - Google Patents

Abstract

The present invention relates to a composition for skin cell regeneration or anti-wrinkle. Verbascoside according to the present invention increases the total amount of collagen of skin fibroblast cells so that an effect of skin cell regeneration or anti-wrinkle is exhibited, thereby enabling to be used for a pharmaceutical composition, an external preparation for skin, a cosmetic composition, or health food. The pharmaceutical composition for the skin regeneration or anti-wrinkle includes a compound represented by Chemical Formula 1 as an active ingredient.

Description

Technical Field [0001] The present invention relates to a composition for skin regeneration or anti-wrinkle,

The present invention relates to a composition for skin regeneration or wrinkle improvement.

Collagen is a major substrate protein produced in fibroblasts of the skin and exists in extracellular epilepsy. Its important functions are mechanical rigidity of skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, division of cells and differentiation Growth or wound healing) are known. Such collagen is reduced by aging and photo aging caused by ultraviolet irradiation, which is known to be closely related to the wrinkling of the skin. Also, in recent years, extensive research on skin aging has developed, and important functions of collagen in skin have been revealed.

Effective ingredients promoting collagen synthesis and exhibiting wrinkle-reducing effects are known. For example, retinoic acid, transforming growth factor (TGF) [Non-Patent Document 1], animal-derived placenta protein [Patent Document 1], betulinic acid [Patent Document 2] and chlorella extract [ Patent Documents 3 and 4] are known as collagen synthesis promoting substances. However, the above-mentioned effective ingredients are limited in the amount of use due to safety problems such as irritation and reddening when applied to the skin, or have insufficient effect, so that there is a problem that the effect of improving skin function by promoting collagen synthesis of skin substantially can not be expected.

Japan Patent No. 8-231370 Japan Patent No. 8-208424 Japan Patent No. 9-40523 Japan Patent No. 10-36283

 Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974

Accordingly, the inventors of the present invention have confirmed that verbascoside increases the total amount of collagen of the fibroblasts of the skin, thereby promoting the regeneration of the skin and improving the wrinkles, thereby completing the present invention.

Accordingly, an object of the present invention is to provide a composition for skin regeneration or wrinkle improvement comprising verbascoside as an active ingredient.

As means for solving the above problems,

There is provided a pharmaceutical composition for skin regeneration or wrinkle improvement comprising a compound represented by the following formula (1) as an active ingredient.

 [Chemical Formula 1]

As another means for solving the above problems,

There is provided a cosmetic composition for skin regeneration or wrinkle improvement comprising a compound represented by the following formula (1) as an active ingredient.

[Chemical Formula 1]

The verbascoside according to the present invention increases the total amount of collagen of the fibroblasts of the skin, promotes the regeneration of the skin, and improves the elasticity and wrinkles of the skin. Thus, the verbascoside can be used for medicines, cosmetics or health foods have.

Hereinafter, the configuration of the present invention will be described in detail.

It is preferable that the skin regeneration or wrinkle improving component exhibits highly active skin regeneration or wrinkle reducing activity at a low concentration in order to exert an excellent effect when applied to actual skin and has excellent ability to be absorbed through the skin. Is low in volatility so as to be able to stay for a sufficient period of time to exhibit skin regeneration or wrinkle improving effect and is stable on the composition or on the skin, is easy to be formulated into medicines or cosmetics, and is safe for skin . However, among the known components, the components satisfying all of the above characteristics are not common. For example, some skin regrowth or wrinkle improving agents have excellent skin regeneration or wrinkle reducing activity even at low concentrations in vitro, but they are difficult to apply to real skin because of their ability to permeate and absorb the skin. Other active ingredients have low hydrophilicity and are difficult to formulate into medicines or cosmetics. In addition, some skin regrowth or wrinkle remedying ingredients may be degraded or transformed into other compounds when exposed to heat, light, or oxygen, and the effect may already be lost before application to the skin.

As can be seen from the following examples, verbascoside shows an effect of significantly increasing the total amount of collagen at a low concentration, and thus can be used as an effective ingredient for medicines, cosmetics or health food for skin regeneration or wrinkle improvement have.

Accordingly, the present invention provides a pharmaceutical composition for skin regeneration or wrinkle improvement comprising a compound represented by the following general formula (1) as an active ingredient.

[Chemical Formula 1]

The compound of formula (1) is called verbascoside and may include all possible isomers.

The compound of formula (1) may be synthesized or a commercially available compound may be used.

The compound of Formula 1 may be contained in an amount of 0.00001 to 99.9% by weight.

The pharmaceutical composition for skin regeneration or wrinkle improvement of the present invention may comprise a pharmaceutically acceptable salt of the compound of formula (1).

The pharmaceutically acceptable salt of the compound of Chemical Formula 1 may be an acid addition salt formed using an organic acid or an inorganic acid, and examples of the organic acid include formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, The present invention also relates to the use of a compound selected from the group consisting of malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, gluconic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, Benzenesulfonic acid, p-toluenesulfonic acid or methanesulfonic acid-based salts. The inorganic acid includes, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid or boric acid-based salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.

The above-mentioned acid addition salts may be obtained by a) directly mixing the compound of formula 1 and an acid, or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Lt; RTI ID = 0.0 > acid < / RTI > in a solvent and mixing them.

Separately, additionally saltable forms include, but are not limited to, the salts of gabapentin, gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, lysine, Aspartate and the like.

When the compound of Chemical Formula 1 of the present invention is used as a medicine, it may further contain one or more active ingredients showing the same or similar functions. For example, it may contain known skin regeneration or wrinkle improving ingredients. The addition of additional skin regeneration or wrinkle improving ingredients may further enhance the skin regeneration or wrinkle reducing effect of the composition of the present invention. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use. In one embodiment of the present invention, the composition is a skin regeneration component known in the art and includes one or more species selected from the group consisting of retinoic acid, TGF, protein from animal placenta, betulinic acid or chlorella extract Component. ≪ / RTI > The additional component may be contained in an amount of 0.0001 wt% to 10 wt% based on the total weight of the composition. For example, from 0.0001 wt% to 1 wt%, from 0.0001 wt% to 0.1 wt%, from 0.0001 wt% to 0.001 wt%, from 0.001 wt% to 10 wt%, from 0.001 wt% 0.001 wt% or more to 0.1 wt% or less, 0.01 wt% or more to 10 wt% or less, or 0.01 wt% or more to 1 wt% or less. The content range may be adjusted according to requirements such as skin safety, ease of formulation of the compound of Formula 1, and the like.

In addition, the pharmaceutical composition for skin regeneration or wrinkle improvement of the present invention may further comprise a pharmaceutically acceptable carrier.

Pharmaceutically acceptable carriers may contain various components such as buffer, injectable sterile water, normal saline or phosphate buffered saline, sucrose, histidine, or polysorbate.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and can be administered in the form of a general pharmaceutical preparation, for example, in a variety of oral or parenteral formulations upon clinical administration. In the case of formulation, , Extenders, binders, wetting agents, disintegrating agents, or surfactants.

Solid form preparations for oral administration include tablets, pills, powders, granules or capsules, which may be prepared by mixing the pharmaceutical composition of the present invention with at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin, and the like.

In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions or syrups. In addition to water or liquid paraffin, which is a simple diluent commonly used, various excipients such as wetting agents, sweetening agents, fragrances or preservatives may be included.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations or suppositories. Non-aqueous vehicles or suspending agents include vegetable oils such as propylene glycol, polyethylene glycol or olive oil; And injectable esters such as ethyl oleate may be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao paper, laurin or glycerogelatin can be used.

In the present invention, the term " skin regeneration effect " refers to restoration of skin tissue against damage caused by external or internal causes of the skin. The damage caused by the external cause may be ultraviolet rays, external contaminants, wound or trauma, and the damage caused by the internal cause may be stress.

In the present invention, the term " wrinkle-reducing effect " refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating already-generated wrinkles.

The pharmaceutical composition of the present invention can provide an effect such as skin regeneration or wrinkle improvement which is preferable when an effective amount of the compound of Formula 1 is included. In the present invention, the term "effective amount" means the amount of a compound capable of promoting regeneration of damaged skin or exhibiting an effect of improving wrinkles. The effective amount of the compound of formula (1) contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, the method in which the compound is applied to the skin or the time on the skin. For example, when the composition is commercialized as a pharmaceutical product, the compound of Formula 1 may be contained at a higher concentration than that of a cosmetic product that is routinely applied to skin. Accordingly, the daily dosage is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, based on the amount of the compound of formula (1) 6 times a day.

The pharmaceutical compositions of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy or biological response modifiers.

The present invention can also provide a skin external preparation for skin regeneration or wrinkle improvement comprising the compound of formula (1) as an active ingredient.

When the compound of formula (1) is used as an external preparation for skin, it may further comprise at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, Such as water, an ionic emulsifier, a nonionic emulsifier, a filler, a sequestering agent, a chelating agent, a preservative, a vitamin, a blocker, a wetting agent, a necessary oil, a dye, a pigment, a hydrophilic activator, Such as any other ingredients conventionally used in the field of skin science. The components can also be introduced in amounts commonly used in the field of dermatology.

When the compound of Formula 1 is provided as an external preparation for skin, it may be a formulation such as ointments, patches, gels, creams or sprays.

The present invention can also provide a cosmetic preparation for skin regeneration or wrinkle improvement comprising the compound of Formula 1 as an active ingredient.

When the compound of Chemical Formula 1 is used as a cosmetic, the cosmetic product containing the compound of Chemical Formula 1 as an active ingredient may be prepared in the form of a general emulsion or solubilized formulation. Lotion such as soft lotion or nutrition lotion; Lotion such as facial lotion or body lotion; Creams such as nutritional creams, moisture creams or eye creams; essence; Makeup ointment; spray; Gel; pack; Sunscreen; Makeup base; A foundation such as a liquid type, a solid type or a spray type; powder; Makeup removers such as cleansing creams, cleansing lotions, cleansing oils; Detergents such as cleansing foams, soaps, body wash, and the like.

The cosmetic composition may further contain, in addition to the compound of Formula 1, a lipid, an organic solvent, a solubilizing agent, a thickening agent, a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, The present invention is generally applied to cosmetics such as ionic emulsifiers, nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic active agents, lipophilic active agents, And may contain auxiliary agents used.

In the case of a wash-off type cosmetic such as a make-up removing agent or a detergent in which the active ingredient remains on the skin in a short period of time when the compound of formula (1) is commercialized, a relatively high concentration of the compound of formula . On the other hand, in the case of a leave-on type cosmetics such as lotion, milk, cream or essence whose effective ingredient remains on the skin for a long period of time, the compound of the above formula 1 is contained at a lower concentration than that of the wash- It may be possible. In one embodiment of the present invention, although not limited thereto, the composition may contain 0.000001 wt% to 10 wt% (preferably 0.001 wt% to 10 wt%, more preferably 0.001 wt% to 10 wt% 0.1 to 10% by weight). When the composition of the present invention contains less than 0.000001% by weight of the compound of the formula 1, sufficient skin regeneration or wrinkle-reducing effect can not be expected. When the composition contains more than 10% by weight, This is to prevent skin safety problems.

The present invention also relates to a health food for skin regeneration or wrinkle improvement comprising the compound of formula (1).

Herein, the term " health food " means a food prepared by adding the compound of formula (1) to food materials such as beverage, tea, spice, gum and confectionery, or by encapsulation, powdering or suspension, But it has the advantage that there is no side effect that can occur when a drug is taken for a long time using a food as a raw material, unlike a general medicine.

Since the health food of the present invention thus obtained can be taken on a daily basis, a high skin regeneration or wrinkle reducing effect can be expected, which is very useful.

When the compound of Chemical Formula 1 is used as a food additive, the compound of Chemical Formula 1 may be added as it is or may be used together with other food or food ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). Generally, the composition of the present invention is added in an amount of not more than 15 parts by weight, preferably not more than 10 parts by weight, based on the raw material, when the food or beverage is produced. However, in case of long-term ingestion for health and hygiene purposes, the active ingredient may be contained in an amount not exceeding the above range and there is no problem in terms of safety.

There is no particular limitation on the kind of the food. Examples of the food to which the above substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, or vitamin complexes, and includes all health foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as additional components such as ordinary beverages. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose, sucrose; Polysaccharides such as dextrin, cyclodextrin; Xylitol, sorbitol, erythritol, and the like. Sweeteners include natural sweeteners such as tau Martin and stevia extract; Synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.

In addition to the above, the health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acid, protective colloid thickener, pH adjusting agent, Glycerin, an alcohol or a carbonating agent, and the like. In addition, the health food of the present invention may contain natural fruit juice, fruit juice drink, or pulp for the production of vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, the present invention will be described in detail with reference to examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

Reference Example  One: Bear Basco side ( Verbascoside Material information

Verbascoside

CAS No .: 61276-17-3

Where to buy: Tauto Biotech Co., Ltd.

Experimental Example  1: Increase effect of total collagen

Compounds of the following formula were added to the culture medium of human-derived fibroblasts and the total amount of collagen was measured at the cellular level. The total amount of synthesized collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immunoassay Kit). To evaluate the cytotoxicity of human fibroblasts before experimentation at concentrations of 10 ppm, 1 ppm, 0.1 ppm, 0.01 ppm, and 0.001 ppm of the test substance (method for MTT test by culturing fibroblasts [Reference: Mossman T. ), And the total amount of collagen was measured by selecting a concentration without cytotoxicity. The results are shown in Table 1.

In the experiment, the final concentrations of the compounds of formula (1) were 2 ppm, 5 ppm, and 10 ppm, respectively. Each sample was added to the culture medium of human fibroblasts and cultured for 1 day. Then, the culture solution was taken and analyzed with PICP EIA kit The total amount of collagen was measured at 450 nm using a spectrophotometer. For the comparison of the effects, the total amount of collagen was measured by the same method for the culture medium of the fibroblasts to which nothing was added (control group) and the sample added with vitamin C to the final concentration of 52.8 ppm. The total amount of collagen was measured as a UV absorbance, and the rate of increase of the total amount of collagen was calculated by the ratio of the total amount of collagen relative to the control, and the results are summarized in Table 1 below.

Increased effect of total collagen (number of repeats = 6) sample Collagen growth rate (%) The compound of formula (1)
(2 ppm) 22 The compound of formula (1)
(5 ppm) 68 The compound of formula (1)
(10 ppm) 83 Control group
(No additives) - Vitamin C
(52.8 ppm) 26

As can be seen from the results of Table 1, the compound of formula (1) (10 ppm) showed better collagen growth rate than vitamin C (52.8 ppm), which is known to be capable of collagen synthesis. Therefore, it was found that the compound of Chemical Formula 1 can be used for skin regeneration and wrinkle improvement.

Experimental Example  2: Wrinkle improvement effect experiment

Using 6-week-old hairless mice, the wrinkle-improving effect of the compound of formula (1) was tested on the wrinkles induced by light. As a sample, the compound of formula (1) was applied to 1,3-butylene glycol at 0.2%, and the test method was as follows.

Hairless mice were irradiated with 2MED for 3 weeks and 10 weeks using a solar simulator to form wrinkles. The control group treated with 1,3-butylene glycol to which no sample was added and the control group treated with 0.2% The degree of improvement was qualitatively evaluated in the group treated with 0.1 ml / cm ² (0.2 mg / cm ² as the compound of the formula (1)) for 6 weeks twice a day.

The degree of wrinkle improvement was judged by naked eyes through visual observation and photographing, and the judgment criteria were three stages of no improvement, little improvement, and considerable improvement compared with those before the sample treatment in the sample treatment group and the control group Table 2 shows the results.

Wrinkle improvement effect on mice (number of each group = 10) sample No improvement Slight improvement A significant improvement Control group 10 0 0 The compound of formula (1) One 4 5

As can be seen from the results of Table 2 above, it can be confirmed that the compound of Chemical Formula 1 has a high effect of improving wrinkles.

Manufacturing example  1 and Comparative Example  One: Ointment for external skin Prescription example

Composition Production Example 1 (% by weight) Comparative Example 1 - the compound of formula 1
- diethyl sebacate
- Writers
- polyoxyethylene oleyl ether phosphate
- Sodium benzoate
-vaseline 0.5
8
5
6
Suitable amount
to 100 -
8
5
6
Suitable amount
to 100

Manufacturing example  2 and Comparative Example  2: Cosmetics  Of creamy Prescription example

Composition Production Example 2 (% by weight) Comparative Example 2 - the compound of formula 1
- Stearic acid
- Cetanol
- potassium hydroxide
-glycerin
- propylene glycol
-antiseptic
-incense
-Purified water 0.2
15.0
1.0
0.7
5.0
3.0
Suitable amount
Suitable amount
to 100 -
15.0
1.0
0.7
5.0
3.0
Suitable amount
Suitable amount
to 100

Manufacturing example  3 and Comparative Example  3: Cosmetics  Of flexible lotion Prescription example

Composition Production Example 3 (% by weight) Comparative Example 3 - the compound of formula 1
-ethanol
- polyoxyethylene sorbitan polylauric acid
- Paraoxybenzoic acid methyl
-glycerin
-1,3-butylene glycol
-incense
- Pigment
-Purified water 0.1
10.0
1.0
0.2
5.0
6.0
Suitable amount
Suitable amount
to 100 -
10.0
1.0
0.2
5.0
6.0
Suitable amount
Suitable amount
to 100

Manufacturing example  4 and Comparative Example  4: Cosmetics  Of nutritional lotion Prescription example

Composition Production Example 4 (% by weight) Comparative Example 4 - the compound of formula 1
- Vaseline
- sesquioleic acid sorbitan
- polyoxyethylene oleyl ethyl
- Paraoxybenzoic acid methyl
- propylene glycol
-ethanol
-Carboxyvinyl polymer
- potassium hydroxide
- Pigment
-incense
-Purified water 0.05
2.0
0.8
1.2
Suitable amount
5.0
3.2
18.0
0.1
Suitable amount
Suitable amount
to 100 -
2.0
0.8
1.2
Suitable amount
5.0
3.2
18.0
0.1
Suitable amount
Suitable amount
to 100

Manufacturing example  5 and Comparative Example  5: Cosmetics  Pack of Prescription example

Composition Production Example 5 (% by weight) Comparative Example 5 - the compound of formula 1
-glycerin
- propylene glycol
- Polyvinyl alcohol
-ethanol
- polyoxyethylene oleyl ether
- Paraoxybenzoic acid methyl
- Pigment
-incense
-Purified water 0.05
5.0
4.0
15.0
8.0
1.0
0.2
Suitable amount
Suitable amount
to 100 -
5.0
4.0
15.0
8.0
1.0
0.2
Suitable amount
Suitable amount
to 100

Manufacturing example  6 and Comparative Example  6: Cosmetics  Of the essence Prescription example

Composition Production Example 6 (% by weight) Comparative Example 6 - the compound of formula 1
- propylene glycol
-glycerin
- aqueous solution of sodium hyaluronate (1%)
-ethanol
- Polyoxyethylene hardened castor oil
- Paraoxybenzoic acid methyl
-incense
-Purified water 0.2
10.0
10.0
5.0
5.0
1.0
0.1
Suitable amount
to 100 -
10.0
10.0
5.0
5.0
1.0
0.1
Suitable amount
to 100

Experimental Example  3

The effect of improving the wrinkles was tested in healthy 35 to 50 year old women against the essence of the above-described Production Example 6 and Comparative Example 6. [

30 women aged 35 to 50 years were divided into two groups by 15 persons. Group 1 contained the essence of Preparation Example 6 containing 0.2% of the compound of Formula 1, Group 2 contained the essence of Comparative Example 6, 2 times a day for 3 months.

After 3 months, the improvement of wrinkles was evaluated by image analysis of questionnaires and wrinkles. The subjects' questionnaires were judged to have no improvement, slight improvement, and considerable improvement compared to before use with regard to wrinkle improvement and elasticity improvement, and the results are shown in Table 9.

Wrinkle improvement effect (persons) sample No improvement Slight improvement A significant improvement Comparative Example 6 10 5 0 Production Example 6 - 9 6

As shown in Table 9, it can be seen that the wrinkle-improving effect is excellent when the production example according to the present invention is used.

Immediately after the experiment, the replica was collected from the same area under the eye. The image was analyzed by image analysis to determine the degree of wrinkles The density of wrinkles was measured by dimensional analysis. The results of the measurement of the wrinkle density by image analysis are shown in Table 10 as averages of the reduction rate relative to the wrinkle density before use.

Wrinkle improvement effect sample Wrinkle density reduction rate (%) Comparative Example 9% Manufacturing example 43%

As can be seen from Table 10, when the preparation of Example 1 according to the present invention was applied, the density of wrinkles was significantly decreased before use.

Claims (2)

A pharmaceutical composition for skin regeneration or wrinkle improvement comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

A cosmetic composition for skin regeneration or wrinkle improvement comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]