KR20110101715A - Composition for improving skin wrinkle - Google Patents

Abstract

The present invention relates to a wrinkle improving composition comprising a chalcone derivative as an active ingredient. The chalcone derivative of the present invention not only promotes collagen synthesis but also inhibits collagenase activity, and is excellent in solubility and stability, and thus is suitable for use as an active ingredient of a wrinkle improving composition. Therefore, the composition of the present invention comprising a chalcone derivative provides an excellent wrinkle improvement effect.

Description

Composition for improving skin wrinkles

The present invention relates to a composition for improving wrinkles, which exhibits excellent collagen synthesis promoting activity and collagenase inhibitory activity.

Collagen is a major substrate protein produced by skin fibroblasts and is present in extracellular epilepsy.Its important functions include mechanical firmness of skin, resistance of connective tissue and tissue binding, support of cell adhesion, cell division and differentiation. Induction of growth or wound healing) is known (van der Rest et al., 1990). This collagen decreases with age and light aging by UV irradiation, which is known to be closely associated with wrinkle formation of the skin (Arthur K. Balin et al., "Aging and the skin", 1989). In addition, in recent years, extensive research on aging of the skin has been developed an important function of collagen in the skin.

Conventionally, products that combine collagen with cosmetics have been released from the skin moisturizing effect of collagen, but these cosmetics are applied to the surface of the collagen, and it is not expected to moisturize by the percutaneous absorption of collagen as a polymer, thereby improving the essential skin function. I can't say.

On the other hand, it is known that the active ingredients that promote the collagen synthesis to exhibit the wrinkle improvement effect. For example, retinoic acid, transforming growth factor (TGF) [Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974], protein derived from animal placenta [Japanese Patent No. Hei 8-231370], betulinic acid [Japanese Patent Hei 8-208424], Chlorella extract [Japanese Patent Hei 9-40523, Hei 10- 36283] are known as collagen synthesis promoting substances. However, the active ingredients are limited in the amount of use due to safety problems such as irritation and redness when applying the skin, or there is a problem in that the effect of improving the skin function is not expected by substantially promoting collagen synthesis of the skin. Therefore, there is an urgent need for the development of components that are safe for the living body, the active ingredients are stable, and above all, the anti-wrinkle activity that is superior to the conventional collagen synthesis promoting substance.

On the other hand, chalcone derivatives are known to protect the plants from harmful ultraviolet rays as well as to affect the color of the plant as a constituent of the yellow pigment of the plant [Natural Chemical Research, Woowonsik, Seoul National University Press]. The chalcones are present in the genus Coreopsis. Representative chalcones include 2 ', 6'-dihydroxy-4'-methoxychalcone, cartamine, butane, and the like, which are contained in plants such as cinnamon, pepper, safflower and the like. Dehydrochalcones are mainly found in the Rosaceae and Rhododendron plants, and phloridzin, a dihydrocalcon present in apples, is associated with apple's resistance to disease. Chalcone derivatives have a physiological activity that inhibits the proliferation of various types of cells, and are known to prevent aging and have anticancer effects [Medicinal Plant Book, Jong Hee Park, Co-author Jeon, Shin Il Sang; Tanaka M.K. Et al., Cancer Res., 56, 4904-4909, 1996].

Accordingly, the present inventors have strong collagen synthesis promoting activity and collagenase inhibitory activity, are safe for skin, easy to manufacture formulations, and have a chalcone derivative in the process of screening an active ingredient having stability during cosmetic preparation and storage. The present invention has been completed by revealing the same characteristics.

Accordingly, the present invention provides a composition for improving wrinkles comprising a chalcone derivative as an active ingredient.

In order to achieve the above object, the present invention is characterized by a wrinkle improving composition comprising a chalcone derivative as an active ingredient.

The chalcone derivative of the present invention is not only excellent in collagen synthesis promoting activity and collagenase inhibitory activity, but also excellent in solubility and stability, and thus it is very suitable for use as an active ingredient of a composition for improving wrinkles. Therefore, the composition of the present invention containing a chalcone derivative as an active ingredient provides an excellent wrinkle improvement effect.

The present invention relates to a wrinkle improving composition comprising a chalcone derivative represented by Formula 1 as an active ingredient;

 [Formula 1]

In Formula 1, each R is independently H, OH or OCH ₃ .

More preferably, the chalcone derivative relates to a wrinkle improving composition which is a compound represented by the following Chemical Formula 1a.

[Formula 1a]

In order to achieve an excellent wrinkle improvement effect when applied to the skin, the wrinkle improving ingredient shows high activity at the low concentration, has excellent ability to absorb and penetrates the skin, and can stay for a sufficient time to show the effect of improving wrinkles. It is desirable to have low volatility, to keep the active ingredient stable on the composition or the skin, to be easily formulated into medicine or cosmetics, and to be safe for the skin. However, among the known wrinkle improvement components, wrinkle improvement components that satisfy all of the above characteristics are rare. For example, some wrinkle improving ingredients have excellent wrinkle improving activity even at low concentrations in vitro, but are difficult to apply to actual skin due to their poor ability to absorb and penetrate the skin. Other anti-wrinkle ingredients are less hydrophilic and difficult to formulate in medicine or cosmetics. In addition, some wrinkle improving ingredients may decompose or be transformed into other compounds when exposed to heat, light, or oxygen, and the wrinkle improving effect may already disappear before being applied to the skin.

As can be seen in the following examples, the chalcone derivatives show an excellent inhibitory activity of collagenase activity at low concentrations and excellent collagen synthesis promoting effect when compared to retinoic acid, which is a known wrinkle improvement component. In addition, the high solubility in the hydrophilic solvent showed a low volatility, excellent skin permeability, and easy formulation when applying the product. In addition, the stability with the passage of light, heat or time was found to be excellent. In addition, even at low concentrations it has been shown to be very safe for the skin because it shows a sufficient wrinkle improvement effect.

Therefore, the chalcone derivative may be used as an active ingredient exhibiting wrinkle improvement efficacy in medicines or cosmetics. Therefore, the present invention also provides a method for improving wrinkles comprising using a chalcone derivative of Formula 1 for the preparation of a pharmaceutical composition for improving wrinkles or a cosmetic composition for improving wrinkles and applying an effective amount of a chalcone derivative of Formula 1 to the skin.

The chalcone derivative can be used as a known compound by synthesizing or using a commercially available compound.

In the present invention, 'wrinkle improvement' refers to inhibiting or inhibiting wrinkles generated on the skin or alleviating wrinkles already generated.

The wrinkle improvement composition of the present invention may provide a desirable wrinkle improvement effect when an effective amount of a chalcone derivative of Formula 1 is included. In the present invention, the term 'effective amount' means an amount of a compound capable of inhibiting or inhibiting generation of wrinkles on the skin or alleviating wrinkles already produced. The effective amount of the chalcone derivative of Formula 1 included in the composition for improving wrinkles of the present invention will vary depending on the form in which the composition for improving wrinkles is commercialized, the method of applying the compound to the skin, and the time to stay on the skin. For example, when the composition for improving wrinkles is commercialized as a medicament for dermatological treatment according to the generation of wrinkles on the skin, it may include a chalcone derivative of Formula 1 at a higher concentration than when it is commercialized to cosmetics that are applied to the skin on a daily basis. Could be. Even in the case of cosmetics, wash-off type cosmetics such as makeup remover and cleanser, in which the active ingredient stays on the skin within a short time, may include a relatively high concentration of chalcone derivative of Formula 1 . On the other hand, in the case of leave-on type cosmetics such as lotion, emulsion, cream, essence, etc., in which the active ingredient stays on the skin for a long time, the chalcone derivative of Formula 1 has a lower concentration than the wash-off type cosmetics. It may be included. Although not limited thereto, in one embodiment of the present invention, the composition for improving wrinkles may include the chalcone derivative of Formula 1 in an amount of 0.0001 wt% to 10 wt% based on the total weight of the composition. When the wrinkle improving composition of the present invention contains less than 0.0001% by weight of the chalcone derivative of Formula 1, sufficient anti-wrinkle effect may not be expected, and when it contains more than 10% by weight, an unwanted reaction such as allergy or the like may occur. This is to prevent safety because there may be a problem.

The wrinkle improvement composition of the present invention may further include a known wrinkle improvement component in addition to the chalcone derivative of the formula (1). Including an additional wrinkle improving component may further enhance the wrinkle improving effect of the composition of the present invention. The addition of the anti-wrinkle component may take into account the safety of the skin, ease of formulation, and stability of the active ingredients according to the combined use. In one embodiment of the present invention, the composition for improving wrinkles is a wrinkle improving component known in the art, one or more selected from the group consisting of retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract or It may further comprise two or more wrinkle improving ingredients. Additional anti-wrinkle ingredients may be included in an amount of 0.0001% to 10% by weight based on the total weight of the composition, the content range of which is to promote collagen synthesis or collagenase inhibitory activity, skin safety, formulated with the chalcone derivative of Formula 1 It may be adjusted according to requirements such as ease of use.

In the present invention, the wrinkle improving composition may be a pharmaceutical composition or a cosmetic composition. When the composition for improving wrinkles is formulated in medicine or cosmetics, it may include a pharmacologically known and excipient which acts as a carrier for the active ingredient. When formulating into a medicament, reference may be made to what is disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA, and when formulating into a cosmetic, the International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance Association , Inc., Washington, 1995. Such documents are incorporated as part of this specification.

When the composition for improving wrinkles of the present invention is a cosmetic composition, the composition is not limited thereto, such as a lotion such as a flexible lotion or a nourishing lotion, an emulsion such as a facial lotion or a body lotion, a nutrient cream, a moisture cream, an eye cream, or the like. Foundations, such as creams, essences, ointments, sprays, gels, packs, sunscreens, makeup bases, liquids, solids or sprays, makeup removers such as powders, cleansing creams, cleansing lotions, cleansing oils, cleansing foams, soaps And detergents such as body washes and the like. In this case, the cosmetic composition may include a surfactant, an emulsifier, a soap acid, a solvent, a binder, a diluent, a lubricant, a stabilizer, a flavor, a water, a lower alcohol, a thickener, a chelating agent, a pigment, a preservative, a colorant, a preservative, an antibiotic, an antioxidant, Defoamers, antibacterial agents, antidepressants, enzymes, plant or mineral oils, fats, fluorescent substances, fungicides, hydrogenic agents, moisturizers, fragrances, fragrance carriers, preservatives, proteins, silicones, solubilizers, sugar derivatives, sunscreens, vitamins It may contain one or two or more pharmacologically acceptable excipients selected from the group consisting of plant extracts and waxes.

Advantages and features of the present invention and methods for achieving them will be apparent with reference to the embodiments described below in detail. However, the present invention is not limited to the embodiments disclosed below, but may be implemented in various different forms, only the embodiments are to make the disclosure of the present invention complete, and common knowledge in the technical field to which the present invention belongs. It is provided to fully inform the person having the scope of the invention, which is defined only by the scope of the claims.

Example  One: Calcon  Derivative Collagenase  Confirmation of active inhibitory effect

The inhibitory effect of collagenase activity of the compound of formula 1a (dihydroxymethoxychalcone; C ₁₆ H ₁₄ O ₄ , MW 270.28) was confirmed as follows.

[Formula 1a]

In order to observe the inhibitory effect of collagenase activity, collagenase decomposed Gly-Leu binding of commercially available substrate Dabcyl-r-Abu-Pro-GLu-Gly-Leu-Glu (EDANS) -Ala-Lys-NH ₂ Thus, the N-terminus of Dabcyl group and the C-terminus of EDNAS are experiments using the mechanism of action as quencher.

Compounds of formula 1a by concentration in 96-well plates [AK Scientific, Inc., USA, Cat No. : V1575] was added and the reaction buffer and commercially available substrates were reacted at 37 ° C. for 1 hour, and then 5 μl of EDTA was added to terminate the reaction. At this time, the degree of color development was measured by measuring the absorbance at 340 nm / 520 nm using a flurometer (Bob Beekman et al., FEBS, 390, 221-225, 1996). As a negative control, a group without addition of the compound of Formula 1a was used, and a group containing 1% of retinoic acid was used as a positive control.

Collagenase activity inhibition rate was calculated by the following equation 1, the results are shown in Table 1 below.

[Equation 1]

TABLE 1

Inhibition of Collagenase Activity According to Concentration

As can be seen from Table 1, the compound of Formula 1a was found to have excellent collagenase activity inhibitory effect.

Example  2: Carlton  Confirmation of Collagen Synthesis Promoting Effect of Derivatives

The compound of formula 1a was added to the culture medium of human-derived fibroblasts to test collagen synthesis promoting effect at the cellular level.

Biosynthetic collagen was measured using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme ImmunoAssay KIT).

The compound of Formula 1a was added to the culture medium of human fibroblasts in a final concentration of 0.01 μg / ml, 0.1 μg / ml, 1 μg / ml, 2 μg / ml and 5 μg / ml and cultured for 1 day. As a negative control, a group not treated with the compound of Formula 1a was used, and as a positive control, Vit. The group treated with C was used. After incubation, the culture medium was taken, and the degree of collagen biosynthesis at each concentration was measured at 450 nm using a spectrophotometer with PICP EIA Kit. Collagen biosynthesis was calculated relative to the negative control without the addition of any collagen synthesis promoter. The results are shown in Table 2 below.

TABLE 2

Collagen Biosynthesis Effect at the Cell Level According to Concentration

As can be seen from the results of Table 2, it can be seen that the compound of Formula 1a has excellent collagen biosynthesis performance against human fibroblasts.

Example  3: in vivo Evaluation of wrinkle improvement in

The wrinkle-improving effect of the compound of Formula 1a was tested for wrinkles induced by light using a 6 week old hairless mouse.

The compound of Formula 1a was dissolved in 0.5% in 1,3-butylene glycol and used as a sample. The test method is as follows.

The hairless mouse was irradiated with 2MED for 3 days and 10 weeks a week using a solar simulator to form wrinkles, and a control group treated with dipropylene glycol without adding a sample and 0.1% of the compound of Formula 1a. Was evaluated qualitatively in the group treated with 0.5 ml / cm ² (2.5 mg / cm ² as a compound of Formula 1a) twice a day for 6 weeks.

Determination of the degree of wrinkle improvement was first visually judged by the sample treatment site, and the criterion was judged by three stages of no improvement, slight improvement, and significant improvement compared to the sample treatment group and the control group before the sample treatment. Shown in

[Table 3]

Wrinkle improvement effect on mouse

Example  4: Calcon  Evaluation of stability of derivative

After dissolving the compound of Formula 1a in 0.1% in 90% ethanol, the stability was evaluated by exposure to the following conditions: light (natural light, 2 weeks), heat (80 ° C., 8 hours), over time (shading, 25 ° C., 3) month)

Table 4 shows the results of analyzing the stability of the compound of Formula 1a.

[Table 4]

Stability Analysis of Compounds of Formula 1a

As can be seen from Table 4, the compound of Formula 1a was found to be stable to flow in light, heat and time.

Manufacturing example  1 and Comparative example  1: Preparation of skin external ointment

As in the composition of Table 5, an external skin ointment containing the compound of Formula 1a was prepared according to a conventional method. In addition, the external skin ointment prepared with the remaining components except for the compound of Formula 1a was prepared in Comparative Example 1.

TABLE 5

Manufacturing example  2 and Comparative example  2: Preparation of Cream

As in the composition of Table 6, a cream containing a compound of Formula 1a was prepared according to a conventional method. In addition, a cream prepared with the remaining ingredients except for the compound of Formula 1a was prepared in Comparative Example 2.

TABLE 6

Manufacturing example  3 and Comparative example  3: Preparation of flexible lotion

As in the composition of Table 7 below, a flexible lotion containing a compound of Formula 1a was prepared according to a conventional method. In addition, a flexible lotion prepared with the remaining components except for the compound of Formula 1a was prepared in Comparative Example 3.

TABLE 7

Manufacturing example  4 and Comparative example  4: manufacturing of nutritional lotion

As in the composition of Table 8, a nutritional lotion containing a compound of Formula 1a was prepared according to a conventional method. In addition, the nutritional lotion prepared with the remaining ingredients except for the compound of Formula 1a was prepared in Comparative Example 4.

[Table 8]

Manufacturing example  5 and Comparative example  5: manufacture of the pack

As shown in Table 9, a pack including a compound of Formula 1a was prepared according to a conventional method. In addition, a pack prepared with the remaining components except for the compound of Formula 1a was prepared in Comparative Example 5.

TABLE 9

Manufacturing example  6 and Comparative example  6: Preparation of Essence

As shown in the following Table 10, an essence comprising the compound of Formula 1a was prepared according to a conventional method. In addition, an essence prepared with the remaining components except for the compound of Formula 1a was prepared in Comparative Example 6.

TABLE 10

Experimental Example : Calcon  Confirmation of Wrinkle Improvement Effect of Derivatives

For the essences of Preparation Example 6 and Comparative Example 6 Wrinkle improvement effect was carried out in healthy 35 to 50 year old women as follows.

Thirty females from 35 to 50 years old were divided into two groups of 15 persons, group 1 containing the essence of Preparation Example 6 containing the compound of formula (I), group 2 using the essence of Comparative Example 6 on the face part 2 It was applied six times a week.

After 2 months, the improvement of wrinkles was evaluated by subject's questionnaire and image analysis of wrinkles. The subject's questionnaire was judged in three stages of no improvement, slight improvement, and significant improvement in comparison with before use regarding wrinkle improvement and elasticity enhancement, and the results are shown in Table 11 below.

TABLE 11

As can be seen in Table 11, when using the essence of Preparation Example 6 according to the present invention it can be seen that the wrinkle improvement effect is excellent.

Image analysis of wrinkles was performed by taking a replica under the eyes (Xantopren, Bayer) before the experiment was started, and immediately after the experiment was finished, replicas were taken from the same area under the eyes. The density of wrinkles was measured by two-dimensional analysis. The measurement results of the wrinkle density by image analysis are shown in Table 12 by averaging the reduction ratio for the wrinkle density before use.

TABLE 12

As can be seen in Table 12, it can be seen that when the essence of Preparation Example 6 according to the present invention is applied, the essence of Comparative Example 6 is significantly reduced.

Claims (8)

The composition for improving wrinkles comprising a chalcone derivative represented by Formula 1 as an active ingredient;
[Formula 1]

In Formula 1, each R is independently H, OH or OCH ₃ .
According to claim 1, wherein the chalcone derivative is a wrinkle improvement composition is a compound represented by the formula (1a).
[Formula 1a]

According to claim 1, wherein the chalcone derivative is a wrinkle improving composition comprising 0.0001 to 10% by weight based on the total weight of the composition.
The composition for improving wrinkles according to claim 1, further comprising one or two or more wrinkle improving components selected from the group consisting of retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract.
According to claim 4, The wrinkle improving component Wrinkle improvement composition comprising 0.0001 to 10% by weight based on the total weight of the composition.
The composition of claim 1, wherein the composition is formulated in one kind selected from the group consisting of lotion, latex, cream, essence, cosmetic ointment, spray, gel, pack, sunscreen, makeup base, foundation, powder, makeup remover and cleanser. Wrinkle composition for the improvement.
According to claim 1, Wrinkle improvement composition to add a pharmacologically acceptable excipient in addition to the active ingredient.
The method of claim 7, wherein the pharmacologically acceptable excipients are surfactants, emulsifiers, soap acids, solvents, binders, diluents, lubricants, stabilizers, flavors, water, lower alcohols, thickeners, chelating agents, pigments, preservatives, colorants , Preservatives, antibiotics, antioxidants, antifoams, antibacterial agents, antidepressants, enzymes, plant or mineral oils, fats, fluorescent substances, fungicides, combustibles, humectants, fragrances, fragrance carriers, preservatives, proteins, silicones, solubilizers Wrinkle improvement composition is one or two or more selected from the group consisting of sugar derivatives, sunscreens, vitamins, plant extracts and waxes.