KR100371028B1 - Cosmetic composition containing Salvia militiorrhira Bge. extracts and polyethoxylated retinamide - Google Patents

Abstract

The present invention relates to a cosmetic composition having excellent safety and effective in preventing and treating acne, and more specifically, two substances having different mechanisms of action, that is, the effect of inhibiting the activity of five alpha-reductase, sebum secretion effect. The present invention relates to a cosmetic composition having excellent effects on preventing and treating acne by containing salvia extract, which has excellent antibacterial and anti-inflammatory effects, and polyethoxylated retinamide having excellent anti-follicle formation inhibition and exfoliation effect.

Description

Cosmetic composition containing salvia extract and polyethoxylated retinamide, which have excellent skin safety and are effective in preventing and treating acne. Cosmetic composition containing Salvia militiorrhira Bge. extracts and polyethoxylated retinamide}

The present invention relates to a cosmetic composition having excellent safety and effective in preventing and treating acne, and more particularly, salvia extract excellent in activity inhibitory effect, sebum secretion inhibitory effect, antibacterial effect and anti-inflammatory effect of 5 alpha-reductase. The present invention relates to a cosmetic composition having excellent effect on preventing and treating acne by containing polyethoxylated retinamide having excellent anti-follicle formation inhibition and exfoliation effect.

Acne mainly occurs in puberty men and women and refers to chronic inflammatory diseases of the hair follicle sebaceous glands characterized by the formation of comedones, papules, pustules, cysts, or nodules. The cause of acne is still not clearly identified, but it is recognized as the orthodoxy in the previous research reports that three important causes are directly involved in acne, if genetic and environmental factors are excluded. The first is the excessive secretion of sebum, the formation of sebum is caused by the action of male hormones, and the abnormal increase of the male hormone or related mechanisms, sebaceous glands become hyperfunction, resulting in excess sebum. Second is the closure of pores due to hyperkeratosis. The generated sebum should be discharged smoothly out of the skin, but the pores are blocked due to the exaggeration of the hair follicles, thereby suppressing the smooth discharge of sebum, and consequently, the sebum is stagnated in the hair follicles to form microsurfaces. Third, due to the presence of propionibacterium acnes , this is explained as an important cause of acne lesion deterioration. As acne bacteria proliferate in the sebaceous glands, triglycerides that make up sebum are converted into free fatty acids and act as irritants or acne-producing substances. To promote acne production. It also progresses further and involves inflammatory reactions.

Therefore, until now, evaluation for the purpose of alleviating acne has been carried out using a method of evaluating sebum secretion control, hyperkeratosis, and bactericidal activity against acne bacteria using the above-described mechanism of action.

In order to treat such acne, there have been attempts to have a therapeutic effect by smoothing the secretion of sebum by exfoliating pores using salicylic acid or vitamin A derivative retinoic acid, or using benzoyl peroxide to exfoliate the skin. Attempts have been made to cure through removal and strong antimicrobial activity. However, salicylic acid preparations can cause skin redness, swelling or skin repellency, as well as poor therapeutic effects.Retinoic acid preparations have effects through inhibition of hyperkeratosis, but contact dermatitis, erythema, dry skin and peeling Many side effects have been reported in benzoyl peroxide formulations, such as allergic contact dermatitis, scarring, and severe erythema. In addition, relatively low side effects of Azelaic Acid, which have been relatively recently introduced, have not been reported to have superior clinical effects compared to existing therapeutic products.

In view of these problems, the present inventors have studied to develop a cosmetic that is excellent in the prevention and treatment of acne and excellent in the safety of the skin even for a long time use, the result is using both salvia extract and polyethoxylated retinamide having different mechanisms at the same time. When the effect is increased, the safety was found to be excellent and completed the present invention.

Dansam used in the present invention is a medicine that has been handed down for a long time, and the name of the product is red, red, and purple. It is included in major documents such as <Agreement Bogam> and has been included in one of the five ginsengs and has been considered as precious as ginseng. Salvia extract used in the present invention is extracted and purified from the root of perennial herbaceous plant Salvia militiorrhira Bge. Occupies. The structural formula is as follows.

The research on salviae extract was actively led by the Chinese Placebo Science Institute since the late 70s, and is very important for the study of ingredients and clinical pharmacology of salviae, including cardiovascular, cell membrane protection, immune enhancing and other wound healing, skin disease and acne treatment. Brought about development. (Wang Jeong-bang (1980), Chinese Academy of Medicine, Vol. 2, No. 3, 187-188, Ko, Ok-gye (1983), The Combined Magazine of the Midwest, Vol 3, No. 5, 300-301, Wang Jung-bang (1988), China) Dermatology Magazine, Vol 21, No3, 167-168, Taean Jang (1989), Chinese Dermatology Magazine, Vol 22, No.4, 283-284)

The polyethoxylated retinamide used in the present invention is a raw material in which polyethylene glycol (PEG) is added to retinoic acid to increase skin safety and improve effects. Vitamin A (retinol) has been reported in many papers as well as in reducing wrinkles and inhibiting pores hyperkeratosis, which is effective in healing and preventing acne. ( Hughes BR, Norris JFB, Cunliffe WJ (1992); Clin Exper Dermatol 17: 165-168, Foster RH, Brogden RN, Benfield P (1998): Tazarotene; Drugs 55: 705-711, Orfanos CE, Ehlert R, Gollnick H (1987); Drugs 34: 459-503, Verschoore M, Langer A, Wolska H, Jablonska S (1991); Br J Dermatol 124: 368-371, Shalita A, Weiss JS, Chalker DK , (1996); J Am Acad Dermatol 34: 482-485)

However, the existing vitamin A (retinol) has side effects such as damage to normal cells of the stratum corneum, and also the raw material itself is unstable in light, oxygen, temperature and water, so the raw material itself is used in general cosmetics. Difficult to do Attempts have been made to introduce various inclusion techniques or to use derivatives in cosmetics to enhance stability. However, these derivatives have improved stability compared to retinol, but are difficult to absorb skin and still have side effects. Therefore, the inventors of the present invention synthesized polyethoxylated retinamide having improved stability, skin absorption and safety by adding polyethylene glycol to retinol, and used in cosmetics. The structural formula is as follows.

Hereinafter, the present invention will be described in detail.

The present invention contains 0.001-10.0 parts by weight of salvia extract and polyethoxylated retinamide in cosmetics, ie skins, lotions, creams, foundations, packs and essences in an appropriate ratio. 10.0 parts by weight or more, the solubility occurred when blended into the product. In addition, polyethoxylated retinamide is less effective at 0.001 parts by weight or less, and at 10.0 parts by weight or more, the difference in effect on the added dose is not efficient and economical, and the stability of the formulation is poor, making it difficult to use.

Therefore, when adding salvia extract and polyethoxylated retinamide to cosmetics, it is preferable to add 0.001- 10.0 parts by weight, and gel-type essences and emulsified creams applied in the embodiments of the present invention can be easily prepared by conventional manufacturing methods. It can be seen that the properties of the composition in the present invention is easy to apply to any of the different formulations, namely lotion, lotion, essence, pack, foam cleansing, etc. and is not limited to the following examples.

Examples 1-3 and Comparative Example 1

As shown in Table 1, Examples 1 to 3 were prepared by combining the salvia extract and polyethoxylated retinamide in the gel product, Comparative Example 1 was prepared by removing all the active ingredients.

According to the composition of Table 1, the aqueous phase and the ethanol phase were completely dissolved by stirring at 40 degrees Celsius according to the composition of Table 1, and then slowly adding the ethanol phase to the aqueous phase while stirring at 4000 to 5000 rpm for 2 to 4 minutes, and then gradually adding a neutralizer. After stirring at 4000 to 5000rpm again for 4 to 5 minutes, it was cooled and prepared.

Gel product cosmetic composition content of Examples 1 to 3 and Comparative Example 1 division Raw material name Example 1 Example 2 Example 3 Comparative Example 1 Awards Purified water-based glycerin dipropylene glycol carboxyvinyl polymer (2 wt% aqueous solution) Total 1003.05.010.0 Total 1003.05.010.0 Total 1003.05.010.0 Total 1003.05.010.0 Alcoholic Ethanol Polyoxyethylene Cured Castor Oil Paraoxy Benzoic Acid Methyldan Ginseng Extract Polyethoxylated Retinamide Flavor 10.00.30.10.50.1 10.00.30.10.10.1 10.00.30.10.10.5 10.00.30.1--appropriate corrector Triethanolamine (10% weight aqueous solution) 2.0 2.0 2.0 2.0

Examples 4-6 and Comparative Examples 2-4

As shown in Table 2, Examples 4 to 6 were prepared by mixing salvia extract and polyethoxylated retinamide in an emulsified cream product, and Comparative Example 2 was prepared by removing all of the active ingredients, and Comparative Examples 3 and 4 One active ingredient was prepared one by one.

According to the composition of Table 2, the oil and water phases are heated to 75 degrees Celsius, respectively, and dissolved.Then, the oil phase is slowly added to the water phase using a homomixer, and then stirred at 4000 to 5000 rpm for 2 to 4 minutes, followed by gradually adding a neutralizer. After stirring for 4 to 5 minutes at 4000 to 5000rpm, after cooling, the additive was added at 45 degrees Celsius and stirred for 2 minutes at 4000 to 5000rpm to cool to room temperature.

Cosmetic composition contents of the emulsion type cream products of Examples 4 to 6 and Comparative Examples 2 to 4 division Raw material name Example 4 Example 5 Example 6 Comparative Example 2 Comparative Example 3 Comparative Example 4 Awards Purified water-based glycerin dipropylene glycol ethylenediaminetetraacetic acid carboxyvinyl polymer (2% by weight aqueous solution) preservative Total 1003.05.00.0212.0 Total 1003.05.00.0212.0 Total 1003.05.00.0212.0 Total 1003.05.00.0212.0 Total 1003.05.00.0212.0 Total 1003.05.00.0212.0 Paid Cetostearyl Alcohol Stearic Acid Hydrophilic Monostearic Acid Magnetic Emulsified Monostearic Acid Squalanoctyl Dodecyl Myristate Trioctanoin Polysorbate 60 Solbitan Stearate Sweet Salmon Extract 1.50.51.00.53.04.05.01.00.50.5 1.50.51.00.53.04.05.01.00.50.1 1.50.51.00.53.04.05.01.00.50.1 1.50.51.00.53.04.05.01.00.5- 1.50.51.00.53.04.05.01.00.50.1 1.50.51.00.53.04.05.01.00.5- corrector Triethanolamine (10% weight aqueous solution) 1.2 1.2 1.2 1.2 1.2 1.2 additive Polyethoxylated Retinamide Flavor 0.1 quantity 0.1 0.5 - - 0.1

Experimental Example 1. Inhibitory effect of 5 alpha-reductase activity

Excess sebum secretion, which is one of the causes of acne, is known to be closely related to testosterone, a testosterone. The process of testosterone is 5 alpha-reductase in skin cells. Is converted to dihydrotestosterone (DHT) to promote sebum secretion by enhancing the activity of sebum secretory cells (Rosenfield RL and Deplewski D. Role of androgen in the developmental biology of the pilosebaceous unit. American Journal of Medicine 1995; 16: 80s-88s). Therefore, experiments on the inhibition of 5 alpha-reductase activity of Salvia ginseng extract were confirmed whether sebum secretion inhibitory effect. The experimental method is as follows.

5 Testosterone (3H-1) with dithiothreitol, NADPH, and radioisotopes bound to 30 μl of Phosphate Buffered Saline (PBS / pH 6.6) to measure the activity of alpha-reductase. 10 µl of 2,4,5,6,7-testosterone), 40 µl of 5 alpha-reductase enzyme extract, and 100 ml of Salvia Militiorrhiza extract at the appropriate concentration were added to 100 µl. The amount of converted dihydrotestosterone (DHT) was measured using a mixture of radioisotopes and radioisotopes. Inhibition rate (%) was calculated using the amount of converted dihydrotestosterone (DHT) and the amount of testosterone, thereby confirming the inhibitory effect of the activity of Salvia extract on 5 alpha-reductase enzyme. .

% Inhibition = Conversion rate from T to DHT with no test material × 100

Conversion rate from T to DHT with test material

T: testosterone

DHT: dihydrotestosterone

the results are as follow.

Inhibition Rate of 5 Alpha-reductase Activity of Salviae Radix Extract Salvia extract concentration 0.5% 0.1% 0.01% 0.001% Inhibition rate 100% 46.8% 32.8% 21.3%

From the above results, it was found that Salvia extract was excellent in inhibiting 5 alpha-reductase activity.

Experimental Example 2. Sebum secretion inhibition evaluation experiment

In order to evaluate the sebum secretion inhibitory effect of Examples 1 to 3 and Comparative Example 1, 40 healthy men and women were randomly selected to observe the sebum secretion inhibitory effect using sebumape (sebotape). The experimental method is as follows.

First, before evaluating the sebum secretion inhibitory effects of Examples 1 to 3 and Comparative Example 1, the normal sebum secretion rate at the forehead region, which is the site to be used in the experiment, was measured using sebum tape, and then Examples 1 to 3 and Comparative Example. After three weeks of 1, sebum secretion rate was measured using sebum tape at the same site where normal rate of sebum secretion was measured. The sebum tape was attached to the sebum for 30 minutes and then peeled off to measure the amount of sebum secreted in the sebum tape using an image analyzer. The determination was made using the sebum secretion rate, and the unit of sebum secretion rate is mg / cm ² / min, which means the amount of sebum secreted per unit time and unit area. The results are shown in Table 4.

Sebum secretion inhibitory effect of Examples 1 to 3 and Comparative Example 1 division Sebum secretion rate (Comparative Example-Example) / Comparative Example × 100 Comparative Example 1 Example 1 Example 2 Example 3 19.5011.6012.0011.96 -40.5% 38.5% 38.7%

In the results of the table it can be seen that the case of Examples 1 to 3 reduces the sebum secretion rate compared to the case of Comparative Example 1, it can be seen that the secretion of sebum secretion is also reduced accordingly.

Experimental Example 3. Acne Bacteria ( Propionibacterium acnes) Antimicrobial activity against

In order to measure the bactericidal activity of acne bacteria of Salvia ginseng extract, propionibacterium acnes (P. acnes), which were stored in the bacterium, in a bacterium, was cultured in BHI (Brain Heart Infusion) solid medium three days before the experiment, MIC was determined by inoculating pre-cultured P. acnes in concentration-containing BHI solid medium and observing the growth of bacteria after 3 days or more. The results are shown in Table 5.

MIC (minimum blocking concentration) of Salvia extract MIC (Mole) Salvia extract <500 ppm

As can be seen in Table 5, Salvia extract strongly inhibits P. acnes.

Experimental Example 4. Evaluation of the effect of dissolving cotton cloth using rabbit ears

Embryo dissolution effects were evaluated using experimental methods using rabbit ears, which are widely known as acne efficacy evaluation methods (AMKligman et al., British Journal of Dermatology, 100, 699-702, 1979). Experimental method was applied 0.5 ml of isopropyl myristate in rabbit ears for 2 weeks to induce cotton cloth, and then in each ear Examples 1 to 3, and the other ear in Comparative Example 1 0.5ml each for 2 weeks Applied. After 2 weeks of application, the surface mitigation effect was evaluated by visual inspection. Also, a hole mount was made in rabbit ears, and the area of the surface was measured and evaluated using an image analyzer. Seven animals were used for each experiment. In the case of visual inspection, the test was divided into seven stages of '0', 0.5, '1', 1.5, '2', 2.5, and '3', and the area of the cotton cloth was compared based on mm ² .

The criteria for visual judgment are as follows.

0: no difference from control

0.5: moderate symptoms between 0 and 1

1: hyperemia, capillary bleeding, weak pore keratosis and enlarged pores

1.5: moderate symptoms between 1 and 2

2: moderate pores keratosis and enlarged pores

2.5: moderate symptoms between 2 and 3

3: severe pore keratosis and pores hypertrophy, typical scleroderma observation

The results are shown in Table 6 and Table 7.

Cotton cloth dissolution effect of Examples 1 to 3 and Comparative Example 1 through visual determination division Cotton area (Comparative Example-Example) / Comparative Example × 100 Comparative Example 1 Example 1 Example 2 Example 3 1.671.041.090.97 -37.7% 34.7% 41.9%

Comparison of Cotton Dissolution Effects by Comparing Cotton Area Using Image Analyzer division Cotton area (Comparative Example-Example) / Comparative Example × 100 Comparative Example 1 Example 1 Example 2 Example 3 1.6581.0151.0520.978 -38.8% 36.6% 41.0%

As can be seen from the above results, it can be seen that Examples 1 to 3 are superior to the cotton cloth dissolution effect compared to Comparative Example 1 both in the visual determination and the comparison of the surface area of the cotton using an image analyzer.

Experimental Example 5. Evaluation test for hyperkeratosis inhibitory ability

Hyperkeratosis is one of the causes of acne, and if there is a substance that can prevent such hyperkeratosis, it may play an important role in acne relief and prevention. Accordingly, the following experiment was conducted to evaluate the exfoliation effect of the polyethoxylated retinamide, that is, the hyperkeratosis inhibitory effect.

All the cells that make up the skin are constantly produced during the life of the living organism, die after being properly metabolized and then separated into the skin. In order to maintain skin homeostasis, the rate of cell production and detachment is kept constant. Therefore, in general, the regeneration rate of the skin can be measured indirectly by measuring the peeling rate of the stratum corneum, and the peeling rate of the skin is measured by measuring the discoloration of the skin according to the peeling of the skin (Jean- Luc Leveque, Cutaneous Investigation in Health and Desease, 33-40, 1989). The discoloration of the skin was using dihydroxyacetone (DHA), which is used in self-tanning products. Detailed experimental method is as follows.

Select 20 men in their mid 20s and early 30s, select the inside of the upper arm where the skin color is relatively bright, and measure the brightness of the skin before coloring it with a colorimeter. 0.4 ml of Roxacetone solution was stained using a Hill top chamber. Two arms were used per person, two samples were applied per arm, and four samples were applied per person. After 24 hours, the pigmented area was measured with a colorimeter, and polyethoxylated retinamide was prepared at a concentration of 0.01%, 0.1%, and 1%, respectively, and applied 0.4 ml twice a day for 30 minutes, and then daily with a colorimeter. Measured. 24 hours after application of dihydroxyacetone, the colorimetric value measured as 100 was calculated in terms of%, which was decolorized daily. The determination was made by the time (days) when the colored portion returned to the normal color. The results are shown in Table 8.

Inhibitory Effect of Polyethoxylated Retinamide on Hyperkeratinization density Reduction (Control-Example) / control × 100 Control0.01% 0.1% 1.0% 18.31 Day 12.44 Day 12.19 Day 11.44 Day 32.1% 33.4% 37.5%

As can be seen from the above results, polyethoxylated retinamide has an effect of inhibiting hyperkeratosis according to the concentration, about 32-38%, and the skin colored with dihydroxyacetone returns to normal skin color within a short time. You can see it coming. This means that the exfoliation effect of polyethoxylated retinamide is excellent, and the above effects were reaffirmed through actual examples. That is, the effect of inhibiting hyperkeratosis for Examples 4 to 6 was carried out in the same manner as above. The results are shown in Table 9 below.

Hyperkeratinization inhibitory effect of Examples 4 to 6 and Comparative Example 2 division Reduction (Comparative Example-Example) / Comparative Example × 100 Comparative Example 2 18.20 days Example 4 12.33 days 32.3% Example 5 12.12 days 33.4% Example 6 11.50 days 36.8%

As can be seen from the above results, Examples 4 to 6 was found to be superior to Comparative Example 2 in the effect of inhibiting hyperkeratinization about 32-37%.

Experimental Example 6. Anti-inflammatory Test

In order to examine the anti-inflammatory effect on salvia extract, mouse left ear was used as control site and right ear as test site. Before application of the sample, the ears were cleaned with ethanol, and 20 μl of sample was continuously applied once a day for 4 days. One hour after the last application, ethanol was applied to the left ear and arachidonic acid (2 mg / ear) was applied to the right ear. After 1 hour, the degree of ear edema was repeated three times with a micrometer.

The anti-inflammatory effect was determined as the degree of edema inhibition based on the arachidonic acid treatment group and the results are shown in Table 10.

Ear thickness and inflammation inhibition rate by topical application sample density(%) menstruum Ear thickness (㎛) % Inhibition Before sample processing After sample processing Sweet Salmon Extract Stearyl Glycyrretinate Indomethacin 0.30.30.32mg / ear Ethanol Ethanol Ethanol Ethanol 249244252254 395407365431 17.57.936.2-

※ Inhibition Rate (%) = (A―B) / A × 100

A: Average thickness of control ears (thickness of arachidonic acid-treated ears-thickness of untreated ears)

B: thickness of the sample-coating group ear thickness (thickness of the sample-treated ear-thickness of the untreated ear)

As shown in Table 10, salvia extract showed 17.5% inhibition rate, which is higher than Stearyl Glycyrretinate, which is known to have good anti-inflammatory effect. Saliva extract showed a 99% significance level with arachidonic acid.

Experimental Example 7. Skin primary irritation test (closed patch test)

In order to examine the skin irritation in comparison with the above example, a certain amount (0.2 g) of each sample was applied to the back of the healthy adult male and female 50 hours for 24 hours, and then the pin chamber was removed for 4 hours. Next, the change of skin condition was visually read and the results are shown in Table 11.

As shown in the table, the irritation was lower than that of the comparative example containing no salvia extract and polyethoxylated retinamide. It was confirmed that it is safe for the skin.

Skin primary irritation test result sample Number of test subjects Judgment result Stimulus ++ + +- - Example 1 Example 2 Example 3 Comparative Example 1 Example 4 Example 5 Example 6 Comparative Example 2 Comparative Example 3 Comparative Example 4 50505050505050505050 ---------- ---------- -113--12-2 50494947505049485048 0.000.020.020.060.000.000.020.040.000.04

<Judge criteria>

-: No erythema or unusual phenomenon.

+-: Slightly redder than the surroundings

+: Significantly redder than the surroundings

++: Reddens and swells more heavily than the surroundings.

Experimental Example 8. Evaluation of acne relief effect

In order to see the acne alleviating effect of Example 5 and Comparative Examples 2 to 4, a blind test was performed on 120 healthy men and women between 20 and 30 years old with acne. The experimental method was randomly divided into four groups of 30 people, and Example 5 and Comparative Examples 2 to 4 were evaluated in each group after Example 5 and Comparative Examples 2 to 4 were contained in the same container. Experimental method was applied twice a day for 2 months for Example 5 and Comparative Examples 2 to 4. The evaluation was conducted by combining a questionnaire and gross findings on whether the acne symptoms worsened and alleviated through an interview after two months of application. The results are shown in Table 12 below.

Acne Relief Effect (Unit: figures) division In effect Slightly effective I do not know no effect Example 5 6/10 2/10 2/10 0/10 Comparative Example 2 0/10 1/10 3/10 6/10 Comparative Example 3 3/10 3/10 2/10 2/10 Comparative Example 4 2/10 1/10 3/10 4/10

In the above results, the effect of 'accepting' and 'having a slight effect' to recognize the acne relief effect was 80% in Example 5, Comparative Example 2 without the active ingredient was about 10%. In addition, Comparative Example 3 shows an effect of 60%, Comparative Example 4 has an effect of about 30%, it can be seen that the acne relieving effect was superior to Comparative Examples 3 and 4 where Example 5 was used alone.

As described above and can be seen through the examples, the present invention relates to a cosmetic composition having excellent safety and effective in preventing and treating acne. It contains excellent salvia extract, antibacterial and anti-inflammatory effect, and polyethoxylated retinamide with excellent anti-follicle formation and exfoliation effect.

Claims (3)

A cosmetic composition having an anti-acne effect, characterized in that it contains salvia extract and polyethoxylated retinamide. The cosmetic composition having an anti-acne effect according to claim 1, which comprises 0.001-10.0 wt% of Salvia extract and 0.001-10.0 wt% of polyethoxylated retinamide. The cosmetic composition having an anti-acne effect according to claim 2, wherein the extract contains 0.01-5% by weight of Dansam extract and 0.01-5% by weight of polyethoxylated retinamide.